Allopurinol adherence among patients with gout: an Italian general practice database study.

AIMS: Allopurinol is used as long-term therapy to reduce the occurrence of gout flares. This study estimated the impact of patient adherence to allopurinol on hyperuricaemia (serum uric acid levels, sUA > 6 mg/dl) and the identification of non-adherence predictors. METHODS: The Italian Health Search-CSD Longitudinal Patient Database was accessed to identify outpatients aged ≥ 18 years with gout and prescribed with allopurinol during the years 2002-2011. Patients with a proportion of days covered ≥ 80% were considered adherent to allopurinol. Data on sUA levels over the first year of therapy were categorised in three time-windows (30-89; 90-149; 150-365 days). Logistic regressions were used to estimate the association between adherence and hyperuricaemia, as well as non-adherence predictors. RESULTS: A total of 3727 patients were included. In the interval 0-29 days, the proportion of patients adherent to allopurinol was 45.9%, while up to 89, 149 and 365 days the percentages were 16.7%, 10.0% and 3.2%, respectively. The proportions of hyperuricaemic patients for each time-window were 43.1%, 42.4%, 32.6% and 59.0%, 64.0%, 66.4% among adherent and non-adherent patients, respectively. In the multivariable analysis, adherence was associated with a significant lower risk of hyperuricaemia. The adjusted ORs were 0.49 (95% CI: 0.33-0.73), 0.40 (95% CI: 0.24-0.67) and 0.23 (95% CI: 0.15-0.34) for the first, second and third time-window, respectively. Patients with hypertension (adjusted OR = 0.64, 95% CI: 0.42-0.99) and history of gout flares (adjusted OR = 0.55, 95% CI: 0.32-0.95) were significantly adherent to allopurinol. CONCLUSIONS: Adherence monitoring in patients with gout is pivotal to ensure the effectiveness of therapy. To gain a better patient adherence, the communication between physicians and patients should be improved.

Vaginal lactoferrin in asymptomatic patients at low risk for pre-term labour for shortened cervix: cervical length and interleukin-6 changes.

A total of 3,324 singleton pregnant women were screened for pre-term delivery and 128 women were finally randomised and analysed for outcome showing borderline cervical length (25-29 mm) and elevated cervico-vaginal interleukin 6 levels. To verify if vaginal administration of lactoferrin might have an influence on these variables, two groups of 64 patients were formed. Study cases were submitted to lactoferrin for 21 days; controls received no treatment. An inverse relation was found between interleukin 6 levels and cervical length. On day 30 from the beginning of the treatment, study cases showed a decrease in interleukin 6 levels and an increase in cervical length. A greater number of women with regular uterine contractions and reduced cervical consistency before the 37th week of gestation were found in the controls. Our data show that lactoferrin could play a role in reducing the number of women at risk for pre-term birth for shortened cervical length and elevated interleukin 6 levels.

Analysis of extracellular superoxide dismutase in fibroblasts from patients with systemic sclerosis.

Systemic sclerosis (SSc) is a chronic disease of connective tissue characterized by vascular damage, autoantibody production and extensive fibrosis of skin, skeletal muscles, vessels and visceral organs. Fibrosis is a biological process involving inflammatory response and reactive oxygen species (ROS) accumulation leading to fibroblast activation. Extracellular superoxide dismutase (SOD3), a copper and zinc superoxide dismutase, which is expressed in selected tissues, is secreted into the extracellular space and catalyzes the dismutation of superoxide radical to hydrogen peroxide and molecular oxygen. Moreover, SOD3 is associated to inflammatory responses in some experimental models. In this paper we analysed, by RT-PCR and immunofluorescence, SOD3 expression and intracellular localization in dermal fibroblasts from both healthy donors and patients affected by diffuse form of SSc. Moreover, we determined SOD3 enzymatic activity in fibroblast culture medium with the xanthine/xanthine oxidase method. Increased expression of SOD3 mRNA was detected in systemic sclerosis fibroblasts (SScF), as compared to control healthy fibroblasts (HF), and SOD3 immunofluorescence staining displayed a characteristic pattern of secretory proteins in both HF and SScF. Superoxide dismutase assay demonstrated that SOD3 enzymatic activity in SScF culture medium is four times more than in HF culture medium. These data suggest that an alteration in SOD3 expression and activity could be associated to SSc fibrosis.

Neuropeptide expression in the airways of COPD patients and smokers with normal lung function.

