Generation of the VESPA response to rapid contrast fluctuations is dominated by striate cortex: evidence from retinotopic mapping.

The VESPA (visual-evoked spread spectrum analysis) method derives an impulse response function of the visual system from scalp electroencephalographic (EEG) data using the controlled modulation of some feature of a visual stimulus. Recent research using VESPA responses to modulations of stimulus contrast has provided new insights into both early visual attention mechanisms and the specificity of visual-processing deficits in schizophrenia. To allow a fuller interpretation of these and future findings, it is necessary to further characterize the VESPA in terms of its underlying cortical generators. To that end, we here examine spatio-temporal variations in the components of the VESPA as a function of stimulus location. We found that the first two VESPA components (C1/P1) each have a posterior dorsal midline focus and reverse in polarity across the horizontal meridian, consistent with retinotopic projections to calcarine cortex (V1) for the stimulus locations tested. Furthermore, the focal scalp topography of the VESPA was strikingly constant across the entire C1-P1 timeframe (50-120 ms) for each stimulus location, with negligible global scalp activity visible at the zero-crossing dividing the two. This indicates a common focal source underpinning both components, which was further supported by a significant correlation between C1 and P1 amplitudes across subjects (r=0.54; p<0.05). These results, along with factors implicit in the method of derivation of the contrast-VESPA, lead us to conclude that these responses are dominated by activity from striate cortex. We discuss the implications of this finding for previous and future research using the VESPA.

'Getting your life back on track after stroke': a Phase II multi-centered, single-blind, randomized, controlled trial of the Stroke Self-Management Program vs. the Stanford Chronic Condition Self-Management Program or standard care in stroke survivors.

BACKGROUND: Self-management is seen as a primary mechanism to support the optimization of care for people with chronic diseases such as symptomatic vascular disease. There are no established and evidence-based stroke-specific chronic disease self-management programs. Our aim is to evaluate whether a stroke-specific program is safe and feasible as part of a Phase II randomized-controlled clinical trial. METHODS: Stroke survivors are recruited from a variety of sources including: hospital stroke services, local paper advertisements, Stroke South Australia newsletter (volunteer peer support organization), Divisions of General Practice, and community service providers across Adelaide, South Australia. Subjects are invited to participate in a multi-center, single-blind, randomized, controlled trial. Eligible participants are randomized to either; * standard care, * standard care plus a six week generic chronic condition self-management group education program, or, * standard care plus an eight week stroke specific self-management education group program. Interventions are conducted after discharge from hospital. Participants are assessed at baseline, immediate post intervention and six months. STUDY OUTCOMES: The primary outcome measures determine study feasibility and safety, measuring, recruitment, participation, compliance and adverse events. Secondary outcomes include: * positive and active engagement in life measured by the Health Education Impact Questionnaire, * improvements in quality of life measured by the Assessment of Quality of Life instrument, * improvements in mood measured by the Irritability, Depression and Anxiety Scale, * health resource utilization measured by a participant held diary and safety. CONCLUSION: The results of this study will determine whether a definitive Phase III efficacy trial is justified.

How useful is an online tool to facilitate guideline implementation? Feasibility study of using eGLIA by stroke clinicians in Australia.

BACKGROUND: The success of guidelines is determined by their use in the real world. The GuideLine Implementability Appraisal (GLIA) tool was developed as a quality-improvement tool to assist guideline developers and guideline users identify potential problems in implementing recommendations. The objective of this study was to assess the feasibility of using the electronic version of GLIA (eGLIA) by implementers of a clinical guideline for acute stroke management in Australia. METHODS: Health professionals who had no previous experience with the eGLIA tool but who are involved in implementing guidelines volunteered for the study. These health professionals were provided background information about the tool and were provided a short training session (<30 min). The participants were asked to consider at least two recommendations from the guideline document. Time spent, numbers of recommendations reviewed and subjective feedback of the process were used for evaluation. RESULTS: 40 participants completed the study, representing nursing and allied health professions from different geographical regions of Australia. The median number of recommendations per participant completed was 2 (range 2-10), taking an average of 47 min (range 15-120 min) to complete or about 22 min per recommendation. Ninety-four per cent of participants agreed or strongly agreed that eGLIA was useful, while 77% indicated they would use the tool again. eGLIA helped participants think systematically about implementation, although only 72% agreed that the tool allowed them to clearly identify potential barriers to implementation. CONCLUSION: This study suggests that eGLIA may be a useful tool which is relatively easy to use for implementers of guidelines. eGLIA enables a detailed, systematic evaluation of guidelines. Further refinement of the tool is recommended to better assist implementers to clearly identify barriers to implementation and therefore facilitate greater implementation. Further work is also warranted to determine the effect of using eGLIA as part of an implementation strategy and if it improves health outcomes.

