Pharmacokinetic Analysis of Gd-DTPA Enhancement in dynamic three-dimensional MRI of breast lesions

The purpose of this study was to demonstrate that dynamic MRI covering both breasts can provide sensitivity for tumor detection as well as specificity and sensitivity for differentiation of tumor malignancy. Three-dimensional gradient echo scans were used covering both breasts. Before Gd-DTPA bolus injection, two scans were obtained with different flip angles, and after injection, a dynamic series followed. Thirty-two patients were scanned according to this protocol. From these scans, in addition to enhancement, the value of T1 before injection was obtained. This was used to estimate the concentration of Gd-DTPA as well as the pharmacokinetic parameters governing its time course. Signal enhancement in three-dimensional dynamic scanning was shown to be a sensitive basis for detection of tumors. In our series, all but two mam-mographically suspicious lesions did enhance, and in three cases, additional enhancing lesions were found, two of which were in the contralateral breast. The parameter most suited for classification of breast lesions into benign or malignant was shown to be the pharmacokinetically defined permeability k31, which, for that test, gave a sensitivity of 92% and a specificity of 70%. Our three-dimensional dynamic MRI data are sensitive for detection of mammographically occult breast tumors and specific for classification of these as benign or malignant

Mechanical tension in the median nerve: The effects of joint positions

Stretch tests are attractive in the diagnosis of nerve root or peripheral nerve lesion. Interpretation of the test results is often difficult since the distribution of tensile forces along the nerve caused by the test manoeuvre is not known. In this study the effect on median nerve tension of 22 positions of the arm was measured with ‘buckle’ force transducers. With the elbow in full extension and the hand in neutral position, altering the position of the shoulder significantly influenced tension in the proximal part of the median nerve; tension in the distal part was not influenced. With the shoulder in 90 ° abduction, dorsiflexion of the hand combined with an extended elbow resulted in an increased tension in both distal and proximal parts of the median nerve. Dorsiflexion of the hand combined with flexion of the elbow caused an increase in tension only in the distal part. At all sites of the median nerve the median nerve upper limb tension test caused a significantly higher tension than the radial and ulnar nerve upper limb tension tests. This study provides insight in the normal distribution of tensile forces along the median nerve and can have clinical consequences. For differentiating nerve root from peripheral nerve lesions a specific provocative tension test for the median nerve is advocated. The results of this study provide a theoretical basis for differentiating between lesions in the proximal and distal parts of the median nerve

Chronologic Change and Clinicopatiologic Characteristics of Gastric Cancer Patients Over 70 Years of Age

Chronologic change and clinicopathology of 299 gastric cancer patients over 70 years of age (old group) were examined by comparing with those of 307 patients under 50 years of age (young group), and the histogenesis was discussed. The patients of the old group increased significantly in frequency from 9.9 % in the 1960's to 33.9 % in the 1990's, and the patients of the young group decreased clearly from 23.5 % in the 1960's to 9.4 % in the 1990's. However, no significant difference was found in the frequency of patients between 50 and 69 among 4 periods from the 1960's to the 1990's. In 6 out of 12 clinicopathologic factors, significant difference were found between both groups; male, tumor of lower 3rd of the stomach, macroscopic localized type in advanced cancer and protruded and elevated types in early cancer, liver metastasis, differntiated adenocarcinoma and venous invasion were significantly more in the old group than in the young group. From the results, it is suggested that the frequency of gastric cancer in Japan increases recently in the old group and decreases in the young group. Histogenetically, differentiated adenocarcinoma originating from intestinal metaplasia is suggested to arise more frequently in the former than in the latter

