The identification of novel therapeutic targets for the treatment of malignant brain tumors.

A two-step strategy was developed consisting of differential display reverse transcriptase polymerase chain reaction (DDRT-PCR) with cultured normal human fetal astrocytes and U-373MG glioma cells followed by reverse Northern analysis of normal brain and primary tumor tissues. hu-dek, alpha-NAC, ribosomal proteins L7a and L35a, and five novel genes were identified. Since none of these genes has been previously shown to be associated with malignant brain tumor formation, this approach may be useful to identify novel targets for the diagnosis and treatment of brain tumors.

Beta1,6-N-acetylglucosamine-bearing N-glycans in human gliomas: implications for a role in regulating invasivity.

The metastatic potential of tumor cells has been shown to be correlated with the expression of tri- and tetra-antennary beta1,6-N-acetylglucosamine (beta1,6-GlcNAc)-bearing N-glycans, which are recognized by Phaseolus vulgaris leukoagglutinating lectin (L-PHA). The expression of beta1,6-GlcNAc-bearing N-glycans also has been used as a marker of tumor progression in human breast and colon cancers. In this report, the role of N-glycan branching in regulating glioma migration and invasion was examined. The expression of beta1,6-GlcNAc-bearing N-glycans was found in human glioma specimens, whereas astrocytes from normal adult brain were negative. The expression of N-acetylglucosaminyltransferase V (GnT-V) mRNA, which is responsible for the biosynthesis of beta1,6-GlcNAc-bearing N-glycans, was high in glioma cell lines with robust ets-1 expression. To study the molecular mechanism of GnT-V expression in human glioma cells, an inducible ets-1 gene was stably transfected into SNB-19 cells using a tetracycline repressor system. GnT-V mRNA expression was increased by the induction of c-ets-1, suggesting that the Ets-1 transcription factor directly regulates the transcription of GnT-V. Stable transfection of GnT-V into human glioma U-373 MG cells resulted in changes in cell morphology and focal adhesions and a marked increase in glioma invasivity in vitro. L-PHA has little effect on cell migration. On the contrary, Phaseolus vulgaris erythroagglutinating lectin (E-PHA), which recognizes bisecting beta1,4-GlcNAc-bearing N-glycans, strongly inhibits cell migration (haptotaxis) on a fibronectin substrate in U-373 MG transfectants and other glioma cell lines tested. These results suggest that the increased beta1,6-GlcNAc-bearing N-glycan expression found in malignant gliomas is modulated by GnT-V through the Ets-1 transcription factor, and that the branching of complex type N-glycans plays a major role in glioma invasivity.

Recurrence of vestibular (acoustic) schwannomas in surgical patients where preservation of facial and cochlear nerve is the priority.

The risk of tumour recurrence was measured in a series of surgically treated vestibular (acoustic) schwannoma patients where preservation of facial and cochlear nerve function was a routine objective. This report describes the influence of this surgical philosophy on the hazards of tumour recurrence or continued growth from residual tumour cells left in situ. A series of 116 consecutive vestibular schwannoma patients underwent primary surgical resection in a general community hospital by a single neurosurgeon. Recurrence of a tumour was assessed radiologically. Eighteen patients experienced a recurrence. No relationship was found between recurrence and age, residual coagulated morsels of tumour, preoperative tumour size, or opening of the internal auditory canal. Time to recurrence ranged from six to one hundred and forty-eight months and all but two recurrent lesions were non symptomatic. Lifelong follow-up of these patients is therefore, suggested.

alpha2,3-sialyltransferase mRNA and alpha2,3-linked glycoprotein sialylation are increased in malignant gliomas.

CMP-NeuAc: Galbeta1,3(4)GlcNAc alpha2,3-sialyltransferase (alpha2,3-ST) mRNA was expressed in human glioma specimens, human fetal astrocytes, and a panel of brain tumor cell lines. Maackia amurensis agglutinin staining revealed the presence of alpha2,3-linked sialic acids on glioma cell surfaces and extracellular matrices whereas normal human adult astrocytes were negative. Increased expression of alpha2,3-linked glycoprotein sialylation may play a role in glial tumorigenesis.

Intracranial chondroma arising from the cranial vault: CT and MR appearance.

A case of intracranial chondroma arising from the right parietal bone in a 37-year-old woman is presented. CT and MRI findings as well as the differential diagnosis of the lesion are discussed.

Prospective surveillance for perioperative venous thrombosis. Experience in 2643 patients.

