Medical challenges of internal conflicts

The most prevalent menace since the end of the cold war is the occurrence of civil wars and local and regional conflicts. The term "low intensity conflict" describes the new threat environment and covers a multitude of phenomena, such as civil wars, guerrilla warfare, terrorism and counterinsurgency operations occurring between routine, peaceful inter- or intrastate competition, and a sustained conventional conflict. There is a great challenge to alert the physicians in general, and the surgical community of the world in particular, to the new threat environment and the medical challenges involved in treating casualties of low intensity conflicts. Specifically, a new international body of surgeons might be required to coordinate the recruitment, training, and creditation for surgeons with special expertise in the management of victims of such conflicts and to facilitate research and general knowledge of the medical challenges of modern conflicts.     

Spatiotemporal imaging of human brain activity using functional MRI constrained magnetoencephalography data: Monte Carlo simulations

The goal of our research is to develop an experimental and analytical framework for spatiotemporal imaging of human brain function. Preliminary studies suggest that noninvasive spatiotemporal maps of cerebral activity can be produced by combining the high spatial resolution (millimeters) of functional MRI (fMRI) with the high temporal resolution (milliseconds) of electroencephalography (EEG) and magnetoencephalography (MEG). Although MEG and EEG are sensitive to millisecond changes in mental activity, the ability to resolve source localization and timing is limited by the ill-posed "inverse" problem. We conducted Monte Carlo simulations to evaluate the use of MRI constraints in a linear estimation inverse procedure, where fMRI weighting, cortical location and orientation, and sensor noise statistics were realistically incorporated. An error metric was computed to quantify the effects of fMRI invisible ("missing") sources, "extra" fMRI sources, and cortical orientation errors. Our simulation results demonstrate that prior anatomical and functional information from MRI can be used to regularize the EEG/MEG inverse problem, giving an improved solution with high spatial and temporal resolution. An fMRI weighting of approximately 90% was determined to provide the best compromise between separation of activity from correctly localized sources and minimization of error caused by missing sources. The accuracy of the estimate was relatively independent of the number and extent of the sources, allowing for incorporation of physiologically realistic multiple distributed sources. This linear estimation method provides an operator-independent approach for combining information from fMRI, MEG, and EEG and represents a significant advance over traditional dipole modeling.     

Ultrarapid metabolizers of debrisoquine: characterization and PCR-based detection of alleles with duplication of the CYP2D6 gene

During a six-month period 2,221 haemocultures obtained from patients hospitalized in the Faculty Hospital Olomouc were examined. In all 304 isolated bacteria the sensitivity was assessed by the standard dilution micromethod and moreover all positive haemocultures were examined the "direct" disc method. Agreement between the results of the two methods was proved in 84% of pairs of tests and within a range from 67 to 100%, depending on the type of antimicrobial preparation. Based on these findings it may be stated that assessment of the sensitivity by the "direct" method agrees significantly with assessment of the sensitivity according to minimal inhibitory concentrations (MIC). In patients with septicaemia this procedure makes it possible to change empirical antibiotherapy by 24 hours sooner to aimed therapy.     

In vitro growth and drug sensitivity of tumor colony-forming units from human tumor xenografts

