Vaginal compared with intramuscular progestogen for preventing preterm birth in high-risk pregnant women (VICTORIA study): a multicentre, open-label randomised trial and meta-analysis.

OBJECTIVE: To compare the efficacy of two types of progestogen therapy for preventing preterm birth (PTB) and to review the relevant literature. DESIGN: A multicentre, randomised, open-label, equivalence trial and a meta-analysis. SETTING: Tertiary referral hospitals in South Korea. POPULATION: Pregnant women with a history of spontaneous PTB or short cervical length (<25 mm). METHODS: Eligible women were screened and randomised at 16-22 weeks of gestation to receive either 200 mg of vaginal micronised progesterone daily (vaginal group) or an intramuscular injection of 250 mg 17α-hydroxyprogesterone caproate weekly (IM group). Stratified randomisation was carried out according to participating centres and indications for progestogen therapy. This trial was registered at ClinicalTrials.gov (NCT02304237). MAIN OUTCOME MEASURE: Preterm birth (PTB) before 37 weeks of gestation. RESULTS: A total of 266 women were randomly assigned and a total of 247 women (119 and 128 women in the vaginal and IM groups, respectively) were available for the intention-to-treat analysis. Risks of PTB before 37 weeks of gestation did not significantly differ between the two groups (22.7 versus 25.8%, P = 0.571). The difference in PTB risk between the two groups was 3.1% (95% CI -7.6 to 13.8%), which was within the equivalence margin of 15%. The meta-analysis results showed no significant differences in the risk of PTB between the vaginal and IM progestogen treatments. CONCLUSION: Compared with vaginal progesterone, treatment with intramuscular progestin might increase the risk of PTB before 37 weeks of gestation by as much as 13.8%, or reduce the risk by as much as 7.6%, in women with a history of spontaneous PTB or with short cervical length. TWEETABLE ABSTRACT: Vaginal and intramuscular progestogen showed equivalent efficacy for preventing preterm birth before 37 weeks of gestation.

Blood lactate concentration and shock index associated with massive transfusion in emergency department patients with primary postpartum haemorrhage.

BACKGROUND: We hypothesised that lactate concentrations are independently associated with massive transfusion in patients with primary postpartum haemorrhage. Moreover, combining lactate concentrations with the shock index, defined as the ratio of heart rate to systolic arterial blood pressure, can improve the predictive performance for massive transfusion. METHODS: We retrospectively analysed patients with primary postpartum haemorrhage in the emergency department of a tertiary referral centre in Korea between January 1, 2004 and December 31, 2015. RESULTS: Of the 302 patients, 101 (33.4%) patients required massive transfusion. Lactate concentration was independently associated with the requirement for massive transfusion [odds ratio, 1.56; 95% confidence interval (CI), 1.31-1.87; P<0.01]. The area under the receiver operating characteristic curve of lactate concentration and shock index for massive transfusion was 0.788 (95% CI: 0.736-0.840; P<0.01) and 0.776 (95% CI: 0.717-0.836; P<0.01), respectively. Lactate elevation (>4.0 mM L-1) was associated with 86.1% specificity and 67.8% positive predictive value for massive transfusion. When combining elevated lactate concentrations (>4.0 mM L-1) with a shock index >1.0, the specificity and positive predictive value increased to 95.5% and 82.4%, respectively. CONCLUSIONS: Point-of-care testing of lactate concentrations in the emergency department may be useful to predict massive transfusion requirements in primary postpartum haemorrhage. Combining initial lactate concentrations with the shock index improves the predictive performance for massive transfusion requirements and may contribute to rapid risk stratification of patients with primary postpartum haemorrhage in need of transfusion and further focus on early interventions to control bleeding.

Molecular genetic, cardiac and neurodevelopmental findings in cases of prenatally diagnosed rhabdomyoma associated with tuberous sclerosis complex.