The clinical impact and cost implication of endoscopic ultrasound on use of endoscopic retrograde cholangiopancreatography in a Canadian university hospital.

BACKGROUND: Endoscopic ultrasound (EUS) is a safe alternative to endoscopic retrograde cholangiopancreatography (ERCP) for diagnostic biliary imaging in choledocholithiasis. Evidence linking a decline in diagnostic ERCP with the introduction of EUS in clinical practice is limited. OBJECTIVE: To assess the clinical impact and cost implications of a new EUS program on diagnostic ERCP at a tertiary referral centre. PATIENTS AND METHODS: A retrospective review was performed of data collected during the first year of EUS at the University of Alberta Hospital (Edmonton, Alberta). Patients were referred for ERCP because of suspicion of choledocholithiasis based on clinical, biochemical and/or radiological parameters. If they were assessed to have an intermediate probability of choledocholithiasis, EUS was performed first. ERCP was performed if EUS suggested choledocholithiasis, whereas patients were clinically followed for six months if their EUS was normal. Cost data were assessed from a third-party payer perspective, and cost savings were expressed in terms of ERCP procedures avoided. RESULTS: Over 12 months, 90 patients (63 female, mean age 58 years) underwent EUS for suspected biliary tract abnormalities. EUS suggested choledocholithiasis in 20 patients (22%), and this was confirmed by ERCP in 17 of the 20 patients. EUS was normal in 69 patients, and none underwent a subsequent ERCP during a six-month follow-up period. One patient had pancreatic cancer and did not undergo ERCP. The sensitivity and specificity of EUS for choledocholithiasis were 100% and 96%, respectively. A total of 440 ERCP procedures were performed over the same 12-month period, suggesting that EUS resulted in a 14% reduction in ERCP procedures (70 of 510). There were no complications of EUS. The cost of 90 EUS procedures was $42,840, compared with $108,854 for 70 ERCP procedures. The cost savings for the first year were $66,014. CONCLUSION: EUS appears to be accurate, safe and cost effective in diagnostic biliary imaging for suspected choledocholithiasis. The impact of EUS is the avoidance of ERCP in selected cases, thereby preventing the risk of complications. Diagnostic ERCP should not be performed in centres and regions with physicians trained in EUS.

Access to stroke care units in Australian public hospitals: facts and temporal progress.

BACKGROUND: There is level I evidence that management of stroke patients in stroke units (SU) improves outcomes (death and institutionalization) by approximately 20%. In Australia, there is uncertainty as to the proportion of incident cases that have access to SU. Recent national and State-based policy initiatives to increase access to SU have been taken. However, objective evidence related to SU implementation progress is lacking. The aims of the study were (i) to determine the number of SU in Australian acute public hospitals in 2004, (ii) to describe hospitals according to national SU policy criteria and (iii) to compare results to the 1999 survey to track progress. METHODS: The method used in the study was a cross-sectional, postal survey technique. The participants were clinical representatives considered appropriate to describe stroke care within survey hospitals. RESULTS: The outcome of the study was presence of a SU according to an accepted definition. Response rate was 261/301 (87%). Sixty-one sites (23%) had either a SU and/or a dedicated stroke team. Fifty sites claimed to have a SU (19%). New South Wales with 23 had the most number of SU. Based on policy criteria, up to 64 sites could have a SU. In 1999, there were 35 public hospitals with a SU. CONCLUSION: Access to SU in Australian public hospitals remains low compared with other countries (Sweden, 70%). Implementation strategies supported by appropriate health policy to improve access are needed.

