Effects of insect host chemical secretions on the entomopathogenic nematode Steinernema carpocapsae.

Given the threat presented by parasites and pathogens, insects employ various defences to protect themselves against infection, including chemical secretions. The red flour beetle Tribolium castaneum releases a secretion containing the benzoquinones methyl-1,4-benzoquinone (MBQ) and ethyl-1,4-benzoquinone (EBQ) into the environment. These compounds have known antimicrobial effects; however, their role in defence against macroparasites is not known. Entomopathogenic nematodes, such as Steinernema carpocapsae, present a serious threat to insects, with successful infection leading to death. Thus, quinone-containing secretions may also aid in host defence. We tested how exposure to the individual components of this quinone secretion, as well as a mix at naturally-occurring proportions, affected the survival and thrashing behaviour of S. carpocapsae, as well as their virulence to a model host (Galleria mellonella). Exposure to high concentrations of MBQ and EBQ, as well as the quinone mix, significantly increased nematode death but did not consistently reduce thrashing, which would otherwise be expected given their toxicity. Rather, quinones may act as a host cue to S. carpocapsae by triggering increased activity. We found that exposure to quinones for 24 or 72 hours did not reduce nematode virulence, and surviving nematodes remained infective after non-lethal exposure. Our results indicate that quinone secretions likely serve as a defence against multiple infection threats by reducing S. carpocapsae survival, but further research is required to contextualize their roles by testing against other nematodes, as well as other helminths using insects as hosts.

Wastewater-based epidemiology in hazard forecasting and early-warning systems for global health risks.

With the advent of the SARS-CoV-2 pandemic, Wastewater-Based Epidemiology (WBE) has been applied to track community infection in cities worldwide and has proven succesful as an early warning system for identification of hotspots and changingprevalence of infections (both symptomatic and asymptomatic) at a city or sub-city level. Wastewater is only one of environmental compartments that requires consideration. In this manuscript, we have critically evaluated the knowledge-base and preparedness for building early warning systems in a rapidly urbanising world, with particular attention to Africa, which experiences rapid population growth and urbanisation. We have proposed a Digital Urban Environment Fingerprinting Platform (DUEF) - a new approach in hazard forecasting and early-warning systems for global health risks and an extension to the existing concept of smart cities. The urban environment (especially wastewater) contains a complex mixture of substances including toxic chemicals, infectious biological agents and human excretion products. DUEF assumes that these specific endo- and exogenous residues, anonymously pooled by communities' wastewater, are indicative of community-wide exposure and the resulting effects. DUEF postulates that the measurement of the substances continuously and anonymously pooled by the receiving environment (sewage, surface water, soils and air), can provide near real-time dynamic information about the quantity and type of physical, biological or chemical stressors to which the surveyed systems are exposed, and can create a risk profile on the potential effects of these exposures. Successful development and utilisation of a DUEF globally requires a tiered approach including: Stage I: network building, capacity building, stakeholder engagement as well as a conceptual model, followed by Stage II: DUEF development, Stage III: implementation, and Stage IV: management and utilization. We have identified four key pillars required for the establishment of a DUEF framework: (1) Environmental fingerprints, (2) Socioeconomic fingerprints, (3) Statistics and modelling and (4) Information systems. This manuscript critically evaluates the current knowledge base within each pillar and provides recommendations for further developments with an aim of laying grounds for successful development of global DUEF platforms.

Age, pathology and CA-125 are prognostic factors for survival in patients with brain metastases from gynaecological tumours.

