Diagnostic Performance of Coronary Angiography by 64-Row CT

Background: The accuracy of multidetector computed tomographic (CT) angiography involving 64 detectors has not been well established. Methods: We conducted a multicenter study to examine the accuracy of 64-row, 0.5-mm multidetector CT angiography as compared with conventional coronary angiography in patients with suspected coronary artery disease. Nine centers enrolled patients who underwent calcium scoring and multidetector CT angiography before conventional coronary angiography. In 291 patients with calcium scores of 600 or less, segments 1.5 mm or more in diameter were analyzed by means of CT and conventional angiography at independent core laboratories. Stenoses of 50% or more were considered obstructive. The area under the receiver-operating-characteristic curve (AUC) was used to evaluate diagnostic accuracy relative to that of conventional angiography and subsequent revascularization status, whereas disease severity was assessed with the use of the modified Duke Coronary Artery Disease Index. Results: A total of 56% of patients had obstructive coronary artery disease. The patient-based diagnostic accuracy of quantitative CT angiography for detecting or ruling out stenoses of 50% or more according to conventional angiography revealed an AUC of 0.93 (95% confidence interval [CI], 0.90 to 0.96), with a sensitivity of 85% (95% CI, 79 to 90), a specificity of 90% (95% CI, 83 to 94), a positive predictive value of 91% (95% CI, 86 to 95), and a negative predictive value of 83% (95% CI, 75 to 89). CT angiography was similar to conventional angiography in its ability to identify patients who subsequently underwent revascularization: the AUC was 0.84 (95% CI, 0.79 to 0.88) for multidetector CT angiography and 0.82 (95% CI, 0.77 to 0.86) for conventional angiography. A per-vessel analysis of 866 vessels yielded an AUC of 0.91 (95% CI, 0.88 to 0.93). Disease severity ascertained by CT and conventional angiography was well correlated (r=0.81; 95% CI, 0.76 to 0.84). Two patients had important reactions to contrast medium after CT angiography. Conclusions: Multidetector CT angiography accurately identifies the presence and severity of obstructive coronary artery disease and subsequent revascularization in symptomatic patients. The negative and positive predictive values indicate that multidetector CT angiography cannot replace conventional coronary angiography at present. (ClinicalTrials.gov number, NCT00738218.).

Prognostic Value of Dobutamine Stress Echocardiography With Early Injection of Atropine With Versus Without Chronic Beta-Blocker Therapy in Patients With Known or Suspected Coronary Heart Disease

Although a new protocol of dobutamine stress echocardiography with the early injection of atropine (EA-DSE) has been demonstrated to be useful in reducing adverse effects and increasing the number of effective tests and to have similar accuracy for detecting coronary artery disease (CAD) compared with conventional protocols, no data exist regarding its ability to predict long-term events. The aim of this study was to determine the prognostic value of EA-DSE and the effects of the long-term use of beta blockers on it. A retrospective evaluation of 844 patients who underwent EA-DSE for known or suspected CAD was performed; 309 (37%) were receiving beta blockers. During a median follow-up period of 24 months, 102 events (12%) occurred. On univariate analysis, predictors of events were the ejection fraction (p <0.001), male gender (p <0.001), previous myocardial infarction (p <0.001), angiotensin-converting enzyme inhibitor therapy (p = 0.021), calcium channel blocker therapy (p = 0.034), and abnormal results on EA-DSE (p <0.001). On multivariate analysis, the independent predictors of events were male gender (relative risk [RR] 1.78, 95% confidence interval [CI] 1.13 to 2.81, p = 0.013) and abnormal results on EA-DSE (RR 4.45, 95% CI 2.84 to 7.01, p <0.0001). Normal results on EA-DSE with P blockers were associated with a nonsignificant higher incidence of events than normal results on EA-DSE without beta blockers (RR 1.29, 95% CI 0.58 to 2.87, p = 0.54). Abnormal results on EA-DSE with beta blockers had an RR of 4.97 (95% CI 2.79 to 8.87, p <0.001) compared with normal results, while abnormal results on EA-DSE without beta blockers had an RR of 5.96 (95% CI 3.41 to 10.44, p <0.001) for events, with no difference between groups (p = 0.36). In conclusion, the detection of fixed or inducible wall motion abnormalities during EA-DSE was an independent predictor of long-term events in patients with known or suspected CAD. The prognostic value of EA-DSE was not affected by the long-term use of beta blockers. (C) 2008 Elsevier Inc. All rights reserved. (Am J Cardiol 2008;102:1291-1295)

