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This pilot study explores the possibility of predicting post-concussion symptom recovery at one week post-injury using only objective diffusion tensor imaging (DTI) data inputs to a novel artificial intelligence (AI) system composed of Genetic Fuzzy Trees (GFT). Forty-three adolescents age 11 to 16 years with either mild traumatic brain injury or traumatic orthopedic injury were enrolled on presentation to the emergency department. Participants received a DTI scan three days post-injury, and their symptoms were assessed by the Post-Concussion Symptom Scale (PCSS) at 6 h and one week post-injury. The GFT system was trained using one-week total PCSS scores, 48 volumetric magnetic resonance imaging inputs, and 192 DTI inputs per participant over 225 training runs. Each training run contained a randomly selected 80% of the total sample followed by a 20% validation run. Over a different randomly selected sample distribution, GFT was also compared with six common classification methods. The cascading GFT structure controlled an effectively infinite solution space that classified participants as recovered or not recovered significantly better than chance. It demonstrated 100% and 62% classification accuracy in training and validation, respectively, better than any of the six comparison methods. Recovery sensitivity and specificity were 59% and 65% in the GFT validation set, respectively. These results provide initial evidence for the effectiveness of a GFT system to make clinical predictions of trauma symptom recovery using objective brain measures. Although clinical and research applications will necessitate additional optimization of the system, these results highlight the future promise of AI in acute care.

The goals of the current study were to determine whether topological organization of brain structural networks is altered in youth with bipolar disorder, whether such alterations predict treatment outcomes, and whether they are normalized by treatment. Youth with bipolar disorder were randomized to double-blind treatment with quetiapine or lithium and assessed weekly. High-resolution MRI images were collected from children and adolescents with bipolar disorder who were experiencing a mixed or manic episode (n = 100) and healthy youth (n = 63). Brain networks were constructed based on the similarity of morphological features across regions and analyzed using graph theory approaches. We tested for pretreatment anatomical differences between bipolar and healthy youth and for changes in neuroanatomic network metrics following treatment in the youth with bipolar disorder. Youth with bipolar disorder showed significantly increased clustering coefficient (Cp) (p = 0.009) and characteristic path length (Lp) (p = 0.04) at baseline, and altered nodal centralities in insula, inferior frontal gyrus, and supplementary motor area. Cp, Lp, and nodal centrality of the insula exhibited normalization in patients following treatment. Changes in these neuroanatomic parameters were correlated with improvement in manic symptoms but did not differ between the two drug therapies. Baseline structural network matrices significantly differentiated medication responders and non-responders with 80% accuracy. These findings demonstrate that both global and nodal structural network features are altered in early course bipolar disorder, and that pretreatment alterations in neuroanatomic features predicted treatment outcome and were reduced by treatment. Similar connectome normalization with lithium and quetiapine suggests that the connectome changes are a downstream effect of both therapies that is related to their clinical efficacy.

OBJECTIVES: Altered activity in the ventrolateral prefrontal and anterior cingulate cortices, as well as subcortical and amygdala projection sites, were previously reported during a first manic episode in youth with bipolar disorder and observed to be associated with treatment response. To extend these findings, we investigated functional connectivity among these regions in first-episode manic participants who remitted after eight weeks of treatment compared to those that did not. METHODS: Forty-two participants with bipolar disorder (60% female) during their first manic episode were recruited and received eight weeks of treatment. Twenty-one remitted following treatment. Participants completed fMRI scans, at baseline and following eight weeks of treatment, while performing a continuous performance task with emotional and neutral distractors. A healthy comparison group (n=41) received fMRI evaluations at the same intervals. Differences in functional connectivity of the amygdala and caudate with the rostral anterior cingulate and ventrolateral prefrontal cortices at baseline (and changes in functional connectivity following treatment) were modeled between groups. RESULTS: At baseline, non-remitters showed an increase in positive connectivity between right anterior cingulate and caudate and a loss of negative connectivity between right anterior cingulate and amygdala, compared to healthy participants. Individuals who remitted following treatment showed an increase in negative connectivity between amygdala and left anterior cingulate eight weeks following treatment. CONCLUSIONS: Results provide evidence of alterations in anterior cingulate-amygdala and caudate functional connectivity in bipolar disorder non-remitters during a first manic episode and changes in anterior cingulate functional connectivity associated with remission suggesting targets to predict treatment response. Registered at ClinicalTrials.Gov; Functional and Neurochemical Brain Changes in First-episode Bipolar Mania. NCT00609193. URL: https://clinicaltrials.gov/ct2/show/NCT00609193?term=strakowski&rank=1

Children of individuals with bipolar disorder (bipolar offspring) are at increased risk for developing mood disorders, but strategies to predict mood episodes are unavailable. In this study, we used support vector machine (SVM) to characterize the potential of proton magnetic resonance spectroscopy (1H-MRS) in predicting the first mood episode in youth bipolar offspring. From a longitudinal neuroimaging study, 19 at-risk youth who developed their first mood episode (converters), and 19 without mood episodes during follow-up (non-converters) were selected and matched for age, sex and follow-up time. Baseline 1H-MRS data were obtained from anterior cingulate cortex (ACC) and bilateral ventrolateral prefrontal cortex (VLPFC). Glutamate (Glu), myo-inositol (mI), choline (Cho), N-acetyl aspartate (NAA), and phosphocreatine plus creatine (PCr + Cr) levels were calculated. SVM with a linear kernel was adopted to classify converters and non-converters based on their baseline metabolites. SVM allowed the significant classification of converters and non-converters across all regions for Cho (accuracy = 76.0%), but not for other metabolites. Considering all metabolites within each region, SVM allowed the significant classification of converters and non-converters for left VLPFC (accuracy = 76.5%), but not for right VLPFC or ACC. The combined mI, PCr + Cr, and Cho from left VLPFC achieved the highest accuracy differentiating converters from non-converters (79.0%). Our findings from this exploratory study suggested that 1H-MRS levels of mI, Cho, and PCr + Cr from left VLPFC might be useful to predict the development of first mood episode in youth bipolar offspring using machine learning. Future studies that prospectively examine and validate these metabolites as predictors of mood episodes in high-risk individuals are necessary.

