Pulmonary infiltrates in neutropenic patients with acute leukemia during chemotherapy: outcome and prognostic factors

STUDY OBJECTIVE: To determine predictors of mortality from pulmonary infiltrates in neutropenic patients with acute leukemia during chemotherapy, and the significance of those factors related to the underlying malignancy and its therapy as well as of those related to the severity of the illness associated with pulmonary infiltrates. DESIGN: A historical cohort study. SETTING: A university teaching hospital and tertiary referral center. PATIENTS AND METHODS: Overall, 53 patients with neutropenia during chemotherapy and with first episodes of pulmonary infiltrates during a 4-year period were studied. Prognostic analysis included 38 variables. Multivariate analyses were performed by logistic regression. RESULTS: The survival rate from pneumonia was 57% (30/53). The following eight parameters were significantly associated with death in univariate analysis: comorbidity present; development of "late" pulmonary infiltrates (> or = 14 days after hospital admission); heart rate > or = 100 beats/min; a ratio heart rate/systolic blood pressure (HR/SBP) > or = 1.2; urea nitrogen > 7 mmol/L; radiographic score > or = 3; neutropenia < 1.0x10(9)/L at the treatment end point; and failed complete remission. In a multivariate model including only parameters available at diagnosis of pulmonary infiltrates, the presence of a ratio HR/SBP > or = 1.2 and of a radiographic score > or = 3 remained independently associated with death. In a second model also including the evolutionary parameter neutropenia < or = 1.0x10(9)/L at the treatment end point, both parameters remained significant together with neutropenia <1.0x 10(9)/L at the treatment end point. The presence of a ratio HR/SBP > or = 1.2 was a strong marker of early death. CONCLUSION: Both therapy- and malignancy-associated neutropenia as well as the severity of illness associated with pulmonary infiltrates are independent prognostic factors. Patients with a ratio HR/SBP > or = 1.2 at diagnosis of pulmonary infiltrates suffer from potentially reversible acute illness, are at risk for early death and, therefore, may be appropriate candidates for treatment in an ICU.     

The artificial heart and neuromonitoring? Technical and clinical aspects

There is a steady progress in the development of artificial heart and circulatory assist devices. There is also no doubt that further advances in energy systems, materials, and electronics will provide for smaller and more reliable electrically driven blood pumps, but the present engineering design appears to be adequate to provide devices satisfactory for initial clinical use. Due to problems in the availability of suitable donor hearts, the concept of replacing the natural heart with an artificial heart as a "bridge to transplantation" has gained attention in recent years. The present paper shows technical and clinical aspects of multivariable electrophysiologic neuromonitoring in a patient with an artificial heart assist device in the intensive care unit. The data (EEG, 40 Hz brain oscillations, brainstem auditory- and somatosensory evoked potentials) are discussed with respect to the influence of the artificial heart on their quality and reliability. Reasons for artifacts and problems of interpretation are shown.     

Binding conformation prediction between human acetylcholinesterase and cytochrome c using molecular modeling methods

The acetylcholinesterase (AChE) is important to terminate acetylcholine-mediated neurotransmission at cholinergic synapses. The pivotal role of AChE in apoptosome formation through the interactions with cytochrome c (Cyt c) was demonstrated in recent study. In order to investigate the proper binding conformation between the human AChE (hAChE) and human Cyt c (hCyt c), macro-molecular docking simulation was performed using DOT 2.0 program. The hCyt c was bound to peripheral anionic site (PAS) on hAChE and binding mode of the docked conformation was very similar to the reported crystal structure of the AChE and fasciculin-II (Fas-II) complex. Two 10ns molecular dynamics (MD) simulations were carried out to refine the binding mode of docked structure and to observe the differences of the binding conformations between the absent (Apo) and presence (Holo) of heme group. The key hydrogen bonding residues between hAChE and hCyt c proteins were found in Apo and Holo systems, as well as each Tyr341 and Trp286 residue of hAChE was participated in cation-pi (π) interactions with Lys79 of hCyt c in Apo and Holo systems, respectively. From the present study, although the final structures of the Apo and Holo systems have similar binding pattern, several differences were investigated in flexibilities, interface interactions, and interface accessible surface areas. Based on these results, we were able to predict the reasonable binding conformation which is indispensable for apoptosome formation.     

