Association between levels of pentraxin 3 and incidence of chronic kidney disease in the elderly.

OBJECTIVE: Higher levels of the novel inflammatory marker pentraxin 3 (PTX3) predict cardiovascular mortality in patients with chronic kidney disease (CKD). Yet, whether PTX3 predicts worsening of kidney function has been less well studied. We therefore investigated the associations between PTX3 levels, kidney disease measures and CKD incidence. METHODS: Cross-sectional associations between serum PTX3 levels, urinary albumin/creatinine ratio (ACR) and cystatin C-estimated glomerular filtration rate (GFR) were assessed in two independent community-based cohorts of elderly subjects: the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS, n = 768, 51% women, mean age 75 years) and the Uppsala Longitudinal Study of Adult Men (ULSAM, n = 651, mean age 77 years). The longitudinal association between PTX3 level at baseline and incident CKD (GFR <60 mL(-1) min(-1) 1.73 m(-2) was also analysed (number of events/number at risk: PIVUS 229/746, ULSAM 206/315). RESULTS: PTX3 levels were inversely associated with GFR [PIVUS: B-coefficient per 1 SD increase -0.16, 95% confidence interval (CI) -0.23 to -0.10, P < 0.001; ULSAM: B-coefficient per 1 SD increase -0.09, 95% CI -0.16 to -0.01, P < 0.05], but not ACR, after adjusting for age, gender, C-reactive protein and prevalent cardiovascular disease in cross-sectional analyses. In longitudinal analyses, PTX3 levels predicted incident CKD after 5 years in both cohorts [PIVUS: multivariable odds ratio (OR) 1.21, 95% CI 1.01-1.45, P < 0.05; ULSAM: multivariable OR 1.37, 95% CI 1.07-1.77, P < 0.05]. CONCLUSIONS: Higher PTX3 levels are associated with lower GFR and independently predict incident CKD in elderly men and women. Our data confirm and extend previous evidence suggesting that inflammatory processes are activated in the early stages of CKD and drive impairment of kidney function. Circulating PTX3 appears to be a promising biomarker of kidney disease.

Hyperoxia affects the regional pulmonary ventilation/perfusion ratio: an electrical impedance tomography study.

BACKGROUND: The way in which hyperoxia affects pulmonary ventilation and perfusion is not fully understood. We investigated how an increase in oxygen partial pressure in healthy young volunteers affects pulmonary ventilation and perfusion measured by thoracic electrical impedance tomography (EIT). METHODS: Twelve semi-supine healthy male volunteers aged 21-36 years were studied while breathing room air and air-oxygen mixtures (FiO2) that resulted in predetermined transcutaneous oxygen partial pressures (tcPO2) of 20, 40 and 60 kPa. The magnitude of ventilation (ΔZv) and perfusion (ΔZQ)-related changes in cyclic impedance variations, were determined using an EIT prototype equipped with 32 electrodes around the thorax. Regional changes in ventral and dorsal right lung ventilation (V) and perfusion (Q) were estimated, and V/Q ratios calculated. RESULTS: There were no significant changes in ΔZv with increasing tcPO2 levels. ΔZQ in the dorsal lung increased with increasing tcPO2 (P = 0.01), whereas no such change was seen in the ventral lung. There was a simultaneous decrease in V/Q ratio in the dorsal region during hyperoxia (P = 0.04). Two subjects did not reach a tcPO2 of 60 kPa despite breathing 100% oxygen. CONCLUSION: These results indicate that breathing increased concentrations of oxygen induces pulmonary vasodilatation in the dorsal lung even at small increases in FiO2. Ventilation remains unchanged. Local mismatch of ventilation and perfusion occurs in young healthy men, and the change in ventilation/perfusion ratio can be determined non-invasively by EIT.

Cardiac dysfunction after burns.