Neurogenic mechanisms seem to play a role in the pathogenesis of chronic obstructive pulmonary disease (COPD), as suggested by a number of in vitro data. However, few studies have investigated the presence of neuropeptides in the airways of patients with COPD, and they have yielded conflicting results. The aim of this study is to compare the expression of the neuropeptide substance P (SP), vasoactive intestinal peptide (VIP), and neuropeptide Y (NPY) in the airways of smokers with and without COPD. Surgical lung samples were obtained from 15 smokers with COPD and 16 smokers with normal lung function, who underwent lobectomy for a solitary lung carcinoma. Airway expression and distribution of SP, VIP, and NPY were identified by immunohistochemistry and analyzed by a computerized image analysis system. Compared to smokers with normal lung function, COPD patients exhibited an increased immunoreactivity for SP and VIP, paralleled by a decreased NPY expression in the epithelium and glands, and a decreased expression of all these three neuropeptides in the smooth muscle layer. Therefore, in the present study we have documented a different expression and distribution of the neuropeptides SP, VIP, and NPY in the airways of smokers with and without COPD. These findings suggest a possible involvement of such neuropeptides in the pathogenesis of some changes occurring in COPD.

In vitro cultured progenitors and precursors of cardiac cell lineages from human normal and post-ischemic hearts.

The demonstration of the presence of dividing primitive cells in damaged hearts has sparked increased interest about myocardium regenerative processes. We examined the rate and the differentiation of in vitro cultured resident cardiac primitive cells obtained from pathological and normal human hearts in order to evaluate the activation of progenitors and precursors of cardiac cell lineages in post-ischemic human hearts. The precursors and progenitors of cardiomyocyte, smooth muscle and endothelial lineage were identified by immunocytochemistry and the expression of characteristic markers was studied by western blot and RT-PCR. The amount of proteins characteristic for cardiac cells (alpha-SA and MHC, VEGFR-2 and FVIII, SMA for the precursors of cardiomyocytes, endothelial and smooth muscle cells, respectively) inclines toward an increase in both alpha-SA and MHC. The increased levels of FVIII and VEGFR2 are statistically significant, suggesting an important re-activation of neoangiogenesis. At the same time, the augmented expression of mRNA for Nkx 2.5, the trascriptional factor for cardiomyocyte differentiation, confirms the persistence of differentiative processes in terminally injured hearts. Our study would appear to confirm the activation of human heart regeneration potential in pathological conditions and the ability of its primitive cells to maintain their proliferative capability in vitro. The cardiac cell isolation method we used could be useful in the future for studying modifications to the microenvironment that positively influence cardiac primitive cell differentiation or inhibit, or retard, the pathological remodeling and functional degradation of the heart.

Differential expression and cytoplasm/membrane distribution of endoglin (CD105) in human tumour cell lines: Implications in the modulation of cell proliferation.

Endoglin (CD105, an accessory component of the TGF-beta receptor complex) expression and distribution on different human tumour cells and its role in cellular proliferation were evaluated. We examined: 1) sixteen human carcinoma cell lines, 2) eight human sarcoma cell lines, 3) five miscellaneous tumour cell lines. HECV (endothelial cells) were employed as a positive control for endoglin expression. Normal Human Dermal Fibroblasts (NHDF) and 293 cells (epithelial kidney cells) were used as normal controls for connective and epithelial tissues, respectively. The results showed that CD105 was poorly expressed in the majority of human carcinoma cells (10/16), whereas it was highly expressed in most human sarcoma cells (7/8), and differently expressed by miscellaneous tumour cell lines. These data reflect endoglin expression by the normal counterparts of tumour cell lines, i.e. NHDF and 293 cells. However, CD105 levels in sarcoma cell lines, even though consistently lower than in NHDF, were significantly higher than those observed in carcinoma cells. Interestingly, CD105 presented a strong expression in the cytoplasm of MDA-MB-453 (breast carcinoma), NPA (papillary thyroid carcinoma), COLO-853 (melanoma) and SaOS-2 (osteosarcoma), but was weakly expressed on their cell membrane. This differential expression in the cytoplasm and on the membrane of some tumour cells, suggests a complex mechanism of translocation for this protein. The analysis of clonal growth in soft agar of some cell lines, characterized by high CD105 expression, showed an increased colony formation potential that was antagonized by the addition of anti-CD105 blocking mAb. The results indicated that endoglin is differentially expressed in human carcinoma and sarcoma cells and its overexpression modulates the proliferative rate of human solid tumour cells. Moreover, these data suggest that CD105 is involved in the regulation of TGF-beta effects in human solid malignancies, and therefore it could play an important role in tumour diagnosis and treatment.

