The effect of the respiratory cycle on liver stiffness values as measured by transient elastography.

The findings of several studies suggest that liver stiffness values can be affected by the degree of intrahepatic congestion respiration influence intrahepatic blood volume and may affect liver stiffness. We evaluated the influence of respiration on liver stiffness. Transient elastography (TE) was performed at the end of inspiration and at the end of expiration in patients with chronic liver disease. The median values obtained during the inspiration set and during the expiration set were defined as inspiratory and expiratory liver stiffness, respectively. A total of 123 patients with chronic liver disease were enrolled (mean age 49years; 64.2% men). Liver cirrhosis coexisted in 29 patients (23.6%). Expiratory liver stiffness was significantly higher than inspiratory liver stiffness (8.7 vs 7.9kPa, P=0.001), while the expiratory interquartile range/median ratio (IQR ratio) did not differ from the inspiratory IQR ratio. Expiratory liver stiffness was significantly higher than inspiratory liver stiffness in 49 (39.8%) patients (HE group), expiratory liver stiffness was significantly lower than inspiratory stiffness in 15 (12.2%) patients, and there was no difference in 59 (48.0%) patients. Liver cirrhosis was more frequent in those who had a lower liver stiffness reading in expiration, and only the absence of liver cirrhosis was significantly associated with a higher reading in expiration in multivariate analysis. In conclusion, liver stiffness was significantly elevated during expiration especially in patients without liver cirrhosis. The effect of respiration should be kept in mind during TE readings.

Pharmacokinetics and pharmacodynamics of benidipine using a slow receptor-binding model.

PURPOSE: This study examined the relationship between the plasma concentration of benidipine, a long-lasting antihypertensive agent with Ca(2+)-channel-blocking properties, and its cardiovascular effects (reduction in blood pressure and increase in heart rate) in order to assess the usefulness of pharmacokinetic-pharmacodynamic (PK-PD) modelling in describing this relationship. METHODS: Two groups of 24 healthy volunteers received either a 4- or 8-mg benidipine hydrochloride tablet; 11 additional subjects received a placebo. Serial blood sampling and PD measurements were performed over 8 h thereafter. Plasma concentrations of benidipine were measured with a validated LC/MS/MS system, and the effects on blood pressure and heart rate were assessed during the same period. A two-compartment open model with lag time was used to explain the PK properties, and the PD model was characterized by slow receptor binding, reflecting the binding of benidipine to the ion-channel receptor. RESULTS: Benidipine reached mean peak plasma concentrations of 1.04 and 3.85 ng/mL at 0.5 and 0.75 h after 4 and 8 mg doses, respectively. Peak cardiovascular effects were detected approximately 2 h after the administration of either dose. Maximal decreases in diastolic blood pressure with 4 and 8 mg of benidipine were 7.79 and 14.75 mmHg, respectively, and maximal increases in heart rate were 7.32 and 17.56 bpm, respectively. No significant changes in systolic blood pressure were observed. The cardiovascular effects were analysed according to a slow receptor-binding model. CONCLUSIONS: The tested PK-PD model successfully described the relationship between the plasma concentration of benidipine and its cardiovascular effects.

An instrumented glove for grasp specification in virtual-reality-based point-and-direct telerobotics.

Hand posture and force, which define aspects of the way an object is grasped, are features of robotic manipulation. A means for specifying these grasping "flavors" has been developed that uses an instrumented glove equipped with joint and force sensors. The new grasp specification system will be used at the Pennsylvania State University (Penn State) in a Virtual Reality based Point-and-Direct (VR-PAD) robotics implementation. Here, an operator gives directives to a robot in the same natural way that human may direct another. Phrases such as "put that there" cause the robot to define a grasping strategy and motion strategy to complete the task on its own. In the VR-PAD concept, pointing is done using virtual tools such that an operator can appear to graphically grasp real items in live video. Rather than requiring full duplication of forces and kinesthetic movement throughout a task as is required in manual telemanipulation, hand posture and force are now specified only once. The grasp parameters then become object flavors. The robot maintains the specified force and hand posture flavors for an object throughout the task in handling the real workpiece or item of interest. In the Computer integrated Manufacturing (CIM) Laboratory at Penn State, hand posture and force data were collected for manipulating bricks and other items that require varying amounts of force at multiple pressure points. The feasibility of measuring desired grasp characteristics was demonstrated for a modified Cyberglove impregnated with Force-Sensitive Resistor (FSR) (pressure sensors in the fingertips. A joint/force model relating the parameters of finger articulation and pressure to various lifting tasks was validated for the instrumented "wired" glove. Operators using such a modified glove may ultimately be able to configure robot grasping tasks in environments involving hazardous waste remediation, flexible manufacturing, space operations and other flexible robotics applications. In each case, the VR-PAD approach will finesse the computational and delay problems of real-time multiple-degree-of-freedom force feedback telemanipulation.

Adenosine-mediated photoreaction of 4,5',8-trimethylpsoralen with alcohols.

Irradiation of thin films consisting of 4,5',8-trimethylpsoralen (TMP), adenosine and small amounts of alcohols led to TMP-alcohol photoadducts in addition to TMP-adenosine photoadducts. Four TMP-ethanol and two TMP-methanol adducts have been separated and characterized. Covalent bonds were formed between the 4-carbon of TMP and the alpha-carbon to the hydroxy group in the alcohols. The TMP-alcohol photoadducts were formed only in the TMP film containing small amounts of alcohol and adenosine. Furthermore, no photoadduct of TMP and ribose was detected upon photolysis of a TMP-ribose film, suggesting that the adenine moiety plays a specific role in the reaction. The interaction of adenosine with psoralens in a dry film may be related to the DNA sequence selectivity observed for the photoreaction of psoralens with DNA.

A novel photoadduct of 4,5',8-trimethylpsoralen and adenosine.

A novel photoadduct of 4,5',8-trimethylpsoralen (TMP) and adenosine was isolated and purified by reverse-phase liquid chromatography. The structure of the photoproduct was determined by various spectral methods and found to be a TMP-adenosine 1:1 adduct resulting from the covalent bond formation between the carbon C(4) of TMP and ribose 4'-carbon of adenosine.

Study of the skin concentrations after administration of the various phototoxic drugs.

The skin concentrations of 8-methoxypsoralen (8-MOP), 5-methoxypsoralen (5-MOP), and 4, 5', 8-trimethylpsoralen (TMP) were studied in the guinea pig following oral administration and bathing. The skin concentration of phototoxic drugs after oral administration peaked at 1.5 hours, and the concentration of 8-MOP was 3.5 times greater than that of 5-MOP. The skin concentration of TMP was not detected in our study (limit of sensitivity 5ng/ml). The skin concentrations of phototoxic drug after bathing decreased in the order of 5-MOP, TMP, and 8-MOP.