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PubMed2000

Validation of a precision radiochromic film dosimetry system for quantitative two-dimensional imaging of acute exposure dose distributions.

We present an evaluation of the precision and accuracy of image-based radiochromic film (RCF) dosimetry performed using a commercial RCF product (Gafchromic MD-55-2, Nuclear Associates, Inc.) and a commercial high-spatial resolution (100 microm pixel size) He-Ne scanning-laser film-digitizer (Personal Densitometer, Molecular Dynamics, Inc.) as an optical density (OD) imaging system. The precision and accuracy of this dosimetry system are evaluated by performing RCF imaging dosimetry in well characterized conformal external beam and brachytherapy high dose-rate (HDR) radiation fields. Benchmarking of image-based RCF dosimetry is necessary due to many potential errors inherent to RCF dosimetry including: a temperature-dependent time evolution of RCF dose response; nonuniform response of RCF; and optical-polarization artifacts. In addition, laser-densitometer imaging artifacts can produce systematic OD measurement errors as large as 35% in the presence of high OD gradients. We present a RCF exposure and readout protocol that was developed for the accurate dosimetry of high dose rate (HDR) radiation sources. This protocol follows and expands upon the guidelines set forth by the American Association of Physicists in Medicine (AAPM) Task Group 55 report. Particular attention is focused on the OD imaging system, a scanning-laser film digitizer, modified to eliminate OD artifacts that were not addressed in the AAPM Task Group 55 report. RCF precision using this technique was evaluated with films given uniform 6 MV x-ray doses between 1 and 200 Gy. RCF absolute dose accuracy using this technique was evaluated by comparing RCF measurements to small volume ionization chamber measurements for conformal external-beam sources and an experimentally validated Monte Carlo photon-transport simulation code for a 192Ir brachytherapy source. Pixel-to-pixel standard deviations of uniformly irradiated films were less than 1% for doses between 10 and 150 Gy; between 1% and 5% for lower doses down to 1 Gy and 1% and 1.5% for higher doses up to 200 Gy. Pixel averaging to form 200-800 microm pixels reduces these standard deviations by a factor of 2 to 5. Comparisons of absolute dose show agreement within 1.5%-4% of dose benchmarks, consistent with a highly accurate dosimeter limited by its observed precision and the precision of the dose standards to which it is compared. These results provide a comprehensive benchmarking of RCF, enabling its use in the commissioning of novel HDR therapy sources.

Brachytherapy↗

PubMed2005

Transcriptional interference mediated by retrotransposons within the genome of their host: lessons from alleles of the white gene from Drosophila melanogaster.

Systematic sequencing of model genomes has accelerated our knowledge on genome structure and shown that a large proportion of intergenic regions are made up of mobile element families. Among them, retrotransposons that are mobilized via an RNA intermediate and thus do not excise during their replication cycle are certainly essential factors able to imprint novel and heritable transcriptional regulation within the genome of their host. Today, a crucial complement to the systematic sequencing data is thus to elucidate the potential role of these elements in the regulation of nearby genes, and ultimately in the evolution of eukaryotic genomes.

Animals↗

PubMed2000

[Antiseptic agents: chlorhexidine].

Chlorhexidine is a broad spectrum antiseptic widely used in clinical practice. This antiseptic works rapidly and its effects last for six hours. Since it is not absorbed through the skin nor through mucus, its systematic toxicity is minimum. It keeps on working in contact with organic matter and, since it is transparent, it does not hide the evolution of injuries. In this article, the authors review the properties and indications for this antiseptic; they also comment on some studies having lesser known indications.

Anti-Infective Agents, Local↗

PubMed2000

The malaria cauldron of Southeast Asia: conflicting strategies of contiguous nation states.

The past half-century or so has witnessed dramatic failures but also some successes in control of malaria in the world at large. South and Southeast Asia have had their share of both outcomes, a scenario that reflects many variables in control programs: technology, management strategy, human and financial resources. However, at least equally culpable have been major wars and minor conflicts, economic growth and stagnation, inequity of opportunity, urbanisation, deforestation, changing transport and communications. The history of malaria is thus an integral part of the broader political and economic evolution of the region, as well as the story of the wisdom and unwisdom of malaria specialists. In positive reflection on the latter, systematic organisational effort using standard tools of trade has seen the gradual elimination of major malaria foci from central plain regions of a number of nations in this large region, with residual foci at forested border areas. In many cases there is good evidence of sustainability of elimination in defined areas but the differing success stories reflect in part conflicting strategies in neighboring nation states. On the other hand, physical conflicts, population migration, inequitable economic change, border instability and many other socio-economic variables can be clearly seen to undermine the most ingenuous strategies. Undoubtedly the single most important negative ingredient is the rise and spread of multi-drug resistant falciparum malaria that has its epicenter in Southeast Asia, from which it threatens the world in insidious fashion. Containment of this phenomenon has been the focus of attention for 30 years, more particularly the past decade, and represents the greatest challenge at this time in predicting the continuing impact of malaria globally on human history. So too does the compelling necessity to link malaria control with macro and micro economic planning. This challenge impinges on the sovereignty of individual nations in this region, for they exist in contiguity, so that successful applications of technology require collaborative political determination.

Animals↗

PubMed2006

[Senegalese case of thromboangeitis obliterans or Buerger's disease].

INTRODUCTION: Thromboangeitis obliterans (TAO) is an inflammatory, non atheromatous arteriopathy of smoking young adults. It is diagnosed on an association of non specific criteria that we discuss throughout this case. CASE REPORT AND DISCUSSION: A forty years old tabagical, Senegalese black man, had peripheral destructive lesions preceded by Raynaud phenomenon. He was admitted in our Internal Medicine department in November 2002. Actually this clinical presentation was evolving since 11 years. At that time, hypo aesthesia and ulceration of the fingers led to successive amputations in the leprology centre. The diagnosis of Hansen disease had been suspected but there were no evidence of mycobacterium. At the admission in our service, biological tests showed a moderated non-specific inflammatory syndrome. Ultra sound Doppler and arteriography showed a peripheral arterial stenosis without atheromatous lesions, in favour of TAO. To meet all the criteria the patient didn't have any thrombotic or systemic disease. The evolution was favourable after tobacco weaning. CONCLUSION: TAO can bring to difficulties of diagnosis by its way of presentation. Physicians should practice a systematic vascular screening in case of distal arteriopathy.

Adult↗

PubMedDate not supplied

[The pH of feces in children with acute diarrhea during the first hours of oral rehydration].

We studied 108 children between 3 and 36 months of age with acute diarrhea and dehydration when their diarrhea continued more than 24 hours following initiation of ORT and in whom we measured pH and glucose of stools with strips in all evacuations. According to the average stool pH and glucose in the first six hours, the patients were grouped in pH < or = 5.5 and > 5.5 and a glucose < or = 1+ and > 1+. The pH of stools < or = 5.5 increased significantly (P < or = .0005) in children between > 6-12 hours and by 48 hours, it was similar to those with an initial average pH 6.6 Stool glucose declined considerably between > 12 and 24 hours. Contrary to what we expected to find, children with pH > 5.5 excreted more stools and had a higher ORT intake in the first 24 hours. The systematic studies of pH and glucose of stools did not appear to be useful for children with acute diarrhea who had a satisfactory evolution.

Acute Disease↗

PubMed1988

[Animal pharmacokinetics in the quantitative estimation of clinical pharmacokinetics of antitumor agents].

Animal extrapolation of antitumor drug pharmacokinetics deals with either the determination of equations describing drug disposition or the determination of physiological parameters governing this distribution. Papers on this subjects show the need for numerous animal species to predict quantitative evolution curves and the lack of precision in the obtained results. Practical interest of such studies is limited since the pharmacokinetic parameters are systematically evaluated in man during phase I trials. On the contrary, analysis of the mechanism of drug distribution cannot be performed without interspecies scaling to evaluate physiological parameters which are not measurable in humans.

Animals↗

PubMed1983

[Correlations between coronary and ventricular angiography and the exercise test after myocardial infarction].

The aim of this study to assess the predictive value of exercise stress testing (ET) compared with coronary angiography-left ventriculography (CLV) in 102 patients undergoing physical rehabilitation (PH) after myocardial infarction (MI). The ET was optimised in its performance by the PH and in its interpretation by the selection of the parameters according to the site of MI. In anterior MI, angina (30%) and ischemic ST depression outside the acute period (35%) had little predictive value of multivessel disease which was demonstrated in 40% of cases; on the other hand, ST elevation in the same area as MI (65%) had an 88% predictive value for severe LV impairment which was found in 66% of cases. In inferior MI, ischemic ST depression (75%) more than angina (27%) was of greater predictive value (82%) for multivessel disease which was demonstrated in 59% of cases. The sensitivity was 97% and the specificity 64%; the LAD artery was diseased in 48% of cases. LV function was preserved in 63% of cases, but ET was not useful in the prediction of this parameter. In all cases of MI, the absence of ST changes predicted single vessel disease in 94%; ventricular arrhythmias (5%) stopped the patients reaching a discriminative exercise level but indicated poor LV function. The extreme values of heart rate and double product improved the correlations between ET and CLV. Therefore, ET may provide some of the information of CLV before the usual evolutive criteria and may help avoid this investigation in patients with favourable results, especially with inferior infarction. Although it has no absolute value, systematic ET is justified after MI as it enables the most severe cases to be distinguished from the most benign.

Adult↗

PubMed1996

50 years ago: the Nuremberg Doctors' Tribunal. Part 1: The descent towards medicalised murder.

This series of four parts is an attempt to summarise some aspects of medicine during the Third Reich. Its aim is not to provide a systematic review but to remind us of this darkest chapter in the history of medicine and its consequences. The paper summarises the complex evolution of "race hygiene" during the Third Reich and tries to show how politics were medicalised by this idea. On the basis of "race hygiene", involuntary sterilisation was a first step followed by involuntary euthanasia of (mostly) handicapped psychiatric patients. The know-how acquired during these activities was used in the "Final Solution". It presented a level of medical barbarism only to be exceeded by criminal medical research conducted in some concentration camps.

Eugenics↗

PubMed2001

Systematic esophageal endoscopy screening in patients previously treated for head and neck squamous-cell carcinoma.

BACKGROUND: An attempt was made to improve metachronous oesophageal cancer prognosis through bi-annual systematic esophageal endoscopy screening in patients treated for head and neck cancer. PATIENTS AND METHODS: Bi-annual esophageal endoscopy, without a staining procedure, was performed in 1560 patients from 1987 to 1997. The distribution of previous head and neck cancer was oral cavity (20%), oropharynx (30%), hypopharynx (34%), and larynx (16%). All patients had initial panendoscopic inspection before HNSCC treatment. Esophageal tumors were considered to be second synchronous primaries when discovered within the first six months of initial tumor diagnosis. RESULTS: Fifty metachronous esophageal asymptomatic cancers (42 T1 and 7 in situ carcinomas) were diagnosed by endoscopy. The median time between the HNC and the esophageal carcinoma was 43 months (7-137 months). Metachronous esophageal carcinoma was discovered in 2.6% of patients with oral cavity tumor, 5.7% of patients with oropharynx tumor, 2.3% of patients with hypopharynx tumor, and 1.7% of patients with larynx tumor. Causes of death were: 41.1% related to esophageal tumor with tumor progression, metastatic evolution, or treatment toxicity; 28.9% related to non malignant causes; 26.6% related to a cancer that was not of esophageal origin. CONCLUSIONS: Over a 10-year period, systematic bi-annual esophageal endoscopy uncovered metachronous esophageal tumors in 3.2% of 1560 patients originally treated for head and neck carcinoma, developing in a median time of 47 months. Patients with initial oropharyngeal tumors had a significantly higher risk of metachronous esophageal SCC, compared to the other tumor sites (P < 0.02 with Fisher exact test). Given the elevated death rate not related to the esophageal cancer and the median survival of 16 months, any potential benefit from this time-consuming procedure is debatable.

Adult↗

PubMed1997

Eukaryotic molecular biodiversity: systematic approaches for the assessment of symbiotic associations.

'Biodiversity' addresses the wealth of species that constitute the biosphere. Notwithstanding that they have been regarded as mental constructs in the past, species are really existing entities that form and disappear in the course of evolution. Molecular techniques allow to trace the dynamics of speciation and to determine the relatedness of species and the genetic diversity within populations. These techniques also permit to recognize the incredible diversity of protists: their importance for the global conversion of biomass and energy had been greatly underestimated until recently. Because it is not possible to 'count' all species living on earth, a variety of approaches have been used to estimate global biodiversity. Such estimations are extrapolations of historical trends or of punctual assessments of the biodiversity of selected ecosystems. Therefore, new concepts are required to calculate global biodiversity. Systematic approaches that evaluate small, complex biotopes exhaustively, or that calculate the number of symbionts or parasites on the basis of their potential hosts have already led to a substantial revision of earlier estimations. Here, an evaluation of potential animal hosts for methanogenic archaea and intestinal protists is described that reveals the importance of host taxonomy for the assessments. If molecular techniques can confirm the presumed specificity of symbiotic and parasitic associations a substantial revision of the current assumptions about the biodiversity of such organisms will be necessary.

Animals↗

PubMed2000

Gene family evolution and homology: genomics meets phylogenetics.

With the advent of high-throughput DNA sequencing and whole-genome analysis, it has become clear that the coding portions of the genome are organized hierarchically in gene families and superfamilies. Because the hierarchy of genes, like that of living organisms, reflects an ancient and continuing process of gene duplication and divergence, many of the conceptual and analytical tools used in phylogenetic systematics can and should be used in comparative genomics. Phylogenetic principles and techniques for assessing homology, inferring relationships among genes, and reconstructing evolutionary events provide a powerful way to interpret the ever increasing body of sequence data. In this review, we outline the application of phylogenetic approaches to comparative genomics, beginning with the inference of phylogeny and the assessment of gene orthology and paralogy. We also show how the phylogenetic approach makes possible novel kinds of comparative analysis, including detection of domain shuffling and lateral gene transfer, reconstruction of the evolutionary diversification of gene families, tracing of evolutionary change in protein function at the amino acid level, and prediction of structure-function relationships. A marriage of the principles of phylogenetic systematics with the copious data generated by genomics promises unprecedented insights into the nature of biological organization and the historical processes that created it.

Animals↗

PubMed1991

[Various characteristics of the evolution of endoparasites].

Evolution of parasite--host systems should be treated as a specific kind of co-evolution. Although its course is in accordance with the general rules of organic world evolution, it has some peculiarities. One of them is retardation or acceleration of endoparasites' phylogenesis, as compared with the hosts' one. The second one is different speed of phylogenetic changes of endoparasites belonging to the same systematic group. These changes can be significantly limited, as well. Phylogenetic changes of Euglenida--intestinal parasites of Copepoda--are considerably limited, even in comparison with the scale of changes of such species which begin their parasitic life by infecting Copepoda eggs.

Animals↗

PubMed2006

Designed divergent evolution of enzyme function.

It is generally believed that proteins with promiscuous functions divergently evolved to acquire higher specificity and activity, and that this process was highly dependent on the ability of proteins to alter their functions with a small number of amino acid substitutions (plasticity). The application of this theory of divergent molecular evolution to promiscuous enzymes may allow us to design enzymes with more specificity and higher activity. Many structural and biochemical analyses have identified the active or binding site residues important for functional plasticity (plasticity residues). To understand how these residues contribute to molecular evolution, and thereby formulate a design methodology, plasticity residues were probed in the active site of the promiscuous sesquiterpene synthase gamma-humulene synthase. Identified plasticity residues were systematically recombined based on a mathematical model in order to construct novel terpene synthases, each catalysing the synthesis of one or a few very different sesquiterpenes. Here we present the construction of seven specific and active synthases that use different reaction pathways to produce the specific and very different products. Creation of these enzymes demonstrates the feasibility of exploiting the underlying evolvability of this scaffold, and provides evidence that rational approaches based on these ideas are useful for enzyme design.

Alkyl and Aryl Transferases↗

PubMed2006

Insights into the coupling of duplication events and macroevolution from an age profile of animal transmembrane gene families.

The evolution of new gene families subsequent to gene duplication may be coupled to the fluctuation of population and environment variables. Based upon that, we presented a systematic analysis of the animal transmembrane gene duplication events on a macroevolutionary scale by integrating the palaeontology repository. The age of duplication events was calculated by maximum likelihood method, and the age distribution was estimated by density histogram and normal kernel density estimation. We showed that the density of the duplicates displays a positive correlation with the estimates of maximum number of cell types of common ancestors, and the oxidation events played a key role in the major transitions of this density trace. Next, we focused on the Phanerozoic phase, during which more macroevolution data are available. The pulse mass extinction timepoints coincide with the local peaks of the age distribution, suggesting that the transmembrane gene duplicates fixed frequently when the environment changed dramatically. Moreover, a 61-million-year cycle is the most possible cycle in this phase by spectral analysis, which is consistent with the cycles recently detected in biodiversity. Our data thus elucidate a strong coupling of duplication events and macroevolution; furthermore, our method also provides a new way to address these questions.

