Perioperative complications in acoustic neuroma (vestibular schwannoma) surgery.

OBJECTIVE: Retrospective study and review of the complications other than those related to the facial nerve and hearing, encountered in acoustic neuroma surgery. Also, an evaluation of hospital stay and its relation with various factors. STUDY DESIGN: Retrospective case review. SETTING: Tertiary neurotologic and skull base referral center. PATIENTS: A series of 707 patients who underwent surgical removal of acoustic neuroma from April 1987 to December 2001. INTERVENTIONS: The surgical approaches used were the enlarged translabyrinthine approach, the enlarged middle fossa approach, and the retrosigmoid approach. In a small number of cases, the operations were performed through other approaches. MAIN OUTCOME MEASURES: The duration of hospital stay and appearance of complications in the perioperative period along with their management. Results related to the facial nerve and hearing were not considered in this study. RESULTS: The most frequent complication was abdominal subcutaneous hematoma (site of fat harvest), which occurred in 23 patients (3.2%). Cerebrospinal fluid leak was present in 20 patients (2.8%), 15 of whom needed revision surgery. Other complications included VIth cranial nerve dysfunction in 12 cases (1.68%), subdural hematoma in 3 cases (0.4%), cerebellopontine angle hematoma in 4 cases (0.6%), cerebellar edema in 2 cases (0.28%), brainstem hematoma in 1 case (0.14%), transitory aphasia in 1 case (0.14%), and lower cranial nerve dysfunction in 1 case (0.14%). Mortality occurred in only one case (0.14%). Medical complications seldom occurred. The postoperative hospital stay ranged from 2 to 36 days, with an average of 6.4 days. The overall hospital stay diminished over time from 10.2 days in 1987 to 1990, to 4.9 days in 2001. There was a significant relation between hospital stay and tumor size, approach used, and presence/absence of complications. CONCLUSIONS: Perioperative complications in acoustic neuroma surgery do exist, but this study demonstrated how low the incidence is. The authors believe that the low percentage of complications is mainly attributable to the majority of operations being carried out in specialized clinics, where they are considered routine operations. They believe that following individualized approaches, depending on tumor size and on the preoperative function of the cranial nerves, is the proper way to reach a significant reduction in complications while maintaining a high percentage of total tumor removal. The results of this study, considered as a basis of comparison with other studies, will certainly be useful in preoperative patient counseling.     

Management of jugular paragangliomas: the Gruppo Otologico experience.

OBJECTIVE: The objective of this study was to review the outcome of surgical management in patients of jugular paragangliomas. STUDY DESIGN: We conducted a retrospective case review. SETTING: Tertiary care otology and skull base center. MATERIALS AND METHODS: Fifty-five patients with the diagnosis of a jugular paraganglioma (Fisch Class C and D Glomus Jugulare) were managed over a period of 15 years. All patients with adequate follow up and complete records (53 cases) were reviewed with emphasis on the results of surgical management and the factors influencing them. INTERVENTION: All 53 patients were managed with a view to surgically extirpate the tumor. The primary approach was the infratemporal fossa approach-Type A used in the majority of the patients. In eight cases, the procedure was staged owing to the presence of large intracranial extension. Three patients required additional procedures to ameliorate the after-effects of lower cranial nerve resection. RESULTS: Gross total tumor removal was achieved in 49 patients. There were five cases of recurrence. Coupled with the residual tumors in five patients, the surgical control achieved was 83%. There was no perioperative mortality. There were two cases of postoperative cerebrospinal fluid leak, both of which required surgical exploration and closure. The facial nerve was resected in seven patients. The overall preservation rate of clinically uninvolved lower cranial nerves was 75%. CONCLUSIONS: The low level of complications along with a high surgical control achieved makes surgery the primary mode of treatment in the vast majority of these tumors, regardless of the size and location.     

Management of the internal carotid artery in tumors of the lateral skull base: preoperative permanent balloon occlusion without reconstruction.