Over 2.3 million people in the United States live with bipolar disorder. Sixty percent of those with a bipolar disorder diagnosis attempt suicide at least once in their lifetime, and up to 19% die by suicide. However, the neurobiology of suicide attempts in bipolar disorder remains unclear. Here, we studied the neuroanatomical basis for suicide attempt history in bipolar disorder by measuring gray matter volumes (GMV) to identify differences in brain-volumes in 121 participants with bipolar disorder type I, and healthy participants (n=40). The bipolar group consisted of individuals with suicide attempt history (n=23) and no suicide attempt history (n=58). All participants completed behavioral/diagnostic assessments and MRI measures of GMV. We focused on a predefined frontolimbic circuitry in bipolar disorder versus (vs.) healthy to first identify diagnostic GMV markers and to specifically identify markers for suicide attempt history. We found reduced GMV markers for bipolar diagnosis (i.e., bipolarHighlightsSuicide is a major health problem especially in bipolar disorder but the neurobiological basis for suicide attempts remains obscure. We identified an anterior cingulate and dorsolateral prefrontal cortical volume correlate for suicide attempt history and suicidal ideation and thereby demonstrates a convergent brain marker for suicidal behaviors.

Functional magnetic resonance imaging (fMRI) and magnetic resonance spectroscopy (MRS) studies provide an exciting opportunity to understand the neural substrates that underlie the pathophysiology of bipolar disorder. This chapter reviews fMRI and MRS meta-analyses from the past 10 years to examine whether meta-analytic results differ from those otherwise expected on the basis of individual studies considered in isolation. Across different meta-analytic studies, and predominantly consistent with extant fMRI hypotheses, the most replicated findings are an overactivity of amygdala, especially during emotional processing, and underactivity of right ventrolateral prefrontal cortex during emotional or cognitive processing in bipolar disorder. These functional abnormalities appear to present during mania or depression, but not during euthymia, suggesting they are related to mood state, symptom severity, or both. Additionally, they appear to be rather specific to bipolar disorder, as opposed to major depressive disorder or schizophrenia. Recent prospective studies also suggest that clinical improvement associates with normalization of functional abnormalities or functional connectivity between prefrontal cortex and amygdala. MRS meta-analyses, although more limited than fMRI, suggest elevated glutamate in prefrontal cortex and decreased N-acetylaspartate in the basal ganglia and hippocampus. Additional studies employing multimodal imaging or longitudinal designs could help to advance the understanding of these neurofunctional and neurochemical brain abnormalities and to develop better preventive and therapeutic strategies for this condition.

OBJECTIVE To examine effects of participating in collegiate football on neural health several years after retirement. We hypothesized that relative cortical thinning and loss of white matter integrity would be observed in former players. DESIGN Former NCAA Division I football players were compared with demographically similar track-and-field athletes with regard to cortical thickness and white matter integrity. SETTING Participants participated in MRI scans at the Center for Imaging Research at the University of Cincinnati. PARTICIPANTS Eleven former football players and 10 demographically similar track-and-field athletes. MAIN OUTCOME MEASURES Normalized cortical thickness was compared between groups using 2-tailed Student t test. As a secondary analysis, Spearman correlation coefficient was calculated between cortical thickness and number of concussions. Fractional anisotropy for regions-of-interest placed in frontal white matter tracts and internal capsule were compared between groups using 2-tailed Student t test. RESULTS Football players showed significantly lower cortical thickness within portions of both the frontal and temporal cortex. Affected frontal regions included left frontal pole and right superior frontal gyrus. Affected temporal regions included portions of the superior temporal gyrus, left inferior temporal gyrus, and right middle and superior temporal gyri. Cortical thickness inversely correlated with number of reported concussions over most of these regions. In addition, fractional anisotropy was lower in the right internal capsule of former football players, relative to controls. CONCLUSIONS These findings suggest that at least some consequences of high-level collegiate football play persist even after the cessation of regular head blows. Longer-term studies are warranted to examine potential cognitive and functional implications of sustained cortical atrophy.

Lateral and medial epicondylitis are common pathologic conditions and can be debilitating problems for athletes. Lateral epicondylitis occurs much more commonly than medial epicondylitis but both can create significant and persistent symptoms that limit performance. Nonoperative management is the mainstay of treatment for both conditions with more invasive treatments, including surgical intervention, reserved for recalcitrant cases. Both pathological entities can be operatively managed by using either percutaneous, formal open, or arthroscopic surgical techniques.

Objectives The objective of this clinical trial was to evaluate the long-term effect of endothelin receptor antagonism with bosentan on the morbidity and mortality of patients with severe chronic heart failure. Background Endothelin may play a role in heart failure, but short-term clinical trials with endothelin receptor antagonists have reported disappointing results. Long-term trials are lacking. Methods In 2 identical double-blind trials, we randomly assigned 1,613 patients with New York Heart Association functional class IIIb to IV heart failure and an ejection fraction Results Bosentan did not influence clinical status at 9 months in either trial (p = 0.928 and p = 0.263). In addition, 321 patients in the placebo group and 312 patients in the bosentan group died or were hospitalized for heart failure (hazard ratio [HR]: 1.01; 95% confidence interval [CI]: 0.86 to 1.18; p = 0.90). The bosentan group experienced fluid retention within the first 2 to 4 weeks, as evidenced by increased peripheral edema, weight gain, decreases in hemoglobin, and an increased risk of hospitalization for heart failure, despite intensification of background diuretics. During follow-up, 173 patients died in the placebo group and 160 patients died in the bosentan group (HR: 0.94; 95% CI: 0.75 to 1.16). About 10% of the bosentan group showed meaningful increases in hepatic transaminases, but none had acute or chronic liver failure. Conclusions Bosentan did not improve the clinical course or natural history of patients with severe chronic heart failure and but caused early and important fluid retention.

