Morphometry of the human pulmonary vasculature

Huang, W., R. T. Yen, M. McLaurine, and G. Bledsoe.Morphometry of the human pulmonary vasculature.J. Appl. Physiol. 81(5):2123-2133, 1996.The morphometric data on the branching patternand vascular geometry of the human pulmonary arterial and venous treesare presented. Arterial and venous casts were prepared by the siliconeelastomer casting method. Three recent innovations are used to describethe vascular geometry: the diameter-defined Strahler ordering model isused to assign branching orders, the connectivity matrix is used todescribe the connection of blood vessels from one order to another, anda distinction between vessel segments and vessel elements is used toexpress the series-parallel feature of the pulmonary vessels. A totalof 15 orders of arteries were found between the main pulmonary arteryand the capillaries in the left lung and a total of 15 orders of veinsbetween the capillaries and the left atrium in the right lung. Theelemental and segmental data are presented. The morphometric data arethen used to compute the total cross-sectional areas, blood volumes, and fractal dimensions in the pulmonary arterial and venous trees.

     

Balance study in asymptomatic subjects: Determination of significant variables and reference patterns to improve clinical application

Postural control is essential when carrying out everyday activities and its possible disorders have a very significant impact on personal autonomy. To provide the means to accurately measure postural control in the clinical environment, this study checks and discusses the suitability of procedures for a new balance assessment system with a stabilometric platform (MoveHuman-Dyna © UZ-IDERGO), which meets the criteria of clinical stabilometric standardisation established by the International Society for Posture and Gait Research (ISPGR) at the Bologna meeting (2009). The study was applied to a sample of 30 healthy volunteers (12 women, 18 men) aged between 18 and 30 years. A total of six balance tests were performed: four variations of the Romberg test, one test for a study of the limits of stability (LoS) and one test for rhythmic weight shift (RWS). Analysis of the results confirms that the variables assessed yielded similar values to other studies, the consistency of values between tests was checked, and preliminary reference values were obtained for asymptomatic subjects. We propose the following variables as the most significant for balance diagnosis: CoP mean speed, RMS, Range of CoP displacement and area. As a result of the study, the system is considered of interest in the medical/legal and forensic settings to assess the balance control and degree of collaboration during the tests.     

The pixie earlobe: a method of correction

A simple method for the correction of the pixie earlobe is documented. This technique preserves the natural free border of the earlobe.     

Synchronicity of systolic deformation in healthy pediatric and young adult subjects: a two-dimensional strain echocardiography study

Two-dimensional speckle tracking echocardiography (2DSTE) offers valuable information in the echocardiographic assessment of ventricular myocardial function. It enables the quantification and timing of systolic ventricular myocardial deformation. In addition, 2DSTE can be used to identify mechanical dyssynchrony, which is an important parameter in predicting the response to cardiac resynchronization therapy for heart failure. Detailed knowledge of normal timing of systolic deformation and its degree of synchronicity in children is lacking. We aimed to establish the normal timing of left ventricular myocardial systolic deformation using 2DSTE in a large cohort of healthy children and young adults. Transthoracic echocardiograms were acquired in 195 healthy subjects (139 children and 56 young adult <40 yr of age) and were retrospectively analyzed. Time to peak systolic longitudinal, circumferential, and radial strain was determined by means of speckle tracking. Strong, statistically significant relations between age as well as various anthropometric variables (e.g., heart rate) and timing of systolic deformation (P < 0.0001) were present. The extent of dyssynchronous deformation increased with age. This is the first report that establishes reference values per cardiac segment for time to peak systolic myocardial strain values in all three directions assessed with 2DSTE in a large pediatric and young adult cohort. We emphasize the need for using age-specific reference values as well as heart rate correction for the adequate interpretation of 2DSTE measurements.     

