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Biomedical subjects

E A Tanagho

Publications and source records attributed to E A Tanagho.

At least 19 recordsLinked to original sources

Intrathecal administration of substance P in the rat: the effect on bladder and urethral sphincteric activity.

At the lumbosacral spinal cord level in the rat, substance P-positive neurons are present in dense concentration in the dorsal horn and the sacral parasympathetic nucleus. We undertook the present study to investigate the effect of intrathecal substance P (10 micrograms at the L6-S1 level) on urinary bladder and urethral sphincteric activity and to compare these effects with those of intravenous and intra-arterial administration. Three different bladder pressure responses were triggered by intrathecal substance P: (A) an immediate, strong bladder contraction (n = 5); (B) augmentation of the micturition reflex, as indicated by strong detrusor contractions in response to intravesical saline perfusion (n = 4); and (C) a slow, gradual increase to a high, steady peak (n = 8). The sphincteric electromyographic (EMG) activity was consistently increased. When substance P was given intravenously (n = 10) and intra-arterially (n = 3), the form, duration, and maximal amplitude of bladder contractions (owing to a direct smooth-muscle action) were comparable with those of Group A. The effects in intrathecal Groups B and C suggest that substance P provides a tonic influence on motor horn cells and on the preganglionic neurons in the sacral parasympathetic nucleus at the lumbosacral spinal cord level, where neuronal circuits controlling bladder and sphincteric activity are located.

Animals

Implantable penile venous compression device: initial experience in the acute canine model.

We have designed a venous compression device implantable at the base of the penis outside the tunica albuginea. Because it does not require exposure of individual veins for ligation, the risk to the cavernous nerve is practically nil. It occludes the venous return only temporarily, and thus collaterals are less likely to occur. In this preliminary acute study in dogs (N = 13), the penile venous compression device was shown to be effective and safe in controlling penile venous drainage and maintaining rigid erection.

Animals

Effect of intracavernous simultaneous injection of acetylcholine and vasoactive intestinal polypeptide on canine penile erection.

We investigated the effects of intracavernous injection of a combination of acetylcholine (ACh) and vasoactive intestinal polypeptide (VIP) on the erectile response in eleven adult male dogs. The minimum dose of ACh which increased the intracavernous pressure in eight dogs varied from 0.2 to 40 micrograms, and the minimum dose of VIP varied from 0.2 to 5 micrograms. When the minimum doses of ACh and VIP were injected simultaneously, a strong increase of intracavernous pressure (the mean increase was 102 cm. H2O from the baseline level) and a sustained erection (mean 5 min.) were observed in all eight dogs. The effect of simultaneous injection of both drugs was not additive but synergistic. Pretreatment with VIP-antibody and atropine intracavernously suppressed the erectile response induced by cavernous nerve stimulation. VIP may increase the affinity of muscarinic receptors for ACh in canine corpus cavernosum because pretreatment with atropine alone before the simultaneous injection of ACh and VIP completely abolished the effect of the combination. We conclude that ACh and VIP may play a cooperative role in canine penile erection.

Acetylcholine

Response of bladder, urethral and intracavernous pressure to ventral lumbosacral root stimulation in Sprague-Dawley and Wistar rats.

Six Sprague-Dawley and six Wistar rats were used for electrostimulation of the L5 to S2 ventral roots. Landmarks for identification of the roots were developed; bladder, urethral and intracavernous pressures were recorded; and tail and leg movements were checked. Urethral sphincter contraction was elicited by stimulation of the L5-L6 ventral roots, while bladder contraction and penile erection were mediated by the L6-S1 ventral roots. The best sphincteric response and intracavernous pressure rise were obtained by stimulation of the L6 ventral root, and the highest bladder pressures by stimulation of the S1 ventral root. Stimulation of the S1-S2 ventral roots provoked ipsilateral tail movement; of L6, tail movement, hindleg muscle twitch, and slight toe spread; and of L5, hindleg stretch and plantar flexion. No significant differences were found between the two strains of rats, although a higher bladder pressure was recorded during stimulation of the L6 ventral root in Sprague-Dawley rats, which might be explained by a small caudal shift of the sacral parasympathetic nucleus in the Wistar strain.

Animals

Selective sacral rhizotomy in the management of the reflex neuropathic bladder: a report on 17 patients with long-term followup.