Search for Chronic Beryllium Disease Among Sarcoidosis Patients in Ontario, Canada

Chronic beryllium disease (CBD) is clinically similar to other granulomatous diseases such as sarcoidosis. It is often misdiagnosed if a thorough occupational history is not taken. When appropriate, a beryllium lymphocyte proliferation tests (BeLPT) need to be performed. We aimed to search for CBD among currently diagnosed pulmonary sarcoidosis patients and to identify the occupations and exposures in Ontario leading to CBD. Questionnaire items included work history and details of possible exposure to beryllium. Participants who provided a history of previous work with metals underwent BeLPTs and an ELISPOT on the basis of having a higher pretest probability of CBD. Among 121 sarcoid patients enrolled, 87 (72%) reported no known previous metal dust or fume exposure, while 34 (28%) had metal exposure, including 17 (14%) with beryllium exposure at work or home. However, none of these 34 who underwent testing had positive test results. Self-reported exposure to beryllium or metals was relatively common in these patients with clinical sarcoidosis, but CBD was not confirmed using blood assays in this population.

Imaging and lung cancer

Lung cancer remains the most common cause of cancer-related mortality in Scotland, accounting for 28.9% of all cancer deaths in 2007. Current guidelines recommend assessment of patient fitness and operability by a multidisciplinary team when selecting management options. Two of the most important prognostic markers are the stage of disease and ECOG performance status. In 1996, the International Association for the Study of Lung Cancer (IASLC) launched a worldwide TNM staging project to create international databases that would be used to continue the excellent efforts of Dr. Cliff Mountain, who pioneered this approach to lung cancer staging in 1973. Successive iterations of tumor, nodule, metastasis (TNM) staging for lung cancer have addressed shortcomings identified by the oncology community. Similarly, the IASLC recognized that it is important that further revisions continue to be made to ensure that the international staging system for lung cancer remains fit for its purpose. The last work of the International Staging Committee (ISC) was the conduct of the study that informed the seventh edition of the international staging system for lung cancer, in 2010. This review of image and staging in non small cell lung cancer (NSCLC), includes a summary of the different noninvasive tests currently available for staging non small cell lung cancer.

AT(1) blockade during lactation as a model of chronic nephropathy: mechanisms of renal injury

Suppression of the renin-angiotensin system during lactation causes irreversible renal structural changes. In this study we investigated 1) the time course and the mechanisms underlying the chronic kidney disease caused by administration of the AT(1) receptor blocker losartan during lactation, and 2) whether this untoward effect can be used to engender a new model of chronic kidney disease. Male Munich-Wistar pups were divided into two groups: C, whose mothers were untreated, and L(Lact), whose mothers received oral losartan (250 mg.kg(-1).day(-1)) during the first 20 days after delivery. At 3 mo of life, both nephron number and the glomerular filtration rate were reduced in L(Lact) rats, whereas glomerular pressure was elevated. Unselective proteinuria and decreased expression of the zonula occludens-1 protein were also observed, along with modest glomerulosclerosis, significant interstitial expansion and inflammation, and wide glomerular volume variation, with a stable subpopulation of exceedingly small glomeruli. In addition, the urine osmolality was persistently lower in L(Lact) rats. At 10 mo of age, L(Lact) rats exhibited systemic hypertension, heavy albuminuria, substantial glomerulosclerosis, severe renal interstitial expansion and inflammation, and creatinine retention. Conclusions are that 1) oral losartan during lactation can be used as a simple and easily reproducible model of chronic kidney disease in adult life, associated with low mortality and no arterial hypertension until advanced stages; and 2) the mechanisms involved in the progression of renal injury in this model include glomerular hypertension, glomerular hypertrophy, podocyte injury, and interstitial inflammation.