Determination of endogenous glycosaminoglycans derived disaccharides in human plasma by HPLC: validation and application in a clinical study

SB-424323 is a new, orally active anti-thrombotic agent presently in phase-II clinical development, with limited hemorrhagic risk and a unique mechanism of action involving the induction of glycosaminoglycans (GAGs) biosynthesis. The objective of the present study was to develop a simple and rapid high performance liquid chromatography (HPLC) method for determination of endogenous GAGs derived disaccharides in plasma samples from a phase-II clinical study of SB-424323. Sample preparation was a simple heat treatment of the diluted plasma followed by digestion of endogenous GAGs with chondroitinase ABC to yield unsaturated disaccharides, 2-acetamido-2-deoxy-3-O-(beta-D-gluco-4-enepyranosyluronic acid)-D-galactose (DeltaDi-0S), 2-acetamido-2-deoxy-3-O-(beta-D-gluco-4-enepyranosyluronic acid)-4-O-sulfo-D-galactose (DeltaDi-4S), and 2-acetamido-2-deoxy-3-O-(beta-D-gluco-4-enepyranosyluronic acid)-6-O-sulfo-D-galactose (DeltaDi-6S). These disaccharides were recovered and purified using centrifugal filtration through a filter with 3000 molecular weight cut-off along with externally added internal standard 2-acetamido-2-deoxy-3-O-(2-O-sulfo-beta-D-gluco-4-enepyranosyluronic acid)-D-galactose (DeltaDi-UA2S). A gradient reverse phase HPLC separation was developed on a Waters Symmetry C(18) column (4.6 mm x 150 mm, 5 microm) with a gradient mobile phase system consisting of 0.8 mM tetrabutylammonium hydrogen sulfate and 2mM sodium chloride and acetonitrile at a flow rate of 1.0 mL/min. The eluate was monitored with an ultraviolet detector set at 230 nm. Plasma standard curves were linear (r(2)> or =0.994) in the concentration range 1.0-20 microg/mL with a lower limit of quantification (LLOQ) of 1.0 microg/mL for each of the disaccharide. The mean measured quality control (QC) concentrations for the disaccharides deviated from the nominal concentrations in the range of -8.92 to 5.61% and -16.3 to 16.7%, for inter and intra-day, respectively. The inter and intra-day precision in the measurement of QC samples, were in the range of 3.21 to 18.2% relative standard deviation (R.S.D.) and 0.32 to 20.9% R.S.D., respectively. The inter and intra-day precision in the measurement of endogenous GAGs derived disaccharides in human control plasma, were in the range of 5.8 to 15.9% R.S.D. and 1.17 to 7.74% R.S.D., respectively. Stability of the processed samples was confirmed up to 48 h in the auto-sampler. The method is simple, reliable, and easily adaptable to analysis of large number of samples under logistics of a clinical study. The present method has been used to investigate the GAGs levels in the plasma of patients in a phase II clinical study of SB-424323.     

A study of gait acceleration and synchronisation in healthy adult subjects

Accelerometry-based gait analysis is widely recognised as a promising tool in healthcare and clinical settings since it is unobtrusive, inexpensive and capable of providing insightful information on human gait characteristics. In order to expand the application of this technology in daily environments, it is desirable to develop reliable gait measures and their extraction methods from the acceleration signal that can differentiate between normal and atypical gait. Important examples of such measures are gait cycle and gait-induced acceleration magnitude, which are known to be closely related to each other depending on each individual's physical condition. In this study, we derive a model equation with two parameters which captures the essential relationships between gait cycle and gait acceleration based on experiments and physical modelling. We also introduce as a new gait parameter a set of indexes to evaluate the synchronisation behaviour of gait timing. The function and utility of the proposed parameters are examined in 11 healthy subjects during walking under various selected conditions.     

Practical application of flavonoid-poor menu meals to the study of the bioavailability of bilberry anthocyanins in human subjects

Practical application of flavonoid-poor menus was evaluated on the bioavailability of anthocyanins as model flavonoids. Detectable amounts of flavonoids were not found in plasma and urine collected from 13 participants, who took the menus. After ingesting bilberry anthocyanins (919 μmol), average plasma AUC_0-6h, C_max, T_max values and urinary recovery were 386.0 nmol h/mL, 139.1 nM, 1.31 h and 0.21%, respectively.     

