Imaging of cavitary necrosis in complicated childhood pneumonia.

The aim of this study was to illustrate the chest radiographs (CR) and CT imaging features and sequential findings of cavitary necrosis in complicated childhood pneumonia. Among 30 children admitted in the Pediatric Intensive Care Unit for persistent or progressive pneumonia, respiratory distress or sepsis despite adequate antibiotic therapy, a study group of 9 children (5 girls and 4 boys; mean age 4 years) who had the radiographic features and CT criteria for cavitary necrosis complicated pneumonia was identified. The pathogens identified were Streptococcus pneumoniae( n=4), Aspergillus( n=2), Legionella( n=1), and Staphylococcus aureus( n=1). Sequential CR and CT scans were retrospectively reviewed. Follow-up CR and CT were evaluated for persistent abnormalities. Chest radiographs showed consolidations in 8 of the 9 patients. On CT examination, cavitary necrosis was localized to 1 lobe in 2 patients and 7 patients showed multilobar or bilateral areas of cavitary necrosis. In 3 patients of 9, the cavitary necrosis was initially shown on CT and visualization by CR was delayed by a time span varying from 5 to 9 days. In all patients with cavities, a mean number of five cavities were seen on antero-posterior CR, contrasting with the multiple cavities seen on CT. Parapneumonic effusions were shown by CR in 3 patients and in 5 patients by CT. Bronchopleural fistulae were demonstrated by CT alone ( n=3). No purulent pericarditis was demonstrated. The CT scan displayed persistent residual pneumatoceles of the left lower lobe in 2 patients. Computed tomography is able to define a more specific pattern of abnormalities than conventional CR in children with necrotizing pneumonia and allows an earlier diagnosis of this rapidly progressing condition. Lung necrosis and cavitation may also be associated with Aspergillus or Legionella pneumonia in the pediatric population.

Fatal myocardial infarction after lung resection in a patient with prophylactic preoperative coronary stenting.

In this report we present the case of a 77-yr-old man who underwent resection of the upper lobe of the left lung for a carcinoma, six weeks after percutaneous transluminal coronary angioplasty (PTCA) with stenting of the left anterior descending (LAD) and circumflex coronary arteries. Antiplatelet therapy with clopidogrel was interrupted two weeks before surgery to allow for epidural catheter placement and to minimize haemorrhage. The surgical procedure was uneventful. In the immediate postoperative period, however, the patient suffered severe myocardial ischaemia. Emergency coronary angiography showed complete thrombotic occlusion of the LAD stent. In spite of successful recanalization, reinfarction occurred and the patient died in cardiogenic shock. Prophylactic preoperative coronary stenting may put the patient at risk of stent thrombosis if surgery cannot be postponed for three months. In such cases, other strategies such as perioperative beta-blockade for preoperative cardiac management should be considered.

Sustained improvement in left ventricular function after bone marrow derived cell therapy in patients with acute ST elevation myocardial infarction. A 5-year follow-up from the Stem Cell Transplantation in Ischaemic Myocardium Study.

BACKGROUND: Intracoronary injection of autologous bone marrow-derived mononucleated cells (BM-MNC) may improve LV function shortly after acute ST elevation myocardial infarction (STEMI), but little is known about the long-term durability of the treatment effect. METHODS: In a single-centre trial a total of 60 patients with acute anterior STEMI, successful reperfusion therapy and a left ventricular ejection fraction (LVEF) of <50% were screened for the study. 23 patients were actively treated with intracoronary infusion of BM-MNC within a median of 3 days. The open-label control group consisted of 19 patients who did not consent to undergo BM-MNC treatment but agreed to undergo regular clinical and echocardiographic follow-up for up to 5 years after AMI. RESULTS: Whereas at 4 months there was no significant difference between the increase in LVEF in the BM-MNC group and the control group (+7.0%, 95%CI 3.6; 10.4) vs. +3.9%, 95%CI -2.1; 10), the absolute increase at 5 years remained stable in the BM-MNC but not in the control group (+7.95%, 95%CI 3.5; 12.4 vs. -0.5%, 95%CI -5.4; 4.4; p for interaction between groups = 0.035). DISCUSSION: In this single-centre, open-labelled study, intracoronary administration of BM-MNC is feasible and safe in the short term. It is also associated with sustained improvement of left ventricular function in patients with acute myocardial infarction, encouraging phase III studies to examine the potential BM-MNC effect on clinical outcome.

