PubMed Health⌕ Search

Biomedical subjects

Anthony J Bella

Publications and source records attributed to Anthony J Bella.

17 recordsLinked to original sources

Isolated septal fibrosis or hematoma--atypical Peyronie's disease?

PURPOSE: Classically Peyronie's disease presents with penile curvature and/or pain, and is associated with a palpable penile plaque. We frequently examine patients with suspected Peyronie's disease ultrasonographically and have noted a subset of patients in whom we could identify only a circumscribed septal lesion. We identified characteristics of these patients. MATERIALS AND METHODS: Of our series of approximately 650 patients with Peyronie's disease 47 were identified with these lesions. RESULTS: Of the 47 patients 22 presented with penile curvature with or without accompanying or preceding pain. Of the 47 patients 17 had a significant history of trauma, although only had the classic stigmata of penile fracture. A total of 16 patients had no history of curvature, 7 presented with only penile shortening or focal lack of rigidity and 5 were incidentally found to have lesions during assessment for other complaints. Three patients presenting after trauma were noted to have septal liquefied hematomas, which we aspirated under ultrasound guidance. Followup ultrasound revealed minimal septal thickening. In 1 of these patients the hematoma was adjacent to more typical-appearing septal fibrosis. CONCLUSIONS: We theorize that these hematomas are due to septal fractures and may represent a forme fruste or possibly a precursor lesion of more typical septal fibrosis. Ultrasonographic evaluation may allow earlier identification and treatment of occult septal injuries or lesions and prevent subsequent fibrosis and its associated symptoms.

Adult↗

Complications of porcine small intestine submucosa graft for Peyronie's disease.

PURPOSE: We report outcomes and complications of the use of porcine small intestine submucosa for correcting penile curvature due to Peyronie's disease. MATERIALS AND METHODS: A retrospective study was performed in patients with severe penile curvature (greater than 60 degrees) requiring surgical correction for sexual function. Preoperatively all patients underwent evaluation, including history, physical and penile duplex ultrasound. Of these patients 19 underwent tunical grafting with 1-layer Surgisis small intestine submucosa. Postoperatively patients were evaluated with clinic visits and telephone interviews to assess results. RESULTS: A total of 19 patients 46 to 69 years old (mean age 54) were treated with tunical incision or excision and grafting with small intestine submucosa between March 2002 and July 2005. Average followup was 15 months (range 3 to 43). Patients reported less penile pain with intercourse after surgery. There was no difference in Sexual Health Inventory for Men scores. Preoperatively 12 men (63%) had erectile dysfunction, defined as Sexual Health Inventory for Men less than 21, while 10 (53%) reported postoperative erectile dysfunction. Seven of the 19 patients (37%) had recurrent penile curvature (greater than 10 degrees) and 5 (26%) had recurrent Peyronie's disease plaque. Our complication rate was 37%, including hematoma at the graft site in 5 cases (26%), graft infection in 1 (5%) and Peyronie's disease recurrence requiring plication in 1 (5%). CONCLUSIONS: Small intestine submucosa carries potential for grafting applications because it is easy to use and readily available. Our experience resulted in a 37% complication rate, which exceeds those previously reported with saphenous vein graft repair.

Aged↗

Upregulation of penile brain-derived neurotrophic factor (BDNF) and activation of the JAK/STAT signalling pathway in the major pelvic ganglion of the rat after cavernous nerve transection.

