Intravesical infusion of resiniferatoxin by a temporary in situ drug delivery system to treat interstitial cystitis: a pilot study.

PURPOSE: Interstitial cystitis (IC), a syndrome characterized by motor and sensory dysfunction of the lower urinary tract, represents a diagnostic and therapeutic challenge even to highly skilled physicians. We investigated the technical feasibility and the clinical efficacy of a prolonged intravesical instillation of RTX by in situ drug delivery system in patients with IC. MATERIAL AND METHODS: 5 female patients (mean age 48.7 years) received a prolonged infusion of a saline solution containing 10nM of resiniferatoxin at the flow rate 25microl/h by the MiniMed 407C Infusion Pump (MiniMed Sylmar, CA, USA), connected to sovrapubic 5Fr mono Pigtail catheter, for 10 days. All patients reported frequency, nocturia and urgency, and symptoms of pelvic pain for at least six months. They showed the absence of urinary tract infection within the last three months, the absence of functional disorders of lower urinary tract and no other vesical or urethral pathology. The pre-treatment (PT) frequency/volume (FV) chart and a pain score (VAS score) were recorded. Patients were evaluated after 30 days from the end of infusion (primary end point, PEP) and after three months (secondary end point, SEP). RESULTS: At PEP frequency reduced from 11.3+/-1.39 to 7.4+/-1.51 (p<0.01) and nocturia from 3.6+/-0.54 to 1.2+/-0.44 (p<0.01). A highly significant reduction of pain score was observed at PEP: it decreased to 2.4+/-0.54 from 6.7+/-0.83 (p<0.01). The pain score remained significantly lower at SEP (3.2+/-0.44 p<0.05). Nocturia was also statistically reduced at SEP (1.9+/-0.74) as well as frequency (8.7+/-1.76). No side effects were reported during the infusion as well as after the removal of the catheter. CONCLUSION: The present study demonstrates that the prolonged intravesical instillation of a drug by in situ drug delivery system is a feasible procedure and seems to support the efficacy of RTX in the treatment of IC patients. However further studies are necessary and mandatory to confirm our results and to define the exact action mechanism of prolonged infusion of RTX, the dosage and the treatment schedule.

Urodynamic and clinical evidence of acute inhibitory effects of intravesical nociceptin/orphanin FQ on detrusor overactivity in humans: a pilot study.

PURPOSE: Management of neurogenic incontinence is complex and available treatments are not satisfactory. Nociceptin/orphanin FQ, a recently discovered neuropeptide, has been reported to inhibit the voiding reflex in the rat. These experimental results prompted us to investigate the urodynamic and clinical effects of intravesical instillation of nociceptin/orphanin FQ in humans. MATERIAL AND METHODS: Our study involved 5 normal subjects (group 1) with a mean age of 40.4 years (range 21 to 54) and 9 patients (group 2) 40.4 years (24 to 54). All patients in group 2 presented with detrusor hyperreflexia refractory to standard therapy. They were invited to undergo a filling cystometrogram with saline solution and after 30 minutes, a new one with a solution containing 1 microM. nociceptin/orphanin FQ. The urodynamic parameters that were recorded included bladder capacity, volume threshold for the appearance of detrusor hyperreflexia and maximum bladder pressure. Clinical and urodynamic followup was performed after 15 days. The data were statistically analyzed with 1-way analysis of variance followed by the Dunnett test for multiple comparison considered statistically significant with p <0.05. RESULTS: Intravesical instillation of 1 microM. nociceptin/orphanin FQ in group 1 did not produce significant functional changes. This infusion in group 2 produced a statistically significant increase in mean bladder capacity and volume threshold for the appearance of detrusor hyperreflexia from 164 plus or minus standard deviation (SD) 84 to 301 +/- 118 and 93 plus or minus SD 41 to 231 +/- 104 ml. (p <0.05, respectively). Mean maximum bladder pressure decreased from 79 plus or minus SD 25 to 54 +/- 44 cm. water but was not statistically significant (p = 0.19). After 15 days an absence of clinical improvement was noticed in group 2, and the urodynamic control did not show any significant changes compared to the values before nociceptin/orphanin FQ treatment. No severe symptomatic reactions were observed during infusion of 1 microM. nociceptin/orphanin FQ. CONCLUSIONS: Our results demonstrate that nociceptin/orphanin FQ is able to elicit a robust inhibitory effect on voiding reflex in group 2 but not 1. The ideal dosage, route of administration of nociceptin/orphanin FQ and treatment interval are not yet established.