Genetic variability of Apolipoprotein E in different populations from Venezuela.

The genetic variation at the Apolipoprotein E locus (APOE) is an important determinant of plasma lipids and has been implicated in various human pathological conditions. The objective of the present study was to estimate the distribution of APOE alleles in five Venezuelan communities: two Amerindian tribes (Bari and Yucpa), one Negroid population from Curiepe, one Caucasoid population from Colonia Tovar and the Mestizo urban population living in Caracas. The APOE*3 allele was the most common allele in all populations studied. However, a significant increase in the APOE*2 allele frequency in the Mestizo (18.96%) and Negroid (16.25%) populations was found. Similar to results reported in other Native American populations we have found that the APOE*2 allele is completely absent in the Bari and Yucpa Amerindians. Frequencies found in the Colonia Tovar population are in agreement with those reported in the population of Germany, indicating a high degree of relatedness. The results support the notion that the distribution of the APOE alleles shows ethnic variability.

Basal lamina structural alterations in human asymmetric aneurismatic aorta.

Basal lamina (BL) is a crucial mechanical and functional component of blood vessels, constituting a sensor of extracellular microenvironment for endothelial cells and pericytes. Recently, an abnormality in the process of matrix microfibrillar component remodeling has been advocated as a mechanism involved in the development of aortic dilation. We focused our attention on BL composition and organization and studied some of the main components of the Extracellular Matrix such as Tenascin, Laminins, Fibronectin, type I, III and IV Collagens. We used surgical fragments from 27 patients, submitted to operation because of aortic root aneurysm and 5 normal aortic wall specimens from heart donors without any evidence for aneurysmal or atherosclerotic diseases of the aorta. Two samples of aortic wall were harvested from each patient, proximal to the sinotubular junction at the aortic convexity and concavity. Each specimen was processed both for immunohistochemical examination and molecular biology study. We compared the convexity of each aortic sample with the concavity of the same vessel, and both of them with the control samples. The synthesis of mRNA and the levels of each protein were assessed, respectively, by RT-PCR and Western Blot analysis. Immunohistochemistry elucidated the organization of BL, whose composition was revealed by molecular biology. All pathological samples showed a wall thinner than normal ones. Basal lamina of the aortic wall evidentiated important changes in the tridimensional arrangement of its major components which lost their regular arrangement in pathological specimens. Collagen I, Laminin alpha2 chain and Fibronectin amounts decreased in pathological samples, while type IV Collagen and Tenascin synthesis increased. Consistently with the common macroscopic observation that ascending aorta dilations tend to expand asymmetrically, with prevalent involvement of the vessel convexity and relative sparing of the concavity, Collagen type IV is more evident in the concavity and Tenascin in the convexity.

Erratum - Analysis of extracellular superoxide dismutase and Akt in ascending aortic aneurysm with tricuspid or bicuspid aortic valve.

This correct the article published on European Journal of Histochemistry 2014;58:200-206 doi: 10.4081/ejh.2014.2383.

Verapamil upregulates sensitivity of human colon and breast cancer cells to LAK-cytotoxicity in vitro.

Pretreatment of human colon cancer LoVo-H cells and human breast cancer ZR-75 1A cells with low doses of verapamil, a Ca2+ channel blocker, for 48 h has a slight growth stimulatory effect and substantially increases cell sensitivity to lymphokine-activated killer (LAK) mediated cytotoxicity in the standard 51Cr release assay. The role of intracellular Ca2+ levels in determining verapamil effect is demonstrated by cytochemical evidence of intracellular Ca2+ lowering in verapamil-treated cells and by the reversal by the Ca2+ ionophore A-23187 of verapamil-induced sensitivity to LAK-mediated cytotoxicity.

Altered expression of integrins in RSV-transformed chick epiphyseal chondrocytes.