OBJECTIVES: Increasing attention is being focused on identifying novel approaches to recover cavernous nerve (CN) function after injury or secondary to disease states such as diabetes mellitus. We examined penile brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (NT-3) expression, and activation of the Janus kinase (JAK)/signal transducer and activator of transcription (STAT) molecular pathway in the major pelvic ganglion (MPG) after CN injury in the rat. METHODS: Five groups of eight male Sprague-Dawley rats (4 mo, 250-300 g) were used in this study. The penis and MPG with attached CN segment were harvested at 0 h (controls), 12, and 24 h, as well as at 5 and 12 d after CN axotomy, for protein, messenger RNA (mRNA), and immunohistochemical analysis. RESULTS: mRNA and protein expression of BDNF was upregulated in the penis after injury (p<0.05). Levels of NT-3 were unchanged. The JAK/STAT pathway was activated in the MPG after transection, as evidenced by increased STAT1 (peak: 24 h) and STAT3 (peak: 5 d) phosphorylation (p<0.01 vs. controls). CONCLUSIONS: This study demonstrates increased expression of penile BDNF and upregulation of phosphorylated STAT1 and STAT3 in the MPG in response to CN transection. Activation of the JAK/STAT pathway after injury represents a promising new molecular target for modulating CN survival and regeneration.

Analysis of Variance↗

Nonpalpable scarring of the penile septum as a cause of erectile dysfunction: an atypical form of Peyronie's disease.

INTRODUCTION: Men with nonpalpable isolated septal scars (ISS) identified with color duplex ultrasonography (CDU) comprise a group of previously unrecognized patients with wide-ranging sexual concerns. AIM: We aim to identify the clinical characteristics of patients presenting with this atypical form of Peyronie's disease characterized by the absence of palpable deformity. MATERIALS AND METHODS: Of 482 consecutive patients who presented to a tertiary care erectile dysfunction (ED) clinic and underwent CDU after satisfying inclusion criteria, 27 (5.6%) men with nonpalpable ISS and no dorsal or ventral plaque were identified. MAIN OUTCOME MEASURES: International Index of Erectile Function (IIEF), CDU, and clinical characteristics. RESULTS: The median age of the men with nonpalpable ISS was 49 years. The length of time from onset of symptoms to presentation was 22 months, and the pretreatment IIEF score was 14. The remaining 455 men who underwent CDU were of similar age (48 years) but had a markedly lower IIEF score of 9.5 (statistical median). ISS patients presented with decreased penile rigidity (20), penile shortening (13), chronic pain with erection (13; mean 33 months), and the inability to maintain an erection (7). Fourteen men had failed phosphodiesterase-5 inhibitor therapy, and four reported unsatisfactory results. Management options included retrial with oral agents, intracavernous pharmacotherapy, verapamil injections, and surgery. CONCLUSIONS: The clinician should be suspicious for nonpalpable ISS in men with sexual concerns who present with decreased penile rigidity, length loss, and chronic pain with erection. Our findings support the use of CDU for this patient group, particularly when previous treatment has failed, because men with ISS had a greater likelihood of having no palpable deformity or curvature and ongoing penile pain.

Adult↗

Primary PEComa of the bladder treated with primary excision and adjuvant interferon-alpha immunotherapy: a case report.

BACKGROUND: Perivascular epithelioid cell tumors (PEComas) are rare mesenchymal neoplasms of uncertain malignant potential, which have in common the co-expression of muscle and melanocytic immunohistochemical markers. CASE PRESENTATION: A 48-year-old man presented with dysuria, passage of urinary sediment and lower abdominal discomfort. A three centimeter mass was identified by cystoscopy in the posterior midline of the bladder. Computerized tomography suggested an enterovesical fistula. The patient underwent laparotomy, partial cystectomy and partial small bowel resection. Pathological examination revealed PEComa of the bladder. The patient underwent adjuvant interferon-alpha immunotherapy. Subsequent follow-up procedures, including cystoscopy and imaging, have not revealed evidence of recurrence. The patient is clinically free of disease 48 months after surgery. CONCLUSION: This case represents the second documented PEComa of bladder and demonstrates that adjuvant therapies, including anti-angiogenic and immunotherapy, may be considered for patients with locally advanced or metastatic genitourinary PEComa.

Chemotherapy, Adjuvant↗

The effect of intracavernosal growth differentiation factor-5 therapy in a rat model of cavernosal nerve injury.