Intravesical resiniferatoxin for the treatment of hypersensitive disorder: a randomized placebo controlled study.

PURPOSE: Present therapeutic approaches to control hypersensitive disorder of the lower urinary tract and bladder pain are clinically and scientifically unsatisfactory. We performed a randomized placebo controlled study with followup after 1 and 3 months using intravesical resiniferatoxin to treat hypersensitive disorder and bladder pain. MATERIALS AND METHODS: We prospectively randomized 18 patients into 2 groups to receive a single dose of 10 nM. resiniferatoxin intravesically (group 1) or a placebo saline solution only (group 2). All patients had at least a 6-month history of frequency, nocturia, urgency and symptoms of pelvic pain as well as no urinary tract infection within the last 3 months, functional disorders of the lower urinary tract, or other vesical or urethral pathology. Pretreatment voiding pattern and pain score were recorded. Patients were evaluated after 30 days (primary end point) and 3 months (secondary end point). RESULTS: The 2 groups were adequately homogeneous in regard to patient age, sex ratio, disease duration, voiding pattern and pain score. At the primary end point mean frequency plus or minus standard error of mean was decreased from 12. 444 +/- 0.70 voids to 7.111 +/- 0.67 and nocturia from 3.777 +/- 0. 27 to 1.666 +/- 0.16 (p <0.01). We observed a lesser significant improvement in mean frequency in group 1 at the secondary end point to 10.444 +/- 0.94 voids (p <0.05). No significant modification was noted in patients assigned to placebo. Mean pain score significantly decreased in group 1 at the primary end point from 5.555 +/- 0.29 to 2.666 +/- 0.23 (p <0.01) but not at the secondary end point (4.777 +/- 0.66, p >0.05). No statistically significant improvement in mean pain score was observed in placebo group 2. During resiniferatoxin infusion 4 group 1 patients noticed a light warm or burning sensation at the suprapubic and/or urethral level. CONCLUSIONS: Intravesical resiniferatoxin may significantly improve the voiding pattern and pain score in patients with hypersensitive disorder and bladder pain. Because resiniferatoxin did not cause a significant warm or burning sensation at the suprapubic and/or urethral level, it may be considered a new strategy for treating hypersensitive disorder and bladder pain. However, further studies are necessary to confirm our results and define the resiniferatoxin mechanism of action, dose and necessary treatment schedule.

Urodynamic assessment during intravesical infusion of capsaicin for the treatment of refractory detrusor hyperreflexia.

PURPOSE: Parameters to predict outcome and the urodynamic effects during infusion of capsaicin, seem not to have been assessed in patients with chronic cord injury. We monitored bladder activity urodynamically during infusion of high dosage of capsaicin. MATERIAL AND METHODS: Thirty patients, 18 women and 12 men (average age 29 years, range 20-59 years), suffering from chronic spinal myelopathy, who presented a refractory detrusor hyperreflexia, were studied. They received saline solution containing 10(-3) M capsaicin at a flow rate of 2 ml min(-1) for 15 min (total volume 30 c.c.). The detrusor activity was monitored by a real-time cystometrogram during infusion and 15 min after the end of the infusion itself. New filling cystometrograms were recorded after 30 days and after 6 months. RESULTS: We obtained a clinical and significant urodynamic improvement in 15 of the 30 patients (50%), confirming that intravesical capsaicin may represent a therapeutic option for a selected group of patients suffering from refractory detrusor hyperreflexia due to chronic spinal upper motor neuron lesion. Best results were observed in patients who showed, during the infusion of capsaicin, early uninhibited bladder contractions which disappeared within 10-12 min from the beginning of the infusion (desensitisation). The patients of this group presented a significant increase of mean cystomanometric capacity after 6 months (from 190.7 to 396.7 ml). No significant clinical or urodynamic improvement was observed in the group of patients in whom uninhibited activity of detrusor was recorded for all the time of infusion. CONCLUSION: Our results support the idea of a major complexity of spinal reflex in paraplegic patients and may offer a clue to explain the failure of therapy with capsaicin. The present results support a new approach in the treatment of detrusor hyperreflexia. The ideal dosage and treatment interval are not at present established and further studies are needed to explain substantial differences in the outcome according to different urodynamic responses.

Intravesical resiniferatoxin for the treatment of detrusor hyperreflexia refractory to capsaicin in patients with chronic spinal cord diseases.

