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Biomedical subjects

W J G Hellstrom

Publications and source records attributed to W J G Hellstrom.

14 recordsLinked to original sources
PubMed2005

Gene and stem cell therapy for erectile dysfunction.

Erectile dysfunction (ED) is defined as the inability to attain and/or maintain penile erection sufficient for satisfactory sexual performance. ED is a highly prevalent health problem with considerable impact on the quality of life of men and their partners. Although the treatment of ED with oral phosphodiesterase type V (PDE5) inhibitors is effective in a wide range of individuals, it is not efficacious in all patients. The failure of PDE5 inhibitors happens mainly in men with diabetes, non-nerve sparing radical prostatectomy, and high disease severity. Therefore, improved therapies based on a better understanding of the fundamental issues in erectile physiology and pathophysiology have recently been proposed. Here, we summarize studies on ED treatment using gene and stem cell therapies. Adenoviral-mediated intracavernosal transfer of therapeutic genes, such as endothelial nitric oxide synthase (eNOS), calcitonin gene-related peptide (CGRP), superoxide dismutase (SOD), and RhoA/Rho kinase and mesenchymal stem cell-based cell and gene therapy strategy for the treatment of age- and diabetes-related ED are the focus of this review.

Animals↗
PubMed2004

Effect of combination endothelial nitric oxide synthase gene therapy and sildenafil on erectile function in diabetic rats.

Erectile dysfunction associated with diabetes mellitus is caused in part by disordered endothelial smooth muscle relaxation, neuropathy, and a decrease in cavernosal nitric oxide synthase (NOS) activity. The purpose of this study was to determine whether a combination of sildenafil and adenoviral gene transfer of endothelial NOS (eNOS) could enhance the erectile response in diabetic rats. Five groups of animals were utilized: (1) age-matched control rats, (2) streptozotocin (STZ)-induced diabetic rats (60 mg/kg i.p.), (3) STZ-rats + sildenafil (2 mg/kg i.v.), (4) STZ-rats transfected with AdCMVbetagal or AdCMVeNOS, and (5) STZ-rats transfected with AdCMVeNOS +sildenafil (2 mg/kg i.v.). At 2 months after i.p. injection of STZ, groups 4 and 5 were transfected with the adenoviruses and 1-2 days after transfection, all animals underwent cavernosal nerve stimulation (CNS) to assess erectile function. Cyclic 3',5'-guanosine monophosphate (cGMP) levels were assessed in the cavernosal tissue. STZ-diabetic rats had a significant decrease in erectile function as determined by the peak intracavernosal pressure (ICP) and total ICP (area under the erectile curve; AUC) after CNS when compared to control rats. STZ-diabetic rats+AdCMVeNOS had a peak ICP and AUC, which were similar to control animals. STZ-diabetic rats administered sildenafil demonstrated a significant increase in peak ICP at the 5 and 7.5 V settings, while the AUC was significantly increased at all voltage (V) settings. The increase in both ICP and AUC of STZ-diabetic rats transfected with AdCMVeNOS at all V settings was greater than STZ-diabetic rats transfected with AdCMVbetagal. STZ-diabetic rats transfected with AdCMVeNOS and administered sildenafil had a significant increase in total ICP that was greater than eNOS gene therapy alone. Cavernosal cGMP levels were significantly decreased in STZ-diabetic rats, but were increased after transfection with AdCMVeNOS to values greater than control animals. In conclusion, overexpression of eNOS and cGMP in combination with sildenafil significantly increased both the peak ICP and total ICP to CNS in the STZ-diabetic rat, which was similar to the response observed in control rats. Moreover, the total erectile response was greater in STZ-diabetic rats receiving eNOS gene therapy plus sildenafil than STZ-rats receiving sildenafil or eNOS gene therapy alone.

Adenoviridae↗
PubMed2004

Feline penile erection induced by topical glans penis application of combination alprostadil and SEPA (Topiglan).

