The Toronto IBD Global Endoscopic Reporting [TIGER] Score: A Single, Easy to Use Endoscopic Score for Both Crohn's Disease and Ulcerative Colitis Patients.

BACKGROUND AND AIMS: We constructed the Toronto IBD Global Endoscopic Reporting [TIGER] score for inflammatory bowel disease [IBD]. The aim of our study was to develop and validate the TIGER score against faecal calprotectin [FC], C-reactive protein [CRP], and IBD Disk. METHODS: A cross-sectional study was performed among 113 adult patients (60 Crohn's disease [CD] and 53 ulcerative colitis [UC]). In the development and usability phase, blinded IBD experts reviewed and graded ileocolonoscopy videos. In the validity phase the TIGER score was compared with: [1] the Simple endoscopic Score for CD [SES-CD] and the Mayo endoscopic score in CD and UC, respectively; [2] FC and CRP; and [3] IBD Disk. RESULTS: Inter-observer reliability of the TIGER score per segment between reviewers was excellent: interclass correlation coefficient [ICC] = 0.94 [95% CI: 0.92-0.96]. For CD patients, overall agreement per segment between SES-CD and TIGER was 91% [95% CI: 84-95] with kappa coefficient 0.77 [95% CI: 0.63-0.91]. There was a significant correlation between TIGER and CRP [p <0.0083], and TIGER and FC [p <0.0001]. In addition, there was significant correlation between TIGER and IBD Disk [p <0.0001]. For UC patients, overall agreement per segment between Mayo endoscopic score and TIGER was 84% [95% CI: 74%-90%] and kappa coefficient 0.60 [95% CI: 0.42-0.808]. There was a significant correlation between TIGER and FC [p <0.0001]. There was a significant correlation between TIGER and IBD Disk [p <0.0001]. CONCLUSIONS: The TIGER score is a reliable and simple novel endoscopic score that can be used for both CD and UC patients and captures full endoscopic disease burden.

Anterior hypopituitarism secondary to biopsy-proven IgG4-related hypophysitis in a young man.

IgG4-related disease (IgG4-RD) is an immune-mediated fibro-inflammatory condition which can affect various organs including the pituitary gland. The true annual incidence of this condition remains widely unknown. In addition, it is unclear whether IgG4 antibodies are causative or the end result of a trigger. With no specific biomarkers available, the diagnosis of IgG4-related hypophysitis remains a challenge. Additionally, there is a wide differential diagnosis. We report a case of biopsy-proven IgG4-related hypophysitis in a young man with type 2 diabetes mellitus. Learning points: IgG4-related hypophysitis is part of a spectrum of IgG4-related diseases. Clinical manifestations result from anterior pituitary hormone deficiencies with or without diabetes insipidus, which can be temporary or permanent. A combination of clinical, radiological, serological and histological evidence with careful interpretation is required to make the diagnosis. Tissue biopsy remains the gold standard investigation. Disease monitoring and long-term management of this condition is a challenge as relapses occur frequently.

Association between schizophrenia and an autoimmune bullous skin disease-pemphigus: a population-based large-scale study.

AIMS: Immunological hypotheses have become increasingly prominent suggesting that autoimmunity may be involved in the pathogenesis of schizophrenia. Schizophrenia was found to be associated with a wide range of autoimmune diseases. However, the association between pemphigus and schizophrenia has not been established yet. We aimed to estimate the association between pemphigus and schizophrenia using a large-scale real-life computerised database. METHODS: This study was conducted as a cross-sectional study utilising the database of Clalit Health Services. The proportion of schizophrenia was compared between patients diagnosed with pemphigus and age-, gender- and ethnicity-matched control subjects. Univariate analysis was performed using χ2 and Student's t-test and a multivariate analysis was performed using a logistic regression model. RESULTS: A total of 1985 pemphigus patients and 9874 controls were included in the study. The prevalence of schizophrenia was greater in patients with pemphigus as compared to the control group (2.0% v. 1.3%, respectively; p = 0.019). In a multivariate analysis, pemphigus was significantly associated with schizophrenia (OR, 1.5; 95% CI, 1.1-2.2). The association was more prominent among females, patients older than 60 years, and Jews. CONCLUSIONS: Pemphigus is significantly associated with schizophrenia. Physicians treating patients with pemphigus should be aware of this possible association. Patients with pemphigus should be carefully assessed for comorbid schizophrenia and be treated appropriately.