BACKGROUND: Patients who undergo neurosurgical procedures are at high risk for perioperative deep vein thrombosis (DVT) and pulmonary embolism (PE), which have been reported in 6% to 43% of these patients. OBJECTIVES: To (1) determine the utility of prospective DVT surveillance in patients who undergo neurosurgical procedures by using venous duplex ultrasound scanning (VDUS), (2) assess the efficacy of DVT prophylaxis (elastic stockings and intermittent pneumatic compression), (3) identify subgroups of patients who are at higher risk, and (4) determine whether DVT surveillance would reduce the incidence of fatal PE. DESIGN: All patients had undergone preoperative VDUS of both lower extremities, and postoperative VDUS was performed on days 3 and 7, and weekly thereafter until patients were ambulatory or discharged. PATIENTS: During a 5-year period, 2643 patients who underwent neurosurgical procedures were enrolled in prospective DVT surveillance. SETTING: University-affiliated community hospital. RESULTS: Acute DVT was diagnosed in 147 (5.6%) of the 2643 patients. Eighty-one percent of the patients with acute DVT were asymptomatic at the time of diagnosis. Deep vein thrombosis developed de novo in the proximal veins in 98% of the patients. Patients in whom a craniotomy was done had a significantly higher risk for DVT (7.7%, P = .006), and patients who underwent cervical or lumbar spinal surgical procedures had a significantly lower risk (1.5%, P < .001). Among those patients in whom a craniotomy was performed for treatment of a tumor and who had DVT, 87% had malignant neoplasms. Significant lower-extremity neuromotor dysfunction was present in 69% of all patients with DVT, and this finding predominated among patients with DVT in the subgroups with a lower risk. A PE was diagnosed in 5 patients (0.19%) while they were hospitalized, and a PE was fatal in 2 (0.07% of all patients). CONCLUSIONS: Most perioperative DVTs were clinically silent and formed spontaneously in proximal venous segments where there would be a risk for a PE. The overall incidence of DVT (5.6%) was low, suggesting effective DVT prophylaxis. Patients who underwent spinal surgical procedures were at a significantly lower risk for DVT, and future surveillance is not indicated in this patient group unless other conditions exist (paralysis, malignancy). Patients in whom a craniotomy was performed had a significantly higher risk of DVT, particularly when other risk factors existed. The low incidence of a fatal PE (0.07%) reflected that early detection and treatment of proximal DVT were facilitated by prospective VDUS surveillance in these patients.

The expression of CMP-NeuAc: Gal beta 1,4GlcNAc alpha 2,6 sialyltransferase [EC 2.4.99.1] and glycoproteins bearing alpha 2,6-linked sialic acids in human brain tumours.

The expression of CMP-NeuAc: Gal beta 1,4GlcNAc alpha 2,6 sialyltransferase (alpha 2,6-ST) [EC 2.4.99.1] and glycoproteins bearing alpha 2,6-linked sialic acids were examined in primary human brain tumours and cell lines. 79% (19/24) of the meningiomas expressed alpha 2,6-ST mRNA, 42% (10/24) of which showed very high expression. alpha 2,6-ST mRNA expression was undetectable in normal brain tissue. In contrast, only 1/13 of the gliomas examined expressed detectable alpha 2,6-ST mRNA. Metastases to the brain did not express measurable amounts of alpha 2,6-ST mRNA. Less expression was found in malignant (i.e. anaplastic) compared to benign (i.e. meningothelial) meningiomas. Two-dimensional SDS-PAGE of glioma and meningioma proteins, followed by Sambucus nigra lectin staining, revealed the presence of a glycoprotein bearing alpha 2,6-linked sialic acids, M(r) = 53 kDa and a pI = 7.0 (MEN-1) that appeared in all seven of the meningiomas examined, but was expressed at barely detectable levels, if at all, in seven out of the seven glioblastomas examined. Thus, decreased alpha 2,6-ST expression may play a role in the aggressive nature of anaplastic meningiomas, but appears to be virtually absent in all tumours of glial origin.

The preservation of hearing and facial nerve function in a consecutive series of unilateral vestibular nerve schwannoma surgical patients (acoustic neuroma).

Between January 1981 and February 1992, 102 non-NF-2 patients underwent removal of a unilateral vesitbular schwannoma. There were 54 women and 48 men. Eighty-six percent of patients with normal facial function preoperatively retained normal function (House score 1 or 2) postoperatively. Of the 64 patients with a functional cochlear nerve preoperatively, five had normal hearing (PTA < 25 dB, SB > 70%), five had near normal hearing (PTA < 45 dB, SD > 70%), four patients had preserved hearing (PTA < 50 dB, SD > 50%), and three patients had preserved cochlear nerve function (PTA > 50 dB, SD < 50%) after surgery. Hearing preservation was obtained in patients whose tumors were larger than 3 cm. Radiological follow-up revealed 10 patients with recurrent tumor, all but one asymptomatic.