A novel technique of concurrent esophagoscopy and transgastrostomy gastroscopy to dilate a completely obstructed distal esophageal stricture in a child following fundoplication.

We report a successful dilation of a completely obstructed distal esophageal stricture in a 4-year-old boy with combined immune deficiency syndrome, at 2 and half years after fundoplication and gastrostomy tube insertion. Barium studies and esophagoscopy had revealed complete obstruction of the lower esophagus. Transgastrostomy gastroscopy demonstrated a pinhole lumen through the fundoplication wrap; a guide wire was passed into the esophagus; and the stricture was dilated with Savary dilators. We presumed that the stricture was secondary to chronic esophagitis. The stricture was identified and successfully dilated using a novel technique of concurrent esophagoscopy and transgastrostomy gastroscopy.

A comparison of covert and overt attention as a control option in a steady-state visual evoked potential-based brain computer interface.

EEG data were recorded from occipital scalp regions of subjects who attended to an alternating checkerboard stimulus in one visual field while ignoring a similar stimulus of a different frequency in the opposite visual field. Classification of left/right spatial attention is attempted by extracting steady-state visual evoked potentials (SSVEPs) elicited by the stimuli to assess the potential use of such a spatial selective attention paradigm in a brain computer interface (BCI). Experimental setup and analysis procedure in a previous study in which eye movement is permitted are replicated in order to quantify differences in classification performance using overt and covert attention. Four variations of the basic paradigm, involving both feedback and addition of extra mental load, are studied for comparison. The average accuracy is found to be reduced by approximately 20% in the switch from overt to covert attention when no other specifications of the task are changed.

The representation of "false cognates" in the bilingual lexicon.

The results of repetition priming studies with homographs such as BANK suggest that semantic constraints restrict priming to the specific meaning invoked during the study phase. Cross-language priming studies with "false cognates" (words with similar form but unrelated meanings) suggest that form similarity may be sufficient to support repetition priming, and they do not therefore support this claim. The relevant studies have used language cues (e.g., seeing the word ESTATE in the context of other Italian words) as distinct from semantic cues (e.g., INVERNO-ESTATE) to constrain meaning, however, so that interpretation is correspondingly uncertain. The experiment described in this paper was designed to answer this question: Does sequential exposure to the English word pair MANOR-ESTATE during the study phase facilitate lexical decision to the second of these words during sequential exposure to the Italian word pair INVERNO-ESTATE (i.e., winter-summer) during the test phase of the experiment? In the experiment reported below, interpretation of false cognates was constrained by meaning rather than language, and cross-language repetition priming was eliminated for false cognates. The results suggest that lexical representation in bilinguals is organized along morphological lines rather than by language.

A case of Histoplasma capsulatum causing granulomatous liver disease and Addisonian crisis.

A 56-year-old man with persistently elevated liver enzyme levels, fatigue, lethargy and a 9.0 kg weight loss over six months underwent a percutaneous liver biopsy that demonstrated multiple granulomas. Screening serologies were positive for histoplasmosis, and he was started on itraconazole treatment. He returned to hospital the same night with coffee-ground emesis and in Addisonian crisis requiring parenteral steroids and intensive care unit support. An abdominal computed tomography scan revealed bilaterally enlarged, nonenhancing adrenal glands suggestive of infarcts, presumed secondary to histoplasmosis. Treatment was initiated with amphotericin B, and Histoplasma capsulatum was cultured from his urine and cerebrospinal fluid. A serum immunodiffusion test was also positive for both H and M bands, indicating active infection with Histoplasmosis species. His serum and urine samples were also weakly positive for the antigen. Despite complications of renal failure, pneumonia and congestive heart failure, he recovered with medical therapy and was discharged home to complete a prolonged course of itraconazole therapy. While hepatic granulomas often reflect an occult disease process, the cause may remain undiscovered in 30% to 50% of patients despite exhaustive investigations. H capsulatum is an uncommon cause of granulomatous liver disease, and with its protean clinical presentation, a high index of suspicion is needed to make the diagnosis and avoid the potentially high fatality rate associated with disseminated infection.