OBJECTIVE: Resiniferatoxin (RTX), a substance isolated from some species of Euphorbia, a cactus-like plant, shows pharmacological effects similar to those of capsaicin. We have studied the possibility of treating detrusor hyperreflexia refractory to intravesical capsaicin in patients with chronic spinal cord injuries, thereby providing insight into the mechanism of action of RTX on sensory neurons and its possible future pharmacological and clinical use. MATERIALS AND METHODS: RTX saline solution (30 ml at a concentration of 10(-5) M) was instilled into the bladder of 7 patients with detrusor hyperreflexia, refractory to intravesical capsaicin therapy, and left in place for 30 min. Effects on bladder function were monitored during the treatment and at follow-up (15 days and 4 weeks later). RESULTS: Fifteen days after RTX, the mean cystomanometric capacity increased significantly from 190 ml +/- 20 ml to 407.14 ml +/- 121.06 (p < 0.01), and it remained high four weeks later (421.66 +/- 74.40 p < 0.01). After 15 days, four patients had a pharmacologically induced detrusor areflexia. They emptied their bladders by clean intermittent catheterization. After four weeks, only two patients still had a pharmacologically induced detrusor areflexia. Clinically, three patients remained dry, and the other three reported a significant improvement in their incontinence and symptoms (frequency, urgency and nocturia). CONCLUSIONS: By interfering with sensory unmyelinated fibers, intravesical RTX seems to be a promising treatment option for selected cases of detrusor hyperreflexia. The ideal dosage and treatment interval have not yet been established, and further studies are necessary to confirm our preliminary results.

Urodynamic effects of intravesical resiniferatoxin in humans: preliminary results in stable and unstable detrusor.

PURPOSE: Resiniferatoxin, a substance isolated from some species of euphorbia, a cactus-like plant, presents pharmacological effects similar to those of capsaicin. We studied the urodynamic effects of intravesical resiniferatoxin* in normal subjects and patients with unstable detrusor contraction to provide insight into the action mechanism of the molecule on sensory neurons and possible future pharmacological and clinical use. MATERIALS AND METHODS: A total of 15 subjects with normal (8 patients) or unstable detrusor muscle (1 with detrusor instability and 6 with detrusor hyperreflexia) underwent urodynamic assessment during and after intravesical instillation of resiniferatoxin. Volume required to elicit the first desire to void, maximum bladder capacity and maximum bladder pressure were recorded during instillation of resiniferatoxin at a flow rate of 20 ml. per minute (normal subjects) or 15 minutes after instillation of 30 cc of a saline solution containing 10(-8) M. of resiniferatoxin and kept for 30 minutes in patients with unstable detrusor. The experiment was examined by the analysis of variance for repeated measures and post hoc comparisons were performed by Tukey-Kramer procedure. A p value <0.05 was accepted as significant. RESULTS: Resiniferatoxin did not decrease the volume required to elicit the first desire to void and did not produce warm or burning sensations at the suprapubic/urethral level during infusion in subjects with normal detrusor function. In patients with bladder hyperactivity mean bladder capacity increased from 175.28 ml. plus or minus standard deviation 36.05 to 280.85 ml. plus or minus standard deviation 93.33 (p <0.01) immediately after treatment, and no significant modification of bladder pressure was recorded. Four weeks after treatment, bladder capacity remained increased in 2 patients but mean capacity did not increase significantly from 175.28 ml. plus or minus standard deviation 36.053 to 216.71 plus or minus standard deviation 86.91. The 2 patients with stable increase of bladder capacity reported significant clinical improvement of frequency, nocturia and incontinence 4 weeks later. CONCLUSIONS: Our results suggest that in humans there may be substantial differences in urodynamic effects between resiniferatoxin and capsaicin when the drugs are instilled into the bladder. Further studies, in vitro and in vivo, are necessary to define the pharmacological and clinical effects of resiniferatoxin. Because resiniferatoxin did not produce warm or burning sensations at the suprapubic/urethral level during infusion and seems to have rapid desensitization, it could be an interesting alternative to intravesical capsaicin in the treatment of select cases of bladder hyperactivity.

Iatrogenic external iliac artery disruption during open pelvic lymph node dissection: successful repair with hypogastric artery transposition.

We report the first case of a wide, iatrogenic, proximal disruption of the right external iliac artery, occurring during staging open lymph node dissection for prostate cancer, which was repaired by hypogastric artery transposition. The hypogastric artery was mobilized and rotated anteriorly, and sutured to the distal segment of the external iliac artery. This is a feasible, innovative and safe technique which permits, by a single anastomosis, the secure reconstruction of a vascular axis to the leg when other procedures are not accessible.

