Atelectasis is inversely proportional to transpulmonary pressure during weaning from ventilator support in a large animal model.

BACKGROUND: In mechanically ventilated, lung injured, patients without spontaneous breathing effort, atelectasis with shunt and desaturation may appear suddenly when ventilator pressures are decreased. It is not known how such a formation of atelectasis is related to transpulmonary pressure (PL ) during weaning from mechanical ventilation when the spontaneous breathing effort is increased. If the relation between PL and atelectasis were known, monitoring of PL might help to avoid formation of atelectasis and cyclic collapse during weaning. The main purpose of this study was to determine the relation between PL and atelectasis in an experimental model representing weaning from mechanical ventilation. METHODS: Dynamic transverse computed tomography scans were acquired in ten anaesthetized, surfactant-depleted pigs with preserved spontaneous breathing, as ventilator support was lowered by sequentially reducing inspiratory pressure and positive end expiratory pressure in steps. The volumes of gas and atelectasis in the lungs were correlated with PL obtained using oesophageal pressure recordings. Work of breathing (WOB) was assessed from Campbell diagrams. RESULTS: Gradual decrease in PL in both end-expiration and end-inspiration caused a proportional increase in atelectasis and decrease in the gas content (linear mixed model with an autoregressive correlation matrix; P < 0.001) as the WOB increased. However, cyclic alveolar collapse during tidal ventilation did not increase significantly. CONCLUSION: We found a proportional correlation between atelectasis and PL during the 'weaning process' in experimental mild lung injury. If confirmed in the clinical setting, a gradual tapering of ventilator support can be recommended for weaning without risk of sudden formation of atelectasis.

Two-center double-capture interference in fast He2+ + H2 collisions.

We report the first observation of Young-type interference effects in a two-electron transfer process. These effects change strongly as the projectile velocity changes in fast (1.2 and 2.0 MeV) He(2+) + H(2) collisions as manifested in strong variations of the double-electron capture rates with the H(2) orientation. This is consistent with fully quantum mechanical calculations, which ignore sequential electron transfer, and a simple projectile de Broglie wave picture assuming that two-electron transfer probabilities are higher in collisions where the projectile passes close to either one of the H(2) nuclei.

Evidence of wave-particle duality for single fast hydrogen atoms.

We report the direct observation of interference effects in a Young's double-slit experiment where the interfering waves are two spatially separated components of the de Broglie wave of single 1.3 MeV hydrogen atoms formed close to either target nucleus in H++H2 electron-transfer collisions. Quantum interference strongly influences the results even though the hydrogen atoms have a de Broglie wavelength, lambda_{dB}, as small as 25 fm.

The inheritance of rheumatoid arthritis in Iceland.

OBJECTIVE: Rheumatoid arthritis (RA) is the most common form of inflammatory arthritis. Although there is a large body of evidence suggesting that RA is immune mediated, the etiology remains unresolved. Twin studies have shown disease concordance rates of approximately 15% in monozygotic twins and 4% in dizygotic twins, while the estimated risk ratio for siblings of RA patients ranges from 5 to 8. Our goal was to use genealogic data from Iceland to further investigate the genetic component of RA. METHODS: Data were obtained from a population-based, computerized genealogy database that was developed to examine multigenerational relationships among individuals in the relatively homogeneous population of Iceland. Using an algorithm, the minimum founder test, we calculated the least number of founders required to account for a list of RA patients, and compared it with 1,000 sets of same-sized matched control groups. In addition, we estimated the kinship coefficient and risk ratios for relatives of the RA patients. RESULTS: Several familial clustering tests demonstrated that the RA patients were more related to each other than were the average control set of Icelanders. A significantly fewer number of founders was necessary to account for our patient list than for the random sets of matched controls (P < 0.001), and the average pairwise identity-by-descent sharing was greater among the patients than among the control sets (P < 0.001). In addition, there was an increased risk of RA in first- and second-degree relatives of the patients; e.g., for siblings, the risk ratio was 4.38 (95% confidence interval 3.26-5.67), and for uncles/aunts, the risk ratio was 1.95 (95% confidence interval 1.52-2.43). CONCLUSION: The familial component of RA is shown to extend beyond the nuclear family, thus providing stronger evidence for a significant genetic component to RA.

Intranasal vaccination: pharmaceutical evaluation of the vaccine delivery system and immunokinetic characteristics of the immune responses.

