High proportion of patients with bleeding of unknown cause in persons with a mild-to-moderate bleeding tendency: Results from the Vienna Bleeding Biobank (VIBB).

INTRODUCTION: Data on clinical characteristics and the prevalence of underlying coagulopathies in patients with mild-to-moderate bleeding disorders (MBDs) are scarce. AIM: We established the Vienna Bleeding Biobank (VIBB) to characterize and thoroughly investigate Austrian patients with MBDs. RESULTS: Four hundred eighteen patients (female = 345, 82.5%) were included. A platelet function defect (PFD) was diagnosed in 26 (6.2%) and a possible PFD in 30 (7.2%) patients. Eight patients (1.9%) were diagnosed with von Willebrand disease (VWD) (type 1 n = 6; type 2 n = 2), and 29 patients had low VWF (30-50 IU/dL). Deficiencies in factor VIII, IX, XI or XIII were found in 11 (2.6%), 3 (0.7%), 3 (0.7%) and 1 patient(s), 2 patients had dysfibrinogenaemia, and further 2 had possible PFD and FXI deficiency. Probable causal mutations were detected in 8 of 11 patients with FVIII deficiency, 2 of 3 patients with FIX deficiency and 2 of 8 patients with VWD. Three hundred three patients (72.5%) had normal results in the coagulation assays and were categorized as patients with bleeding of unknown cause (BUC). The bleeding score did not differ between patients with and without established diagnosis. A diagnosis of a bleeding disorder was more frequently made in men than in women (49.3% vs 22.9%). Male sex (OR 3.55, 95% CI: 2.02-6.22; P < .001) and blood group 0 (OR 1.86, 95% CI: 1.17-2.94; P = .008) were independently associated with diagnosis of a bleeding disorder. CONCLUSION: The high rate of patients with BUC despite in-depth haemostatic assessment underlines the incompleteness of available routine laboratory tests. Males with MBDs were more likely to be diagnosed with an established bleeding disorder than females.

Plasma clot properties in patients with a mild-to-moderate bleeding tendency of unknown cause.

In a large proportion of patients with mild bleeding disorders (MBDs) no diagnosis can be established by routine coagulation tests. We investigated whether alterations in plasma clot properties account for MBDs of unknown cause. Ninety-five patients with MBDs of unknown origin and 98 age- and sex-matched healthy controls were investigated. Furthermore, data of 25 patients with a deficiency of factor VIII were analyzed. Plasma clot characteristics in the absence and presence of recombinant tissue plasminogen activator (rtPA) represented by the lag phase, rate of protofibril formation (Vmax), fibrin structure (ΔAbs), time to peak (TTP), half lysis time (t50 and area under the curve (AUC) were measured in turbidometric clot formation and lysis assays. In the fibrinolysis assay, Vmax was lower in patients than in healthy controls. No differences in the other parameters of clot formation and lysis were detected between the groups. There was no clear association of plasma clot properties with the clinical severity of bleeding in patients with MBDs. Patients with known decreased factor VIII levels also showed a lower Vmax. Fibrinogen levels were positively associated with each of the assessed parameters in both groups, with the strongest association with ΔAbs, indicating altered fibrin structure. Factor VIII activity correlated with altered clot characteristics similar to fibrinogen, especially in patients, with the strongest positive correlation to Vmax. This cohort of patients with MBDs of unknown origin showed a lower rate of fibrin formation in the fibrinolysis assay, but otherwise similar plasma clot properties compared to healthy controls.

The mind's scalpel in surgical education: a randomised controlled trial of mental imagery.