OBJECTIVE: Rhabdomyoma is the most common type of cardiac tumor in fetuses and is often associated with tuberous sclerosis complex (TSC) with neurologic sequelae. The purpose of this study was to investigate the cardiac and neurodevelopmental outcomes of fetal rhabdomyoma. METHODS: We reviewed the clinical characteristics of 23 cases of cardiac rhabdomyoma diagnosed prenatally by fetal echocardiography at the Asan Medical Center between January 1998 and December 2009. We also reviewed postnatal results of brain magnetic resonance imaging, echocardiography, renal ultrasound examination and molecular genetic analysis to confirm the presence of cardiac rhabdomyoma with or without TSC. RESULTS: Among 23 cases, outcome data were available for 17 (73.9%) and six cases (26.1%) were lost to follow-up. The survival rate was 100.0% (17/17). Among the 17 cases with outcome data, spontaneous tumor regression occurred in eight (47.1%), and no change in tumor size and number was observed in the remaining nine cases (52.9%). There was no evidence of long-term cardiac dysfunction caused by persisting rhabdomyomas, regardless of tumor size. TSC was found in nine patients (52.9%), of whom five (55.6%) showed neurodevelopmental morbidity. We identified mutations in one of the TSC1 or TSC2 genes in four of nine TSC infants whose parents allowed us to perform molecular genetic analysis. Three of these (75.0%) were found to have neurologic impairment. Seven (77.8%) of nine TSC cases were non-familial. CONCLUSIONS: The overall outcome of isolated cardiac rhabdomyoma appears to be favorable. We suggest that systematic postnatal evaluation of TSC be performed even in cases of cardiac rhabdomyoma without a family history of TSC. Molecular characterization of TSC1 and TSC2 might be helpful in predicting short- and long-term neurodevelopmental outcomes.

Reading nutrition labels is associated with a lower risk of metabolic syndrome in Korean adults: the 2007-2008 Korean NHANES.

BACKGROUND AND AIMS: Several studies demonstrated that reading nutrition labels was associated with healthier food choices, despite some controversy. This study investigated the association between the use of nutrition labels and metabolic syndrome (MetS) in Korean adults. METHODS AND RESULTS: This cross-sectional study included 7756 individuals who participated in the 2007-2009 Korean National Health and Nutrition Examination Survey (KNHANES). A self-reported questionnaire was used to determine participant's awareness of nutrition labels. Modified Asian criteria based on a harmonizing definition of MetS were adopted. Individuals in the group that read nutrition labels (the Reading Group) were youngest and leanest, but their daily caloric intake fell between that of the group that did not read nutrition labels (the Non-Reading Group) and the group that did not know about them (the Not-Knowing Group). The prevalence of MetS was 16.8% in the Reading Group, 27.2% in the Non-Reading Group, and 47.3% in the Not-Knowing Group. In comparison to participants in the Reading Group, the odds ratios (95% confidence interval) for MetS in the participants in the Non-Reading Group and Not-Knowing Group were 1.85 (1.60-2.14) and 4.44 (3.79-5.20), respectively, when not adjusted. The relationship between the use of nutrition labels and MetS remained statistically significant even after adjusting for covariates such as age, sex and socioeconomic status including household income and education level [1.27 (1.05-1.53) in the Non-Reading Group and 1.34 (1.05-1.70) in the Not-Knowing Group]. CONCLUSION: Reading nutrition labels appeared to be associated with a lower prevalence of MetS in a nationally representative sample of Korean adults.

Protective effect of fetal pulmonary sequestration in two cases of postnatal manifestation of congenital diaphragmatic hernia.

We describe two cases of postnatally diagnosed congenital diaphragmatic hernia (CDH) combined with pulmonary sequestration, both of which were diagnosed as isolated pulmonary sequestration on prenatal ultrasound. In these cases, prenatal ultrasonography demonstrated only a hyperechoic mass on the left lower lung and the diaphragm seemed intact. In each case both lungs showed otherwise normal development throughout pregnancy. Pulmonary sequestration may serve as a 'protector', preventing herniation of abdominal contents into the thoracic cavity. The co-occurrence of CDH may be obscured by a lung mass, especially on the left lower lung, and therefore it is necessary to deliver these infants at a tertiary center and parents should be counseled about the possibility of postnatal CDH.

Relationship between non-alcoholic fatty liver disease and pulmonary function.