Prospective study of biliary strictures to determine the predictors of malignancy.

BACKGROUND: There have been few prospective studies regarding the investigation of biliary strictures, principally because of rapid technological change. The present study was designed to determine the sensitivity of various imaging studies for the detection of biliary strictures. Serum biochemistry and imaging studies were evaluated for their role in distinguishing benign from malignant strictures. METHODS: Thirty-one patients with suspected noncalculus biliary obstruction were enrolled consecutively in the study. A complete biochemical profile, ultrasound, Disida scan and cholangiogram (endoscopic retrograde cholangiopancreatography [ERCP] or percutaneous cholangiogram) were obtained at study entry. Stricture etiology was determined based on cytology, biopsy and/or clinical follow-up at one year. RESULTS: Twenty-nine of 31 patients had biliary strictures, of which 15 were malignant. The mean age of the malignant cohort was 73.9 years versus 53.9 years in the benign cohort (P<0.001). Statistically significant differences between the malignant and benign groups, respectively, were as follows: alanine transaminase 235.2 versus 66.9 U/L (P=0.004), aspartate transaminase 189.8 versus 84.5 U/L (P=0.011), alkaline phosphatase 840.2 versus 361.1 U/L (P=0.002), bilirubin 317.8 versus 22.1 micromol/L (P<0. 001) and bile acids 242.5 versus 73.2 micromol/L (P=0.001). Threshold analysis using receiver operative characteristic (ROC) curves demonstrated that a bilirubin level of 75 micromol/L was most predictive of malignant strictures. Intrahepatic duct dilation was present in 93% of malignant strictures versus 36% of benign strictures (P=0.002). Common hepatic duct dilation was less discriminatory (malignant 13.5 versus benign 9.6 mm; P=0.11). Ultrasound was highly sensitive (93%) in the detection of the primary tumour in the bile duct or pancreas, or in the visualization of nodal or liver metastases. In benign disease, ultrasound failed to detect evidence of intrahepatic or extrahepatic biliary dilation in most cases. Disida scans were not able to distinguish between malignant or benign strictures and could not accurately localize the level of obstruction. The sensitivity of Disida scan for the diagnosis of obstruction was 50%. Cholangiographic characterization of strictures revealed an equal distribution of smooth (eight of 13) and irregular (five of 13) strictures in the malignant group. Ten of 13 benign strictures were characterized as smooth. Malignant strictures were significantly longer than benign ones - 30.3 versus 9.2 mm (P=0.001). Threshold analysis using ROC curves showed that strictures greater than or equal to 14 mm were predictive of malignancy (sensitivity 78%, specificity 75%, log odds ratio 11.23). CONCLUSIONS: A serum bilirubin level of 75 micromol/L or higher, or a stricture length of greater than 14 mm was highly predictive of malignancy in patients with a biliary stricture. Ultrasound was useful in predicting malignant strictures by detecting either intrahepatic duct dilation or by visualizing the tumour (primary or metastases). Strictures with a 'benign' cholangiographic appearance are frequently malignant. Disida scan did not add additional information. ERCP is necessary to diagnose benign strictures, which tend to be less extensive at presentation.

Defining the role of fiberoptic sigmoidoscopy in the investigation of patients presenting with bright red rectal bleeding.

OBJECTIVE: This study was done to determine whether sigmoidoscopy could theoretically constitute sufficient investigation for some patients with bright red rectal bleeding. METHODS: One hundred and forty-three patients undergoing investigative colonoscopy for bright red rectal bleeding and whose source of bleeding was identified were studied. The investigation took place in a large urban hospital over an 11-month period. Data obtained included changes in stool pattern, characteristics of the bleeding, lesions identified, and the distance of the lesion from the anus. RESULTS: In patients younger than 55 yr, all serious lesions except for one malignancy in a patient with massive bleeding lay within 60 cm of the anus and theoretically within reach of the fiberoptic sigmoidoscope. The mixing of red blood with stool was commonly due to distal lesions, especially hemorrhoids. CONCLUSIONS: In young persons with bright red rectal bleeding, fiberoptic sigmoidoscopy may prove to constitute appropriate initial investigation.