The distribution of congenital anomalies within the VACTERL association among tumor necrosis factor antagonist-exposed pregnancies is similar to the general population.

OBJECTIVE: To compare the distribution of congenital anomalies within the VACTERL association (vertebral defects, anal atresia, cardiac, tracheoesophageal, renal, and limb abnormalities) between patients exposed to tumor necrosis factor-α (TNF-α) antagonist and the general population. METHODS: Analysis for comparison of proportional differences to a previous publication between anomaly subgroups, according to subgroup definitions of the European Surveillance of Congenital Anomalies (EUROCAT), a population-based database. RESULTS: Most EUROCAT subgroups belonging to the VACTERL association contained only one or 2 records of TNF-α antagonist exposure, so comparison of proportions was imprecise. Only the category "limb abnormalities" showed a significantly higher proportion in the general population. CONCLUSION: The high number of congenital anomalies belonging to the VACTERL association from a report of pregnancies exposed to TNF-α antagonists could not be confirmed using a population-based congenital anomaly database.

Tumor necrosis factor-α in human American tegumentary leishmaniasis

Tumor necrosis factor-alpha (TNF-α) is a cytokine produced by activated macrophages and other cells. In order to verify whether the serum levels of TNF-α in American tegumentary leishmaniasis patients are associated with the process of cure or aggravation of the disease, 41 patients were studied: 26 cases of cutaneous leishmaniasis (CL) and 15 of mucocutaneous leishmaniasis (MCL). During active disease the serum levels of TNF-α of MCL patients were significantly higher than those of CL patients and control subjects (healthy individuals and cutaneous lesions from other etiologies). The MCL patients had serum titers of TNF-α significantly lower at the end of antimonial therapy than before therapy. After a six-month follow-up, the MCL patients had serum levels of TNF-α similar to those observed at the end of the therapy as well as to those of CL patients and control subjects. No significant variation in the serum levels of TNF-α was observed in CL patients throughout the study period (before, at the end of therapy and after a six-month follow-up). The possible relationship between the high TNF-α serum levels and severity of the disease is discussed.

Maturation of marginal zone and follicular B cells requires B cell activating factor of the tumor necrosis factor family and is independent of B cell maturation antigen.

B cells undergo a complex series of maturation and selection steps in the bone marrow and spleen during differentiation into mature immune effector cells. The tumor necrosis factor (TNF) family member B cell activating factor of the TNF family (BAFF) (BLyS/TALL-1) plays an important role in B cell homeostasis. BAFF and its close homologue a proliferation-inducing ligand (APRIL) have both been shown to interact with at least two receptors, B cell maturation antigen (BCMA) and transmembrane activator and cyclophilin ligand interactor (TACI), however their relative contribution in transducing BAFF signals in vivo remains unclear. To functionally inactivate both BAFF and APRIL, mice transgenic for a soluble form of TACI were generated. They display a developmental block of B cell maturation in the periphery, leading to a severe depletion of marginal zone and follicular B2 B cells, but not of peritoneal B1 B cells. In contrast, mice transgenic for a soluble form of BCMA, which binds APRIL, have no detectable B cell phenotype. This demonstrates a crucial role for BAFF in B cell maturation and strongly suggests that it signals via a BCMA-independent pathway and in an APRIL-dispensable way.

Interactions of tumor necrosis factor (TNF) and TNF receptor family members in the mouse and human.

Ligands of the tumor necrosis factor superfamily (TNFSF) (4-1BBL, APRIL, BAFF, CD27L, CD30L, CD40L, EDA1, EDA2, FasL, GITRL, LIGHT, lymphotoxin alpha, lymphotoxin alphabeta, OX40L, RANKL, TL1A, TNF, TWEAK, and TRAIL) bind members of the TNF receptor superfamily (TNFRSF). A comprehensive survey of ligand-receptor interactions was performed using a flow cytometry-based assay. All ligands engaged between one and five receptors, whereas most receptors only bound one to three ligands. The receptors DR6, RELT, TROY, NGFR, and mouse TNFRH3 did not interact with any of the known TNFSF ligands, suggesting that they either bind other types of ligands, function in a ligand-independent manner, or bind ligands that remain to be identified. The study revealed that ligand-receptor pairs are either cross-reactive between human and mouse (e.g. Tweak/Fn14, RANK/RANKL), strictly species-specific (GITR/GITRL), or partially species-specific (e.g. OX40/OX40L, CD40/CD40L). Interestingly, the receptor binding patterns of lymphotoxin alpha and alphabeta are redundant in the human but not in the mouse system. Ligand oligomerization allowed detection of weak interactions, such as that of human TNF with mouse TNFR2. In addition, mouse APRIL exists as two different splice variants differing by a single amino acid. Although human APRIL does not interact with BAFF-R, the shorter variant of mouse APRIL exhibits weak but detectable binding to mouse BAFF-R.

