Cationic liposomes formulated with DMPC and a gemini surfactant traverse the cell membrane without causing a significant bio-damage.

Cationic liposomes have been intensively studied both in basic and applied research because of their promising potential as non-viral molecular vehicles. This work was aimed to gain more information on the interactions between the plasmamembrane and liposomes formed by a natural phospholipid and a cationic surfactant of the gemini family. The present work was conducted with the synergistic use of diverse experimental approaches: electro-rotation measurements, atomic force microscopy, ζ-potential measurements, laser scanning confocal microscopy and biomolecular/cellular techniques. Electro-rotation measurements pointed out that the interaction of cationic liposomes with the cell membrane alters significantly its dielectric and geometric parameters. This alteration, being accompanied by significant changes of the membrane surface roughness as measured by atomic force microscopy, suggests that the interaction with the liposomes causes locally substantial modifications to the structure and morphology of the cell membrane. However, the results of electrophoretic mobility (ζ-potential) experiments show that upon the interaction the electric charge exposed on the cell surface does not vary significantly, pointing out that the simple adhesion on the cell surface of the cationic liposomes or their fusion with the membrane is to be ruled out. As a matter of fact, confocal microscopy images directly demonstrated the penetration of the liposomes inside the cell and their diffusion within the cytoplasm. Electro-rotation experiments performed in the presence of endocytosis inhibitors suggest that the internalization is mediated by, at least, one specific pathway. Noteworthy, the liposome uptake by the cell does not cause a significant biological damage.

Effects of vagus nerve stimulation on cortical excitability in epileptic patients.

Vagus nerve stimulation (VNS) is used as adjunctive treatment for medically refractory epilepsy, but little is known about its mechanisms of action. The effects of VNS on the excitatory and inhibitory circuits of the motor cortex were evaluated in five patients with epilepsy using single- and paired-pulse transcranial magnetic stimulation (TMS). Patients were examined with the stimulator on and off. VNS determined a selective and pronounced increase in the inhibition produced by paired-pulse TMS with no effects on the excitability by single-pulse TMS.

Comparison of descending volleys evoked by transcranial and epidural motor cortex stimulation in a conscious patient with bulbar pain.

OBJECTIVE: To compare the pattern of activation of motor cortex produced by transcranial magnetic stimulation and epidural electrical stimulation. METHODS: The spinal volleys evoked by transcranial magnetic stimulation and epidural electrical stimulation over the cerebral motor cortex were recorded from an electrode inserted into the cervical epidural space of one conscious subject who also had a cortical epidural electrode over the motor area. The volleys were termed D- and I-waves according to their latency. Magnetic stimulation was performed with a figure-of-eight coil and the induced current flowed either in a postero-anterior (PA) or in latero-medial (LM) direction. RESULTS: At active motor threshold intensity LM magnetic stimulation evoked a D wave whereas PA stimulation evoked an I(1) wave with later I waves being recruited at increasing stimulus intensities. Electrical epidural stimulation evoked both a D wave and I waves. However, the D wave evoked by electrical epidural stimulation had a longer latency than the LM D wave, suggesting either a more proximal site of activation of the pyramidal axon or activation of slightly faster conducting set of corticospinal fibres by LM stimulation. The I3 wave evoked by electrical epidural stimulation also had a longer latency than the PA I3-wave CONCLUSIONS: Epidural stimulation of the motor cortex can produce repetitive excitation of corticospinal neurones. The order of recruitment of the volleys, and the latency of the D and I3 waves may be slightly different to that seen after transcranial magnetic stimulation. SIGNIFICANCE: Our findings suggest that there may be subtle differences in the populations of neurones activated by the two forms of stimulation.

Management of recurrent craniopharyngioma.