Effect of DNA Repair Protein Rad18 on Viral Infection

Host factors belonging to the DNA repair machineries are assumed to aid retroviruses in the obligatory step of integration. Here we describe the effect of DNA repair molecule Rad18, a component of the post-replication repair pathway, on viral infection. Contrary to our expectations, cells lacking Rad18 were consistently more permissive to viral transduction as compared to Rad18(+/+) controls. Remarkably, such susceptibility was integration independent, since retroviruses devoid of integration activity also showed enhancement of the initial steps of infection. Moreover, the elevated sensitivity of the Rad18(−/−) cells was also observed with adenovirus. These data indicate that Rad18 suppresses viral infection in a non-specific fashion, probably by targeting incoming DNA. Furthermore, considering data published recently, it appears that the interactions between DNA repair components with incoming viruses, often result in inhibition of the infection rather than cooperation toward its establishment

Beta-Blocking Agents and Electroconvulsive Therapy

In this review we want to summarize the results of the placebo-controlled randomized clinical trials with betablocking adrenergic agents during electroconvulsive therapy (ECT), and review the effect on seizure duration and cardiovascular variables. We sea

Development, behaviour and autism in individuals with SMC1A variants

Introduction: Development and behaviour in Cornelia de Lange Syndrome (CdLS), including autism characteristics, have been described infrequently stratified to genetic cause and only a few studies have considered behavioural characteristics in relation to developmental level. Here, we describe the behavioural phenotype in individuals with CdLS with SMC1A variants. Methods: We performed an international, interdisciplinary study on 51 individuals with SMC1A variants. Results of questionnaire studies are compared to those in individuals with Down Syndrome and with Autism Spectrum Disorder. Results on cognition and self-injurious behaviour (SIB) are compared to those in individuals with CdLS caused by NIPBL variants. For Dutch participants with SMC1A variants we performed direct in-person assessments of cognition, autism, and added an interview and questionnaire on adaptive behaviour and sensory processing. Results: Individuals with SMC1A variants show a higher cognitive level and less SIB than individuals with NIPBL variants. Individuals with SMC1A variants without classic CdLS phenotype but with a Rett-like phenotype show more severe intellectual disability and more SIB compared to those with a CdLS phenotype. Autism is less present if outcomes in direct in-person assessments are evaluated taking developmental level into account compared to results based on a questionnaire. Conclusions: Behaviour in individuals with CdLS should be evaluated taking genetic cause into account. Detailed interdisciplinary approaches are of clinical importance to inform tailored care and may eventually improve quality of life of patients and families

Baseline urinary metabolites predict albuminuria response to spironolactone in type 2 diabetes

The mineralocorticoid receptor antagonist spironolactone significantly reduces albuminuria in subjects with diabetic kidney disease, albeit with a large variability between individuals. Identifying novel biomarkers that predict response to therapy may help to tailor spironolactone therapy. We aimed to identify a set of metabolites for prediction of albuminuria response to spironolactone in subjects with type 2 diabetes. Systems biology molecular process analysis was performed a priori to identify metabolites linked to molecular disease processes and drug mechanism of action. Individual subject data and urine samples were used from 2 randomized placebo controlled double blind clinical trials (NCT01062763, NCT00381134). A urinary metabolite score was developed to predict albuminuria response to spironolactone therapy using penalized ridge regression with leave-one-out cross validation. Bioinformatic analysis identified a set of 18 metabolites linked to a diabetic kidney disease molecular model and potentially affected by spironolactone mechanism of action. Spironolactone reduced UACR relative to placebo by median -42% (25th to 75% percentile -65 to 6) and -29% (25th to 75% percentile -37 to -1) in the test and replication cohorts, respectively. In the test cohort, UACR reduction was higher in the lowest tertile of the baseline urinary metabolite score compared with middle and upper tertiles -58% (25th to 75% percentile -78 to 33), -28% (25th to 75% percentile -46 to 8), -40% (25th to 75% percentile -52% to 31), respectively, P= 0.001 for trend). In the replication cohort, UACR reduction was -54% (25th to 75% percentile -65 to -50), -41 (25th to 75% percentile -46% to 30), and -17% (25th to 75% percentile -36 to 5), respectively, P= 0.010 for trend). We identified a set of 18 urinary metabolites through systems biology to predict albuminuria response to spironolactone in type 2 diabetes. These data suggest that urinary metabolites may be used as a tool to tailor optimal therapy and move in the direction of personalized medicine