Surgical removal of small petroclival meningiomas

Treatment of large petroclival meningiomas causing brain stem compression is surgical removal followed by radiotherapy or radiosurgery if the lesion was partially resected. The management of small petroclival meningiomas is, however, controversial. Clinical observation, radiosurgery and surgical removal are the options of treatment. The natural history of these tumours is not well known. Published series of patients treated with radiosurgery are not comparable with surgical series because the latter also includes large size tumours. In this paper we present a series of 18 patients with small petroclival meningiomas (diameter <= 2.8cm) treated with radical surgical removal. Total resection (Simpson`s Grade 1) [43] was possible with minimal morbidity and no mortality. Background. We present a series of small petroclival meningiomas (SPM) treated by radical surgical removal and compare the outcome with other management modalities proposed for these lesions. Methods. Eighteen patients with SPM were surgically treated at our department of neurological surgery. The tumours were classified as small when they had a diameter < 3.0cm. Headaches (n = 12), diplopia (n = 8), facial hypoaesthesia (n = 3) and tinnitus (n = 6) were the most frequent symptoms at presentation. The approaches used were retrosigmoid (n = 14), fronto-orbito-zygomatic (n = 3) and presigmoid (n = 1). The post-operative follow-up ranged from 1 to 110 months (mean 41.8 months). Findings. Radical tumour resection (Simpson`s Grades 1 and 2) was achieved in all patients. There was no major morbidity or mortality related to the surgical procedure. Transient abducent nerve palsy was the only post-operative complication. The pre-operative cranial nerves deficits improved after surgery. Only one patient had persistent diplopia postoperatively. Conclusion. Radical surgical removal of SPM is possible with minimal morbidity and may cure the patient. The effectiveness and outcome of surgery for small petroclival meningiomas should be compared with series treated by radiosurgery.

Mania as the first manifestation of Wilson`s disease

Background: Although mental changes are frequent in Wilson`s disease, severe psychiatric disorders occur uncommonly and usually accompany the neurological picture. There are few reports in the literature of Wilson`s disease patients with typical bipolar affective disorder (BPAD). Case report: The authors report the case of a patient with Wilson`s disease whose initial manifestation was a manic episode followed by depression. Tremor in the upper limbs appeared one year after the onset of symptoms. The diagnosis of Wilson`s disease was established three years after the first symptoms appeared, based on the neuropsychiatric picture, the detection of Kayser-Fleischer rings and the results of diagnostic tests indicating chronic liver disease and copper excess. ATP7B genotyping and magnetic resonance imaging of the brain with proton spectroscopy study were also performed. The patient became asymptomatic two years after starting treatment with penicillamine and remained non-symptomatic controlled during the eight-year follow-up period, without any specific treatment for the BPAD. Conclusions: To our knowledge, this is a singular report of a case of Wilson`s disease in which a manic episode preceded the onset of neurological symptoms. The association between Wilson`s disease and bipolar disorder is discussed.

K/DOQI-recommended intact PTH levels do not prevent low-turnover bone disease in hemodialysis patients

The guidelines proposed by the Kidney Disease Outcomes Quality Initiative (K/DOQI) suggested that intact parathyroid hormone (iPTH) should be maintained in a target range between 150 and 300 pg ml(-1) for patients with stage 5 chronic kidney disease. Our study sought to verify the effectiveness of that range in preventing bone remodeling problems in hemodialysis patients. We measured serum ionized calcium and phosphorus while iPTH was measured by a second-generation assay. Transiliac bone biopsies were performed at the onset of the study and after completing 1 year follow-up. The PTH levels decreased within the target range in about one-fourth of the patients at baseline and at the end of the study. The bone biopsies of two-thirds of the patients were classified as showing low turnover and a one-fourth showed high turnover, the remainder having normal turnover. In the group achieving the target levels of iPTH 88% had low turnover. Intact PTH levels less than 150 pg ml(-1) for identifying low turnover and greater than 300 pg ml(-1) for high turnover presented a positive predictive value of 83 and 62%, respectively. Our study suggests that the iPTH target recommended by the K/DOQI guidelines was associated with a high incidence of low-turnover bone disease, suggesting that other biochemical markers may be required to accurately measure bone-remodeling status in hemodialysis patients.

