Choice of neurosurgical approach in the treatment of cranial base lesions

The authors describe a series of surgical approaches that they found particularly useful for the exposure and removal of lesions involving the skull base. These are: 1) fronto-naso-orbital approach; 2) frontotemporo-orbito-zygomatic approach; 3) subtemporal transpetrosal approach; 4) temporo-suboccipital transpetrosal approach (retrolabyrinthine presigmoid; transsigmoid; translabyrintine amend transcochlear presigmoid); 5) dorsolateral approach to the foramen magnum and lower clivus.As the approaches are complex and carry potential risks of morbidity, not only it is important to have a good knowledge of basic anatomy but also to closely follow the indications for each one. In this type of surgery where it is often difficult to achieve complete removal of the lesion by a single route of attack, more than one approach may be employed in different surgical steps. Finally, all these approaches demand extremely scrupulos surgical reconstruction to avoid dangerous postoperative complications that may jeopardize the previous work of the surgeon.     

Immunological changes among workers occupationally exposed to styrene

The functional status of the immune system was investigated in a group of 71 workers exposed to styrene and in 65 control subjects, recruited according to the same selection criteria and comparable as to sex, age, and confounding variables. Air and biological monitoring were used to characterize styrene exposure (median of the main urinary metabolites in the next-morning spot samples: 106 mg/g creatinine). Phenotypic analysis of peripheral blood lymphocytes (PBL) by automated flow cytometry revealed a reduced proportion of T lymphocyte subsets (CD3⁺, CD4⁺ and CD4⁺45⁺), with no changes in CD8⁺, and a higher proportion of B lymphocytes (CD19⁺) among styrene-exposed workers. The exposed workers showed a higher proportion of activation markers, namely DR and interleukin-2 receptors (CD25). Immunoglobulin subclasses were comparable in the two groups. An increased prevalence of abnormally low values was apparent for CD2⁺, CD3⁺, CD4⁺, CD4⁺45⁺ and CD11b subsets among workers exposed to styrene, whereas CD19⁺, DR⁺ and CD25⁺ showed an increased prevalence of abnormally high values. Natural killer-related phenotypes (CD56⁺, CD56+16⁺, and CD56⁺16^–) were more expressed among styrene workers, with average increase of 30%. However, the frequency distribution of the lytic activity of natural killer cells against K-562 target cells was shifted towards lower values in the exposed workers as compared to control subjects. Dose-response relationships between indices of internal dose and prevalence of abnormal values were detectable for T lymphocyte subsets, NK phenotypes, and activation markers. These findings suggest that moderate exposure to styrene is associated with an altered distribution of lymphocyte subsets. The decreased proportion of T lymphocytes, mainly of T helper-inducer cells, could hamper regulatory functions, thus suggesting a negative modulation by styrene exposure. Since a proper balance between immunocycte subsets is important for immunological responses, such changes should be regarded as adverse effects.     

Identification of the central vestibular projections in man: a positron emission tomography activation study

The cerebral representation of space depends on the integration of many different sensory inputs. The vestibular system provides one such input and its dysfunction can cause profound spatial disorientation. Using positron emission tomography (PET), we measured regional cerebral perfusion with various vestibular stimulations to map central vestibular projections and to investigate the cerebral basis of spatial disorientation. We showed that the temporoparietal cortex, the insula, the putamen, and the anterior cingulate cortex are the cerebral projections of the vestibular system in man and that the spatial disorientation caused by unilateral vestibular stimulation is associated with their asymmetric activation.     

Malaria vaccines

Significant progress has been made in the development of the malaria vaccine during the last 20 years. Ninety percent of the 300–500 million clinical cases of malaria per year worldwide occur in Africa. Thus, research must be directed toward the 1 million African children under 5 years of age who die every year of malaria. An asexual blood-stage vaccine, capable of reducing severe and complicated malaria and malaria-related mortality, is therefore an important public health tool in these countries. Although knowledge of the parasite's biology is incomplete, research has allowed insight into some of the mechanisms that the parasite uses to evade host immunity. This is the basis for adopting an antigenic cocktail approach toward obtaining a synthetic or recombinant subunit vaccine such as the synthetic Colombian Malaria vaccine SPf 66. During the development of Spf66, field trials under both low and high malaria endemicity areas in Latin America and Africa have been carried out. The results from these studies showed a protective efficacy ranging between 38.8 and 60.2% againstPlasmodium falciparum malaria. Given the characteristics of the normal immune response to malaria (relatively short-lived and not completely effective), it is understandable that the main goal is to try to increase the host's natural immunity. The best candidates for designing a malaria vaccine are the proteins required for parasite survival, those with low mutation rates and conserved epitopes. Because these proteins play an important role in multiple or alternative steps during the invasion process, they should be the targets against which a protective immune response should be elicited. The interaction between the malaria parasite and its host is complex. It is therefore crucial to define new ways of improving the immune response—such as directly modifying the chemical structure of epitopes or using new adjuvants or DNA immunization techniques—to produce novel vaccines against this disease.     

