are there some things at stake in Lyotardian thought for feminist theorizations?

Elektronische Version der gedr. Ausg. 199

Genomic and dental investigations of individuals and families with non-syndromic cleft lip and/ or cleft palate, Van der Woude and popliteal pterygium syndromes

Van der Woude syndrome (VWS) is the most common oral cleft syndrome, accounting for two percent of all cleft lip and/or cleft palate (CL/P) cases. The main characteristics of VWS are lip pits (LP), cleft lip (CL), cleft lip and palate (CLP), cleft palate (CP) and/or hypodontia (H). Popliteal pterygium syndrome (PPS) has the same orofacial characteristics as VWS, combined with systemic anomalies. In 2002, the gene responsible for VWS/ PPS was found to be the interferon regulatory factor 6 gene (IRF6), located on chromosome 1, regio q32.2 The gene encodes for a transcription factor containing both a DNA binding domain and a protein binding domain. Non-syndromic (NS) cleft lip with or without cleft palate (CL±P) occurs without associated malformations in any other organs in approximately 70% of the affected subjects. The inheritance pattern for NSCL/P is complex, with a probable co-segregation of several genes and environmental factors. The IRF6 gene has been proposed to be part of the cause of NSCL/P. The aim of this thesis was to investigate individuals and families, mostly of Swedish and Finnish origin, with NSCL/P, VWS and PPS, with regard to their phenotypes, including dental anomalies, to detect mutations of the IRF6 gene in the syndromic cases and to investigate whether the IRF6 gene is responsible for the cleft phenotype in the nonsyndromic individuals. In Study I, 129 individuals affected with NS unilateral (U) CL±P were analysed for dental characteristics. Malformed lateral incisors were common in NSUCL, while hypodontia was more common in the NSUCLP phenotype. In the total material, hypodontia was found in 29.5% inside and in 15.5% outside the region of the cleft. Most of the existing lateral incisors were positioned distal to the cleft in both the primary and the permanent dentition. Study II revealed IRF6 gene mutation in 59% of the 17 VWS/ PPS families studied using direct sequencing of all exons of the gene. In Study III, the IRF6 gene was investigated in 17 Swedish NSCL/P families, using direct sequencing of the gene, in one affected and one healthy individual of each family. We could not detect any mutation in the protein-coding region of the gene. However, two noncoding SNPs – rs861019, a non-coding polymorphism in exon 2, and rs7552506, located in intron 3 – showed an association with the NSCLP phenotype. In Study IV, we tested two SNPs of IRF6, rs642961 in the promoter and rs2235371 in exon 7 (Val274Ile), for association with our entire sample set of NSCL/P, VWS and PPS families (119 families). In all but the Finnish VWS/ PPS families, the “A” allele of rs642961 was identified as a risk allele; transmission to an affected child occurred in a large majority on the same chromosome as the detected IRF6 mutation. The SNP rs642961, located in the AP-2a binding site in the promoter of the IRF6 gene, has previously been shown to be associated with NSCL±P but our results do not support this. However, we did find a significant risk (p=0.013) for transmission of the G-C haplotype (rs642961-rs2235371) to affected individuals in the NSCP subgroup of Swedish families. Of the 16 VWS/ PPS families found to have a mutation in IRF6 (Studies II and IV), 31% had a de novo mutation, that is, a mutation occurring in the proband only and not in the healthy parents. To conclude, NSCL/P is a complex anomaly, where disturbed dental development is a frequent finding. NSCL/P is not dependent on a single gene, as in Mendelian inherited VWS. Dividing our material into sub-phenotypes resulted in rather small groups, but we did find a significant risk with a haplotype of IRF6 in the NSCP group, and also an association for two SNPs of the IRF6 gene with NSCLP. Our results on NSCL/P emphasize the need for additional evaluation of the IRF6 gene and other genes/modifiers, to further clarify their roles in the development of the NSCL/P phenotype