Intravesical capsaicin for treatment of severe bladder pain: a randomized placebo controlled study.

PURPOSE: Present therapeutic approaches to control bladder pain are clinically and scientifically unsatisfactory, and pain in the lower urinary tract remains a challenge even to the skilled urologist. A randomized placebo controlled study was done to evaluate intravesical capsaicin for severe bladder pain. Followup was 6 months. MATERIALS AND METHODS: A total of 36 patients was prospectively randomized into those receiving 10 microM. intravesical capsaicin twice weekly for 1 month (group 1) or placebo (group 2). All patients had pelvic pain for at least 6 months, and had no urinary tract infection within the last 3 months, functional disorders of the lower urinary tract, or other vesical or urethral pathology. Pretreatment voiding pattern and pain score were recorded. Patients were evaluated immediately at the end of treatment (primary end point) and 6 months later (secondary end point). RESULTS: Both groups were adequately homogeneous with regard to age, sex ratio, duration of disease, voiding pattern and pain score. At both end points group 1 had significant improvement in frequency and nocturia but no improvement in urgency. No change was noted in group 2. A significant decrease in pain score was found in group 1 at the primary (mean plus or minus standard deviation 3.22 +/- 0.42, p < 0.01) and secondary (3.83 +/- 0.47, p < 0.01) end points compared to before treatment (5.61 +/- 0.40, chi-square with 2 degrees of freedom 29.25, p < 0.0001). A significant improvement was also observed in the placebo group, in which the pretreatment pain score (5.47 +/- 0.37) was decreased at the primary (4.47 +/- 0.36, p < 0.01) and secondary (4.48 +/- 0.34, p < 0.01, chi-square with 2 degrees of freedom 12.71, p < 0.002) end points. There were no statistically significant differences between the 2 groups. CONCLUSIONS: We confirmed the beneficial effect of intravesical instillation of capsaicin on voiding pattern in patients with hypersensitive disorders (frequency and nocturia). We could not confirm improvement in pain score after capsaicin treatment compared to placebo. Possibly a larger dose of capsaicin would be more effective in controlling pain and neurological disease of the bladder.

Pseudosarcoma of the urinary bladder.

A case of pseudosarcoma of the urinary bladder is described in a woman aged 23. The tumor presenting with symptoms of cystitis arised in the left wall and invaded vesical cavity and pelvis. Histological, histochemical, immunohistochemical and electron microscope studies revealed a fibroblastic and myofibroblastic proliferation with atypias, accompanied by inflammatory infiltrates and rich vascularity. The tumor was furthermore characterized by extensive necrosis, involving the muscularis propria, and infiltrated the perivesical fat. The favourable outcome four years after partial cystectomy suggests the diagnosis of pseudosarcoma. The differential diagnosis and the pathogenesis of this rare lesion is discussed.

Vesical dysfunction in systemic sclerosis (scleroderma)

There have been only a few reports on the involvement of the urinary tract in patients with systemic sclerosis, a disease of the connective tissue characterized by thickening and fibrosis of the skin, abnormality of the small arteries, and involvement of the gastrointestinal tract, heart, lung and kidney. We report the urodynamic assessment and histological examination of 9 women with scleroderma. Three patients voided less than 100 ml. with a significant residual volume and 4 presented with detrusor areflexia during a filling cystometrogram. Histopathological examination in all patients with detrusor areflexia demonstrated the presence of arterial lesions and derangement of the capillary bed of the detrusor musculature. Our data provide evidence for the functional and histological involvement of the bladder in patients with systemic sclerosis.

Vesical-renal reflex: diuresis and natriuresis activated by intravesical capsaicin.

In the last years the role of capsaicin sensitive innervation, in the activation of the micturition reflex, has been reported in many papers. In our experience, upon the intravesical administration of capsaicin in humans, we noticed an increase of diuresis. No interaction is known about the sensory innervation of the bladder and renal function, so we studied the possibility of the existence of a vesical-renal reflex arc. Twenty-one patients (9 men and 12 women) were randomised to receive intravesical infusion of saline solution containing 10 microM capsaicin. Urine output, glomerular renal filtrate (GRF) and effective plasma renal flow (EPRF), measured by Technetium-99m diethylenetetramine-penta-acetic acid (DTPA) renal scintigraphy, were recorded over twenty minutes before and after the intravesical administration of capsaicin. Urine density, [Na+] and [K+] concentration, and prostaglandin E2 excretion were also determined before and after intravesical administration of capsaicin or vehicle. Installation of saline solution containing 10 microM capsaicin produced a significant increase of mean urine output, an increase of GRF, of EPRF and of [Na+] and [K+] urine concentration. An increase, not statistically significant, was observed of PgE2 excretion. None of the patients treated with vehicle showed any modification of parameters examined. The present findings demonstrate a hitherto unrecognized effect: increased diuresis following selective chemical stimulation of bladder efferents with capsaicin. The renal diuretic response to intravesical capsaicin represents a working hypothesis about the possible involvement of a vesical-renal reflex arc organized at spinal or supraspinal level.