Probiotics administration following sleeve gastrectomy surgery: a randomized double-blind trial.

BACKGROUND: Probiotics are commonly used after bariatric surgery; however, uncertainty remains regarding their efficacy. Our aim was to compare the effect of probiotics vs placebo on hepatic, inflammatory and clinical outcomes following laparoscopic sleeve gastrectomy (LSG). METHODS: This randomized, double-blind, placebo-controlled, trial of 6-month treatment with probiotics (Bio-25; Supherb) vs placebo and 6 months of additional follow-up was conducted among 100 morbidly obese nonalcoholic fatty liver disease (NAFLD) patients who underwent LSG surgery. The primary outcome was a reduction in liver fat content, measured by abdominal ultrasound, and secondary outcomes were improvement of fibrosis, measured by shear-wave elastography, metabolic and inflammatory parameters, anthropometrics and quality of life (QOL). Fecal samples were collected and analyzed for microbial composition. RESULTS: One hundred patients (60% women, mean age of 41.9±9.8 years and body mass index of 42.3±4.7 kg m-2) were randomized, 80% attended the 6-month visit and 77% completed the 12-month follow-up. Fat content and NAFLD remission rate were similarly reduced in the probiotics and placebo groups at 6 months postsurgery (-0.9±0.5 vs -0.7±0.4 score; P=0.059 and 52.5 vs 40%; P=0.262, respectively) and at 12 months postsurgery. Fibrosis, liver-enzymes, C-reactive protein (CRP), leptin and cytokeratin-18 levels were significantly reduced and QOL significantly improved within groups (P⩽0.014 for all), but not between groups (P⩾0.173 for all) at 6 and 12 months postsurgery. Within-sample microbiota diversity (alpha-diversity) increased at 6-month postsurgery compared with baseline in both study arms (P⩽0.008) and decreased again at 12 months postsurgery compared with 6 months postsurgery (P⩽0.004) but did not reach baseline values. CONCLUSIONS: Probiotics administration does not improve hepatic, inflammatory and clinical outcomes 6- and 12 months post-LSG.

Endoscopic resection of large colorectal adenomas - clinical experience of a tertiary referral centre.

AIM: Colorectal cancer is a leading cause of cancer-related mortality. Adenomatous polyps are typically resected endoscopically to prevent cancer while giant and complex polyps are managed surgically. No criteria clearly define the indications for surgical vs endoscopic resection. Our aim was to evaluate factors associated with the short-term efficacy and safety of endoscopic resection of large (≥ 20 mm) and giant (≥ 40 mm) adenomas. METHOD: Consecutive cases with colonic adenomas larger than 20 mm resected endoscopically were included. Endoscopic, clinical and histological details of polyps were recorded as well as the need for surgical resection. RESULT: A total of 351 resections were included. The average adenoma diameter was 30.34 ± 10.66 mm. Surgery was recommended in 21 (5.98%) cases. In a multivariate analysis for efficacy, two variables were independent risk factors for surgery: adenoma size [OR 1.08 (95% CI: 1.04-1.12)] and caecal location [5.97(1.60-22.33)]. Postpolypectomy complications were documented in 85 (24.2%) cases: bleeding 69 (19.7%), perforations 8(2.3%) and significant discomfort 15(4.3%). Twenty-one patients (6.0%) developed serious complications requiring further hospitalization. In multivariate analysis for safety, independent risk factors for postpolypectomy complications included adenoma size [1.04 (1.06-1.01)], polyp morphology [sessile 2.55 (1.45-4.51), flat 2.40 (1.04-5.52)] and submucosal adrenaline injection [1.87 (1.11-3.20)]. Increments of 1 mm in adenoma diameter beyond 20 mm increased the need for surgery by 8% and the risk of complications by 4%. CONCLUSION: Resection of large or giant adenomas is generally a safe procedure. Although adenoma size and morphology are significant predictors of efficacy and safety, each case should be individually evaluated in a specialist unit for feasibility of endoscopic resection.

Association of Dynamics in Lean and Fat Mass Measures with Mortality in Frail Older Women.