Effect of exercise-induced arterial hypoxemia on quadriceps muscle fatigue in healthy humans

The effect of exercise-induced arterial hypoxemia (EIAH) on quadriceps muscle fatigue was assessed in 11 male endurance-trained subjects [peak O2 uptake (V̇o2 peak) = 56.4 ± 2.8 ml·kg−1·min−1; mean ± SE]. Subjects exercised on a cycle ergometer at ≥90% V̇o2 peak to exhaustion (13.2 ± 0.8 min), during which time arterial O2 saturation (SaO2) fell from 97.7 ± 0.1% at rest to 91.9 ± 0.9% (range 84–94%) at end exercise, primarily because of changes in blood pH (7.183 ± 0.017) and body temperature (38.9 ± 0.2°C). On a separate occasion, subjects repeated the exercise, for the same duration and at the same power output as before, but breathed gas mixtures [inspired O2 fraction (FiO2) = 0.25–0.31] that prevented EIAH (SaO2 = 97–99%). Quadriceps muscle fatigue was assessed via supramaximal paired magnetic stimuli of the femoral nerve (1–100 Hz). Immediately after exercise at FiO2 0.21, the mean force response across 1–100 Hz decreased 33 ± 5% compared with only 15 ± 5% when EIAH was prevented (P < 0.05). In a subgroup of four less fit subjects, who showed minimal EIAH at FiO2 0.21 (SaO2 = 95.3 ± 0.7%), the decrease in evoked force was exacerbated by 35% (P < 0.05) in response to further desaturation induced via FiO2 0.17 (SaO2 = 87.8 ± 0.5%) for the same duration and intensity of exercise. We conclude that the arterial O2 desaturation that occurs in fit subjects during high-intensity exercise in normoxia (−6 ± 1% ΔSaO2 from rest) contributes significantly toward quadriceps muscle fatigue via a peripheral mechanism

Twin-twin transfusion syndrome (TTTS) : outcomes with special reference to cardiovascular function

Background Fetal environment has become a subject for increasing interest when studying health and disease in adults. Monozygous (MZ) twins, especially gestations complicated with twin - twin transfusion syndrome (TTTS), offer a unique opportunity to study adverse developmental programming of the cardiovascular system. TTTS affects about 10% of pregnancies with a common placenta because of unbalanced blood flow across deep arteriovenous connecting vessels . The d ivergent hemodynamic load s of the donor and the recipie nt fetus often result in myocardial hypertrophy of the recipient heart. The aims of this thesis were to evaluate intrauterine environmental contributions to vascular functions in twins with discordant birth weight (Paper I), to study long term effects of TTTS on cardiac structure and function (Paper II and IV) and to determine infant survival and neonatal outcome after fetoscopic laser coagulation therapy of TTTS in Sweden (Paper III). Methods and Results An observational study of 31 twin - pairs, mean age 8 years, with discordant weight at birth, showed that systolic blood pressure (SBP) was higher and endothelial function lower in the at birth smaller twin. In MZ twins with a history of TTTS (n= 9 pairs), there was no significant difference in SBP, but do nor twins had narrower carotid arteries than recipient twins and carotid strain was higher (Paper I). Echocardiography of 11 TTTS twin - pairs, mean age 9.6 years, prenatally treated with amnioreductions, showed no difference in cardiac structure but recip ients had significantly lower diastolic ventricular filling compared with donors (Paper II). When examining a laser treated cohort of 19 TTTS twin - pairs, mean age 4.5 years, and 19 age - matched singleton controls, we found signs of a minor decrease in early diast olic ventricular filling in recipients compared with donors, but no difference s in heart function or structure compared with controls (Paper IV). From a hospital - based register of the first Swedish cohort of laser treated TTTS pregnancies (n = 71), we found that overall survival from treatment to one - year of age was 46%, and that in 61% of gestations, at least one twin survived infancy. Mean gestational age at birth was 30 weeks and mechanical ventilation was needed in 46% of live born twins (Paper III). Conclusions Exposure to fetal growth retardation may contribute to higher blood pressure , arterial narrowing and endothelial dysfunction in childhood (Paper I). Fetal and infant survival after fetoscopic laser coagulation of TTTS is still l imited . I f very preterm delivery is necessary, the neonatal team has to prepare for taking care of two high risk neonates mostly requiring respiratory support (Paper III). Despite different and severe fetal cardiac loading conditions, our long - term follow - up studie s of twins surviving TTTS showed an overall cardiac structure and function within normal range. The signs of reduced diastolic function found in the group treated with amnioreductions (Paper II) were less pronounced in the laser treated cohort (Paper IV). These observations indicate that the cardiac morbidity caused by TTTS resolves in childhood. This has important implications as clinical decision making in TTTS frequently involves choosing between accepting increased fetal cardiac morbidity in the recipi ent twin and delivery of two very preterm babies