Gastric cancer and other endoscopic diagnoses in patients with benign dyspepsia.

BACKGROUND: It has been suggested that endoscopy could be replaced with non-invasive assessment of helicobacter status in the initial work up of young dyspeptic patients without sinister symptoms. AIMS: To determine the incidence of gastro-oesophageal malignancy in young dyspeptic patients. METHODS: The Alberta Endoscopy Project captured clinical and demographic data on all endoscopies performed from April 1993 to February 1996 at four major adult hospitals in Alberta. The endoscopic and histological diagnosis in a subgroup of patients under 45 years of age without alarm symptoms that had undergone gastroscopy was reviewed. In addition, a random list of 200 patients was generated and their medical records reviewed in order to assess the proportion with symptoms suitable for a non-invasive management strategy. RESULTS: Gastroscopy was performed in 7004 patients under 45 years. In 3634 patients (56% female) alarm type symptoms were absent; 78.9% of patients had symptoms amenable to a non-invasive initial approach, giving a corrected sample size of 2867 patients (correction factor 0.789). Three gastric cancers, one case of moderate dysplasia, 10 biopsy proved cases of Barrett's oesophagus, and 19 oesophageal strictures/rings were detected within this sample. The corrected prevalence of gastric cancer in this select population was 1.05 per thousand patients. DISCUSSION: Endoscopy yielded three gastric cancers in this sample of under 45 year old dyspeptic patients without sinister symptoms. While initial non-invasive screening with one-week triple therapy for helicobacter positive individuals is unlikely to have a detrimental outcome the physician is advised to consider endoscopy in patients with persisting, recurrent, or sinister symptoms.

The utility of endoscopy in the management of patients with gastroesophageal reflux symptoms.

OBJECTIVE: The utility of endoscopy in the management of patients with symptoms of gastroesophageal reflux disease (GERD) is unclear. The purpose of this prospective study was to assess the impact of endoscopy on the subsequent management of patients with uncomplicated reflux symptoms. METHODS: A total of 742 patients underwent endoscopy for symptoms of GERD. Endoscopists recorded the therapy before endoscopy, the findings of endoscopy, and the treatment recommendations after endoscopy. RESULTS: There was no difference in pre-endoscopy therapy or grade of esophagitis in subjects undergoing endoscopy for failed therapy versus GERD symptoms alone. After endoscopy, the most common strategy for patients taking omeprazole was to maintain or increase the dose. For those taking an H2 blocker before endoscopy, the most common outcome was to switch the patient to omeprazole, independent of the grade of esophagitis. CONCLUSIONS: Most patients undergoing endoscopy for symptoms of GERD were switched to omeprazole regardless of the endoscopic findings. No esophageal cancer was identified and the incidence of Barrett's esophagus was low. It appears that endoscopy itself did not change the management of patients receiving H2-blocker therapy. A trial of a proton pump inhibitor before endoscopy should be considered.

Cholestatic hepatocellular injury with azathioprine: a case report and review of the mechanisms of hepatotoxicity.