OBJECTIVE: The relationship between body composition and mortality in frail older people is unclear. We used dual-x-ray absorptiometry (DXA) data to examine the association between dynamics in whole-body composition and appendicular (4 limbs) and central (trunk) compartments and all-cause mortality in frail older women. DESIGN: Prospective study with up to 19 years of follow up. SETTING: Community dwelling older (≥65) women. PARTICIPANTS: 876 frail older participants of the Women's Health Initiative Observational Study with a single measure of body composition and 581 participants with two measures. MEASUREMENTS: Frailty was determined using modified Fried's criteria. All-cause mortality hazard was modeled as a function of static (single-occasion) or dynamic changes (difference between two time points) in body composition using Cox regression. RESULTS: Analyses adjusted for age, ethnicity, income, smoking, cardiovascular disease, diabetes, stroke, number of frailty criteria and whole-body lean mass showed progressively decreased rates of mortality in women with higher appendicular fat mass (FM) (P for trend=0.01), higher trunk FM (P for trend=0.03) and higher whole-body FM (P for trend=0.01). The hazard rate ratio for participants with more than a 5% decline in FM between two time points was 1.91; 1.67 and 1.71 for appendicular, trunk and whole-body compartment respectively as compared to women with relatively stable adiposity (p<0.05 for all). Dynamics of more than 5% in lean mass were not associated with mortality. CONCLUSION: Low body fat or a pronounced decline in adiposity is associated with increased risks of mortality in frail older women. These results indicate a need to re-evaluate healthy weight in persons with frailty. .

Indications for episiotomy performance - a cross-sectional survey and review of the literature.

Our objective was to assess the reported reasons for episiotomy performance in Israel and to review the relevant professional literature. Using anonymous questionnaires, a survey was conducted among obstetricians and midwives in four northern Israel hospitals, and the accoucheurs were asked to score their agreement with 13 proposed indications for episiotomy. Overall, 84 doctors and 32 midwives completed the questionnaires. 86.1% of the responders reported performing episiotomy in all or most cases of shoulder dystocia, and more than half reported performing it in most cases of vacuum deliveries, fetal macrosomia and advanced perineal tear in previous delivery. Subjective assessment of perineal characteristics constituted a justified reason for episiotomy for 15.8-43.9% of the accoucheurs. In conclusion, there is a wide variation in reported reasons for episiotomy between the obstetricians, and many of these indications are not congruent with international practice guidelines. Uniform protocols and educational programmes are needed to guide episiotomy practice.

Facial reconstruction after pre maxillary resection in a bilateral cleft lip and palate patient - a case report Technologies for resection and reconstruction of mandibular lesions.

Loss of the premaxilla is a rare event while treating patients with bilateral cleft lip and palate. Its resection is no longer an acceptable method of treatment in modern practice. Nowadays, most cases of premaxillary loss are secondary to treatment and manipulation of the premaxilla, and not due to intentional resection. In the following case presentation we present the treatment of a seven years old boy, presented to our institution after being treated for bilateral cleft lip and palate by resection of the premaxilla. Through a series of operations including bone grafting, distraction of the maxilla, and cartilaginous graft we managed to reconstruct a proper facial habitus, a convex facial profile and nasal projection. Restoring the bony structure of the face is a significant challenge. Due to the complex three dimensional anatomy, the presence of critical structures and the variety and uniqueness of each deficiency it is essential to form the optimal surgical plan and to execute it precisely. Development of computer aided manufacturing (CAD/ CAM - computer assisted design / computer assisted manufacturing) and advances in manufacturing technologies and material science brought a whole array of options and tools for the purpose of planning and performing computer assisted surgery. CAD/CAM technology allow for various application: Manufacturing of a physical anatomical model, Using the 3D model for hardware pre-bending, Manufacturing of cutting jigs and intraoperative fixation templates, Manufacturing of custom made implants. The surgeon may choose which of the application to use in any specific case or combine all of these abilities according to the complexity of the case. Two cases presenting the applications of these technologies will be reviewed.

[Technologies for resection and reconstruction of mandibular lesions].

Restoring the bony structure of the face is a significant challenge. Due to the complex three dimensional anatomy, the presence of critical structures and the variety and uniqueness of each deficiency it is essential to form the optimal surgical plan and to execute it precisely. Development of computer aided manufacturing (CAD/CAM - computer assisted design / computer assisted manufacturing) and advances in manufacturing technologies and material science brought a whole array of options and tools for the purpose of planning and performing computer assisted surgery. CAD / CAM technology allow for various application: Manufacturing of custom made implants. The surgeon may choose which of the application to use in any specific case or combine all of these abilities according to the complexity of the case. Two cases presenting the applications of these technologies will be reviewed.

Morbidity associated with episiotomy in vacuum delivery: a systematic review and meta-analysis.

