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Biomedical subjects

C J Robinson

Publications and source records attributed to C J Robinson.

At least 19 recordsLinked to original sources

Comparison of direct bladder and sacral nerve stimulation in spinal cats.

Neuroprosthetic techniques have been used to facilitate voiding via electrical stimulation for bladder management following spinal cord injury (SCI), but high urethral resistance has been a problem. This problem was investigated here in the chronic, spinal, male cat (C6-T1) using direct bladder and sacral nerve stimulation. Direct bladder stimulation was only conducted during terminal procedures with an open abdomen and with four hook electrodes inserted into the bladder wall. Sacral stimulation was conducted daily during the 10 weeks post-SCI and during terminal procedures. Stimulation was conducted with both implanted epidural electrode and surface electrodes over the sacral bone. Both of these sacral methods stimulated anterior and posterior roots. However, these sacral methods were generally ineffective for inducing voiding during the study. In three of the five animals investigated, stimulation did not empty the bladder. In the remaining two animals, the bladder was emptied with sacral stimulation, but only after return of bladder reflex activity, 2 to 4 weeks post-injury. When poor voiding occurred in spite of high bladder pressures, it indicates high urethral resistance. This was confirmed using video cystourethrography where the membranous urethra was observed to remain closed following stimulation. Direct bladder stimulation was then compared to sacral nerve stimulation during terminal procedures. Direct bladder stimulation induced voiding at a high rate both during and after stimulation, whereas sacral nerve stimulation with implanted electrodes induced voiding at a lower rate and only after stimulation. A simple urethral resistance measure, the ratio of bladder pressure to voiding rate, was lower with direct bladder stimulation than sacral nerve stimulation. Stimulation-facilitated voiding has also been associated with the development of bladder wall hypertrophy. This problem was investigated by evaluating bladder wall thickness postmortem in three groups of animals: the first group was the spinal-stimulated animals detailed above; the additional two groups were a spinal-nonstimulated but instrumented group maintained for 10 weeks following injury, and an intact group of animals. The stimulated spinal cats tended to have the thickest bladder wall followed by the nonstimulated spinal cats. The wall thickness of intact animals served as a control.

Animals

Immunology.

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Acute Disease

Reduced gastrointestinal absorption of calcium in dementia.

Several reports have suggested that the neurodegenerative change in Alzheimer-type dementia (ATD) may be related to alterations in calcium homoeostasis. The absorption of radiocalcium (45Ca) in 26 ATD subjects and 11 patients with multi-infarct dementia (MID) was compared to 24 normal age- and sex-matched controls. The absorption of radiocalcium was significantly lower in both ATD and MID when compared to controls. The reduced 45Ca absorption in ATD occurred in the presence of normal plasma concentrations of PTH and vitamin D metabolites and the serum concentrations of calcium and aluminium were in the normal range. The data suggest that the reduced uptake of radioactive calcium observed in ATD is a non-specific derangement.

Aged

Reflex responses to ankle perturbations during electrical stimulation of muscle: 1. Measurement techniques and preliminary examples.

Electrical stimulation of muscle has been proposed as a technique to restore function to paralyzed muscles. But, from a control stand-point, little is known about how such artificial activation interacts with the still intact spinal reflex loops. We have developed instrumentation to measure and compare ankle compliance and muscle EMG activity when the ankle is subjected to perturbations in torque or angular position from bias positions that are achieved volitionally or via electrical muscle stimulation. We deliver precise torque or position perturbations (step, ramp, sinusoidal, random) to the ankle via a pivoting footplate driven by a computer-controlled torque motor. Angular displacement, torque, acceleration, and 2 to 4 channels of electromyographic (EMG) data are collected on analog (VHS) tape and simultaneously digitized and stored. Torque or position biases to normal ankle equilibrium position are applied volitionally (for the neurologically intact) or via electrical stimulation of the Gastroc/Soleus or the Tibialis Anterior muscle (for either the neurologically intact or spinal cord injured). A special stimulator/recording amplifier permits the recording of EMG signals from the muscle being stimulated. An overview of the features and response characteristics of the perturbation system and a comparison from preliminary studies of responses at different biases achieved volitionally versus those achieved by stimulation are presented.