Autotransplantation for intractable loin pain: report of a case with long-term followup.

We report a case of autotransplantation performed 21 years ago in a patient suffering from intractable loin pain. Long-term followup, the pathogenesis of pain in regard to renal innervation and the value of autotransplantation as a form of complete sensory denervation are discussed.

Gastropyeloplasty: an alternative procedure in reconstruction of the renal pelvis.

We report our first experience with the use of a small gastric patch for reconstruction of the renal pelvis. We performed left gastropyeloplasty based on the right gastroepiploic artery in 1 patient suffering from recurrent urinary tract infections and renal stones, and moderate renal failure. The use of a gastric patch for reconstruction of the renal pelvis prevented the recurrence of calculi and bacterial infections, and produced an improvement in renal function. We confirm the feasibility of the use of a small gastric patch in reconstruction of the renal pelvis and we argue that there are several possible ways to use stomach in upper urinary tract reconstruction.

Intraurethrally infused capsaicin induces penile erection in humans.

Capsaicin-sensitive primary afferents widely innervate the genitourinary tract and play an important role in the integration of various mechanisms which activate reflexes leading to penile erection. We investigated the effect of intraurethral capsaicin infusion in psychogenically impotent men. The 20 patients were prospectively randomized to four groups, each of five men. Group A received intraurethral infusion of saline solution, group B intraurethral capsaicin (10(-5) M), group C intracavernosal papaverine hydrochloride (8 mg) plus intraurethral saline infusion, and group D intracavernosal papaverine hydrochloride (8 mg) plus intraurethral capsaicin (10(-5) M). The penile response was recorded real-time. Intraurethral capsaicin induced penile erection, as did the papaverine injection, while saline infusion was without effect. The erectile response to intraurethral infusion of capsaicin is suggested to involve activation of a urethra-corpora cavernosa reflex arc. Further studies are necessary to clarify if this arc is integrated at central nervous system level or is locally triggered, and if it may have pathophysiologic implications.

Relief of pain following intravesical capsaicin in patients with hypersensitive disorders of the lower urinary tract.

We have extended our earlier observations on pain relief produced by intravesical instillation of capsaicin (10 microM in saline) in patients with hypersensitive disorders of the lower urinary tract. Patients in group A (n = 15) received intravesical capsaicin on days 0, 14 and 28: on each occasion the drug produced a warm or burning sensation, reduction in bladder capacity and a delayed, transient improvement or disappearance of symptoms. Patients in group B (n = 5) received intravesical capsaicin (10 microM at cystometry) 3 times on day 0. The initial sensation of warmth was experienced on each occasion, indicating that no significant desensitisation has been produced by the first instillation. Clinical improvement similar to that found in group A was observed. Three patients (group C) received warm saline (42 degrees C) at cystometry. This produced a pricking sensation, no change at cystometry and no subjective clinical improvement. Apart from the initial sensation of warmth, no patient in group A or B experienced side effects, either local or systemic. These findings confirm that intravesical instillation of capsaicin has a beneficial effect on patients with hypersensitive bladder disorders. Counter-irritation rather than desensitisation of primary afferents could be a possible mechanism of action. Further studies are needed to establish whether the intravesical administration of capsaicin or capsaicin-like agents represents a new form of treatment for relief of bladder pain.

Cystometric evidence that capsaicin-sensitive nerves modulate the afferent branch of micturition reflex in humans.

Intravesical instillation of capsaicin (0.1 to 10 microM) in six patients (five with hypersensitive disorders of the lower urinary tract, one with benign prostatic hyperplasia) produced a concentration-related reduction of the first desire to void, bladder capacity and pressure threshold for micturition. At a threshold concentration of one microM, capsaicin also produced a warm to burning sensation referred to the suprapubic area during the collecting phase and to the urethra during micturition. All the patients with hypersensitive disorders of the lower urinary tract reported disappearance or marked attenuation of their symptoms for a few days after capsaicin application. In three other patients with hypersensitive disorders of the lower urinary tract, intravesical instillation of capsaicin's vehicle (0.1% ethanol in saline) did not produce significant cystometric changes nor modify the symptomatology. These observations provide the first indication that capsaicin-sensitive structures (nerves?) may be present in the human urinary bladder as they have been shown to occur in various other species.