Background Clinical remission is widely accepted as the primary target outcome for juvenile idiopathic arthritis (JIA). PR-COIN is a quality improvement collaborative that serves as a sample of pediatric rheumatology centers in North America. By measuring disease activity in practice using the ACR provisional criteria for Clinical Inactive Disease (CID), variation in patient outcomes has been previously observed between centers. Objectives The objective of this study was to evaluate differences in patient-level factors that may be driving center-level variation in JIA outcomes. Methods This study used cross-sectional data provided by PR-COIN that was collected by PR-COIN centers from March 2015 to May 2016. For each patient, sociodemographic, clinical, patient-reported, disease activity, and medication variables were extracted from the most recent encounter. Patients with disease duration less than 9 months were excluded. Patients were grouped by CID status (inactive vs active disease) and then compared using descriptive statistics, chi-square for categorical variables, and independent t-tests for continuous variables. Missing data were excluded with each analysis. Analyses were performed using R software. Results There were 2751 patients eligible for analysis from 14 centers, with 33 to 394 patients per center. We identified 1249 patients with inactive disease (47%) and 1428 patients with active disease (53%). Patients with inactive disease were younger (12 vs 13 years), more likely to have persistent oligoarticular subtype (33% vs 23%), and less likely to have enthesitis related arthritis (9% vs 14%). Patients with active disease had higher patient-reported measures of global assessment of disease activity, pain, and functional disability, as well as disease activity measures per definition. More medication usage was observed in patients with active disease compared to inactive disease across multiple categories, including both non-biologic DMARDs (45% vs. 32%) and biologic DMARDs (48% vs 35%). Conclusion This study demonstrates differences in sociodemographic, clinical, and medication factors between patients with inactive and active JIA. Further analysis is needed to adjust center-level measures of JIA disease activity using the observed differences in patient case-mix. By using population data to identify predictors of inactive disease in JIA, there is potential to develop and implement targeted clinical interventions to directly impact care and improve outcomes. Disclosure of Interests: Emily A. Smitherman: None declared, Bin Huang: None declared, Ronald Laxer Consultant for: Eli Lilly Canada, Alexion, Sanofi, C. April Bingham: None declared, Cagri Yildirim-Toruner: None declared, Beth Gottlieb: None declared, Jennifer E. Weiss: None declared, Tzielan Lee: None declared, Sheetal Vora: None declared, Jon (Sandy) Burnham: None declared, Julia G. Harris: None declared, Judyann C. Olson: None declared, Mileka Gilbert: None declared, Michelle Batthish Speakers bureau: Novartis, Abbvie, Michael Shishov: None declared, Dustin Fleck: None declared, Esi Morgan: None declared

We examined the effects of lisdexamfetamine (LDX) treatment on ventral prefrontal cortex (VPFC) and striatal brain activation in binge eating disorder (BED). We hypothesized that participants with BED have an abnormal brain response to palatable food cues, and that VPFC and striatal regions would respond to such cues after LDX treatment. Twenty women with moderate to severe BED consented to a 12-week, open-label trial of LDX with fMRI before and after treatment. Twenty obese women without BED served as healthy controls and received one fMRI. LDX was started at 30 mg/d with a target of 70 mg/d at week 12. At baseline, women with BED showed greater activation in ventrolateral prefrontal cortex (VLPFC), striatum, and globus pallidus to food pictures and brain activation to food pictures predicted clinical outcome at 12 weeks. After 12 weeks of LDX treatment, BED women showed significant reductions in globus pallidus activation. Reductions in ventromedial prefrontal cortex (VMPFC) and thalamus activation specifically correlated with binge eating and obsessive-compulsive symptom reductions, respectively. Results suggest that BED is characterized by an abnormally large VPFC-subcortical brain response to palatable foods that LDX treatment helps modify. Moreover, VPFC-subcortical activation at baseline is a potential biomarker of LDX response.

1. Dustin E. Fleck, MD* 2. Mark F. Hoeltzel, MD* 1. *Division of Pediatric Rheumatology, Department of Pediatrics, University of Michigan, Ann Arbor, MI * ADHD: : attention-deficit/hyperactivity disorder ANA: : antinuclear antibody POTS: : postural tachycardia syndrome Primary care clinicians are challenged to evaluate an array of different hand and foot color changes in kids, as treatment may range from reassurance of a benign, self-limited condition to further diagnostic evaluation and treatment with vasodilator pharmacotherapy. The most common and well-known causes of these color changes are Raynaud phenomenon, acrocyanosis, and the more rare but serious erythromelalgia. Clinicians should be aware of the clinical presentation, symptoms, etiologic origins, diagnostic evaluation, treatment, and potential complications of Raynaud phenomenon, acrocyanosis, and erythromelalgia in children. After completing this article, readers should be able to: 1. Identify the various causes of hand and foot color change in children and adolescents. 2. Recognize the differences in signs and symptoms of acrocyanosis, erythromelalgia, and Raynaud phenomenon. 3. Recognize complications associated with acrocyanosis, erythromelalgia, and Raynaud phenomenon. 4. Describe current treatments for acrocyanosis, erythromelalgia, and Raynaud phenomenon. ### Clinical Presentation Acrocyanosis is a clinically benign process that is known to cause alarm in patients and their parents. Acrocyanosis typically presents as symmetrical blue and/or purple discoloration in the peripheral extremities, usually either the hands or the feet (Figs 1, 2, 3, 4). In infants, acrocyanosis also includes the perioral area but not the lips or tongue, where central cyanosis becomes a concern. It is often seen after bathing, after feeding, or in a cool environment. It is evanescent and benign. The bluish discoloration in acrocyanosis is often asymptomatic, without clear demarcation of color change. Acrocyanosis episodes can be either precipitated or exacerbated by external factors, such as cold temperatures. Acrocyanosis may also be a process secondary to an underlying systemic disease or a side effect of certain medications. Figure 1. Teenage …

Pathologic changes to the biceps tendon including subluxation are frequently encountered in patients with subscapularis tears. Operatively managing these combined lesions can be difficult depending on the status of the subscapularis tendon and the degree of biceps medialization. The presented technique is an effective and relatively simple method that simultaneously and efficiently provides for secure tenodesis of the biceps and fixation of subscapularis tendon detachment.

