Frontal plane dynamics of the centre of mass during quadrupedal locomotion on a split-belt treadmill.

Our previous study of cat locomotion demonstrated that lateral displacements of the centre of mass (COM) were strikingly similar to those of human walking and resembled the behaviour of an inverted pendulum (Park et al. 2019 J. Exp. Biol.222, 14. (doi:10.1242/jeb.198648)). Here, we tested the hypothesis that frontal plane dynamics of quadrupedal locomotion are consistent with an inverted pendulum model. We developed a simple mathematical model of balance control in the frontal plane based on an inverted pendulum and compared model behaviour with that of four cats locomoting on a split-belt treadmill. The model accurately reproduced the lateral oscillations of cats' COM vertical projection. We inferred the effects of experimental perturbations on the limits of dynamic stability using data from different split-belt speed ratios with and without ipsilateral paw anaesthesia. We found that the effect of paw anaesthesia could be explained by the induced bias in the perceived position of the COM, and the magnitude of this bias depends on the belt speed difference. Altogether, our findings suggest that the balance control system is actively involved in cat locomotion to provide dynamic stability in the frontal plane, and that paw cutaneous receptors contribute to the representation of the COM position in the nervous system.

Water handling in patients receiving haloperidol decanoate.

OBJECTIVE: To determine whether water handling in patients receiving haloperidol decanoate (HD) was impaired. DESIGN: Prospective, controlled trial of water handling in patients without symptomatic hyponatremia receiving HD. Eligibility for study inclusion required that patients had received HD for at least 4 months, were not taking any medication reported to cause inappropriate antidiuretic hormone secretion or hyponatremia (excluding haloperidol), and would agree to participate in the study. An age- and gender-matched healthy control subject was enrolled for each study patient. Baseline laboratory values were obtained within 48 hours prior to the standard water-loading test to screen for abnormalities in electrolytes, kidney function, and liver function. A 20-mL/kg water-load test was administered to each patient. Urine volume and osmolality were measured every hour for 4 hours. SETTING: A community mental health (CMH) outpatient psychiatric facility for the patients receiving HD and Saint Mary's Health Services for the controls. PARTICIPANTS: Fifteen patients receiving HD from the CMH facility and 15 age- and gender-matched control subjects were enrolled. MAIN OUTCOMES MEASURES: Impaired water handling was defined as a failure to dilute urine to less than 100 mmol/kg or a failure to excrete more than 65% of a water load in 4 hours. RESULTS: Five patients receiving HD were excluded because of protocol refusal or violation. Five of 10 evaluable patients receiving HD had abnormal water handling. Two of these could not lower their urine osmolality to less than 100 mmol/kg, 2 could not excrete more than 65% of the water load, and 1 did not meet either criteria. None of the healthy volunteers had abnormal free water handling. The difference between the study patients and the control subjects was statistically significant (p = 0.0097). CONCLUSIONS: Fifty percent of our study patients receiving HD had abnormal free water handling. This finding, combined with our clinical observations of symptomatic hyponatremia in other patients receiving the drug, suggests the need to investigate the incidence of hyponatremia and to design a useful screening tool to identify patients at risk. In the meantime, clinicians should be aware of the potential for impaired water handling in patients receiving HD.

In vivo interaction of ketoconazole and sucralfate in healthy volunteers.

Absorption of ketoconazole is impaired in subjects with an increased gastric pH due to administration of antacids, H2-receptor antagonists, proton pump inhibitors, or the presence of hypochlorhydria. Sucralfate could provide an attractive alternative in patients receiving ketoconazole who require therapy for acid-peptic disorders. Twelve healthy human volunteers were administered a single 400-mg oral dose of ketoconazole in each of three randomized treatment phases. In phase A, ketoconazole was administered orally with 240 ml of water. In phase B, ketoconazole and sucralfate (1.0 g) were administered simultaneously with 240 ml of water. In phase C, ketoconazole was administered with 240 ml of water 2 h after administration of sucralfate (1.0 g) orally with 240 ml of water. A 680-mg oral dose of glutamic acid hydrochloride was administered 10 min prior to and with each dose of ketoconazole, sucralfate, or ketoconazole plus sucralfate. Simultaneous administration of ketoconazole and sucralfate led to a significant reduction in the area under the concentration-time curve and maximal concentration of ketoconazole in serum (78.12 +/- 12.20 versus 59.32 +/- 13.61 micrograms.h/ml and 12.34 +/- 3.07 versus 8.92 +/- 2.57 micrograms/ml, respectively; P < 0.05). When ketoconazole was administered 2 h after sucralfate, the observed ketoconazole area under the concentration-time curve was not significantly decreased compared with that of ketoconazole alone. The time to maximal concentrations in serum and the ketoconazole elimination rate constant were not significantly different in any of the three treatment phases. In patients receiving concurrent administration of ketoconazole and sucralfate, doses should be separated by at least 2 h.

Modification of gastric pH with oral glutamic acid hydrochloride.

The extent to which oral glutamic acid hydrochloride decreases mean gastric pH in fasting persons with and without simulated hypochlorhydria was studied. Healthy nonsmoking men were randomly assigned to one of two drug regimens followed by the other regimen after a one-week washout period. In regimen 1 the fasting subjects received two 680-mg doses of glutamic acid hydrochloride given 10 minutes apart. Regimen 2 was the same, except that an oral dose of ranitidine 300 mg (as the hydrochloride salt) was administered one to two hours before the first dose of glutamic acid hydrochloride to simulate hypochlorhydria. Gastric pH was monitored radiotelemetrically before and after glutamic acid hydrochloride administration by using the Heidelberg capsule technique. Six men 20 to 28 years of age participated in the study. For regimen 1, the gastric pH before glutamic acid hydrochloride was given was not significantly different from that after administration (grand medians, 1.4 and 1.3, respectively). In regimen 2, the median gastric pH increased to greater than 4.0 within two hours after ranitidine treatment. Median gastric pH after the second dose of glutamic acid hydrochloride was significantly lower than before the first dose (grand medians, 1.6 and 6.2, respectively). The time to minimum pH was 2 to 15 minutes, and pH remained less than 3.0 for a mean of 45 minutes. Glutamic acid hydrochloride alone did not decrease fasting gastric pH, but it significantly reduced pH in subjects with simulated hypochlorhydria produced by orally administered ranitidine.