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.     

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.     

Burn depth assessment by dual-wavelength light emitting diodes-excited photoacoustic imaging in rats

Accurate burn depth assessment is crucial to determine treatment plans for burn patients. We have previously proposed a method for performing burn depth assessments based on photoacoustic (PA) imaging, and we have demonstrated the validity of this method, which allows the successful detection of PA signals originating from the blood under the bloodless burned tissue, using rat burn models. Based on these findings, we started a clinical study in which we faced two technical issues: (1) When the burn depth was shallow, PA signals due to skin contamination and/or melanin in the epidermis (surface signals) could not be distinguished from PA signals originating from the blood in the dermis; (2) the size of the system was too large. To solve these issues, we propose a burn depth diagnosis based on dual-wavelength light emitting diodes (LEDs)-excited PA imaging. The use of LEDs rendered the system compact compared to the previous one that used a conventional solid-state laser. We replicated human burned skin by applying a titrated synthetic melanin solution onto the wound surface in albino rat burn models and measured their burn depths by PA excitation at 690 and 850 nm, where melanin and haemoglobin show greatly different absorption coefficients. As a result, the surface signals were eliminated by subtracting the PA signals at 690 nm from those at 850 nm. The resultant estimated burn depths were strongly correlated with the histological assessment results. The validity of the proposed method was also examined using a burn model of rats with real melanin.     

Dynamic particle image velocimetry flow analysis of the flow field immediately downstream of bileaflet mechanical mitral prostheses

New dynamic particle image velocimetry (PIV) technology was applied to the study of the flow field associated with prosthetic heart valves. Four bileaflet prostheses, the St. Jude Medical (SJM) valve, the On-X valve with straight leaflets, the Jyros (JR) valve, and the Edwards MIRA (MIRA) valve with curved leaflets, were tested in the mitral position under pulsatile flow conditions to find the effect of the leaflet shape and overall valve design on the flow field, particularly in terms of the turbulent stress distribution, which may influence hemolysis, platelet activation, and thrombus formation. Comparison of the time-resolved flow fields associated with the opening, accelerating, peak, and closing phases of the diastolic flow revealed the effects of the leaflet shape and overall valve design on the flow field. Anatomically and antianatomically oriented bileaflet valves were also compared in the mitral position to study the effects of the orientation on the downstream flow field. The experimental program used a dynamic PIV system utilizing a high-speed, high-resolution video camera to map the true time-resolved velocity field inside the simulated ventricle. Based on the experimental data, the following general conclusions can be made. High-resolution dynamic PIV can capture true chronological changes in the velocity and turbulence fields. In the vertical measuring plane that passes the centers of both the aortic and mitral valves (A-A section), bileaflet valves show clear and simple circulatory flow patterns when the valve is installed in the antianatomical orientation. The SJM, the On-X, and the MIRA valves maintain a relatively high velocity through the central orifice. The curved leaflets of the JR valve generate higher velocities with a divergent flow during the accelerating and peak flow phases when the valve is installed in the anatomical orientation. In the velocity field directly below the mitral valve and normal to the previous measuring plane (B-B section), where characteristic differences in valve design on the three-dimensional flow should be visible, the symmetrical divergent nature of the flow generated by the two inclined half-disks installed in the antianatomical orientation was evident. The SJM valve, with a central downward flow near the valve, is contrasted with the JR valve, which has a peripherally strong downward circulation with higher turbulent stresses. The On-X valve has a strong central downward flow attributable to its large opening angle and flared inlet shape. The MIRA valve also has a relatively strong downward central flow. The MIRA valve, however, diverts the flow three-dimensionally due to its peripherally curved leaflets.