Peptide amphiphile nanofiber hydrogel delivery of Sonic hedgehog protein to the penis and cavernous nerve suppresses intrinsic and extrinsic apoptotic signaling mechanisms, which are an underlying cause of erectile dysfunction.

Erectile dysfunction (ED) is a common and debilitating condition with high impact on quality of life. An underlying cause of ED is apoptosis of penile smooth muscle, which occurs with cavernous nerve injury, in prostatectomy, diabetic and aging patients. We are developing peptide amphiphile (PA) nanofiber hydrogels as an in vivo delivery vehicle for Sonic hedgehog protein to the penis and cavernous nerve to prevent the apoptotic response. We examine two important aspects required for clinical application of the biomaterials: if SHH PA suppresses intrinsic (caspase 9) and extrinsic (caspase 8) apoptotic mechanisms, and if suppressing one apoptotic mechanism forces apoptosis to occur via a different mechanism. We show that SHH PA suppresses both caspase 9 and 8 apoptotic mechanisms, and suppressing caspase 9 did not shift signaling to caspase 8. SHH PA has significant clinical potential as a preventative ED therapy, by management of intrinsic and extrinsic apoptotic mechanisms.

Hyperdiploid Precursor B-acute Lymphoblastic Leukemia Presenting as a Cavernous Sinus Mass in a 4-Year-old Male.

Risk stratification and appropriate treatment selection for children with precursor B-acute lymphoblastic leukemia (B-ALL) have improved outcomes. We report the case of a 4-year-old male with a lymphomatous cavernous sinus mass, a previously undescribed presentation of newly diagnosed hyperdiploid B-ALL. Few case reports in the literature describe lymphomatous involvement in this region, but none are associated with pediatric B-ALL. This case presented unique treatment and risk assignment challenges given the intracranial location of this tumor and proximity to the central nervous system.

Transvenous Embolization of Carotid Cavernous Fistula through Inferior Petrosal Sinus with Detachable Coils and Ethylene Vinyl Alcohol Copolymer.

Carotid cavernous fistula (CCF) is a rare disease caused by abnormal communications between the internal carotid artery (direct fistula) or meningeal branches of the external carotid artery (indirect fistula) and the cavernous sinus (CS). Trauma is the most common cause of CCF. The clinical presentation of CCF is closely related to the venous drainage pattern. Orbital and neuro-ophthalmological symptoms are the most common clinical presentation of CCF with drainage through the superior ophthalmic vein (SOV). Endovascular embolization by arterial or venous approaches is the most common management of CCF. Transvenous embolization using detachable coils and ethylene-vinyl alcohol copolymer (EVOH) is an alternative method for the treatment of CCF. Endovascular embolization offers different options to treat CCF by minimally invasive approach decreasing morbidity and residual fistulas. The purpose of this article is to report our treatment experiences via the inferior petrosal sinus (IPS), and immediate-term outcomes of endovascular embolization of CCF by using detachable coils and EVOH.

Acinic cell carcinoma of parotid gland with cavernous sinus metastasis: A case report.

Acinic cell carcinoma (AciCC) is a low-grade malignancy which rarely metastasizes to bone or cavernous sinuses. A 62-year-old male patient, previously treated for AciCC of right parotid with surgery and local radiotherapy, presented 10 years later with progressive visual impairment and restriction of ocular movements. Magnetic resonance imaging of the head and orbit showed an expansile lobulated mass with heterogeneous signal intensity in bilateral cavernous sinus with encasement of the internal carotid artery on both sides. Fluorodeoxyglucose positron emission tomography/computed tomography showed multiple lytic lesions with increased uptake in the left clavicle (with soft tissue component), sternum, multiple cervico-dorso-lumbar vertebrae, and ribs. Biopsy from the clavicular lesion showed AciCC. He was treated with palliative radiotherapy to cavernous sinuses and other metastatic site followed by palliative chemotherapy with six cycles of paclitaxel and carboplatin. He had a partial response to palliative treatment and had good symptomatic relief at 12 months of follow-up.

A review of eight cases of cavernous sinus thrombosis secondary to sphenoid sinusitis, including a12-year-old girl at the present department.

Cavernous sinus thrombosis (CST) is a severe disease which can result from infection of any of the tissues drained by the cavernous sinus. We here review eight cases, including a 12-year-old girl, all secondary to sphenoid sinusitis. The clinical manifestations, laboratory data, imaging findings, pathogens, medications, surgical treatment and clinical outcomes were analyzed. All eight patients had headache and five of them fever. All cases were associated with one or more ophthalmic symptoms. In four cases, computed tomography/magnetic resonance imaging showed isolated sphenoid sinusitis. In three cases, streptococci were isolated from blood culture and two cases showed Staphylococcus aureus in blood and sinus cultures. In seven cases, surgery was undertaken. All eight subjects received antibiotics, and 5 were administered intravenous ceftriaxone and metronidazole. Six subjects received anticoagulation therapy and one received corticosteroids. No mortality was recorded. Three cases showed sequelae, including Lemierre syndrome, ophthalmic complaints, and cranial nerve paralysis. In conclusion, the management of CST should include intravenous antibiotic therapy, combined with endonasal sinus surgery.