BACKGROUND AND PURPOSE: Brain metastases originating from gynaecological tumours are a rare phenomenon, but have an increasing incidence due to better targeted therapies. This study aimed to identify factors that predict survival in these patients, which can be used in creating a robust prognostic tool for shared decision making. MATERIALS AND METHODS: We identified a consecutive cohort of 73 patients treated for gynaecological brain metastases in two tertiary institutions. Baseline demographics, pathology and serum CA-125 were included in a multivariable Cox proportional hazards model. RESULTS: Median overall survival in our cohort was 14.4 months, with a one-year survival of 56.4% and a two-year survival of 39.1%. Thirty-eight patients (52.1%) had ovarian carcinoma as the primary malignancy. The following factors were significantly associated with survival: age (HR 1.05 per year), CA-125 (HR 1.02 par 50 U/ml), and uterine and vulvar primary tumours (when compared to ovarian carcinoma, with HRs 3.07 and 8.70). A post-hoc analysis with primary tumour site reclassified into ovary versus non-ovary showed a HR of 0.50 for ovarian primary tumour type. CONCLUSION: We have found that age, pathology and CA-125 are prognostic factors for survival in patients with brain metastases from gynaecological tumours. Our findings may provide a foundation for future development of prediction models, for the benefit of both patients and physicians.

Brain cancer survival in Canada 1996-2008: effects of sociodemographic characteristics.

Background: Literature suggests that factors such as rural residence and low socioeconomic status (ses) might contribute to disparities in survival for Canadian cancer patients because of inequities in access to care. However, evidence specific to brain cancer is limited. The present research estimates the effects of rural or urban residence and ses on survival for Canadian patients diagnosed with brain cancer. Methods: Adults diagnosed with primary malignant brain tumours during 1996-2008 were identified through the Canadian Cancer Registry. Brain tumours were classified using International Classification of Diseases for Oncology (3rd edition) site and histology codes. Hazard ratios (hrs) and 95% confidence intervals (cis) were estimated using Cox proportional hazards models. Events were restricted to individuals whose underlying cause of death was cancer-related. Postal codes were used to match patient records with Statistics Canada data for rural or urban residence and neighbourhood income as a surrogate measure of ses. Results: Of 25,700 patients included in the analysis, 78% died during the study period, 21% lived in rural areas, and 19% were in the lowest income group. A modest variation in survival by rural compared with urban residence was observed for patients with glioblastoma (first 5 weeks after diagnosis hr: 0.86; 95% ci: 0.79 to 0.99) and oligoastrocytoma (first 3 years after diagnosis hr: 1.41; 95% ci: 1.03 to 1.93). Small effects of low compared with high income were seen for patients with glioblastoma (first 1.5 years after diagnosis hr: 1.15; 95% ci: 1.08 to 1.22) and diffuse astrocytoma (first 6 months after diagnosis hr: 1.17; 95% ci: 1.00 to 1.36). Conclusions: Our analysis did not yield evidence of strong effects of rural compared with urban residence or ses strata on survival in brain cancer. However, some variation in survival for patients with specific histologies warrants further research into the mechanisms by which rural or urban residence and income stratum influences survival.

Depression and survival of glioma patients: A systematic review and meta-analysis.

INTRODUCTION: There is currently a lack of a well-formed consensus regarding the effects of depression on the survival of glioma patients. A more thorough understanding of such effects may better highlight the importance of recognizing depressive symptoms in this patient population and guide treatment plans in the future. OBJECTIVE: The aim of this meta-analysis was to study the effect of depression on glioma patients' survival. METHODS: A meta-analysis was conducted according to the PRISMA guidelines. PubMed, Embase, and Cochrane databases were searched for studies that reported depression and survival among glioma patients through 11/06/2016. Both random-effects (RE) and fixed-effect (FE) models were used to compare survival outcomes in glioma patients with and without depression. RESULTS: Out of 619 identified articles, six were selected for the meta-analysis. Using RE model, the various measures for survival outcomes displayed worsened outcomes for both high and low-grade glioma patients with depression compared to those without depression. For binary survival outcomes, the overall pooled risk ratio for survival was 0.70 (95% CI: 0.47, 1.04; 6 studies; I2 = 54.9%, P-heterogeneity = 0.05) for high grade gliomas (HGG) and 0.28 (95% CI: 0.04, 1.78; I2 = 0%, P-heterogeneity = 1.00; one study) for low grade gliomas (LGG) was. A sub-group analysis in the HGG group by depression timing (pre- versus post-operative) revealed no differences between depression and survival outcomes (P-interaction = 0.47). For continuous survival outcomes, no statistically significant difference was found among the high and low-grade glioma groups (P-interaction = 0.31). The standardized mean difference (SMD) in survival outcomes was -0.56 months (95%CI: -1.13, 0.02; 4 studies, I2 = 89.4%, P-heterogeneity < 0.01) for HGG and -1.69 months (95%CI: -3.26, -0.13; one study; I2 = 0%, P-heterogeneity = 1.00) for LGG. In patients with HGG, the pooled HR of death also showed a borderline significant increased risk of death among depressive patients (HR 1.42, 95% CI: 1.00, 2.01). Results using the FE model were not materially different. CONCLUSIONS: Depression was associated with significantly worsened survival regardless of time of diagnosis, especially among patients with high-grade glioma.

