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Biomedical subjects

W Heizer

Publications and source records attributed to W Heizer.

6 recordsLinked to original sources

Human development of grip force modulation relating to cyclic movement-induced inertial loads.

The present study examines the development of grip force modulation relating to self-induced loads during repetitive vertical arm movements at different frequencies with a hand-held object. One hundred and thirty-four 3- to 6-year-old children and 16 adults were asked to move a lightweight object up and down at increasing rates from 0.5 Hz up to individual maximal arm movement rates (> 2.5 Hz). Grip forces were measured by a uni-axial force transducer and the inertial forces (tangential forces) were calculated from the measurements by accelerometers within the object. Generally, the quality of anticipatory grip force control improved from movement frequencies of 1 Hz to 2.5 Hz and decreased above 2.5 Hz. At movement frequencies below 1 Hz, the phase lag between grip and load force cycles was longer in children than in adults (children: median = 17 ms; adults: median = 0 ms); however, there were no significant differences between the age groups above 1.5 Hz. The grip-to-load force ratio and the grip force modulation were not significantly different from the adults up to 2.5 Hz. The fine coupling of grip and load forces (precise temporal and gain control) showed age effects among the 3- to 6-year-old children, mainly between 3- and 4-year-olds, and in adults extremely good coupling at medium arm movement frequencies. However, concerning the pure temporal coordination of grip and inertial forces, there were only differences between the 3-year-old children and the other groups at arm movement frequencies above 2.5 Hz. The results show that, during cyclic movements with hand-held loads, temporal control is well established at the age of 4 years whereas the fine gain control needs a longer time to develop. The anticipatory control is dependent on the arm movement frequency and, therefore, how rapidly the inertial loads change. The high level of anticipatory control during self-induced repetitive actions in children of 3-6 years of age is interpreted as an early developing ability to predict precisely cyclic self-induced inertial loads of hand-held objects when the object properties are known by proprioception. The timing, which is possibly related to cerebellar functions, is, to some extent, developed earlier than the gain control, which may be associated with cortical functions.

Adult↗

Development of externally guided grip force modulation in man.

We examined the development of externally guided changes of grip force with respect to force rate and direction of force change. Sixty-nine children, 3-6 years of age, and 17 adults produced increasing or decreasing isometric forces on a small cylindrical sensor using a pinch grip with visual feedback. Force changes were instructed with a visual tracking task. Ramp-like paradigms with both force increase and force decrease and two different target force rates were used (0.5 N/s, 1.25 N/s). Precision of force tracking showed clear age effects and was influenced by the required force rates and directions of force change. In adults, tracking errors were much more dependent on target force rate and direction than in children. Up to four years of age, the children tended to overshoot the target force change in a 'jump and wait' manner in all conditions except for fast target force decreases. Older children tended to overshoot only in the condition with slow target force decrease. Adults showed close undershooting in all conditions when following the target. Adults used either a continuous 'following' strategy or a 'see and catch-up' strategy. The distinct effects on tracking errors suggest an age-related change of strategies from a feedforward strategy with intermittent use of sensorimotor feedback towards a fairly parallel and well-integrated feedback and feedforward processing. A critical age appears to be around five to six years. We suggest that these age effects may reflect distinct developmental velocities of neuronal subpopulations of the cortex and of the cerebello-cortical connections.

Adult↗

Externally guided control of static grip forces by visual feedback-age and task effects in 3-6-year old children and in adults.

This study has been devised to examine the visual feedback control of static grip force levels by pinch and by hand grip during pre-school age and in adults. 69 3-6-year old children and 17 adults were asked to establish and hold grip force levels defined by a visual target and feedback on the dominant and non-dominant hand by hand grip and by pinch grip. From 3 to 6 years of age, the time needed to establish requested grip force levels decreased by a third and the precision increased two-fold for hand grip but four-fold for pinch grip; in contrast to younger children, 5-6-year olds showed a marked superiority of 60% for the pinch grip compared to hand grip, decreasing to about 40% in adults. In the case of pinch grip, all individuals had worse results on higher force levels (children: 50%, adults: 32%). The young children generally tended to use too much force. Older children and adults were better by 75% under the condition of visual feedback vs. internal proprioceptive control (after withdrawing visual feedback). In contrast to previous findings in anticipatory grip force regulation, externally guided force regulation begins to develop during late nursery age. Specific developmental effects were found for grip style and for the ability to use visual feedback and to change from external to internal (proprioceptive) control, and to a lesser extent for force magnitude but not for hand laterality and gender. The findings are interpreted by different developmental velocities of motor areas which are responsible for force regulation mechanisms and for grip style.