OBJECTIVE: To evaluate the role of mental imagery (MI) in resident training for a complex surgical procedure. DESIGN: Randomised controlled trial. SETTING: Eight centres across Canada and the USA. POPULATION: Junior gynaecology residents who had performed fewer than five vaginal hysterectomies (VH). METHODS: After performing a pretest VH, junior gynaecology residents were randomised to standard MI versus textbook reading (No MI) and then performed a test VH. Surgeons blinded to group evaluated resident performance on the pretest and test VH via global rating scales (GRS), procedure-specific scales and intraoperative parameters. Residents evaluated their own performance. MAIN OUTCOME MEASURE: Change in surgeon GRS score from pretest to test VH. The study was powered to detect a 20% difference in score change. RESULTS: Fifty residents completed the trial (24 MI, 26 No MI). There was no difference in GRS score change via blinded assessment from pretest to test evaluation between groups (mean change 13% [SD 17] versus 7% [SD 14], P = 0.192). There was no difference in procedure-specific score change. There was a significant difference in self-scored GRS score change between groups (mean change 19% [SD 12] versus 9% [SD 11], P = 0.005). Residents also felt more confident performing a VH (mean change 19% [SD 16] MI versus 11% [SD 10] No MI, P = 0.033). CONCLUSIONS: No difference was observed in the surgical performance of residents after MI. Improved resident self-confidence may be attributable to MI or the effect of unblinding on trial participants.

Hip-spine syndrome: A cadaveric analysis between osteoarthritis of the lumbar spine and hip joints.

BACKGROUND: Authors have recently proposed the concept of "hip-spine syndrome", however there exists limited evidence available to differentiate whether these concomitant arthritides are due to anatomic/structural causes, or systemic/metabolic effects. Exploring this relationship has important implications during the evaluation and treatment of both spine and hip disorders-a common clinical presentation of many patients. The purpose of this experiment was to investigate the individual contribution of hip arthritis towards the development of spine arthritis, with knee arthritis also being analyzed as a negative (systemic) control. HYPOTHESIS: Hip and spine arthritis are caused by both metabolic and anatomic causes. METHODS: A large, well-organized osteological database was queried, and osteoarthritis of the spine, hip, and knee joints was quantified using a validated scoring criteria. Six hundred and twenty-five specimens were chosen for analysis. Multivariate linear regression models were created to quantify the independent contributions of age, gender, race, height, and arthritis of the spine and hip joints. RESULTS: Age was the strongest predictor of arthritis at each site (standardized betas>0.281, P<0.001 for all). Hip arthritis was a stronger predictor of spine arthritis than was knee arthritis (standardized betas 0.215 and 0.155, respectively, P<0.001 for both). Spine arthritis was also a stronger predictor of hip arthritis than was knee arthritis (standardized betas 0.232 and 0.173, P<0.001 for both). CONCLUSIONS: Anatomic/structural influences about the lumbosacral-pelvic junction contribute towards the development of arthritis that is separate from any systemic/metabolic effects. Surgeons performing total hip arthroplasty should remain aware of these relationships, although future research is necessary regarding optimal surgical treatment of these patients. LEVEL OF EVIDENCE: N/A (cadaveric study).

Relationship between pelvic incidence and osteoarthritis of the hip.

OBJECTIVES: Sagittal alignment of the lumbosacral spine, and specifically pelvic incidence (PI), has been implicated in the development of spine pathology, but generally ignored with regards to diseases of the hip. We aimed to determine if increased PI is correlated with higher rates of hip osteoarthritis (HOA). The effect of PI on the development of knee osteoarthritis (KOA) was used as a negative control. METHODS: We studied 400 well-preserved cadaveric skeletons ranging from 50 to 79 years of age at death. Each specimen's OA of the hip and knee were graded using a previously described method. PI was measured from standardised lateral photographs of reconstructed pelvises. Multiple regression analysis was performed to determine the relationship between age and PI with HOA and KOA. RESULTS: The mean age was 60.2 years (standard deviation (sd) 8.1), and the mean PI was 46.7° (sd 10.7°). Multiple regression analysis demonstrated a significant correlation between increased PI and HOA (standardised beta = 0.103, p = 0.017). There was no correlation between PI and KOA (standardised beta = 0.003, p = 0.912). CONCLUSION: Higher PI in the younger individual may contribute to the development of HOA in later life.Cite this article: Dr J. J. Gebhart. Relationship between pelvic incidence and osteoarthritis of the hip. Bone Joint Res 2016;5:66-72. DOI: 10.1302/2046-3758.52.2000552.

Decreasing pelvic incidence is associated with greater risk of cam morphology.