Limited ecoclinal variation found in Malva parviflora (small-flowered mallow) across the Mediterranean-climatic agricultural region of Western Australia

Malva parviflora L. populations were collected from 24 locations across the Mediterranean-climatic agricultural region of Western Australia and grown in Perth in a common garden experiment. Seventeen morphometric and taxonomic measurements were taken and genetic variation was investigated by performing principal components analysis (PCA). Taxonomic measurements confirmed that all plants used in the study were M. parviflora. Greater variation occurred within populations than between populations. Separation between populations was only evident between northern and southern populations along principal components 2 (PC2), which was due mainly to flowering time. Flowering time and consequently photoperiod were highly correlated with latitude and regression analysis revealed a close relationship (r(2) = 0.6). Additionally, the pollination system of M. parviflora was examined. Plants were able to self-pollinate without the need for external vectors and the pollen ovule ratio (31 +/- 1.3) revealed that M. parviflora is most likely to be an obligate inbreeder with a slight potential for outcrossing. The limited variation of M. parviflora enhances the likelihood of suitable control strategies being effective across a broad area.

The effects of air pollution on hospitalizations for cardiovascular disease in elderly people in Australian and New Zealand cities

OBJECTIVE: The goal of this study was to estimate the associations between outdoor air pollution and cardiovascular hospital admissions for the elderly. DESIGN: Associations were assessed using the case-crossover method for seven cities: Auckland and Christchurch, New Zealand; and Brisbane, Canberra, Melbourne, Perth, and Sydney Australia. Results were combined across cities using a random-effects meta-analysis and stratified for two adult age groups: 15-64 years and >= 65 years of age (elderly). Pollutants considered were nitrogen dioxide, carbon monoxide, daily measures of particulate matter (PM) and ozone. Where multiple pollutant associations were found, a matched case-control analysis was used to identify the most consistent association. RESULTS: In the elderly, all pollutants except 03 were significantly associated with five categories or cardiovascular disease admissions. No associations were found for arrhythmia and stroke. For a 0.9-ppm increase in CO, there were significant increases in elderly hospital admissions for total cardiovascular disease (2.2%), all cardiac disease (2.8%), cardiac failure (6.0%), ischemic heart disease (2.3%), and myocardial infarction (2.9%). There was some heterogeneity between cities, possibly due to differences in humidity and the percentage of elderly people. In matched analyses, CO had the most consistent association. CONCLUSIONS. The results suggest that air pollution arising from common emission sources for CO, NO2, and PM (e.g., motor vehicle exhausts) has significant associations with adult cardiovascular hospital admissions, especially in the elderly, at air pollution concentrations below normal health guidelines. RELEVANCE TO CLINICAL AND PROFESSIONAL PRACTICE: Elderly populations in Australia need to be protected from air pollution arising from outdoor sources to reduce cardiovascular disease.

Overweight and obesity increase the risk of coronary heart disease: A pooled analysis of 30 prospective studies

The importance of overweight as a risk factor for coronary heart disease (CHD) remains unsettled. We estimated the relative risk (RR) for CHD associated with underweight (body mass index, BMI < 20 kg/m2), overweight (25 – 30 kg/m2) and obesity (= 30 kg/m2), compared with normal weight (20 – 25 kg/m2) in a random effects meta-analysis of 30 prospective studies, including 389,239 healthy, predominantly Caucasian persons. We also explored sources of heterogeneity between studies and examined effects of systematic adjustment for confounding and intermediary variables. Pooled age-, sex- and smoking-adjusted RRs (95% confidence interval) for overweight, obesity and underweight compared with normal weight were 1.33 (1.24 – 1.43), 1.69 (1.44 – 1.99) and 1.01 (0.85 – 1.20), respectively. Stratified analyses showed that pooled RRs for BMI were higher for studies with longer follow-up (= vs. < 15 years) and younger populations (< vs. = 60 years). Additional adjustment for blood pressure, cholesterol levels and physical activity decreased the RR per 5 BMI units from 1.28 (1.21 – 1.34) to 1.16 (1.11 – 1.21). We conclude that overweight and obesity are associated with a substantially increased CHD risk in Caucasians, whereas underweight is not. Prevention and reduction of overweight and obesity, therefore, remain of importance for preventing CHD.

