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Biomedical subjects

P A Hardy

Publications and source records attributed to P A Hardy.

At least 19 recordsLinked to original sources

A modified equivalent annulus model for the hollow fiber hemodialyzer.

Experimental approaches to optimize hollow fiber hemodialyzer design are expensive and time-consuming. Computer modeling is an effective way to study mass transfer in the hemodialyzer because a substantial reduction in experimental time and cost can be achieved. This paper presents a two-dimensional modified "equivalent annulus" model, which employs Navier-Stokes (N-S) equations to describe blood and dialysate flow, and Kedem-Katchalsky (K-K) equations to calculate transmembrane flow. N-S equations and K-K equations must be coupled together in the process of computing. The corresponding experiments were designed to validate this model, and experimental results agreed well with numerical results. The distribution of velocity, pressure and solute concentration were investigated in detail, presenting a clear insight into dialyzer mass transfer. This model can be applied to help optimize hemodialyzer design.

Algorithms↗

Measuring the thickness of articular cartilage from MR images.

We have developed an algorithm to estimate and display the spatial distribution of the thickness of articular cartilage in human knees. We used a simulation to derive the most appropriate formula for estimating thickness in digital images. The algorithm was tested by imaging a thickness phantom and comparing the results with the known dimensions of the phantom. The results demonstrated that the maximum error encountered in estimating thickness is one pixel while the average error is 0.4 pixels. We imaged a human knee on a cadaver in two separate sessions and used the two image sets to derive thickness maps of the patellar articular cartilage. The thickness maps generated independently from these image sets were very similar, indicating the reliability of the method in deriving accurate thickness estimates. J. Magn. Reson. Imaging 2001;13:120-126.

Algorithms↗

Recombinant Semliki forest virus infects and kills human prostate cancer cell lines and prostatic duct epithelial cells ex vivo.

Semliki Forest Virus (SFV) is a broad host range RNA virus capable of high-level recombinant protein expression and apoptosis induction in many cell types. We have successfully used a recombinant, replication deficient SFV vector to express the LacZ marker gene product in seven human prostate cell lines, as well as in human prostate tissue explants. Flow cytometry revealed that 40-60% of PPC-1 prostate cancer cells died 24-72 h after infection with SFV-LacZ virus. Most human prostate cancer cell lines expressed high levels of recombinant protein. Infection of human prostate tissue ex vivo led to similarly high expression levels but the recombinant beta-galactosidase was confined to duct epithelial cells. Infection of cell and tissue cultures resulted in detachment of adherent cells from the culture surface and detachment of epithelial cells from the basement membrane of tissue. Our results indicate that SFV may be useful in targeting recombinant protein expression and apoptosis to prostatic duct epithelial cells.

Apoptosis↗

Chronic ethanol exposure and withdrawal influence NMDA receptor subunit and splice variant mRNA expression in the rat cerebral cortex.

Chronic ethanol exposure and subsequent withdrawal are known to change NMDA receptor activity. This study examined the effects of chronic ethanol administration and withdrawal on the expression of several NMDA receptor subunit and splice variant mRNAs in the rat cerebral cortex. Ethanol dependence was induced by ethanol vapour exposure. To delineate between seizure-induced changes in expression during withdrawal and those due to withdrawal per se, another group of naive rats was treated with pentylenetetrazol (PTZ) injection (30 mg/kg, i.p.). RNA samples from the cortices of chronically treated and withdrawing animals were compared to those from pair-fed controls. Changes in NMDA receptor mRNA expression were determined using ribonuclease protection assays targetting the NR2A, -2B, -2C and NR1-pan subunits as well as the three alternatively spliced NR1 inserts (NR1-pan describes all the known NR1 splice variants generated from the 5' insert and the two 3' inserts). The ratio of NR1 mRNA incorporating the 5' insert vs. that lacking it was decreased during ethanol exposure and up to 48 h after withdrawal. NR2B mRNA expression was elevated during exposure, but returned to control levels 18 h after withdrawal. Levels of NR2A, NR2C, NR1-pan and both 3' NR1 insert mRNAs from the ethanol-treated groups did not alter compared with the pair-fed control group. No changes in the level of any NMDA receptor subunit mRNA was detected in the PTZ-treated animals. These data support the hypothesis that changes in NMDA receptor subunit composition may underlie a neuronal adaptation to the chronic ethanol-inhibition and may therefore be important in the precipitation of withdrawal hyperactivity.

Administration, Inhalation↗

Characterization of the calcaneal fat pad in diabetic and non-diabetic patients using magnetic resonance imaging.

It is well known that diabetic patients have a high incidence of foot ulceration. The purpose of this study was to determine whether magnetic resonance (MR) imaging can detect changes in the composition of the calcaneal fat pad in diabetic feet. MR data were collected in vitro from amputated specimens (eight from diabetic patients and eight from non-diabetic patients) as well as in vivo from age-matched diabetic and control subjects (four subjects each group.) Three types of images were acquired: spin lattice (T1), spin-spin (T2), and magnetization transfer (MT). The in vitro results showed statistically significant differences in the T1, T2, and MT parameters between the two disease groups. The same trends were shown in the study of live subjects but the differences were not statistically significant. The differences are believed to arise from changes in the composition of the tissues as a result of the progression of diabetes.