Dispatching rule for non-identical parallel machines with sequence-dependent setups and quality restrictions

This paper proposes a dispatching rule that guarantees a predetermined minimum quality level for non-identical parallel machines with multiple product types. Manufacturers are focusing on improving the overall quality of their products, as the demand for top quality products is increasing. Such changes increase the possibility of neglecting another crucial factor in manufacturing schedules, namely due date. Traditionally, jobs are dispatched with the focus on meeting due dates. That is, jobs are assigned to machines without consideration of product quality. This approach opens the possibility of manufacturing poor quality products. Realizing the shortcomings of the existing dispatching rules, manufacturers are tempted to dispatch jobs with the objective of maximizing product quality. With such an attempt, jobs are likely to be assigned to high performance machines only. In turn, waiting times will increase and job delays are inevitable. This research proposes a dispatching rule that satisfies both criteria, reducing due date delays, while ensuring a predefined product quality level. A quality index is introduced to standardize various product qualities. The index is used to ensure a predetermined quality level, whilst minimizing product delays. Simulations compare various dispatch methods, evaluating them based on mean tardiness and product quality.     

Intelligent adaptive process control using dynamic deadband for semiconductor manufacturing

This paper proposes an efficient control method to minimize process error and to reduce process variance in semiconductor manufacturing. The photolithography (photo) process forms a complex semiconductor circuit and is important for quality. Obstacles to the process include the facility itself, vibration, wear and tear, product/process changes and environmental influences. Control methodologies being currently used to address these issues often amplify the variation of the process by failing to perform adequate process control. Therefore, this paper proposes an effective process control method to reduce process variance by quickly detecting and identifying process disturbances and accurately reflecting the degree of change to process control. This study proposes dynamic deadband control that uses a region (band) to detect the status of a process change. It adjusts the process control based on the changes detected. In this research, the semiconductor manufacturing company is supported to perform control that is more precise and reduces fluctuations by producing products of uniform quality. In addition, it can contribute to yield due to the quality incentive and increased process control of semiconductor manufacturing.     

Real-time approximation of molecular interaction interfaces based on hierarchical space decomposition

The interaction interface between two molecules can be represented as a bisector surface equidistant from the two sets of spheres of varying radii representing atoms. We recursively divide a box containing both sphere-sets into uniform pairs of sub-boxes. The distance from each new box to each sphere-set is conservatively approximated by an interval, and the number of sphere-box computations is greatly reduced by pre-partitioning each sphere-set using a kd-tree. The subdivision terminates at a specified resolution, creating a box partition (BP) tree. A piecewise linear approximation of the bisector surface is then obtained by traversing the leaves of the BP tree and connecting points equidistant from the sphere-sets. In 124 experiments with up to 16,728 spheres, a bisector surface with a resolution of 1/2⁴ of the original bounding box was obtained in 28.8 ms on average.     

Proteinase activity in the isolates of Trichomonas vaginalis according to their pathogenicity

Ten axenic isolates of Trichomonas vaginalis were subcutaneously injected to the BALB/c mice in order to assess their pathogenicity by means of so-called "mouse assay" method. All the isolates revealed neutral and acid proteinase activities both in their lysates and in culture media, but the specific activities of both proteinases in the severely pathogenic group were significantly higher than the mildly pathogenic group (p < 0.05). In the SDS-PAGE system in which the electrophoretic gels contained 0.4% gelatin as the substrate, five different banding patterns of trichomonal proteinases were detected, and the patterns were closely related with the pathogenicity of the isolates of T. vaginalis. All five bands might be regarded as cysteine proteinases group in the inhibitor assays. The cytotoxicity of the lysates of T. vaginalis to the target Chinese hamster ovarian (CHO) cell line was also significantly different according to the pathogenicity of the isolates, and generally lower in the lysates treated with cysteine proteinase inhibitors than in the control lysates. In summarizing the results, it might be considered that the proteinases of T. vaginalis showing five electrophoretic banding patterns are closely related with the pathogenicity and cytotoxicity of the isolates of T. vaginalis.     

