Search PubMed⌕ Search

Biomedical subjects

Antonella Giannantoni

Publications and source records attributed to Antonella Giannantoni.

17 recordsLinked to original sources

Must colposuspension be associated with sacropexy to prevent postoperative urinary incontinence?

OBJECTIVES: This prospective, randomised study investigated whether a prophylactic procedure, performed during colposacropexy for prolapse repair, prevents ex novo postoperative incontinence. Sixty-six consecutive continent patients with advanced prolapse were randomised into two groups: group A underwent sacropexy combined with a Burch colposuspension; no anti-incontinence procedure was performed in group B patients. METHODS: Work-up included clinical assessment (Halfway System and International Continence Society [ICS] classification for prolapse and Ingelman Sunderberg scale for incontinence), the Urogenital Distress Inventory and Impact Incontinence Quality of Life questionnaires, urogynaecologic ultrasound scans, and complete urodynamic testing that included the urethral pressure profile and Valsalva leak point pressure with reduced prolapse. Check-ups were done at 3, 6, 12 mo postoperatively and then yearly. Mean follow-up time was 39.5 mo. RESULTS: The mean age (+/- standard deviation) was 62+/-9 yr. All patients presented with grade (G) 3-4 prolapse. Postoperative incontinence was present in 12 of the 34 patients in group A: 7 G1; 4 G2, and 1 G3. Postoperative incontinence was present in 3 of the 32 patients in group B: 2 G1, 1 G3. The frequency of postoperative incontinence was significantly greater in patients who had undergone colposuspension (p<0.05). CONCLUSIONS: These preliminary data cast doubt on whether colposuspension should be performed during sacropexy for severe urogenital prolapse as prophylaxis for postoperative incontinence because it seems to emerge as overtreatment. Incontinence developed ex novo in 35% of continent patients treated with colposuspension combined with sacropexy.

Adult↗

New frontiers in intravesical therapies and drug delivery.

OBJECTIVES: The intravesical route permits site-specific delivery of drugs with a reduced side-effect profile as compared to oral delivery systems, either by avoiding first-pass metabolism or by obtaining a local effect. We investigated mechanisms related to urothelium permeability and new physical and chemical developments in intravesical drug delivery that potentially permit successful treatment of several bladder dysfunction. METHODS: A literature review. RESULTS: Pharmacologic agents increasing urothelial permeability and useful for clinical purposes have been described, such as dimethylsulfoxide, protamine sulphate, chitosan, and nystatin. Among physical approaches, electromotive drug administration appears to be more effective than intravesical passive diffusion in delivering drugs through the urothelium into deeper layers of the bladder. Experimental and clinical reports demonstrated that electric current significantly increases the transport of local anaesthetics, mytomicin C, oxybutynin, resiniferatoxin, epinephrine, and dexamethasone. Among new chemical approaches, cell-penetrating peptides posses the ability to translocate macromolecular drugs across membranes of urothelial cells. The therapeutic benefits of sustained delivery afforded by thermosensitive hydrogel, which forms a depot for hydrophilic and hydrophobic drugs, have been demonstrated by delivering anti-inflammatory drugs. Liposomes improve the aqueous solubility of several hydrophobic drugs such as taxol, amphotericin, and capsaicin. CONCLUSIONS: Electromotive drug administration, new in situ delivery systems, and bioadhesive liposomes may make it possible to extend intravesical therapy and drug administration to many bladder diseases. Research to expand knowledge of the chemical and physical properties of the bladder and processes regulating drug transport across biologic membranes is needed to make this a reality.

Absorption↗

Botulinum A toxin intravesical injections in the treatment of painful bladder syndrome: a pilot study.

