Treatment of complicated pleural effusion with intracavitary urokinase in children

Intrapleural administration of fibrinolytic agents such as urokinase (UK) has been advocated as an alternative method to manage complicated pleural effusion (CPE). Despite the increasing number of empyemas successfully treated with UK in adults, the experience in children is limited to a few cases. We report the results of image-guided catheter drainage (IGCD) with intracavitary instillation of UK in six children with CPE. Urokinase (25,000-100, 000 IU) was diluted in 20 mL of normal saline and instilled into the pleural cavity via a percutaneously placed drainage catheter. After 4 hr, the clamped catheter was released and connected to water-seal suction at a negative pressure of 20 cm H(2)O. UK instillation was repeated daily until no further drainage occurred. During IGCD, repeated radiographic and ultrasound imaging determined the location and amount of any remaining pleural fluid. Mean duration of hospital stay before initiating UK therapy was 4.3 days. Mean duration of catheter drainage before initiating UK therapy was 3.5 days, and the mean total drainage was 86 mL. All patients had an increase in chest tube drainage within 24 hr after the first instillation of UK. The mean net total drainage after UK instillation was 281 mL, most of the drainage being occurring in the first 2 days of treatment. Mean hospital stay following UK treatment was 5.8 days, and the average total duration of hospital stay was 13.8 days. No complications and no adverse events occurred during treatment with UK. Complete resolution of the consequences of the pleural effusion was observed in all patients at follow-up. Our results suggest that IGCD with adjunctive UK therapy is a reliable, simple, and safe approach to treat CPE, and it can reduce the risks associated with thoracotomy and decortication.     

Factors affecting the therapeutic choice in patients with multivessel coronary artery disease. The Studio Lombardo Angiografia Multivasali (SLAM) Study Group.

OBJECTIVE: To assess how clinical and angiographic findings are related to the decision to carry out coronary angioplasty (PTCA) or coronary bypass grafting in patients with multivessel coronary artery disease. DESIGN: Prospective survey carried out in 14 centres in the Lombardia region of Italy. PATIENTS: 1468 consecutive patients under going coronary arteriography for known or suspected ischaemic heart disease between May and October 1994, who were found to have multivessel coronary artery disease. MAIN OUTCOME MEASURES: Multivariate analysis was undertaken using stepwise logistic regression to identify the clinical and angiographic variables correlated with revascularisation (v medical treatment) in all of patients, and with surgery (v angioplasty) in the subset of revascularised patients. RESULTS: In all patients the clinical decision after coronary arteriography was made by physicians of each participating centre on the basis of their experience and clinical judgment: 53% of patients had bypass surgery, 28% had PTCA, and 19% continued medical treatment. The choice of a revascularisation procedure was directly related to a clinical diagnosis of unstable angina (P < < 0.001), the presence of left anterior descending artery disease (P < < 0.001), and to an ejection fraction > or = 40% (P < < 0.001), and inversely related to history of previous coronary bypass surgery (P < < 0.001). In revascularised patients, bypass surgery was the preferred treatment in patients with left anterior descending artery disease (P < < 0.001), three-vessel disease (P < < 0.001), and in those with at least one occluded vessel (P = 0.008). The choice of PTCA was significantly related to history of previous PTCA (P < < 0.001) or coronary bypass surgery (P < < 0.001), to a clinical diagnosis of non-Q wave myocardial infarction (P = 0.002), and to the possibility of implanting an intracoronary stent (P = 0.01). CONCLUSIONS: Bypass surgery is still the most widely used treatment for patients with multivessel coronary artery disease. This analysis provides a basis for comparison with future developments in the treatment of such patients. Further advancements in PTCA technology are needed to tilt the balance in favour of this less invasive procedure.     