Focus group: implications for program evaluation of mental health services

The focus group is a qualitative research method that involves group interaction based on a selected topic. It generally involves eight to 12 individuals who discuss a particular topic under the direction of a moderator who promotes interaction and guides the discussion on the topic of interest. This paper presents theoretical perspectives and a review of focus group methodology applied in related disciplines. A research project, which applied the focus group methodology, is described to illustrate important principles in utilizing this qualitative research technique. Information related to preparation for focus group sessions, structure, setting, participants, principles related to conducting the session and analysis are presented. The relevance of this methodology for research and practice in mental health also is discussed.     

Dolichol-bound oligosaccharides and the transfer of distal monosaccharides in the synthesis of glycoproteins by normal and tumor mammary epithelial cells

Summary The main dolichol diphosphate-bound oligosaccharides present in primary cultures of both normal and tumor mouse mammary epithelial cells had the same size, yielded the same pattern after acetolysis and paper chromatography, had the same number of mannose residues susceptible to-mannosidase degradation, and were composed of the same monosaccharide residues. This is the first demonstration that normal and tumor mammary cells have dolichol diphosphate-bound oligosaccharides with very similar, if not identical, structures. These compounds are intermediates in the synthesis of asparagine-linked oligosaccharides. On the other hand, normal and tumor cells showed differences in the specific activities of the enzymes involved in the transfer of the distal monosaccharides from the sugar nucleotides to glycoproteins. Sialyl- and fucosyl-transferases were elevated and galactosyl- and N-acetylglucosaminyltransferases were diminished in mammary tumor cells. The intact tumor cells showed an increased fucosylation of glycoproteins of the asparagine-linkage type. Address for reprints: Roberto L. Ceriani, M.D., Ph.D., Bruce Lyon Memorial Research Laboratory, Children's Hospital Medical Center, 51st and Grove Streets, Oakland, CA 94609, USA.     

Expression of Epstein-Barr virus latent membrane protein-1 in Hodgkin and Reed-Sternberg cells of classical Hodgkin's lymphoma: associations with presenting features, serum interleukin 10 levels, and clinical outcome.

PURPOSE: EBV-latent membrane protein-1 (LMP-1) is often expressed in Hodgkin and Reed-Sternberg (HRS) cells of classical Hodgkin's lymphoma (cHL), but its clinical significance is controversial. We correlated LMP-1 with presenting features, including serum interleukin 10 levels and clinical outcome. EXPERIMENTAL DESIGN: Patients were eligible if they had biopsy-proven cHL, were untreated, HIV-1 negative, and had available archival tissue. LMP-1 expression was determined by immunohistochemistry. RESULTS: We identified 577 patients with cHL with a median age of 30 years, 55% of whom were male. LMP-1 was expressed in HRS cells of 124 patients (21%) and was detected in 78 of 461 (17%) patients with nodular sclerosis compared with 44 of 112 (39%) with mixed cellularity (P < 0.001 by Fisher's exact test). Patients with tumors with LMP-1-positive HRS cells had higher serum interleukin 10 levels (P = 0.009 by Mann-Whitney test). For the 303 patients treated with doxorubicin, bleomycin, vinblastine, and dacarbazine or equivalent regimens, the 5-year failure-free survival (FFS) for those with LMP-1-positive tumors was 74% compared with 81% for those with LMP-1-negative tumors (P = 0.23, by log-rank test). Overall survival (OS) at 5 years for patients with LMP-1-positive tumors was 90 versus 91% for patients with LMP-1-negative tumors (P = 0.8 by log-rank test). Expression of LMP-1 was not associated with different FFS and OS in patients treated with other regimens or with radiotherapy alone. CONCLUSIONS: LMP-1 was expressed by HRS cells in 21% of cHL and correlated with mixed cellularity type and higher serum interleukin 10 levels. The presence of LMP-1 was not associated with FFS or OS in uniformly treated patients.     

The relationship between dietary fat intake and risk of colorectal cancer: evidence from the combined analysis of 13 case-control studies

The objective of this study was to examine the effects of the intakeof dietary fat upon colorectal cancer risk in a combined analysis of datafrom 13 case-control studies previously conducted in populations withdiffering colorectal cancer rates and dietary practices. Original datarecords for 5,287 cases of colorectal cancer and 10,470 controls werecombined. Logistic regression analysis was used to estimate odds ratios (OR)for intakes of total energy, total fat and its components, and cholesterol.Positive associations with energy intake were observed for 11 of the 13studies. However, there was little, if any, evidence of anyenergy-independent effect of either total fat with ORs of 1.00, 0.95, 1.01,1.02, and 0.92 for quintiles of residuals of total fat intake (P trend =0.67) or for saturated fat with ORs of 1.00, 1.08, 1.06, 1.21, and 1.06 (Ptrend = 0.39). The analysis suggests that, among these case-control studies,there is no energy-independent association between dietary fat intake andrisk of colorectal cancer. It also suggests that simple substitution of fatby other sources of calories is unlikely to reduce meaningfully the risk ofcolorectal cancer.