OBJECTIVE: We evaluated the efficacy and tolerability of botulinum A toxin (BTX-A) intravesical injections in patients affected by painful bladder syndrome with increased urinary frequency, refractory to conventional treatment modalities. METHODS: Twelve women and two men were prospectively included in the study. Under short general anaesthesia patients were given injections of 200 U of commercially available BTX-A diluted in 20 ml 0.9% NaCl. Injections were performed submucosally in the trigone and bladder floor under cystoscopic control. Voiding chart, the Visual Analog Scale (VAS) for pain, and urodynamics were performed before treatment and 1 and 3 mo afterward. RESULTS: Overall, 12 patients (85.7%) reported subjective improvement at 1 and 3 mo follow-up. The mean VAS score was significantly reduced at 1 and 3 mo after treatment (p<0.05 for both); at the same time points daytime and nighttime urinary frequency significantly decreased (p<0.01 and p<0.05, respectively), and bladder cystometric capacity significantly increased (p<0.01). Two patients reported incomplete bladder emptying. We did not detect any systemic side effects during or after treatment. CONCLUSIONS: The results of this pilot study indicate that BTX-A intravesical injections are effective in the short-term management of painful bladder syndrome. By modulating afferent C-fiber activity within the bladder walls, BTX-A significantly improves urodynamic parameters and reduces bladder pain and urinary frequency.

Administration, Intravesical↗

Botulinum A toxin for the treatment of benign prostatic hyperplasia/lower urinary tract symptoms.

Botulinum neurotoxin (BoNT) has been called the most poisonous poison and a potential bioterrorism weapon, and yet modern medicine has been able to harvest the elegant and specific activity of this toxin to treat a variety of medical conditions. BoNT application recently has been extended to prostate disorders, and this article reviews the literature on the mechanisms of action and clinical efficacy of BoNT treatment in the prostate. BoNT has demonstrated promising preliminary results for male lower urinary tract symptoms, and translational research suggests novel mechanism of action of BoNT in the prostate. It is important to remember that the application of BoNT in the prostate is not approved by the regulatory agencies and caution should be applied until larger randomized clinical studies are completed.

Botulinum Toxins, Type A↗

Botulinum-A toxin injections into the detrusor muscle decrease nerve growth factor bladder tissue levels in patients with neurogenic detrusor overactivity.

PURPOSE: We investigated the effects of BTX-A on visceral afferent nerve transmission by measuring bladder tissue NGF levels in patients with neurogenic detrusor overactivity before and after intravesical treatment with BTX-A. We also compared the bladder tissue NGF content with clinical and urodynamic data. MATERIALS AND METHODS: A total of 23 patients underwent clinical evaluation and urodynamics with detection of the UDC threshold, maximum pressure and maximum cystometric capacity before, and at the 1 and 3-month followups. Endoscopic bladder wall biopsies were also obtained at the same time points. NGF levels were measured in tissue homogenate by enzyme-linked immunosorbent assay (Promega, Madison, Wisconsin). RESULTS: At 1 and 3 months mean catheterization and incontinent episodes were significantly decreased (p <0.05 and <0.001, respectively). On urodynamics we detected a significant increase in the UDC threshold and maximum cystometric capacity, and a significant decrease in UDC maximum pressure at the 1 and 3-month follow-ups compared to baseline (each p <0.001). At the same time points we detected a significant decrease in NGF bladder tissue content (each p <0.02). CONCLUSIONS: BTX-A intravesical treatment induces a state of NGF deprivation in bladder tissue that persists at least up to 3 months. As caused by BTX-A, the decrease in acetylcholine release at the presynaptic level may induce a decrease in detrusor contractility and in NGF production by the detrusor muscle. Alternatively BTX-A can decrease the bladder level of neurotransmitters that normally modulate NGF production and release.

Administration, Intravesical↗

Sequential BCG and electromotive mitomycin versus BCG alone for high-risk superficial bladder cancer: a randomised controlled trial.