OBJECTIVES: The spinopelvic relationship (including pelvic incidence) has been shown to influence pelvic orientation, but its potential association with femoroacetabular impingement has not been thoroughly explored. The purpose of this study was to prove the hypothesis that decreasing pelvic incidence is associated with increased risk of cam morphology. METHODS: Two matching cohorts were created from a collection of cadaveric specimens with known pelvic incidences: 50 subjects with the highest pelvic incidence (all subjects > 60°) and 50 subjects with the lowest pelvic incidence (all subjects < 35°). Femoral version, acetabular version, and alpha angles were directly measured from each specimen bilaterally. Cam morphology was defined as alpha angle > 55°. Differences between the two cohorts were analysed with a Student's t-test and the difference in incidence of cam morphology was assessed using a chi-squared test. The significance level for all tests was set at p < 0.05. RESULTS: Cam morphology was identified in 47/100 (47%) femurs in the cohort with pelvic incidence < 35° and in only 25/100 (25%) femurs in the cohort with pelvic incidence > 60° (p = 0.002). The mean alpha angle was also greater in the cohort with pelvic incidence < 35° (mean 53.7°, sd 10.7° versus mean 49.7°, sd 10.6°; p = 0.008). CONCLUSIONS: Decreased pelvic incidence is associated with development of cam morphology. We propose a novel theory wherein subjects with decreased pelvic incidence compensate during gait (to maintain optimal sagittal balance) through anterior pelvic tilt, creating artificial anterior acetabular overcoverage and recurrent impingement that increases risk for cam morphology.Cite this article: W. Z. Morris, C. A. Fowers, R. T. Yuh, J. J. Gebhart, M. J. Salata, R. W. Liu. Decreasing pelvic incidence is associated with greater risk of cam morphology. Bone Joint Res 2016;5:387-392. DOI: 10.1302/2046-3758.59.BJR-2016-0028.R1.

On-line laser-photometric monitoring of aerosol deposition in ventilated rabbit lungs.

A photometric technique was developed for on-line measurement of aerosol deposition in isolated, ventilated, and perfused rabbit lungs. A jet nebulizer was used for aerosolization of saline (hygroscopic particles) and di(2-ethylhexyl) sebacate (nonhygroscopic particles). Aerosol concentration (laser photometer, constructed for measurements in rabbit lungs) and flow rate (commercial pneumotachograph) were continuously monitored at the inlet of the tracheal cannula. Computer-assisted data processing allowed the breath-by-breath calculation of inhaled and exhaled aerosol mass, thus providing the deposition fraction. With the use of hygroscopic particles, however, this approach was hampered by the humidity-induced particle growth in the airways, leading to an overestimation of the aerosol concentration in exhaled air. This effect was corrected by an algorithm using a "particle growth factor" derived breath by breath from the photometer signal. To test the reliability of this approach, saline particles carrying technetium-99m label were aerosolized into rabbit lungs with the use of various ventilator settings, and the aerosol deposition was assessed in parallel by photometry and by radioactivity detection over the lung and over a trap in the exhaled-air circuit. Superimposable curves of cumulative aerosol deposition, with changes in kinetics dependent on the ventilator mode, were obtained. For a given ventilator setting, absolute values of the deposition fraction were 0.32 +/- 0.04 (radiotracer quantification) and 0.36 +/- 0.04 (photometry; means +/- SD; n = 4). We conclude that the presented laser-photometric technique allows reliable on-line monitoring of the deposition of both nonhygroscopic and hygroscopic aerosol particles in ventilated lungs.

Convective and diffusive gas transport in canine intrapulmonary airways.

The significance of convective and diffusive gas transport in the respiratory system was assessed from the response of combined inert gas and particle boluses inhaled into the conducting airways. Particles, considered as "nondiffusing gas," served as tracers for convection and two inert gases with widely different diffusive characteristics (He and SF6) as tracers for convection and diffusion. Six-milliliter boluses labeled with monodisperse di-2-ethylhexyl sebacate droplets of 0.86-microns aerodynamic diameter, 2% He, and 2% SF6 were inspired by three anesthetized mechanically ventilated beagle dogs to volumetric lung depths up to 170 ml. Mixing between inspired and residual air caused dispersion of the inspired bolus, which was quantified in terms of the bolus half-width. Dispersion of particles increased with increasing lung depth to which the boluses were inhaled. The increase followed a power law with exponents less than 0.5 (mean 0.39), indicating that the effect of convective mixing per unit volume was reduced with depth. Within the pulmonary dead space, the behavior of the inert gases He and SF6 was similar to that of the particles, suggesting that gas transport was almost solely due to convection. Beyond the dead space, dispersion of He and SF6 increased more rapidly than dispersion of particles, indicating that diffusion became significant. The gas and particle bolus technique offers a suitable approach to differential analysis of gas transport in intrapulmonary airways of lungs.