To investigate the feasibility of using tissue obtained from human tumor xenografts for in vitro screening of antineoplastic agents, we grew human tumor colony-forming units (CFU) in semisold agar from xenografts serially passaged in nude mice. Growth of human tumor CFU was accomplished from nine xenografts representing five different histological tumor types (ovarian carcinoma, adenocarcinoma of the colon, malignant melanoma, epidermoid carcinoma of the lung, and malignant astrocytoma). Cloning efficiency ranged from 0.04 to 0.1% and showed significant variability both between tumor types and between individual animals bearing the same type of xenograft. A high percentage of tumor CFU was in S phase [47 +/- 20% (S.D.)] as determined by the thymidine "suicide" technique. The number of tumor CFU observed increased linearly with increasing numbers of cells plated. In vitro drug sensitivity of the tumor CFU was assessed to Adriamycin, cis-platinum, and melphalan. The patterns of drug sensitivity were found to be reproducible and stable over a period of 9 months. Drug sensitivity curves to Adriamycin for five xenografts representing four tumor types showed complex patterns with plateau portions similar to those described for tumor CFU from primary tumors. The rank order of sensitivity of the tumors was compared to that of normal granulocyte-macrophage progenitors and, with the exception of the melanomas, was found to correlate well with clinical experience (order of sensitivity = colon less than ovary less than bone marrow). Growth of human tumor CFU from xenografts represents a reproducible and stable means for the study of the biology of tumor CFU and has potential applications as a means for screening new anticancer agents.     

Propagation dynamics of ultra-short high-power laser pulses in air: supercontinuum generation and transverse ring formation

Numerical and semi-analytical results of the propagation of high-power ultra-short near IR laser pulses propagating in ionizing air are presented.     

Growth rate characteristics of acoustic neuromas associated with neurofibromatosis type 2

Neurofibromatosis type 2 (NF2) is a dominantly inherited disorder characterized by the occurrence of bilateral acoustic neuromas (ANs and other central nervous system tumors. Magnetic resonance images and audiologic data on 22 patients with NF2 who underwent multiple studies at the National Institutes of Health between 1983 and 1993 were reviewed to determine the growth characteristics of ANs in these patients. The average growth rate of ANs in NF2 patients was 0.30 cm3 per year and was significantly higher in older patients (0.75 cm3 per year) than in younger ones (0.12 cm3 per year). Larger ANs were more commonly found in patients with concomitant spinal tumors or meningiomas. NF2 patients with spinal tumors but not meningiomas demonstrated faster growth rates than patients without additional tumor burden. The data from this study suggest that older patients or patients with associated spinal tumors have faster growing ANs and therefore should be followed closely and treated aggressively.     

New protein genetic studies in six Amazonian Indian populations

A total of 732 individuals affiliated with six Amazonian Indian populations were variously studied in relation to 26 protein genetic systems. Eleven of them were found to be monomorphic in these groups, in accordance with previous investigations. Similarities and dissimilarities (the latter involving the Rh, Duffy, haptoglobin and transferrin systems) were observed in relation to earlier investigations in four of these populations (Galibi, Palikour, Mundurucu and Tenharim). A dimeric, cathodal variant of albumin was found among two Galibi subjects, and the fairly common occurrence of CP* ACAY among some South American Indian populations was confirmed. The results in the six populations were compared with those from 29 others. When relationships are searched for among tribes of the same linguistic group, the factor that seems to be most influential is geographical localization, an exception being the pattern observed among the Cayapo subgroups. The latter shows genetic differences of the same level of magnitude as those observed among Ge-speaking tribes.     

Cleavage motifs of the yeast 20S proteasome beta subunits deduced from digests of enolase 1

The 436-amino acid protein enolase 1 from yeast was degraded in vitro by purified wild-type and mutant yeast 20S proteasome particles. Analysis of the cleavage products at different times revealed a processive degradation mechanism and a length distribution of fragments ranging from 3 to 25 amino acids with an average length of 7 to 8 amino acids. Surprisingly, the average fragment length was very similar between wild-type and mutant 20S proteasomes with reduced numbers of active sites. This implies that the fragment length is not influenced by the distance between the active sites, as previously postulated. A detailed analysis of the cleavages also allowed the identification of certain amino acid characteristics in positions flanking the cleavage site that guide the selection of the P1 residues by the three active beta subunits. Because yeast and mammalian proteasomes are highly homologous, similar cleavage motifs might be used by mammalian proteasomes. Therefore, our data provide a basis for predicting proteasomal degradation products from which peptides are sampled by major histocompatibility complex class I molecules for presentation to cytotoxic T cells.