According to Einstein's equivalence principle, inertial accelerations during translational motion are physically indistinguishable from gravitational accelerations experienced during tilting movements. Nevertheless, despite ambiguous sensory representation of motion in primary otolith afferents, primate oculomotor responses are appropriately compensatory for the correct translational component of the head movement. The neural computational strategies used by the brain to discriminate the two and to reliably detect translational motion were investigated in the primate vestibulo-ocular system. The experimental protocols consisted of either lateral translations, roll tilts, or combined translation-tilt paradigms. Results using both steady-state sinusoidal and transient motion profiles in darkness or near target viewing demonstrated that semicircular canal signals are necessary sensory cues for the discrimination between different sources of linear acceleration. When the semicircular canals were inactivated, horizontal eye movements (appropriate for translational motion) could no longer be correlated with head translation. Instead, translational eye movements totally reflected the erroneous primary otolith afferent signals and were correlated with the resultant acceleration, regardless of whether it resulted from translation or tilt. Therefore, at least for frequencies in which the vestibulo-ocular reflex is important for gaze stabilization (>0.1 Hz), the oculomotor system discriminates between head translation and tilt primarily by sensory integration mechanisms rather than frequency segregation of otolith afferent information. Nonlinear neural computational schemes are proposed in which not only linear acceleration information from the otolith receptors but also angular velocity signals from the semicircular canals are simultaneously used by the brain to correctly estimate the source of linear acceleration and to elicit appropriate oculomotor responses.

Normal urine inhibits both the growth and the aggregation of calcium oxalate monohydrate (COM) crystals but the molecules that inhibit aggregation are not well defined. We have developed a spectrophotometric assay method to measure the aggregation of COM crystals in vitro under conditions that avoid simultaneous crystal growth. At pH 7.2 and 90 mM NaCl, Tamm-Horsfall glycoprotein (THP) and nephrocalcin (NC), a major urinary inhibitor of COM crystal growth, inhibit COM crystal aggregation at concentrations as low as 2 X 10(-9) and 1 X 10(-8) M, respectively. When increasing NaCl to 270 mM or lowering pH to 5.7, inhibition by both glycoproteins, but more markedly by THP, is decreased. Urinary NC from calcium oxalate renal stone formers (SF NC) and NC isolated from calcium oxalate renal stones (stone NC) both inhibit COM crystal aggregation 10-fold less than NC from normal urine. Citrate is ineffective even at millimolar concentrations. Thus THP and NC are two major inhibitors of COM crystal aggregation in normal urine; SF NC and stone NC are defective aggregation inhibitors.

Tamm-Horsfall glycoprotein (THP) inhibits self-aggregation of calcium oxalate monohydrate (COM) crystals and may therefore be part of the natural defenses against deposition of COM in the kidney in the form of stones or nephrocalcinosis. We have studied THP from six patients with severe nephrolithiasis and have found that their THP inhibits COM self-aggregation less than normal THP under conditions of NaCl and THP concentration and pH similar to those of human urine. The reason for the reduced inhibition of COM crystal aggregation seems to be an enhanced self-aggregation of patient THP, which removes it from effective interactions with the COM crystals. In one family, the father and the oldest son both excreted THP that behaved abnormally and in similar ways, whereas THP from the other son and from the wife behaved normally.

1. The spatial organization of the vestibuloocular reflex (VOR) was studied in six rhesus monkeys by applying fast, short-lasting, passive head and body tilts immediately after constant-velocity rotation (+/- 90 degrees/s) about an earth-vertical axis. Two alternative hypotheses were investigated regarding the reference frame used for coding angular motion. 1) If the vestibular system is organized in head-centered coordinates, postrotatory eye velocity would decay invariably along the direction of applied head angular acceleration. 2) Alternatively, if the vestibular system codes angular motion in inertial, gravity-centered coordinates, postrotatory eye velocity would decay along the direction of gravity. 2. Horizontal VOR was studied with the monkeys upright. Pitch (roll) tilts away from upright elicited a transient vertical (torsional) VOR and shortened the time constant of the horizontal postrotatory slow phase velocity. In addition, an orthogonal torsional (after pitch tilts) or vertical (after roll tilts) response gradually built up. As a result, the eye velocity vector transiently deviated in the roll (pitch) plane and then gradually rotated in the same direction as gravity in the pitch (roll) head plane until the orthogonal component reached a peak value. Subsequently, the residual postrotatory eye velocity decayed along a line parallel to gravity. 3. The time constant of the horizontal postrotatory response was maximal in upright position (21.5 +/- 5.7 s, mean +/- SD) and minimal after tilts to prone (3.8 +/- 0.7 s), supine (4.5 +/- 1.2 s), and ear-down (5.2 +/- 1.6 s) positions. A similar dependence on head orientation relative to gravity characterized the dynamics of the resultant eye velocity vector in the pitch and roll planes. 4. Torsional VOR was studied with the monkeys in supine or prone position. Pitch (yaw) tilts from the supine or prone position toward upright (ear-down) position elicited a transient vertical (horizontal) VOR and shortened the time constant of the torsional postrotatory response while a horizontal (vertical) orthogonal component slowly built up. As a result the eye velocity vector gradually rotated in the pitch (yaw) plane until the orthogonal component reached a peak value. Subsequently residual postrotatory eye velocity decayed along a line parallel to gravity. 5. The time constant of the torsional postrotatory response in supine/prone positions was 16.5 +/- 6.8 s. After tilts from supine/prone positions toward upright position, time constants decreased and were minimal after tilts to upright position (2.7 +/- 0.7 s).(ABSTRACT TRUNCATED AT 400 WORDS)

Background: The hypothesis was that torasemide, due to more predictable pharmacokineticsypharmacodynamics, induces greater improvements in functional and social limitation than furosemide and reduces the frequency of hospitalisations in primary care patients with chronic heart failure (CHF). Patients and Methods: Prospective, randomized, unblinded study in primary care, 237 patients with CHF (NYHA II-IV), all on ACE inhibitors. Randomisation: torasemide (ns122) or furosemide (ns115), treated for 9 months. Endpoints: Clinical efficacy, quality of life, safety, tolerability, hospitalisations. Results: Clinical improvement was observed in both groups, but the trend to improve by at least one NYHA class was significant only in torasemide-(Ps0.014), but not in furosemide-treated patients. There were no differences with regard to adverse events and hospitalisation due to CHF. Overall, tolerability (Ps0.0001) and improvement in daily restrictions (Ps0.0002) were significantly higher, number of mictions at 3, 6 and 12 h after diuretic intake (P-0.001 at all time points) and urgency to urinate (P-0.0001) significantly lower in torasemide-vs. furosemide-treated patients. Conclusion: CHF patients treated with torasemide gain a higher benefit in quality of life than furosemide treated patients, due to torasemide's dual effect on both clinical status and social function.