The transnasal approach to advanced lesions of the sphenoid sinus and pituitary.

The techniques of transseptal transsphenoidal hypophysectomy are discussed in detail in this article. The span of disease that may be treated by this method in addition to the need for a team approach of otolaryngologists and neurosurgeons is illustrated with several pertinent case reports.

Management of athletic injuries of the cervical spine and spinal cord.

Injuries to the cervical spine among athletes present inherent difficulties, especially in advising for return to contact sports. Experience with the acute care of 63 patients who sustained cervical spine injuries while participating in organized sporting events is analyzed. Forty-five patients had permanent injury to the vertebral column and/or spinal cord, while 18 suffered only transient spinal cord symptoms. Football mishaps accounted for the highest number of injuries, followed by wrestling and gymnastics. Twelve patients had complete spinal cord injury, 14 patients had incomplete spinal cord injury, and 19 patients had injury to the vertebral column alone. The majority of the spinal cord lesions occurred at the C4 and C5 levels, while bony injuries of C4 through C6 predominated. Twenty-five patients required surgical stabilization, and 20 were treated with orthosis only. There was no instance of associated systemic injuries, and hospital complications were few. The mean time of hospitalization was 19.1 days for injured patients and 3.0 days for patients with transient symptoms. A classification was developed to assist in the management of these patients: Type 1 athletic injuries to the cervical spine are those that cause neurological injury; patients with Type 1 injuries are not allowed to participate in contact, competitive sporting events. Type 2 injuries consist of transient neurological deficits without radiological evidence of abnormalities; these injuries usually do not prohibit further participation in contact sports unless they become repetitive. Type 3 injuries are those that cause radiological abnormality alone; these represent a heterogeneous group.(ABSTRACT TRUNCATED AT 250 WORDS)

Diving injuries of the cervical spine.

From 1975 to 1986, 2435 patients were admitted to the Northwestern University-Midwest Regional Spinal Cord Injury Unit. Of these, 220 patients (9.0%) had documented neck fractures from diving accidents, representing the largest series of acute diving injuries yet analyzed. The average age of these patients was 21 years, and males predominated. Two hundred twelve patients (96.4%) were admitted within 48 hours of injury. Associated injuries were rare: none had intracranial mass lesions or systemic injuries, and only nine were near-drowning victims who required endotracheal intubation. The most common levels of injury were C-5 (140 fractures) and C-6 (85 fractures), with 70 patients having fractures at more than one level. Neurological injury was sustained in 154 (70.0%) patients, while 66 (30.0%) patients were neurologically intact. One hundred forty-seven (66.8%) patients underwent posterior cervical fusion, and anterior fusion was performed in 36 (16.4%), allowing for early ambulation and an average hospital stay of 17 days. Hospitalization was relatively uncomplicated, with urinary tract infection in 121 (55.0%), pneumonia in nine (4.1%), and deep vein thrombosis in 24 (10.9%). Long-term follow up averaged 5 years and was obtained in 160 (72.7%) patients. Sixteen (10.0%) improved neurologically, five (3.1%) deteriorated, and 139 (86.9%) were unchanged. Notably, this large study shows that diving accidents occur in a young, healthy population who sustain essentially no other associated intracranial or systemic injuries and have few serious hospital complications. Such patients may be mobilized early in their care after either internal or external stabilization. Subsequent long-term neurological improvement can be expected to occur in about 10% of patients. The importance of water safety and injury prevention is stressed.

Plastic artificial eyes: overview and technique.

Eye prosthetics and its practitioners have evolved through self-development studies, to become an integral part of the ophthalmic plastic surgery multidisciplinary team. Eye prosthetics is a distinct art and science in dealing with the many facets of eye surgery. The ocularist must have in his armamentarium alternate procedures, flexibility, cooperation, and become knowledgeable of all the options available to him. This in turn will offer opportunities for providing the plastic artificial eye patients with the best final results possible.

Duplex venous scanning for the prospective surveillance of perioperative venous thrombosis.

A total of 361 patients undergoing a variety of major neurosurgical procedures were entered into a prospective surveillance program using duplex ultrasound scanning for detection of perioperative deep venous thrombosis (DVT). All patients had duplex scans of the major veins of both legs preoperatively, on the third and seventh postoperative days, and at weekly intervals thereafter if hospitalized. All patients received elastic stocking and intermittent mechanical calf compression. Perioperative DVT was diagnosed by duplex scan in 17 cases (4.7%); 2 cases were present preoperatively and the remaining 15 cases developed after surgery. Venography detected only one false-positive scan in this series. One patient with DVT died, but the postmortem examination revealed no pulmonary embolism. The results of serial venous scans were normal in 344 cases. There were no in-hospital pulmonary embolisms in any patient with normal venous scan results. Two patients (0.6%) with normal serial scan results had fatal pulmonary embolism 1 and 3 weeks after discharge. Duplex venous scanning was useful for prospective DVT surveillance of a high-risk group. The overall incidence of DVT (4.7%) is below that expected in such patients, suggesting the effectiveness of the program of prophylaxis. Scan results were reliable for therapeutic decisions and did not jeopardize patient safety.