OBJECTIVE: To present our experience with permanent preoperative balloon occlusion of the internal carotid artery while dealing with different abnormalities of the lateral skull base and a comparison with the results mentioned in the literature. STUDY DESIGN: Retrospective case review. SETTING: Private neurotologic and skull base tertiary referral center. PATIENTS: Fifteen patients who underwent preoperative balloon occlusion of the internal carotid artery and surgery subsequently for various abnormalities of the lateral skull base between 1989 and 2002. INTERVENTIONS: Each patient was subjected to four-vessel angiography along with the manual cross-compression test and balloon test occlusion to assess the efficacy of the collateral circulation. After angiography, each patient underwent a preoperative balloon occlusion, after which a lateral skull base procedure was performed for removal of the abnormality. MAIN OUTCOME MEASURES: Only those patients showing evidence of adequate collateral cerebral circulation and a less than 1-second delay between the angiographic phases of the two cerebral hemispheres on angiography were considered fit for preoperative balloon occlusion. While under going the preoperative balloon occlusion, the patients were clinically assessed for the development of any neurologic symptoms and signs. Long-term follow-up after surgery was also based on the development of symptoms and signs of neurovascular compromise. RESULTS: A major complication in the form of long-lasting hemiplegia occurred in one patient (6.7%). This complication was the result of technical factors rather than an effect of cerebral ischemia, because it was caused by an intimal dissection produced by the catheter. A defect in the visual field occurred in one patient (6.7%) that resolved partially after antiplatelet therapy. There was no mortality in our series related to preoperative balloon occlusion of the internal carotid artery. CONCLUSION: Preoperative balloon occlusion of the internal carotid artery can still be considered a viable option for the management of the internal carotid artery during lateral skull base surgery. Proper preoperative evaluation of the adequacy and efficacy of the collateral cerebral circulation reduces the chances of postoperative neurovascular complications.     

Structural and biological characterization of three novel mastoparan peptides from the venom of the neotropical social wasp Protopolybia exigua (Saussure).

The venom of the Neotropical social wasp Protopolybia exigua(Saussure) was fractionated by RP-HPLC resulting in the elution of 20 fractions. The homogeneity of the preparations were checked out by using ESI-MS analysis and the fractions 15, 17 and 19 (eluted at the most hydrophobic conditions) were enough pure to be sequenced by Edman degradation chemistry, resulting in the following sequences: Protopolybia MPI I-N-W-L-K-L-G-K-K-V-S-A-I-L-NH2 Protopolybia-MP II I-N-W-K-A-I-I-E-A-A-K-Q-A-L-NH2 Protopolybia-MP III I-N-W-L-K-L-G-K-A-V-I-D-A-L-NH2 All the peptides were manually synthesized on-solid phase and functionally characterized. Protopolybia-MP I is a hemolytic mastoparan, probably acting on mast cells by assembling in plasma membrane, resulting in pore formation; meanwhile, the peptides Protopolybia-MP II and -MP III were characterized as a non-hemolytic mast cell degranulator toxins, which apparently act by virtue of their binding to G-protein receptor, activating the mast cell degranulation.     

Enoxaparin for the prevention of venous thromboembolism associated with central vein catheter: a double-blind, placebo-controlled, randomized study in cancer patients.

PURPOSE: The extent of venous thromboembolism (VTE) associated with central vein catheters (CVC) in cancer patients remains unclear. The aim of this study was to evaluate the efficacy and safety of the low molecular weight heparin, enoxaparin, in the prevention of VTE. PATIENTS AND METHODS: In a multicenter, double-blind study, consecutive cancer patients scheduled for CVC insertion were randomly assigned to receive either subcutaneous enoxaparin 40 mg once a day or placebo. Treatment was started 2 hours before CVC insertion and continued for 6 weeks. The primary end points of the study were deep vein thrombosis (DVT), confirmed by venography of the CVC limb performed 6 weeks after randomization, or clinically overt pulmonary embolism, confirmed by objective testing during the study drug administration. Patients were assessed for bleeding complications. RESULTS: Three hundred eighty-five patients were randomized, of which 321 (83.4%) underwent venography. A venography was adequate for adjudication in 155 patients in each treatment group. A DVT was observed in 22 patients (14.1%) treated with enoxaparin and in 28 patients (18.0%) treated with placebo, corresponding to a relative risk of 0.78 (95% CI, 0.47 to 1.31). No major bleeding occurred. Five patients (2.6%) in the enoxaparin group and two patients (1.0%) in the placebo group died during the treatment period. CONCLUSION: In this study, no difference in the rate of CVC-related VTE was detected between patients receiving enoxaparin and patients receiving placebo. The dose of enoxaparin used in this study proved to be safe. Clinical trials evaluating higher enoxaparin doses could optimize the efficacy of this agent for this indication.     

