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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
PubMed1998

Bladder acellular matrix graft in rats: its neurophysiologic properties and mRNA expression of growth factors TGF-alpha and TGF-beta.

To assess the neurophysiologic properties and molecular mechanisms of the bladder acellular matrix graft (BAMG), we performed cystometric and neurophysiologic studies in male Sprague-Dawley rats (n = 46) at varying intervals. The animals were assigned to 3 groups: 1) normal, 2) partial cystectomy (>50%), and 3) partial cystectomy (>50%) and grafting with a BAMG of equal size. Additionally, matrix-grafted and host bladders were processed for analysis of mRNA expression of transforming growth factor (TGF)-alpha, TGF-beta1, TGF-beta2, and TGF-beta3 by reverse transcriptase polymerase chain reaction. Matrix-grafted bladders showed a significantly higher bladder capacity at 3 and 6 weeks and 4 months than those with partial cystectomy alone, and a significantly higher bladder capacity at 4 months than in normal controls (P < or = 0.01). Residual urine volume was significantly increased at 4 months. Electrostimulation of the pelvic nerve provoked generalized bladder contractions, a response that was reduced by atropine and hexamethonium. Variable induction of TGF-alpha, TGF-beta1, TGF-beta2, and TGF-beta3 gene transcription was evident in the BAMG, with prominent mRNA expression of TGF-alpha and TGF-beta1 6 months after surgery. These cystometric results and detrusor responses to stimulation provide further evidence that graft components do not interfere with host components. Matrix-grafted rat bladders generate, although not increased over time, adequate intravesical pressure responses to produce sustained voiding. Gene expression of different growth factors may be significant in understanding their role in the development and differentiation of the BAMG for partial bladder replacement.

Animals↗
PubMed1998

The latissimus dorsi bladder myoplasty to assist detrusor function.

The objective of this study was to evaluate whether an innervated skeletal muscle might augment detrusor function. In four dogs we performed the latissimus dorsi myoplasty, a transfer of the latissimus muscle as an innervated free flap wrapped around the bladder. Stimulation of the latissimus dorsi free flap initially achieved an average bladder pressure of 45.8 +/- 8.41 cm H2O, sufficient for partial evacuation. After 4 months the muscle generated a maximal pressure of 82 cm H2O, resulting in an evacuation of 27.7%. For selected patients, the latissimus dorsi bladder myoplasty may provide an alternative to intermittent catheterization in the future.

Animals↗
PubMed1998

The impact of sacral root anatomy on selective electrical stimulation for bladder evacuation.

Although different structures have been studied with electrostimulation to elicit bladder evacuation, only the sacral root remains feasible for clinical application at present. However, the resultant concomitant contractions of the bladder and sphincteric muscles have been the principal problem over the last few decades. Attempts to identify fibers within the sacral ventral root that innervate the detrusor predominantly have been made by microsurgery alone or in combination with advanced electrical blocking techniques. This article evaluates our past and present efforts to achieve voiding in light of the mixed nature of sacral root anatomy.

Animals↗
PubMed1998

Functional rat bladder regeneration through xenotransplantation of the bladder acellular matrix graft.

OBJECTIVE: To determine the decreased antigenicity of the bladder acellular matrix graft (BAMG) through xenotransplantation and to assess the in vivo and in vitro functional properties of the rat urinary bladder thus regenerated. MATERIALS AND METHODS: After partial cystectomy (> 50%), BAMGs prepared from hamster, rabbit and dog urinary bladders were grafted to male and female Sprague-Dawley rats; 10 control rats underwent partial cystectomy only. Urinary storage and voiding function were monitored in 15 animals using a specially designed 'micturition cage' and cystometry. After 4 months, organ-bath studies and histological techniques were used to evaluate bladder regeneration in vitro in the grafted animals. RESULTS: Clinically relevant antigenicity was not evident; no animal died from rejection and all bladder wall components regenerated in all BAMG xenografts. However, the degree and quality of regeneration varied. Muscularization, peak pressure, and bladder capacity were higher in the hamster BAMG-grafted animals, whereas in vitro contractility and compliance were best in the dog BAMG-regenerated bladders. All grafted bladders had significantly better capacity and compliance than the autoregenerated bladders after partial cystectomy alone. CONCLUSIONS: The present in vivo and in vitro studies show that BAMG-augmentation cystoplasty can lead to morphological and functional regeneration of the rat bladder, preserving its low-pressure reservoir function. Because BAMG-regenerated bladders show functional innervation that is similar to normal bladders, they can work in coordination with the host bladder components, thus generating adequate intravesical pressure to produce sustained voiding. The decreased antigenicity makes heterologous BAMG transplants feasible without immunosuppression.

