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Biomedical subjects

J S Wheeler

Publications and source records attributed to J S Wheeler.

At least 19 recordsLinked to original sources
PubMed1998

Home monitoring of bladder pressure and volume in individuals with spinal cord injury and multiple sclerosis.

Individuals with spinal cord injury and multiple sclerosis are at high risk for developing kidney dysfunction due to high bladder pressures. We have developed a device for frequent monitoring of bladder pressures at home in those patients who use intermittent catheterization to empty their bladders. Of eight subjects enrolled in the study, only five conducted home recording of pressure. Vesical and abdominal pressures measured at home were significantly lower than clinical cystometric pressures. However, subtracted detrusor pressures obtained from home records and cystometric records were not significantly different. The home detrusor pressures were consistent over a large time and volume range. Therefore, the home monitoring method could be used to establish a normal range of bladder pressures at home and to rapidly identify high bladder pressures in advance of upper urinary tract deterioration.

Adult↗
PubMed1997

Short-term bladder-wall response to implantation of microstimulators.

This study examined the histological response of the bladder wall serosa to the implantation of wireless microstimulators secured with a single polypropylene suture. Two to three microstimulators were implanted in each of three casts for an eight week implantation period to allow sufficient time for a bladder-wall injury-response to develop. Gross observation revealed encapsulation of the microstimulators with no perforation to the bladder lumen or migration from the bladder wall. Histological evaluation confirmed that all the microstimutators were encapsulated with a thin connective tissue sheath and a thickened subserosal layer. There was no remarkable difference in tissue morphology compared with normal bladder wall sections for five of seven stimulators. Two microstimulators in one cat revealed a moderate to severe inflammatory response confined to a small area around the stimulator. In a second cat, a suture extended through the bladder wall. The microstimulators were observed with a scanning electron microscope after explantation. The electrode surfaces, bonding interface between silicon and glass and insulating films that were exposed to biological fluids were carefully inspected. All these observations indicate that the glass capsule reliably protected the sealed cavity of the microstimulators from moisture. These results indicate the microstimulator should be considered for further studies such as effects of stimulation and long-term implantation.

Animals↗
PubMed1997

Direct bladder stimulation with suture electrodes promotes voiding in a spinal animal model: a technical report.

To determine the efficacy of a new electrode for direct bladder stimulation, five male cats were instrumented during anesthesia. Multistranded, 316LVM, stainless-steel, wire electrodes were implanted on the bladder wall serosa above the trigone area. The electrodes were made with a needle attached to the end that was cut off after suturing the electrode in place. Additional instrumentation included tubes for pressure recording and filling, and hook electrodes for leg and pelvic floor EMG recording. Bladder filling and stimulation studies were conducted in tethered animals 1 to 2 weeks following recovery. Chronic studies were conducted following recovery in tethered animals. To test these electrodes in a spinal cord injury (SCI) model, a T-1 level complete lesion was performed on the above instrumented animals. Spinal animals had successful direct bladder stimulation that induced active contractions and voiding both before and after SCI, but voiding rates were higher more than 2 weeks after SCI and at larger initial bladder volumes. Optimum stimulation parameters consisted of 40 pulses per second, 300 microseconds to 1 ms pulse duration, a stimulation period of 3 to 4 s, and 10 to 40 mA. Urethral resistance, indicated by a urethral function measure, showed that stimulation had no adverse effect on urethral function, and fluoroscopy showed an open membranous urethra during stimulation and voiding. The cat has a small penile urethra that is the flow rate controlling zone. The suture electrode did not corrode, erode into the bladder, or become dislodged, and appears suitable for chronic implantation.

Animals↗
PubMed1997

Use of the HIV-1 protease for excision of growth-hormone-releasing factor from synthetic and recombinant peptide precursors.

An autolysis-resistant mutant of the HIV-I protease was employed for removal of metabolically stabilized and highly bioactive analogues of bovine growth-hormone-releasing factor (bGRF) from their larger either synthetic or recombinant precursors. The N-terminal four amino acids in two selected model GRF analogues, Y1IDAIFTSSYRKVLAQLSARKLLQDILSRQVF32-OH (I; GRF32) and Y1IDAIFTSSYRKVLAQLSARKLLQDILSRQ30-OH (IA; GRF30), conform well to the specificity of the HIV-I protease for residues in the P1' to P4' positions of its peptide substrates. A variety of amino acids were tried in the N-terminal extension (positions P4-P1) to fit the protease substrate specificity for the 8 amino acids in positions P4-P4'. A synthetic precursor of I, extended N-terminally with RQVF-, a sequence representing the four C-terminal residues in I, was effectively cleaved by the protease at the Phe-1-Tyr1 bond (... RQVF-decreases-YIDA ...) to release GRF32. However, when several soluble fusion proteins linked to GRF32 by the RQVF sequence were expressed in Escherichia coli, attempts to cleave out the core GRF32 met with variable, and only limited, success. By random mutagenesis in a propeptide segment, [MGQSVAQVF]-decreases-GRF30, (II) was identified as a construct that showed reasonably high-level expression in E. coli and was effectively processed by the HIV-I protease. A yield of 5 mg of pure GRF30 was obtained/litre of culture medium after a single HPLC purification step.