BACKGROUND: The role of episiotomy in vacuum deliveries is controversial. OBJECTIVES: To perform a meta-analysis of the literature examining this subject. SEARCH STRATEGY: The search was conducted in four databases. SELECTION CRITERIA: Two investigators independently selected original research examining the effects of episiotomy on any neonatal and maternal outcomes during vacuum delivery. DATA COLLECTION AND ANALYSIS: The effect estimates were presented as odds ratios (ORs) with 95% confidence intervals (95% CIs). MAIN RESULTS: Fifteen articles were included, encompassing a total of 350 764 vacuum deliveries. A non-significant relationship was shown between mediolateral episiotomy and obstetric anal sphincter injuries (OASIS) in nulliparous women (OR 0.68, 95% CI 0.43-1.07; six studies), whereas an increased risk was demonstrated in parous women (OR 1.27, 95% CI 1.05-1.53; two reports). A higher risk of OASIS with median episiotomy use was shown in nulliparous (OR 5.11, 95% CI 3.23-8.08; two studies) as well as in parous (OR 89.4, 95% CI 11.8-677.1; one study) women. Lateral episiotomy was related to lower OASIS risk in nullipara (OR 0.59, 95% CI 0.49-0.70; single paper). Mediolateral episiotomy was linked to increased rates of postpartum haemorrhage (OR 1.82, 95% CI 1.16-2.86) and analgesia use (OR 2.10, 95% CI 1.39-3.17; two reports). Overall, the quality of evidence was rated as low to very low. AUTHOR'S CONCLUSIONS: Mediolateral and median episiotomy in parous woman may increase the rate of OASIS at vacuum delivery, whereas lateral episiotomy in nulliparous women could be associated with a decreased risk of OASIS. The suboptimal quality of the available evidence necessitates high-quality well-designed randomised trials. TWEETABLE ABSTRACT: Episiotomy in vacuum delivery does not appear to be of benefit, and might even increase maternal morbidity.

The management of pre-hypertension in primary care: Is it adequate?

BACKGROUND: Pre-hypertension (pHT) is frequently diagnosed in the primary care setting, but its management by primary care physicians (PCPs) is not well characterized. METHODS: All individuals aged 30-45 years who were insured by Clalit Health services in the Tel Aviv district and had their blood pressure (BP) measured from January 2006 to December 2010 were evaluated. Individuals were divided into three groups based on their initial BP value: optimal (< 120/80 mmHg), normal (systolic BP 120-129 or diastolic 80-84 mmHg) and borderline (130-139/85-89 mmHg). Groups were compared regarding clinical and laboratory follow-up performed by their PCP. RESULTS: Of the 20,214 individuals included in the study, 6576 (32.5%) had values in the pHT range. Of these, 2126 (32.3% of those with pHT) had BP values defined as "borderline" and 4450 (67.6% of those with pHT) had BP values defined as "normal". The number of follow-up visits by the PCP and repeat BP measurement were similar in those with "optimal" BP and pHT. A third and fourth BP measurement were recorded more frequently in those with pHT. In those with pHT, there were more recorded BP measurements than in those with borderline BP (3.35 ± 3 vs. 3.23 ± 2.6), but the time from the initial to the second measurement and a record of a third and fourth measurement were the same in the two groups. CONCLUSION: Identification of pHT does not lead to a significant change in follow-up by PCPs, irrespective of BP values in the pHT range.

Elevated alanine aminotransferase independently predicts new onset of depression in employees undergoing health screening examinations.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is the most common cause of elevated alanine aminotransferase (ALT). NAFLD is associated with insulin resistance and hepatic inflammation. Similarly, patients with depression exhibit insulin resistance and increased inflammatory markers. However, no study has shown a clear association between elevated ALT and the development of depression. The aim of the study was to test whether elevated ALT, a surrogate marker for NAFLD, predicts the development of depression. METHOD: The present prospective cohort study investigated 12 180 employed adults referred for health examinations that included fasting blood tests and anthropometric measurements between 2003 and 2010. Exclusion criteria were: baseline minor/major depression, excessive alcohol consumption and other causes for ALT elevation. Depression was evaluated by the eight-item Patient Health Questionnaire (PHQ-8) score. RESULTS: The final cohort included 5984 subjects [69.4% men, aged 45.0 (s.d. = 10.24) years]. The incidence rate of minor and major depression was 3.8% and 1.4%, respectively. Elevated ALT was a significant independent predictor for the occurrence of minor [odds ratio (OR) 2.02, 95% confidence interval (CI) 1.40-2.92] and major (OR 3.132, 95% CI 1.81-5.40) depression after adjusting for age, gender, body mass index, education level, serum levels of lipids, glucose, smoking and physical activity. Adding subjective health and affective state parameters (sleep disturbances, self-rated health, anxiety and burnout) as potential mediators only slightly ameliorated the association. Persistently elevated ALT was associated with the greatest risk for minor or major depression as compared with elevation only at baseline or follow-up (p for trend < 0.001). CONCLUSIONS: Elevated ALT was associated with developing depressive symptoms, thus suggesting that NAFLD may represent an independent modifiable risk factor for depression.

