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Biomedical subjects

P Beneforti

Publications and source records attributed to P Beneforti.

At least 19 recordsLinked to original sources

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.

Administration, Intravesical

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.

Arteries

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.

Administration, Intravesical

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.

Female

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.

Administration, Intravesical

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.

Female

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.

Adult

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.

Capsaicin

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.

Administration, Intravesical

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)

Aged

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.

Adult

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.

Administration, Intravesical

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.

Aged

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.

Adult

Contractile response of the human isolated urinary bladder to neurokinins: involvement of NK-2 receptors.

The contractile response to substance P (SP), neurokinin A (NKA) and arginin-neurokinin B (Arg-NKB) (a water soluble analogue of NKB) was investigated in detrusor muscle strips from the dome of the urinary bladder obtained from patients undergoing total cystectomy for carcinoma of the bladder base. Spontaneous activity and response to nerve stimulation indicated that the material used in this study has characteristics similar to those described for 'normal' human detrusor muscle. All neurokinins induced a concentration-related contraction with sensitivity at nM concentrations and the following rank order of potency: NKA (90) greater than Arg-NKB (22) greater than SP (1). These findings indicate the involvement of NK-2 receptors in the contractile response of human detrusor muscle to neurokinins.

Aged

Relaxation of isolated corpus cavernosum induced by smooth-muscle relaxant drugs. A comparative study.

Intracavernous injection of vasoactive substances are used in the treatment and investigation of impotence. We studied the effects induced by some pharmacological agents on strips of human erectile tissue. Specimens of corpus cavernosum were obtained from 16 men undergoing cystectomy or penectomy for bladder or penile malignancy. Strip preparations were mounted in thermostically controlled baths containing Krebs solution. Pharmacologic effects were monitored by means of an isotonic transducer. Papaverine was shown to be the substance able to cause the biggest relaxation effect. The authors compared the action of other drugs having a relaxant effect, studied the antagonist effects of epinephrine and dopamine on the pharmacologically relaxed preparations, and stressed that the relaxation of the erectile tissue has a determinant role in the appearance and maintenance of erection.

Adult

Biological, diagnostic and therapeutic aspects of a case of renal cell carcinoma occurring with bladder and contralateral adrenal metastasis.

We report a case of renal cell carcinoma occurring with bladder and contralateral adrenal metastasis discovered preoperatively with computerized tomography. Surgical treatment consisted of radical nephrectomy, with preservation of the ipsilateral adrenal gland, contralateral adrenalectomy, and transvesical resection of the bladder neoplasm. The hypothesis for the mechanism(s) of spread and treatment modalities are discussed.

Adrenal Gland Neoplasms