Shoulder ultrasonography in the diagnosis of polymyalgia rheumatica: a case-control study

OBJECTIVE: Magnetic resonance imaging (MRI) showed that subacromial/subdeltoid bursitis is the most frequent shoulder lesion in polymyalgia rheumatica (PMR). We evaluated whether shoulder ultrasonography (US) was as effective as MRI in the detection of this lesion and assessed the sensitivity and specificity of bilateral subacromial/subdeltoid bursitis in the diagnosis of PMR. METHODS: A case-control study of 57 consecutive case patients with untreated PMR and 114 controls seen over a 6 month period in 3 secondary referral rheumatology centers. Control patients consisted of the next 2 consecutive patients with bilateral shoulder aching and stiffness observed after the case patient. In all case and control patients the glenohumeral joint space, bursae, and long head biceps tendon were assessed by bilateral shoulder US. The first 24 case patients were also examined by bilateral shoulder MRI. RESULTS: US showed subacromial/subdeltoid bursitis in 55/57 (96%) patients with PMR and in 25/114 (22%) controls (p < 0.001). The lesion was bilateral in 53/55 (96%) case patients and in 1/25 (4%) controls (p < 0.001). The frequency of glenohumeral joint synovitis and biceps tenosynovitis did not differ significantly between case patients and controls. In 100% of case patients MRI showed subacromial/subdeltoid bursitis confirming US findings. The sonographic evidence of bilateral bursitis had a sensitivity of 92.9%, specificity of 99. 1%, and positive predictive value of 98. 1% for the diagnosis of PMR. CONCLUSION: US and MRI were equally effective in confirming bilateral subacromial and subdeltoid bursitis in PMR. This finding, in view of its high sensitivity and specificity, could be used as a new diagnostic criterion for PMR.     

Binding assay for thyrotropin receptor autoantibodies using the recombinant receptor protein.

We have characterized a transfected Chinese hamster ovary cell line, JP09, which expresses high levels of the human TSH receptor (TSH-R). Based on a theoretical biological activity for TSH of 40 IU/mg, JP09 has approximately 90,000 receptors per cell, having a dissociation constant of 1.64 x 10(3) mU/L or 1.47 x 10(-9) mol/L. We have used JP09 to prepare solubilized TSH-Rs which have formed the basis of a binding assay for thyroid-binding inhibiting immunoglobulins in unfractionated sera. We have compared the JP09 assay with the TRAK assay (which is based on solubilized porcine TSH-R) and found a highly positive correlation between the two assays, r = 0.83 P < 0.0001, in 55 sera from patients with autoimmune thyroid disease. JP09 can be adapted to growth in suspension culture, permitting large scale production. The tracer in the assay is bovine [125I]TSH; surprisingly, despite the use of a hTSH-R, hTSH had no effect on the binding of the tracer up to 10(3) mU/L and only a minor effect at 10(4) mU/L.     

Amyloid-β oligomer synaptotoxicity is mimicked by oligomers of the model protein HypF-N

Protein misfolded oligomers are thought to be the primary pathogenic species in many protein deposition diseases. Oligomers by the amyloid-β peptide play a central role in Alzheimer's disease pathogenesis, being implicated in synaptic dysfunction. Here we show that the oligomers formed by a protein that has no link with human disease, namely the N-terminal domain of HypF from Escherichia coli (HypF-N), are also synaptotoxic. HypF-N oligomers were found to (i) colocalize with post-synaptic densities in primary rat hippocampal neurons; (ii) induce impairment of long-term potentiation in rat hippocampal slices; and (iii) impair spatial learning of rats in the Morris Water Maze test. By contrast, the native protein and control nontoxic oligomers had none of such effects. These results raise the importance of using HypF-N oligomers as a valid tool to investigate the pathogenesis of Alzheimer's disease, with advantages over other systems for their stability, reproducibility, and costs. The results also suggest that, in the context of a compromised protein homeostasis resulting from aggregation of the amyloid β peptide, a number of oligomeric species sharing common synaptotoxic activity can arise and cooperate in the pathogenesis of the disease.     