The purpose of this study was to analyze the effect of some pharmaceutical excipients when used for mucosal vaccine formulations and to characterize the achieved immune response. After conducting various pharmaceutical evaluations of the formulations, immunokinetic studies were performed in mice, guinea pigs, and rabbits. The kinetics and the characteristics (antibody isotypes, etc.) of the immune response were studied, as well as the induced level of toxin neutralizing IgG antibodies, which are usually used as the only measures of the potency of vaccines. Results in mice show that intranasal vaccination results in a potent and rapid immune response, similar to that seen after subcutaneous immunization. In guinea pigs and rabbits, however, the subcutaneous immunization produced significantly stronger response than did intranasal vaccination. The most promising excipients were found to be either Polysorbate 20 or Cremophor EL in an aqueous mixture together with caprylic/capric glyceride. The results indicate that nontoxic and pharmaceutically acceptable excipients can be used for mucosal vaccination, providing an interesting alternative to parenteral vaccination.

Edge detection in medical images using a genetic algorithm.

An algorithm is developed that detects well-localized, unfragmented, thin edges in medical images based on optimization of edge configurations using a genetic algorithm (GA). Several enhancements were added to improve the performance of the algorithm over a traditional GA. The edge map is split into connected subregions to reduce the solution space and simplify the problem. The edge-map is then optimized in parallel using incorporated genetic operators that perform transforms on edge structures. Adaptation is used to control operator probabilities based on their participation. The GA was compared to the simulated annealing (SA) approach using ideal and actual medical images from different modalities including magnetic resonance imaging (MRI), computed tomography (CT), and ultrasound. Quantitative comparisons were provided based on the Pratt figure of merit and on the cost-function minimization. The detected edges were thin, continuous, and well localized. Most of the basic edge features were detected. Results for different medical image modalities are promising and encourage further investigation to improve the accuracy and experiment with different cost functions and genetic operators.

Plasma viscosity in the monitoring of therapy in rheumatoid arthritis patients.

Plasma viscosity (PV) was compared with erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) and clinical measures in the monitoring of parenteral gold therapy in a longitudinal study of 40 consecutive rheumatoid arthritis (RA) patients. Significant correlations with the combined clinical variables were only found for differences in PV and not for the other laboratory tests. PV but not ESR or CRP discriminated significantly between active and inactive disease. The sensitivity and specificity for PV above the normal range as a sign of disease activity was 89% and 73%, respectively, which was superior compared with ESR and CRP. The advantages of PV over CRP and ESR justify wider use of this test and warrant further studies of PV in the monitoring of other therapies in RA patients.

On whole blood viscosity measurements in healthy individuals and in rheumatoid arthritis patients.

Different methods of measuring whole blood viscosity using a couette rotational viscometer were compared to establish its use in clinical rheumatological practice. The relationship between blood viscosity and hematocrit was approximately exponential and no significant differences in the slopes were found between healthy controls and rheumatoid arthritis patients. Correction of native blood viscosity to a standard hematocrit of 40% by extrapolation from a standard regression curve, established by concentration/dilution of samples from healthy persons to correct for hematocrit differences and at shear rate 92s-1, was the best method for differentiating between viscosities of patients and controls. It was also the least laborious method, requiring the smallest amounts of blood and having the lowest method error. Native blood viscosity, corrected blood viscosity, plasma viscosity and red cell aggregation were all significantly higher and hematocrit significantly lower in rheumatoid arthritis patients than in controls.

Viscosity of plasma and blood in rheumatoid arthritis.

Blood rheology was studied in 130 consecutive RA outpatients, 33 with and 97 without extra-articular disease (EAD), and compared with that in 88 blood donors. All rheological variables were significantly elevated in the RA patients compared with the controls. Painful joint count (PJC), morning stiffness (MS) and radiographic changes (RC) correlated significantly with plasma viscosity (PV), CRP, ESR and fibrinogen concentration (FC), but only in the group without EAD. Corrected blood viscosity (CBV) at a shear rate of 92/s correlated significantly only with MS. Multiple regression with PJC, MS and RC as dependent variables showed significant associations of PJC with PV, MS and CRP and RC with PV. Multiple regression with PV as the dependent variable showed significant associations with FC and IgG. RA patients with EAD had higher PV (P < 0.01), CBV at 92/s (P < 0.05) and ESR (P < 0.05) than the RA patients without EAD. Differences in profiles of viscosity variables between subgroups of EAD in RA patients were observed.

Plasma, serum and whole-blood viscosity variations with age, sex, and smoking habits.

To study the influence of age, sex, and smoking habits on rheology, the authors measured plasma (PV), serum (SV), native (NBV), and corrected (CBV) blood viscosity with a computerized rotational viscometer in 152 blood donors (86 men and 66 women) and in 20 healthy persons (4 men and 16 women) attending smoke aversion treatment. None of the viscosity measures or erythrocyte sedimentation rate changed significantly with age, whereas hematocrit (HC) and fibrinogen concentration (FC) both increased with ageing (p < 0.05 and p < 0.001, respectively). Higher (p < 0.001) values of NBV and HC were found in men than in women, whereas higher values were found in women than in men for FC (p < 0.01) and ESR (p < 0.001). In blood donors, moderate smoking (mean twelve cigarettes/day) significantly influenced only ESR, which was higher (p < 0.001) in smokers than in nonsmokers. In heavy smokers (mean twenty-one cigarettes/day), however, higher (p < 0.001) PV, SV, and NBV were found, as well as higher (p < 0.01) FC and HC as compared with nonsmoking blood donors.