Adult↗

Influence of gastrointestinal site of drug delivery on the absorption characteristics of ranitidine.

The absorption characteristics of ranitidine after delivery to three locations in the gastrointestinal tract were compared in an open-label study of eight healthy males. Subjects received ranitidine HCl (150 mg) for injection via a nasoenteric tube directly into their stomach, jejunum, or cecum sequentially in three separate periods (24 hr apart). Plasma samples were collected at periodic time intervals for 12 hr following each dosing and analyzed for ranitidine concentration by high-pressure liquid chromatography. Mean concentrations following cecal dosing were lower (P less than 0.05) than concentrations following gastric or jejunal dosing at each sampling time except baseline. Mean concentrations following gastric and jejunal dosing were similar except at 2 hr (gastric greater than jejunal). Mean pharmacokinetic parameters for cecal administration were different (P less than 0.05) from either the gastric or the jejunal periods with the exception of Tmax. There was no difference in any pharmacokinetic parameter after gastric or jejunal dosing. The relative bioavailability after cecal administration was less than 15% of that observed after administration into the stomach or jejunum. Additionally, Wagner-Nelson analysis indicated that the rate of ranitidine absorption was much slower following cecal administration than after gastric or jejunal dosing. Two plasma concentration peaks were observed in three of eight subjects after gastric dosing, in eight of eight subjects after jejunal dosing, and in zero of eight subjects after cecal dosing. These data demonstrate that the absorption profile of ranitidine is equivalent, in extent and duration, after delivery to the stomach or jejunum, while absorption from the cecum is significantly less.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Protein digestion in human and rat small intestine: role of new neutral endopeptidases.

Two new phosphoramidon-insensitive neutral endopeptidases were identified and partially characterized in the brush-border membrane of rat and human intestine using N-CBZ-L-Ala-L-Arg-L-Arg-4-methoxy-beta-naphthylamide (Z-Ala-Arg-Arg-MNA) and azocasein or alpha-casein as substrates. Activities in the brush-border membrane of both rat and human intestine were maximum at neutral to alkaline pH, were inhibited by metal chelating and thiol reagents, and were insensitive to phosphoramidon. The results also indicate that these endopeptidases are distinct from pancreatic proteases. The biochemical properties of the enzyme hydrolyzing Z-Ala-Arg-Arg-MNA were shown to be different from that hydrolyzing azocasein or alpha-casein. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis and gel filtration revealed that several native intact protein substrates were rapidly degraded to small molecular weight peptides and amino acids when incubated with rat or human brush-border membrane preparations. During in vivo intestinal perfusion in rats, 11% of the total administered alpha-casein was hydrolyzed and absorbed by the intestine. The results suggest that phosphoramidon-insensitive endopeptidases in the intestinal brush-border membrane may be of nutritional and physiological importance in protein digestion.

Animals↗

Human intestinal brush border peptidases.

Hydrolysis of small peptides, like disaccharide hydrolysis, is an important function of the intestinal brush border, but little is known of the individual human peptidases. The purposes of this study were to detect all human brush border enzymes hydrolyzing dipeptides and tripeptides, identify the most discriminating substrate for each enzyme in order to permit assays in crude mixtures, and begin biochemical characterization of each enzyme. Four brush border peptidases were identified. Enzymes I (aspartate aminopeptidase, E.C. 3.4.11.7) and III (amino-oligopeptidase, E.C. 3.4.11.2) are known brush border enzymes. Enzymes II (membrane Gly-Leu peptidase) and IV (zinc stable Asp-Lys peptidase) have not been identified in human brush border previously. They are distinct from dipeptidyl aminopeptidase IV, carboxypeptidase, and gamma-glutamyl transferase. The substrate most discriminating for each enzyme is alpha-Glu-beta-naphthylamide for I (100% of the brush border activity for this substrate is due to enzyme I), glycylleucine for II (80%), leucyl-beta-naphthylamide for III (91%), and aspartyl-lysine in 5 mM Zn2+ for IV (63%). The enzymes are immunologically distinct and antibodies to each one localize to the brush border on immunohistochemical staining. Purification of 142-, 79-, 158-, and 46-fold was achieved for enzymes I through IV, respectively. Biochemical characteristics include slightly alkaline pH optima, molecular weights of 91,000-190,000, and evidence of metal ion involvement in activity. These studies provide necessary information for determining the role of brush border peptidase deficiencies in human disease.

Aminopeptidases↗