Open lung biopsy in children with respiratory failure

OBJECTIVE: To evaluate benefits and risks of open lung biopsy in children with respiratory failure. DESIGN: Retrospective chart review. SETTING: A 36-bed pediatric critical care unit in a tertiary care, university-based hospital. PATIENTS: We studied 31 patients with respiratory failure who underwent 33 open lung biopsies. MEASUREMENTS AND MAIN RESULTS: The charts of all children in the critical care unit with respiratory failure who underwent an open lung biopsy over a 10-yr period (1989-98) were reviewed. Of 33 open lung biopsies performed, 76% (25 of 33) led to a relevant change in medical management. Complications were seen in 45% of patients, predominantly attributable to airleak (33%) without affecting respiratory function. An infectious agent was detected by open lung biopsy in ten patients; bronchoalveolar lavage performed before open lung biopsy failed to isolate the infection in eight of ten patients. CONCLUSIONS: In children with undiagnosed or persisting respiratory failure, open lung biopsy is a useful diagnostic procedure that leads to significant changes in medical management and increases the diagnostic yield for infections. Despite the relatively high complication rate, open lung biopsy should be performed routinely in this group of patients.     

The F11 receptor (F11R/JAM-A) in atherothrombosis: overexpression of F11R in atherosclerotic plaques

F11R is the gene name for an adhesion protein, called the F11-receptor, aka JAM-A, which under normal physiological conditions is expressed constitutively on the surface of platelets and localized within tight junctions of endothelial cells (EC). Previous studies of the interactions between human platelets and EC suggested that F11R/JAM-A plays a crucial role in inflammatory thrombosis and atherosclerosis. The study reported here obtained in-vivo confirmation of this conclusion by investigating F11R/JAM-A protein and mRNA in patients with aortic and peripheral vascular disease and in an animal model of atherosclerosis. Molecular and immunofluorescence determinations revealed very high levels of F11R/JAM-A mRNA and F11R/JAM-A protein in atherosclerotic plaques of cardiovascular patients. Similar results were obtained with 12-week-old atherosclerosis-prone apoE-/- mice, an age in which atherosclerotic plaques are well established. Enhanced expression of the F11R/JAM-A message in cultured EC from human aortic and venous vessels was observed following exposure of the cells to cytokines. Determinations of platelet adhesion to cultured EC inflamed by combined cytokine treatment in the presence of F11R/JAM-A - antagonists provided data indicating that de novo expression of F11R/JAM-A on the luminal surface of inflamed EC has an important role in the conversion of EC to a thrombogenic surface. Further studies of these interactions under flow conditions and under in-vivo settings could provide a final proof of a causal role for F11R/JAM-A in the initiation of thrombosis. Based on our in-vitro and in-vivo studies to date, we propose that therapeutic drugs which antagonize the function of F11R/JAM-A should be tested as novel means for the prevention and treatment of atherosclerosis, heart attacks and stroke.     

Effects of the calcium antagonist, isradipine, and nifedipine on resting and exercise haemodynamics and the neurohumoral system in patients with stable chronic angina

In a randomized double-blind study, the haemodynamic and anti-ischaemic effects of the new dihydropyridine calcium channel blocker isradipine (5 mg and 10 mg thrice daily (t.i.d.) were investigated over 1 week in nine patients with coronary artery disease and chronic effort angina and compared with nifedipine (20 mg t.i.d.) and placebo. In standardized exercise stress tests and exercise radionuclide ventriculography, haemodynamics improved under medication compared with placebo: resting end-diastolic and end-systolic volume index decreased on isradipine 5 mg, 10 mg and on nifedipine, and ejection fraction at rest increased with all medications. Resting mean arterial pressure was reduced compared with placebo accompanied by a decrease in systemic vascular resistance (P less than 0.05) and systolic wall tension (P less than 0.05). Cumulative ST-segment depression was significantly reduced by all three medications (-48%, -23%, -36%), while the increase in work capacity was insignificant. No significant change was found for either heart rate, double product, cardiac index, or stroke work index. Resting plasma levels of noradrenaline, adrenaline and renin activity increased with all three medications (except adrenaline at isradipine 5 mg). Isradipine has favourable effects comparable with those of nifedipine in patients with chronic stable angina and can be safely administered in these patients.     

Decorrelation of retinal response to natural scenes by fixational eye movements

Under natural viewing conditions the input to the retina is a complex spatiotemporal signal that depends on both the scene and the way the observer moves. It is commonly assumed that the retina processes this input signal efficiently by taking into account the statistics of the natural world. It has recently been argued that incessant microscopic eye movements contribute to this process by decorrelating the input to the retina. Here we tested this theory by measuring the responses of the salamander retina to stimuli replicating the natural input signals experienced by the retina in the presence and absence of fixational eye movements. Contrary to the predictions of classic theories of efficient encoding that do not take behavior into account, we show that the response characteristics of retinal ganglion cells are not sufficient in themselves to disrupt the broad correlations of natural scenes. Specifically, retinal ganglion cells exhibited strong and extensive spatial correlations in the absence of fixational eye movements. However, the levels of correlation in the neural responses dropped in the presence of fixational eye movements, resulting in effective decorrelation of the channels streaming information to the brain. These observations confirm the predictions that microscopic eye movements act to reduce correlations in retinal responses and contribute to visual information processing.Much effort has been devoted to understanding how the neural code of the retina and downstream neurons can represent visual information efficiently given the statistical structure of the natural world (1–6). Although these theories have contributed tremendously to current understanding of early visual processing, they do not consider the observer’s motor activity but rather rely on the simplifying assumption that the input to the retina is a stationary image. However, even during fixation on a single point, small movements of the eye, head, and other parts of the body continually modulate visual input signals. Experiments have shown that elimination of retinal image motion leads to fading of vision (7, 8). Therefore, eye movements are essential for the normal functioning of the visual system.It has been proposed that, rather than simply preventing adaptation in neural responses, fixational eye movements are a critical stage of information processing, in which predictable spatial correlations are discarded to enable encoding of luminance discontinuities by synchronous neural activity (9, 10). Thus, fixational eye movements counterbalance the spectral density of natural scenes and yield temporal modulations with equalized power over a broad range of spatial frequencies. Because spectral equalization is equivalent to decorrelation in space, this theory predicts that fixational eye movements should attenuate correlations in the responses of the retinal ganglion cells. Modeling results have provided support to this hypothesis (9, 10).     

