The system of modified transcochlear approaches for intradural skull base lesions

The modified transcochlear approach was used to manage 27 patients with intradural tumours of petroclival region and prepontine cistern. Total tumour removal was possible in 21 cases. Planned subtotal removal was done in 2 elderly patients; one was a chordoma with involvement of the cavernous sinus and extending upto the optic chiasma while the other was a petroclival meningioma involving the cavernous sinus with normal abducent nerve function. The remaining 4 cases are awaiting their second stage. The modified transcochlear approach is systematized and further classified into types A, B, C and D depending upon its extensions. The basic surgical technique with its extensions, details of the classification, indications of each type and results are presented in this report.     

Effect of concomitant hormone replacement therapy containing estradiol and levonorgestrel on the pharmacokinetics of selegiline

OBJECTIVE: The aim of this study was to investigate the effect of hormone-replacement therapy (HRT) on the pharmacokinetics of the selective monoamine oxidase B inhibitor selegiline and its primary metabolites desmethylselegiline and l-metamphetamine. METHODS: In this randomised, double-blind, cross-over trial, 12 healthy female subjects received once daily for 10 days either HRT containing 2 mg estradiol valerate and 250 microg levonorgestrel or matched placebo. On day 10, they took a single 10-mg oral dose of selegiline. The serum concentrations of selegiline, desmethylselegiline and metamphetamine were measured for 32 h. RESULTS: There was a 59% difference ( P=0.14) in the area under the serum concentration-time curve (AUC) of selegiline during the HRT compared with the placebo phase, but only a little or no concomitant reduction in the AUC of desmethylselegiline (-7%, P=0.071) or metamphetamine (2%, P=0.614) was observed. Maximum plasma concentration (C(max)) of selegiline was not changed, but a small, statistically significant, reduction in the C(max) of desmethylselegiline (-17%, P=0.03) was seen during the HRT phase. The C(max) of methamphetamine was slightly but not significantly reduced (-5%, P=0.06). The unchanged AUC ratios of desmethylselegiline/selegiline and metamphetamine/selegiline indicate that the primary metabolism of selegiline was not affected by HRT. All study treatments were well tolerated. CONCLUSION: Unlike oral contraceptives, HRT is not likely to have clinically significant pharmacokinetic interaction with selegiline.     

Synthesis and evaluation for biological activity of 3-alkyl and 3-halogenoalkyl-quinoxalin-2-ones variously substituted. Part 4

A new series of 3-isopropyl-, 3-trifluoromethyl- and 3-bromomethylquinoxaline-2-ones variously substituted on the benzo-moiety were synthesized and submitted to a preliminary in vitro evaluation for antibacterial, antifungal and anti-HIV activities. Furthermore, all compounds were also tested for cytotoxicity. Results of the screening showed that compound 10 exhibits moderate antimicrobial activity against Staphylococcus aureus (MIC = 33 microM), and that 25 and 26 showed interesting cytotoxicity versus mock-infected MT-4 cells. All the other compounds were inactive.     

Placenta growth factor-1 antagonizes VEGF-induced angiogenesis and tumor growth by the formation of functionally inactive PlGF-1/VEGF heterodimers

Tumor growth and metastasis require concomitant growth of new blood vessels, which are stimulated by angiogenic factors, including vascular endothelial growth factor (VEGF), secreted by most tumors. Whereas the angiogenic property and molecular mechanisms of VEGF have been well studied, the biological function of its related homolog, placenta growth factor (PlGF), is poorly understood. Here we demonstrate that PlGF-1, an alternatively spliced isoform of the PlGF gene, antagonizes VEGF-induced angiogenesis when both factors are coexpressed in murine fibrosarcoma cells. Overexpression of PlGF-1 in VEGF-producing tumor cells results in the formation of PlGF-1/VEGF heterodimers and depletion of the majority of mouse VEGF homodimers. The heterodimeric form of PlGF-1/VEGF lacks the ability to induce angiogenesis in vitro and in vivo. Similarly, PlGF-1/VEGF fails to activate the VEGFR-2-mediated signaling pathways. Further, PlGF-1 inhibits the growth of a murine fibrosarcoma by approximately 90% when PlGF-1-expressing tumor cells are implanted in syngeneic mice. In contrast, overexpression of human VEGF in murine tumor cells causes accelerated and exponential growth of primary fibrosarcomas and early hepatic metastases. Our data demonstrate that PlGF-1, a member of the VEGF family, acts as a natural antagonist of VEGF when both factors are synthesized in the same population of cells. The underlying mechanism is due to the formation of functionally inactive heterodimers.     