During the last 6 years 24 patients with cervical or thoracic spinal cord injuries and a severe reflex neuropathic bladder underwent selective dorsal sacral rhizotomy with the aid of intraoperative neurostimulation and urodynamic monitoring. Preoperative and postoperative evaluation was available in 17 patients. Followup ranged from 2 months to 5 years (mean 32 months). Mean bladder capacity increased significantly after rhizotomy (from 148 +/- 28.1 to 377 +/- 52.9 ml., p less than 0.001), as did mean volume to first contraction (from 99 +/- 28.6 to 270 +/- 39.3 ml., p less than 0.001). No significant changes in bowel or erectile function were noted. Continence was improved in 94%, with 14 patients remaining completely dry and voiding with electrical stimulation or intermittent self-catheterization. The long-term results of selective sacral rhizotomy compare favorably to more aggressive alternatives, such as augmentation cystoplasty or urinary diversion.

Adult

Effects of adenosine on canine penile erection.

We investigated the hemodynamic effects of intracavernous injection of adenosine on canine penile erection. In all ten dogs studied, adenosine induced a dose-dependent increase of intracavernous pressure (ICP). Adenosine (0.67 to 15 micrograms/kg., B.W.) increased arterial blood flow by 83 to 325 percent above baseline levels and also increased venous resistance, which resulted in a full erection (ICP = 80 to 140 cm. H2O) for one to 7 minutes. The repeatability of the adenosine effect was confirmed in eight dogs. We found that adenosine, by virtue of its smooth muscle relaxation properties, can induce a dose-dependent increase of ICP and cause a full erection in dogs.

Adenosine

Interstitial cystitis: increased sympathetic innervation and related neuropeptide synthesis.

To investigate the possibility of a neural deterioration of the bladder wall in interstitial cystitis, bladder tissue from 10 patients with interstitial cystitis was compared with that from 10 control subjects by means of immunohistochemistry. An enhanced innervation of the bladder in the submucosa and detrusor muscle was found to represent an increase of sympathetic but not cholinergic neurons. In interstitial cystitis the number of neurons positive for vasoactive intestinal polypeptide and neuropeptide Y was higher and carried a larger number of axonal varicosities, whereas the number of neurons positive for substance P and calcitonin-gene-related peptide was not significantly different in both groups. We conclude that interstitial cystitis is associated with increased sympathetic outflow into the bladder and altered metabolism of vasoactive intestinal polypeptide and neuropeptide Y. Since similar changes have been observed in other inflammatory diseases of a presumably autoimmune nature, such as rheumatoid arthritis, Crohn's disease and colitis ulcerosa, the pathophysiology of interstitial cystitis may share common pathways with the latter. Experience in these diseases may facilitate a better understanding of the pathophysiology of interstitial cystitis and suggest new therapeutic concepts.

Adrenergic Fibers

Pelvic pain without pelvic organs.

We report on 4 patients with persistent, severe pelvic pain unresponsive to removal of the bladder, uterus, ovaries and fallopian tubes. Of the patients 3 had a diagnosis of interstitial cystitis and 1 had voiding dysfunction. We conclude that severe pelvic pain may not be responsive to the elimination of pelvic organs and alternative organ-preserving therapies should be considered.

Adult

Site of deafferentation and electrode placement for bladder stimulation: clinical implications.

Based on the clinical experience of treating neurogenic bladders by the electrical stimulation of the ventral sacral roots, neuroanatomical and neurophysiologic studies were designed to study the mechanism of detrusor-sphincter dyssynergia during electrical stimulation of the sacral roots. An experimental model was developed to decrease the stimulation response of the pelvic floor and external urethral sphincter muscles while preserving bladder contraction. The significance of the site of deafferentation and electrode implantation was evaluated under functional and clinical aspects. Our results indicate that a combination of intradural deafferentation and extradural electrode implantation may offer maximal deafferentation efficiency with minimal surgical risk. Intradural deafferentation is facilitated by a consistent arrangement of sacral roots with the dorsal roots running laterally to the ventral roots at the site of their exit from the dura. Detrusor-sphincter dyssynergia can be reduced by selective division of ventral sacral rootlets innervating the striated musculature of the pelvic floor and the urethral sphincter.

Afferent Pathways

The effect of magnetic resonance imagers on implanted neurostimulators.

This in-vitro study was designed to investigate the safety of various implanted neurostimulators in magnetic resonance (MR) imagers. The effects of the static and changing magnetic fields and the radio frequency (RF) electromagnetic field generated by 0.35 and 1.5 T MR imagers on the voltage output of four models of implantable passive neurostimulators and two models of implantable self-powered neurostimulators was studied. The neurostimulators were mounted on a support and placed in the imagers. An oscilloscope monitored the voltages at the outputs of the neurostimulators. For an Avery single-channel stimulator, located at the isocenter, the amplitude of the output pulses induced by the 0.35 T imager was 6V; from a 1.5 T imager, it was 12 V. These amplitudes can cause discomfort and possible harm to a patient if the typical therapeutic value is 1-5 V. The amplitude of the stimulator receiver's output decreased to relatively safe values beyond 40 cm from the isocenter. By contrast, there was no significant voltage output from the Medtronic SE-4 receiver. For two models of self-powered neurostimulators, the Medtronic Itrel and the Cordis MK II, the programmed stimulus parameters were not affected by the pulsed magnetic fields of the MR imagers. However, the RF fields at the isocenter heated the metal case of the stimulators. The rotational and linear forces produced by the fixed magnet on the Cordis MK II were judged to be too strong for a patient with this implant to be scanned. The study showed that patients with certain types of implanted neurostimulators can be scanned safely under certain conditions.