OBJECTIVE: To determine whether the intracavernosal application of growth differentiation factor-5 (GDF-5) influences nerve regeneration and erectile function after cavernosal nerve injury in a rat model. MATERIALS AND METHODS: Thirty-two male Sprague-Dawley rats were randomly divided into four equal groups: eight had a sham operation (uninjured controls), while 24 had bilateral cavernosal nerve crush. The crush-injury groups were treated at the time of injury with an impregnated collagen sponge implanted into the right corpus cavernosum. The sponge contained no GDF-5 (injured controls), 2 microg (low concentration), or 20 microg GDF-5 (high concentration). Erectile function was assessed by cavernosal nerve electrostimulation at 8 weeks. Midshaft penile tissue samples were histochemically evaluated for neuronal nitric oxide synthase (nNOS)-containing fibres in the dorsal penile nerve. RESULTS: There was no erectile dysfunction in the uninjured control group, as shown by a mean (sem) maximal increase in intracavernosal pressure (ICP) of 149.5 (17.0) cmH(2)O on stimulation. By comparison, the ICP decreased in the injured control group, by 21.3 (6.7) cmH(2)O. After cavernosal nerve injury, the recovery of erectile function was greatest in the low-concentration GDF-5 group; the maximum ICP increase was 40.8 (13.3) cmH(2)O, vs 24.3 (5.9) cmH(2)O for 20 microg GDF-5. Histologically, the low-concentration group had significantly more nNOS-containing nerve fibres, at 163 (24.7), than the high-concentration group, at 76 (17.3), or injured controls, at 67 (23.8). By contrast, the uninjured controls had a mean of 538 (40.6) nerve fibres in the dorsal nerve. CONCLUSION: Bilateral cavernosal nerve crush resulted in erectile dysfunction with accompanying neurological changes in the rat. The intracavernosal application of GDF-5 enhanced the recovery of erectile function and n-NOS nerve preservation, with a 2-microg dose giving the most promising results.

Animals↗

Minimally invasive intracorporeal incision of Peyronie's plaque: initial experiences with a new technique.

OBJECTIVES: Minimally invasive repairs represent an attractive treatment approach for the surgical correction of Peyronie's disease. We describe a novel intracorporeal incision technique and the results of our ongoing experience. METHODS: In selected patients who had consented to surgical treatment of a localized Peyronie's scar, saline erection confirmed the degree and location of penile deformity. The skin was mobilized using a subcoronal, circumferential incision. After limited mobilization of the neurovascular bundle, a 1-cm incision lateral to the plaque allowed for the introduction of a triangle-shaped scalpel designed for endoscopic carpal tunnel release into the corpora. Multiple intracorporeal incisions were made, preserving the outer layer of the tunica. Saline erection confirmed curvature correction. A single pair of ventral plication sutures was required in select cases. The small corporotomy, Buck's fascia, and skin were then reapproximated. Patients were discharged home within 24 hours. RESULTS: In 23 patients, the degree of curvature ranged from 30 degrees to 90 degrees (median 60 degrees). All patients had stable curvature and difficulty with intromission. The mean follow-up was 25 months. Correction of the deformity was successful in all but 2 patients (less than 10 degrees residual curvature), with 80% of patients reporting erections sufficient for intercourse and treatment satisfaction of 85%. CONCLUSIONS: These results indicate good correction of curvature, minimal difficulties with erectile function, and high patient-reported satisfaction using our technique at a follow-up of 25 months. We continue to offer intracorporeal incision as a primary treatment option for discrete plaques less than 2 cm, using grafting techniques for larger and complex lesions.

Adult↗

Brain-derived neurotrophic factor (BDNF) acts primarily via the JAK/STAT pathway to promote neurite growth in the major pelvic ganglion of the rat: part I.

