Michael P. Joseph

p300/MDM2 Complexes Participate in MDM2-Mediated p53 Degradation

Control of p53 turnover is critical to p53 function. E1A binding to p300/CBP translates into enhanced p53 stability, implying that these coactivator proteins normally operate in p53 turnover control. In this regard, the p300 C/H1 region serves as a specific in vivo binding site for both p53 and MDM2, a naturally occurring p53 destabilizer. Moreover, most of the endogenous MDM2 is bound to p300, and genetic analysis implies that specific interactions of p53 and MDM2 with p300 C/H1 are important steps in the MDM2-directed turnover of p53. A specific role for p300 in endogenous p53 degradation is underscored by the p53-stabilizing effect of overproducing the p300 C/H1 domain. Taken together, the data indicate that specific interactions between p300/CBP C/H1, p53, and MDM2 are intimately involved in the MDM2-mediated control of p53 abundance.

The treatment of traumatic optic neuropathy: the International Optic Nerve Trauma Study.

OBJECTIVE To compare the visual outcome of traumatic optic neuropathy treated with corticosteroids, treated with optic canal decompression surgery, or observed without treatment. DESIGN Comparative nonrandomized interventional study with concurrent treatment groups. PARTICIPANTS A total of 133 patients with traumatic optic neuropathy (127 unilateral and 6 bilateral) who had an initial visual assessment within 3 days of injury. At least 1 month of follow-up was required for inclusion in the primary analysis. INTERVENTIONS On the basis of treatment received within 7 days of injury, patients with unilateral injuries were categorized as being in one of three treatment groups: untreated (n = 9), corticosteroid (n = 85), or optic canal decompression surgery (n = 33). MAIN OUTCOME MEASURE Visual acuity. RESULTS Visual acuity increased by > or = 3 lines in 32% of the surgery group, 57% of the untreated group, and 52% of the steroid group (P = 0.22). The surgery group had more patients whose initial vision was no light perception. After adjustment for the baseline visual acuity, there were no significant differences between any of the treatment groups. There was no indication that the dosage or timing of corticosteroid treatment or the timing of surgery was associated with an increased probability of visual improvement. CONCLUSIONS No clear benefit was found for either corticosteroid therapy or optic canal decompression surgery. The number of patients studied was sufficient to rule out major effects in the treatment groups, although clinically relevant effects in specific subgroups could have been missed. These results and the existing literature provide sufficient evidence to conclude that neither corticosteroids nor optic canal surgery should be considered the standard of care for patients with traumatic optic neuropathy. It is therefore clinically reasonable to decide to treat or not treat on an individual patient basis.

Neuroendocrine tumors of the sinonasal tract. Results of a prospective study incorporating chemotherapy, surgery, and combined proton-photon radiotherapy.

The authors report the results of a prospective study of patients with malignant neuroendocrine tumors of the sinonasal tract who received multimodality treatment incorporating high‐dose proton‐photon radiotherapy.

Optic Canal Decompression in Indirect Optic Nerve Trauma

BACKGROUND The proper management of neurogenic visual loss after blunt head trauma is controversial. Non-treatment, corticosteroids, and surgical decompression of the optic canal are all currently considered to be reasonable alternatives. The goal of this study was to identify factors affecting improvement in patients treated with canal decompression. METHODS A retrospective analysis of 31 cases in which transethmoidal decompression of the optic canal had been performed for neurogenic visual loss after closed head trauma was conducted. Each patient was alert and free of injury to the globe when evaluated before surgery. Surgery was performed within 6 days of injury, and all were given perioperative steroids. RESULTS Visual acuity improved in 22 (71%) patients, with 6 (19%) regaining visual acuity of 20/40 or better. The mean improvement from preoperative visual deficit was 42.0% +/- 6.6%, with a median improvement of 45.2%. Both univariate and multivariate analysis suggested that vision improved more in patients who were younger than 40 years of age than in patients who were 40 years of age or older. Interval between injury and surgery, preoperative visual acuity, and the presence of optic canal fracture did not affect outcome. CONCLUSION Any future randomized trials of therapy should stratify patients based on age. Enrollment of patients with no light perception or who experienced delay between injury and treatment may be reasonably considered.