Amino Acid Sequence↗
PubMed1996

Identification of signal-induced IkappaB-alpha kinases in human endothelial cells.

Activation of the nuclear transcription factor-kappaB is an early event in endothelial activation. NF-kappaB activation is regulated by the inducible phosphorylation and subsequent degradation of the inhibitory subunit IkappaB-alpha. We identified two discrete kinases of approximately 36 and 41 kDa in the cytoplasm of human umbilical vein endothelial cells that specifically bind to and phosphorylate the IkappaB-alpha subunit. IkappaB-alpha kinase activity is transiently elevated following treatment with either tumor necrosis factor alpha, interleukin-1beta, or bacterial lipopolysaccharides and precedes activation of either mitogen-activated kinase or Jun kinase. Furthermore, activation of the IkappaB-alpha kinases precedes both the appearance of hyperphosphorylated IkappaB-alpha and its subsequent degradation, as well as the translocation of NF-kappaB to the nucleus. Deletion mutagenesis of the IkappaB-alpha polypeptide revealed that these kinases bind in or around the ankyrin repeat domains and phosphorylate residues within the C terminus. These kinases, however, were not identical to casein kinase II and displayed a pharmacologic profile distinct from other known kinases. These kinases may represent components of a signal transduction pathway regulating IkappaB-alpha levels in vascular endothelium.

Ankyrins↗
PubMed1996

Preliminary noninvasive back-pressure recordings of bladder pressure.

Obstructive voiding is best evaluated with urodynamics, including bladder pressure and urine flow rates. Until recently, the recording of bladder pressure required the use of a urethral catheter. In preliminary observations, a noninvasive back-pressure method using an external condom catheter has been introduced to determine bladder pressure. This device uses a side tube for pressure recording and an outlet tube that is clamped for short periods of time. We have investigated design criteria for back-pressure recording techniques. In the laboratory setting using a plastic model, we determined that a low compliance condom is needed. In addition, a back flow of fluid during the clamping procedure helps to obtain quick back pressures and facilitates evaluation of pressure when low flow rates are present. These modified condom devices were evaluated in four male subjects. Back pressures were not statistically different than bladder pressures recorded with a urethral catheter. The use of back pressures in the evaluation for obstructive uropathy can be enhanced by using a pressure and flow nomogram.

Humans↗
PubMed1995

Direct bladder stimulation with percutaneous electrodes and impedance monitoring of volume in an SCI animal model.

Bladder responses to percutaneous electrodes were investigated with stimulation in three male spinal cats. The animals had been spinalized (T1 level lesion) 10 weeks prior to these studies and had been instrumented with chronic bladder had been spinalized (T1 level lesion) 10 weeks prior to these studies and had been instrumented with chronic bladder wall electrodes and suprapubic bladder catheters for filling and pressure recording. percutaneous stimulation in tethered animals was conducted wit hook electrodes inserted with a needle in the abdomen bilaterally adjacent to the bladder trigone. Stimulation was conducted with 40 Hz pulse trains of 10 to 30 mA for three seconds. Stimulation with both percutaneous and chronic electrodes induced high bladder pressures and voiding. In addition, with chronically implanted electrodes, impedance monitoring of bladder volume was found to be an effective recording technique.

Animals↗
PubMed1994

Urodynamic measure of urethral cross-sectional area: application for obstructive uropathy.

A conductance formula was developed based on pressure (P) and flow (Q) data collected from rigid tubes with a cross-sectional area in the range of the flow controlling zone of the urethra. Curve fitting of data resulted in an exponential formula and a simple proportionality constant related tube of differing cross-sectional area. The resulting formula estimates cross-sectional area based on P and Q data and is in the form of a conductance ratio because Q is in the numerator and P is in the denominator. The formula is AEFm = 3.5 Q/P0.58, where AEFm is the area equivalent factor-male and Q is measured in ml/sec and P is cm H2O. To further introduce the estimate of cross-sectional area, urodynamics were retrospectively reviewed from 19 males over the age of 50 with complaints of prostatism. The AEFm was plotted on standard urodynamic records much like P and Q data. The onset of voiding was characterized by a rapid increase in urethral area. Maximal cross-sectional area obtained at maximal flow was 2.9 +/- 1.4 mm2. The maximal urethral area per unit of applied detrusor pressure, an estimate of urethral compliance, was 0.06 +/- 0.6 mm2/cm H2O. This latter measure may help to compare patients with widely different detrusor pressures. The urodynamic data from two young adult males is also presented for comparison. Their average maximal urethral cross-sectional area was 7.1 mm2. Their average area per unit of applied detrusor pressure was 0.15 mm2/cm H2O. These larger values contrast sharply with the BPH group. The AEFm clearly shows urethral function in terms of the principal factor regulating the urine flow rate, the urethral cross-sectional area.