Effect of formulation on methylphenidate release patterns

Attention-deficit hyperactivity disorder (ADHD) is the most common psychiatric disorder in children. Currently, the most widely prescribed therapy for ADHD is methylphenidate. Several formulations of methylphenidate have been developed that modify the delivery of the drug into the body. These include immediate-release (IR) tablets and modified-release preparations including sustained-release tablets, controlled-delivery capsules and tablets, and transdermal delivery systems. The IR tablet is taken two or three times daily and has been demonstrated to show efficacy through its rapid onset of action. The modified-release formulations deliver methylphenidate at a controlled rate and are administered once daily; they were developed to mimic the efficacy of the IR tablet by controlling drug release. The latest formulation development efforts have been directed towards combining the rapid release and onset of action of an IR component with an extended-release component that would maintain drug levels and allow for once-daily administration. The rationale for the development of various delivery systems of methylphenidate stems from the need for drug coverage for at least 8 hours for ADHD patients. This would maintain efficacy over the entire school day and would eliminate the need for repeated administrations while the patient was at school. Early formulation development targeted a constant-release profile or an apparent zero-order input with the intention of maintaining plasma drug levels at a constant level for the required time period. However, it was demonstrated that the constant delivery of methylphenidate did not provide equivalent efficacy to the repeated administration of the IR product over the school day and resulted in tolerance to the effects of the drug. This suggested that sustained-release formulations that maintained constant drug levels over the treatment period would not result in the optimal therapeutic condition. In contrast, a drug delivery profile that maintained a drug release pattern with increase-release kinetics would be able to overcome the tolerance that was observed with the constant delivery formulations. Therefore, the formulation development for modified-release once-daily administration products of methylphenidate has been targeted to mimic the repeated administrations of IR methylphenidate.     

Temperature-sensitive hydrogels

Thermo-sensitive polymers are appealing materials for several therapeutic applications, such as in regenerative medicine and in situ drug release. These macromolecules are characterized by the ability to undergo swelling/deswelling processes during temperature change-induced phase transitions. Swelling and shrinking temperatures depend on the specific physicochemical properties, namely salt concentration or pH, of the thermo-sensitive gels as well as the incubation environment. An understanding of the mechanisms underlying the gel-swelling equilibrium and kinetics is necessary for the selection of an appropriate gel in relation to the specific pharmaceutical application. Thermo-sensitive polymers used in medicine include polyacrylamides, polyvinyls, polyethers, polysaccharides, and polyphosphazenes. A few of them have been successfully used as 3-dimentional supports for cell cultivation, allowing for the production of scaffolds with excellent biologic properties for application in regenerative medicine. Stem cells that can undergo specific differentiation under the appropriate stimulation have also been cultivated. The ability of drug/polymer solutions to turn into gels at physiologic temperature has been exploited for local drug delivery. The prolonged in situ presence and slow drug release enhances the therapeutic performance of antibiotics used in urogenital pathologies, anti-inflammatory agents, and anticancer drugs. The reduced toxicity as well as lower fluctuations in peak-to-trough drug concentrations make these systems superior to traditional gels. Thermo-sensitive hydrogels have also been demonstrated to be interesting formulations for the delivery of biotechnological drugs. Proteins and oligonucleotides can be loaded under mild conditions, stabilized, and released at a controlled rate. Finally, thermo-reversible polymers have been investigated for protein conjugation to enhance the physicochemical, biologic, immunologic, and pharmacokinetic properties of biotechnological products.