Early treatment with ACE inhibitors of even moderate heart failure is clinically beneficial, even though haemodynamic measurements cannot adequately quantitate such improvement. Neurohumoral assessment is, however, supposed to be more accurate. In 55 patients with moderate heart failure (ejection fraction < or = 35%), we investigated the dose-dependent effects of ACE inhibition with quinapril taken orally (2.5, 5 or 10 mg b.i.d.) following a placebo-controlled, parallel design protocol over 12 weeks. Plasma components of the renin angiotensin system, catecholamines and ANF were measured together with haemodynamics both at rest and during exercise. Before ACE inhibitor treatment, median PRA, Ang I and II and catecholamines were normal, while ANF was increased. All these parameters, including ACE activity, rose during exercise. Chronic inhibition of ACE activity was dose-dependent and the maximal fall in Ang II occurred with quinapril 20 mg.day-1. Humoral changes appeared more assessible than haemodynamic alterations even though many of these changes were reasonably correlated. The effects of chronic ACE inhibition on circulating neurohumoral components in patients with moderate heart failure are small and dose-dependent. Since humoral changes are related to haemodynamics they should account for the clinical benefit. Appropriately high doses of ACE inhibitors should be chosen for treatment of heart failure.

Objectives Individualized treatment for bipolar disorder based on neuroimaging treatment targets remains elusive. To address this shortcoming, we developed a linguistic machine learning system based on a cascading genetic fuzzy tree (GFT) design called the LITHium Intelligent Agent (LITHIA). Using multiple objectively defined functional magnetic resonance imaging (fMRI) and proton magnetic resonance spectroscopy (1H-MRS) inputs, we tested whether LITHIA could accurately predict the lithium response in participants with first-episode bipolar mania. Methods We identified 20 subjects with first-episode bipolar mania who received an adequate trial of lithium over 8 weeks and both fMRI and 1H-MRS scans at baseline pre-treatment. We trained LITHIA using 18 1H-MRS and 90 fMRI inputs over four training runs to classify treatment response and predict symptom reductions. Each training run contained a randomly selected 80% of the total sample and was followed by a 20% validation run. Over a different randomly selected distribution of the sample, we then compared LITHIA to eight common classification methods. Results LITHIA demonstrated nearly perfect classification accuracy and was able to predict post-treatment symptom reductions at 8 weeks with at least 88% accuracy in training and 80% accuracy in validation. Moreover, LITHIA exceeded the predictive capacity of the eight comparator methods and showed little tendency towards overfitting. Conclusions The results provided proof-of-concept that a novel GFT is capable of providing control to a multidimensional bioinformatics problem—namely, prediction of the lithium response—in a pilot data set. Future work on this, and similar machine learning systems, could help assign psychiatric treatments more efficiently, thereby optimizing outcomes and limiting unnecessary treatment.

The purpose of this study was to explore the correlates of online health information-seeking behaviors among Hispanic residents of a low-income urban neighborhood.Data were collected with a community survey from 1045 unique participants at ambulatory care clinics in a largely Hispanic immigrant community in northern Manhattan, New York. A descriptive correlational analysis was conducted using logistic regression.A majority of the participants were born outside the United States (85.7%), and half (50.3%) had completed high school. A logistic regression revealed that five independent variables were significantly correlated with online health information-seeking behaviors: age, education, marital status, primary language, and health literacy. Age and Spanish as preferred language were negatively associated with online health information-seeking (OR = 0.93 and 0.50), whereas education and health literacy were positively associated with online health information-seeking (OR = 4.28 and 1.28).The findings have implications for designing online health information resources and interventions appropriate for the populations they are likely to reach. Furthermore, the findings highlight the need for special efforts to ensure access to reliable health information for immigrant populations and those with low health literacy.

Objectives Cigarette smoking is highly prevalent among individuals with bipolar disorder (BD) and may adversely affect symptoms of the disorder as well as co-occurrence of other substance use disorders. However, anecdotal reports suggesting that smoking cessation caused a worsening of mood in smokers with BD have raised concerns about quitting. In this study, we prospectively evaluated the course of BD, alcohol use disorders, and cannabis use disorders in relation to smoking and examined the relationship between smoking abstinence and changes in mood.

Treating septic arthritis of the hip with coexisting advanced degenerative disease is challenging. The use of primary total hip arthroplasty (THA) has led to postoperative infection rates as high as 22%. Insertion of antibiotic spacers with subsequent reimplantation of a THA controls infection and improves pain and function in patients with periprosthetic infections.We asked whether two-stage exchange for patients with degenerative joint disease (DJD) and coexisting septic arthritis would control infection and improve pain relief and function both during the period after insertion of the spacer and after conversion to THA.We retrospectively reviewed 14 patients with severe DJD and either active or recent septic arthritis treated with débridement and insertion of a primary antibiotic-loaded cement spacer between 1996 and 2008. Ten patients underwent subsequent exchange to a permanent hip arthroplasty. Four patients did not undergo exchange to a permanent THA: two died from unrelated causes and two elected not to proceed with exchange because their spacer provided adequate function. We obtained a modified Harris hip score. The minimum clinical followup was 7 months (average, 28 months; range, 7-65 months) after insertion of the spacer.Mean pain scores improved from 6 to 34, and overall Harris hip scores improved from 11 to 67 at last followup with the spacer. Those who underwent definitive THA had further improvement in their mean Harris hip scores to 93.Articulating antibiotic spacers offer acceptable pain relief and function while the infection is treated in this unique group of patients.Level IV, therapeutic study. See Guidelines for Authors for a complete description of levels of evidence.

Although advances in the clinical criteria of various axis I psychiatric disorders are continually being made, there is still considerable overlap in the clinical features, and diagnosis is often challenging. As a result, there has been substantial interest in using morphometric magnetic resonance imaging to better characterize these diseases and inform diagnosis. Region of interest and voxel-based morphometry studies are reviewed herein to examine the extent to which these goals are being met across various psychiatric disorders. It is concluded based on the studies reviewed that specific patterns of regional loss, although present in certain axis I disorders, are not, as yet, diagnostically useful. However, advances in outcome and treatment monitoring show considerably more promise for rapid application in psychiatry.