Chondrocytes have been shown to express both in vivo and in vitro a number of integrins of the beta1-, beta3- and beta5-subfamilies (Biorheology 37 (2000) 109). Normal and v-Src-transformed chick epiphyseal chondrocytes (CEC) display different adhesion properties. While normal CEC with time in culture tends to increase their adhesion to the substrate by organizing focal adhesions and actin stress fibers, v-Src-transformed chondrocytes display a refractile morphology and disorganization of actin cytoskeleton. We wondered whether the reduced adhesion and spreading of v-Src-transformed chondrocytes could be ascribed to changes in integrin expression and/or function. Integrin expression by normal CEC is studied and compared to v-Src-transformed chick chondrocytes, using monoclonal and polyclonal antibodies to integrins alpha- and beta-chains. We show the presence of alpha1-, alpha3-, alphav-, alpha6-, beta1- and beta3-chains on CEC, with very low levels of alpha2- and alpha5-chains. Alphav chain associates with multiple beta subunits in normal and transformed chondrocytes. With the exception of alpha1- and alpha2-chains, the levels of the integrin chains analyzed are higher in transformed chondrocytes as compared with normal chondrocytes. In spite of the increased levels of integrin expression, transformed chondrocytes exhibit loss of focal adhesion and actin stress fibers and low adhesion activity on several extracellular matrix constituents. These observations raise the possibility that, in addition to its effects on global pattern of integrin expression, v-Src can influence integrin function in chondrocytes.

Pharmacological evidence that the activation of the Na(+)-Ca2+ exchanger protects C6 glioma cells during chemical hypoxia.

1. In C6 glioma cells exposed to chemical hypoxia a massive release of lactate dehydrogenase (LDH) occurred at 3 and 6 h, coupled with an increased number of propidium-iodide positive dead cells. 2. Extracellular Na+ removal, which activates the Na(+)-Ca2+ exchanger as a Na+ efflux pathway and prevents Na+ entrance, significantly reduced LDH release and the number of propidium iodide positive C6 cells. 3. During chemical hypoxia, in the presence of extracellular Na+ ions, a progressive increase of [Ca2+]i occurred; in the absence of extracellular Na+ ions [Ca2+]i was enhanced to a greater extent. 4. The blockade of the Na(+)-Ca2+ exchanger by the amiloride derivative 5-(N-4-chlorobenzyl)-2',4'-dimethylbenzamil (CB-DMB), lanthanum (La3+) and the Ca2+ chelator EGTA, completely reverted the protective effect exerted by the removal of Na+ ions on C6 glioma cells exposed to chemical hypoxia. 5. The inhibition of the Na(+)-Ca2+ antiporter enhanced chemical hypoxia-induced LDH release when C6 glioma cells were incubated in the presence of physiological concentrations of extracellular Na+ ions (145 mM), suggesting that the blockade of the Na(+)-Ca2+ antiporter during chemical hypoxia can lead to increased cell damage. 6. Collectively, these results suggest that activation of the Na(+)-Ca2+ exchanger protects C6 glioma cells exposed to chemical hypoxia, whereas its pharmacological blockade can exacerbate cellular injury.

Is the CCR5-59029-G/G genotype a protective factor for cardiomyopathy in Chagas disease?

Investigated were two CCR5 gene polymorphisms, the CCR5 Delta 32 deletion and the pCCR5 59029 A-->G promoter point mutation, in 107 ethnically mixed Venezuelan patients serologically positive for Trypanosoma cruzi (34 asymptomatic, 38 arrhythmic, 35 cardiomyopathic). No difference in the distribution of CCR5 Delta 32 among asymptomatic and symptomatic patients was found. We have observed an increase of the 59029-G phenotype among asymptomatic compared with symptomatic chagasic patients (68% vs. 58%), in agreement with previously reported data (57% vs. 31%). This frequency difference, although not statistically significant, is more marked when the 59029-G allele is present in homozygous form. However, a similar distribution of the G/G genotype is present among asymptomatic patients and patients with heart failure. Because it has been reported that the 59029G/G genotype associates with lower CCR5 expression, 37% of our T. cruzi-infected patients with heart failure are genetically predisposed to express low levels of CCR5 on the surface of CD8(+) T cells, contrary to what would be expected if an inflammatory response is required for severe cardiac damage. If confirmed, the possible protection that might be conferred by the G/G genotype may be due to the existence of other genes in linkage disequilibria.

HLA-C(*)03 is a risk factor for cardiomyopathy in Chagas disease.