Although histologically benign, craniopharyngioma can regrow either from macroscopic remnants of the tumour left behind at operation, or even after an apparently gross total removal. Recurrence rates vary significantly in the literature, depending on the efficacy of surgical treatment and also on the growth potential of the tumour itself. The main factor influencing tumour regrowth is obviously the extent of surgical resection, as total removal carries a much lesser risk of recurrence compared to subtotal or partial resections (although in such cases radiation therapy can lower this risk significantly). Other factors involved are the duration of follow-up and patient's age at operation, as children tend to relapse more frequently than adults. Even in the "microsurgery" era, characterized by high percentages of total resections, recurrences remain high and continue to represent a major problem of craniopharyngioma treatment. Twenty-seven children and adolescents were operated on for craniopharyngioma at the Department of Neurosurgery, Section of Pediatric Neurosurgery, Catholic University Medical School, Rome between June 1985 and June 1997. Total tumour resection was achieved in 18 cases, subtotal in 7 and partial in 2 instances. One patient died post-operatively. Post-operative neuroradiological investigations confirmed the operative findings, although 3 children with an apparently gross total removal showed a residual non-enhancing calcium fleck adherent to the hypothalamus (which remained stable at the following examinations). Three of the 9 patients with less than total removal underwent post-operative radiation therapy. Out of the 26 surviving patients 6 presented a recurrence of their craniopharyngioma, 2 after an apparently gross total removal and 4 after a subtotal or partial resection (one of them had received radiation therapy). The diagnosis was merely neuroradiological in 5 cases, as only one child presented a clinical picture suggestive of tumour regrowth. Surgery was the first therapeutic option in all the cases. Total tumour resection was accomplished in 3 cases, subtotal in 2 and partial in the last one. One child died post-operatively. Four of the 5 survivors received radiation therapy. All the patients are presently alive and stable (mean follow-up: 5.6 yrs). The authors conclude that surgery should be the first therapeutic option in case of recurrent craniopharyngioma and that radiation therapy should also be considered but only as adjuvant therapy.

Prognosis of medulloblastoma in infants.

The prognosis of medulloblastoma in children less than 3 years old is usually considered to be rather poor. However, recent experiences with this type of tumour seem to indicate that survival in this specific subgroup of patients can be longer than expected. Nineteen infants with posterior fossa tumours treated by the authors in the period 1983-1994, all of them with symptoms presenting during the 1st year of life and all operated on before the end of the 2nd year of life, have been retrospectively analysed. Total tumour removal was achieved in 14 cases, subtotal in 1 and partial in 3. One subject underwent only a biopsy of the tumour. In 14 patients a CSF shunt was inserted. Chemotherapy was administered to 18 out of the 19 patients in the series. At the time of the study, 11 children had died (57.9%) and 8 were alive (42.1%; mean survival 86.5 months). One patient died of complications secondary to the surgical treatment. Three patients died because of local recurrence of the tumour after apparent total excision, death supervening 5, 12 and 18 months after the surgical treatment. A further 2 patients in whom total tumour removal had been performed died 3 and 17 months after surgery of local recurrence of the disease associated with regional metastases. Progression of the residual tumour, accompanied by metastatic dissemination in 3 cases, accounted for death in the other 5 patients who did not survive. Brain stem infiltration appeared to be the most significant adverse prognostic factor. All 8 long-term survivors had their tumour totally excised. Five of them underwent radiotherapy when at least 2 years old. On the basis of the results, the authors conclude that the current prognosis of infants with medullo-blastoma is not necessarily any worse than that of older children with the same disease and that chemotherapy can be particularly useful in this subgroup of patients, as shown by 3 long-term survivals obtained in children treated with this type of therapy only.

[Optic gliomas in the first year of life]. / Gliomi delle vie ottiche ad esordio clinico nel primo anno di vita.

BACKGROUND: Optic gliomas are mainly observed in pediatric patients. Twenty-five percent of cases are diagnosed in the first year of life. Infants with optic gliomas must be considered distinctly from the rest of pediatric patients with this type of lesion, because of the more invasive nature of the tumour and a worse prognosis. Most authors think that surgical treatment of optic gliomas has to be limited to a diagnostic biopsy of the lesion and, in selected cases, to partial decompressive excision. Chemotherapy is useful in the control of the disease, particularly when combined with surgery. Radiotherapy has important secondary effects on the immature brain, and its use is restricted to patients who have reached the 2nd year of life. METHODS: We report our observations on 11 patients with optic gliomas diagnosed in the first year of life, and treated at the Section of Pediatric Neurosurgery of the Catholic University of Rome between 1980 and 1994. RESULTS: In 45.4% of cases the tumour involved the intracranial optic nerve, the optic chiasm, the optic tract and the thalamus. Nystagmus was the most frequent clinical sign, and it was observed in all cases. Signs of intracranial hypertension were observed in 72.6% of cases. We performed a partial decompressive excision of the tumour in 82% of patients. In 2 of these cases we have observed a spontaneous disappearance of the tumour residue and in 5 cases a prolonged time of survival. Mortality has been lower in our group of patients, compared with other authors' experience (36.4% vs 50-80%). Also morbidity has been lower. A severe neurological worsening was observed in two patients and a complete blindness in other two cases (18.1% vs 66.6-100%). CONCLUSIONS: We think that the lower morbidity and mortality observed in our patients can, at least in part, be ascribed to a more aggressive surgical treatment of the lesions.