Experimental data for total deposition in the respiratory tract of children.

Up to now only few experimental data for total deposition of inhaled aerosol particles are available for children. In this study 29 healthy children aged between 3 and 14 years volunteered for the determination of 1 micron, 2 microns and 3 microns particles for spontaneous and controlled breathing. It turns out that total deposition values for children are higher than for adults. The effect is significant for all particle sizes (Kruskal-Wallis). For the applied breathing patterns deposition decreases as a function of body height. For inhalation risk assessments the number of particles deposited per unit time (deposition rate) rather than the deposition per breath has to be taken. During spontaneous breathing at rest the deposition rate is on average higher for children than for adults.

Deposition of inspired aerosol particles within the respiratory tract of patients with obstructive lung disease.

Total deposition of monodisperse aerosol particles in the size range between 1 micron and 3 microns was measured in patients with obstructive lung disease and in normal people using equal breathing conditions for both groups. It turns out that for breathing conditions at rest, deposition for patients is higher, especially in the case of 1 micron particle: A second breathing pattern similar to forced exercise, but including a breath holding interval of 6 s after inhalation, is applied to throw some light on the effect of time-dependent deposition mechanisms. The results show less differences between both groups, indicating that enhanced gravitational deposition during respiratory pauses compensates for differences in lung morphometry.

Effects of age and temporal placement of a modeled skill on children's performance on a balance task.

The present investigation explored the effect of age and temporal placement of a modelled skill on performance on a balance task. 60 boys, aged 7 and 9 yr., were randomly assigned to one of three conditions. The model was presented before any trials were attempted, midway, or not at all during 12 trials. A 2 (age) X 3 (model condition) X 12 (trials) repeated-measures design was utilized. Analysis of variance indicated significant effects of age, temporal appearance of the model, and an interaction of model by age for time on-balance. Model affected younger subjects but not older ones. Treatment did not affect off-balance errors. Findings for age and temporal placement are not consistent with some previous research.

Lupus anticoagulant and thrombosis in splenic marginal zone lymphoma.

INTRODUCTION: Splenic marginal zone lymphoma (SMZL) is a rare low-malignant Non-Hodgkin lymphoma (NHL), in which immune mediated paraneoplastic phenomena such as autoimmune hemolytic anemia (AIHA), autoimmune thrombocytopenia (ITP) and C1 esterase inhibitor deficiency are relatively common. MATERIALS AND METHODS: We performed a multicenter retrospective study in 70 patients on the prevalence and clinical features of antiphospholipid antibodies (aPLA) in SMZL. RESULTS AND CONCLUSIONS: Nine patients (13%) had the diagnosis of a lupus anticoagulant (LA). The occurrence of venous thromboembolic events was significantly higher in LA positive patients compared to LA negative patients (4/9 [44%] vs 5/61 [8%], p = 0.002), especially within 12 months after splenectomy (3/6 [50%] vs 2/28 [7%], p = 0.007). None of the patients with LA had a persistent complete remission of LA after splenectomy, but complete remission of LA was achieved in 2/2 patients after rituximab-bendamustine immuno-chemotherapy. In conclusion, our data show a relatively high prevalence of aPLA in SMZL and an increased risk of postsplenectomy thrombosis in these patients. The fact that rituximab-bendamustine was effective for eradicating LA may be considered as an argument for using immuno-chemotherapy as first line therapy in SMZL patients with LA.

Effects of vaginal hysterectomy on anorectal sensorimotor functions--a prospective study.

BACKGROUND: While bowel and bladder dysfunction are recognized consequences of a radical hysterectomy, the effects of a simple hysterectomy on anorectal sensorimotor functions, particularly rectal sensation, vary among studies and the effects on rectal compliance remain unknown. Our aims were to prospectively evaluate anorectal sensorimotor functions before and after a hysterectomy. METHODS: Anal pressures, rectal compliance, capacity, sensation, and bowel symptoms were assessed before, at 2 months, and at 1 year after a simple vaginal hysterectomy for benign indications in 19 patients. Rectal staircase (0-44 mmHg, 4-mmHg steps), ramp (0-200 mL at 50, 200 and 600 mL min(-1)) and phasic distentions (8, 16, and 24 mmHg above operating pressure) were performed. KEY RESULTS: Anal resting (63 ± 4 before, 56 ± 4 mmHg after) and squeeze pressures (124 ± 12 before, 124 ± 12 mmHg after), rectal compliance and capacity (285 ± 12 before, 290 ± 11 mL 1 year after), and perception of phasic distentions were not different before vs after a hysterectomy. Sensory thresholds for first sensation and the desire to defecate were also not different, but pressure and volume thresholds for urgency were somewhat greater (Hazard ratio = 0.7, 95% CI [0.5, 1.0]) 1 year after (vs before) a hysterectomy. Rectal pressures were higher (P < 0.0001) during fast compared with slow ramp distention; this rate effect was greater at 1 year after a hysterectomy, particularly at 100 mL (P = 0.04). CONCLUSIONS & INFERENCES: A simple vaginal hysterectomy has relatively modest effects (i.e., somewhat reduced rectal urgency and increased stiffness during rapid distention) on rectal sensorimotor functions.

Dysfunctional urinary voiding in women with functional defecatory disorders.

BACKGROUND: While pelvic floor dysfunction may manifest with bladder or bowel symptoms, the relationship between functional defecatory disorders and dysfunctional voiding is unclear. Our hypothesis was that patients with defecatory disorders have generalized pelvic floor dysfunction, manifesting as dysfunctional urinary voiding. METHODS: Voiding was assessed by a symptom questionnaire, a voiding diary, uroflowmetry, and by measuring the postvoid residual urine volume in this case-control study of 28 patients with a functional defecatory disorder (36 ± 2 years, mean ± SEM) and 30 healthy women (36 ± 2 years). KEY RESULTS: Women with a defecatory disorder frequently reported urinary symptoms: urgency (61%), frequency (36%), straining to begin (21%), or finish (50%) voiding, and the sense of incomplete emptying (54%). Fluid intake and output, the minimum voided volume, and the shortest duration between voids measured by voiding diaries were higher (P < 0.05) in patients than in controls. Uroflowmetry revealed abnormalities in seven controls and 22 patients. The risk of abnormal voiding by uroflowmetry was higher in patients (OR 8.0; 95% CI, 2.3-26.9) than in controls. Patients took longer than controls (P < 0.01) to attain the maximum urinary flow rate (12 ± 2 VS 4 ± 0 s) and to empty the bladder (29 ± 4 VS 20 ± 2 s), but the maximum urinary flow rate and postvoid residual volumes were not significantly different. CONCLUSIONS & INFERENCES: Symptoms of dysfunctional voiding and uroflowmetric abnormalities occurred more frequently, suggesting of disordered urination, in women with a defecatory disorder than in healthy controls.

Optimization of response functions of light scattering instruments for size evaluation of aerosol particles.

Response functions of light scattering instruments for size evaluation of aerosol particles depend on the polarization and wavelength distribution of the radiation illuminating the particles, size, and shape of the illumination and collection aperture, spectral transmission of the radiation through the instrument, spectral sensitivity of the photodetector, and the optical properties of the particle material. Analytical expressions of response functions as a function of all these parameters are derived, and satisfactory agreement between theoretical and experimental response functions was obtained. Extensive calculations of response functions show that diameter distributions of airborne particles of unknown optical properties can be evaluated with great accuracy by low angle scattering of polychromatic radiation of continuous wavelength distribution.

Biological variability of regional deposition of aerosol particles in the human respiratory tract.

Regional deposition of inhaled particles was studied experimentally for 9 health subjects breathing the same aerosol under the same breathing conditions in order to evaluate intersubject variability of regional deposition. A great intersubject variability of extrathoracic, tracheobronchial and alveolar deposition was found. The highest one was observed for particle deposition in the extrathoracic airways. This biological variability of regional deposition has to be taken into account for considerations of health related aspects of aerosol inhalation.