Previous studies have shown the effect of class 1 as detected by serology or class 2 HLA genes by oligotyping upon susceptibility or resistance to the cardiomyopathy that develops in approximately one third of the Trypanosoma cruzi chronically infected patients. Low and intermediate resolution DNA typing of class 1 alleles was performed in a sample of 113 serologically positive individuals with and without cardiomyopathy. A polymerase chain reaction-sequence-specific oligonucleotide probe method using primers and probes from the British Society of Histocompatibility and Immunogenetics as modified for the VII Latin American Histocompatibility Workshop by D. Middleton, and LiPA kits from Innogenetics were used. Several alleles (A(*)11, A(*)31, B(*)15, B(*)35, B(*)45, B(*)49, B(*)51, and C(*)03) showed increased frequencies among patients with cardiac damage versus the asymptomatic group, but only the last one remained significant after correction of the p value (OR = 5.8, p(c) = 0.03). HLA-C(*)03 showed linkage disequilibrium with B(*)40 and B(*)15 and although both haplotypes were increased in cardiopathic patients compared with asymptomatic individuals, the difference is not significant. These results suggest that the HLA-C*03 allele could confer susceptibility to the development of cardiomyopathy among Venezuelan T. cruzi seropositive individuals and contrast with the protective effect conferred by the HLA B40 Cw3 haplotype among Chilean chagasic patients. Further studies will be needed to confirm the role of this allele on the cardiomyopathy of Chagas disease.

Extended HLA haplotypes in a Carib Amerindian population: the Yucpa of the Perija Range.

Eleven MHC loci haplotypes have been defined among a Carib speaking Amerindian population; the Yucpa, inhabiting the northern section of the Perija Range, on the limits between Colombia and Venezuela. This tribe has been known with the name of "Motilones mansos" and is located close to the Chibcha-Paeze speaking Bari or "Motilones bravos." Seventy-three full blooded Yucpa living at the villages of Aroy, Marewa, and Peraya, were selected using a genealogy previously collected by an anthropologist and tested for Bf-C4AB complement allotypes and by serology, high resolution PCR-SSO and SBT typing for HLA class 1 and class 2 alleles. Combinations of 6 HLA-A, 6 HLA-B, 5 HLA-C, 1 Bf, 3 C4AB, 3 DQA1, 3DQB1 and 2 DPA1 and 2 DPB1 alleles present in this population originate 17 different haplotypes, 3 of which represent 63% of the haplotypic constitution of the tribe. The presence of 13 individuals homozygous for 11-loci haplotypes corroborates the existence of the following allelic combinations: DRB1*0411 DQA1*03011 DQB1*0302 DPA1*01 DPB1*0402 with HLA-A*6801 C*0702 B*3909 BfS C4 32 (f = 0.3372) or with A*0204 C*0702 B*3905 (f = 0.1977) and a third haplotype which differs only in DRB1*0403 and A*2402 (f = 0.0930). The results demonstrate the isolation of the tribe and the existence of high frequencies of a reduced number of "Amerindian" ancestral and novel class 1 and class 2 alleles (B*1522, DRB1*0807) with significant linkage disequilibria. These results will be useful to test the hypothesis that differentiation of Amerindian tribal groups will have to rely on haplotypes and micropolymorphism rather than allelic lineage frequencies due to the uniformity shown thus far by the putative descendants of the original Paleo-Indians.

Phorbol 12-myristate 13-acetate (pma) induces neuroendocrine-like differentiation and reverses Doxorubicin-resistance of human colon-carcinoma cells in-vitro.

Human colon carcinoma LoVo/DX cells, which have been selected from parental LoVo for resistance to doxorubicin, express a typical multidrug resistant (MDR-1) phenotype. We have investigated whether phorbol 12-myristate 13-acetate (PMA) which often induces phenotypical changes in human tumor cells could, at the same time, modulate differentiation and sensitivity of LoVo/DX cells to doxorubicin. After 48 h exposure to 100 nM PMA, morphological changes became evident on LoVo/DX cells which showed elongated cytoplasm and dendritic-like structures: moreover immunocytochemical findings were suggestive of neuroendocrine-like differentiation. Under the same experimental conditions, LoVo/DX became sensitive to doxorubicin and showed enhanced intracellular drug-accumulation and reduced membrane expression of the 170 kD glycoprotein GP-170, which is the cellular product of the mdr1 gene. We conclude that pharmacological induction of tumor cell differentiation by PMA is paralleled by abrogation of drug resistance in a colon carcinoma MDR-1 cell line.

Behavior of SaOS-2 cells cultured on different titanium surfaces.