Serological tests for cytomegalovirus (CMV) after cardiac transplantation were performed at six to eight-week intervals on 26 patients (3 females and 23 males; mean age 46 [15-62] years) with angiographic or ultimately autopsy evidence of coronary atherosclerosis (group 1) and 24 patients (5 females and 19 males; mean age 45 [25-56] years) without coronary disease in the transplanted heart. A positive result meant an at least fourfold increase in CMV IgG titre, demonstration of CMV IgM or direct viral isolation from blood or other body fluid. In 20 patients of group 1 (77%) a CMV infection had occurred after the transplantation, but in only six patients (25%) in the group 2 (P less than 0.0001). These results are interpreted as demonstrating a relationship between CMV infection and rapidly progressive coronary atherosclerosis after cardiac transplantation.

Die chronische koronare Herzkrankheit mit dem Hauptsymptom der stabilen Angina Pectoris ist eine der haufigsten Erkrankungen der Industrienationen. Ziel der Behandlung der chronischen koronaren Herzerkrankung ist primar eine Verbesserung der Prognose, jedoch ist die Steigerung der krankheitsbedingt eingeschrankten Lebensqualitat bei gleichzeitig niedriger Komplikationsrate der Therapiemasnahme fur den Patienten ebenfalls von entscheidender Bedeutung. Als Behandlungsoptionen stehen neben Lebensstilanderungen und der medikamentosen Therapie seit Ende der 60er-Jahre auch die aortokoronare Bypassoperation sowie seit 1977 die perkutane transluminale Koronarangioplastie bzw. perkutane Koronarintervention zur Verfugung. Sowohl die operativen als auch die interventionellen Revaskularisationsverfahren sind seitdem kontinuierlich weiterentwickelt und verbessert worden. Parallel dazu sind auch bei der medikamentosen Therapie grose Fortschritte erzielt worden, sodass diese 3 Therapieoptionen je nach Befundkonstellation um das beste Behandlungskonzept wetteifern.

Durch Senkung des kardiovaskularen Risikofaktors Cholesterins mittels HMG-CoA-Reduktasehemmer („Statine“) konnen das Herzinfarkt- und Schlaganfallrisiko sowie die Sterblichkeit reduziert werden. Die absolute Risikoreduktion hangt von dem individuellen Risiko des Patienten, von der Hohe des LDL-Cholesterins vor Therapie und der erzielten absoluten LDL-Cholesterinsenkung ab. Dieser Tatsache wird durch die nach Risiko abgestuften Zielwerte der aktuellen Leitlinien Rechnung getragen. Das Prinzip der Ausrichtung einer Statintherapie an Lipidzielwerten betont die Bedeutung von Lebensstilmasnahmen (Ernahrung, korperliche Aktivitat) fur alle Patienten und auf jeder Stufe der Therapie. Statine sind fur die grose Mehrheit der Patienten nebenwirkungs- und risikoarm. Aktuell gibt es keinen eindeutigen klinischen Beleg fur differenzielle „pleiotrope“ Effekte zwischen verschiedenen Statinen. In Zusammenschau der vorliegenden Studien gibt es bei Einsatz von Dosierungen mit gleicher LDL-Senkung bislang keinen Beleg fur eine unterschiedliche Wirksamkeit verschiedener Statine in Bezug auf kardiovaskulare Endpunkte. Fur alle Patienten mit koronarer Herzerkrankung wird eine Senkung des LDL-Cholesterins unter 100 mg/dl durch ein Statin empfohlen.

A standardized documentation of echocardiographic studies is necessary to provide comparability of data and to realize software-based documentation and electronic communication, both essential for quality management in echocardiography. Therefore, the subgroup on "Standardization and LV function" of the working group on cardiovascular ultrasound of the German Cardiac Society developed a consensus report for documentation of echocardiographic studies, which was first published in 2000. This report represents the current update of the standardized documentation for echocardiography; its impact for quality management in conjunction with the "guidelines echocardiography" is discussed.

Objectives Several lines of evidence suggest that abnormalities within portions of the extended limbic network involved in affective regulation and expression contribute to the neuropathophysiology of bipolar disorder. In particular, portions of the prefrontal cortex have been implicated in the appearance of manic symptomatology. The effect of atypical antipsychotics on activation of these regions, however, remains poorly understood. Methods Twenty-two patients diagnosed with bipolar mania and 26 healthy subjects participated in a baseline functional magnetic resonance imaging scan during which they performed a continuous performance task with neutral and emotional distractors. Nineteen patients with bipolar disorder were treated for eight weeks with quetiapine monotherapy and then rescanned. Regional activity in response to emotional stimuli was compared between healthy and manic subjects at baseline; and in the subjects with bipolar disorder between baseline and eight-week scans. Results At baseline, functional activity did not differ between subjects with bipolar disorder and healthy subjects in any region examined. After eight weeks of treatment, subjects with bipolar disorder showed a significant decrease in ratings on the Young Mania Rating Scale (YMRS) (p

BACKGROUND AND OBJECTIVE Coronary angioplasty (CAG) has become an acceptable method of treating an acute coronary syndrome (myocardial infarction [MI] or unstable angina [UA]). It was the aim of this study to determine whether the results of such emergency treatment differed from those after elective CAG. PATIENTS AND METHODS Results of emergency CAG in 581 patients (aged 60 +/- 11 years; 77% males) admitted to the authors' hospital between July 1994 and December 1996 were compared with those of elective CAG in 2,460 patients (aged 61 +/- 10, admitted during the same period. Follow-up information was obtained after 22.4 +/- 11 months in 93.2% of the patients by examination, written answers to annual questionnaires, data being collected on survival, repeat cardia catheterizations, other interventions, aorto-coronary bypass, occurrence of myocardial infarction, the patients' general state and drugs received. RESULTS 19 of 517 patients (3.7%) of the group who had undergone elective CAG had died during the follow-up period, compared with 107 of 2436 of the emergency cohort (4.4%; not significant). There were also no significant differences regarding repeat cardiac catheterization, interventions, coronary bypass or re-admission. The proportion of subsequent emergency CAG among all CAGs was 16.8% in the emergency cohort, 8.8% after elective angiography (p < 0.001). CONCLUSION Coronary angiography performed in patients with an acute coronary syndrome has no prognostic significance regarding mortality and morbidity after the acute phase of the disease.