The trigeminocardiac reflex in Onyx embolisation of intracranial dural arteriovenous fistula.

We investigated the incidence of the trigeminocardiac reflex (TCR) during ethylene vinyl alcohol copolymer (Onyx Liquid Embolic System, ev3 Neurovascular, Irvine, CA, USA) embolisation of intracranial dural arteriovenous fistulas (DAVFs) and evaluated the post-procedural recovery of these patients. Between June 2006 and July 2009, 21 patients (11 females, 10 males) with a mean age of 61years (range: 25-85years) underwent 28 Onyx embolisations of intracranial DAVFs at our institution. The case histories of these patients were reviewed retrospectively. A TCR occurred in three (10.7%) of the embolisations, with bradycardia lower than 60 beats/minute and a drop in mean arterial blood pressure of 20% or more. The reflex was blunted promptly with intravenous atropine, and follow-up of these patients showed no complications that might have been directly related to it. The TCR may occur during Onyx embolisation of intracranial DAVFs. Recognition of this phenomenon allows for early detection and appropriate intraoperative management.

Intensive chemotherapy failure in Burkitt's lymphoma with cavernous sinus involvement.

Burkitt's lymphoma is an aggressive B-cell lymphoma with rapid proliferative index, which makes it disseminate easily to distal sites, especially to bone marrow and the central nerve system. We report here a 22-year-old woman with Burkitt's lymphoma involving multiple organs, including kidneys, breasts, left ovary, and bone marrow at the time of diagnosis. The patient responded well to intensive chemotherapy before the onset of retro-orbital pain, vomiting, and photophobia. The contrast-enhanced T1-weighted image in a second magnetic resonance image (MRI) showed a 2 x 1.9 cm mass in her left cavernous sinus that was not found in her initial MRI. Central nervous system (CNS)-directed high-dose chemotherapy and whole-brain radiation could not change the final failed treatment outcome caused by the cavernous sinus involvement disseminating to her entire CNS. Further study should provide well-designed therapeutic strategies to Burkitt's patients with cavernous sinus involvement.

Onyx embolisation of cavernous sinus dural arteriovenous fistula via direct percutaneous transorbital puncture.

The cavernous sinus dural arteriovenous fistulas of three patients were successfully embolised by using Onyx (Onyx Liquid Embolic System, MTI, Irvine, CA, USA) as the sole embolic agent, through direct percutaneous transorbital punctures of the cavernous sinuses. Our early experience suggests that this direct approach, coupled with the unique physical properties of Onyx, is a safe and effective alternative to treat cavernous sinus dural arteriovenous fistulas when the conventional transvenous routes are inaccessible.

Five years follow-up of invasive prolactinomas with special reference to the control of cavernous sinus invasion.

BACKGROUND: Few data are presently available on the effective control of cavernous sinus (CS) invasion of invasive prolactinomas. The aim of this retrospective study, through a mean period of 5 years follow up, is to observe the tumor shrinkage of CS invasive prolactinomas, as well as PRL normalization with bromocriptine therapy. METHODS: 68 patients met the criteria of invasive prolactinomas (Grade III or IV in the classification scheme of Knosp and colleagues; serum PRL level greater than 200 ng/ml). 33 patients underwent bromocriptine therapy as the initial treatment, and 14 of these 33 had combined treatment with microsurgery and/or radiotherapy. The other 35 patients received microsurgery as the primary treatment, after which two patients had normal PRL without taking bromocriptine and other 33 patients received bromocriptine treatment after microsurgery. RESULTS: Tumor volume on magnetic resonance images had completely disappeared in 50 patients (74%), while all the other 18 patients had residual tumor in the parasellar areas, invading the CS, and 14 patients had a secondary empty sella due to tumor shrinkage. Of those 14 patients, seven still had elevated PRL levels; five had optic chiasmal herniation by different degrees (P < 0.05). There were 49 patients with normal PRL levels (72%); five patients with PRL levels more than 200 ng/ml. After the treatment, 14 patients with tumor volume disappearance on MR images and PRL normalization therefore withdrew from bromocriptine therapy. During a subsequent one-and-a-half-year follow-up, tumor recurrence and PRL increase were not found in those 14 patients. Twenty-seven patients maintained normal PRL levels with low-dose bromocriptine, of which 20 patients had their tumor disappear while seven patients had CS residual tumor. CONCLUSIONS: About three-fourths of prolactinomas with CS invasion can be effectively controlled not only with regard to tumor volume disappearance but also in serum PRL normalization. Residual tumor in the CS areas with PRL normalization and no pressure symptoms can be treated with low-dose of bromocriptine so as to achieve long-term tumor volume control and endocrine control. Great attention should be paid to CS residual tumors accompanying the empty sella, especially in cases with optic chiasmal herniation.