Liver afferents contribute to water drinking-induced sympathetic activation in human subjects: a clinical trial

Water drinking acutely increases sympathetic activity in human subjects. In animals, the response appears to be mediated through transient receptor potential channel TRPV4 activation on osmosensitive hepatic spinal afferents, described as osmopressor response. We hypothesized that hepatic denervation attenuates water drinking-induced sympathetic activation. We studied 20 liver transplant recipients (44±2.6 years, 1.2±0.1 years post transplant) as model of hepatic denervation and 20 kidney transplant recipients (43±2.6 years, 0.8±0.1 years post transplant) as immunosuppressive drug matched control group. Before and after 500 ml water ingestion, we obtained venous blood samples for catecholamine analysis. We also monitored brachial and finger blood pressure, ECG, and thoracic bioimpedance. Plasma norepinephrine concentration had changed by 0.01±0.07 nmol/l in liver and by 0.21±0.07 nmol/l in kidney transplant recipients (p<0.05 between groups) after 30-40 minutes of water drinking. While blood pressure and systemic vascular resistance increased in both groups, the responses tended to be attenuated in liver transplant recipients. Our findings support the idea that osmosensitive hepatic afferents are involved in water drinking-induced sympathetic activation in human subjects. TRIAL REGISTRATION: ClinicalTrials.gov NCT01237431.     

Standardization and clinical application of a radioimmunoassay for human calcitonin.

A radioimmunoassay for the measurement of Human Calcitonin (HCT) is described. Serum levels of HCT in normal subjects and in individuals under different pathological conditions have been studied with this method. HCT labelling is performed following the chloramine T method of Hunter and Greenwood. Adding successively Quso G-32 (a finely powdered silica) and an anion exchange resin (AGI-X10 resin), to the tracer, reduces both the damaged fraction and the free isotope which originate during storage. Purification of the labelled hormone is carried out through a Sephadex G-50 gel column. Sera stored at --20 degrees C preserves its immunoreactivity up to 4 months after extraction. The mean basal HCT levels in 110 fasting normal persons is 277 +/- 123 pg/ml (undetectable 8.28%). No significant correlation between HCT levels and various serum ions has been observed. Basal HCT values in seven patients with medullary thyroid carcinoma (MTC), oscillated between 5 and 110 ng/ml, while in six other patients with non medullary thyroid carcinoma the values remained within normal range. Both a calcium infustion and a pentagastrin injection are used to stimulate HCT secretion. The increase of HCT basal levels produced by the latter in normal controls and in patients with MTC, is faster and more intense. Calcium infusion produced a significant correlation between calcium and the increased HCT levels only in patients affected with MTC.     

Thomsen-Friedenreich-related carbohydrate antigens in normal adult human tissues: a systematic and comparative study

A broad variety of normal human tissues were examined for the expression of Thomsen-Friedenreich (TF)-related histo-blood group antigens. TF (Galβ1-3GalNAcα1-R), Tn (TF precursor, GalNAcα1-R), sialosyl-Tn (NeuAcα2-6GalNAcα1-R), considered to be useful in cancer diagnosis and immunotherapy, and sialosyl-TF, the cryptic form of TF. These antigens or, more correctly, glycotopcs, were determined by immunohistochemistry with at least two monoclonal antibodies (mAbs) each (except sialosyl-TF) as well as by lectin histochemistry. For a better dissection of sialosyl-TF and TF glycotopes, tissue sections were pretreated with galactose oxidase or the galactose oxidase-Schiff sequence. Staining with mAbs appeared to be more restricted than with the lectins used. Distribution patterns among normal epithelia were different for all four antigens. These antigens were also detected in some non-epithelial tissues. They can be classified in the following sequence according to the frequency of their occurrence in normal tissues: sialosyl-TF> >sialosyl-Tn>Tn>TF. Most of the positively staining sites for TF, Tn, and sialosyl-Tn are located in immunologically privileged areas. The complex results obtained with anti-TF mAbs (after treatment of the tissue sections with sialidase fromVibrio cholerae) and the lectins amaranthin and jacalin revealed a differential distribution of the subtypes of sialosyl-TF [NeuAcα2-3Galβ1-3GalNAcα1-R and Galβ1-3 (NeuAcα2-6)GalNAcα1-R] in normal human tissues. From our data it can be inferred that TF, Tn, and sialosyl-Tn are promising targets for a cancer vaccine.     