Objectives The Cholesterol Lowering Atherosclerosis PTCA Trial (CLAPT) is a prospective, randomized trial with blinded angiographic end-points to assess the effect of 2-year's treatment with lovastatin initiated 4 weeks prior to PTCA, compared to usual care on non-dilated coronary segments and on dilated coronary lesions in male patients with total cholesterol between 200 and 300mg.dl−1who underwent elective PTCA. Methods and Results Two hundred and twenty six patients were randomized 4 weeks prior to PTCA to special care (diet plus lovastatin n=112) or usual care (diet; n=114). One hundred and ninety-nine patients underwent PTCA at baseline and were finally included in the study. Quantitative coronary angiographic assessment was performed on blinded cinefilms at baseline (PTCA) and repeated after 4 and 24 months in 91% and 81% of the patients. The primary end-point was a change in the mean segment diameter of non-dilated segments. The mean lovastatin dose was 33mg.day−1. Total- and LDL-cholesterol decreased by 21% and 29% in the special care group and by 7% and 11% in the usual care patients. After 2 years, the mean segment diameter of non-dilated segments decreased by 0·03mm in the usual care group and 0·004mm in the special care group ( P =0·27). The decrease in the mean segment diameter of dilated lesions was 0·17mm (usual care) and 0·06mm (special care) ( P =0·04) after 4 months; 0·16mm (usual care) and 0·002mm (special care) after 24 months, respectively ( P =0·05). In both groups, the mean segment diameter of dilated lesions increased between 4 and 24 months after PTCA compared to a decrease in mean segment diameter of non-dilated segments ( P 50% diameter stenosis at follow-up) occurred in 28·4% of usual care and 22·2% of special care patients ( P =0·17). Conclusions Lovastatin reduced the progression of dilated lesions in men with elective PTCA. Independent of treatment allocation, the dilated lesions regressed and the non-dilated segments progressed during the study follow-up. Four weeks of pre-treatment with lovastatin did not influence the rate of restenosis. Lovastatin had no statistically significant effect on non-dilated segments.

Ziel: Bei dynamischen Kontrastmittel- (KM) Studien konnen spezifische Merkmale der Zeit/Intensitats-Kurve (ZIK) eines jeden Bildpunktes verwendet und in Form von Parameterbildern dargestellt werden. Aufbauend auf bestehenden Konzepten der zweidimensionalen Analyse der KM-Dynamik soll eine dreidimensionale Erweiterung mit adaquater computergraphischer Visualisierung realisiert werden. Methode: Bildgebung: Intravenose KM-Injektion; First-pass-Analyse mit CT bei schneller Akquisition einer einzigen Schicht; Untersuchung der langerfristigen KM-Anreicherung mit 40 MR-Schichten (6 Sequenzen alle 90 s=240 Bilder). Softwareentwicklungen: ZIK beliebiger ROIs/VOIs; Parameterbilder: 1. Maximum-Intensitats-Projektion (TMIP) aller Pixel als Funktion uber die Zeit; 2. zeitliche KM-Gradienten (TG) anhand der ZIK-Amplitude; 3. ZIK-Steigung/Gefalle; 4. Zeitpunkte der ZIK-Maxima; 5. Korrelationskoeffizienten zu Vergleichs-ZIK. Die berechneten 3D-Daten der KM-Anreicherung wurden mittels multiplanarer Reformatierung, MIP, Oberflachenrekonstruktion, Volume Rendering und Textur-Mapping visualisiert und animiert. Ergebnisse: TMIP und TG erlaubten bei First-pass-Analysen die simultane oder getrennte Prasentation unterschiedlicher Zeitraume des KM-Bolus. Die Korrelationsbilder gestatteten die Hervorhebung von Regionen, die Ahnlichkeiten zu vorgegebenen ZIK-Mustern aufwiesen. Computergraphische Techniken gestatteten 1. ein anatomisch/funktionales Mapping von Originalbild und KM-Anreicherungsverhalten sowie 2. die fusionierte Darstellung von KM-Anreicherungsbetrag und farbkodierter Zeit des KM-Maximums in einem gemeinsamen Bild. Schlusfolgerungen: Die exakte Quantifizierung von Prasenz, Grad und Ankunftszeit des Kontrastmittels in lokalen Bildregionen unterstutzt die Beurteilung der Vaskularisation sowie von ischamischen bzw. nekrotischen Arealen.

PURPOSE The aim of the study was to establish the prognostic value and clinical implications of blood flow velocity measurements by Doppler guide wires during peripheral laser-assisted percutaneous transluminal angioplasty (PTLA). METHODS 39 patients presenting with symptomatic peripheral arterial obstructive disease underwent angiography and blood flow velocity assessment by Doppler guide wire (0.018") prior to and following PTLA. Both quantitative angiography (QCA) for measurement of luminal diameters and Doppler assessment of maximum peak velocities (MPV) were performed 2 cm proximal, over and 2 cm distal to stenoses. The results were compared with the following clinical endpoints: 1. Short-term clinical improvement by AHA-criteria during first follow-up examination and 2. criteria for patency suggested by Rutherford [12] within 1 year (1-22 months). RESULTS Angiography demonstrated initial success of PTLA in all patients. Relative diameter stenosis decreased from 70 +/- 0.04% to 17 +/- 0.05%. Mean clinically category improved from 2.7 +/- 0.1 to 1.2 +/- 0.1 following intervention. Mean grade of clinical improvement was 2.8 +/- 0.1. 22/39 patients demonstrated event-free follow-up examinations. Doppler measurements of MPV post PTLA in the proximal reference segment correlated with clinical outcome. MPV > or = 90 cm/s was associated with good primary success, unlimited walking capacity and event-free follow-up. MPV > or = 70 cm/s predicted an improvement of short-term clinical outcome by 2 grades (predictive value 80%). MPV or = 90 cm/s in a proximal reference segment following PTLA predicts good clinical outcome, whereas MPV < 70 cm/s is associated with minor primary clinical success and increased rates of restenosis.