BACKGROUND: It has been observed that non-alcoholic fatty liver disease (NAFLD) is associated with an increased risk of cardiovascular disease and insulin resistance. Pulmonary function is also known to be related with cardiovascular disease and metabolic syndrome. AIMS: The objective of this study was to investigate the association between NAFLD and pulmonary function. METHODS: We performed a cross-sectional study to examine the association of NAFLD based on abdominal sonographic findings and pulmonary function in 2119 Korean men between the ages of 30 and 75. Forced vital capacity (FVC) and forced expiratory volume in 1 s (FEV(1)) were compared according to the presence of NAFLD. Univariate and multivariate logistic regression analyses were conducted to evaluate the relationship of NAFLD with FVC and FEV(1) as pulmonary function tests. RESULTS: The subjects with NAFLD had lower FVC and FEV(1) than their non-steatotic counterparts, and FVC and FEV(1) gradually decreased according to the grade of hepatic steatosis. After adjusting for age, body mass index, smoking status, blood pressure, fasting plasma glucose, total cholesterol, hypertension, diabetes, triglyceride and high-density lipoprotein cholesterol, the FVC and FEV(1) were found to be inversely associated with the presence of NAFLD. CONCLUSION: NAFLD was independently associated with reduced pulmonary function, and the severity of NAFLD was inversely correlated with pulmonary function.

Benign Uterine Neoplasm as a Cause of Prepubertal Bleeding.

BACKGROUND: Vaginal bleeding in the prepubertal child has several etiologies, including structural anomalies, endocrinologic dysfunction, infection, trauma, foreign body, and hematologic disorders. CASE: An 8-year-old premenarcheal girl presented with vaginal bleeding. On ultrasound, she was found to have an intramural hyperechogenic mass in the left uterine fundus. This was biopsied and showed smooth muscle. She was subsequently started on a GnRH agonist to suppress bleeding and has since been followed with serial ultrasounds. We have 6 years of follow-up imaging showing a presumed adenomyoma versus fibroid that has been stable in size. SUMMARY AND CONCLUSION: We present a novel case of adenomyosis presenting as prepubertal bleeding. Pelvic imaging is prudent to exclude structural etiologies as the cause of prepubertal vaginal bleeding.

Regional and annual patterns in respiratory virus co-infection etiologies and antibiotic prescriptions for pediatric mycoplasma pneumoniae pneumonia.

OBJECTIVE: Mycoplasma pneumoniae (M. pneumoniae) pneumonia is the second-most common cause of community-acquired pneumonia (CAP). This study aimed at investigating into the prevalence of macrolide-resistant M. pneumoniae (MRMP) with respiratory virus co-infection and the antibiotic prescriptions in children with CAP in four provinces in Korea, and to assess the variations in the findings across regions and throughout the year. PATIENTS AND METHODS: This prospective study was conducted in 29 hospitals in Korea between July 2018 and June 2020. Among the enrolled 1,063 children with CAP, all 451 patients with M. pneumoniae underwent PCR assays of M. pneumoniae and respiratory viruses, and the presence of point mutations of residues 2063 and 2064 was evaluated. RESULTS: Gwangju-Honam (88.6%) showed the highest prevalence of MRMP pneumonia, while Daejeon-Chungcheong (71.3%) showed the lowest, although the differences in prevalence were not significant (p=0.074). Co-infection of M. pneumoniae pneumonia and respiratory virus was observed in 206 patients (45.4%), and rhinovirus co-infection (101 children; 22.2%) was the most frequent. The prevalence of MRMP pneumonia with respiratory virus co-infection and the antibiotic prescriptions differed significantly among the four provinces (p < 0.05). The monthly rate of MRMP pneumonia cases among all cases of M. pneumoniae pneumonia and tetracycline or quinolone prescriptions did not differ significantly among the four regions (trend p > 0.05) during the study period. CONCLUSIONS: The prevalence of M. pneumoniae pneumonia with virus co-infection and antibiotic prescriptions could differ according to region, although the MRMP pneumonia rate showed no difference within Korea.

Metabolic syndrome and its association with white blood cell count in children and adolescents in Korea: the 2005 Korean National Health and Nutrition Examination Survey.