Adipose tissue: a new target for electroporation-enhanced DNA vaccines.

DNA vaccines delivered using electroporation (EP) have had clinical success, but these EP methods generally utilize invasive needle electrodes. Here, we demonstrate the delivery and immunogenicity of a DNA vaccine into subcutaneous adipose tissue cells using noninvasive EP. Using finite element analysis, we predicted that plate electrodes, when oriented properly, could effectively concentrate the electric field within adipose tissue. In practice, these electrodes generated widespread gene expression persisting for at least 60 days in vivo within interscapular subcutaneous fat pads of guinea pigs. We then applied this adipose-EP protocol to deliver a DNA vaccine coding for an influenza antigen into guinea pigs. The resulting host immune responses elicited were of a similar magnitude to those achieved by skin delivery with EP. The onset of the humoral immune response was more rapid when the DNA dose was spread over multiple injection sites, and increasing the voltage of the EP device increased the magnitude of the immune response. This study supports further development of EP protocols delivering gene-based therapies to subcutaneous fat.

Innovation in neurosurgery: less than IDEAL? A systematic review.

BACKGROUND: Surgical innovation is different from the introduction of novel pharmaceuticals. To help address this, in 2009 the IDEAL Collaboration (Idea, Development, Exploration, Assessment, Long-term follow-up) introduced the five-stage framework for surgical innovation. To evaluate the framework feasibility for novel neurosurgical procedure introduction, two innovative surgical procedures were examined: the endoscopic endonasal approach for skull base meningiomas (EEMS) and the WovenEndobridge (WEB device) for endovascular treatment of intracranial aneurysms. METHODS: The published literature on EEMS and WEB devices was systematically reviewed. Identified studies were classified according to the IDEAL framework stage. Next, studies were evaluated for possible categorization according to the IDEAL framework. RESULTS: Five hundred seventy-six papers describing EEMS were identified of which 26 papers were included. No prospective studies were identified, and no studies reported on ethical approval or patient informed consent for the innovative procedure. Therefore, no clinical studies could be categorized according to the IDEAL Framework. For WEB devices, 6229 articles were screened of which 21 were included. In contrast to EEMS, two studies were categorized as 2a and two as 2b. CONCLUSION: The results of this systematic review demonstrate that both EEMS and WEB devices were not introduced according to the (later developed in the case of EEMS) IDEAL framework. Elements of the framework such as informed consent, ethical approval, and rigorous outcomes reporting are important and could serve to improve the quality of neurosurgical research. Alternative study designs and the use of big data could be useful modifications of the IDEAL framework for innovation in neurosurgery.

Ischemic stroke after radiation therapy for pituitary adenomas: a systematic review.

Radiation therapy is widely used for the treatment of residual and recurrent pituitary adenomas and proved to effectively control tumor growth. However, it is suggested that this treatment might result in an increased risk of ischemic stroke. This review aims to evaluate the radiotherapy-related risk of stroke in pituitary adenoma patients. PubMed and Embase databases were systematically searched for current literature on ischemic stroke risk after radiotherapy in pituitary adenoma, in accordance with the PRISMA statement. Two authors independently selected eligible studies and extracted data. The New Castle Ottawa-scale was used for quality assessment. Out of 264 publications, 11 studies were selected, including 4394 irradiated patients. Incidence of ischemic stroke ranged from 0 to 11.6% (mean 6.7%). While one large, long term follow-up study showed a threefold increased risk of stroke after radiation therapy, another nationwide study of high quality found no significant difference in stroke risk after irradiation. Four studies, which applied stereotactic radiosurgery (SRS) or Gamma-knife surgery (GKS), found no ischemic strokes. Included studies described different radiation techniques and regimens and different lengths of follow-up. In conclusion, complications of cerebral ischemia after radiotherapy for pituitary adenoma are infrequently reported. Moreover, after correction for several confounders, no significant difference in ischemic stroke rate between irradiated and non-irradiated patients could be identified.