Animals↗
PubMed1998

Composition and biomechanical properties of the bladder acellular matrix graft: comparative analysis in rat, pig and human.

OBJECTIVE: To compare the composition and mechanical properties of the newly developed bladder acellular matrix graft (BAMG) with the normal urinary bladder in rat, pig and human. MATERIALS AND METHODS: Rat, pig and human urinary bladders were harvested and divided into control and experimental groups. For the latter, BAMGs were prepared, and light and transmission electron microscopic studies performed. Strips from the normal bladders and the BAMGs (10 in each group) were tested under tension, and the ultimate tensile strength, maximum strain, and elastic modulus were determined from stress/strain curves. RESULTS: Both types I and III collagen, as well as elastic fibres, were observed as major components of the matrix scaffold. There were more collagen type I fibres in the rat than in the pig and human BAMGs, whereas the pig, and particularly the human, both showed higher levels of type III collagen and elastic fibres. These different matrix scaffold patterns were confirmed by electron microscopy. Results from biomechanical testing showed no significant differences for strength, strain or elastic modulus between BAMG and control bladder strips, except in the rat where the maximum strain values were significantly lower. CONCLUSION: There are variations in the acellular matrix structure with similar biomechanical properties between the BAMG and the normal urinary bladder in three different species. These results may underscore the potential of the BAMG. Furthermore, this in vitro model provides a suitable method to study the mechanical properties of the urinary bladder and may serve as a diagnostic tool for various investigations.

Animals↗
PubMed1998

Erectile response to transurethral alprostadil, prazosin and alprostadil-prazosin combinations.

PURPOSE: Transurethral alprostadil has been shown to be efficacious in many men with erectile dysfunction. We compared transurethral alprostadil and prazosin alone, and in combination to treat this disorder. MATERIALS AND METHODS: In this double-blind, placebo controlled study the erectile responses to transurethral alprostadil, prazosin and alprostadil-prazosin combinations were assessed in 234 men 26.8 to 81.5 years old with complete organic erectile dysfunction. Patients self-administered a random sequence of 7 doses in the clinic in 4 weeks. The erectile response was assessed using categorical and visual analog scales. RESULTS: Full penile enlargement or rigidity was achieved by 165 of the 234 men (70.5%) after at least 1 active dose of medication. The most effective alprostadil dose (500 microg.) resulted in full penile enlargement or rigidity in 51.8% of administrations, whereas the most effective prazosin dose (2,000 microg.) and placebo resulted in a similar response in 12.7 and 2.7%, respectively (p <0.001). The 500/2,000 microg. alprostadil/prazosin combination, which resulted in full enlargement or rigidity in 58.9% of doses, was only slightly better than the most effective dose of alprostadil alone (500 microg.). However, combinations of 125/500 and 250/500 microg. alprostadil/prazosin were more effective (p <0.01) than 125 and 250 microg. alprostadil given alone, respectively. The most common side effect of therapy was penile pain, which rarely led to study discontinuation. Hypotension most commonly developed at the higher alprostadil-prazosin combination. CONCLUSIONS: Transurethral alprostadil and alprostadil-prazosin combinations produced erections in men with complete organic erectile dysfunction. This combination therapy may be an option in patients who do not respond to transurethral alprostadil alone.

Adrenergic alpha-Antagonists↗
PubMed1998

In vitro functional properties of the rat bladder regenerated by the bladder acellular matrix graft.

PURPOSE: To assess the response of rat urinary bladder regenerated by the homologous bladder acellular matrix graft (BAMG) to in vitro electrical and pharmacologic stimuli. MATERIALS AND METHODS: In Sprague-Dawley rats, partial cystectomy (>50%) was performed, followed by BAMG augmentation cystoplasty. After 4 months, organ bath studies of tissue strips in 10 were used to compare the contractility of the BAMG regenerates and the corresponding host detrusor smooth muscle. RESULTS: The BAMG regenerates exhibited contractile activity to electrical field stimulation and a qualitatively identical pattern of response to muscarinic, purinergic, alpha- and beta-adrenergic drug administration and nitric oxide. At 4 months after surgery, the maximum forces of contraction of the BAMG regenerates to carbachol stimulation amounted to close to 80% of the host bladder response. With electrical field stimulation, they equaled 44% and 62% of the host bladder response after 2.5 and 4 months, respectively. Histological and immunohistochemical studies confirmed the presence of receptors for neurotransmitters that these functional in vitro studies implied. CONCLUSIONS: The present study provides further evidence that augmentation cystoplasty with the BAMG leads to functional regeneration of the rat bladder detrusor smooth muscle.

Animals↗
PubMed1997

Free ureteral replacement in rats: regeneration of ureteral wall components in the acellular matrix graft.