Reduced ejection fraction after myocardial infarction: is it sufficient to justify implantation of a defibrillator?

BACKGROUND: Improved survival after prophylactic implantation of a defibrillator in patients with reduced left ventricular ejection fraction (EF) after myocardial infarction (MI) has been demonstrated in patients who experienced remote MIs in the 1990s. The absolute survival benefit conferred by this recommended strategy must be related to the current risk of arrhythmic death, which is evolving. This study evaluates the mortality rate in survivors of MI with impaired left ventricular function and its relation to pre-hospital discharge baseline characteristics. METHODS: The clinical records of patients who had sustained an acute MI between 1999 and 2000 and had been discharged from the hospital with an EF of < or = 40% were included. Baseline characteristics, drug prescriptions, and invasive procedures were recorded. Bivariate and multivariate analyses were performed using a primary end point of total mortality. RESULTS: One hundred sixty-five patients were included. During a median follow-up period of 30 months (interquartile range, 22 to 36 months) 18 patients died. The 1-year and 2-year mortality rates were 6.7% and 8.6%, respectively. Variables reflecting coronary artery disease and its management (ie, prior MI, acute reperfusion, and complete revascularization) had a greater impact on mortality than variables reflecting mechanical dysfunction (ie, EF and Killip class). CONCLUSIONS: The mortality rate among survivors of MIs with reduced EF was substantially lower than that reported in the 1990s. The strong decrease in the arrhythmic risk implies a proportional increase in the number of patients needed to treat with a prophylactic defibrillator to prevent one adverse event. The risk of an event may even be sufficiently low to limit the detectable benefit of defibrillators in patients with the prognostic features identified in our study. This argues for additional risk stratification prior to the prophylactic implantation of a defibrillator.

Real-time imaging of regional myocardial function using fast-SENC.

A technique for fast imaging of regional myocardial function using a spiral acquisition in combination with strain-encoded (SENC) magnetic resonance imaging (MRI) is presented in this paper. This technique, which is termed fast-SENC, enables scan durations as short as a single heartbeat. A reduced field of view (FOV) without foldover artifacts was achieved by localized SENC, which selectively excited the region around the heart. The two images required for SENC imaging (low- and high-tuning) were acquired in an interleaved fashion throughout the cardiac cycle to further shorten the scan time. Regional circumferential contraction and longitudinal shortening of both the left ventricle (LV) and right ventricle (RV) were examined in long- and short-axis views, respectively. The in vivo results obtained from five human subjects and five infarcted dogs are presented. The results of the fast-SENC technique in a single heartbeat acquisition were comparable to those obtained by conventional SENC in a long acquisition time. Therefore, fast-SENC may prove useful for imaging during stress or arrhythmia.

Dietary fish oil is antihypertrophic but does not enhance postischemic myocardial function in female mice.

Clinically and experimentally, a case for omega-3 polyunsaturated fatty acid (PUFA) cardioprotection in females has not been clearly established. The goal of this study was to investigate whether dietary omega-3 PUFA supplementation could provide ischemic protection in female mice with an underlying genetic predisposition to cardiac hypertrophy. Mature female transgenic mice (TG) with cardiac-specific overexpression of angiotensinogen that develop normotensive cardiac hypertrophy and littermate wild-type (WT) mice were fed a fish oil-derived diet (FO) or PUFA-matched control diet (CTR) for 4 wk. Myocardial membrane lipids, ex vivo cardiac performance (intraventricular balloon) after global no-flow ischemia and reperfusion (15/30 min), and reperfusion arrhythmia incidence were assessed. FO diet suppressed cardiac growth by 5% and 10% in WT and TG, respectively (P < 0.001). The extent of mechanical recovery [rate-pressure product (RPP) = beats/min x mmHg] of FO-fed WT and TG hearts was similar (50 +/- 7% vs. 45 +/- 12%, 30 min reperfusion), and this was not significantly different from CTR-fed WT or TG. To evaluate whether systemic estrogen was masking a protective effect of the FO diet, the responses of ovariectomized (OVX) WT and TG mice to FO dietary intervention were assessed. The extent of mechanical recovery of FO-fed OVX WT and TG (RPP, 50 +/- 4% vs. 64 +/- 8%) was not enhanced compared with CTR-fed mice (RPP, 60 +/- 11% vs. 80 +/- 8%, P = 0.335). Dietary FO did not suppress the incidence of reperfusion arrhythmias in WT or TG hearts (ovary-intact mice or OVX). Our findings indicate a lack of cardioprotective effect of dietary FO in females, determined by assessment of mechanical and arrhythmic activity postischemia in a murine ex vivo heart model.

Defectos paradójicos en regiones con necrosis miocárdica. análisis mediante gated-spect de perfusión miocárdica.

Objectius: Valorar el significat dels defectes paradoxals (DP) segmentaris (captació en esforç més gran que en repòs) a la gated-SPECT (Single Photon Emission Computer Tomography) de perfusió miocàrdica amb compostos tecneciats en regions amb necrosi miocàrdica. Material i mètodes: Es van revisar 1764 SPECT de perfusió miocàrdica estrès-repòs consecutives de pacients amb infart (IM) previ i es van identificar 117 pacients (6,6%) en els quals els DPs corresponien a una regió amb necrosi miocàrdica. Es van valorar els criteris gammagràfics de viabilitat (intensitat del defecte, valor d'aquesta intensitat ponderat pel nombre de segments compromesos-VIP-, la motilitat i l'engrossiment miocàrdic sistòlic) en els segments d'aquestes regions i les característiques de l'artèria responsable en els 96 pacients en els quals s'havia practicat una coronariografia. Resultats: Es van analitzar 160 necrosis, 125 (75%) paradoxals (67 (54%) en regió AnteroSeptoApical i 58 (46%) en regió InferoLateral) i 35 (25%) no paradoxals (19 (54%) ASA i 16 ( 46%) IL). Els valors de severitat de la necrosi i del VIP van ser inferiors en l'estudi d'estrès respecte al repòs i la diferència d'aquests va ser sempre negativa, evidenciant un comportament gammagràfic paradoxal. Per contra, aquests valors van ser inferiors al repòs respecte a l'estrès en les necrosi no paradoxals posant de manifest un comportament gammagràfic de mínima o nul reversibilitat. Així mateix, es van trobar alteracions lleus en la motilitat i engrossiment de les necrosi paradoxals i moderats en les necrosi no paradoxals. Es van trobar 102 necrosis amb DP i coronariografia dels quals, 84 (88%) tenien permeabilitat a l'artèria responsable de la necrosi i 12 pacients (12%) tenien circulació colateral per compensar l'oclusió de l'artèria responsable. Conclusions: Tots els segments amb DP en regions amb necrosi complien criteris gammagràfics de viabilitat en les imatges d'estrès, considerant aquestes imatges millors per a l'avaluació d'aquest tipus de lesions. El vas responsable de la regió amb DP es trobava permeable o bé presentava circulació colateral evident en els casos en què la coronària es trobava closa.

Detection of circulant tumor necrosis factor-alpha , soluble tumor necrosis factor p75 and interferon-gamma in Brazilian patients with dengue fever and dengue hemorrhagic fever

Pro-inflammatory cytokines are believed to play an important role in the pathogenesis of dengue infection. This study reports cytokine levels in a total of 54 patients examined in Recife, State of Pernambuco, Brazil. Five out of eight patients who had hemorrhagic manifestations presented tumor necrosis factor-alpha (TNF-alpha) levels in sera which were statistically higher than those recorded for controls. In contrast, only one out of 16 patients with mild manifestations had elevated TNF-alpha levels. The levels of interleukin-6 (IL), IL-1beta tested in 24 samples and IL-12 in 30 samples were not significantly increased. Interferon-g was present in 10 out of 30 patients with dengue. The data support the concept that the increased level of TNF-alpha is related to the severity of the disease. Soluble TNF receptor p75 was found in most patients but it is unlikely to be related to severity since it was found with an equivalent frequency and levels in 15 patients with dengue fever and another 15 with dengue hemorrhagic fever.