Very late stent thrombosis complicating a previously lost and partially crushed stent: Demonstration by optical coherence tomography

Stent thrombosis (ST) is the most dramatic complication of coronary stenting. Mechanisms of ST are multiple, including procedural and patient-related factors. A considerable burden of metal inside the coronary has been associated with ST as suggested by the higher rate of ST in case of multiple overlapping or complex two stents procedure in bifurcation lesions. However, occasional stent loss and failure to retrieve it may be a substrate of ST, especially if multiple layers of stent struts are incompletely crushed. Here, we describe a case of very late ST on a partially crushed stent previously lost inside the coronary circulation, using optical coherence tomography (OCT) for guidance during the procedure.     

Impact of drug-eluting balloon (pre- or post-) dilation on neointima formation in de novo lesions treated by bare-metal stent: the IN-PACT CORO trial

The efficacy of DEB in modifying the high restenosis risk associated with BMS implantation is doubtful. Optical coherence tomography (OCT) may allow precise assessment of neointimal formation after stent implantation. We performed a single-center, prospective, 1:2 randomized trial comparing BMS implantation alone (BMS group) vs. additional DEB (DEB group). DEB patients were further randomized 1:1 to DEB before stenting (pre-DEB group), or after stenting (post-DEB group). Primary endpoint was OCT-assessed neointimal hyperplasia (expressed both as mean in-stent neointimal area and as percentage obstruction of the mean stent area) at 6 months. Secondary endpoints were the percentage of uncovered and malapposed stent struts. Thirty patients were enrolled and randomized to BMS (n = 10), pre-DEB (n = 10), post-DEB (n = 10). At 6-month OCT follow-up, DEB significantly reduced neointimal area compared with BMS: mean neointimal area 2.01 ± 0.89 vs. 3.03 ± 1.07 mm² (p = 0.02), percentage area obstruction 24.56 ± 12.50 vs. 37.51 ± 12.26 % (p = 0.02). The percentage of uncovered and malapposed stent struts did not differ significantly between BMS and DEB. In the comparison between pre-DEB and post-DEB, no significant difference was observed for both primary and secondary endpoints. In de novo coronary lesions treated with BMS, DEB use could be associated with a mild reduction in neointimal hyperplasia at 6 months; this effect could be unrelated to the timing of DEB dilation (pre- or post-stenting).Clinical Trial Registration Information: http://www.clinicaltrials.gov. Identifier: NCT01057563.     

Endothelin-1 and acute myocardial infarction: a no-reflow mediator after successful percutaneous myocardial revascularization.

AIMS: No-reflow after a primary percutaneous coronary intervention (PCI) is associated with a high incidence of left ventricular (LV) failure and a poor prognosis. Endothelin-1 (ET-1) is a potent endothelium-derived vasoconstrictor peptide and an important modulator of neutrophil function. Elevated systemic ET-1 levels have recently been reported to predict a poor prognosis in patients with acute myocardial infarction (AMI) treated by primary PCI. We aimed to investigate the relationship between systemic ET-1 plasma levels and no-reflow in a group of AMI patients treated by primary PCI. METHODS AND RESULTS: A group of 51 patients (age 59+/-9.9 years, 44 males) with a first AMI, undergoing successful primary or rescue PCI, were included in the study. Angiographic no-reflow was defined as coronary TIMI flow grade < or =2 or TIMI flow 3 with a final myocardial blush grade < or =2. Blood samples were obtained from all patients on admission for ET-1 levels measurement. No reflow was observed in 31 patients (61%). Variables associated with no-reflow at univariate analysis included culprit lesion of the left anterior coronary descending artery (LAD) (67 vs. 29%, P=0.006) and ET-1 plasma levels (3.95+/-0.7 vs. 3.3+/-0.8 pg/mL, P=0.004). At multivariable logistic regression analysis, ET-1 was the only significant predictor of no-reflow (P=0.03) together with LAD as the culprit vessel (P=0.04). CONCLUSION: ET-1 plasma levels predict angiographic no-reflow after successful primary or rescue PCI. These findings suggest that ET-1 antagonists might be beneficial in the management of no-reflow.