OBJECTIVES: To evaluate ureteral replacement by a free homologous graft of acellular matrix in a rat model. METHODS: In 30 male Sprague-Dawley rats, a 0.3 to 0.8-cm midsegment of the left ureter was resected and replaced with an acellular matrix graft of equal length placed on a polyethylene stent. The animals were killed at varying intervals, and the grafted specimens were prepared for light and electron microscopy. RESULTS: In all animals, the acellular matrix graft remained in its original position without evidence of incrustation or infection, and histologic examination showed complete epithelialization and progressive infiltration by vessels. At 10 weeks, smooth muscle fibers were observed; at 12 weeks, nerve fibers were first detected; at 4 months, smooth muscle cells had assumed regular configuration. CONCLUSIONS: The ureteral acellular matrix graft appears to promote the regeneration of all ureteral wall components.

Animals↗
PubMed1997

Neurostimulation for bladder evacuation: is sacral root stimulation a substitute for microstimulation?

OBJECTIVE: To determine by anatomical and functional studies whether stimulation of sacral rootlets might permit selective stimulation of autonomic fibres, thus avoiding the detrusor/sphincter dyssynergia characteristic of current techniques of neurostimulation for bladder evacuation. MATERIALS AND METHODS: In 10 male mongrel dogs, the S2 root was isolated and its constituent rootlets followed from their origin in the spinal cord to the point of exit from the dura. The entire root and the individual rootlets were then stimulated, including intra- and extra-dural stimulation and at proximal, mid and distal levels. RESULTS: Neuroanatomical and histological findings showed that rootlets of ventral S2 maintain their identity throughout their intradural course; some carry predominantly autonomic fibres, some predominantly somatic and some a mixture of the two. CONCLUSION: It appears surgically feasible to identify, isolate and sever the predominantly somatic rootlets intradurally, sparing the predominantly autonomic rootlets for inclusion in extradural electrode placement around the entire sacral root, thus eliminating sphincteric interference with detrusor contraction for voiding at low pressure.

Animals↗
PubMed1997

Reproduction of functional smooth muscle tissue and partial bladder replacement.

OBJECTIVE: To find a means of bladder augmentation that would avoid the complications encountered with the use of bowel segments, using a newly developed acellular biomaterial, the bladder acellular matrix graft (BAMG), as a homologous graft. MATERIALS AND METHODS: Thirty-four rats underwent a partial cystectomy (40-50%) and grafting with a BAMG of equal size. Eleven rats died within the first 72 h. probably from urinary leakage caused by obstruction of the bladder neck with stones or coagula; the surviving 23 were killed at varying intervals after cystectomy and examined. RESULTS: After providing initial bladder enlargement, the graft was progressively infiltrated by the vessels and smooth muscle cells of the host: furthermore, the mucosal lining was complete within 10 days. After 4 weeks, all bladder wall components were evident histologically in the graft. The ingrowth was complete after 8 weeks, except for neural regeneration, which was only partial. At 12 weeks, the bladder wall muscle structure in the graft was so well developed that it was difficult to delineate the junction between host bladder and BAMG. Neural regeneration continued to improve. Normal bladder capacities were maintained throughout the study. CONCLUSION: The BAMG appears to serve, without rejection, as a framework of collagen and elastin for the ingrowth of all bladder wall components. The reason for the better acceptance of the BAMG than of other bladder augmentation grafts requires further investigation.

Animals↗
PubMed1997

Continence mechanism of the isolated female urethra: an anatomical study of the intrapelvic somatic nerves.

PURPOSE: A neuroanatomical study was initiated to gain better insight into the continence mechanism of the isolated urethra in women. MATERIALS AND METHODS: We performed a detailed gross and histological neuroanatomical study to identify the intrapelvic somatic pathway from the sacral spinal cord to the female urethral sphincter. Gross anatomical dissection was performed in 5 formalin fixed female adult pelvises by tracing the autonomic nerves from the pelvic plexus and the spinal somatic nerves from S2-S4 to the urethral sphincter. Immunohistochemical staining of urethral step sections with a neuropeptide specific antibody was performed to demonstrate the course of the periurethral somatic nerves in relation to the vaginal wall. RESULTS: Our study demonstrated an intrapelvic somatic pathway derived from the S2, S3 and S4 sacral roots, distinct from the peripheral pudendal nerve, supplying the levator ani and the urethra. The somatic nerves travel beneath the endopelvic fascia in close relation to the inferior vascular pedicle of the bladder and are susceptible to injury during radical pelvic surgery. Mixed autonomic fibers from the pelvic plexus travel along the course of the ureter and are also intimately associated with the vascular pedicle of the bladder. Immunohistochemical staining of urethral step sections demonstrated that the periurethral nerves travel in close relation to the lateral and anterior vaginal wall. CONCLUSIONS: We believe that the identification of intrapelvic somatic pathways to the urethra provides a basis for developing surgical techniques to preserve urethral somatic innervation during radical pelvic surgery in women.