Serum bile acid levels as a predictor for the severity of liver fibrosis in patients with chronic hepatitis C.

Serum bile acids (SBAs) are commonly elevated in cholestatic liver diseases, but it is unclear if SBA levels are also elevated in noncholestatic chronic liver diseases and whether those levels correlate with disease severity. We analysed SBA levels of 135 consecutive patients with chronic hepatitis C virus infection and correlated these levels with the degree of liver fibrosis as determined by liver biopsy. In addition, we assessed the accuracy of SBA levels as a noninvasive predictor for liver fibrosis by its comparison to the patients' FibroTest scores. Two-thirds (90/135 patients, 67%) of the study patients had nonsevere liver fibrosis (Metavir F0-F2), and the others (45/135, 33%) had severe fibrosis or cirrhosis (Metavir F3-F4). The SBA levels were significantly higher in patients with severe fibrosis as compared to nonsevere fibrosis (11.46 ± 10.01 vs 6.37 ± 4.69, P < 0.0001). Furthermore, a receiver operator characteristics curve based on a model that included serum bile acids, age, body mass index, serum AST, glucose and cholesterol levels suggested that this combination reliably predicts the degree of liver fibrosis and is not inferior to the current noninvasive FibroTest score (areas under the curve of 0.837 vs 0.83, respectively, P = 0.87). We conclude that measurement of SBA levels may have a clinical role as a simple noninvasive tool to assess the severity of HCV-induced liver disease. Combined with widely available laboratory parameters, SBA levels can predict disease severity with a high degree of accuracy.

Capsule endoscopy with PILLCAM ESO for detecting esophageal varices: a meta-analysis.

AIM: The aim of the present study was to perform meta-analysis of studies that compare diagnostic capabilities of esophageal capsule endoscopy (ECE) against conventional esophago-gastro-duodenoscopy (EGD) in detecting esophageal varices. METHODS: A literature search is done for studies that compared the performance of ECE and EGD in screening and surveillance of esophageal varices. Data was extracted to estimate the pooled sensitivity, pooled specificity, positive diagnostic ratio, negative diagnostic ratio and diagnostic odds ratio. RESULTS: We included 9 studies and total number of patients was 631. There were 12 capsule failures so data was available for 619 patients. The pooled sensitivity and specificity of CE for detecting esophageal varices were 83% and 85% respectively. The pooled positive likelihood and negative likelihood ratios are 4.09 and 0.25, respectively. Pooled diagnostic odds ratio was 24.92. CONCLUSION: In our meta- analysis PillCam ESO performed well in detecting esophageal varices but it was not comparable to EGD; it can be an acceptable alternative in certain situations but cannot be recommended to replace EGD.

The management of an early-missed abortion after radical trachelectomy--a case report and a review of the literature.

UNLABELLED: Radical trachelectomy (RT) has been reported for almost 20 years. This case report describes and addresses the issue of the clinical management of early-missed abortion in a patient after RT with a cerclage. CASE: A 35-year-old woman who had a RT 2 years ago due to cervical carcinoma stage IB1 presented with a missed abortion of an 8-week gestational age. At the end of the RT, a cerclage suture was inserted in the remaining internal oss of the cervix. The patient went through a cervical dilatation followed by suction curettage guided by ultrasonography without compromising the cerclage. This case report suggests that dilatation and suction curettage without compromising the cervical cerclage is a feasible option in the clinical management of early abortion in a patient after RT.

Gene delivery into prostate cancer cells by holmium laser application.

New approaches to treat prostate cancer (PCA) are utilizing gene therapy and aim to correct the disease at the genetic level. Getting a gene efficiently into the target cell is the subject of much interest. We used a holmium laser for transfecting rat PCA cells with the reporter gene pEGFP. By FACS analysis and fluorescence microscopy, we could demonstrate that cellular delivery of plasmid DNA was possible with high efficiencies up to 41.3%. Therefore, transfection of PCA cells by holmium laser might offer a promising new gene transfer strategy to PCA with minimal invasiveness.