The effect of aerial haze on the contrast and resolution of a photographic image in direct application to a low-altitude, remote, pilotless imaging system

A study of the effect of aerial haze on photographic images acquired through the use of a remotely-piloted imaging system has been completed. The project involved the design, construction, and implementation of a remotely-controlled airborne imaging system for the express purpose of collecting scientific data relating the contrast of an image to the altitude at which that image was exposed. Data was collected and analyzed and the results are presented here. The system was also evaluated with respect to its usefulness as a collector of scientific data. The conclusion drawn is that aerial haze had no effect on the contrast of an image at low altitudes (below 1000 feet) for the conditions under which the data was collected

Effect of acute severe hypoxia on peripheral fatigue and endurance capacity in healthy humans

Effect of acute severe hypoxia on peripheral fatigue and endurance capacity in healthy humans. Am J Physiol Regul Integr Comp Physiol 292: R598–R606, 2007. First published September 7, 2006; doi:10.1152/ajpregu.00269.2006.—We hypothesized that severe hypoxia limits exercise performance via decreased contractility of limb locomotor muscles. Nine male subjects [mean SE maximum O2 uptake (V˙ O2 max) 56.5 2.7 ml kg 1 min 1] cycled at 90% V˙ O2 max to exhaustion in normoxia [NORM-EXH; inspired O2 fraction (FIO2) 0.21, arterial O2 saturation (SpO2) 93 1%] and hypoxia (HYPOX-EXH; FIO2 0.13, SpO2 76 1%). The subjects also exercised in normoxia for a time equal to that achieved in hypoxia (NORM-CTRL; SpO2 96 1%). Quadriceps twitch force, in response to supramaximal single (nonpotentiated and potentiated 1 Hz) and paired magnetic stimuli of the femoral nerve (10–100 Hz), was assessed pre- and at 2.5, 35, and 70 min postexercise. Hypoxia exacerbated exercise-induced peripheral fatigue, as evidenced by a greater decrease in potentiated twitch force in HYPOX-EXH vs. NORM-CTRL ( 39 4 vs. 24 3%, P 0.01). Time to exhaustion was reduced by more than two-thirds in HYPOX-EXH vs. NORM-EXH (4.2 0.5 vs. 13.4 0.8 min, P 0.01); however, peripheral fatigue was not different in HYPOX-EXH vs. NORM-EXH ( 34 4 vs. 39 4%, P 0.05). Blood lactate concentration and perceptions of limb discomfort were higher throughout HYPOX-EXH vs. NORM-CTRL but were not different at end-exercise in HYPOX-EXH vs. NORM-EXH. We conclude that severe hypoxia exacerbates peripheral fatigue of limb locomotor muscles and that this effect may contribute, in part, to the early termination of exercise