An assessment of grafts in the posterior cricoid lamina

Subglottic stenosis is a recognized complication of prolonged intubation. To date, there is no uniformly successful operative procedure for severe subglottic stenosis, fulfilling the criteria of decannulation and a serviceable voice. The surgical ideals for such a procedure should include the use of autogenous grafting material, avoidance of internal stenting, and limited manipulation of the mucosa. This study was intended to assess the fate of isolated hyoid and thyroid alar grafts interposed in the posterior cricoid lamina. Additionally, anterior/posterior splits with and without anterior grafting were evaluated. Seventeen dogs were used in the determinate animal model. Vocal cord mobility was evaluated by direct laryngoscopy prior to sacrifice. Graphic gross anatomical specimens depict the effects of anterior/posterior splitting on the cricoid cartilage. Clinical correlations are suggested.

Lingual tonsillectomy: A treatment for inflammatory lesions of the lingual tonsil†‡

Lingual tonsillectomy is a surgical treatment that is seldom performed because lingual tonsillitis is infrequently diagnosed. We have reviewed a group of patients with lingual tonsillitis or lingual tonsil hyperplasia who were treated with lingual tonsillectomy. Lingual tonsil lesions, the anatomy and histology of the lingual tonsil, and surgical approaches to lingual tonsillectomy are discussed.

Botulinum A toxin for the treatment of adult-onset spasmodic torticollis.

Thirty-five patients with adult-onset idiopathic torticollis were treated by local injections of botulinum A toxin into dystonic cervical muscles. Substantial improvement with respect to reduction and elimination of pain was found in 81 percent, improvement in posture deformity and involuntary spasms in 70 percent, increased range of motion of the neck in 78 percent, reduction in visible sternocleidomastoid hypertrophy in 86 percent, and improvement in tremor in 65 percent. The syndrome was divided into four subtypes based on pattern of dystonic muscle groups involved in the dystonia, head and shoulder posture, and sternocleidomastoid muscle hypertrophy. Injection strategy based on this subdivision is described.

Transfacial transclival approach for midline posterior circulation aneurysms.

OBJECTIVE To evaluate the use of an anterior, transfacial transclival approach to midline posterior circulation aneurysms in five patients. SURGICAL APPROACH A skin incision is made on the right side of the nose with subsequent bony and cartilaginous disarticulation of the nasal complex. The nose remains attached along the left side and is reflected laterally. Removal of the nasal septum and bilateral ethmoidectomy, medial maxillectomy (usually bilateral), and opening of the sphenoid yield a large triangular exposure of the anterior clivus. After removal of the clivus with a drill, the vertebral and basilar arteries are exposed through a midline dural opening. RESULTS The approach provided excellent exposure of basilar artery trunk aneurysms with room available for temporary clip placement in three patients. In a fourth patient, a midline posterior inferior cerebellar artery aneurysm was clipped using this technique. A basilar trunk dissection was treated by proximal basilar occlusion through this exposure in a fifth patient. Although three patients developed transient cerebrospinal fluid leaks with symptoms of meningitis, no permanent neurological morbidity resulted from the use of the approach. CONCLUSION The transfacial transclival approach to midline aneurysms of the basilar trunk and its branches provided excellent exposure for surgical treatment in five patients. No patient had postoperative palatal dysfunction and cosmetic results were excellent. Cerebrospinal fluid leak and meningitis continue to be the major drawbacks to the use of this approach, although the availability of modern broad-spectrum antibiotics lessens the chance of permanent neurological sequelae.

Traumatic optic neuropathy: Result in 45 consecutive surgically treated patients

The management of traumatic optic neuropathy remains controversial. In this report, we present the results of 45 patients treated with extracranial optic nerve decompression after at least 12 to 24 hours of corticosteroid therapy without improvement. Vision improved in 32 patients after surgery (71%), and the mean percentage of improvement from preoperative visual deficit was 40.7% ± 6.9% (median improvement 41.2%). Worsening of vision occurred in none of the patients as a result of the surgery, and no intraoperative or postoperative complications were encountered. We present a treatment protocol for traumatic optic neuropathy with the use of megadose corticosteroids and optic nerve decompression.

Sebaceous carcinoma: diuretic use, lacrimal system spread, and surgical margins

Twenty cases of adnexal sebaceous carcinoma managed by contemporary methods, including monitoring of surgical margins, were reviewed. Eight of 20 patients were taking diuretic medications. The initial clinical diagnosis was incorrect in all cases, and 50% of cases were misdiagnosed by the pathologist interpreting the initial biopsy. The canaliculus was identified in 7 cases, and was involved by tumor in 3 cases. Tumor was identified in the lacrimal sac and inferior turbinate in an additional case. Thus, tumor spread into the lacrimal excretory system was documented by histologic findings in 4 cases.