A systematic review with meta-analysis of survival, quality of life and cost-effectiveness of home parenteral nutrition in patients with inoperable malignant bowel obstruction.

BACKGROUND AND AIMS: Inoperable bowel obstruction is the most common and judicious indication for long term parenteral nutrition in patients with palliative malignancy. Considerable uncertainty exists about the survival length, quality of life (QOL) and associated health economics of home parenteral nutrition (HPN) for this patient group. METHODS: A systematic review was carried out for survival length and QOL of adult patients treated with HPN due to malignancy causing inoperable bowel obstruction in the palliative phase. Whenever possible, individual patient data were extracted to allow meta-analyses. Health economic evaluation was undertaken to calculate cost and incremental cost effectiveness ratio (ICER). RESULTS: Twelve studies involving 437 patients, met the inclusion criteria. Meta-analyses of extracted survival length data, representing the largest published cohort of HPN patients with palliative malignancy and inoperable bowel obstruction (n = 244 patients), revealed a mean survival of 116 days, median 83 days, with 45% and 24% still alive at 3 and 6 months, and only 2% survival at one year. Limited evidence suggests QOL deteriorated before death in a highly symptomatic group. The ICER is £176,587 per quality adjusted life year. CONCLUSIONS: This is the first health economic evaluation and systematic review of survival and QOL for patients with inoperable bowel obstruction receiving HPN during the palliative phase of malignancy. Meta-analyses reveal a short survival and health economic analysis demonstrates high associated costs. This information can be used by clinicians to inform and guide selection of patients in this cohort for HPN treatment.

Impressions of defensive medical practice and medical litigation among South African neurosurgeons.

From a litigation perspective, neurosurgery is considered a 'super high-risk' field, and this has been associated with rapidly increasing malpractice cover costs. In 2013 the annual Medical Protection Society fee for cover was R250,900. We wished to determine whether high malpractice cover was influencing how neurosurgeons managed patients. A 40-question online survey asking questions on defensive medicine was distributed to determine perceptions around liability risk and whether these influenced how patients were managed. Eighty-four per cent of respondents agreed that a medicolegal crisis existed, and over half (53.8%) had been sued for malpractice during their career. Altering practice behaviour to minimise the risk of a lawsuit is common. The increasing number of legal claims against respondents in this survey has resulted in most neurosurgeons practising defensive medicine. Arguably this will result in increased healthcare costs, inferior patient care and decreased access to skilled surgeons.

Chronic lung disease and HIV infection are risk factors for recurrent tuberculosis in a low-incidence setting.

SETTING: Programmatic data from the United States on tuberculosis (TB) recurrence are limited. OBJECTIVES: To determine the TB recurrence rate and to determine if chronic lung disease (CLD) and human immunodeficiency virus (HIV) infection are risk factors for recurrence in this population. DESIGN: Nested case-control study among TB cases reported to the Tennessee Department of Health between 1 January 2000 and 31 December 2006. Time at risk for recurrence was through 31 December 2007. Multiple imputation accounted for missing data. RESULTS: Of 1431 TB cases, 20 cases recurred (1.4%, 95%CI 0.9-2.1). Median time at risk for recurrence was 4.5 years (interquartile range 2.7-6.1). Initial and recurrent Mycobacterium tuberculosis isolates were available for genotyping for 15 patients; 12 were consistent with relapse (0.8%, 95%CI 0.4-1.5) and three with re-infection (0.2%, 95%CI 0.04-0.6). HIV infection (OR 5.01, P = 0.04) and CLD (OR 5.28, P = 0.03) were independently associated with recurrent TB, after adjusting for a disease risk score. HIV infection was a risk factor for TB re-infection (P < 0.001). CONCLUSIONS: In this low-incidence US population, the TB recurrence rate was low, but CLD and HIV were independent risk factors for recurrence. HIV infection was also a risk factor for TB re-infection.