Electric Stimulation Therapy

Perineal pudendal neurotomy versus selective neurotomy of the S2 somatic contribution to the pudendal nerve. Effects on sacral-root-stimulated bladder and urethral responses in the dog.

In 10 dogs that underwent bilateral electrode implantation on the S2 ventral root, 5 then underwent a bilateral total perineal neurotomy of the pudendal nerve (group A) at 3 months and 5 bilateral division of the S2 somatic contribution to the pudendal nerve (group B). The effects of these 2 types of neurotomy on the bladder and urethral responses to electrostimulation were compared after another 3 months. In group A, the proximal and mid-urethral responses decreased significantly [69.1% (p = 0.004) and 79.6% (p = 0.002), respectively]. A decrease in bladder response [26% (p = 0.089)], although not significant, was also found. In group B, the decrease in the proximal urethral response was significant [67.8% (p = 0.012)]; the mid-urethral response (56.8%) was not statistically significant (p = 0.134). The bladder response decreased by 73.6% (p = 0.034). Thus, although pudendal neurotomy can be effective in reducing the outlet resistance, the pudendal nerve may have an important role in the regulation of micturition in the dog. Preoperative testing of the effect of a pudendal neurotomy by temporary nerve blocks is warranted to avoid undesirable side effects such as a decrease in bladder excitability.

Animals

The sympathetic role as an antagonist of erection.

The effects of the lumbar and pelvic sympathetic system on penile erection were studied in a canine model. Erection was induced by cavernous nerve stimulation and detumescence by sympathetic trunk stimulation. Erection induced by cavernous nerve stimulation normally subsides slowly. After discontinuation of electrical stimulation the intracavernous pressure drops within a mean of 291 s to 50% and after a mean of 372 s to 10% of the highest level. However, stimulation of the sympathetic trunk at the level of L4-S1 applied directly after discontinuation of cavernous nerve stimulation accelerated this drop of intracavernous pressure significantly: to 50% after a mean of 19 s and to 10% after a mean of 36 s. If stimulation of the sympathetic trunk was initiated 20 s before cavernous nerve stimulation, the pressure rise was aborted completely. Neurostimulation of the hypogastric nerves alone or in combination with cavernous nerve stimulation did not change the intracavernous pressure. These results were not altered after neurotomy of the pudendal or hypogastric nerves. The main pathway of the fibers from the sympathetic trunk to the penis seems to run via the pelvic plexus. The stimulation voltage and frequency to induce erection or detumescence were equivalent. Our results suggest that an elevated central sympathetic tone may be one of the causes of psychogenic impotence.

Animals

Characterization of prostate cancer, benign prostatic hyperplasia and normal prostates using transrectal 31phosphorus magnetic resonance spectroscopy: a preliminary report.

We assessed the ability of 31phosphorus (31P) transrectal magnetic resonance spectroscopy to characterize normal human prostates as well as prostates with benign and malignant neoplasms. With a transrectal probe that we devised for surface coil spectroscopy we studied 15 individuals with normal (5), benign hyperplastic (4) and malignant (6) prostates. Digital rectal examination, transrectal ultrasonography and magnetic resonance imaging were used to aid in accurate positioning of the transrectal probe against the region of interest within the prostate. The major findings of the in vivo studies were that normal prostates had phosphocreatine-to-adenosine triphosphate (ATP) ratios of 1.2 +/- 0.2, phosphomonoester-to-beta-ATP ratios of 1.1 +/- 0.1 and phosphomonoester-to-phosphocreatine ratios of 0.9 +/- 0.1. Malignant prostates had phosphocreatine-to-beta-ATP ratios that were lower (0.7 +/- 0.1) than those of normal prostates (p less than 0.02) or prostates with benign hyperplasia (1.1 +/- 0.2, p less than 0.01). Malignant prostates had phosphomonoester-to-beta-ATP ratios (1.8 +/- 0.2) that were higher than that of normal prostates (p less than 0.02). Using the phosphomonoester-to-phosphocreatine ratio, it was possible to differentiate metabolically malignant (2.7 +/- 0.3) from normal prostates (p less than 0.001), with no overlap of individual ratios. The mean phosphomonoester-to-phosphocreatine ratio (1.5 +/- 0.5) of prostates with benign hyperplasia was midway between the normal and malignant ratios, and there was overlap between individual phosphomonoester-to-phosphocreatine ratios of benign prostatic hyperplasia glands with that of normal and malignant glands. To verify the in vivo results, we performed high resolution magnetic resonance spectroscopy on perchloric acid extracts of benign prostatic hyperplasia tissue obtained at operation and on a human prostatic cancer cell line DU145. The extract results confirmed the differences in metabolite ratios observed in vivo. We conclude that transrectal 31P magnetic resonance spectroscopy can characterize metabolic differences between the normal and malignant prostate.