Adult↗
PubMed1994

Osteomyelitis of the pubis: complication of a Stamey urethropexy.

Osteomyelitis pubis is a rare pyogenic infection of the anterior pelvis. Prior pelvic surgery is the factor that usually causes this problem. To my knowledge endoscopic urethropexy, that is the Stamey procedure, has not been reported as a predisposing cause. A case of pubic osteomyelitis following a Stamey urethropexy is reported.

Aged↗
PubMed1994

Management of incontinent SCI patients with penile stimulation: preliminary results.

We investigated dorsal penile stimulation for control of incontinence in nine spinal cord impaired (SCI) patients, using a battery-powered home-use stimulator connected to surface electrodes (Unipatch). The efficacy of the penile stimulation was assessed by urodynamic evaluation (NL-2, LifeTech) and surface electrodes (Unipatch); baseline and repeat cystometries (CMG) with and without stimulation were done. Stimulation for home use was begun at threshold parameters for inducing perineal contractions and, after two weeks, was adjusted based upon results. Two subjects successfully completed the study and became continent. One of these patient's CMG demonstrated hyperreflexia and his volume increased from 110 ml to 150 ml after the stimulation protocol. The most effective stimulating parameters were 5 pps, 250 microsec, pulse width and 40 ma current. The other patient also had a hyperreflexic bladder and improved on the protocol. The remaining seven patients did not complete the study for several reasons. Three patients had CMG's that demonstrated areflexia. Stimulation did not alter their bladder function and they dropped out of the program. Three other subjects withdrew because of bothersome sensations even at subthreshold levels and they complained that the technique was cumbersome. Finally, one patient with significant hyperreflexia and incontinence withdrew after trying unsuccessfully and diligently for 10 days. Our encouraging results in two patients with hyperreflexic bladders and decreased sensation suggest that this modality may be effective in this patient group.

Adult↗
PubMed1994

Dynamic bulbocavernosus reflex: dyssynergia evaluation following SCI.

High urethral resistance caused by detrusor-sphincter dyssynergia (DSD) occurs following spinal cord injury (SCI) and results in poor voiding. A major pelvic floor reflex that may be involved in DSD is the bulbocavernosus reflex (BC) and evaluation of this reflex during the micturition cycle may provide additional information regarding this role. The periodic BC observed during micturition via cystometry is described as a dynamic bulbocavernosus reflex (DBC). The DBC was induced in upper motor neuron SCI patients using periodic dorsal penile nerve stimulation; the evoked reflex response was recorded with an anal sphincter pressure sensing balloon. Stimulation of 15-50 mA was applied at the base and dorsal side of the penis with surface electrodes, pulsed at a rate of 0.25 Hz. By applying the stimulation during cystometry, the BC reflex could be evaluated throughout the entire micturition cycle. Results showed that the DBC increased during bladder filling and bladder contractions. These findings indicate that an enhanced BC reflex is a major factor causing increased urethral resistance during micturition.

Adult↗
PubMed1993

Inhibiting the hyperreflexic bladder with electrical stimulation in a spinal animal model.

Uninhibited bladder contractions are a problem in spinal cord injured patients. Accordingly, methods using electrical stimulation to inhibit the bladder were investigated in chronic spinal cord injured (C6-T1) male cats. In unanesthetized, restrained animals, spontaneous bladder contractions were observed after the bladder was filled above the micturition threshold. In 3 of the 5 cats studied, this bladder activity could be inhibited with stimulation of either sacral nerves or pudendal nerves. Pudendal nerve stimulation, however, was more selective than sacral nerve stimulation for inhibition with fewer side effects such as leg spasms. Tibial nerve stimulation was ineffective and caused leg spasms and increased bladder activity. Finally, high-frequency stimulation (1,000 Hz) of the sacral nerves was shown to block bladder contractions in 2 of 3 cats investigated. However, this method had adverse side effects such as leg flexion and secondary bladder contractions. We conclude that pudendal nerve/pelvic floor stimulation at low frequency is a relatively effective method in this model.

Animals↗
PubMed1993

Measurement of total urethral compliance in females with stress incontinence.

Urodynamic evaluation of stress incontinence has failed to result in consistent diagnostic parameters. Using retrospective female bladder pressure and urine flow data, we evaluated two parameters based on a conductance formula. This formula was derived from fitting a classical fluid dynamic equation to published data of voiding cystourethography. The Area Equivalent Factor-female at maximal flow represents maximal urethral opening and this value further divided by the pressure is the total urethral compliance. A stress incontinent group had a strong trend toward greater maximal urethral opening and total urethral compliance than a continent group. These parameters may, therefore, have potential in the evaluation and understanding of stress urinary incontinence.

Adult↗