OBJECTIVES: Using transoesophageal echocardiography (TEE) we investigated the occurrence, and the association of possible abnormalities of motion of the regional wall of the heart (WMA) or diastolic dysfunction with raised troponin concentrations, or both during fluid resuscitation in patients with severe burns. PATIENTS AND METHODS: Ten consecutive adults (aged 36-89 years, two women) with burns exceeding 20% total burned body surface area who needed mechanical ventilation were studied. Their mean Baux index was 92.7, and they were resuscitated according to the Parkland formula. Thirty series of TEE examinations and simultaneous laboratory tests for myocyte damage were done 12, 24, and 36h after the burn. RESULTS: Half (n=5) the patients had varying grades of leakage of the marker that correlated with changeable WMA at 12, 24 and 36h after the burn (p< or =0.001, 0.044 and 0.02, respectively). No patient had WMA and normal concentrations of biomarkers or vice versa. The mitral deceleration time was short, but left ventricular filling velocity increased together with stroke volume. CONCLUSION: Acute myocardial damage recorded by both echocardiography and leakage of troponin was common, and there was a close correlation between them. This is true also when global systolic function is not deteriorated. The mitral flow Doppler pattern suggested restrictive left ventricular diastolic function.

Human cardiovascular dose-response to supplemental oxygen.

AIM: The aim of the study was to examine the central and peripheral cardiovascular adaptation and its coupling during increasing levels of hyperoxaemia. We hypothesized a dose-related effect of hyperoxaemia on left ventricular performance and the vascular properties of the arterial tree. METHODS: Oscillometrically calibrated arterial subclavian pulse trace data were combined with echocardiographic recordings to obtain non-invasive estimates of left ventricular volumes, aortic root pressure and flow data. For complementary vascular parameters and control purposes whole-body impedance cardiography was applied. In nine (seven males) supine, resting healthy volunteers, aged 23-48 years, data was collected after 15 min of air breathing and at increasing transcutaneous oxygen tensions (20, 40 and 60 kPa), accomplished by a two group, random order and blinded hyperoxemic protocol. RESULTS: Left ventricular stroke volume [86 +/- 13 to 75 +/- 9 mL (mean +/- SD)] and end-diastolic area (19.3 +/- 4.4 to 16.8 +/- 4.3 cm(2)) declined (P < 0.05), and showed a linear, negative dose-response relationship to increasing arterial oxygen levels in a regression model. Peripheral resistance and characteristic impedance increased in a similar manner. Heart rate, left ventricular fractional area change, end-systolic area, mean arterial pressure, arterial compliance or carbon dioxide levels did not change. CONCLUSION: There is a linear dose-response relationship between arterial oxygen and cardiovascular parameters when the systemic oxygen tension increases above normal. A direct effect of supplemental oxygen on the vessels may therefore not be excluded. Proximal aortic and peripheral resistance increases from hyperoxaemia, but a decrease of venous return implies extra cardiac blood-pooling and compensatory relaxation of the capacitance vessels.

Acute hyperoxaemia-induced effects on regional blood flow, oxygen consumption and central circulation in man.

AIM: Despite numerous in vitro and animal studies, circulatory effects and mechanisms responsible for the vasoconstriction seen during hyperoxaemia are yet to be ascertained. The present study set out to: (i) set up a non-invasive human model for the study of hyperoxia-induced cardiovascular effects, (ii) describe the dynamics of this effect and (iii) determine whether hyperoxaemia also, by vasoconstriction alters oxygen consumption (O(2)). METHODS: The study comprised four experiments (A, B, C and D) on healthy volunteers examined before, during and after 100% oxygen breathing. A: Blood flow (mL min(-1).100 mL(-1) tissue), venous occlusion plethysmography was assessed (n = 12). B: Blood flow was recorded with increasing transcutaneous oxygen tension (P(tc)O(2)) levels (dose-response) (n = 8). C: Heart rate (HR), stroke volume, cardiac output (CO) and systemic vascular resistance (SVR) was assessed using echocardiography (n = 8). D: O(2) was measured using an open circuit technique when breathing an air-O(2) mix (fraction of inhaled oxygen: F(i)O(2) = 0.58) (n = 8). RESULTS: Calf blood flow decreased 30% during O(2) breathing. The decrease in calf blood flow was found to be oxygen dose dependent. A similar magnitude, as for the peripheral circulation, of the effect on central parameters (HR/CO and SVR) and in the time relationship was noted. Hyperoxia did not change O(2). An average of 207 (93) mL O(2) per subject was washed in during the experiments. CONCLUSION: This model appears suitable for the investigation of O(2)-related effects on the central and peripheral circulation in man. Our findings, based on a more comprehensive (central/peripheral circulation examination) evaluation than earlier made, suggest significant circulatory effects of hyperoxia. Further studies are warranted to elucidate the underlying mechanisms.