The objective of this study was to evaluate the efficacy of topically applied prostaglandin E1 (PGE(1))+5% SEPA (soft enhancement of percutaneous absorption) on the glans penis in a feline erection model. Erectile response after glans penis administration of PGE(1)+5% SEPA cream (Topiglan, MacroChem Co., Lexington, MA, USA) was compared to the erectile response after intracavernosal administration of the triple-drug combination (1.65 mg papaverine, 25 microg phentolamine, and 0.5 microg PGE(1)). The placebo cream and increasing concentrations (0.25%, 2.5 mg/ml; 0.5%, 5 mg/ml; and 1%, 10 mg/ml) of PGE(1)+5% SEPA were applied in a total volume of 0.1 ml via a plastic needle-less syringe. The control triple-drug combination was administrated intracavernosally via a 30-gauge needle at the completion of each experiment to serve as a control reference. With each application of placebo, PGE(1)+SEPA, and the triple-drug combination, changes in intracavernosal pressure and systemic blood pressure were continuously monitored. Topical application of PGE(1)+SEPA induced increases in intracavernosal pressure in a dose-dependent manner, with minimal effects on systemic blood pressure. The increases obtained with 1% PGE(1) Topiglan cream were similar to the intracavernosal pressure values elicited by the standard intracavernosal triple-drug combination. These data demonstrate that topical glans penis application of PGE(1)+SEPA can induce an erectile response in cats with minimal systemic adverse effects. Oral pharmacological agents are the first-line treatment for male ED. Studies investigating the effectiveness of noninvasive modalities such as topical therapy should continue, because these agents have the potential to avoid the systemic effects commonly seen with oral therapies. Additionally, topical therapy may also benefit patients who are unresponsive to oral agents or have explicit contraindications. Topical PGE(1) application to the glans penis may become an important treatment option in selected patients suffering from erectile dysfunction.

Adjuvants, Pharmaceutic↗
PubMed2003

Antimicrobial activity of antibiotic-soaked, Resist-coated Bioflex.

This study investigates whether a hydrophilic coating (Resist), designed to inhibit bacterial adherence, applied to inflatable penile prostheses can prolong the effect of intraoperative antibiotics. The activity of antibiotic-soaked Bioflex (penile prosthetic substrate material) discs with and without Resist was examined by measuring the zone of inhibition following in vivo exposure in four groups of rabbits: 1, 2, 3 and 5 days' duration of disc implantation. Coated and uncoated discs were soaked in an aqueous solution of gentamicin and bacitracin. The implanted antibiotic-soaked discs were extracted, and the zone of inhibition against four microorganisms in vitro demonstrated that the Resist coating was especially effective against Staphylococcus epidermidis, and statistically significant improvements were observed for the coated over the uncoated substrate up to 3 days following implantation. This effect, and the anti-adherence properties of Resist, may prevent adhesion and colonization of some microorganisms to penile implants and reduce chances for infection.

Animals↗
PubMed2003

History, epidemiology, and clinical presentation of Peyronie's disease.

Peyronie's disease is a localized connective tissue disorder that involves the tunica albuginea of the penis. The formation of fibrotic plaques in the tunica albuginea and surrounding cavernosal tissue alters penile anatomy and can cause different degrees of bending and narrowing, as well as penile pain and erectile dysfunction. Although long recognized as an important clinical entity of the male genitalia, the etiology of this disease has remained poorly understood. Recent studies have demonstrated that this disorder may be more prevalent than previously reported. The following review will examine the history, epidemiology, and clinical presentation of Peyronie's disease.

Erectile Dysfunction↗
PubMed2003

Surgical approaches for advanced Peyronie's disease patients.

Surgical therapy for Peyronie's disease (PD) is reserved for patients with severe penile deformity that fails to improve with medical treatment and impedes sexual intercourse. The surgical treatment of PD consists of either correction of the penile deformity or insertion of a penile prosthesis in patients with concomitant erectile dysfunction (ED). Plaque incision/excision combined with grafting procedures or plication techniques are suitable in Peyronie's patients having an adequate penile vascular supply. When patients with Peyronie's disease have both penile deformity and ED, penile prosthesis implantation with or without excision or incision of the tunica is the current standard of care.

Humans↗
PubMed2003

Three-piece inflatable penile prosthesis components (surgical pearls on reservoirs, pumps, and rear-tip extenders).

Erectile dysfunction (ED) is a major quality-of-life disorder that affects greater than 30 million American men each year. Since the introduction of Viagra, more and more men are presenting with ED that is not responding to oral or local therapies. Penile prosthesis implantation is recognized as the most effective, although most invasive, ED therapy with a high satisfaction rate. With an aging population both aware of and requesting therapy for ED, the number of penile prosthesis implantations will remain stable, especially at centers specializing in ED treatment. Therefore, a better understanding of the techniques used for placement of the penile prosthesis is necessary. The following review will discuss the techniques and a few clinical pearls in the placements of inflatable penile prostheses.