INTRODUCTION: Identification of the molecular mechanism of cavernous nerve regeneration is essential for future development of neuroprotective and regenerative strategies. AIM: To identify specific signal transduction pathway(s) associated with brain-derived neurotrophic factor (BDNF) enhanced cavernous nerve regeneration in an in vitro model. MATERIALS AND METHODS: Using 6-month-old male Fisher rats, inhibitors of four candidate signaling pathways were added to BDNF-treated explant cultures of major pelvic ganglia with attached cavernous nerve fragments. Study groups comprised of controls, BDNF alone at 50 ng/mL, or BDNF 50 ng/mL and inhibitors against MEK, PI3-K, PKA, and JAK/STAT pathways at increasing concentrations. MAIN OUTCOME MEASURE: The maximal neurite length for each tissue culture was measured and the mean maximal length +/- standard deviation was determined for all groups at 24, 36, and 48 hours. RESULTS: The JAK/STAT specific inhibitor AG490 significantly reduced BDNF-enhanced neurite growth. Maximum neurite lengths at 24, 36, and 48 hours for BDNF 50 ng/mL treated groups were 182.3, 348.1, and 528.1 microm, compared with AG490 at 25 microM (86.4, 165.1, 278.3 microm), 50 microM (78.8, 151.7, 235.3 microm), and 100 microM (71.83, 107.0, 219.6 microm) (P < 0.05). Neurite measures for BDNF with 25 and 50 microM U0126 (MEK pathway) were reduced to 402.0 and 424.3 microm at 48 hours, respectively (P < 0.05), likely reflecting an accessory molecular pathway. A similar observation was made for 100 uM LY294002 (PI3-K). No difference was observed for PKA inhibition. CONCLUSION: The JAK/STAT pathway is the major signal-transduction pathway of BDNF-enhanced cavernous nerve growth in an in vitro rat model.

Animals↗

Brain-derived neurotrophic factor (BDNF) acts primarily via the JAK/STAT pathway to promote neurite growth in the major pelvic ganglion of the rat: part 2.

INTRODUCTION: Surgical and radiation therapies of bladder and prostate cancers may damage cavernous nerves and cause erectile dysfunction (ED). We previously showed that brain-derived neurotrophic factor (BDNF) could restore erectile function in a neurogenic ED rat model. We now investigated the signaling mechanism of BDNF in major pelvic ganglia (MPG) explants. AIM: To identify the signaling mechanism that mediates the neurotrophic effect of BDNF in cultured MPG. METHODS: Major pelvic ganglia was isolated from male rats for immunohistochemistry and immunofluorescence staining to locate BDNF receptors, pan-neurotrophin 75 (p75), tropomyosin-related kinase B (TrkB), and tropomyosin-related kinase C (TrkC). The dorso-caudal region of MPG was treated with BDNF to determine the optimal dosage for promoting neurite growth. Specific kinase inhibitors AG490, KT5720, LY294002, and U0126 were then used to treat MPG either alone or prior to BDNF treatment. The treated MPG was examined for neurite growth and for expression and phosphorylation of JAK2, STAT1, and STAT3 by Western blot analysis. MAIN OUTCOME MEASURES: Lengths of neurite growth from MPG were measured to quantify the effects of BDNF and to identify specific signaling pathways. Ratios of phosphorylated vs. unphosphoryated proteins of JAK2, STAT1, and STAT2 in control and treated MPG were determined to confirm JAK/STAT as the principal signaling pathway. RESULTS: Tropomyosin-related kinase B and TrkC were localized to neurons whereas p75 to perineuronal satellite glial cells (SGC). The optimal dosage of BDNF for promoting MPG neurite growth was between 25 and 50 ng/mL. Among the four specific kinase inhibitors, AG490 was the strongest in suppressing MPG neurite growth as well as BDNF-induced phosphorylation of JAK2, STAT1, and STAT3. CONCLUSIONS: In rat MPG, TrkB and TrkC were expressed in neurons, whereas p75 in SGC. Optimal BDNF dosage for promoting MPG neurite growth was between 25 and 50 ng/mL. BDNF promotes MPG neurite growth primarily by activating the JAK/STAT pathway.