BACKGROUND AND AIMS: To estimate the prevalence of metabolic syndrome (MS) and determine its association with white blood cell (WBC) count as a marker of low-grade systemic inflammation in children and adolescents in Korea. METHODS AND RESULTS: We investigated the prevalence of MS and its association with WBC count in 928 children and adolescents. MS was defined as having 3 or more conditions based on the modified criteria of the National Cholesterol Education Program-Adult Treatment Panel III (NCEP-ATP III). The odds ratios (ORs) for MS were also calculated using multivariate logistic regression analysis across WBC count quartiles (Q1, <5200; Q2, 5200-6100; Q3, 6200-7200; and Q4, >or=7300 cells/microL for boys; Q1, <5200; Q2, 5200-6000; Q3, 6100-7000; and Q4, >or=7100 cells/microL for girls). The prevalence of MS in children and adolescents in Korea was 6.7% (8.5% in boys, 4.5% in girls, P<0.001). MS was more prevalent in overweight and obese children and adolescents in both boys and girls. The mean WBC counts continuously increased with each additional component of MS in both boys and girls. The ORs (95% CIs) for MS in each WBC quartile were 1.00, 1.56 (0.43-5.67), 4.47 (1.42-14.07), and 5.25 (1.71-16.07) in boys and 1.00, 1.05 (0.15-7.61), 2.89 (0.55-15.17), and 7.47 (1.61-36.67) in girls after adjusting for age, household income, and residential area. CONCLUSION: In summary, this study shows that a substantial number of children and adolescents in Korea have MS, and elevated WBC count may be a surrogate marker for MS.

Long-term exposure to air pollution and the risk of non-lung cancer: a meta-analysis of observational studies.

AIMS: Several meta-analyses of observational studies report a long-term correlation between air pollution and the risk of cancer, particularly lung carcinoma. The aim of this study was to review and quantify evidence for an association between air pollution and the risk of developing non-lung cancers. METHODS: We searched PubMed, EMBASE, Cochrane Library, and the reference lists of the included studies as well as those recorded in previous meta-analyses conducted before January 2019. A random-effects model was used to derive overall risk estimates per pollutant. RESULTS: A total of 20 studies, including 5 case-control and 15 prospective cohort studies, were used in the final analysis. The risk of developing non-lung cancer was 1.09 (95% confidence interval (CI): 1.01-1.18, I2 = 72.9%) per NO2 increases of 10 µg/m3. There was also a significant association between exposure to PM2.5 and PM10 and the risk of non-lung cancer when the male and female populations were combined (pooled odds ratio/relative risk (OR/RR) = 1.22, 95% CI: 1.11-1.34; I2 = 0.0% and pooled OR/RR = 1.26, 95% CI: 1.05-1.52; I2 = 43.9%, respectively). Regarding the type of cancer, significant harmful effects of PM2.5 were observed for liver cancer populations (pooled OR/RR = 1.21, 95% CI: 1.10-1.32; I2 = 0.0%). Different types of cancer were positively associated with the incidence of non-lung cancer and PM10 in the random-effect meta-regression analysis. CONCLUSIONS: Long-term exposure to air pollutants appears to be associated with an increased risk of non-lung cancer. Care should be taken in interpretation, because the results for specific cancers were restricted.

Correlation between pre-operative brain magnetic resonance angiography findings and intra-operative cerebral oxygen saturation during coronary artery bypass graft surgery.

Coronary artery bypass graft (CABG) patients often have cerebrovascular disease and pre-operative brain magnetic resonance angiography (MRA) frequently reveals cerebral vasculature stenosis. This study was designed to investigate whether pre-operative MRA findings correlated with regional cerebral oxygen saturation (ScO(2)) in 120 patients undergoing on-pump or off-pump CABG. Following MRA examination, patients were divided into six groups of 20 patients each based on MRA findings (no stenosis, mild stenosis or severe stenosis) and procedure (on-pump or off-pump CABG). Mean ScO(2) values over 3 min were determined at seven periods during surgery. Patients with severe cerebrovascular stenosis showed significantly lower ScO(2) than other groups during off-pump CABG. During on-pump CABG, ScO(2) decreased significantly during cardiopulmonary bypass in all groups and was significantly lower in the severe stenosis group. Pre-operative MRA and intra-operative ScO(2) monitoring may help to identify patients at increased risk of brain damage during or following CABG.