Experimental determination of the regional deposition of aerosol particles in the human respiratory tract.

The experimental techniques and the results of inhalation studies with radioaerosols on normal non-smokers for mouth-breathing are described and discussed. Monodisperse iron oxide particles tagged with 198Au are produced with a spinning top generator in the aerodynamic size range between 1 to 10 micrometers. An aerosol inhalation apparatus enables the subjects to breathe under standardized conditions with respect to tidal volume and breathing frequency. The calculation of total deposition is based upon measurements of the number of in- and exhaled particles per breath by means of photometric methods and pneumotachography. The retention of the radioactive particles present in the body after aerosol administration is measured with a body counter designed and constructed for these experiments. Retention measurements as functions of time after inhalation are carried out in extrathoracic-, chest- and stomach-position. The body counter consists of four shielded NaF(TI)-detectors. The geometrical arrangement, the collimation and the shielding of the four detectors have been optimized by computer calculations in such a way that the response of the counter is independent of the distribution of activity within the chest. Another characteristic feature of the body counter is its low sensitivity to neighboring organs and to neighboring regions within the respiratory tract. For the evaluation of extrathoracic deposition, the activity measured in the stomach immediately after inhalation is added to extrathoracic activity. The elimination of material from the chest (intrathoracic airways) is found to be much slower for the material deposited in the alveolar region (non-ciliated air spaces) than for the amount deposited in the tracheobronchial tree (ciliated airways). This allows the intrathoracic deposition to be divided into tracheobronchial and alveolar deposition by means of the different slopes of the normalized chest retention function. Different normalized chest retention functions are presented and analysed with respect to their different elimination rates belonging to the tracheobronchial and alveolar region. Total, tracheobronchial, alveolar and extrathoracic deposition data are reported in the aerodynamic diameter range between 1 and 10 micrometers.

Use of aerosols to estimate pulmonary air-space dimensions.

Single-breath inhalations of monodisperse aerosols were performed with a group of normal subjects to determine aerosol recovery from the human lung after periods of breath holding. Aerosols of monodisperse nonhygroscopic droplets of bis(2-ethylhexyl) sebacate of between 0.5 and about 2.5 micron diam were used for the inhalation. The inhalation apparatus allows continuous monitoring of particle number concentration and flow rate close to the mouth. Experiments were designed to find the optimum experimental conditions for the principal concept of Palmes et al (In: Inhaled Particles and Vapours. London: Pergamon, 1976, vol. II. p. 339-347) to evaluate pulmonary air-space dimensions by means of aerosols. The experimental results obtained for various respiratory flow rates (125, 250, and 500 cm3 X s-1), settling velocities of the particles (10(-3) to 1.5 X 10(-2) cm X s-1) and volumes of inspired aerosols (500, 1,000, and 2,000 cm3) are compared with the results derived from a mathematical model for the particle deposition during respiratory pauses. Monodisperse aerosols with particles between 1 and about 1.5 micron diam. inspired for breath holding into the lung region of interest, may provide optimum conditions for the sizing of air spaces by means of aerosols.

[A reminder of the legacy of Sigmund Freud]. / Pipomenutí odkazu Sigmunda Freuda.

In September 1989 fifty years elapsed since the death of Sigmund Freud, the founder of psychoanalysis. The authors recall selected topical ideas from the work of Freud. At the same time they draw attention to the importance of his studies for the left-wing student movement in Czechoslovakia between the two world wars. Initial attempts of a close association of psychology with the nervous substrate did not succeed but led later to the original explanation of converse mechanisms. In his own way Freud anticipated contemporary bio-psycho-social concepts. Gradually subconsciousness was conceived as Freud's most important discovery. Energy for mental life was sought in the sphere of instincts, in particular the sexual instinct, Freud extrapolated his reflections into the social sphere and elaborated his understanding of group psychology, using mechanisms of the individual psychic make-up. From this he derived regulatory mechanisms of civilization. Freud believed in reason represented to him by science. He considered religion illusionary happiness and warned also against the so-called chemical path. He denounced war unequivocally and had his own ideas how to reduce its probability.