Human isolated small intestine: motor responses of the longitudinal muscle to field stimulation and exogenous neuropeptides.

(1) Longitudinal muscle strips from the human small intestine (jejunum/ileum) responded to electrical field stimulation (1-50 Hz) with frequency-related primary contractions which were largely atropine- (3 microM) sensitive. When the tone was raised by addition of galanin (0.3-1 microM), prostaglandin (PG) E2 (1-10 microM) or neurokinin A (NKA, 0.1 microM), a frequency-related relaxation was evident which was potentiated by atropine. All the responses to field stimulation were abolished by tetrodotoxin (1 microM), thus indicating their neural origin. (2) The atropine-sensitive primary contraction to field stimulation was virtually abolished by omega conotoxin fraction GVIA (CTX, 0.1-0.3 microM) while the relaxations were CTX-resistant. The field stimulation-induced relaxations, which were observed in the presence of atropine and guanethidine (3 microM), were also unaffected by apamin (0.1 microM). (3) NKA and substance P (SP) produced a concentration- (1 nM-1 microM for both peptides) related contraction, NKA being about 53 times more potent than SP. [Pro9]SP sulphone and [MePhe7]-NKB, selective agonists of the NK-1 and NK-3 receptor, respectively, were barely effective. On the other hand, [beta Ala8]NKA(4-10), a selective NK-2 receptor agonist, had a potent contractile activity, similar to that of NKA. (4) Galanin (1 nM-1 microM) produced an atropine- and tetrodotoxin-resistant concentration-related contraction of longitudinal muscle of human isolated small intestine. The response to galanin did not show any sign of fading and was particularly suitable to study the evoked relaxations.(ABSTRACT TRUNCATED AT 250 WORDS)

Further studies on the motor response of the human isolated urinary bladder to tachykinins, capsaicin and electrical field stimulation.

1. Muscle strips from the dome of the human urinary bladder responded to field stimulation with contractions which were atropine- (3 microM) and tetrodotoxin- (1 microM) sensitive. These contractions were sensitive to omega conotoxin (CTX, 0.1 microM). The atropine- and tetrodotoxin-resistant contractions produced by field stimulation were totally unaffected by CTX. 2. DMPP (30-100 microM), a nicotinic agonist, produced transient bladder contractions which were hexamethonium- and atropine-sensitive. 3. Tachykinins produced a contraction of the human bladder. Among several synthetic tachykinin analogs only those having activity at the NK-2 receptor produced a consistent contractile response. 4. Either capsaicin (1 microM) or calcitonin gene-related peptide (10 nM-0.1 microM) had no motor effect. At 10 microM, capsaicin exerted a depressant effect on nerve-mediated contractions but this effect did not exhibit desensitization. 5. These findings provide evidence that NK-2 receptors are the main if not the sole mediators of the contractile response of the muscle from the dome of the human isolated bladder to tachykinins. 6. No evidence was found for a tachykininergic component in the excitatory response to field stimulation nor for motor responses mediated by capsaicin-sensitive nerves. 7. CTX-sensitive calcium channels are probably present on cholinergic nerve terminals in the human bladder muscle.

Revascularization of the right ischemic kidney by gastroduodenal artery.

Hepatorenal bypass can successfully accomplish revascularization of the right renal artery when the aorta or the iliac vessels cannot be used for a standard renal bypass or renal autotransplantation. The use of the hepatic circulation can be increased by the gastroduodenal to renal artery bypass procedure. Herein we report a clinical case of severe hypertension in a patient with a solitary functional kidney and an extensive atheromatous alteration of the aortoiliac segment. It has been corrected by means of a gastroduodenal end-to-side renal saphenous vein bypass graft.

Specific motor effects of capsaicin on human jejunum.

Capsaicin (1 microM) produced a biphasic effect on the motility of longitudinal muscle strips from human jejunum e.g. an initial inhibitory effect on nerve-mediated contractions followed by a delayed increase in motility. Neither effect was observed upon a second application of the drug, indicating desensitization, a proposed marker of the action of capsaicin on sensory nerves. Both substance P and neurokinin A produced a contraction of isolated human jejunum, while calcitonin gene-related peptide had a small and inconsistent inhibitory effect.