Erectile Dysfunction↗
PubMed2003

Testicular-sparing surgery: a reasonable option in selected patients with testicular lesions.

OBJECTIVE: To describe our experience of inguinal exploration in patients who had a reasonable chance of having a benign testicular lesion. PATIENTS AND METHODS: From 1995 to 2002, 11 patients (mean age 43 years, range 27-63) with testicular masses that were suspected to be benign underwent inguinal exploration. RESULTS: In nine of the 11 patients, frozen-section analysis and the final pathological results were similar, and two underwent inguinal orchidectomy. In seven patients the testicle was spared. Finally, because of an uncertain pathological diagnosis and patient age, two patients underwent orchidectomy. CONCLUSIONS: Inguinal exploration and testicular-sparing surgery are reasonable options in patients with peripheral intratesticular lesions, on the basis of preoperative ultrasonographic characteristics, and if there is a possibility of the mass being benign because of age, race, physical examination and tumour markers.

Adult↗
PubMed2003

Penile epithelioid sarcoma and the case for a histopathological diagnosis in Peyronie's disease.

OBJECTIVES: To devise a set of clinical criteria that would identify which penile abnormality could be malignant and warrant biopsy, between Peyronie's disease (a pathological fibrosis involving the tunica albuginea of the penis) and epithelioid sarcoma (ES) of the penis (a rare malignant condition which can resemble Peyronie's disease in clinical presentation). PATIENTS AND METHODS: The pathology reports and histological slides of men with Peyronie's disease who underwent penile biopsy were reviewed for ES. The medical charts of suspicious cases were then reviewed by a pathologist, unaware of the origin, for consistencies in signs, symptoms and clinical findings. These consistencies were then to be used to develop criteria for biopsy. Thirty-two men underwent penile biopsy from 1992 to 2001. RESULTS: Because there were no actual cases of ES, a specific set of criteria for ES could not be established. A review of previously published cases was then used for comparison with the present patients. CONCLUSIONS: Many of the previously reported cases included signs and symptoms of urethral narrowing or compression, causing lower urinary tract symptoms. In addition, the penile nodule size was reported to progressively enlarge over time. Because of the high prevalence of Peyronie's disease and low prevalence of ES, biopsy of every penile nodule is not judicious. However, signs and symptoms of urethral obstruction, and a progressively growing and persistently painful nodule should suggest a possible malignancy and warrant biopsy.

Adult↗
PubMed2003

Comparison of cadaveric pericardial, dermal, vein, and synthetic grafts for tunica albuginea substitution using a rat model.

OBJECTIVE: To evaluate in an animal model the intermediate and long-term efficacy of cadaveric pericardium, dermis, vein and Gore-Tex per thousand as grafting materials for tunica albuginea substitution after plaque excision for Peyronie's disease. MATERIALS AND METHODS: The study comprised 100 male Sprague-Dawley rats (300-325 g) divided into five equal groups: group 1, sham-operated controls; and groups 2-5 which underwent wedge excision of the tunica albuginea and replacement with either cadaveric pericardium, dermis, vein or Gore-Tex grafts. Ten rats in each group had the cavernosal nerve stimulated electrically to assess erectile function at 4 months, and the remaining 10 rats at 6 months. After death the sampled tissues were fixed in 10% formalin, paraffin-embedded, and stained with Masson's trichrome and Verhoff's van Giesen for collagen and elastic fibres. RESULTS: Erectile function, assessed by cavernosal nerve stimulation, did not differ significantly in any of the groups (P > 0.05). The histological assessment of penile cross-sections showed minimal fibrosis surrounding the patch in the dermal and vein grafts, and moderate to severe fibrosis in the Gore-Tex graft at 4 and 6 months. In the pericardial graft there was a moderate degree of fibrosis at 4 months with only minimal fibrosis at 6 months. CONCLUSIONS: These results show that cadaveric pericardium allows complete penile expansion and is strong enough to withstand normal intracorporal pressures. There was minimal fibrosis in the pericardial, dermal and vein grafts, and moderate fibrosis in the Gore-Tex graft at 6 months. The pericardial graft is a satisfactory grafting material when used for tunica albuginea substitution, including the surgical management of Peyronie's disease.