Sequence-based differentiation of strains in the Mycobacterium avium complex

The complete 16S-23S rDNA internal transcribed spacer (ITS) was sequenced in 35 reference strains of the Mycobacterium avium complex. Twelve distinct ITS sequences were obtained, each of which defined a "sequevar"; a sequevar consists of the strain or strains which have a particular sequence. ITS sequences were identified which corresponded to M. avium (16 strains, four ITS sequevars) and Mycobacterium intracellulare (12 strains, one ITS sequevars). The other seven M. avium complex strains had ITS sequences which varied greatly from those of M. avium and M. intracellulare and from each other. The 16S-23S rDNA ITS was much more variable than 16S rDNA, which is widely used for genus and species identification. Phylogenetic trees based on the ITS were compatible with those based on 16S rDNA but were more detailed and had longer branches. The results of ITS sequencing were consistent with the results of hybridization with M. avium and M. intracellulare probes (Gen-Probe) for 30 of 31 strains tested. Serologic testing correlated poorly with ITS sequencing. Strains with the same sequence were different serovars, and those of the same serovar had different sequences. Sequencing of the 16S-23S rDNA ITS should be useful for species and strain differentiation for a wide variety of bacteria and should be applicable to studies of epidemiology, diagnosis, virulence, and taxonomy.     

An Exploratory Study: Supporting Collaborative Multimedia Systems Design

Multimedia systems design generally requires a collaborative effort from a group of designers with a variety of backgrounds and tasks, such as content experts, instructional designers, media specialists, users, and so forth. However, currently available design tools on the market are mainly designed for a single user. Tools intended to support a collaborative design process should coordinate independent activities of individual designers.This research investigated support for work groups engaged in designing multimedia systems. Specifically, it discussed a new collaborative design environment, called the KMS (Knowledge Management System)-based design environment, in which multimedia designers could share their design knowledge freely. Through two experimental groups, the research investigated impacts of the KMS-based design environment on their collaborative design activities (knowledge creating, knowledge securing, knowledge distributing, and knowledge retrieving activities). The research findings showed that the KMS-based design environment was a promising environment for collaborative multimedia systems design. More specifically, the research findings indicated that the KMS-based design environment supported creating, securing, and retrieving knowledge, but it did not support distributing knowledge. In addition, the research found that the social interactions between group members played important roles in the success of the collaborative multimedia systems design and that the KMS-based design environment did not support the socialization of group members. Furthermore, the research found that the inability of the KMS-based design environment to support the socialization was linked to its low performance level in supporting the knowledge distributing activity. The research explored the desired features of a collaborative support tool for multimedia systems design.     

A-IMilano apoprotein. Decreased high density lipoprotein cholesterol levels with significant lipoprotein modifications and without clinical atherosclerosis in an Italian family

Significant hypertriglyceridemia with a very marked decrease of high density lipoproteins (HDL)-cholesterol levels (7-14 mg/dl) was detected in three members (father, son, and daughter) of an Italian family. The three affected individuals did not show any clinical signs of atherosclerosis, nor was the atherosclerotic disease significantly present in the family. Lipoprotein lipase and lecithin:cholesterol acyltransferase activites were normal or slightly reduced. Morphological and compositional studies of HDL in the subjects showed a significant enlargement of the lipoprotein particles (approximately 120 vs. approximately 94 A for control HDL) and a concomitant increase in the triglyceride content. Analytical isoelectric focusing of HDL apoproteins provided evidence for multiple isoproteins in the apoprotein(apo)-A-I range, with nine different bands being detected instead of the usual four bands observed in normal subjects. Two-dimensional immunoelectrophoresis against apo-A antiserum indicated a clear reduction of apo-A in the alpha electrophoretic region, with splitting of the protein "peak." The observation in otherwise clinically healthy subjects of hypertriglyceridemia, reduced HDL-cholesterol, and marked apoprotein abnormalities, without a significant incidence of atherosclerotic disease in the family suggests this is a new disease entity in the field of lipoprotein pathology, very probably related to an altered amino acid composition of the apo-A-I protein (see Weisgraber et al. 1980. J. Clin. Invest. 66: 901-907).