Ankle Joint

The detergent Solulan C-24 reveals properties of the olfactory adenylate cyclase system.

The detergent Solulan C-24 has been shown to activate the olfactory adenylate cyclase, with loss of the odorant modulation, at concentrations too low to cause significant solubilization. The activation is synergistic with that of nonhydrolysable GTP analogues, forskolin and AlF4-. These effects are not reversible. Solulan causes the cyclase activity to become subject to ATP inhibition, which is competitively relieved by GTP gamma S, and increases the GTP gamma S concentration required for half-maximal stimulation of the system. This suggests a change in the GTP-binding site of the stimulatory G-protein. Activation by GTP gamma S, without Solulan, indicates that the cyclase catalytic unit, rather than the available G-protein, may be limiting in the system. We suggest that Solulan may remove an inhibitory control on the cyclase activity.

Adenylyl Cyclases

Surface stimulation techniques for bladder management in the spinal dog.

Electrical stimulation of the bladder wall or sacral nerves may be effective for bladder management in the spinal cord injured patient. However, extensive surgery has been required for electrode implantation. We compared urodynamic responses using surface and minimally invasive epidural stimulating techniques in the chronic spinal male dog. Various surface stimulating techniques were effective: 1) sacral monopolar electrical stimulation with negative electrodes over S2 sacral foramina and positive electrodes on the legs, 2) sacral bipolar electrical stimulation with electrodes only over sacral foramina, 3) perineal monopolar electrical stimulation, and 4) perineal tactile stimulation. Urodynamic responses were similar to those for sacral epidural electrodes implanted adjacent to sacral nerves. Voiding was obtained both during stimulation and poststimulation. Stimulating parameters that were effective for daily voiding with sacral surface electrodes were 10 pps, 30 to 45 ma, 0.6 ms pulse duration, and 2 to 5 sec stimulation train duration.

Animals

Urethral responses to sacral stimulation in chronic spinal dog.

Urethral activity was investigated in the awake chronic spinal-injured canine using urodynamic recordings, video cystofluoroscopy, and urethral pressure recordings without anesthesia. Bladder contractions and voiding were induced by electrical stimulation with epidural electrodes inserted into the sacral canal. Urethral pressure remained elevated during stimulation and for 1-3 s afterward. Poststimulation voiding occurred with three different patterns: 1) pulsatile voiding in which squirting of urine was associated with contractions in the membranous urethra; 2) "on and off" voiding in which pulsatile flow was interrupted for brief periods of time; and 3) steady-stream voiding in which nonpulsatile flow was followed by pulsatile flow. Viewing these voiding patterns with fluoroscopy indicated that the proximal membranous urethra was important in all of the patterns. We conclude that in the chronic spinal-injured canine the skeletal muscle within the membranous urethra (rhabdosphincter) is involved in responses to sacral stimulation and various voiding patterns.

Animals

Sacral epidural electrodes for voiding in the chronic spinal dog.

Recent reports have shown that electrical stimulation of the bladder wall or sacral nerves is effective for bladder management in the spinal cord injured (SCI) patient. However, less invasive methods are needed for electrode implantation. A modified percutaneous procedure for implanting needle electrodes in the sacral canal was evaluated. Stimulation with these electrodes were effective for inducing voiding with little residual volume after the recovery of bladder reflexes, 3 weeks after experimental spinal cord injury in the dog. An optimum electrode arrangement involved a single midline monopolar electrode located between sacral foramina L7 and S1. However, at low stimulating current, lateral electrodes adjacent to sacral nerves were more effective than midline electrodes for inducing voiding. Stimulation parameters that were effective for daily voiding were 10 pps, 1.5-5 mA, 0.3 ms pulse duration, and 2- to 3-second stimulation periods.

Animals

Photometric assays for FcRI-dependent binding, phagocytosis, and antibody-dependent cellular cytotoxicity mediated by monomeric IgG gamma 2a in murine peritoneal macrophages.