Azathioprine is a drug commonly used for the treatment of inflammatory bowel disease, organ transplantation and various autoimmune diseases. Hepatotoxicity is a rare, but important complication of this drug. The cases reported to date can be grouped into three syndromes: hypersensitivity; idiosyncratic cholestatic reaction; and presumed endothelial cell injury with resultant raised portal pressures, venoocclusive disease or peliosis hepatis. The components of azathioprine, 6-mercaptopurine and the imidazole group, may play different roles in the pathogenesis of hepatotoxicity. The strong association with male sex, and perhaps with human leukocyte antigen type, suggests a genetic predisposition of unknown type. Many of the symptoms of hepatotoxicity, such as nausea, abdominal pain and diarrhea, can be nonspecific and can be confused with a flare-up of inflammatory bowel disease. As well, the subtype resulting in portal hypertension can occur without biochemical abnormalities. A 63-year-old man with Crohn's disease who is presented developed the rare idiosyncratic form of azathioprine hepatotoxicity, but also had a severe disabling steroid myopathy, peripheral neuropathy, resultant deep venous thrombosis and pulmonary embolism related to immobility, and a nosocomial pneumonia. His jaundice and liver enzyme levels improved markedly on withdrawal of the drug, returning to almost normal in five weeks. Treating inflammatory bowel disease effectively while trying to limit iatrogenic disease is a continuous struggle. Understanding the risks of treatment is the first important step. There must be a low threshold for obtaining liver function tests, especially in men, and alertness to the need to discontinue the drug or perform a liver biopsy should patients on azathioprine develop liver biochemical abnormalities, unexplained hepatomegaly or signs of portal hypertension.

Endoscopists' opinions of indications for upper gastrointestinal endoscopy.

OBJECTIVE: To determine whether endoscopists and general internists agreed with the characterization of appropriateness for endoscopy of various clinical scenarios, as previously reported by the RAND Corporation. DESIGN: Mail survey. STUDY SAMPLE: All endoscopists in western Canada and a random sample of general internists who did not perform endoscopy. METHODS: Questionnaires were sent to 179 endoscopists in western Canada who were asked to rate the 53 scenarios for endoscopy on a nine-point scale ranging from most appropriate to most inappropriate. A similar questionnaire was sent to 39 general internists practising in the province of Alberta. RESULTS: Response rate was 72% of endoscopists (n = 128) and 64% of general internists (n = 25). Among the endoscopists, there was agreement with the RAND classification for 32 scenarios. All 18 indications previously thought to be appropriate were considered to be appropriate. However, endoscopists agreed with only six of 16 equivocal and eight of 19 indications considered inappropriate. Discrepancies were reviewed by five experienced endoscopists and most appeared to be related to a concern regarding possible malignancy linked in part with the definition of failure to respond to medical therapy; and to a refusal to request a barium meal before endoscopy. Among general internists, there was agreement with RAND in 26 scenarios. When the appropriateness rankings of endoscopists and general internists were compared, there was agreement in 40 of 53 scenarios. Significant discrepancies in ratings were identified in scenarios in which barium studies were described as being normal, known or not done. CONCLUSIONS: The equivocal and inappropriate ratings developed by the RAND Corporation are not uniformly accepted by the endoscopy community or general internists. Use of the RAND indications for assessing quality assurance can be challenged.

Comparison of the utilization of endoscopy units in selected teaching hospitals across Canada.

There is no information on the number of endoscopic procedures performed at major teaching hospitals across Canada. The directors of endoscopy units at eight teaching hospitals from Halifax to Vancouver volunteered demographic information on the unit at their location. There was a very wide range of endoscopic utilization, with approximately comparable rates of out-patient versus in-patient procedures and of gastroscopies versus colonoscopies, but there was no obvious linking of the ratios of in-patients:out-patients versus total number of designated gastrointestinal beds or total number of hospital beds. Thus, the appropriateness of endoscopic procedures needs to be based on standards of practice and accepted indications. The number of endoscopies performed per endoscopy unit support staff varied widely (from 323.7 to 1065.3 per year), and it would be interesting to learn whether this represents an opportunity for cost-saving in some units.

Esophageal candidiasis in AIDS. Successful therapy with clotrimazole vaginal tablets taken by mouth.

In this paper we describe the results of oral therapy of esophageal candidiasis with clotrimazole vaginal tablets in 25 homosexual men with AIDS, of whom 19 had oral candidiasis and 16 had esophageal symptoms. Therapy with clotrimazole vaginal tablets, 100 mg, taken by mouth cleared the esophageal symptoms, oral candidiasis, and esophageal lesions completely in all 25 men. Clotrimazole vaginal tablets are a useful alternative to other antifungal agents for the treatment of esophageal candidiasis in AIDS patients.