A case of multiple primary tumors of the anterior skull base.

We report a case of synchronous olfactory bulb meningioma and undifferentiated carcinoma of the nose and paranasal sinuses that involved and destroyed the anterior skull base and mimicked intracranial invasion by a carcinoma. The heterogeneity of tissue types in the skull base gives rise to a diverse variety of benign and malignant neoplasms which have totally different prognoses. Synchronous development of benign and malignant primary tumors both originating from and involving the skull base at the same location is very rare and may cause confusion for both the skull base surgeon and neuroradiologist.     

Immunohistochemical detection of VEGF in the bone marrow of patients with acute myeloid leukemia. Correlation between VEGF expression and the FAB category

We studied vascular endothelial growth factor (VEGF) expression in bone marrow sections obtained from 3 healthy donors and 41 patients with acute myeloid leukemia (AML) of various French-American-British (FAB) subtypes by immunohistochemical analysis using an anti-VEGF antibody. In normal bone marrow, the anti-VEGF antibody reacted with myeloid progenitor cells and megakaryocytes but not with erythroid cells or mature granulocytic cells. High levels of VEGF were found in the bone marrow in patients with AML-M1, -M2, -M3, -M4, -M4Eo, and -M5. In these leukemias, the vast majority of myeloblasts (> 90%) expressed VEGF. By contrast, in AML-M0, the percentage of VEGF-positive blasts was lower in most cases (median, 42%), and if at all detectable, these blast cells contained only trace amounts of VEGF. In AML-M3 and -M4Eo, maturing granulocytes failed to express VEGF similar to granulocytes in normal bone marrow. In AML-M6, myeloblasts exhibited VEGF, whereas erythroid cells did not. In AML-M7, blast cells and megakaryocytes were identified as major sources of VEGF. In summary, VEGF expression in the bone marrow is restricted to certain stages of differentiation and maturation of myeloid cells and correlates with the FAB category.     

Anti-Tumor Activity of Four Ayurvedic Herbs in Dalton Lymphoma Ascites Bearing Mice and Their Short-Term In Vitro Cytotoxicity on DLA-Cell-Line

The anti-tumor activity and chemopreventive potential of four Ayurvedic herbs viz. Curcuma longa L., Ocimum sanctum L., Tinospora cordifolia (Wild) Miers ex Hook.f & Thomas and Zizyphus mauritiana Lam. were evaluated using Dalton Lymphoma ascites (DLA) tumor model in Swiss Albino mice. The outcome was assessed using survival time, peritoneal ascitic fluid (Tumor volume) and hematological indices as parameters. Animals were divided into five groups (n = 6) viz. one DLA control and four Herb + DLA treated groups. All the four herb + DLA groups were pre-treated with respective herbs for 7 days and hematological indices were measured for entire five groups. On day-8 animals were inoculated with 1×10⁶ DLA cells i.p., and Herb + DLA groups were continued with oral herbal treatment for 21-days. Hematological parameters and tumor volume were assessed to find the effects of herbs. Short term in vitro cytotoxicity was determined by Trypan Blue exclusion method and LDH leakage assay using different concentrations of herbal extracts and 5-FU as a positive control and IC₅₀ for each herbal extract and 5-FU were determined. Oral administration of crude herb increased the survival time and decreased the peritoneal ascitic fluid content significantly. Hb, RBCs and total WBC which were altered by DLA inoculation were restored significantly by all the herbs except O. sanctum. All the four herbs showed in vitro cytotoxic activity against DLA cell-line. Moreover inter group comparison of all the four herbs for anti-tumor activity showed efficacy in the following order- T. cordifolia > Z. mauritiana ≥ C. longa > O. sanctum respectively.     

