The effect of carbon dioxide in the airways and alveoli on ventilation; a vagal reflex studied in the dog

1. The inhalation of CO(2) produces a tachypnoea only in the presence of intact vagus nerves; the present study was designed to examine the mechanism of this phenomenon in the dog.2. Closed-chest cardiopulmonary bypass was established in dogs weighing 16-24 kg, anaesthetized with chloralose. When the ;bypass' was established pulmonary blood flow ceased, P(A, CO2) was reduced and the respiratory rate slowed. 3-10% CO(2) in O(2) could then be inhaled without change in the level of P(a, CO2) set at the oxygenator.3. The addition of CO(2) in these concentrations to the inspired oxygen resulted in an increase in respiratory frequency, maximal at the first breath and sustained for the 1 min period of exposure. The increase in respiratory frequency was due to a shortening of expiratory duration. Inspiratory duration did not change. The response was absent after vagotomy.4. Inert gases in O(2), given as a control, had no effect on breathing.5. The effect of raising P(a, CO2) (by increasing the concentration of CO(2) in the gas equilibrating the blood in the oxygenator), was primarily to increase tidal volume.6. The ventilatory effect of inspiring CO(2)/O(2) mixtures was shown to be additive to the effect of raising P(a, CO2).7. These experiments show that an afferent vagal reflex originating from the lungs causes tachypnoea, when a dog, on ;bypass', inhales low concentrations of CO(2) in O(2).     

Three-dimensional modeling of the anatomy of the heart and great vessels

Summary The anatomic constraints imposed on a total artificial heart (TAH) require specific anatomic studies. A thoracic anatomic study was performed with a scanning device equipped with three-dimensional (3-D) reconstruction software on 15 male patients, between the ages of 41 to 63 years (52 ± 6 years). All were candidates for heart transplantation. The 3-D reconstructions of the cardiovascular structures obtained from surgical anatomy data specific to TAH implantation allowed a volumetric measurement of these structures. A modeling diagram of these structures permitted reproducible quantitative measurements of the 35 geometrical parameters which characterized shape, orientation, and position of these structures within the thorax. Most of the measured parameters were characterized by low variability (coefficient of variation from 10 to 25%).

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Modélisation tridimensionnelle de l'anatomie du cur et des gros vaisseaux

Résumé Les contraintes anatomiques imposées au cur artificiel total (CAT) nécessitent des études anatomiques spécifiques. Une étude anatomique thoracique a été réalisée avec un scanner doté d'un logiciel de reconstruction tridimensionnelle (3-D) chez 15 patients, tous de sexe masculin, agés de 41 à 63 ans (52 ± 6 ans), et candidats à une transplantation cardiaque. Les reconstructions 3-D des structures cardio-vasculaires réalisées selon les données de l'anatomie chirurgicale propre à l'implantation du CAT ont permis la mesure volumétrique de ces structures. Un schéma de modélisation de ces structures a permis des mesures quantitatives reproductibles de 35 paramètres géométriques caractéristiques de la forme, de l'orientation, de la position de ces structures dans le thorax. Les résultats de ces mesures ont pu être exprimés en termes statistiques. La plupart des paramètres mesurés étaient caractérisés par une faible variabilité (coefficients de variations de 10 à 25%).

     

How to use Chlamydia antibody testing in subfertility patients

Screening for tubal factor subfertility by means of Chlamydia antibody testing (CAT) was introduced into the initial work-up of subfertile couples several years ago. The results reported, however, are heterogeneous, and no uniformity exists in cut-off levels of titres, or in definitions of tubal factor subfertility. We performed a prospective cohort study to evaluate the implications of varying the definitions of tubal pathology and of modifying the cut-off levels on the clinical impact of CAT in predicting tubal factor subfertility. In 227 consecutive patients who attended our fertility clinic, the Chlamydia IgG antibody titre was determined and related to tuboperitoneal abnormalities at laparoscopy as a reference standard. According to received operating characteristic (ROC) curve analysis, a titre of 16 is the optimum cut-off level. Increasing the cut-off level improves specificity and positive likelihood ratio (LR+), at the expense of sensitivity and negative LR (LR-). Changing the definition of tubal factor subfertility from unspecified tuboperitoneal abnormalities into extensive adhesions and/or bilateral distal tubal occlusion improves LR+, LR- and kappa significantly. We conclude that CAT is more accurate in predicting severe distal tubal pathology than unspecified tuboperitoneal abnormalities. Although from a statistical point of view a titre of 16 is the optimum cut-off level, from a clinical point of view 32 or 64 may be preferable, depending on the aim of screening and the inception cohort.      