Plasma viscosity in giant cell arteritis as a predictor of disease activity.

Thirty one patients with giant cell arteritis (GCA) receiving standardised prednisolone treatment were followed up for one year with analyses of plasma viscosity, erythrocyte sedimentation rate (ESR), C reactive protein (CRP), and fibrinogen concentration. On the day of diagnosis all patients had an increased plasma viscosity and ESR, whereas the concentration of CRP was normal in three patients and fibrinogen concentration and haptoglobin values were normal in one patient. IgG levels were increased in two patients. Plasma viscosity correlated significantly with the ESR, IgG level, and fibrinogen concentration. Laboratory variables in subgroups of patients with GCA proved by biopsy were not different from the whole group of patients with GCA. The follow up showed that CRP normalised faster than the ESR, plasma viscosity, and fibrinogen concentration. Plasma viscosity and the ESR paralleled clinical findings more closely and predicted flare ups better than the other variables. Plasma viscosity had advantages over the ESR for predicting flare ups and in the clinical monitoring of treatment with glucocorticoids.

The influence of heparin-coated and uncoated extracorporeal circuits on blood rheology during cardiac surgery.

The effect of heparin-coated perfusion circuits on blood trauma during clinical cardiopulmonary bypass (CPB) was studied in order to find out if traumatic changes in the blood could be minimized. Twenty-four patients undergoing coronary artery bypass surgery were randomized prospectively to CPB with heparin-coated circuits (HCC) or non-coated circuits (NCC). The trauma to blood was assessed by measuring damage to blood cells by estimating red and white cell rheology changes. These were measured as red cell filtration rate (RFR) and white cell filtration rate (WFR) using standard microfiltration methods. Furthermore, changes in plasma hemoglobin (P-Hb), whole blood and plasma viscosity were simultaneously assessed. The RFR was significantly reduced in both groups during CPB by 10% in the HCC and 32% in the NCC groups (p less than 0.01). When comparing the HCC and NCC groups, a significant difference was first seen after 30 minutes of bypass (p less than 0.05) and increased at the end of CPB (p less than 0.01). Similar results were seen regarding WFR (15% and 36%, p less than 0.01). After 30 minutes of bypass, a significant difference was seen between HCC and NCC groups (p less than 0.05). Furthermore, a significant increase in P-Hb levels were seen during CPB in both patient groups. At the end of CPB, there was a significant difference in P-Hb levels (HCC 305+/-90 mg/L; NCC 455+/-78 mg/L, p less than 0.01) when comparing the two groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Rheological and immunological findings in dockers with vibration-induced white fingers.

The aim of the present study was to characterize rheological and immunological features involved in the pathogenesis of vibration-induced white fingers (VWF). Plasma viscosity, at two shear rates (580 s-1 and 1164 s-1), levels of immunoglobulins (IgG, IgM, IgA), circulating immune complexes, rheumatoid factor, antinuclear antibodies, fibronectin, fibrinogen, hemoglobin and erythrocyte sedimentation rate were analysed in 30 male dockers with VWF and in 30 healthy male referents unexposed for hand-arm vibrations. Decreased plasma viscosity was observed among the men with VWF, although formal significance (P less than 0.05) was only obtained at shear rate 580 s-1. The decrease was mainly seen among smokers. In the study there were no significant differences between the VWF group and the referents with regard to immunoglobulin levels, autoantibodies and other plasma proteins. From the study it is concluded that workers with VWF may have a decreased plasma viscosity. The biological relevance of this observation is uncertain and deserves further study.

Clinical assessment of rheumatic diseases using viscoelastic parameters for synovial fluid.

For the first time it is clearly exhibited that synovial fluid (SF) is thixotropic. Although no hysteresis loops were observed for SF, not even at high shear rates, thixotropy may be exhibited by measuring the rate of recovery after extensive shearing. The rebuilding of the structure in a small-amplitude oscillatory state following the high-shear-rate state reveals the thixotropic behaviour. Five different viscoelastic parameters for various synovial fluids (SF) were obtained using oscillatory rheometry. It was also shown that for SF in the low frequency range, corresponding to a knee joint almost at rest, the shear loss modulus G" is greater than the shear storage modulus G', since the system is allowed to dissipate energy at rest. However, with movement, G' increases and eventually becomes greater than G" at a characteristic frequency above which the system has insufficient time to dissipate energy and hence responds as an elastic body. This functional behaviour, characteristic for normal SF, broke down in the SF of rheumatoid arthritis. It was also absent in the SF of knee joints with meniscus lesions and ligament defects.