Effects of arterial oxygen content on peripheral locomotor muscle fatigue

The effect of arterial O2 content (Ca(O2)) on quadriceps fatigue was assessed in healthy, trained male athletes. On separate days, eight participants completed three constant-workload trials on a bicycle ergometer at fixed workloads (314 +/- 13 W). The first trial was performed while the subjects breathed a hypoxic gas mixture [inspired O2 fraction (Fi(O2)) = 0.15, Hb saturation = 81.6%, Ca(O2) = 18.2 ml O2/dl blood; Hypo] until exhaustion (4.5 +/- 0.4 min). The remaining two trials were randomized and time matched with Hypo. The second and third trials were performed while the subjects breathed a normoxic (Fi(O2) = 0.21, Hb saturation = 95.0%, Ca(O2) = 21.3 ml O2/dl blood; Norm) and a hyperoxic (Fi(O2) = 1.0, Hb saturation = 100%, Ca(O2) = 23.8 ml O2/dl blood; Hyper) gas mixture, respectively. Quadriceps muscle fatigue was assessed via magnetic femoral nerve stimulation (1-100 Hz) before and 2.5 min after exercise. Myoelectrical activity of the vastus lateralis was obtained from surface electrodes throughout exercise. Immediately after exercise, the mean force response across 1-100 Hz decreased from preexercise values (P < 0.01) by -26 +/- 2, -17 +/- 2, and -13 +/- 2% for Hypo, Norm, and Hyper, respectively; each of the decrements differed significantly (P < 0.05). Integrated electromyogram increased significantly throughout exercise (P < 0.01) by 23 +/- 3, 10 +/- 1, and 6 +/- 1% for Hypo, Norm, and Hyper, respectively; each of the increments differed significantly (P < 0.05). Mean power frequency fell more (P < 0.05) during Hypo (-15 +/- 2%); the difference between Norm (-7 +/- 1%) and Hyper (-6 +/- 1%) was not significant (P = 0.32). We conclude that deltaCa(O2) during strenuous systemic exercise at equal workloads and durations affects the rate of locomotor muscle fatigue development

Intrapulmonary shunting and pulmonary gas exchange during normoxic and hypoxic exercise in healthy humans

Exercise-induced intrapulmonary arteriovenous shunting, as detected by saline contrast echocardiography, has been demonstrated in healthy humans. We have previously suggested that increases in both pulmonary pressures and blood flow associated with exercise are responsible for opening these intrapulmonary arteriovenous pathways. In the present study, we hypothesized that, although cardiac output and pulmonary pressures would be higher in hypoxia, the potent pulmonary vasoconstrictor effect of hypoxia would actually attenuate exercise-induced intrapulmonary shunting. Using saline contrast echocardiography, we examined nine healthy men during incremental (65W + 30 W/2 min) cycle exercise to exhaustion in normoxia and hypoxia (fraction of inspired O-2 = 0.12). Contrast injections were made into a peripheral vein at rest and during exercise and recovery (3-5 min postexercise) with pulmonary gas exchange measured simultaneously. At rest, no subject demonstrated intrapulmonary shunting in normoxia [ arterial P-O2 (Pa-O2) = 98 +/- 10 Torr], whereas in hypoxia (Pa-O2 = 47 +/- 5 Torr), intrapulmonary shunting developed in 3/9 subjects. During exercise, similar to 90% (8/9) of the subjects shunted during normoxia, whereas all subjects shunted during hypoxia. Four of the nine subjects shunted at a lower workload in hypoxia. Furthermore, all subjects continued to shunt at 3 min, and five subjects shunted at 5 min postexercise in hypoxia. Hypoxia has acute effects by inducing intrapulmonary arteriovenous shunt pathways at rest and during exercise and has longterm effects by maintaining patency of these vessels during recovery. Whether oxygen tension specifically regulates these novel pathways or opens them indirectly via effects on the conventional pulmonary vasculature remains unclear

Repeat exercise normalizes the gas-exchange impairment induced by a previous exercise bout in asthmatic subjects