BACKGROUND: The rationale for combining anticancer drugs has not been applied consistently to use of intravesical agents for treatment of superficial bladder cancer, for which immunotherapeutic BCG and chemotherapeutic mitomycin seem to be a potentially effective combination. We aimed to do a prospective, randomised comparison of BCG alone with that of sequential BCG and electromotive mitomycin in patients with stage pT1 bladder cancer. METHODS: After transurethral resection and multiple biopsies, 212 patients with stage pT1 bladder cancer were randomly assigned to: 81 mg BCG infused over 120 min once a week for 6 weeks (n=105); or to 81 mg BCG infused over 120 min once a week for 2 weeks, followed by 40 mg electromotive mitomycin (intravesical electric current 20 mA for 30 min) once a week as one cycle for three cycles (n=107). Complete responders underwent maintenance treatment: those assigned BCG alone had one infusion of 81 mg BCG once a month for 10 months, and those assigned BCG and mitomycin had 40 mg electromotive mitomycin once a month for 2 months, followed by 81 mg BCG once a month as one cycle for three cycles. The primary endpoint was disease-free interval; secondary endpoints were time to progression; overall survival; and disease-specific survival. Analyses were done by intention to treat. This trial has been submitted for registration at the US National Cancer Institute website . FINDINGS: Median follow-up was 88 months (IQR 63-110). Patients assigned sequential BCG and electromotive mitomycin had higher disease-free interval than did those assigned BCG alone (69 months [95% CI 55-86] vs 21 months [15-54]; difference between groups 48 months [42-54], log-rank p=0.0012). Patients assigned sequential BCG and electromotive mitomycin also had lower recurrence (41.9% [32.7-51.5] vs 57.9% [48.7-67.5]; difference between groups 16.0% [2.7-29.3], log-rank p=0.0012); progression (9.3% [3.8-14.8] vs 21.9% [17.9-25.9]; difference between groups 12.6% [3.0-22.2], log-rank p=0.004); overall mortality (21.5% [13.5-29.5] vs 32.4% [23.4-41.4], difference between groups 10.9% [0.6-21.2], log-rank p=0.045); and disease-specific mortality (5.6% [1.2-10.0] vs 16.2% [6.1-23.3], difference between groups 10.6% [2.5-18.7], log-rank p=0.01). Side-effects were mainly localised to the bladder. INTERPRETATION: BCG-induced inflammation might increase the permeability of the bladder mucosa such that mitomycin can reach the target tissue more easily and exert its anticancer effect.

Aged↗

The potential and promise of using botulinum toxin in the prostate gland.

Botulinum neurotoxin (BoNT) has been called the 'most poisonous poison' and a potential bioterrorist weapon. However, it is possible to use the elegant and specific activity of this toxin to treat various medical conditions. Recently, the application of BoNT was extended to prostate disorders, and we review published reports on the mechanisms of action and clinical efficacy of BoNT in the prostate. The information was gathered from Medline, abstracts from recent urological meetings, and from personal experience. BoNT has shown promising preliminary results for male lower urinary tract symptoms, and translational research suggests a novel mechanism of action of BoNT in the prostate. Importantly, the application of BoNT in the prostate is not approved by the regulatory agencies and caution should be used until larger randomized clinical studies are completed.

Animals↗

Association of CYP17, GSTP1, and PON1 polymorphisms with the risk of prostate cancer.

BACKGROUND: Dietary factors, life-style as well as environmental conditions may contribute to the risk of prostate tumor together with genetic susceptibility, that may be an important factor in determining who is more likely to develop prostate malignancy. We have undertaken a case-control study in order to elucidate the association between polymorphisms in some metabolizing genes with the risk of prostate cancer (PCa). METHODS: Polymorphisms of three xenobiotic genes (CYP17, GSTP1, PON1) were characterized in 384 patients with untreated PCa and 360 age-matched control patients with benign prostatic hyperplasia (BPH). All polymorphisms were investigated by PCR/RFLP methods using DNA from lymphocytes. RESULTS: We found that men with the CYP17/A1A1-A1A2 genotypes, GSTP1/IleVal genotype, PON192/QR and PON55/LM-MM genotypes had a significantly higher risk of PCa compared with the others genotypes. CONCLUSIONS: The three polymorphisms appear to be common genetic traits that are associated with an increased risk for PCa: the analysis of them all in each single case may be a predictable factor, particularly among groups exposed to PCa-related carcinogens.

Aged↗

Percutaneous sequential bacillus Calmette-Guèrin and mitomycin C for panurothelial carcinomatosis.