Management of Neuroendocrine Tumors: A Meeting of Experts from Latin America

A panel of experts from Latin America convened in Brazil, in May of 2007, for consensus recommendations regarding the management of neuroendocrine tumors ( NETs) of the gastrointestinal tract and pancreas. The recently introduced World Health Organization classification of NETs represents a step forward, but the former classification of carcinoids into foregut, midgut and hindgut is still likely to be useful in the near future. Macroscopic description of the tumor should be followed by light microscopic examination and immunohistochemical staining, whereas other techniques might not be widely available in Latin America. Surgery remains the mainstay of treatment for patients with potentially curable tumors, and adequate selection is paramount in order to optimize treatment results. Regarding systemic therapy, patients with well-differentiated tumors or islet-cell carcinomas may be categorized as having indolent disease, while patients with poorly differentiated, anaplastic, and small-cell carcinomas, or with atypical carcinoids, may be approached initially as having aggressive disease. Somatostatin analogues play a cytostatic role in indolent tumors, and chemotherapy may play a role against other, more aggressive NETs. Obviously, there is an urgent need for novel therapies that are effective against NETs. Copyright (C) 2008 S. Karger AG, Basel

Neurological manifestations and ATP7B mutations in Wilson`s disease

Wilson`s disease (WD) is a rare inborn metabolic error characterized by deficient biliary copper excretion secondary to ATP7B gene mutations. Neurological presentations are variable in respect to both pattern and age of onset; commonly a movement disorder presents in the second or third decade. The aim of this study was to ascertain genotype correlations with distinct neurological manifestations in 41 WD patients in a Brazilian center for WD. A total of 23 distinct mutations were detected, and the frameshift 3402de1C had the highest allelic frequency (31.7%). An association between 3402de1C and dysphagia was detected (p = 0.01) but the limited number of patients is insufficient to allow one to draw conclusions. Both clinical studies analyzing larger cohorts and basic research on ATP7B protein function could potentially shed more light on our understanding of WD. (c) 2007 Elsevier Ltd. All rights reserved.

Association between Parkinson`s disease and glucocerebrosidase mutations in Brazil

Objective: To evaluate the association between parkinsonism and mutations in the glucocerebrosidase gene (GBA) in Brazilian patients. Methods: We searched for three GBA common mutations (N370S, L444P and G377S) in 65 Brazilian patients affected by PD with disease onset before the age of 55 and compared the results to 267 age- and sex-matched controls. Results: GBA mutations were detected at a significantly higher frequency among Parkinson`s disease patients (2/65 = 3%), when compared to the control group (0/267): P = 0.0379. Conclusion: These results provide further evidence for GBA mutations being a possible hereditary risk factor for PD. (C) 2007 Elsevier Ltd. All rights reserved.

Sex, Clinical Symptoms, and Angiographic Findings in Patients With Diabetes Mellitus and Coronary Artery Disease (from the Bypass Angioplasty Revascularization Investigation [BARI] 2 Diabetes Trial)

Previous studies have reported differences in presenting symptoms and angiographic characteristics between women and men undergoing evaluation for suspected coronary artery disease (CAD). We examined the relation between symptoms and extent of CAD in patients with type 2 diabetes mellitus and known CAD enrolled in the Bypass Angioplasty Revascularization Investigation 2 Diabetes (BARI 2D) trial. Of 1,775 patients (533 women, 30%, and 1,242 men, 70%), women were more likely than men to have angina (65% vs 56%, p < 0.001) or an atypical angina/anginal equivalent (71% vs 58%, p < 0.001). More women reported unstable angina (17% vs 13%, p = 0.047) or were in a higher Canadian Cardiology Society class compared to men (Canadian Cardiology Society classes II to IV 78% vs 68%, p = 0.002). Fewer women than men had no symptoms (14% vs 22%, p < 0.001). Women had a lower mean myocardial jeopardy index (42.5 +/- 24.3 vs 47.9 +/- 24.3, p < 0.001), smaller number of total significant lesions (2.3 +/- 17 1.7 vs 2.7 +/- 1.8, p < 0.001), and fewer jeopardized left ventricular regions (p < 0.001 for distribution) or long-term occlusions (29% vs 42%, p < 0.001). After adjustment for relevant covariates, the odds of having CAD symptoms were still higher in women than men (odds ratio for angina 1.31, 95% confidence interval 1.02 to 1.69; odds ratio for atypical angina 1.52, 95% confidence interval 1.17 to 1.96). In conclusion, in a high-risk group of patients with known CAD and diabetes mellitus, women were more symptomatic than men but had less obstructive CAD. These data suggest that factors other than epicardial CAD severity influence symptom presentation in women in this population. (C) 2011 Elsevier Inc. All rights reserved. (Am J Cardiol 2011;107:980-985)