Animals↗

Malignant neoplasm of perivascular epithelioid cells of the liver.

Neoplasms of perivascular epithelioid cells (PEComas) have in common the coexpression of muscle and melanocytic immunohistochemical markers. Although this group includes entities with distinct clinical features, such as angiomyolipoma, clear cell sugar tumor of the lung, and lymphangioleiomyomatosis, similar tumors have been documented in an increasing diversity of locations. The term PEComa is now generally used in reference to these lesions that are not angiomyolipomas, clear cell sugar tumors, or lymphangioleiomyomatoses. While most reported PEComas have behaved in a benign fashion, malignant PEComas have occasionally been documented. We present a case of hepatic PEComa with benign histologic features, which nonetheless presented with metastases to multiple sites nearly 9 years later. This case represents the second documented malignant PEComa of the liver, as well as the longest follow-up of a surviving patient with a malignant PEComa, emphasizing both the need for criteria that more accurately predict the behavior of PEComas and the necessity of long-term follow-up of patients with PEComas.

Epithelioid Cells↗

Non-arteritic anterior ischemic optic neuropathy (NAION) and phosphodiesterase type-5 inhibitors.

OBJECTIVE: To determine whether a causative relationship exists between non-arteritic anterior ischemic optic neuropathy (NAION) and the use of phosphodiesterase-5 (PDE-5) inhibitors for the treatment of erectile dysfunction. METHODS: A comprehensive review of the literature was performed to identify the contemporary understanding of NAION pathophysiology, epidemiology, and occurrence in men using the oral PDE-5 inhibitors sildenafil (Viagra, Pfizer), vardenafil (Levitra, Bayer AG), and tadalafil (Cialis, Lilly-ICOS LLC) for the treatment of erectile dysfunction. RESULTS: NAION is the second most common acquired optic neuropathy in men aged 50 years and older. Risk factors for NAION, cardiovascular disease, and erectile dysfunction are shared and include age, dyslipidemia, diabetes, hypertension, and cigarette smoking. To date, less than 50 cases of NAION associated with PDE-5 use have been reported to the United State's Food and Drug Administration (FDA) and five Canadian cases alerted to Health Canada. Given the large number of men safely using these agents and a limited number of events, it is not possible to determine whether NAION is directly linked to the use of PDE-5 inhibitors, underlying cardiovascular risk factors, ocular anatomical defects, a combination of these variables, or as yet unidentified factors. CONCLUSIONS: PDE-5 inhibitors have gained widespread use for the treatment of erectile dysfunction due to their safety, efficacy, and ease of use. Their role in the pathogenesis of NAION remains controversial. Reasonable and informed consent regarding the possible but low risk of NAION with the use of sildenafil, vardenafil and tadalafil is recommended. Loss or decreased vision, whether painful or painless, demands urgent patient assessment and immediate cessation of PDE-5 inhibitor use.

3',5'-Cyclic-GMP Phosphodiesterases↗

Tadalafil in the treatment of erectile dysfunction.

Oral phosphodiesterase-5 inhibitors have emerged as the preferred first-line treatment for erectile dysfunction worldwide because of patient convenience, efficacy, and safety. Clinical trials have shown that tadalafil significantly enhances erectile function across a wide range of etiologies and provides a prolonged period of effectiveness independent of food or alcohol. In this review, the pharmacokinetic and pharmacodynamic characteristics, efficacy, and safety of tadalafil are discussed.

3',5'-Cyclic-GMP Phosphodiesterases↗

Serial histopathology results of salvage cryoablation for prostate cancer after radiation failure.