A 59 year old male presented with a 4 month history of lower urinary tract symptoms. Exhaustive urological investigations revealed papillary tumors and carcinoma in situ extending from the prostatic urethra, throughout the bladder, up both ureters and into the renal pelves. Tumors were resected where possible and then bacillus Calmette-Guèrin (BCG) and mitomycin C (MMC) were infused sequentially through bilateral nephrostomy tubes for a total of six BCG and three MMC instillations. Follow up 1 month post treatment demonstrated a complete response which persisted for 2 years. Then there appeared a solitary papillomatous recurrence in the bladder which was successfully resected. Side effects were the occasional fever and BCG induced granulomatous prostatitis which slowly resolved. In conclusion, sequential BCG/MMC instillations were effective treatment for widespread panurothelial carcinomatosis.

Adjuvants, Immunologic↗

A prospective, randomized study using transdermal electromotive administration of verapamil and dexamethasone for Peyronie's disease.

PURPOSE: Uncontrolled studies with intraplaque electromotive administration of verapamil and dexamethasone have demonstrated objective improvements in Peyronie's disease. We performed a prospective controlled study to assess the efficacy of intraplaque electromotive verapamil/dexamethasone vs electromotive lidocaine. MATERIALS AND METHODS: Patients with Peyronie's disease were randomized into a study group (47 patients) and a control group (49 patients). For each treatment session an electrode receptacle was sited over the plaque and filled with either 5 mg verapamil and 8 mg dexamethasone (study group) or 2% lidocaine (control group), and a 2.4 mA electric current was applied for 20 minutes. All patients were scheduled for 4 sessions per week for 6 weeks. Assessment before and after treatment included measurements of plaque volume and penile curvature, and pain on erection (from questionnaire). RESULTS: A total of 37 patients in the study group and 36 in the control group completed treatment courses. In the study group there were significant decreases in median plaque volume from 824 to 348 mm, and in penile curvature from 43 to 21 degrees. In the control group median volume and curvature were unchanged. The difference in results after treatment between the 2 groups was also significant. Significant pain relief occurred in both groups, transient in the control group and permanent in the study group. All patients experienced temporary erythema at the electrode site. There were no other side effects. CONCLUSIONS: Intraplaque electromotive verapamil and dexamethasone induce substantial objective improvement in Peyronie's disease compared to electromotive lidocaine administration.

Administration, Cutaneous↗

Assessment of bladder and urethral sphincter function before and after radical retropubic prostatectomy.

PURPOSE: In a prospective study we analyzed the effects of radical retropubic prostatectomy (RRP) on detrusor and urethral sphincter function by comparing urodynamic status preoperatively with that during longitudinal followup. MATERIALS AND METHODS: A total of 49 consecutive patients underwent urodynamics with pressure flow studies and Valsalva leak point pressure measurements 3 to 7 days before RRP (baseline), and then 1 and 8 months after surgery. We assessed bladder compliance, detrusor overactivity, detrusor contractility and intrinsic sphincter deficiency (ISD). RESULTS: There was no significant change in detrusor overactivity at 1 and 8 months of followup. Decreased bladder compliance was observed in 20.4% of patients at baseline, and in 38.7% and 30.6% at 1 and 8 months, respectively. De novo decreased compliance was detected in 18.4% and 10.2% of patients at the same points. Impaired bladder compliance was comparable to that before surgery in 20% of cases. Impaired detrusor contractility was detected in 42.8% of patients at baseline, and in 61.2% (p <0.05) and 42.8% at 1 and 8 months, respectively. De novo hypocontractility was observed in 28.6% and 10.2% of patients at 1 and 8 months, respectively. A strong association between detrusor overactivity and ISD was observed at 1 and 8 months (p <0.01). CONCLUSIONS: Following RRP detrusor hypocontractility and decreased bladder compliance represent de novo transient dysfunction probably due to bladder denervation and an established condition not influenced by the operation. The strong association between overactivity and ISD suggests that stress urinary incontinence increases urethral afferent nerve activity and induces involuntary detrusor contractions.

Aged↗

Intravesical resiniferatoxin versus botulinum-A toxin injections for neurogenic detrusor overactivity: a prospective randomized study.