Immunohistochemical localization of 3-nitrotyrosine in the nasal respiratory mucosa of patients with vasomotor rhinitis.

CONCLUSION: This study demonstrates that, in the nasal respiratory mucosa of patients with vasomotor rhinitis, oxidative stress following peroxynitrite formation is confined to the respiratory epithelium. This suggests that the role of peroxynitrite in vasomotor rhinitis differs from its role in other diseases of the respiratory tract. The results of this study also support the concept that different pathogenetic mechanisms are probably involved in vasomotor rhinitis. OBJECTIVE: Previous studies indicated that nitric oxide (NO) is involved in the pathogenesis of vasomotor rhinitis, strong expression of NO synthase being detected in the smooth muscle cells of the cavernous sinuses and in the respiratory epithelium. However, most adverse effects of high levels of NO originate from the reaction of NO with superoxide anions to form peroxynitrite. Therefore, in this study we evaluated the involvement of peroxynitrite in the pathogenesis of vasomotor rhinitis. MATERIAL AND METHODS: Sites of peroxynitrite formation were identified by immunolabelling for 3-nitrotyrosine (3NT), its footprint in tissues. Samples of nasal mucosa were obtained from vasomotor rhinitis patients and from control subjects who had undergone corrective surgery of the nasal septum. All samples were obtained by reduction of the inferior turbinate. RESULTS: Examination of specimens from vasomotor rhinitis patients revealed that 3NT is absent in epithelium with a normal appearance, cells of the subepithelial connective tissue, the glands and the blood vessels, including the cavernous sinuses. In contrast, intense 3NT immunolabelling was found in the disrupted respiratory epithelium. 3NT was not present in any of the specimens from control subjects.

Dynamic MR imaging in Tolosa-Hunt syndrome.

OBJECTIVE: To evaluate the cavernous sinuses with dynamic magnetic resonance (MR) imaging in patients with Tolosa-Hunt syndrome (THS). METHODS: The sellar and parasellar regions of five patients with THS and 12 control subjects were examined with dynamic MR (1.5 T) imaging in the coronal plane. Dynamic images were obtained with spin-echo (SE) sequences in three patients, and with fast spin-echo (FSE) sequences in two patients and control subjects. Conventional MR images of the cranium including sellar and parasellar regions were also obtained on T1-weighted pre- and post-contrast SE, and T2-weighted FSE sequences in the coronal plane. RESULTS: MR images revealed affected cavernous sinus with bulged convex lateral wall in three patients and concave lateral wall in two patients. In all control subjects, cavernous sinuses were observed with concave lateral wall. The signal intensity on T1- and T2-weighted images and contrast enhancement on post-contrast images of the affected cavernous sinuses in patients were similar to those of the unaffected cavernous sinuses in patients and control subjects. The dynamic images in all patients disclosed small areas adjacent to the cranial nerve filling-defects within the enhanced venous spaces of the affected cavernous sinus, which showed slow and gradual enhancement from the early to the late dynamic images. No such gradually enhancing area was observed in control subjects except one. The follow-up dynamic MR images after corticosteroid therapy revealed complete resolution of the gradually enhancing areas in the previously affected cavernous sinus. CONCLUSION: Dynamic MR imaging may facilitate the diagnosis of THS.

Enhanced photorelaxation in aorta, pulmonary artery and corpus cavernosum produced by BAY K 8644 or N-nitro-L-arginine.

Segments of endothelium-denuded aorta, pulmonary arterial rings and strips of corpus cavernosum from rabbits were superfused with Krebs medium. Photorelaxation elicited by ultraviolet light (366 nm) was significantly enhanced by either BAY K 8644 (20 nM) or N-nitro-L-arginine (100 and 500 microM) and was associated with increased cyclic GMP. This action of both drugs was greater in pulmonary artery than aorta and corpus cavernosum and persisted in vascular rings for 90 min after drug removal. The effect was significantly attenuated by hemoglobin (10 microM) but was unaltered by superoxide dismutase (30 u/ml). The mechanism of such photosensitization is presently unclear.

Pharmacological effects of adenosine on canine penile erection.

We investigated the pharmacological effects of adenosine on canine penile erection in vivo. Intracavernous injection of adenosine induced a full erection, which was unaffected by hexamethonium and atropine. The erectile response induced by adenosine was augmented by intracavernous pretreatment with dipyridamole and markedly depressed by theophylline. The erectile response induced by cavernous nerve stimulation was also enhanced by dipyridamole and reduced by theophylline. The combination of acetylcholine and adenosine, when injected intracavernously, induced a full erection, and the effect of these drugs was not additive but synergistic. These results suggest that penile erection induced by adenosine is due to a direct relaxing effect on cavernous smooth muscle. We propose that adenosine plays a cooperative role with acetylcholine and also has a physiological role as a neuromodulator in canine penile erection.