Myocardial tissue motion influence on laser Doppler perfusion monitoring using tissue Doppler imaging.

Tissue motion of the beating heart generates large movement artifacts in the laser Doppler perfusion monitoring (LDPM) signal. The aim of the study was to use tissue Doppler imaging (TDI) to localise intervals during the cardiac cycle where the influence of movement artifacts on the LDPM signal is minimum. TDI velocities and LDPM signals were investigated on three calves, for normal heartbeat and during occlusion of the left anterior descending coronary artery. Intervals of low tissue velocity (TDIint, < 1 cm s(-1)) during the cardiac cycle were identified. During occlusion, these intervals were compared with low LDPM signal intervals (LDPMint, <50% compared with baseline). Low-velocity intervals were found in late systole (normal and occlusion) and late diastole (normal). Systolic intervals were longer and less sensitive to heart rate variation compared with diastolic ones. The overlap between LDPMint and TDIint in relation to TDIint length was 84+/-27% (n = 14). The LDPM signal was significantly (p < 0.001, n = 14) lower during occlusion if calculated during minimum tissue motion (inside TDIint), compared with averaging over the entire cardiac cycle without taking tissue motion into consideration. In conclusion, movement artifacts are reduced if the LDPM signal is correlated to the ECG and investigated during minimum wall motion. The optimum interval depends on the application; late systole and late diastole can be used.

Muscle metabolism in fibromyalgia studied by P-31 magnetic resonance spectroscopy during aerobic and anaerobic exercise.

OBJECTIVE: To investigate mechanisms underlying the reduced work capacity of fibromyalgia (FM) patients were compared to healthy controls at specified workloads, using P-31 magnetic resonance spectroscopy (MRS). METHODS: The forearm flexor muscle group was examined with MRS at rest, at sub maximal and at maximal controlled dynamic work as well as at maximal isometric contraction. Aerobic fitness was determined by bicycle ergonometry. RESULTS: Metabolite concentrations and muscle pH were similar for patients and controls at lower workloads. At maximal dynamic and static contractions the concentration of inorganic phosphate was lower and at static contractions the pH decrease was smaller in patients. The performed work by patients was only 50% compared to controls and the patients experienced more pain. Maximal oxygen uptake was lower in the fibromyalgia group. Expired gas-analysis in this group showed ventilatory equivalents at similar relative levels of maximal work capacity. CONCLUSION: Fibromyalgia patients seem to utilise less of the energy rich phosphorous metabolites at maximal work despite pH reduction. They seemed to be less aerobic fitted and reached the anaerobic threshold earlier than the controls.

Perception of risk and subjective health among victims of the Chernobyl disaster.

Several studies have demonstrated that the nuclear power plant accident at Chernobyl in 1986 had a strong impact on the subjective health of the inhabitants in the surrounding regions and that the majority of these health complaints appear to be stress-related. An epidemiological survey among the adult population of the Gomel region in Belarus near Chernobyl showed higher rates of self-reported health problems, psychological distress and medical service use in this region than in a comparable unexposed region. This paper presents an analysis of data on cognitive factors that were collected in this study. The findings support the hypothesis that cognitive variables such as risk perception and sense of control play an important role as mediating factors in the explanation of the observed health differences between the exposed and non-exposed regions. A tentative model is presented to further clarify the role of risk perception in the occurrence of non-specific health complaints after such ecological disasters.

Feasibility and reproducibility of off-line tissue Doppler measurement of regional myocardial function during dobutamine stress echocardiography.