PURPOSE: We investigated the effectiveness and safety of intravesical resiniferatoxin (Sigma Chemical Co., St. Louis, Missouri) and botulinum-A toxin injections into the detrusor muscle in a group of spinal cord injured patients with neurogenic detrusor overactivity unresponsive to conventional anticholinergic therapy. MATERIALS AND METHODS: A total of 25 patients were randomly assigned to receive intravesically 0.6 microM resiniferatoxin in 50 ml of 0.9% NaCl or injections into the detrusor muscle of 300 units botulinum A-toxin diluted in 30 ml 0.9% NaCl. Clinical evaluation and urodynamics were performed at baseline, and at 6, 12 and 18 months after treatment. RESULTS: In both arms there was a significant decrease in catheterization and incontinent episodes, and a significant increase in first detrusor contraction and maximum bladder capacity at 6, 12 and 18-month followup. There were no local side effects with either treatment. Botulinum-A toxin induced a significant decrease in the frequency of daily incontinence episodes (p <0.05), a significant increase in first uninhibited detrusor contraction (p <0.01) in maximum bladder capacity (p <0.01), and a significant decrease in maximum pressure of uninhibited detrusor contractions (p <0.01) compared to resiniferatoxin at 6, 12 and 18-month followup. CONCLUSIONS: In spinal cord injured patients with refractory neurogenic detrusor overactivity, intravesical resiniferatoxin and botulinum-A toxin injections into the detrusor muscle provided beneficial clinical and urodynamic results with decreases in detrusor overactivity and restoration of urinary continence in a large proportion of patients. Botulinum-A toxin injections provided superior clinical and urodynamic benefits compared to those of intravesical resiniferatoxin.

Administration, Intravesical↗

The stability of lidocaine and epinephrine solutions exposed to electric current and comparative administration rates of the two drugs into pig bladder wall.

Intravesical electromotive administration of local anesthetics is clinically successful but electrochemistry, cost and effectiveness limit the choice of drugs to diluted lidocaine HCl 4% mixed with epinephrine. These studies address the stability of lidocaine and epinephrine both over time and when exposed to electric current, i.e. transport rates with passive diffusion and electromotive administration. The drug mixture used was 50 ml lidocaine 4%, 50 ml H2O and 1 ml epinephrine 1/1000. For stability, the solution was placed either in bowls for 7 days or in a two chamber cell with the donor compartment (drugs) separated from the receptor compartment (NaCl solution) by a viable pig bladder wall. This was subjected to 30 mA for 45 min. Stability was measured with mass spectrometry. The cell was also used to determine transport rates with passive diffusion and currents of 20 mA and 30 mA, over 20, 30 and 45 min. Drug measurements in both compartments and bladder were made with HPLC. Lidocaine remained stable throughout the 7 days, epinephrine on day 1 only and both drugs were stable with 30 mA for 45 min. Comparing 20 mA and 30 mA with passive diffusion, there were significant differences in 6/6 donor compartment lidocaine levels, 4/6 receptor compartment levels and 6/6 bladder tissue levels and also in 6/6 epinephrine donor levels and 6/6 tissue levels. The combination lidocaine and epinephrine remains stable for 1 day and when exposed to 30 mA for 45 min. Electric current accelerates the transport of lidocaine and epinephrine.

Anesthetics, Local↗

Pelvic floor muscle behavior during Valsalva leak point pressure measurement in males and females affected by stress urinary incontinence.

PURPOSE: We evaluated pelvic floor muscle (PFM) behavior during Valsalva leak point pressure (VLPP) measurement in males and females affected by stress urinary incontinence and investigated whether VLPP results are influenced by PFM contraction. MATERIALS AND METHODS: A total of 25 females and 14 males underwent surface electromyographic (EMG) recording of PFM activity while performing VLPP. We investigated 2 conditions, VLPP during spontaneous strain (test A), and with simultaneous relaxation of the pelvic floor (test B). We analyzed average EMG activity (microV) at rest and during VLPP in tests A and B, the increasing EMG activity during tests A and B (the difference between average EMG activity during tests A and B and at rest), and the mean duration (seconds) of EMG activity during tests A and B. RESULTS: We detected a significant increase in EMG activity during tests A and B as compared to activity at rest (p <0.0001). Increasing EMG activity during test B was significantly reduced in females (p <0.05) but not in males. During test A patients reporting urinary incontinence showed a significantly lower EMG activity than that of continent patients (p <0.05). A significant reduction in maximum abdominal pressure was detected in test B compared to test A, but there was no difference in VLPP values between tests A and B. CONCLUSIONS: PFM activity significantly increases during VLPP measurement. Eliminating muscular contraction of the pelvic floor does not significantly alter VLPP results.