Twenty-one subjects with asthma underwent treadmill exercise to exhaustion at a workload that elicited approximately 90% of each subject's maximal O2 uptake (EX1). After EX1, 12 subjects experienced significant exercise-induced bronchospasm [(EIB+), %decrease in forced expiratory volume in 1.0 s = -24.0 +/- 11.5%; pulmonary resistance at rest vs. postexercise = 3.2 +/- 1.5 vs. 8.1 +/- 4.5 cmH2O.l(-1).s(-1)] and nine did not (EIB-). The alveolar-to-arterial Po2 difference (A-aDo2) was widened from rest (9.1 +/- 6.7 Torr) to 23.1 +/- 10.4 and 18.1 +/- 9.1 Torr at 35 min after EX1 in subjects with and without EIB, respectively (P < 0.05). Arterial Po2 (PaO2) was reduced in both groups during recovery (EIB+, -16.0 +/- -13.0 Torr vs. baseline; EIB-, -11.0 +/- 9.4 Torr vs. baseline, P < or = 0.05). Forty minutes after EX1, a second exercise bout was completed at maximal O2 uptake. During the second exercise bout, pulmonary resistance decreased to baseline levels in the EIB+ group and the A-aDo2 and PaO2 returned to match the values seen during EX1 in both groups. Sputum histamine (34.6 +/- 25.9 vs. 61.2 +/- 42.0 ng/ml, pre- vs. postexercise) and urinary 9alpha,11beta-prostaglandin F2 (74.5 +/- 38.6 vs. 164.6 +/- 84.2 ng/mmol creatinine, pre- vs. postexercise) were increased after exercise only in the EIB+ group (P < 0.05), and postexercise sputum histamine was significantly correlated with the exercise PaO2 and A-aDo2 in the EIB+ subjects. Thus exercise causes gas-exchange impairment during the postexercise period in asthmatic subjects independent of decreases in forced expiratory flow rates after the exercise; however, a subsequent exercise bout normalizes this impairment secondary in part to a fast acting, robust exercise-induced bronchodilatory response

Gas exchange during exercise in habitually active asthmatic subjects

We determined the relations among gas exchange, breathing mechanics, and airway inflammation during moderate- to maximum-intensity exercise in asthmatic subjects. Twenty-one habitually active (48.2 +/- 7.0 ml.kg(-1).min(-1) maximal O2 uptake) mildly to moderately asthmatic subjects (94 +/- 13% predicted forced expiratory volume in 1.0 s) performed treadmill exercise to exhaustion (11.2 +/- 0.15 min) at approximately 90% of maximal O2 uptake. Arterial O2 saturation decreased to < or =94% during the exercise in 8 of 21 subjects, in large part as a result of a decrease in arterial Po2 (PaO2): from 93.0 +/- 7.7 to 79.7 +/- 4.0 Torr. A widened alveolar-to-arterial Po2 difference and the magnitude of the ventilatory response contributed approximately equally to the decrease in PaO2 during exercise. Airflow limitation and airway inflammation at baseline did not correlate with exercise gas exchange, but an exercise-induced increase in sputum histamine levels correlated with exercise Pa(O2) (negatively) and alveolar-to-arterial Po2 difference (positively). Mean pulmonary resistance was high during exercise (3.4 +/- 1.2 cmH2O.l(-1).s) and did not increase throughout exercise. Expiratory flow limitation occurred in 19 of 21 subjects, averaging 43 +/- 35% of tidal volume near end exercise, and end-expiratory lung volume rose progressively to 0.25 +/- 0.47 liter greater than resting end-expiratory lung volume at exhaustion. These mechanical constraints to ventilation contributed to a heterogeneous and frequently insufficient ventilatory response; arterial Pco2 was 30-47 Torr at end exercise. Thus pulmonary gas exchange is impaired during high-intensity exercise in a significant number of habitually active asthmatic subjects because of high airway resistance and, possibly, a deleterious effect of exercise-induced airway inflammation on gas exchange efficiency