An open-label trial of Korean red ginseng as an adjuvant treatment for cognitive impairment in patients with Alzheimer's disease.

BACKGROUND AND PURPOSE: Ginseng is one of the most popular herbs worldwide. Ginseng has various medical applications, and it seems to have significant effects as a cognition-enhancing drug. In this study, we examined the efficacy of Korean red ginseng (KRG) as an adjuvant therapy to conventional anti-dementia medications in patients with Alzheimer's disease. METHODS: The trial was designed as a 12-week randomized study. Sixty-one patients (24 males and 37 females) with Alzheimer's disease were randomly assigned to one of the following treatment groups: low-dose KRG (4.5 g/day, n = 15), high-dose KRG (9 g/day, n = 15) or control (n = 31). The Alzheimer's Disease Assessment Scale (ADAS), Korean version of the Mini-Mental Status Examination (K-MMSE) and Clinical Dementia Rating (CDR) scale were used to assess the change in cognitive and functional performance at the end of the 12-week study period. RESULTS: The patients in the high-dose KRG group showed significant improvement on the ADAS and CDR after 12 weeks of KRG therapy when compared with those in the control group (P = 0.032 and 0.006 respectively). The KRG treatment groups showed improvement from baseline MMSE when compared with the control group (1.42 vs. -0.48), but this improvement was not statistically significant. CONCLUSIONS: KRG showed good efficacy for the treatment of Alzheimer's disease; however, further studies with larger samples of patients and a longer efficacy trial should be conducted to confirm the efficacy of KRG.

Diagnostic value of the matrix metalloproteinase-8 rapid test for detecting microbial invasion of the amniotic cavity.

The purpose of this paper was to compare the MMP-8 PTD Check (MPC) test with other indirect tests for detecting microbial invasion of the amniotic cavity (MIAC). Amniotic fluid (AF) was analyzed in 155 women for white blood cell (WBC) count, glucose concentration, and an MPC test and evaluated for MIAC using cultures for aerobic/anaerobic bacteria and mycoplasmas and polymerase chain reaction (PCR) of chlamydia. The median AF glucose concentration was lower and the median AF WBC count was higher in women with MIAC than in women without MIAC (p < 0.01 and p < 0.001, respectively). Also, the positive rate of the MPC test was higher in women with MIAC than in women without MIAC (p < 0.001). The sensitivities of AF glucose concentration, AF WBC count, and the MPC test for the detection of MIAC were 58.6%, 75.9%, and 86.2%, respectively. The specificities for the detection of MIAC were 76.2%, 80.2%, and 74.6%, respectively. We conclude that the MPC test is a rapid, easily performed, and accurate indirect method for detecting MIAC.

Chemoprotective and adjuvant effects of immunomodulator ginsan in cyclophosphamide-treated normal and tumor bearing mice.

Ginsan is a polysaccharide extracted from Panax ginseng that is known to have multiple immunomodulatory effects. This study evaluates the chemoprotective effect of ginsan on normal mice and the adjuvant effect on tumor bearing mice in combination with cyclophosphamide (CP). Ginsan (100 mg/kg) was injected 24 h before or after a sublethal dose of a CP treatment. The mice pre-treated with ginsan all died within 10 days whereas up to 53 percent of the mice post-treated with ginsan increased survival to day 30 compared with only 10 percent in the CP alone treated group on day 30. The post-treatment of ginsan accelerated the recovery of the bone marrow cells and blood neutrophils by approximately 1.3- and 1.75-fold compared to CP treated control mice at 5 days after CP administration, respectively. These marked differences in activity between the pre- and post-treatment of ginsan with CP was clarified by examining the mRNA expression levels of several cytokines in spleen cells and the self-renewal potential of hematopoietic progenitor cells, CFU-s. The post-treatment with ginsan increased the mRNA expression levels of TNF-alpha, IL-1beta, IL-6, SCF, and GM-CSF with respect to that of the CP alone or ginsan pre-treated group. Similarly, the number of CFU-s was significantly higher in the mice post-treated with ginsan. The inhibition of tumor growth and survival elongation was also observed when ginsan was administered 24 h after the CP treatment. These results show that the post-treatment with ginsan had an immunomodulating and adjuvant effect in combination with CP, which indicates its wide applications in reducing the adverse effects of chemotherapy and improving the general conditions of patients.