Animals↗
PubMed2002

Intralesional interferon-alpha-2b for the treatment of Peyronie's disease.

Peyronie's disease can best be described as a localized connective tissue disorder that primarily affects the tunica albuginea of the penis. The disease may be attributed to repetitive vascular trauma that initiates an inflammatory process and ultimately leads to the formation of a fibrous penile plaque. The plaque consists mainly of collagen and can significantly alter penile anatomy and function. Patients with Peyronie's disease will most often present with penile curvature, pain on erection, a palpable nodule most commonly located on the dorsal shaft of the penis, and erectile dysfunction. There is no definitive treatment for Peyronie's disease and the treating physician has many options. They may wait for spontaneous resolution of the plaque, choose medical therapy (which includes both oral and intralesional regimens), or opt for surgical management. The main purpose of this article is to discuss the advances in medical therapy for Peyronie's disease, in particular intralesional injection of interferon-alpha-2b (IFN-alpha-2b). Several studies have concluded that IFN-alpha-2b can be an effective modality of treatment and that many patients placed on a regimen of IFN-alpha-2b experienced a significant reduction in penile curvature, diminished pain with erection, and decreased size of the plaque. Further clinical studies are currently being undertaken to determine the precise quantity and frequency of administration of IFN-alpha-2b that is most effective with the least amount of side effects.

Humans↗
PubMed2002

Implications of nitric oxide synthase isoforms in the pathophysiology of Peyronie's disease.

Peyronie's disease is an idiopathic, localized connective tissue disorder of the penis which involves the tunica albuginea of the corpus cavernosum and the adjacent areolar space. Peyronie's disease is characterized by local changes in the collagen and elastic fiber composition of the tunica albuginea. The formation of fibrotic plaques alters penile anatomy and can cause different degrees of bending and narrowing, as well as penile pain and erectile dysfunction. Though long recognized as an important clinical entity of the male genitalia, the etiology of this disease has remained poorly understood. Until recently there have been no studies to examine the role nitric oxide (NO) and nitric oxide synthase (NOS) isoforms may play in the onset and progression of Peyronie's disease. NO is a potent biological mediator with diverse physiological and pathophysiological roles. The purpose of this review is to describe each of the NOS isoforms and their potential roles in the pathophysiology of Peyronie's disease, with particular emphasis on the regulation of endothelial and inducible NOS isoforms.

Animals↗
PubMed2002

Localization of peripheral dopamine D1 and D2 receptors in rat corpus cavernosum.

OBJECTIVE: To detect and locate anatomically peripheral dopamine D1 and D2 receptors in rat cavernosa, as dopamine is important in sexual drive and penile erection through receptors located in the central nervous system. MATERIALS AND METHODS: Corpora cavernosa were obtained from Sprague-Dawley rats; total RNA and membrane proteins were extracted and cryostat sections prepared. The rat brain hypothalamus was used as a control for dopamine D1 and D2 receptors. The presence and expression of peripheral dopamine D1 and D2 receptor mRNAs in rat corpus cavernosa was assessed using reverse transcription and polymerase chain reaction (RT-PCR), and Northern blot hybridization using (32)P-UTP-labelled RNA probes. Concurrently, corresponding proteins from D1 and D2 receptors were assayed and detected by a Western blotting technique. The anatomical location of dopamine D1 and D2 receptor mRNAs in rat penile tissues was identified by in situ hybridization using (35)S-UTP-labelled RNA probes in cryostat sections. Immunohistochemical staining was used to locate peripheral dopamine D1 and D2 receptor proteins in rat corpora cavernosa. RESULTS: Dopamine D1 and D2 receptor gene expression was detected in rat corpora cavernosa. In situ hybridization signals for dopamine D1 and D2 receptor mRNAs were localized to corpus cavernosal tissues and dorsal vessels in the rat penis. Western blot analyses showed peripheral dopamine D1 and D2 receptor proteins in rat corpora cavernosa. Immunohistochemically, peripheral dopamine D1 and D2 receptor proteins were detected in dorsal nerves, dorsal vessels and corpus cavernosal smooth muscle of the rat penile tissues. CONCLUSIONS: Peripheral dopamine D1 and D2 receptors are present in the corpora cavernosa of rats. The functional significance of these receptors and signal transduction pathways in modulating the vascular tone of the penis warrants further investigation.

Animals↗