Adult

Sympathetic inhibition of papaverine induced erection.

We studied the effect of neurostimulation of the lumbar sympathetic trunks on papaverine-induced penile erection in dogs and monkeys. The mean of 124 cm. H2O intracavernous pressure after papaverine injection was reduced under sympathetic trunk stimulation to 40.6 cm. H2O within a mean of 39 sec. In addition the flow of the internal pudendal artery was reduced indicating a decrease of the inflow to the penis. After the sympathetic stimulation was terminated, the intracavernous pressure increased again to the same level as before. This pressure recovery time was delayed after several sympathetic stimulations from 134 sec. (5 min. after papaverine injection) to at least 362 sec. (45 minutes after papaverine injection). Stimulation of the inferior hypogastric plexus had no effect on the intracavernous pressure. The neurostimulation range (3-4V; 20 Hz) was most effective in reducing the papaverine action on penile smooth muscles. The effect of sympathetic trunk stimulation seems to antagonize the relaxing action of papaverine on the cavernous smooth muscles and the cavernous arterioles. Our results imply that high sympathetic tone in some patients with psychogenic impotence may explain their poor response to intracavernous injection of papaverine.

Animals

Penile detumescence: characterization of three phases.

In 22 dogs in which erection was induced by cavernous nerve stimulation, we analyzed the intracavernous pressure changes during detumescence without and with acute clamping of the aorta or electrostimulation of the lumbar sympathetic chains. Additionally, the degree of venous outflow obstruction was assessed by saline perfusion of the cavernous body during aortic occlusion. Detumescence had three distinct phases: an initial phase exhibiting a small pressure increase; a second phase showing a slow pressure decrease; and a third phase in which a fast decrease occurred. The first phase was abolished by aortic clamping, whereas the other phases were not significantly affected. Sympathetic stimulation abolished or prevented the second phase. Perfusion of the cavernous body during the second phase resulted in a pressure rise to off-scale values; however, when initiated during the terminal phase or in the nonstimulated penis, the pressure increase was slight. Our study indicates that the arterial flow rate influences the duration of the first phase of detumescence and that venous drainage is completely restored in the third phase. Furthermore, sympathetic stimulation causes an almost immediate full restoration of venous drainage, as cavernous perfusion initiated with an intracavernous pressure about twice as high as without sympathetic stimulation failed to increase pressure to off-scale values.

Animals

Ultrastructural changes in impotent penile tissue: a comparison of 65 patients.

To determine whether impotence is caused by specific and consistent changes in erectile tissue, we compared the ultrastructure of the corpora cavernosa in 6 controls with that in 59 patients undergoing implantation of a penile prosthesis. The impotent patients were divided into groups based on a medical history of hypertension (10), pelvic surgery (9), alcoholic smokers (8), hypertensive alcoholics (3), hypertensive alcoholic smokers (3), smokers (3), diabetics (8), diabetic smokers (3), Peyronie's disease (3), spinal cord injury (3) and isolated causes (6). Our data demonstrate that different behavioral and/or medical conditions produce similar degenerative tissue responses. There is no single or specific cause of impotence that is manifest by consistent changes in erectile tissue.

Adult

Bladder substitution with ileocaecal (Mainz) pouch. Clinical performance over 2 years.

A series of 11 patients underwent ileocaecal bladder substitution (Mainz pouch) with urethral anastomosis after radical cystectomy and pelvic lymphadenectomy for moderate to high grade transitional cell carcinoma of the bladder. With 12 to 27 months of follow-up (mean 18), 6 patients are voiding and are dry day and night with timed voidings; 4 patients continue intermittent catheterisation because of inability to perform the Valsalva manoeuvre adequately, and 1 has a suprapubic tube because of stricture of the enterourethral anastomosis. Upper tract studies revealed dilation of 4 of 22 renal units and 1 patient required endourological intervention. Serum electrolyte studies revealed slightly elevated chloride levels in 6, mild hypocarbia in 3, and reduced vitamin B12 levels in all patients, but no megaloblastic anaemia. The Mainz pouch appears to have very satisfactory short- and intermediate-term results.

Anastomosis, Surgical