Value systems and delinquency: parental and generational discrepancies in value systems for delinquent and non-delinquent boys.

A sample of 82 delinquent boys in two institutions and a matched sample of 82 nondelinquent boys from three secondary schools ranked values from the Rokeach Value Survey in their order of importance for self, mother and father. Order of rankings was counter-balanced. Results indicated that the sets of rankings (value systems) were more discrepant between boys and their parents and between the parents themselves in the delinquent sample than in the non-delinquent sample, but only in regard to the set of terminal values. Marked differences in the relative importance of particular values occurred between the two groups both in relation to rankings for self and for parents, and (for both groups) between the boys and their parents (generational) and between mother and father (parental). Favourability towards father correlated positively with degree of value similarity between sons and fathers but only for the terminal values.     

Alternative splicing of exon 14 determines nuclear or cytoplasmic localisation of fmr1 protein isoforms

Impaired expression of the FMR1 gene is responsible for the fragile X mental retardation syndrome. The FMR1 gene encodes a cytoplasmic protein with RNA-binding properties. Its complex alternative splicing leads to several isoforms, whose abundance and specific functions in the cell are not known. We have cloned in expression vectors, cDNAs corresponding to several isoforms. Western blot comparison of the pattern of endogenous FMR1 proteins with these transfected isoforms allowed the tentative identification of the major endogenous isoform as ISO 7 and of a minor band as an isoform lacking exon 14 sequences (ISO 6 or ISO 12), while some other isoforms (ISO 4, ISO 5) were not expressed at detectable levels. Surprisingly, in immunofluorescence studies, the transfected splice variants that exclude exon 14 sequences (and have alternate C-terminal regions) were shown to be nuclear. Such differential localisation was however not seen in subcellular fractionation studies. Analysis of various deletion mutants suggests the presence of a cytoplasmic retention domain encoded in exon 14 and of a nuclear association domain encoded within the first eight exons that appear however to lack a typical nuclear localisation signal.      

Rapid identification of Candida dubliniensis using a species-specific molecular beacon

Candida dubliniensis is an opportunistic fungal pathogen that has been linked to oral candidiasis in AIDS patients, although it has recently been isolated from other body sites. DNA sequence analysis of the internal transcribed spacer 2 (ITS2) region of rRNA genes from reference Candida strains was used to develop molecular beacon probes for rapid, high-fidelity identification of C. dubliniensis as well as C. albicans. Molecular beacons are small nucleic acid hairpin probes that brightly fluoresce when they are bound to their targets and have a significant advantage over conventional nucleic acid probes because they exhibit a higher degree of specificity with better signal-to-noise ratios. When applied to an unknown collection of 23 strains that largely contained C. albicans and a smaller amount of C. dubliniensis, the species-specific probes were 100% accurate in identifying both species following PCR amplification of the ITS2 region. The results obtained with the molecular beacons were independently verified by random amplified polymorphic DNA analysis-based genotyping and by restriction enzyme analysis with enzymes BsmAI and NspBII, which cleave recognition sequences within the ITS2 regions of C. dubliniensis and C. albicans, respectively. Molecular beacons are promising new probes for the rapid detection of Candida species.     

The architecture of variant surface glycoprotein gene expression sites in Trypanosoma brucei

Trypanosoma brucei evades the immune system by switching between Variant Surface Glycoprotein (VSG) genes. The active VSG gene is transcribed in one of approximately 20 telomeric expression sites (ESs). It has been postulated that ES polymorphism plays a role in host adaptation. To gain more insight into ES architecture, we have determined the complete sequence of Bacterial Artificial Chromosomes (BACs) containing DNA from three ESs and their flanking regions. There was variation in the order and number of ES-associated genes (ESAGs). ESAGs 6 and 7, encoding transferrin receptor subunits, are the only ESAGs with functional copies in every ES that has been sequenced until now. A BAC clone containing the VO2 ES sequences comprised approximately half of a 330 kb 'intermediate' chromosome. The extensive similarity between this intermediate chromosome and the left telomere of T. brucei 927 chromosome I, suggests that this previously uncharacterised intermediate size class of chromosomes could have arisen from breakage of megabase chromosomes. Unexpected conservation of sequences, including pseudogenes, indicates that the multiple ESs could have arisen through a relatively recent amplification of a single ES.     

A de novo translocation t(3;17)(q26.3;q23.1) in a child with Cornelia de Lange syndrome.

A female infant with Cornelia de Lange syndrome and severe limb reduction defects is described. Chromosome analysis showed a de novo translocation with breakpoints at 3q26.3 and 17q23.1. This is the first reported case of a de novo translocation associated with this syndrome.