AIMS: Off-line post-processing of colour tissue Doppler from digital loops may allow objective quantification of dobutamine stress echocardiography. We assessed the reproducibility of off-line measurements of regional myocardial velocities. METHODS AND RESULTS: Nine observers analysed 10 studies, each making 2400 observations. Coefficients of variation in basal segments from apical windows, at rest and maximal stress, were 9-14% and 11-18% for peak systolic velocity, 16-18% and 17-19% for time-to-peak systolic velocity, 9-17% and 18-24% for systolic velocity time integral, and 18-23% and 21-27% for systolic acceleration. Coefficients of variation for diastolic velocities in basal segments at rest were 11-40%. Coefficients of variation for peak systolic velocity were 10-24% at rest and 14-28% at peak in mid segments, and 19-53% and 29-69% in apical segments. From parasternal windows coefficients of variation for peak systolic velocity were 14-16% in basal posterior, and 19-29% in mid-anterior segments. High variability makes measurement unreliable in apical and basal anterior septal segments. The feasibility of obtaining traces was tested in 92 subjects, and >90% in all basal and mid segments apart from the anterior septum. CONCLUSION: Quantification of myocardial functional reserve by off-line analysis of colour tissue Doppler acquired during dobutamine stress is feasible and reproducible in 11 segments of the left ventricle. The most reliable measurements are systolic velocities of longitudinal motion in basal segments.

T lymphocyte infiltration in non-rheumatic aortic stenosis: a comparative descriptive study between tricuspid and bicuspid aortic valves.

BACKGROUND: The two most common causes of aortic stenosis are primary "degenerative" calcification of tricuspid aortic valves and secondary calcification of congenital bicuspid valves. T lymphocyte infiltration occurs in stenotic tricuspid aortic valves, indicating an inflammatory component, but it has not been shown whether it also occurs in stenotic bicuspid valves. OBJECTIVE: To compare non-rheumatic tricuspid and bicuspid stenotic aortic valves for the presence and distribution of T lymphocytes. SETTING: University hospital. PATIENTS AND DESIGN: Valve specimens were obtained from 29 patients (15 women, 14 men, mean age 69 years (range 52-81 years)), referred to the hospital for aortic valve replacement because of symptomatic aortic valve stenosis. There were 17 tricuspid valves (from 10 women and seven men, mean age 71 years) and 12 bicuspid valves (from five women and seven men, mean age 67 years). To identify mononuclear inflammatory cells, sections were stained with antibodies for CD3 (pan-T cell antigen, Dako 1:400) and then graded histologically according to the degree of T cell infiltrate. RESULTS: T lymphocyte infiltration was present in both tricuspid and bicuspid stenotic aortic valves, without any significant differences in extent or localisation. CONCLUSIONS: Stenotic bicuspid aortic valves show the same degree of T lymphocyte infiltration as degenerative tricuspid aortic valves. Inflammation needs to be considered in the pathogenesis of acquired aortic stenosis, irrespective of the primary valve anomaly.

Adaptive stress response of glutathione and uric acid metabolism in man following controlled exercise and diet.

Ergometer cycling performance as well as acute exercise-induced changes in the metabolism of energy-intermediates and glutathione (GSH) were investigated in skeletal muscle (SM) of 15 healthy young male subjects (VO(2max) approximately 54.7 mL kg(-1) min(-1), age approximately 25 years), before and after 3 days of controlled 'ìoverload-training' in combination with either high (62% of energy intake) or low (26% of energy intake) dietary intake of carbohydrates. The intake of a carbohydrate-rich diet clearly reduced the depletion of SM glycogen following the short-term training period, paralleled with a positive effect on the endurance performance, but not on high-intensity work-performance. An 'delayed over-reaching effect', defined as impaired work-performance, was observed after 2.5 days of recovery from the short-term training period, irrespective of the carbohydrate content of the diet and basal glycogen level in SM. Taken together, the main and novel findings of present investigation are: (1) an acute decrease of reduced GSH content and altered thiol-redox homeostasis in SM induced by strenuous high-intensity exercise; (2) an adaptive elevation of basal GSH level following the short-term training period; (3) an adaptive decrease of basal GSH level following 2.5 days recovery from training; (4) evidence of a relationship between the SM fibre type, physical performance capacity and GSH turnover during acute bouts of exercise; and (5) no evident effect of the level of carbohydrate intake on metabolism of GSH or energy intermediates. Furthermore, the induction of acute oxidative stress in exercising human SM and the adaptive responses to training are suggested to provide a protective antioxidant phenotype to the exercising SM during periods with repeated intense intermittent training.

Structural basis for allosteric substrate specificity regulation in anaerobic ribonucleotide reductases.

BACKGROUND: The specificity of ribonucleotide reductases (RNRs) toward their four substrates is governed by the binding of deoxyribonucleoside triphosphates (dNTPs) to the allosteric specificity site. Similar patterns in the kinetics of allosteric regulation have been a strong argument for a common evolutionary origin of the three otherwise widely divergent RNR classes. Recent structural information settled the case for divergent evolution; however, the structural basis for transmission of the allosteric signal is currently poorly understood. A comparative study of the conformational effects of the binding of different effectors has not yet been possible; in addition, only one RNR class has been studied. RESULTS: Our presentation of the structures of a class III anaerobic RNR in complex with four dNTPs allows a full comparison of the protein conformations. Discrimination among the effectors is achieved by two side chains, Gln-114 and Glu-181, from separate monomers. Large conformational changes in the active site (loop 2), in particular Phe-194, are induced by effector binding. The conformational differences observed in the protein when the purine effectors are compared with the pyrimidine effectors are large, while the differences observed within the purine group itself are more subtle. CONCLUSIONS: The subtle differences in base size and hydrogen bonding pattern at the effector site are communicated to major conformational changes in the active site. We propose that the altered overlap of Phe-194 with the substrate base governs hydrogen bonding patterns with main and side chain hydrogen bonding groups in the active site. The relevance for evolution is discussed.

Two active site asparagines are essential for the reaction mechanism of the class III anaerobic ribonucleotide reductase from bacteriophage T4.

Class III ribonucleotide reductase is an anaerobic enzyme that uses a glycyl radical to catalyze the reduction of ribonucleotides to deoxyribonucleotides and formate as ultimate reductant. The reaction mechanism of class III ribonucleotide reductases requires two cysteines within the active site, Cys-79 and Cys-290 in bacteriophage T4 NrdD numbering. Cys-290 is believed to form a transient thiyl radical that initiates the reaction with substrate and Cys-79 to take part as a transient thiyl radical in later steps of the reductive reaction. The recently solved three-dimensional structure of class III ribonucleotide reductase (RNR) from bacteriophage T4 shows that two highly conserved asparagines, Asn-78 and Asn-311, are positioned close to the essential Cys-79. We have investigated the function of Asn-78 and Asn-311 by site-directed mutagenesis and measured enzyme activity and glycyl radical formation in five single (N78(A/C/D) and N311(A/C)) and one double (N78A/N311A) mutant proteins. Our results suggest that both asparagines are important for the catalytic mechanism of class III RNR and that one asparagine can partially compensate for the lack of the other functional group in the single Asn --> Ala mutant proteins. A plausible role for these two asparagines could be in positioning formate in the active site to orient it toward the proposed thiyl radical of Cys-79. This would also control the highly reactive carbon dioxide radical anion form of formate within the active site before it is released as carbon dioxide. A detailed reaction scheme including the function of the two asparagines and two formate molecules is proposed for class III RNRs.

Clinical outcome or abdominal urethropexy-colposuspension: a long-term follow-up.

The aim of this study was to investigate the long-term results of abdominal urethropexy-colposuspension in terms of cure rate of stress urinary incontinence, complications and side effects. Between 1985 and 1992, 169 women between 27 and 79 years old underwent abdominal urethropexy-colposuspension at Stockholm Söder Hospital. In 1997 they were invited to participate in a long-term follow-up study, 5-11 years after the operation. One hundred and thirty-one women (78%) were willing to attend for a clinical review; 38 were lost to follow-up. At the follow-up visit all women were assessed with medical history, symptoms of incontinence, and their satisfaction and problems after the operation, following a predefined protocol. Peri- and postoperative data were retrieved from the files. The patients underwent a gynecological examination, measurement of residual urine volume and a provocative leakage test. One hundred and nine women (83%) were satisfied with the results of the operation and 22 (17%) were not. Seventy-one (54%) were subjectively completely dry, 48 (35%) had a little leakage and 14 (11%) had frequent leakage; 122 women were continent in the provocation test, and only 9 (7%) demonstrated leakage. The cure rate for stress incontinence was 93%. According to their medical histories 63 (48%) women had mixed incontinence before their operation. At the follow-up examination 43 of these 63 women still had symptoms of urgency. Twenty-six women with genuine stress incontinence before the operation had developed urgency or urge incontinence during the follow-up period. Urge symptoms before operation was a negative prognostic factor for a good outcome in terms of subjective cure of incontinence, but had no impact on objective cure rate or satisfaction of the operation. The cure rate for stress incontinence was high but still there were women who were not satisfied with the operation. Most of these complained of urge incontinence. There were few serious complications. The objective cure rate was better than the subjective cure rate.

Restoring proper radical generation by azide binding to the iron site of the E238A mutant R2 protein of ribonucleotide reductase from Escherichia coli.

The enzyme activity of Escherichia coli ribonucleotide reductase requires the presence of a stable tyrosyl free radical and diiron center in its smaller R2 component. The iron/radical site is formed in a reconstitution reaction between ferrous iron and molecular oxygen in the protein. The reaction is known to proceed via a paramagnetic intermediate X, formally a Fe(III)-Fe(IV) state. We have used 9.6 GHz and 285 GHz EPR to investigate intermediates in the reconstitution reaction in the iron ligand mutant R2 E238A with or without azide, formate, or acetate present. Paramagnetic intermediates, i.e. a long-living X-like intermediate and a transient tyrosyl radical, were observed only with azide and under none of the other conditions. A crystal structure of the mutant protein R2 E238A/Y122F with a diferrous iron site complexed with azide was determined. Azide was found to be a bridging ligand and the absent Glu-238 ligand was compensated for by azide and an extra coordination from Glu-204. A general scheme for the reconstitution reaction is presented based on EPR and structure results. This indicates that tyrosyl radical generation requires a specific ligand coordination with 4-coordinate Fe1 and 6-coordinate Fe2 after oxygen binding to the diferrous site.

Influence of respiration on myocardial signal intensity.

Echocardiographic quantification of myocardial perfusion after IV contrast is possible, based on the intensity of the received intermittent second harmonic signal. To investigate the influence of respiration on the intensity of myocardial signals, we examined nine patients with normal coronary angiograms. At baseline, end-expiratory and end-inspiratory images were obtained in broadband radiofrequency (RF) and intermittent second harmonic modes, the latter repeated during IV contrast at rest and at peak stress. In mid-septum at baseline, end-inspiratory integrated backscatter intensity was 4 dB higher (p < 0.05, both in second harmonic and fundamental domains) than end-expiratory intensity. In second harmonic imaging, contrast increased signal intensity by 4 dB (p < 0.05) in six examined segments, but the increase in the midseptal region (2 dB) was not significant. Contrast-enhanced intensity at end-inspiration was higher (3 dB, p < 0.01) than baseline intensity at end-expiration. We conclude that the increase in myocardial signal intensity during inspiration may resemble the contrast effect in intermittent second harmonic mode. The respiratory variation persists after contrast and may mask or exaggerate the effect of myocardial contrast.

Major and minor axes of the normal mitral annulus.