An ecologic study of geographical variation in multiple sclerosis risk in central Sardinia,Italy

We carried out an ecological study in the most archaic area of Sardinia to obtain a reliable estimate of the prevalence of multiple sclerosis (MS) and to investigate the geographical variation in the prevalence across the 100 administrative communes. To estimate the area-specific prevalence rate, we adopted a Bayesian approach that makes it possible to filter out the random variation from the estimates and to obtain a map that reflects the true geographical variation in MS prevalence. 428 resident cases were identified by the case register, including 69 multiplex families. The overall prevalence was 157 per 100,000 inhabitants. The Bayesian area-specific prevalence ranged from 143 to 262/100,000. The high prevalence and its moderate geographical variation in a genetically homogeneous population, as well as the high number of multiplex families observed in the communes with the highest prevalence, could be interpreted as representing a high susceptibility of the population to MS.     

A new conservative approach in the treatment of postoperative digestive-tract fistulas. Mechanical closure by a balloon-catheter

BACKGROUND: Digestive fistulas represent troublesome complication in patients operated in modern surgical wards where the improved surgical procedures and better intensive care enhance the surgeon to perform more aggressive approaches with a high surgical risk index. The management of a patient presenting a digestive-tract fistula is never easy, being its approach either conservative (TPN) or surgical. We applied an alternative surgical procedure consisting in a mechanical closure of the fistula using a balloon-catheter so as to improve outcome in those patients in whom medical tratment did not show satisfactory RESULTS. METHODS: We treated 7 patients presenting a postoperative fistula following several surgical procedures for neoplasms of the digestive system. These fistulas were closed using a Foley or Fogarthy balloon catheter preceeded by radiological and/or endoscopy controls. Once the catheter was placed, oral nutrition was started and some patients were discharged. A progressive deflation of the balloon was performed until complete removal of the catheter upon approx 10 days. RESULTS: We obtained a complete healing of the fistula in 6 patients, within 10 days since catheter placement. Only one patient required another operation. CONCLUSIONS: Our case-series may seem statistically not significant, but varied concerning location and type of fistulas. We observed an excellent outcome using this procedure which allows very short healing period thanks to an early oral nutrition uptake and a decrease in costs mainly due to a short hospital stay and a minor use of expensive drugs (TPN).     

Lasker's coefficient of isonymy between and within 16 Sardinian villages in the periods 1825-1849, 1875-1899, and 1925-1949.

Coefficients of relationship by isonymy, based on the frequency of common surnames, were used to estimate the biological affinity between (R(ib)) and within (R(iw)) 16 Sardinian villages in the periods 1825-1849, 1875-1899, and 1925-1949. The database for the surname analysis consisted of 13,515 marriages registered in the parishes of villages, all belonging to the Sardinian linguistic area. The values of R(ib) and R(iw) tend to decrease in time. In all three periods, the R(ib) values generally decrease as the geographical distance between villages increases. The negative values of the Bravais-Pearson coefficient of correlation between the matrix of R(ib) values and the matrices of geographical distances (calculated both in a straight line and from road distances) are significant for each period (modified Mantel test), with slightly higher correlation coefficients for road distances. Moreover, the plots of isonymic relationships obtained by nonmetric multidimensional scaling for 1825-1849 and 1925-1949 show that the biological relationships between neighboring villages increase in the latter period. The positive values of the Bravais-Pearson coefficients of correlation between R(iw) and altitude are significant in all three periods, while the correlation between R(iw) and population size is not significant, even when altitude is controlled for. Since altitude is considered an indicator of isolation, the results obtained with the coefficient of relationship by isonymy within villages also support the isolation-by-distance model. R(ib) values provided a reliable picture of the biological relationships between 16 Sardinian villages, while R(iw) values illustrated the biological affinity within the communities for a period of 100 years, from 1825-1849 to 1925-1949.