Combination therapy with amlodipine/valsartan in essential hypertension: a 52-week, randomised, open-label, extension study.

BACKGROUND: A majority of hypertensive patients require > or = 2 agents to achieve target blood pressure (BP). METHODS: This 52-week, multicentre, open-label, randomised extension trial to a previously reported double-blind, placebo-controlled study evaluated the safety and efficacy of amlodipine/valsartan (Aml/Val) combination. Patients who successfully completed the core study without serious drug-related adverse events (AEs) and mean sitting systolic BP (MSSBP)/mean sitting diastolic BP (MSDBP) < or = 150/95 mmHg were eligible to enter the extension and be treated with Aml/Val 2.5/80 or 5/80 mg. After 4 weeks of treatment, patients underwent force-titration to receive 5/160 mg (low dose) or 10/160 mg (high dose) for 48 weeks. Addition of hydrochlorothiazide (HCTZ) 12.5 mg was permitted if BP was > or = 140/90 mmHg at Week 8 or later. Patients could be down-titrated to the prior lower combination dose with or without HCTZ if an intolerable AE occurred. Safety evaluations included monitoring of AEs. Efficacy variables were change from baseline in MSDBP (primary) and MSSBP (secondary). RESULTS: Of 1246 patients randomised, 1075 (86.3%) completed the extension study. At week 52 end-point, change in MSSBP/MSDBP from core study baseline was -22.1/-17.2 mmHg for low-dose regimen and -22.8/-18.1 mmHg for high-dose regimen. For both regimens, reductions in BP were sustained over 52 weeks and mean BP maintained below approximately 135/85 mmHg at all visits. Frequent AEs in the low- and high-dose regimens were peripheral oedema (9.7% and 17.1% respectively), nasopharyngitis (8.1% and 7.2%), and dizziness (5.2% and 7.0%). Incidence of serious AEs was 3.7% with low dose and 4.1% with high dose. CONCLUSION: The combination of Aml/Val with the optional addition of HCTZ produced clinically significant and persistent reductions in BP over 52 weeks with a favourable tolerability profile.

Environmental stress-corrosion cracking of fiberglass: lessons learned from failures in the chemical industry.

Fiberglass reinforced plastic (FRP) composite materials are often used to construct tanks, piping, scrubbers, beams, grating, and other components for use in corrosive environments. While FRP typically offers superior and cost effective corrosion resistance relative to other construction materials, the glass fibers traditionally used to provide the structural strength of the FRP can be susceptible to attack by the corrosive environment. The structural integrity of traditional FRP components in corrosive environments is usually dependent on the integrity of a corrosion-resistant barrier, such as a resin-rich layer containing corrosion resistant glass fibers. Without adequate protection, FRP components can fail under loads well below their design by an environmental stress-corrosion cracking (ESCC) mechanism when simultaneously exposed to mechanical stress and a corrosive chemical environment. Failure of these components can result in significant releases of hazardous substances into plants and the environment. In this paper, we present two case studies where fiberglass components failed due to ESCC at small chemical manufacturing facilities. As is often typical, the small chemical manufacturing facilities relied largely on FRP component suppliers to determine materials appropriate for the specific process environment and to repair damaged in-service components. We discuss the lessons learned from these incidents and precautions companies should take when interfacing with suppliers and other parties during the specification, design, construction, and repair of FRP components in order to prevent similar failures and chemical releases from occurring in the future.

Evaporative tunnel cooling of dairy cows in the southeast. I: effect on body temperature and respiration rate.