Delayed toe transplantation: experimental study and clinical application

Delay of the operation in toe transplantation was performed with circulatory crisis, and 100 percent survival of the transplants was achieved. In 10 cases of toe transplantation in which circulatory crisis occurred, the operation was delayed. The vascular pedicle was divided, and the toe was transferred 17 to 21 hours after the donor toe was dissected. To investigate the mechanism of delayed toe transplantation, experiments in rabbits were carried out. In 36 rabbits, the hind limbs were severed except for the vascular pedicle. The endothelin content and nitric oxide content of the tissues in the hind limb and the arterial wall were tested in postoperative intervals of 4, 8, 16, 24, and 48 hours, respectively. The results showed that in 10 cases of delayed toe transplantation, all toes survived. As for the results of the experiment, there was significant increase of endothelin content and decrease of nitric oxide content in the local tissues and the arterial wall 4 to 8 hours after the operation. In postoperative 16 to 24 hours, endothelin content returned to normal level, and nitric oxide content increased remarkably. It is concluded that delayed pedicle division and toe transfer is an effective method in toe transplantation with vascular variations and circulatory crisis. The mechanism is related to the endothelin and nitric oxide content in the local tissue and the arterial wall. The indications for delayed toe transfer are also discussed.     

Fibular osteoseptocutaneous flap: anatomic study and clinical application

The vascularized fibular graft has been expanded to an osteoseptocutaneous flap by including a cutaneous flap on the lateral aspect of the lower leg. The cutaneous flap can serve not only for postoperative monitoring of the grafted fibula, but also as extra skin coverage to replace substantial skin defects or prevent tight closure of the wound. From anatomic studies of 20 cadaver legs and 15 clinical cases, it has been possible to demonstrate adequate circulation to the skin of the lateral aspect of the lower leg from the septocutaneous branches of the peroneal artery alone. This finding has allowed the development of a new concept and technique to elevate the fibula as an osteoseptocutaneous flap for reconstruction which provides the following advantages: Elevation of the fibular osteoseptocutaneous unit is easy and fast. The cutaneous flap of the fibular osteoseptocutaneous unit can slide almost freely while attached to the paper-thin posterior crural septum without being tethered by a bulky muscle cuff, facilitating the setting of the fibular osteocutaneous flap when the bone and skin are widely separated. Intraoperatively, in a situation in which it is necessary to change from originally selected recipient vessels to ones more suitable, the thin posterior crural septum can be folded around the fibula allowing more flexibility in choice of recipient vessels. The fibular osteoseptocutaneous flap meets the criteria outlined for composite tissue reconstruction of defects of the extremities.(ABSTRACT TRUNCATED AT 250 WORDS)     

Physical activity and energy expenditure in lean and obese adult human subjects.

We compared the physical activity of 11 lean and 11 obese men and women over a 7-day period. There were no significant differences in either the amount of movement recorded with an accelerometer (9.5 (SD 3.9) vs 9.9 (SD 2.6) kcounts.day-1), or in the energy expenditure due to physical activity reflected by the difference between the average daily metabolic rate measured by the doubly labelled water technique and the sleeping metabolic rate measured in a respiration chamber and adjusted for fat-free mass: 112 (SD 33) vs 118 (SD 22) kJ.kg-1.day-1. The obese showed a non-significant loss of body mass of 0.5 (SD 1.1) kg, probably due to reduced intake during the 7-day intake recording period.