Recombinant allergens promote expression of CD203c on basophils in sensitized individuals

BACKGROUND: Traditionally, the diagnosis of type I allergies is based on clinical data, skin test results, and laboratory test results with allergen extracts. During the past few years, several attempts have been made to refine diagnostic assays in clinical allergy by introducing recombinant allergens and novel markers of IgE-dependent cell activation. OBJECTIVES: We have identified the ectoenzyme CD203c as a novel basophil antigen that is upregulated on IgE receptor cross-linkage. In this study we applied CD203c and a panel of recombinant allergens to establish a novel basophil test that allows for a reliable quantification of IgE-dependent responses at the effector cell level. METHODS: Patients allergic to birch (Bet v 1, n = 15; Bet v 2, n = 8) and grass (Phl p 1, n = 15; Phl p 2, n = 10; Phl p 5, n = 14) pollen allergens, as well as 10 nonallergic donors, were examined. Basophils were exposed to various concentrations of recombinant allergens for 15 minutes and then examined for expression of CD203c by means of flow cytometry. CD203c upregulation was correlated with the increase in CD63. RESULTS: Exposure to recombinant allergens resulted in a dose-dependent increase in expression of CD203c on peripheral blood basophils in sensitized individuals, whereas no increase was seen in healthy control subjects. The effects of the recombinant allergens on CD203c expression were also time dependent. There was a good correlation between allergen-induced upregulation of CD203c and upregulation of CD63 (R = 0.76). CONCLUSION: Flow cytometric quantitation of CD203c on blood basophils exposed to recombinant allergens is a useful approach to determine the allergic state in sensitized individuals and represents a basis for a sensitive novel allergy test.     

Cell surface membrane antigen phenotype of human gastrointestinal mast cells

BACKGROUND: Mast cells (MC) are important effector cells of allergic and inflammatory reactions in diverse organs. These cells interact with a number of other immune cells and structural cells in the tissues as well as with proinflammatory mediators and cytokines. The various interactions are considered to be mediated through distinct cell surface membrane receptors on MC. METHODS: In the present study, we have established the cell surface membrane phenotype of human gastrointestinal MC (HGMC) using a panel of monoclonal antibodies and indirect immunofluorescence staining techniques. RESULTS: HGMC were found to react with antibodies against CD29, CD33, CD44, CD45, CD47, CD54, CD55, CD58, CD63, CD117, CD147, CD151, CD172a, and CD203c. By contrast, HGMC did not express detectable amounts of CD1, CD2, CD4, CD5, CD14, CD15, CD16, CD22, CD24, CD25, CD26, CD27, CD28, CD31, CD32, CD34, CD35, CD88, or CD116. The alpha-chain of the IL-3 receptor (CD123) was detectable neither in resting HGMC nor in HGMC exposed to stem cell factor and interleukin-4. CONCLUSIONS: HGMC express a unique profile of surface antigens including the receptor for mast cell growth factor, adhesion-related molecules, and activation-linked membrane antigens.     

The auditory midbrain implant: a new auditory prosthesis for neural deafness-concept and device description.

The auditory midbrain implant (AMI) is a new central auditory prosthesis designed for penetrating stimulation of the human inferior colliculus. The major group of candidates for the AMI consists of neurofibromatosis type 2 (NF2) patients who develop neural deafness because of growth and/or surgical removal of bilateral acoustic neuromas. Because of the absence of a viable auditory nerve, these patients cannot benefit from cochlear implants. An alternative solution has been the auditory brainstem implant (ABI), which stimulates the cochlear nucleus. However, speech perception performance in NF2 ABI patients has been limited. The fact that the ABI is able to produce high levels of speech perception in nontumor patients (with inaccessible cochleae or posttraumatic damage to the cochlear nerve) suggests that limitations in ABI performance in NF2 patients may be associated with cochlear nucleus damage caused by the tumors or the tumor removal process. Thus, stimulation of the auditory midbrain proximal to the damaged cochlear nucleus may be a better alternative for hearing restoration in NF2 patients. We propose the central nucleus of the inferior colliculus (ICC) as the potential site. A penetrating electrode array aligned along the well-defined tonotopic gradient of the ICC should selectively activate different frequency regions, which is an important elementfor supporting good speech understanding. The goal of this article is to present the ICC as an alternative site for an auditory implant for NF2 patients and to describe the design of the first human prototype AMI. Practical considerations for implementation of the AMI will also be discussed.     