The techniques used to mitigate the effects of heat stress on lactating dairy cows are often overwhelmed in the southeastern United States, where elevated heat and humidity often persist for extended periods. A model free-stall barn located at the North Mississippi Branch Experiment Station in Holly Springs was used to evaluate the potential of tunnel ventilation with evaporative cooling to alleviate heat stress in lactating dairy cows. Two studies were conducted using 2 groups of 10 lactating Holsteins housed in the tunnel barn (inside) and 2 groups of matched herdmates housed in an adjacent covered free-stall barn (outside), which was cooled by fans and sprinklers during 2001 or by shade and fans alone in 2003. Peak daytime temperatures inside were 5.2 +/- 0.18 degrees C below that outside in 2001 and 3.1 +/- 0.20 degrees C lower in 2003. Although evaporative cooling increased humidity by 22%, cows housed in the tunnel barn received 84% less exposure to moderate heat stress (temperature-humidity index > 80) in both years. Cooling cows with evaporative tunnel ventilation reduced respiration rates by 15.5 +/- 0.56 breaths/min and rectal temperatures by 0.6 +/- 0.02 degrees C compared with shade and fans alone in 2003. Cooling cows with evaporative tunnel ventilation reduced respiration rates by 13.1 +/- 0.78 breaths/min and rectal temperatures by 0.4 +/- 0.03 degrees C compared with fans and sprinklers in 2001. Thus, tunnel ventilation cooling dramatically reduced the exposure to heat stress and improved the comfort of lactating dairy cows when compared with traditional cooling technologies under the conditions present in the southeastern United States.

Evaporative tunnel cooling of dairy cows in the southeast. II: impact on lactation performance.

Heat stress has a dramatic impact on the dairy industry, reducing production and profitability throughout the southeastern United States. In many regions, management techniques can be used to mitigate the effects of heat stress, but available cooling technologies are often overwhelmed by the conditions of chronic heat stress present in southeastern United States. Although combining tunnel ventilation and evaporative cooling (evaporative tunnel cooling) seems to provide superior cooling for dairy cows, there is a dearth of reports on the impact of this technology on milk production. A model evaporative tunnel cooling facility in northern Mississippi was studied using 2 groups of 10 lactating Holstein cows housed in the tunnel barn and 2 groups of 10 matched herdmates housed in an adjacent naturally ventilated free-stall barn. Two 10-wk trials were performed in 2 yr beginning June 25, 2001, and May 26, 2003, in which cows housed outside were cooled by traditional fans and shade alone (2003) or with sprinklers (2001). In both years, the use of evaporative tunnel cooling decreased exposure to conditions of moderate heat stress by 84%. Cows cooled by evaporative tunnel ventilation increased feed intake by 12 and 11% over cows housed outside in 2001 and 2003, respectively. Evaporative tunnel cooling had no effect on milk composition, but increased milk yield over the 10-wk trial by 2.6 +/- 0.27 and 2.8 +/- 0.19 kg/cow per day in 2001 and 2003, respectively. In addition, somatic cell count was decreased 27 to 49% by evaporative tunnel cooling. Thus, under the range of environmental conditions present, evaporative tunnel cooling reliably reduced exposure to conditions of heat stress and improved milk production of lactating dairy cows during the summer season.

Cat allergen peptide immunotherapy reduces CD4(+) T cell responses to cat allergen but does not alter suppression by CD4(+) CD25(+) T cells: a double-blind placebo-controlled study.

BACKGROUND: We have previously described both modification of allergen immunotherapy using peptide fragments, and reduced regulation of allergen stimulated T cells by CD4(+) CD25(+) T cells from allergic donors when compared with nonallergic controls. It has been suggested that allergen immunotherapy induces regulatory T cell activity: we hypothesized that allergen peptide immunotherapy might increase suppressive activity of CD4(+) CD25(+) T cells. OBJECTIVE: To examine cat allergen-stimulated CD4 T cell responses and their suppression by CD4(+) CD25(+) T cells before and after cat allergen peptide immunotherapy in a double-blind placebo-controlled study. METHODS: Peripheral blood was obtained and stored before and after peptide immunotherapy or placebo treatment. CD4(+) and CD4(+) CD25(+) were then isolated by immunomagnetic beads and cultured with allergen in vitro. RESULTS: Comparing cells from blood taken before with that after peptide immunotherapy there was a significant reduction in both proliferation and IL-13 production by allergen-stimulated CD4+ T cells, whereas no change was seen after placebo. CD4(+) CD25(+) T cells suppressed both proliferation and IL-13 production by CD4(+) CD25(-) T cells before and after therapy but peptide therapy was not associated with any change in suppressive activity of these cells. CONCLUSION: Allergen peptide immunotherapy alters T cell response to allergen through mechanisms other than changes in CD4(+) CD25(+) T cell suppression.