BACKGROUND AND AIM OF THE STUDY: A dilated or abnormally shaped mitral annulus is a common cause of mitral valve regurgitation, and may be cured by annuloplastic surgery. Multiplane transesophageal echocardiography (TEE) is the diagnostic technique of choice. Our aim was to evaluate and suggest two-dimensional TEE reference values from a standardized procedure of measuring the mitral annular major and minor axes, and their cyclic changes. METHODS: The annulus was approximated elliptic in the horizontal plane. The intercommissural (IC, major axis) and anteroposterior (AP, minor axis) distances were measured at end-systole (ES), at maximal valve opening (MO), and at end-diastole (ED) from a mid-esophageal view, in 13 men and eight women with normal echocardiographic findings. Indexed values and reproducibility were calculated. RESULTS: The success rate was 100% at ES, 90% at MO, and 29% at ED. ES distances were largest (p <0.001) and most reproducible (5-5.9%). Body weight, but not height or age, had a significant impact. ES 95% prediction intervals for IC were 27 to 46 mm (16-23 mm/m2) and 22 to 36 mm (13-18 mm/m2) for AP (p <0.001). Corresponding body weight-corrected intervals were 0.39 to 0.59 (IC) and 0.32 to 0.48 (AP) mm/kg. No subject had IC:AP <1.1 together with an AP >0.45 mm/kg. CONCLUSION: Among measurements made at ES, MO and ED, those at ES provided the most reproducible results, and high-quality images were obtained in normal, non-obese subjects. The distances should be judged in relation to body weight or surface area and each other. The largest IC distance and the most elliptic shape were at ES, while the annulus was minimal at ED. The procedure and normal ranges presented may contribute to the evaluation of patients with mitral regurgitation.

Confounded cytosine! Tinkering and the evolution of DNA.

Early in the history of DNA, thymine replaced uracil, thus solving a short-term problem for storing genetic information--mutation of cytosine to uracil through deamination. Any engineer would have replaced cytosine, but evolution is a tinkerer not an engineer. By keeping cytosine and replacing uracil the problem was never eliminated, returning once again with the advent of DNA methylation.

Beat-to-beat changes in stroke volume precede the general circulatory effects of mechanical ventilation: a case report.

BACKGROUND: The haemodynamic as well as the ventilatory consequences of mechanical ventilation can be harmful in critically ill neonates. Newly developed ventilatory lung protective strategies are not always available immediately and in an acute situation the haemodynamic changes caused by mechanical ventilation can affect the oxygen delivery considerably. We report the case of a male neonate who was treated with conventional pressure-controlled mechanical ventilation because of respiratory distress and progressive respiratory acidosis resulting from meconium aspiration. Because of poor arterial oxygenation despite 100% inspired oxygen and increased ventilator settings, echocardiography was performed to exclude central haemodynamic reasons for low oxygen delivery. METHOD: Doppler echocardiography was used for the measurement of stroke volume and cardiac output. Pulse oximetry and aortic blood pressure were monitored continuously. RESULTS: Echocardiography revealed no cardiac malformations or signs of persistent fetal circulation. When inspiratory pressures and duration were increased, beat-to-beat variation in stroke volume preceded decay in cardiac output. Stroke volume variations and oxygen saturation values guided ventilator settings until extracorporal membrane oxygenation could be arranged for. After recovery and discharge 4 weeks later the boy is progressing normally. CONCLUSION: Because oxygen delivery is dependent on both blood flow and arterial oxygen content, measurement of cardiac output as well as left heart oxygen saturation is a useful guide to optimizing oxygen delivery. This case report demonstrates how Doppler echocardiographic monitoring of beat-to-beat changes in stroke volume can be used to detect early negative haemodynamic effects of increased mechanical ventilation settings before cardiac output is affected.

[Hopeful future for echocardiography. Progress within both the function and perfusion areas]. / Förhoppningsfull framtid för ekokardiografin. Utveckling sker inom såväl funktions- som perfusionsområdet.

Echocardiography is presently a feasible method for quantitative estimation of intracardiac flows, pressure levels and for hemodynamic evaluation of valvular disease. The evaluation of regional myocardial function is still based on subjective scrutiny, and no routine method for the estimation of myocardial blood flow is available. We present an overview of newly developed techniques that are beginning to gain purchase in clinical practice. The use of native second harmonic imaging to improve image quality and of tissue Doppler to provide objective measurements of regional myocardial function is discussed. This article describes the transformation of tissue Doppler information into parametric images as in strain rate imaging, and overviews the use of ultrasound contrast agents. Used together with new imaging modalities, myocardial contrast echocardiography holds promise for future quantification of myocardial blood volume and flow. Other emerging echocardiographic technologies discussed are non-invasive measurement of coronary flow reserve and three dimensional cineloop visualization, developed to increase our understanding of cardiovascular physiological and anatomical coupling.