Surface properties may affect the clinical outcome of titanium dental implants. The aim of the present study was to investigate the effects of 3 different titanium surfaces-smooth (S), sandblasted (SB), and titanium plasma-sprayed (TPS)-on proliferation, differentiation, and apoptosis of human osteoblast-like cells, SaOS-2. Cell proliferation was significantly (p < 0.05) higher on the S surface, and synthesis of extracellular matrix proteins was more abundant on TPS and SB than on S surfaces. Analysis of integrin receptors showed a higher expression of alpha2, alpha5, alphaVbeta3, and ss1 on TPS as compared with SB and S surfaces. An increase in alkaline phosphatase activity was detected only on SB and TPS surfaces. Analysis of cell apoptosis did not demonstrate any significant difference among the 3 different surfaces. The results indicate that titanium surface topography affects proliferation and differentiation of osteoblast-like SaOS-2 cells, suggesting that surface properties might be important for bone response around dental implants in vivo.

Expression of GM-CSF receptor and "in vitro" effects of GM-CSF on human fibroblasts.

In the present study the effects of Granulocyte-Macrophage Colony Stimulating Factor (GM-CSF) on fibroblast growth and activity have been studied. In this regard the AA have evaluated in primary cultures of human gengival normal fibroblasts (PG1 cells): a)-the expression of GM-CSF receptor (GM-CSFR) (alfa unit) on the cell surface; b)-the in vitro effects of different doses of GM-CSF on the GM-CSFR expression and on the proliferation and activity of fibroblasts. PG1 cells have been stimulated in vitro with different concentrations of GM-CSF (10, 50, 80, 100 and 150 ng/ml) using promonocytic cell line U937 as positive control for GM-CSFR expression. GM-CSFR was investigated by flow cytometry, with mouse monoclonal antibody (mAb) against the alfa chain of the human GM-CSFR and fluorescein-conjugated goat antimouse immunoglobulin G (IgG). At high GM-CSF concentration (80 ng/ml) the AA observed: 1)-A marked increase of GM-CSFR expression evaluated as fluorescence intensity (about three fold in respect to the controls); 2)-Maximal increase of PG1 cells proliferation. Moreover immunofluorescence on fibroblasts obtained from culture plates showed increased actin stress fibers and fibronectin production with low stimulation by GM-CSF, while higher concentration of this cytokine determined increased proliferation of cells, but a decreased formation of actine fibers and vinculin plaques. These results demonstrate: 1)-The presence of GM-CSFR on the surface of fibroblasts; 2)-The proliferation and the synthesis activity of these cells (in vitro) are modulated by different concentration of GM-CSF. We hypothesize that GM-CSF until 80 ng/ml can upregulate the expression of the receptor. Therefore, on the basis of previous findings of high serum levels of GM-CSF in course of scleroderma, a disease characterized by fibroblast hyperactivity, a possible role of this cytokine in the pathogenic process of this disease can be hypothesized.

Oestrogen and progesterone sensitivity in cultured meningioma cells.

Several studies have detected oestrogen and progesterone receptors in meningioma specimens; recently we have also confirmed the presence of steroid receptors in cultured cells from meningiomas. This paper describes the oestrogen and progesterone receptor assay in cultured cells from 6 meningiomas and the influence of steroid hormones on the cell growth and morphology. Four (66%) of the 6 specimens were positive for both receptors. Growth of cultured cells from tumours without receptors is not appreciably modified by the addition of hormones; the cultured cells from tumours with positive receptors are not essentially influenced by oestrogen, whereas progesterone produces a rapid and marked suppression of the cell growth and modifies their form and adhesivity; also the addition of an oestrogen and progesterone blend produces growth suppression. A similar effect of the progesterone on the cultured cells has also been obtained in a specimen of malignant meningioma. The results of this study suggest that the modulation of progesterone levels may be of therapeutic usefulness, particularly in patients with recurrent malignant meningiomas.

Correlation between sex hormone receptors and peritumoral edema in intracranial meningiomas.

Fifty patients with intracranial meningiomas, verified histologically, are retrospectively analyzed to correlate the peritumoral brain edema with the positivity of estrogen receptors and progesterone receptors. The extent of edema was quantified on CT scan and/or MR. Monoclonal antibodies were used to test the estrogen receptors and the dextran-coated charcoal method was used to test the progesterone receptors. Significant levels of both receptors were found in 41 (82%) specimens. 80% of the cases with positive receptors had brain edema, in contrast to only 2 among 9 cases with negative receptors. Thus, the presence of brain edema has resulted to be correlated to the positivity of sex hormone receptors, although we did not find significant correlation between the amount of receptors and the amount of edema. The suggested mechanisms responsible for the brain edema surrounding intracranial meningiomas are discussed. We can suggest that progesterone may induce the secretion of some substances from meningioma cells, such as prostaglandins and biogenic amines, which may result in vagogenic edema.