PURPOSE: The visual assessment of shape and surface structures of pulmonary nodules (PN) (smooth edges vs. spiculae) serves as a qualitative, subjective criterion in differential diagnosis. These properties must be quantified by computer-assisted evaluation, an adequate mathematical model, and new quantitative shape parameters. METHODS: 12 patients were investigated by high resolution CT. Based on 3D reconstructions with increasing thresholds, the PN surface S, volume V, fractal dimension (FD = In(S)/ In(square root of V)), and fractal index (F1 = square root of S/ square root of V) were calculated. RESULTS: The relations between the reconstruction threshold and the calculated tumour surface, respective volume, are of a fractal nature: S = c1 x thres1/d, V = c2 x thres1/D (c1, c2, d, D: real constants). Whereas the absolute values of surface and volume strongly depend on the chosen threshold (mean volume differences of 249%), the derived parameter of the fractal dimension for a specific PN is nearly constantfor all thresholds under review (r = 0.998, SD = 0.05). CONCLUSIONS: FD and FI are new diagnostic features for the assessment of PN surface structure and morphology. Thus, the assessment of pulmonary nodules can be supported by new quantitative parameters representing surface irregularity due to invasive tumour growth into adjacent tissue.

Aim: Recent developments of the Internet (World Wide Web) allow the integration of audio, video, digital film sequences, and three-dimensional data. The applicability of these innovations for medical documentation is demonstrated. Methods: Our existing software for medical image processing and 3D reconstruction was extended to provide images, film sequences, and complex 3D models in an Internet-compatible data format. Results: The multimedia results of the image processing were integrated into Internet documents. Specialized programs are no longer necessary for visualization. The Internet software allows for user-friendly handling and interactive presentation of the 2D and 3D data. Conclusions: The Internet offers public-domain software for display of images, audio/video, and 3D data. Thus, the tools of the Internet represent an ideal basis for local hospital information systems, computer-aided medical education, and teleconferencing.

Biplane angiography generates just two time equivalent X-ray images. These X-ray systems can be rotated independently from each other (restricted by possible collisions only). The article explains how highly accurate 3D models of vessel systems can be reconstructed, visualized, and quantitatively evaluated from these X-ray images.

In dieser Arbeit wird ein Verfahren zur Bewegungskorrektur bei Subtraktionsbildern aus zwei zeitlich getrennten CT-Untersuchungen vorgestellt. In der ersten CT-Sequenz wird eine Leeraufnahme, in der zweiten Sequenz eine Kontrastmitteluntersuchung durchgefuhrt. Ziel der Bildsubtraktion ist die alleinige Darstellung des Kontrastmittels. Im Vergleich zur konventionellen DSA ist bei der CT-Angiographie eine direkte Subtraktion der Bildpaare nicht moglich, da bei den zeitversetzten Bildern starke Bewegungsartefakte auftreten. Zur Korrektur dieser Storung wurde ein neuartiges Verfahren zur Bestimmung von lokalen Verschiebungsvektoren zwischen den beiden Bildern entwickelt. Anhand dieses Bewegungsmusters wird eine neue, synthetische Maske bestimmt, die dem Kontrastmittelbild maximal deckungsgleich ist. Die anschliesende Subtraktion erfolgt mit diesem berechneten Maskenbild. Die Darstellung der resultierenden 3D-Datensatze erfolgt auf einer Spezialhardware, die schnelle Rotationen und Schnitte erlaubt. Neue diagnostische Moglichkeiten ergeben sich durch die Erzeugung von Ansichten, die mit herkommlichen Untersuchungen nicht gewonnen werden konnen, und bei der Beurteilung von verkalkten Gefasen. Conventional image subtraction of CT sequences is hampered by extended motion artifacts. In this paper a motion correction procedure for the subtraction of images from two time-separate CT investigations is introduced. Native images are obtained in the first CT sequence, and a contrast medium examination is imaged in the second. The aim of image subtraction is sole presentation of the contrast medium. In contrast to conventional digital subtraction angiography (DSA), CT angiography rules out the possibility of direct image subtraction due to occurrence of extended motion artifacts in the time-shifted images. Such shortcomings can now be corrected by means of a new registration method developed for determination of local displacement vectors between the two images. This motion pattern is used to compute a new synthetic mask of maximum congruence with the contrast medium image. The resulting three-dimensional data record is presented by means of a special-purpose hardware enabling fast rotations and cut planes. New diagnostic possibilities can be achieved such as the creation of views that are not obtainable with conventional modalities and the assessment of calcified vessels.

Polyphenol compounds found in berry fruits, in particular flavonoids, have been associated with health benefits including improvement in cognition and neuronal function with aging. Concord grape juice contains polyphenols, including anthocyanins and flavanols, and previous research has shown improvement in a number of human health conditions with grape juice supplementation. In the current study, older adult subjects with mild cognitive impairment consumed Concord grape juice or placebo for 16 weeks and were administered assessments of memory function and brain activation pre- and postintervention. Participants who consumed grape juice showed reduced semantic interference on memory tasks. Relatively greater activation in anterior and posterior regions of the right hemisphere was also observed with functional magnetic resonance imaging in the grape juice treated subjects. These findings provide further evidence that Concord grape juice can enhance neurocognitive function in older adults with mild memory decline.

Numerous essential, physiological effects on the cardiovascular system are attributable to angiotensin II (Ang II). Because of this we can assume that genetic changes in the specific receptor of Ang II (Ang II type I receptor gene, AT1) play a decisive role in the occurrence of cardiovascular disease associated with blood pressure regulation, vascular tone, cardiac and vascular growth process. To test this hypothesis, we examined the presence of polymorphisms within the coding region of the AT1 gene using polymerase chain reaction (PCR) and subsequent non-radioactive sequencing of samples from a control group with no previous history of cardiovascular complaint in individuals or immediate family. Using the Taq-sequencing procedure we found polymorphic sites, especially in the 5′ region of the gene (base pair positions 9, 16, 87, 133, 186), two of which led to an exchange of the amino acid (amino acid 6: Ser ↔ Pro, amino acid 45: Gly ↔ Arg). Together with the silent polymorphism at base pair position 573, which our group established previously, an additional polymorphism in the 3′ region of the gene was discovered. This, however, did not confer any changes in amino acid sequence. In a preliminary study we found no association between [he distribution of the C/T573, polymorphic site and cardiovascular disease, such as essential hypertension (n = 20), coronary artery disease (n = 16) hypertrophic cardiomyopathy (n = 12) or dilated cardiomyopathy (n = 21). Further studies will be needed to determine to what extent the polymorphism described are associated with cardiovascular disease.

