Use of monoclonal antibodies to identify cerebrospinal fluid lymphoblasts in children with acute lymphoblastic leukemia

The identification of small numbers of leukemic cells in the cerebrospinal fluid (CSF) presents a diagnostic problem in the treatment of children with acute lymphoblastic leukemia (ALL). We adapted a latex sphere rosetting technique to allow us to identify simultaneously cell surface markers and cell morphology in 199 CSF samples from 34 patients and 14 control subjects. In patients without leukemic meningitis, the majority of CSF lymphocytes (69%) were found to be mature T cells positive for OKT11. A much smaller number of cells (8%) were found to be B cells positive for la. In these children, only 3% of CSF lymphoid cells expressed the common acute lymphoblastic leukemia antigen (CALLA). Similar results were found in the control subjects. By contrast, 28 CSF samples from nine children with varying numbers of CSF lymphoblasts had much greater proportions of CALLA- and la-positive CSF cells (24% to 96%). Leukemic meningitis was present in one of these patients and later developed in four others. However, three patients with small numbers of lymphoblasts present but with low proportions of CALLA-positive CSF cells (less than 5%) subsequently had normal CSF examinations. We found the use of this rosetting technique valuable in providing information complementary to that obtained from cell morphology alone about the possible malignant nature of small numbers of lymphoblast-like CSF cells seen on cytocentrifuge preparations in children with ALL.     

Optical imaging and electrophysiology of rat barrel cortex. I. Responses to small single-vibrissa deflections

A study was undertaken to investigate the response of the rodent somatosensory barrel cortex to single-whisker, near-threshold vibrissal stimuli. Cortical responses to controlled whisker deflections were recorded by (i) conventional multi-unit extracellular recording within the cytochrome oxidase rich barrels centers and the interbarrel septa, and (ii) intrinsic signal optical imaging, a technique that provides a spatial view of cortical activation thought to be related to the deoxygenation of hemoglobin in activated areas. Barrel cortex neurons responded weakly to whisker deflections of 0.04 degrees. Their response to a series of small stimuli of increasing amplitude was well-fitted by a logarithmic function. Responses to larger stimuli declined monotonically with distance from the center of the barrel column, and were characterized by greater onset and offset firing rates, by greater post-excitatory reduction of firing to below spontaneous levels, and by shorter response latency. In comparison to measurements taken previously from primary vibrissal afferent fibers, we conclude that cortical cells can respond to activity in a very small fraction of first-order sensory neurons.      

Ultrasound of the whole breast utilizing a dedicated automated breast scanner

Innovations in design of a dedicated breast scanner resulted in automation of the scanning process, the production of high resolution images of the whole breast and an efficient mode of image review. The results of clinical evaluation of the prototype of this breast scanner investigating normal breasts as well as benign and malignant breast lesions are presented.     

Randomized And Parallel Algorithms For Distance Matrix Calculations In Multiple Sequence Alignment

Multiple sequence alignment (MSA) is a vital problem in biology. Optimal alignment of multiple sequences becomes impractical even for a modest number of sequences [1] since the general version of the problem is NP-hard. Because of the high time complexity of traditional MSA algorithms, even today's fast computers are not able to solve the problem for large number of sequences. In this paper we present a randomized algorithm to calculate distance matrices, which is a major step in many multiple sequence alignment algorithms. The basic idea employed is sampling (along the lines of [2]). We also illustrate how to parallelize this algorithm. In Section 1 we introduce the problem of multiple sequence alignments. In Section 2 we provide a discussion on various methods that have been employed in the literature for Multiple Sequence Alignment. In this section we also introduce our new sampling approach. We extend our randomized algorithm to the case of non-uniform length sequences as well. We show that our algorithms are amenable to parallelism in Section 3. In Section 4 we back up our claim of speedup and accuracy with empirical data and examples. In Section 5 we provide some concluding remarks.     

Nonanatomical mitral valve replacement in the pulmonary venous confluence for heavily calcified aortic or mitral annulus

Mitral valve replacement surgery after previous aortic valve surgery can be extremely challenging. The presence of heavy calcification and scarring in the aortic and/or mitral annulus can make suture placement nearly impossible. Although novel techniques have been described, even these alternatives might not be feasible. We present a case of nonanatomical mitral valve replacement in the pulmonary venous confluence as a salvage operation. This can provide adequate hemodynamics and survival until a subsequent care plan can be established.     

Management of Moderate Functional Tricuspid Valve Regurgitation at the Time of Pulmonary Valve Replacement: Is Concomitant Tricuspid Valve Repair Necessary?

Congenital heart defects with a component of pulmonary stenosis are often palliated in childhood by disrupting the pulmonary valve. Patients often undergo subsequent pulmonary valve replacement (PVR) to protect the heart from the consequences of pulmonary regurgitation. In the presence of associated moderate functional tricuspid valve (TV) regurgitation, it is unclear what factors contribute to persistent TV regurgitation following PVR. In particular, it is unknown whether PVR alone will reduce the right ventricular (RV) size and restore TV function or whether concomitant TV annuloplasty is required as well. Thirty-five patients were analyzed. Each patient underwent initial palliation of congenital pulmonary stenosis or tetralogy of Fallot, underwent subsequent PVR between 2002 and 2008, and had at least moderate TV regurgitation at the time of valve replacement. Serial echocardiograms were analyzed. Pulmonary and TV regurgitation, along with RV dilation and dysfunction, were scored (0, none; 1, mild; 2, moderate; 3, severe). RV volume and area were also calculated. Potential risk factors for persistent postoperative TV regurgitation were evaluated. One month following PVR, there was a significant reduction in pulmonary valve regurgitation (mean, 3 vs. 0.39; P < 0.0001) and TV regurgitation (mean, 2.33 vs. 1.3; P < 0.0001). There were also significant reductions in RV dilation, volume, and area. There were no significant further improvements in any of the parameters at 1 and 3 years. There was no difference in the degree of TV regurgitation postoperatively between those patients who underwent PVR alone and those who underwent concomitant tricuspid annuloplasty (mean, 1.29 vs. 1.31; P = 0.81). We conclude that following PVR, improvement in TV regurgitation and RV size occurs primarily in the first postoperative month. TV function improved to a similar degree with or without annuloplasty.     

Successful treatment of severe subcutaneous insulin resistance with inhaled insulin therapy

van Alfen‐van der Velden AAEM, Noordam C, de Galan BE, Hoorweg‐Nijman JJG, Voorhoeve PG, Westerlaken C. Successful treatment of severe subcutaneous insulin resistance with inhaled insulin therapy. The potential of inhaled insulin therapy for severe resistance to subcutaneous insulin was tested in a 7‐yr old boy with type 1 diabetes mellitus. The efficiency of 1 mg inhaled insulin (Exubera^®) was examined by a 4‐h euglycemic clamp study. During the clamp, the glucose infusion rate started to increase 25 min after inhalation and peaked 120 min after inhalation. Subsequently, a trial of inhaled insulin monotherapy was initiated consisting of pre‐meal inhalations and one inhalation during the night. Since glycemic control remained fair (HbA1c ～8.5%), this therapy was continued. Over the ensuing 18 months, mild keto‐acidosis occurred twice during gastro‐enteritis. Inhaled insulin was well tolerated and pulmonary function did not deteriorate. We conclude that severe resistance to subcutaneous insulin does not preclude sufficient absorption of insulin delivered by pulmonary.