Women in Neurosurgery: Historical Path to Self-Segregation and Proposal for an Integrated Future.

Despite the rising percentage of women accessing the medical profession over the last few decades, surgical specialties are still largely male-dominated; in particular, a remarkable gender disparity is evident in neurosurgery, where only 19% of practitioners are females. Although women may be reluctant to choose a challenging specialty like neurosurgery due to concerns around how to balance family and career, it must be admitted that prejudices against female neurosurgeons have been deeply rooted for long, prompting many to give up and switch track to less demanding subspecialties. Among those who have persisted, many, if not most, have experienced difficulties in career progression and received unequal treatment in comparison with their male counterparts. In 1989, a group of 8 female neurosurgeons founded Women in Neurosurgery (WINS), an organization that aimed to guarantee inclusivity in neurosurgery, encouraging a better and more egalitarian working environment. Thereafter, WINS sessions were regularly promoted at international conferences, offering female neurosurgeons a platform to report issues related to gender discrimination. Over recent years, the mission of WINS sessions in national and international conferences has taken an unexpected deviation; they have progressively become supplementary scientific sessions with only women neurosurgeons as speakers, thus paving the road to a form of self-segregation. This tendency has also resulted in the establishment of sections of only female neurosurgeons within some national societies. Although there remains a faction that fiercely supports the WINS mindset of reserved spaces for women, such segregation is an upsetting prospect for those who believe that science and professionalism have no gender; a growing part of the global neurosurgical community believes that the conception of a "female neurosurgery" and a "male neurosurgery" is misguided and counterproductive and consider the existence of the WINS as anachronistic and no longer necessary.

Decompression and surgical stabilization in the palliative treatment of vertebral metastases.

Instability of the spine consequent to the diffusion of a primary tumor is a serious complication in cancer patients. The experience of our Service in the surgical treatment of vertebral metastases is reported. Since 1990, 21 patients have undergone surgery. The vertebral metastases were localized at the cervical level in 4 cases, thoracic in 13, and lumbar in 4. Pain was the first symptom in 18 patients. The necessary criterion for intervention was intractable severe pain and/or neurologic deficit. At the thoracic and lumbar levels (17 cases) a posterior approach was always used to perform wide decompressive laminectomy and to stabilize the spine. An anterior approach is unadvisable in light of the risk related to the operation and the long recovery time. In 13 cases Cotrel-Dubousset bars were utilized, in 3 cases Roy-Camille, and in 1 case Louis plates. After surgery, significant pain relief was noted in 85% of patients. Of those with neurologic deficit, improvement in neurologic status was seen in 50%; in 28% neurologic deficit was completely resolved. We conclude that, although palliative, wide laminectomy accompanied by stabilization is a satisfactory treatment of vertebral metastases. Given the appropriate indications, surgical treatment improves the patient's quality of life.

Attenuation of vasospasm and hemoglobin-induced constriction in the rabbit basilar artery by a novel protease inhibitor.

Calcium-activated proteolysis mediated by the protease inhibitor, calpain, has recently been implicated in the pathogenesis of cerebral vasospasm. The effect of one inhibitor of calcium-activated proteolysis, z-Leu-Phe-CONH-morpholene (zLF), on cerebrovascular constriction was examined in two experimental paradigms. In the first paradigm, the rabbit basilar artery (BA) was visualized via a transclival exposure, and its diameter was monitored using videomicroscopy. In the second experimental paradigm two intracisternal injections of autologous blood were administered to mimic a subarachnoid hemorrhage (SAH). The BA was visualized via the transclival exposure, and its luminal diameter was measured. Topical application of oxyhemoglobin (OxyHb), a known pathogenic agent in cerebral vasospasm, elicited vasoconstriction in normal animals, reducing arterial diameter to approximately 75% of resting levels. Pretreatment with zLF (100, 200, or 300 microM) attenuated vasoconstriction induced by OxyHb. In an experimental model of SAH, the diameter of the BA was reduced after the first injection of blood to approximately 67% of normal resting levels when measured 3 to 4 days later. This vasospastic response was reversed significantly by topical application of zLF (100 microM); vascular diameter was increased to approximately 84% of normal resting levels. These findings demonstrate that both acute OxyHb-induced constriction and blood-induced vasospasm are sensitive to an inhibitor of the proteolytic enzyme, calpain. Together, these observations indicate an important role for calcium-activated proteolysis in the development and maintenance of vasospasm after SAH. In addition, it may be inferred from the data that inhibitors of calcium-activated proteolysis may be useful therapeutic agents for treating this form of cerebrovascular disease.

The effects of post-translational side-chain modifications on the stimulatory activity, serum stability and conformation of synthetic peptides carrying T helper cell epitopes.