The collaboration between physicians is supported in the BERMED project by implementing the remote access to distributed patient data and the realisation of computer-based medical conferencing. This requires the integration of the multimedia data in form of a meta-patient record for our medical application systems. These applications are supported by a distributed information management promoting access to different information systems, imaging modalities and digital archival storage systems. The features of image processing are concerned with quantification, segmentation and 3-D-visualisation to obtain additional information. This paper gives an overview of the actual state of the teleconferencing system in radiology.

There is considerable debate over whether bipolar and related disorders that share common signs and symptoms, but are currently defined as distinct clinical entities in DSM-IV and ICD-10, may be better characterized as falling within a more broadly defined “bipolar spectrum”. With a spectrum view in mind, the possibility of broadening the diagnosis of bipolar disorder has been proposed. This paper discusses some of the rationale for an expanded diagnostic scheme from both clinical and research perspectives in light of potential drawbacks. The ultimate goal of broadening the diagnosis of bipolar disorder is to help identify a common etiopathogenesis for these conditions to better guide treatment. To help achieve this goal, bipolar researchers have increasingly expanded their patient populations to identify objective biological or endophenotypic markers that transcend phenomenological observation. Although this approach has and will likely continue to produce beneficial results, the upcoming DSM-IV and ICD-10 revisions will place increasing scrutiny on psychiatry’s diagnostic classification systems and pressure to re-evaluate our conceptions of bipolar disorder. However, until research findings can provide consistent and converging evidence as to the validity of a broader diagnostic conception, clinical expansion to a dimensional bipolar spectrum should be considered with caution.

Several lines of evidence suggest that the neuropathophysiology of bipolar disorder is marked by structural and functional abnormalities in the caudate. We used magnetic resonance spectroscopy imaging (MRSI) to examine potential neurochemical changes in the caudate of adult bipolar patients (BP). 2D-MRSI scans including the caudate were obtained from 25 BP and 9 healthy subjects (HS). BP patients were further divided into medicated ( n =14) and unmedicated ( n =11) groups; the majority of medicated patients received atypical antipsychotics (AAP). Ratios of Cr/Cho, Cho/NAA and Cr/NAA in the caudate were compared between groups, controlling for age, gender and gray/white ratio. BP and HS did not significantly differ on any ratios. The Cr/Cho ratio, however, was significantly greater in medicated BP compared to HS. Conversely, the Cho/NAA ratio was non-significantly lower in medicated BP vs. HS. Medicated BP also showed significantly greater Cr/Cho and significantly smaller Cho/NAA ratios than unmedicated BP. Although we did not observe significant overall differences between BP and HS, our findings suggest the presence of reduced choline levels in the caudate of medicated BP receiving AAP. While speculative, these results suggest that AAP do not cause oxidative injury to neuronal membranes.

Bipolar disorder, characterized by recurrent episodes of mania and commonly depression, is a debilitating mental illness that affects millions of children, adolescents, and adults worldwide. Individuals with bipolar disorder often exhibit symptomatology found in other psychiatric disorders, which may lead to misdi-agnosis. Approximately half of bipolar patients respond to monotherapy of any single agent and often combinations of medications are necessary in order to achieve optimal mood stabilization. Therefore, strategies to improve the accuracy of diagnosis and selection of appropriate treatment modalities are critical to improve the outcome for individuals with bipolar disorder. One such strategy is the identification of biomarkers through the use of neuroimaging techniques, including structural neuroimaging, diffusion tension imaging, functional magnetic resonance imaging, and magnetic resonance spectroscopy. Neuroimaging studies in bipolar disorder have furthered our understanding of the neuropathophys-iology of the illness across the lifespan as well as the neurochemical effects of medications commonly used for mood stabilization. In this chapter, we review the existing neuroimaging literature, focusing on anatomical, functional, and biochemical abnormalities observed in individuals with bipolar disorder that may serve as biomarkers for the illness and treatment response. Future neuroimaging research in bipolar disorder should aim to address current methodological limitations and identify reliable biomarkers that may lead to improved diagnostic accuracy and early, targeted treatment interventions in order to improve patient outcome.

Objective To review the safety/tolerability of quetiapine in four placebo-controlled studies in patients with bipolar I disorder experiencing acute mania. Methods Four double-blind, placebo-controlled studies evaluated quetiapine monotherapy (12 weeks) or quetiapine in combination with lithium (mean serum concentration 0.76 mEq/L) or divalproex (mean serum concentration 68.6 μg/mL) (Li/DVP) (3 and 6 weeks) in patients with acute mania. Pooled data from the two monotherapy studies and the two combination therapy studies have been evaluated in the analysis presented here. Adverse event reporting, Simpson Angus Scale (SAS), and Barnes Akathisia Rating Scale (BARS) scores were recorded. Results Most adverse events were mild to moderate. Common adverse events (≥ 5% and at least twice the placebo rate) with quetiapine monotherapy and combination therapy were somnolence, dry mouth, weight gain, dizziness, asthenia, pharyngitis, and postural hypotension. Treatment-related discontinuations due to adverse events were not significantly different between quetiapine and placebo, nor was the incidence of extrapyramidal symptoms (including akathisia) (quetiapine monotherapy 12.9% vs placebo 13.1%; combination therapy 21.4% vs placebo 19.2%). Mean change from baseline to endpoint in SAS and BARS scores was not significantly different between groups. Mean weight change at treatment end with quetiapine compared with placebo was + 1.8 vs − 0.15 kg in monotherapy; and + 1.97 vs + 0.27 kg with combination therapy. No patients discontinued due to weight gain. The effect of quetiapine monotherapy on serum prolactin levels was no different from placebo. Conclusions Quetiapine monotherapy and combination therapy were well tolerated in the treatment of acute mania.