Adult↗
PubMed1996

Voiding dysfunction in human immunodeficiency virus infections.

PURPOSE: We prospectively evaluated the current spectrum of urodynamic pathology in patients infected with human immunodeficiency virus (HIV) who presented with voiding dysfunction. MATERIALS AND METHODS: We obtained a directed genitourinary and neurological history, and performed a physical examination and urodynamic testing in 18 patients. A 4-channel membrane urethral catheter was used to record intravesical and intraurethral pressures simultaneously. RESULTS: Detrusor hyperreflexia was present in 28% of our patients and detrusor-sphincter dyssynergia in 28%. Detrusor areflexia, previously described as the most frequent abnormality, was uncommon in our series (6% of patients). CONCLUSIONS: This changing proportion of urodynamic diagnoses may reflect a changing pattern of neurological manifestations of HIV infection due to more aggressive management. Urodynamic evaluation remains critical for precise diagnosis and treatment in patients with HIV who present with urinary symptoms.

Adult↗
PubMed1995

Response of guinea pig smooth and striated urethral sphincter to cromakalim, prazosin, nifedipine, nitroprusside, and electrical stimulation.

Prazosin (an alpha-1-adrenergic blocker) and cromakalim (potassium channel opener), given alone, induced significant fatigue of the urethral sphincter at a concentration of 10(-4) M; both drugs combined achieved a significant sphincteric fatigue at a concentration of 10(-5) M each. To 10(-4) M hexamethonium (ganglionic smooth muscle blocker) and 10(-4) M decamethonium (nicotinic blocker of striated muscle) the striated urethral sphincter responded like striated muscle with no detectable function of its smooth muscle component. Therefore, the striated component seems to play a dominant role in sphincteric function. With calcium depletion or in the presence of a calcium channel blocker (10(-4) M nifedipine) the urethral sphincter showed a relative enhancement of response to electrical field stimulation when compared with smooth and skeletal muscle, whose responses were both significantly reduced. This phenomenon could not be explained with calcium-dependent, inhibitory, nitric oxide-releasing nerves, as the NO-synthase blocker N-nitro-L-arginine (10(-5) M to 5 x 10(-5) M) failed to induce the enhancement of sphincter contraction during electrostimulation found with calcium depletion. Still, NO-releasing nerves might play a role in sphincteric relaxation because sodium nitroprusside (10(-5) M) induced a significant relaxation of the urethral sphincter precontracted with 80 mM potassium. The potential to weaken sphincteric closure with drugs, exemplified by the results obtained in response to prazosin and cromakalim, would represent a therapeutic advance in the patient with neurogenic bladder dysfunction.

Amino Acid Oxidoreductases↗
PubMed1995

Intraoperative electrostimulation of the cavernous nerve: technique, results and limitations.

PURPOSE: We studied the feasibility of inducing penile erection intraoperatively by stimulation of the cavernous nerves. MATERIALS AND METHODS: In 16 men undergoing retropubic radical prostatectomy and 6 undergoing penile surgery for venous leakage electrostimulation was applied to both sides of the prostatic apex (prostatectomy group) or the hilum of the penis (venous surgery group). RESULTS: Electrostimulation produced visible erection in 8 of the 16 prostatectomy patients and an increase in intracavernous pressure in 5 of the 6 venous surgery patients. CONCLUSIONS: Electrostimulation of the cavernous nerves intraoperatively to produce penile erection is feasible. However, the technique must be further refined to be clinically useful, that is to localize the neurovascular bundle in men undergoing prostatectomy.

Adult↗
PubMed1995

Reinnervation of the rat bladder with a somatic nerve and a striated muscle flap.

PURPOSE: Current techniques of ventral sacral root stimulation to regain voluntary motor control of the decentralized urinary bladder depend upon intact parasympathetic innervation of the detrusor. We investigated techniques that might allow restoration of motor control of the bladder after efferent parasympathetic impairment. MATERIALS AND METHODS: In a chronic rat model, we evaluated whether motor control of a peripherally denervated bladder could be restored by transplantation of autologous excitable tissues and subsequent electrostimulation. Either a somatic nerve or a striated muscle flap was used as the transplant. RESULTS: Four months after the initial surgery, electrostimulation of the somatic nerve implant provoked bladder contractions--a response that was blocked by atropine. Stimulation of the nerve innervating the striated muscle flap also provoked bladder contractions; these were not affected by atropine and were slightly reduced by hexamethonium. CONCLUSION: Reinnervation of the bladder with somatic nerves or striated muscles is possible in principle. Future experiments will clarify the clinical significance of electrostimulation of such implants.

Animals↗