Association of alcohol consumption pattern with risk of hypertension in Korean adults based on the 2010-2012 KNHANES.

We examined the association between alcohol-drinking pattern and hypertension in Korean adults. This cross-sectional study included 15,052 participants (7054 men and 7998 women) who were included in the 2010-2012 Korean National Health and Nutrition Examination Survey (KNHANES). We categorized alcohol-drinking patterns into three groups based on the Alcohol Use Disorders Identification Test (AUDIT) score: low-risk (score: 0-7), intermediate-risk (score: 8-14), and high-risk (score: ≥15). Hypertension was defined as systolic blood pressure ≥140 mm Hg, diastolic blood pressure ≥90 mm Hg, or current use of anti-hypertensive medications. In the study population, 25.2% of men and 4.6% of women were high-risk drinkers. Hypertension prevalence was 30.8% in men and 20.6% in women. Of the total population, 13.8% of men and 13.6% of women were using anti-hypertensive drugs. Age-adjusted hypertension prevalence was 30.8, 40.9, and 45.3% in men, and 24.6, 27.0, and 32.3% in women in the low-, intermediate-, and high-risk drinking group, respectively. Compared to the low-risk drinking group, the prevalence ratio (95% confidence interval [CI]) for hypertension was 1.664 (1.4331.933) and 2.070 (1.772-2.418) for men and 1.012 (0.774-1.323) and 1.650 (1.080-2.522) for women in the intermediate- and high-risk drinking group, respectively, after adjusting for age and other confounding factors. In conclusion, our study suggests high-risk drinking appears to be associated with a higher risk of hypertension in men and women.

Three-dimensional quantitative structure-activity relationship study of the cannabimimetic (aminoalkyl)indoles using comparative molecular field analysis.

The present study describes the implementation of comparative molecular field analysis (CoMFA) to develop two 3D-QSAR (quantitative structure-activity relationship) models (CoMFA models 1 and 2) of the cannabimimetic (aminoalkyl)indoles (AAIs) for CB1 cannabinoid receptor binding affinity, based on pKi values measured using radioligand binding assays that displace two different agonist ligands, [3H]CP-55940 and [3H]WIN-55212-2. Both models exhibited a strong correlation between the calculated steric-electrostatic fields and the observed biological activity for the respective training set compounds. In light of the basicity of the morpholine nitrogen in the AAIs, separate CoMFA models were built for the AAIs as unprotonated and protonated species. Comparison of the statistical parameters resulting from these CoMFA models failed to provide unequivocal evidence as to whether the AAIs are protonated or neutral as receptor-bound species. Although the training sets of CoMFA model 1 and CoMFA model 2 differed with respect to composition and to the choice of displacement radioligand in each biological assay, their CoMFA StDevCoeff contour plots reveal similarities in terms of identifying those regions around the AAIs that are important for CB1 cannabinoid receptor binding such as the sterically favored region around the C3 aroyl group and the sterically forbidden region around the indole ring. When the experimental pKi values for the training set compounds to displace the AAI radioligand [3H]WIN-55212-2 were plotted against the pKi values as predicted for the same compounds to displace the cannabinoid radioligand [3H]CP-55940, the correlation was moderately strong (r = 0.73). However, the degree of correlation may have been lowered by the structural differences in the compounds comprising the training sets for CoMFA model 1 and CoMFA model 2. Taken together, the results of this study suggest that the binding site region within the CB1 cannabinoid receptor can accommodate a wide range of structurally diverse cannabimimetic analogues including the AAIs.

Glutathione S-transferase-mediated induction of GC-->AT transitions by halomethanes in Salmonella.