Mouse peritoneal macrophages possess distinct Fc receptors (FcR) for binding the various murine IgG isotypes. FcRI binds monomeric IgG gamma 2a, but not monomeric IgG gamma 2b or IgG gamma 1 with high affinity at 4 degrees C and is sensitive to trypsin degradation. We have assessed the functional consequences of the cytophilic binding at 4 degrees C of monomeric IgG gamma 2a to FcRI of mouse peritoneal macrophages using newly developed photometric microassays for quantification of binding, phagocytosis, and antibody dependent cellular cytotoxicity (ADCC) of post-opsonized sheep red blood cell (SRBC) targets. Dose-dependent binding specificity of monomeric IgG gamma 2a, but not IgG gamma 2b or IgG gamma 1 to FcRI of oil-elicited mouse peritoneal macrophages at 4 degrees C for 2 h was confirmed to display typical saturation kinetics both by the photometric assay and by a cellular enzyme-linked immunosorbent assay (CELISA). Binding of monomeric IgG gamma 2a to macrophage FcRI promoted highly efficient phagocytosis of opsonized SRBC in that most cells that were bound were also rapidly internalized by the phagocytic process during a 1 h incubation at 37 degrees C. Upregulation of FcRI-dependent binding and phagocytosis occurred during 24-48 h in vitro culture of macrophages as shown both by the photometric assays and CELISA. Trypsin treatment of macrophages abrogated FcRI-dependent binding and phagocytosis by monomeric IgG gamma 2a, but had little effect on FcRII-dependent functions. Cytophilic binding of monomeric IgG gamma 2a to FcRI failed to trigger ADCC activation. Thus functional characterization of macrophage FcRI-dependent effector functions confirmed the fidelity of binding specificity of monomeric IgG gamma 2a to a trypsin degradable receptor which mediates highly efficient phagocytosis but fails to initiate the signal for ADCC activation. It appears that passively bound immune monomeric IgG gamma 2a could provide an efficient mechanism by macrophages in vivo for FcRI-dependent immune clearance of soluble or particulate cellular antigens without elicitation of potentially harmful cytolytic factors associated with ADCC activation.

Animals

Procainamide induces a transitory impairment of B cell mitogenesis in beagle dogs.

Beagle dogs (3 to 6 years old) were treated with 100-150 mg procainamide HC1/kg/day. After 2, 5, and 9 months of treatment, peripheral blood lymphocytes were isolated and stimulated with pokeweed mitogen. The data demonstrated a suppression of mitogenesis only at 2 and 5 months after procainamide treatment. The lymphocytes from dogs treated for 9 months had a normal response to pokeweed mitogen. At no time during this experiment were any significant levels of serum antinuclear antibodies detected nor was any change in the number of cycling lymphocytes apparent in the experimental versus control groups. The resting membrane potential of both control and experimental groups was similar and pokeweed mitogen depolarized the cells from both groups.

Animals

Spasticity in spinal cord injured patients: 1. Short-term effects of surface electrical stimulation.

Twelve spinal cord injured subjects participated in a study of the short-term effects on leg spasticity of electrical stimulation of the quadriceps. Spasticity was quantified through the use of a normalized relaxation index (R2n) obtained from the pendulum drop test both before and after measurement of isometric quadriceps torque in response to 20 minutes of cyclic electrical stimulation. Two or three baseline evaluations were made on each subject, tests being at least one day apart. By comparing the first prestimulus baseline assessment of spasticity with that obtained poststimulus, we obtained a measure of changes in spasticity brought about by fatiguing exercise. We found that spasticity significantly (p less than or equal to 0.005) decreased after stimulation. To investigate whether this change was due to electrical stimulation or was a function of the performance of the drop test itself (ie, passive range of motion of the knees), drop-to-drop variability during the pendulum drop test both before and after stimulation was assessed. A comparison was made of the R2n value of the last drop before stimulation to that of the first drop afterward, to assess the direct effect of stimulation on spasticity. Spasticity decreased significantly (p less than or equal to 0.05) during the leg ranging inherent in the drop test itself, particularly for subjects with shorter times postinjury. Spasticity also decreased significantly as a direct result of electrical stimulation. This latter change could be accounted for by an interaction of peak quadriceps torque and the initial measure of spasticity before stimulation.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult