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Biomedical subjects

A Pagnamenta

Publications and source records attributed to A Pagnamenta.

16 recordsLinked to original sources
PubMed2003

Single arterial occlusion to locate resistance in patients with pulmonary hypertension.

The purpose of this study was to determine the site of increased resistance using the arterial occlusion technique in patients with severe pulmonary hypertension. Pulmonary vascular resistance was partitioned in arterial and venous components based on double exponential fitting analysis of the pulmonary artery pressure decay curve: after balloon occlusion in 36 patients with pulmonary arterial hypertension (PAH); at baseline and during the inhalation of 20 parts per million of nitric oxide (NO); in four patients with chronic thromboembolic pulmonary hypertension; and in two patients with pulmonary veno-occlusive disease. In the patients with PAH, at baseline, mean pulmonary artery pressure was 56+/-2 mmHg (mean+/-SE), with an arterial component of resistance of 63+/-1%. Inhaled NO did not change the partition of resistance. The arterial component of resistance amounted on average to 42% and 77% in the patients with veno-occlusive disease and the patients with thromboembolic pulmonary hypertension, respectively. However, the partitioning of resistance did not discriminate between these three diagnostic categories. The occlusion technique may help to locate the predominant site of increased resistance in patients with severe pulmonary hypertension, but does not allow for a satisfactory differential diagnosis on an individual basis.

Balloon Occlusion↗
PubMed2001

Extreme length and length variation in the first ribosomal internal transcribed spacer of ladybird beetles (Coleoptera: Coccinellidae).

DNA sequences of the first ribosomal internal transcribed spacer (ITS1) were isolated from 10 ladybird beetle species (Coleoptera: Coccinellidae) representing four subfamilies (Coccinellinae, Chilocorinae, Scymninae, and Coccidulinae). The spacers ranged in length from 791 to 2,572 bp, thereby including one of the longest ITS1s and exhibiting one of the most extreme cases of ITS1 size variation in eukaryotes recorded to date. The causes of length variation were therefore analyzed. Almost no putatively homologous sequence similarities were identified for the taxa included. The only exception was for the subfamily Coccinellinae, which yielded sequence similarities in six regions of approximately 550 nucleotide positions, primarily at the 5' and 3' ends of ITS1. The majority of differences in ITS1 length between taxa could be attributed to the presence of repetitive elements with comparatively long repeat units. Repetition arose several times independently and was confined to the middle of the spacer which, in contrast to the 5' and 3' ends, had not been inferred in previous studies to be subject to functional constraints. These elements were characterized by high rates of evolutionary change, most likely as a result of high substitution rates in combination with inefficient homogenization across repeats. The repeated origin and subsequent divergence of "long" repetitive elements should thus be assumed to be an important factor in the evolution of coccinellid ITS1.

Amino Acid Sequence↗
PubMed2001

Genetic analysis of the connexin-26 M34T variant: identification of genotype M34T/M34T segregating with mild-moderate non-syndromic sensorineural hearing loss.

Mutations in the human gap junction beta-2 gene (GJB2) that encodes connexin-26 have been shown to cause non-syndromic sensorineural hearing loss (NSSNHL) at the DFNB1 locus on 13q11. Functional and genetic data regarding the disease causing potential of one particular GJB2 sequence variant, 101 T-->C (M34T), have proven contradictory. In this study, we found the prevalence of the M34T allele in a cohort of white sib pairs and sporadic cases with NSSNHL from the United Kingdom and Ireland to be 3.179% of chromosomes screened. Significantly, we identified the first M34T/M34T genotype cosegregating in a single family with mid to high frequency NSSNHL. Screening a control population of 630 subjects we identified 25 M34T heterozygotes; however, no M34T homozygotes were detected. Surprisingly, the majority of M34T alleles (88%) were in cis with a 10 bp deletion in the 5' non-coding sequence. This non-coding deletion was also homozygous in the homozygous M34T subjects. Microsatellite analysis of flanking loci in M34T heterozygotes and controls does not define an extensive ancestral haplotype but preliminary data suggest two common alleles in subjects with the M34T allele. In summary, we provide data that support M34T acting as a recessive GJB2 allele associated with mild-moderate prelingual hearing impairment.

Alleles↗
PubMed2000

Continuous versus pulsatile pulmonary hemodynamics in canine oleic acid lung injury.

Pulmonary hypertension occurs commonly in the acute respiratory distress syndrome (ARDS), but associated right ventricular failure is relatively rare. We tested the hypothesis that this apparent contradiction is explained by a peripheral location of the increased pulmonary vascular resistance (Rpva). Experimental ARDS was induced in eight dogs by injection of oleic acid (0.07 ml/kg). Changes in Rpva were evaluated by measurements of pulmonary artery pressure (Ppa) at several levels of flow (Q), which was altered by manipulation of venous return. The analysis of Ppa decay curves after arterial balloon occlusion was used to partition Rpva into arterial and venous segments. Right ventricular afterload was evaluated by determination of pulmonary vascular impedance (Zpva), which was calculated from spectral analysis of Ppa and Q waves. Oleic acid lung injury was associated with an increase in both the slope and the extrapolated pressure intercept of Ppa/Q plots, no change in the partitioning of Rpva, no change in time-domain indices in wave reflection or in pulmonary arterial compliance, and a decrease in both the characteristic impedance and pulsatile component of total right ventricular hydraulic load. We conclude that the site of increased Rpva in oleic acid lung injury is the smallest pulmonary arterioles, which, together with a decreased characteristic impedance, contributes to minimize right ventricular afterload.

Animals↗
PubMed1999

A lack of a functional NAD(P)H:quinone oxidoreductase allele is selectively associated with pediatric leukemias that have MLL fusions. United Kingdom Childhood Cancer Study Investigators.

Rearrangements and fusion of the MLL gene with various alternative partner genes occur in approximately 80% of infant leukemias and are acquired during fetal hemopoiesis in utero. Similar MLL gene recombinants also occur in topoisomerase II-inhibiting drug-induced leukemias. These data have led to the suggestion that some infant leukemia may arise via transplacental fetal exposures during pregnancy to substances that form cleavable complexes with topoisomerase II and induce illegitimate recombination of the MLL gene. A structural feature shared by many topoisomerase II-inhibiting drugs and other chemicals is the quinone moiety. We assayed, by PCR-RFLP, for a polymorphism in an enzyme that detoxifies quinones, NAD(P)H:quinone oxidoreductase (NQO1), in a series (n = 36) of infant leukemias with MLL rearrangements versus unselected cord blood controls (n = 100). MLL-rearranged leukemias were more likely to have genotypes with low NQO1 function (heterozygous CT or homozygous TT at nucleotide 609) than controls (odds ratio, 2.5; P = 0.015). In contrast, no significant allele bias was seen in other groups of pediatric leukemias with TEL-AML1 fusions (n = 50) or hyperdiploidy (n = 29). In the subset of infant leukemias that had MLL-AF4 fusion genes (n = 21), the bias increase in low or null function NQO1 genotypes was more pronounced (odds ratio, 8.12; P = 0.00013). These data support the idea of a novel causal mechanism in infant leukemia involving genotoxic exposure in utero and modulation of impact on a selective target gene by an inherited allele encoding a rate-limiting step in a carcinogen detoxification pathway.

Acute Disease↗
PubMed1999

[Point of view on doping].

Doping is defined as the administration of or use by competing athletes of any substance foreign to the body or of any physiological substance taken in abnormal quantity or taken by an abnormal route of entry into the body with the sole intention of increasing in an artificial and unfair manner his/her performance in competition. The prevalence of doping has been estimated by rigorous methods to be 5-15%. The only two dopings of established efficacy are: anabolic steroids for resistive performance, and blood doping for endurance performance. Although medical control of athletes is reputably poor, reported accidents attributable to doping have been until now very rare. Doping is unfair, and must as such be banned from competitions. Medicalized doping is unethical. More studies are required to improve knowledge of doping as a public health issue. Sports medicine is in need of scientific and moral revalorization.

Anabolic Agents↗
PubMedDate not supplied

Analytic representation of electron central-axis depth dose data.

We have examined a number of analytic representations of electron central-axis depth dose data current in the literature, testing them against sets of standard depth dose data. One of them, a two-parameter model of Shabason and Hendee, is recommended in situations in which good accuracy (approximately 2%) is desired, with the values of the parameters determined by an approximation formula which we have developed elsewhere. For higher accuracy, we have developed a polynomial model which gives, typically, a standard deviation of the fitting polynomial from the data points of 1%, and a maximum deviation of 2%. Fitting polynomials obtained with this method possess the property of having zero slope at the position of actual maximum dose, and generally a fifth-order polynomial (requiring four nonzero coefficients) provided the most acceptable fit. The four parameters involved are determined through inversion of a 4 x 4 matrix, and we have tabulated these four coefficients for the standard data sets. The polynomial model is designed for interpolation in the range between the 100% dose depth and the 10% dose depth, and another fitting curve of the same type can be adjoined to cover depths less than the 100% dose depth.

Computers↗
PubMedDate not supplied

Product representations of teletherapy dose distributions.

Product representations are frequently used for teletherapy dose distributions. For example, the dose in a central plane is often written as the product of two factors, one dependent on the depth and the other on the transverse variable. We have answered the following question: given a (two-dimensional) set of data, how closely is it possible to represent these data by a product of two such factors, and what factors would give a best-fit representation? We thus have developed a quantitative test with which to judge any proposed product representation, for a given set of data. As an example, we have applied our method in analyzing the accuracy of a model proposed by van de Geijn for representing central-plane Cobalt-60 dose data through a product representation on decrement lines intersecting the source.

Humans↗
PubMedDate not supplied

Collimated electron beams and their associated penumbra widths.

The Fermi-Eyges multiple-scattering theory for electrons is applied to calculate profiles of collimated electron beams. The dose profile below the collimator is a convolution of the intensity distribution of the electrons at the level of the collimator and the distribution arising from the propagation of a Gaussian point source from the collimator to the level of the calculation. The electrons at the level of the collimator possess an angular distribution characteristic of the configuration of the electron beam at the vacuum window. Hence, the dose profile and its associated penumbra width can be expressed in terms of the angular moments of the distribution of the electrons at the collimator. The dependence of the penumbra width on the configuration-dependent angular spread of the electrons at the collimator accounts for differences in the size of the penumbra between two broad-beam configurations. These differences are also seen experimentally. We have also studied the dependence of the angular moments of the electrons upon scattering foils present above the collimator and the position of the beam-broadening device in the accelerator head.

Electrons↗
PubMedDate not supplied

Electron dose calculation using multiple-scattering theory: thin planar inhomogeneities.

In this article in our series on electron dose calculation using multiple-scattering theory, we apply the Fermi-Eyges theory to the problem of a thin planar inhomogeneity present in an otherwise-layered medium. We derive expressions for the distribution function P and the location distribution L (which multiplied by the restricted mass collision stopping power is the dose directly deposited by the primary electrons) for various types of incident beams: a completely arbitrary distribution, a Gaussian point source, a pencil beam, an isotropic point source, and a broad parallel beam. We show how divergent-beam dose distributions can be determined from parallel-beam calculations, through use of equivalent configurations dependent upon the depth of dose calculation. Also, we indicate how this work can be applied to the design of wedges (or "compensators") for beam shaping to provide desired dose distributions or to match juxtaposed radiation fields. Explicit formulas for thin plates are then worked out, and we examine the appearance of hot and cold spots distal to the edge of a localized inhomogeneity, for thin half-slabs and for narrow strips. Finally, considering the case of a thin straight wedge-shaped inhomogeneity, we theoretically discover the phenomenon of a "focused hot spot" without an accompanying cold spot, and suggest the design of a "multiple-scattering lens".

Electrons↗