LY293558, a novel AMPA/GluR5 antagonist, is efficacious and well-tolerated in acute migraine.

Glutamatergic hyperactivity is implicated migraine pathogenesis. Also, LY293558, an alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)/kainate (KA) receptor antagonist, is effective in preclinical models of migraine. We therefore tested LY293558 in acute migraine. We conducted a randomized, triple-blind, parallel-group, double-dummy, multicentre trial of 1.2 mg/kg intravenous (IV) LY293558, 6 mg subcutaneous (SC) sumatriptan, or placebo in the treatment of acute migraine. The primary efficacy variable was the headache response rate, i.e. headache score improvement from moderate/severe at baseline to mild/none at 2 h. Of 45 enrolled patients, 44 patients (20M:24F; mean age +/- SD = 40 +/- 9 years) completed the study. Response rates were 69% for LY293558 (P = 0.017 vs. placebo), 86% for sumatriptan (P < 0.01 vs. placebo) and 25% for placebo. LY293558 and sumatriptan were superior to placebo (P < 0.01 for all comparisons) on all other measures of improvement in pain and migraine associated symptoms. Fifteen percent of patients who took LY293558 reported adverse events (AEs) (n = 2; one mild, one severe). Fifty-three percent of patients who took sumatriptan (n = 8; seven mild, one moderate) and 31% of those who received placebo reported AEs (n = 5; four mild, one severe). The efficacy and safety results of LY293558 in this small migraine proof of concept trial, together with supportive preclinical data, provide evidence for a potential role of nonvasoactive AMPA/KA antagonists in treating migraine. Larger trials are needed to further test the hypothesis.

Establishing principles for migraine management in primary care.

Published guidelines for the management of migraine in primary care were evaluated by an international advisory board of headache specialists, to establish evidence-based principles of migraine management that could be recommended for international use. Twelve principles of migraine management were identified, covering screening, diagnosis, management and treatments: Almost all headaches are benign/primary and can be managed by all practising clinicians. Use questions/a questionnaire to assess the impact on daily living and everyday activities, for diagnostic screening and to aid management decisions. Share migraine management between the clinician and the patient. Provide individualised care for migraine and encourage patients to manage their migraine. Follow up patients, preferably with migraine calendars or diaries. Regularly re-evaluate the success of therapy using specific outcome measures and monitor the use of acute and prophylactic medications regularly. Adapt migraine management to changes that occur in the illness and its presentation over the years. Provide acute medication to all migraine patients and recommend it is taken at the appropriate time, during the attack. Provide rescue medication/symptomatic treatment for when the initial therapy fails. Offer to prescribe prophylactic medications, as well as lifestyle changes, to patients who have four or more migraine attacks per month or who are resistant to acute medications. Consider concurrent co-morbidities in the choice of appropriate prophylactic medication. Work with the patient to achieve comfort with mutually agreed upon treatment and ensure that it is practical for their lifestyle and headache presentation. Using these principles, practising clinicians can screen and diagnose their headache patients effectively and manage their migraine patients over the long-term natural history of the migraine process. In this way, the majority of migraine patients can be well treated in primary care, ensuring a structured and individualised approach to headache management, and conserving valuable healthcare resources.

CT appearance of some colonic villous tumors.

OBJECTIVE: A review was made of the CT studies and pathology reports of four patients with surgically resected colonic villous adenomatous tumors, two of whom had focal carcinomatous invasion. CONCLUSION: Two patients had villous tumors with IV contrast-enhancing convolutional gyral patterns. The other two patients had tumor masses that showed oral contrast medium collecting in surface interstices, analogous to findings with barium enemas. One of the latter also had an unusual cluster of mesenteric vessels adjacent to the lesion.