Electromyography↗

Intravesical electromotive mitomycin C versus passive transport mitomycin C for high risk superficial bladder cancer: a prospective randomized study.

PURPOSE: In laboratory studies electromotive mitomycin C (MMC) demonstrated markedly increased transport rates compared with passive transport. We performed a prospective study in patients with high risk superficial bladder cancer to assess the efficacy of intravesical electromotive vs passive MMC using bacillus Calmette-Guerin (BCG) as a comparative treatment. MATERIALS AND METHODS: Following transurethral resection and multiple biopsies 108 patients with multifocal Tis, including 98 with T1 tumors, were randomized into 3 equal groups of 36 each who underwent 40 mg electromotive MMC instillation with 20 mA electric current for 30 minutes, 40 mg passive MMC with a dwell time of 60 minutes or 81 mg BCG with a dwell time of 120 minutes. Patients were scheduled for an initial 6 weekly treatments, a further 6 weekly treatments for nonresponders and a followup 10 monthly treatments for responders. Primary end points were the complete response rate at 3 and 6 months. MMC pharmacokinetics were assessed. RESULTS: The complete response for electromotive vs passive MMC at 3 and 6 months was 53% versus 28% (p = 0.036) and 58% versus 31% (p = 0.012). For BCG the responses were 56% and 64%. Median time to recurrence was 35 vs 19.5 months (p = 0.013) and for BCG it was 26 months. Peak plasma MMC was significantly higher following electromotive MMC than after MMC (43 vs 8 ng/ml), consistent with bladder content absorption. CONCLUSIONS: Intravesical electromotive administration increases bladder uptake of MMC, resulting in an improved response rate in cases of high risk superficial bladder cancer.

Aged↗

Intravesical capsaicin versus resiniferatoxin in patients with detrusor hyperreflexia: a prospective randomized study.

PURPOSE: Capsaicin and resiniferatoxin (Sigma Chemical Co., St. Louis, Missouri) administered intravesically are attractive options for treating detrusor hyperreflexia. Because the 2 agents differ in chemical structure and relative potency, possible differences in their clinical and urodynamic effects were investigated in this prospective comparative study. MATERIALS AND METHODS: A group of 24 spinal cord injured patients with refractory detrusor hyperreflexia were randomly assigned to receive a single dose of 2 mM. capsaicin in 30 ml. ethanol plus 70 ml. 0.9% sodium chloride or 100 nM. resiniferatoxin in 100 ml. 0.9% sodium chloride. Dwell time was 40 minutes with urodynamic monitoring. Urodynamics were performed at baseline before treatment, and after followups of 30 and 60 days. The frequency of daily catheterizations, incontinence episodes and side effects was recorded. RESULTS: There was no significant urodynamic or clinical improvement in the capsaicin arm at 30 and 60 days of followup. In the resiniferatoxin arm the mean uninhibited detrusor contraction threshold plus or minus standard deviation increased from 176 +/- 54 to 250 +/- 107 ml. at 30 days (p <0.05) and to 275 +/- 98 ml. at 60 days (p <0.01). Mean maximum bladder capacity increased from 196 +/- 75 to 365 +/- 113 ml. at 30 days (p <0.001) and to 357 +/- 101 ml. at 60 days (p <0.001). Daily catheterizations and incontinent episodes were significantly decreased at 30 and 60 days of followup. Autonomic dysreflexia, limb spasms, suprapubic discomfort and hematuria developed in most patients who received capsaicin but in none who received resiniferatoxin. CONCLUSIONS: Intravesical administration of resiniferatoxin is superior to that of capsaicin in terms of urodynamic results and clinical benefits in spinal cord injured patients and it does not cause the inflammatory side effects associated with capsaicin.

Administration, Intravesical↗