Effect of statins on lipoprotein receptor expression in cell lines from human mast cells and basophils

Objective Statins are potent inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A reductase and widely used to treat hyperlipidaemia. Apart from their direct lipid-lowering effects, statins may also influence lipid metabolism through modulation of low-density lipoprotein (LDL) receptors. Basophils and mast cells have been reported to express LDL receptors and have been implicated in atherogenesis. The aim of this study was to investigate the effects of statins on the interactions of ¹²⁵I-LDL with purified primary human blood basophils, a human basophil cell line, KU812, and a human mast cell line, HMC-1.Methods Direct binding experiments were carried out with the primary basophils and KU812 as well as HMC-1 cells before and after pretreatment of the cells with atorvastatin, simvastatin, or cerivastatin. The effects of these three statins on the LDL-uptake and degradation as well as on thymidine incorporation in the cells were also studied.Results Primary basophils, HMC-1 and KU812 cells expressed two classes of LDL binding sites. Exposure to atorvastatin, simvastatin or cerivastatin increased significantly (P<0.05) the number of ¹²⁵I-LDL binding sites on primary basophils and HMC-1 as well as KU812 cells. The effects of the statins were dose dependent. The statins also enhanced the uptake and degradation of LDL in primary basophils, HMC-1 and KU812 cells. The increase in the number of LDL binding sites induced by statins was abolished by mevalonic acid (200 mol/l). Statins had no effect on the thymidine incorporation into the cells in an unstimulated condition.Conclusion Our results provide evidence for the upregulation of LDL binding sites on human basophils and mast cells by statins. We hypothesise that effects of statins on the lipid metabolism might also involve basophils and mast cells.     

Treatment of acne using a 3-milligram drospirenone/20-microgram ethinyl estradiol oral contraceptive administered in a 24/4 regimen: a randomized controlled trial

OBJECTIVE: To assess the efficacy of the combined oral contraceptive containing 3-mg drospirenone/20-microgram ethinyl estradiol (3-mg drospirenone/20-microgram ethinyl estradiol) administered as 24 consecutive days of active treatment after a 4-day hormone-free interval (24/4 regimen) compared with placebo for the treatment of moderate acne vulgaris. METHODS: Healthy females aged 14-45 years with moderate acne were randomized in this double-blind study to 3-mg drospirenone/20-microgram ethinyl estradiol (n=270) or placebo (n=268) for six cycles of 28 days. The primary outcome measures of acne lesion counts and Investigator Static Global Assessment scale ratings were assessed at baseline and during cycles 1, 3, and 6. RESULTS: The percentage reduction from baseline to endpoint for total lesions is 46.3% for 3-mg drospirenone/20-microgram ethinyl estradiol 24/4 combination oral contraceptive group and 30.6% for placebo group (P<.001). The likelihood of participants in the 3-mg drospirenone/20-microgram ethinyl estradiol 24/4 regimen group having "clear" or "almost clear" skin as rated by the investigators at endpoint was about threefold (odds ratio 3.13, 95% confidence interval 1.69-5.81; P=.001) greater than in the placebo group. The 3-mg drospirenone/20-microgram ethinyl estradiol 24/4 regimen was well tolerated. CONCLUSION: The low-dose combined oral contraceptive containing 3-mg drospirenone/20-microgram ethinyl estradiol administered in a 24/4 regimen significantly reduced acne lesion counts more effectively than placebo and demonstrated greater improvement in the Investigator Static Global Assessment rating of acne. The safety profile was consistent with low-dose combined oral contraceptive use.