Adipose Tissue↗

Task-dependent effect of limb immobilization on the fatigability of the elbow flexor muscles in humans.

Because short-term limb immobilization produces selective adaptations in the neuromuscular system that probably interact with the task-dependent expression of muscle fatigue, the purpose of this study was to determine the effects of limb immobilization on the ability of human subjects to sustain isometric contractions at low and moderate submaximal forces. Four weeks of elbow joint immobilization caused a substantial decrease in the daily activity of biceps brachii during immobilization, a significant reduction in the cross-sectional area and volume of the elbow flexor muscles as measured by magnetic resonance imaging, and a decline in the maximum voluntary contraction (MVC) activation and force of the elbow flexor muscles. Immobilization had a task-dependent effect on muscle fatigue with a substantially increased endurance time (reduced fatigability) at a low force (20% MVC) and no statistical effect at a moderate force (65% MVC). Despite atrophy of the elbow flexor muscles due to the immobilization, the twitch force elicited in biceps brachii by electrical stimulation was greater after immobilization. The selective improvement of fatigue resistance for the low-force contraction and the absence of a change in the time course of the twitch suggests that the immobilization-induced adaptations included an improved efficacy of some excitation-contraction processes and underscored the major role of these mechanisms in determining the endurance time for low-force, long-duration contractions.

Adult↗

Measurement of magnetic resonance T2 for physiological experiments.

The proton transverse relaxation time (T2) of human skeletal muscles has been increasingly used in magnetic resonance imaging experiments to examine muscle physiology and neuromuscular control. However, little attention has been paid to the experimental factors affecting the accuracy or sensitivity of the T2 measurement. We have explored theoretically and experimentally the structure of several magnetic resonance pulse sequences for measuring T2 of the first dorsal interosseous muscle and found that a multiecho imaging technique using non-slice-selective refocusing pulses (MENSS) produces more accurate T2 estimates than multiecho slice-selective (MESS) imaging methods that are commonly used. Using either technique we acquired four 5-mm-thick transverse images of the first dorsal interosseous muscle with a spatial resolution of 0.6 mm within 5 min. The T2 measured by the MENSS method was closer to the true T2 than was the T2 estimated by the MESS method. After a given amount of exercise, the MENSS technique revealed an average 28 +/- 10% increase in T2 compared with a 13 +/- 3% increase measured with an equivalent MESS technique. We conclude that the MENSS method is a more accurate and sensitive procedure for studying neuromuscular physiology compared with the more commonly used MESS method.

Adult↗

Flumazenil: an unreliable antagonist in baclofen overdose.

We report a case of inadvertent overdose of baclofen given intrathecally resulting in coma. This was unresponsive to flumazenil and required supportive intensive therapy. With the increasing use of baclofen intrathecally for spasticity and its wide interpatient dose variability, there is a need to find a safe antagonist to baclofen for routine medical use.

Adult↗

Plasma concentrations of bupivacaine following single needle lumbar sympathectomy using two volumes of 0.25% bupivacaine plain solution.

Plasma bupivacaine concentrations were measured in 10 patients after lumbar sympathectomy using 10 ml or 20 ml of 0.25% bupivacaine plain solution. A single needle technique was employed, positioned at the L3 level. Mean peak concentrations were greater in the larger volume group and were statistically significant at 20, 30, 60, 90 and 120 min. Plasma bupivacaine levels peaked earlier in the smaller volume group. Some patients in the larger volume group still had plasma bupivacaine levels at or near peak values at 120 min. No patient approached toxic plasma levels of bupivacaine.

Adult↗

Intervertebral disks on MR images: variation in signal intensity with the disk-to-magnetic field orientation.

PURPOSE: To demonstrate and quantitate the magic angle effect in the intervertebral disk. MATERIALS AND METHODS: Magnetic resonance (MR) images of a lumbar intervertebral disk in a healthy volunteer were obtained with MR images with horizontal and vertical magnetic fields. Thin-section spin-echo images of an excised intervertebral disk were obtained with a horizontal field machine at orientations with respect to the main magnetic field between +90 degrees and -90 degrees. T1 and T2 were measured independently in this disk at two orientations. RESULTS: Images of the in vivo disk demonstrated a variation in the signal intensity of the anulus fibrosus that was different for the two MR units. The images obtained in the excised intervertebral disk demonstrated a signal intensity variation with disk orientation that was most pronounced in the anterior portion of the anulus. Relaxation time measurements showed the signal intensity reduction to arise from a reduction in T2 with oblique orientations. CONCLUSION: The observed signal intensity variation with disk orientation arises from an anisotropy in T2 caused by the restriction of water associated with collagen in the anulus. The magic angle effect in intervertebral disks will be observed with vertical magnetic field MR imagers.

Humans↗