Animals↗

PubMed2005

Diversification and independent evolution of troponin C genes in insects.

Troponin C (TpnC), the calcium-binding subunit of the troponin regulatory complex in the muscle thin filament, is encoded by multiple genes in insects. To understand how TpnC genes have evolved, we characterized the gene number and structure in a number of insect species. The TpnC gene complement is five genes in Drosophilidae as previously reported for D. melanogaster. Gene structures are almost identical in D. pseudoobscura, D. suboboscura, and D. virilis. Developmental patterns of expression are also conserved in Drosophila subobscura and D. virilis. Similar, but not completely equivalent, TpnC gene repertoires have been identified in the Anopheles gambiae and Apis mellifera genomes. Insect TpnC sequences can be divided into three groups, allowing a systematic classification of newly identified genes. The pattern of expression of the Apis mellifera genes essentially agrees with the pattern in Drosophilidae, providing further functional support to the classification. A model for the evolution of the TpnC genes is proposed including the most likely pathway of insect TpnC diversification. Our results suggest that the rapid increase in number and sequence specialization of the adult Type III isoforms can be correlated with the evolution of the holometabolous mode of development and the acquisition of asynchronous indirect flight muscle function in insects. This evolutionarily specialization has probably been achieved independently in different insect orders.

Amino Acid Sequence↗

PubMed1986

Renal biopsy in SLE irrespective of clinical findings: long-term follow-up.

We analyzed data from 56 patients with Systemic Lupus Erythematosus (SLE) in whom renal biopsies were done systematically. The data taken into account for the study were: the histologic glomerular lesions at diagnosis, serum creatinine value, degree of proteinuria and qualitative urine sediment analysis at the time of biopsy, patient age at diagnosis and the evolution of renal function until the time the study was made. Therapy was prescribed according to the glomerular histologic lesion. The mean follow-up period from the time of the first biopsy was 8.2 years. At the time of the study, only 3 patients (5.3%) were on dialysis, while the rest of the patients (94.7%) had a satisfactory renal function. Our results indicate that systematic renal biopsy in SLE patients can furnish valuable data concerning the renal status whether there are clinical signs of renal involvement or not. Treatment based on the histologic images alone may considerably improve renal survival in SLE.

Adolescent↗

PubMed2001

Improved measurement of (3)J(H(alpha)(i),N(i+1)) coupling constants in H(2)O dissolved proteins.

A modification to the recently proposed alpha/beta-HN(CO)CA-J TROSY pulse sequence (P. Permi et al., J. Magn. Reson. 146, 255-259 (2000)) makes it possible to determine (3)J(H(alpha)(i), N(i+1)) coupling constants from a single E.COSY-type cross-peak pattern rather than from two (1)H(alpha) spin-state-edited subspectra. Advantages are increased (15)N resolution, critical to extracting accurate (1)H(alpha)-(15)N coupling constants, and minimized differential relaxation due to nested (13)C(alpha) and (15)N evolution periods. Application of the improved pulse sequence to Desulfovibrio vulgaris flavodoxin results in (3)J(H(alpha)(i), N(i+1)) values being systematically larger than those obtained with the original scheme. Parametrization of the coupling dependence on the protein backbone torsion angle psi yields the Karplus relation (3)J(H(alpha)(i), N(i+1))=-1.00 cos(2)(psi-120 degrees )+0.65 cos(psi-120 degrees )-0.15 Hz, with a residual root-mean-square difference of 0.13 Hz between measured and back-calculated coupling constants. The curve compares with data derived from ubiquitin (A. C. Wang and A. Bax, J. Am. Chem. Soc. 117, 1810-1813 (1995)), although spanning a slightly larger range of J values in flavodoxin. The orientation of the Ala39/Ser40 peptide link, forming a type-II beta-turn in flavodoxin, is twisted against X-ray-derived torsions by approximately 10 degrees in the NMR structure as evident from the analysis of straight phi- and psi-related (3)J coupling constants. The remaining deviation of some experimental values from the prediction is likely to be due to strong hydrogen bonding, substituent effects, or the additional dependence on the adjacent torsions straight phi.

Flavodoxin↗