Castleman's disease manifesting in the central nervous system: case report with immunological studies.

Castleman's disease is an uncommon lymphoproliferative disorder that manifests itself as a local or generalized tumor-like condition affecting both lymph nodes and nonnodal tissues, usually in the chest or abdomen. Only two prior examples involving the central nervous system had been reported when this patient was encountered. Very recently, three additional cases have been reported by Severson et al. We report the sixth case of Castleman's disease affecting the central nervous system, which occurred in a 63-year-old woman in whom the diagnosis was made after craniotomy for a mass lesion involving the dura over the frontal regions. Neuroradiological, clinical, and immunopathological characteristics of the case are presented. The lesion was treated with cranial irradiation and the patient is alive and symptom free three years after initial treatment.

The effects of intravenous prostacyclin in a model of microsurgical thrombosis.

Numerous agents have been administered in an attempt to achieve specific biochemical antiplatelet activity. A model of microsurgical trauma was utilized to create a nonocclusive thrombus, similar to what occurs in the postoperative period. Prostacyclin (PGI2) was given in a high intravenous dose which caused in vitro inhibition of platelet aggregation in rats and rabbits. Although hematological and cardiovascular side effects of PGI2 were tolerated, in vivo platelet thrombus formation persisted and constituted 25-75% of the postoperative thrombus. Even though platelets were inhibited by PGI2, other significant stimuli remained at the site of injury for activation and participation of platelets in the formation of a thrombus.

Pediatric spinal injury: the very young.

Maturity of the spine and spine-supporting structures is an important variable distinguishing spinal cord injuries in children from those in adults. Clinical data are presented from 71 children aged 12 years or younger who constituted 2.7% of 2598 spinal cord-injured patients admitted to the authors' institutions from June, 1972, to June, 1986. The 47 children with traumatic spinal cord injury averaged 6.9 years of age and included 20 girls (43%). The etiology of the pediatric injuries differed from that of adult injuries in that falls were the most common causative factor (38%) followed by automobile-related injuries (20%). Ten children (21.3%) had spinal cord injury without radiographic abnormality (SCIWORA), whereas 27 (57%) had evidence of neurological injury. Complete neurological injury was seen in 19% of all traumatic pediatric spinal cord injuries and in 40% of those with SCIWORA. The most frequent level of spinal injury was C-2 (27%, 15 cases) followed by T-10 (13%, seven cases). Upon statistical examination of the data, a subpopulation of children aged 3 years or younger emerged. These very young children had a significant difference in level of injury, requirement for surgical stability, and sex distribution compared to 4- to 12-year-old children.

Laser-sealed arteriotomy: a reliable aneurysm model.

Laser-assisted vascular anastomosis (LAVA) is associated with a significant aneurysm problem when it is applied to small arteries. The etiology of this phenomenon was investigated by creating arteriotomies of different lengths and orientation in the rat carotid artery and sealing them with the milliwatt CO2 laser. It was found that increasing the arteriotomy length from 0.5 to 1.0 mm significantly raised aneurysm occurrence (4/17 vs. 25/28, chi-square: p less than 0.001) regardless of orientation. Systemic hypertension (systolic blood pressure greater than or equal to 170 mm Hg) also significantly affected the aneurysm rate among the 0.5-mm arteriotomy group, raising aneurysm occurrence from 23.5% (4/17) to 100% (14/14) (p less than 0.001). Assuming that the stay-sutures used for LAVA's act as rigid supports, the rate of aneurysm occurrence must be related to the distance between sutures. This phenomenon has been exploited to create a reliable aneurysm model.

Bursting pressure of experimental aneurysms.

The laser-sealed arteriotomy (LSA) technique was used to create experimental aneurysms in the rat carotid artery. Animals were reexplored 2, 4, and 8 weeks following LSA, at which time the aneurysms were measured and subjected to a bursting strength pressure. In addition, a group of hypertensive rats with LSA was also tested 2 weeks after surgery. The LSA procedure produced aneurysms of a stable size and bursting pressure over the time studied. The bursting pressure technique may be applicable for assessing aneurysm therapy in an experimental setting.