Halomethanes are among the most common mutagenic and carcinogenic disinfection by-products present in the volatile/semivolatile fraction of chlorinated drinking water. Recent studies have demonstrated that the mutagenicity of dichloromethane (CH2Cl2) and bromodichloromethane (BrCHCl2) can be mediated by a theta-class glutathione S-transferase (GSTT1-1). These studies used strain RSJ100 of Salmonella, which is a derivative of the base-substitution strain TA1535 (hisG46, rfa, delta uvrB), into which has been cloned the GSTT1-1 gene from rat. In the present report, we have extended these studies by demonstrating that the mutagenicity of two additional brominated trihalomethanes, bromoform (CHBr3) and chlorodibromomethane (CICHBr2), are also mediated by GSTT1-1 in RSJ100. Using a Tedlar bag vaporization technique, the mutagenic potencies (revertants/ppm) for these two compounds as well as the compounds tested previously rank as follows: CHBr3 approximately CICHBr2 > BrCHCl2 approximately CH2Cl2. To explore the mutational mechanism, we determined the mutation spectra of all four halomethanes at the hisG46 allele by performing colony probe hybridizations of approximately 100 revertants induced by each compound. The majority (96-100%) of the mutations were GC-->AT transitions, and 87-100% of these were at the second position of the CCC/GGG target. In contrast, only 15% of mutants induced by CH2Cl2 were GC-->AT transitions in the absence of the GSTT1-1 gene in strain TA100 (a homologue of TA1535 containing the plasmid pKM101). The ability of GSTT1-1 to mediate the mutagenicity of these di- and trihalomethanes and the induction of almost exclusively GC-->AT transitions by these compounds suggest that these halomethanes are activated by similar pathways in RSJ100, possibly through similar reactive intermediates. The implications of these findings are discussed in relation to previous experimental work on the GST-mediated bioactivation of dihalomethanes, which includes the possible formation of GSH intermediates and/or GSH-DNA adducts.

Meningeal solitary fibrous tumor as an unusual cause of expohthalmos: case report and review of the literature.

OBJECTIVE AND IMPORTANCE: We report an extremely rare case of a patient with meningeal solitary fibrous tumor with orbital involvement presenting as unilateral exophthalmos. This rare tumor should be considered in the differential diagnosis for aggressive dural-based lesions. CLINICAL PRESENTATION: A 54-year-old man presented with a protruded eyeball on the right side and left hemiparesis. Computed tomography and magnetic resonance imaging demonstrated a huge mass, markedly enhanced in and around the right anterior clinoid process, which extended to the orbit and middle cranial fossa. Cerebral angiography revealed a richly vascular tumor fed by branches of both the right external and internal carotid arteries. A presumptive diagnosis of meningioma or hemangiopericytoma was considered. INTERVENTION: The tumor was exposed through an orbitozygomatic approach. At surgery, the tumor was grossly firm to hard and had destroyed the dura, orbital roof, anterior clinoid process, temporal bone, and muscle. Histological analysis revealed that the tumor was composed of spindle-cell proliferation in a collagen-rich background, but it exhibited regional variations. The vascular network demonstrated irregular vascular lumina with a "hemangiopericytoma-like" pattern. Histological features included high cellularity and a high degree of pleomorphism. Immunohistochemical analysis of the tumor demonstrated diffuse positive staining for CD34 and vimentin. The tumor displayed no positive staining for cytokeratin, epithelial membrane antigen, glial fibrillary antigenic protein, S-100 protein, and factor XIII. CONCLUSION: Meningeal solitary fibrous tumor is considered a unique pathological entity. Wider use of immunohistochemical screening should enable analysis of the real incidence of these tumors; larger series and longer follow-up duration will allow conclusions to be drawn regarding treatment and prognosis. Differential diagnosis is discussed and the literature is reviewed.

Signal transduction of eicosanoid CB1 receptor ligands.

The eicosanoid ligand, arachidonylethanolamide (anandamide), interacts with the CB1 cannabinoid receptor in the brain to signal its response. Pharmacophoric points of interaction between this agonist and the receptor have been proposed based upon structure-activity relationship studies of ligand binding to the receptor. Three dimensional quantitative structure-activity relationship (3D-QSAR) models have been constructed based upon the corresponding pharmacophoric points predicted for cannabinoid ligands delta9-tetrahydrocannabinol and 9-nor-9beta-hydroxyhexa-hydrocannabinol. A novel data set has been used to test the statistical validity of these models. Once the ligand interacts with the CB1 receptor, signal transduction occurs via G-proteins of the Gi/o family which are shown to be associated with the receptor. Evidence suggests that the juxtamembrane region of the C-terminal of the CB1 receptor is critical for activation of these G-proteins.