PURPOSE: There has been a paucity of long-term followup reports of cryoablation for prostate cancer. In particular, little is known regarding the long-term histological results following salvage cryoablation. We report serial biopsy results of up to 43 months on 106 patients who underwent cryoablation after radical radiotherapy failed. MATERIALS AND METHODS: A total of 110 cryoablation procedures were done in 106 patients for biopsy proven, clinically localized radiation failure. Postoperatively transrectal ultrasound guided biopsy (usually 4 cores) was done at approximately 3, and/or 6, 12 and 24 months, and thereafter as indicated by prostate specific antigen, which was measured every 6 months. RESULTS: Of 818 biopsy cores a total of 23 (2.8%) from 15 patients (14.2%) were positive. Of the positive cores 73.9% were found within year 1 following cryoablation. Residual viable prostate glands and stroma were found in 42.4% and 27.4% of patients, respectively, at various time points. The frequency of various histological features, the most common being necrosis and fibrosis, was tabulated from the serial biopsy histology reports. CONCLUSIONS: The results of serial biopsies have improved our understanding of the histopathological changes as well as the capabilities and limitations of salvage cryoablation. The biopsy positivity rate is acceptable, although the finding of persistent viable prostatic tissue in a substantial proportion of patients implies that vigilant long-term followup is mandatory.

Aged↗

The prognostic significance of metastatic perivesical lymph nodes identified in radical cystectomy specimens for transitional cell carcinoma of the bladder.

PURPOSE: We determined the prognostic significance of metastatic perivesical lymph nodes (PVLN) in transitional cell carcinoma of the bladder (TCC). MATERIALS AND METHODS: A retrospective review of 198 consecutive patients who underwent radical cystectomy for clinically organ confined TCC identified 32 patients with PVLN in pathology specimens. Patient characteristics were compared. Overall survival, disease-specific survival (DSS) and disease-free survival were estimated using Kaplan-Meier actuarial methodology. The log-rank test was used to compare the differences between patients with and without metastatic TCC to PVLN. Cox multivariate regression analysis was used to determine whether the effect of metastatic PVLN on survival was independent of pathological stage. RESULTS: Metastatic TCC was found in the PVLN of 14 patients. Median followup and age were 13.5 months and 66.5 years, respectively. Patients with and without metastatic PVLN had similar characteristics and pathological disease staging. The overall survival, DSS and disease-free survival were significantly less for patients with metastatic TCC in PVLN (p = 0.002, p = 0.013 and p <0.001, respectively), and involvement of PVLN and pelvic nodes (p = 0.001, p = 0.010 and p = 0.041, respectively). Metastatic PVLN was an independent predictor of OS and DSS (p = 0.016 and p = 0.025, respectively). CONCLUSIONS: Metastases to PVLN appear to confer a significantly worse prognosis for patients undergoing radical cystectomy. Patients with identifiable metastatic PVLN may benefit from early adjuvant therapies.

Aged↗

Intracavernous pharmacotherapy for erectile dysfunction.

With the advent of phosphodiesterase type-5 inhibition as oral therapy, intracavernous injection of vasoactive agents has been relegated to second-line therapy for most patients with erectile dysfunction. However, the future of this category of agents remains bright as an ever-expanding number and combination of agents in use and under investigation will likely make intracavernous injection more appealing as greater efficacy, tolerability, and more rapid onset is attained. In this article, functional anatomy and physiology of human penile erection is reviewed, as are current clinical vasoactive agents including prostaglandin E-1, papaverine, and phentolamine. Emerging therapies discussed include guanylate cyclase activators, potassium channel openers, nitric oxide donors, vasoactive intestinal polypeptide, calcitonin gene-related peptide, selective alpha-1 receptor antagonists, and gene therapy. Ongoing research continues to define new roles for this effective and safe technique, which has withstood the test of time, restoring erectile function among patients with diverse ED etiologies and a variety of co-morbidities.

Adrenergic alpha-Antagonists↗