Peptides 31D and VF13, corresponding to the rabies virus nucleo- and glycoproteins, respectively, vigorously stimulate T helper cells of the appropriate specificity. Earlier we showed how internal and external glycosylation affects the major histocompatibility complex molecule (MHC)-binding ability and conformation of these T-cell epitopes (Otvos et al. (1994) Biochim. Biophys. Acta 1224, 68-76; Otvos et al. (1995) Biochim. Biophys. Acta 1267, 55-64). In the current report, we examined the T-helper cell stimulatory ability after introduction of a new set of post-translational modifications. To obtain general information concerning the effects of amino acid side-chain modifications on other biochemical properties of protein fragments, we studied the serum stability and the conformation of the 31D and VF13 peptides. We found that the extent of the reduction of the T-cell stimulatory activity depends upon the location in the sequence of the host amino acid residue. Generally, beta-linked sugars in mid-chain positions had a greater inhibitory effect than alpha-linked sugars attached to identical amino acids. In a case where mid-chain glycosylation just marginally reduced the T-cell stimulatory activity, the beta-linked glycopeptide was significantly more resistant to serum proteases. This finding suggests that addition of beta-linked carbohydrates might be superior to the addition of alpha-linked sugars for vaccine development, and generally for peptide agonist drug design. In addition, data presented here provide the first documentation that phosphorylation and sulfation of tyrosine residues may retain the MHC-binding ability and T-cell stimulatory activity of class II epitopes. The sulfated and the phosphorylated 31D peptides exhibited considerably increased serum stability compared to the unmodified parent peptide. Finally, all post-translational modifications destabilized the dominant alpha-helical or turn structures of the peptides presented in aqueous trifluoroethanol mixtures. While the circular dichroism spectra of the alpha- and beta-linked VF13 glycopeptides with monosaccharides were almost indistinguishable, the structure of the glycopeptides depended upon the length of the sugar moiety. Significantly, incorporation of sulfate or phosphate groups resulted in identical peptide conformations.

Structure-activity relationship of verapamil analogs and reversal of multidrug resistance.

We studied the relationship between the chemical structure and multidrug resistance (MDR) reversal activity of racemic verapamil (VER) and 14 VER analogs (VAs). The LoVo-R human colon carcinoma cell line was used as an experimental model. This cell line exhibited a typical MDR phenotype and overexpressed the MDR1 gene products. Key structural features were identified as being related to MDR reversal and cytotoxic activity. In particular, we demonstrated that the methoxy groups in the VER molecule structure [1.7-Bis-(3.4-dimethoxyphenyl)-3-methylaza-7-cyan-8-methyl-n onane] prevented cytotoxicity when the VAs were used alone, whereas the 7-cyan-8-methyl groups were important for MDR reversal activity and interaction with P-glycoprotein (P-gp). Among the VAs tested, the most active compounds were gallopamil, R-isomer of VER (R-VER), and nor-VER, which potentiated doxorubicin (DOX) cytotoxicity by 52.3 +/- 7.2 (n = 3 +/- SD), 38.9 +/- 6.4 (n = 4 +/- SD), and 35.4 +/- 4.3 (n = 3 +/- SD) times, respectively. The reversal activity of these compounds was similar to that of VER, which enhanced DOX cytotoxicity by 41.3 +/- 5.0 (n = 3 +/- SD) times. The potentiation of DOX cytotoxicity was associated with an increase in DOX uptake in LoVo-R cells and with an increased [3H]azidopine P-gp photolabeling inhibition. Some compounds that had a high reversal potency (i.e. R-VER and nor-VER) showed a lower calcium antagonist activity than VER, and seem useful candidates for the treatment of MDR in cancer patients.

Arteriovenous malformations that rupture during pregnancy: a management dilemma.

Intracranial haemorrhage due to rupture of an arteriovenous malformation (AVM) during pregnancy is a rare but serious condition that warrants prompt recognition. Once the diagnosis is made, the management is primarily based on neurosurgical rather than obstetric considerations. Due to its rarity, no definitive guidelines exist, and the best time to perform elective surgery (i.e., at presentation or at completion of the pregnancy) is ill-defined. This report describes three patients recently treated at our institution who had AVMs that ruptured during pregnancy. These cases well summarize the difficulties encountered in treating such patients. The diagnostic as well as the therapeutic implications of this condition are discussed.

[Cranial fractures during growth. An analysis of the authors' personal cases and therapeutic management of such childhood pathology]. / Le fratture craniche in accrescimento. Analisi della casistica personale e condotta terapeutica di tale patologia infantile.

Growing skull fractures are a rare complication of head injury with a dome fracture. The cases described in literature highlight a higher frequency of this pathology in children under than over three years of age. The authors describe 4 personal cases, underlying the clinical, diagnostic and therapeutic aspects. The aetiological hypothesis of a dural tear and its anatomic-pathological evolution are investigated. The surgical technique of dural and bony repair is also discussed. The authors conclude that this complication must be recognized early in order to obtain very good results after surgical therapy.