Emergence of late cytomegalovirus central nervous system disease in hematopoietic stem cell transplant recipients

Preemptive ganciclovir therapy has reduced the occurrence of early cytomegalovirus (CMV) disease after hematopoietic stem cell (HSC) transplantation. However, late disease is increasingly reported. We describe 2 patients who developed late CMV central nervous system (CNS) disease after haploidentical HSC transplantation. Direct genotypic analysis was used to examine the presence of ganciclovir resistance. One patient had a mixed viral population in the cerebrospinal fluid (CSF), with coexistent wild-type and mutant UL97 sequences. The presence of 2 different strains was confirmed by subclone sequencing of the UL54 gene. One of the strains was different from the concurrent blood strain. The second patient had resistant variant in the lungs. These cases raise concern about the changing natural history of CMV disease in HSC transplantation, with emergence of previously uncommon manifestations following prolonged prophylaxis. Under these circumstances the CNS may be a sanctuary site, where viral persistence and antiviral drug resistance could result from limited drug penetration.     

Molecular imaging of the skeleton: quantitative real-time bioluminescence monitoring gene expression in bone repair and development.

Monitoring gene expression in vivo, noninvasively, is a critical issue in effective gene therapy systems. To date, there are no adequate molecular imaging techniques, which quantitatively monitor gene expression in vivo in skeletal development and repair. The aim of this study was to monitor gene expression in skeletal development and repair, using a real-time molecular imaging system, which quantitatively and noninvasively detects bioluminescence in vivo. Our experimental model consisted of transgenic mice harboring the luciferase marker gene under the regulation of the human osteocalcin (hOC) promoter. A new light detection cooled charge coupled device (CCCD) camera was applied to monitor luciferase expression. In vitro, mesenchymal stem cells (MSCs) isolated from bone marrow of transgenic mice exhibited hOC promoter regulation, detected by luciferase expression that correlated with their osteogenic differentiation. During development from 1 week to 1.5 years, transgenic mice exhibited transgene expression in a wide spectrum of skeletal organs, including calvaria, vertebra, tail, and limbs, reaching a peak at 1 week in most of the skeletal organs. In two skeletal repair models, bone fracture and marrow ablation, the noninvasive CCCD system revealed a peak of luciferase expression at 6 days postsurgery. All quantitative, noninvasive, real-time CCCD measurements correlated with a luciferase biochemical assay and luciferase immunohistochemistry, which demonstrated luciferase expression in hypertrophic chondrocytes and trabecular osteoblasts. Our studies show for the first time (1) the CCCD detection system is a reliable quantitative gene detection tool for the skeleton in vivo, (2) expression of luciferase regulated by the hOC promoter is significantly decreased with age in most skeletal sites, and (3) the dynamics of hOC regulation during mice skeletal development and repair in real time, quantitatively and noninvasively.     

Brachial-basilic autogenous access

The emphasis on autogenous arteriovenous hemodialysis access has increased the focus on the brachial-basilic autogenous configuration currently recommended by the national guidelines when the cephalic vein is not suitable. The brachial-basilic autogenous access has been extensively studied and compared with both prosthetic (arteriovenous graft [AVG]) and other autogenous accesses. The literature suggests that the brachial-basilic autogenous access is superior to AVGs in terms of patency, reintervention rates, and infectious complications. However, controversy still remains with respect to its role in the treatment algorithm and the technical conduct of the operation. This review will address the ongoing issues and controversies surrounding the brachial-basilic autogenous access and define its role for the hemodialysis access surgeon.     

Acute Aortic Dissection Presenting as Rupture of the Femoral Artery

A 44-year-old male with Marfans disease presented acutely with severe chest and left groin pain. A pulsatile mass was present in the left groin and the left leg was pale and pulseless. CT imaging demonstrated the presence of a distal thoracic aortic dissection (AD) involving the left iliofemoral segment with extravasation of contrast into the left groin. The patient was treated with an urgent femoral-femoral bypass, which repaired the femoral artery and restored perfusion to the left lower extremity. Whereas rupture of the aorta into the chest or pericardium is common, femoral artery rupture complicating AD has not been previously reported. This case illustrates the need for peripheral branch intervention when compromised by the dissection process including isolated iliofemoral segments, which are typically benign. Given frank femoral artery rupture, urgent surgical repair was required and resulted in a satisfactory outcome. Presented at the Annual Meeting of the Southern California Vascular Surgical Society, Carlsbad, CA, April 11-13, 2003.