A subset of NSAIDs lower amyloidogenic Abeta42 independently of cyclooxygenase activity.

Epidemiological studies have documented a reduced prevalence of Alzheimer's disease among users of nonsteroidal anti-inflammatory drugs (NSAIDs). It has been proposed that NSAIDs exert their beneficial effects in part by reducing neurotoxic inflammatory responses in the brain, although this mechanism has not been proved. Here we report that the NSAIDs ibuprofen, indomethacin and sulindac sulphide preferentially decrease the highly amyloidogenic Abeta42 peptide (the 42-residue isoform of the amyloid-beta peptide) produced from a variety of cultured cells by as much as 80%. This effect was not seen in all NSAIDs and seems not to be mediated by inhibition of cyclooxygenase (COX) activity, the principal pharmacological target of NSAIDs. Furthermore, short-term administration of ibuprofen to mice that produce mutant beta-amyloid precursor protein (APP) lowered their brain levels of Abeta42. In cultured cells, the decrease in Abeta42 secretion was accompanied by an increase in the Abeta(1-38) isoform, indicating that NSAIDs subtly alter gamma-secretase activity without significantly perturbing other APP processing pathways or Notch cleavage. Our findings suggest that NSAIDs directly affect amyloid pathology in the brain by reducing Abeta42 peptide levels independently of COX activity and that this Abeta42-lowering activity could be optimized to selectively target the pathogenic Abeta42 species.

CT-guided unilateral thalamotomy with macroelectrode mapping for the treatment of Parkinson's disease.

OBJECTIVE: To evaluate the effect of unilateral thalamotomy in patients with Parkinson's disease. METHODS: The junction of the ventralis oralis posterior and ventralis intermedius nuclei targeted under CT-guidance, and confirmed by impedance recording and macrostimulation. RESULTS: At the 6-month assessment the tremor has been completely abolished in 37 patients (82.2%), and reduced in 6 patients (13.3%). The Unified Parkinson's Disease Rating Scale tremor score decreased by 92.5%, rigidity improved by 65.9%. Axial symptoms and bradykinesia showed smaller improvement. The levodopa and anti-cholinergic medication significantly reduced. An improvement in the quality of life measured by the Parkinson's Disease Questionnaire (PDQ-39) has been observed. The dimensions of mobility, activities of daily living, emotional well being, and stigma were significantly (P<0.05) better, other changes were not significant. The single index improved from 47.8+/-7.8 to 28.9+/-6.3. Transient complications noted in 9 patients (20%), mild persistent morbidity observed in 3 patients (6.7%). At the 1, 2 and 3-year follow-up neither contralateral tremor, rigidity, nor bradykinesia progression was statistically significant. CONCLUSIONS: CT-guided thalamotomy with macro-electrode mapping provides a safe, effective and long lasting control of tremor and rigidity, reduces the need for medication, and improves the quality of life.

Physical and functional interactions of Galphaq with Rho and its exchange factors.

Recent reports have shown that several heterotrimeric protein-coupled receptors that signal through Galpha(q) can induce Rho-dependent responses, but the pathways that mediate the interaction between Galpha(q) and Rho have not yet been identified. In this report we present evidence that Galpha(q) expressed in COS-7 cells coprecipitates with the Rho guanine nucleotide exchange factor (GEF) Lbc. Furthermore, Galpha(q) expression enhances Rho-dependent responses. Coexpressed Galpha(q) and Lbc have a synergistic effect on the Rho-dependent rounding of 1321N1 astrocytoma cells. In addition, serum response factor-dependent gene expression, as assessed by the SRE.L reporter gene, is synergistically activated by Galpha(q) and Rho GEFs. The synergistic effect of Galpha(q) on this response is inhibited by C3 exoenzyme and requires phospholipase C activation. Surprisingly, expression of Galpha(q), in contrast to that of Galpha(12) and Galpha(13), does not increase the amount of activated Rho. We also observe that Galpha(q) enhances SRE.L stimulation by activated Rho, indicating that the effect of Galpha(q) occurs downstream of Rho activation. Thus, Galpha(q) interacts physically and/or functionally with Rho GEFs; however this does not appear to lead to or result from increased activation of Rho. We suggest that Galpha(q)-generated signals enhance responses downstream of Rho activation.