Pancreatic mucinous lesions: a retrospective analysis with cytohistological correlation

The diagnosis of mucinous pancreatic lesions, which include mucinous noncystic adenocarcinoma, intraductal papillary mucinous neoplasm (IPMN), mucinous cystic neoplasm (MCN), and mucinous metaplasia, is critical, given different clinical management and prognosis. This retrospective study is done to assess the cytological features and pitfalls associated with these entities in cytological samples.A search for pancreatic cytology specimens with histological confirmation of the various pancreatic mucinous lesions was done from 1988 to 2005: 9 mucinous adenocarcinoma, 14 IPMN, 11 MCN, and 3 mucinous metaplasia. The majority (35/37) had been endoscopic ultrasound-guided fine-needle aspirations. The cellularity, background extracellular mucin, epithelial architecture, mucinous nature of the epithelium, cell shape, and nuclear features were evaluated on the cytology material. Of the 22 cytological features evaluated, the presence of three-dimensional clusters, micropapillary structures, and nuclear atypia, which includes nuclear crowding, increased N/C ratio, anisonucleosis, nuclear membrane contour irregularity, clumpy chromatin, and prominent nucleoli, was found to be consistently associated with mucinous adenocarcinoma. There were no statistically significant cytological features, which helped in differentiating IPMN, MCN, and mucinous metaplasia. There was a relatively high false-positive rate in the IPMN group (5/14, 36%). Review of the histological specimen showed severe dysplastic epithelial change in these cases. One false-positive case of mucinous metaplasia (1/3, 33%) showed marked intraepithelial acute inflammation.The cytological diagnosis of mucinous pancreatic lesions remains challenging, except for mucinous noncystic adenocarcinoma. The findings were largely nonspecific in the differentiation between IPMN, MCN, mucinous metaplasia, and incidentally sampled gastrointestinal epithelium. False-positive diagnosis of adenocarcinoma occurs not infrequently in the setting of IPMN with severe dysplastic epithelial change and in lesions with associated acute inflammation, and can be a pitfall in the diagnosis of these lesions.     

Detection of abnormalities of PRV-1, TPO, and c-MPL genes detected by fluorescence in situ hybridization in essential thrombocythemia

No specific diagnostic markers have been described in essential thrombocythemia (ET). PRV-1 (polycythemia rubra vera-1), TPO (thrombopoietin), and c-MPL (myeloproliferative leukemia virus oncogene) genes are candidate ET molecular markers because of their implication in the pathogenesis of ET. We have studied the status of PRV-1, TPO, and c-MPL genes in 30 ET patients by a fluorescence in situ hybridization (FISH) technique using three noncommercial, locus-specific probes for PRV-1 (BAC RP11-160A19, located at 19q13.2), TPO (BAC RP11-45NP16, located at 3q27), and c-MPL (BAC RP11-297L5, located at 1p34). FISH study showed no PRV-1, TPO, and c-MPL cytogenetic abnormalities in any of the analyzed cases. Our results suggest a lack of structural and numerical rearrangements (deletions, translocations, or amplifications) of PRV-1, TPO, and c-MPL genes in ET patients.     

Illustration of a common framework for relating multiple typing methods by application to macrolide-resistant Streptococcus pyogenes

The studies that correlate the results obtained by different typing methodologies rely solely on qualitative comparisons of the groups defined by each methodology. We propose a framework of measures for the quantitative assessment of correspondences between different typing methods as a first step to the global mapping of type equivalences. A collection of 325 macrolide-resistant Streptococcus pyogenes isolates associated with pharyngitis cases in Portugal was used to benchmark the proposed measures. All isolates were characterized by macrolide resistance phenotyping, T serotyping, emm sequence typing, and pulsed-field gel electrophoresis (PFGE), using SmaI or Cfr9I and SfiI. A subset of 41 isolates, representing each PFGE cluster, was also characterized by multilocus sequence typing (MLST). The application of Adjusted Rand and Wallace indices allowed the evaluation of the strength and the directionality of the correspondences between the various typing methods and showed that if PFGE or MLST data are available one can confidently predict the emm type (Wallace coefficients of 0.952 for both methods). In contrast, emm typing was a poor predictor of PFGE cluster or MLST sequence type (Wallace coefficients of 0.803 and 0.655, respectively). This was confirmed by the analysis of the larger data set available from http://spyogenes.mlst.net and underscores the necessity of performing PFGE or MLST to unambiguously define clones in S. pyogenes.     

Density of Chlamydia pneumoniae is increased in fibrotic and calcified areas of degenerative aortic stenosis

BACKGROUND: The process of aortic degeneration associated with calcified aortic stenosis shares many similarities with coronary artery atherosclerosis. Inflammation and infection are involved in both diseases. Chlamydia pneumoniae has been identified in atherosclerotic plaques. However, the studies about the presence of C. pneumoniae in degenerative aortic stenotic valves are not conclusive. OBJECTIVE: We investigated whether an association exists between the density of C. pneumoniae and fibrosis or calcification in aortic stenosis. DESIGN: Autopsy and surgical specimens were divided into 3 groups: Normal, 11 normal autopsy valves Atherosclerosis, 10 autopsy valves from patients with systemic atherosclerosis and no aortic stenosis and Aortic stenosis, 14 surgical specimens of aortic valves replaced due to aortic stenosis. SETTING: Heart Institute (InCor), University of S?o Paulo Medical School. PATIENTS: Aortic valves from patients aged 52+/-16 years, 69+/-9 years, and 71+/-8 years. INTERVENTION: Specimens were evaluated by immunohistochemical technique (to detect C. pneumoniae antigens), in situ hybridization, and electron microscopy (to quantify the density of C. pneumoniae in the valves). MEASUREMENTS: The aortic stenosis group was analyzed according to 3 subregions: aortic stenosis-preserved, peripheral preserved regions; aortic stenosis-fibrosis, peri-calcified fibrotic tissue; and aortic stenosis-calcification, calcified nodules. RESULTS: The median values of C. pneumoniae antigens were 0.09, 0.30, 0.18, 1.33, and 3.3 in groups Normal, Atherosclerosis, Aortic stenosis-preserved, Aortic stenosis-fibrosis, and Aortic stenosis-calcification, respectively. The amount of C. pneumoniae was greater in the Atherosclerosis and Aortic stenosis-calcification groups than in the Normal group (P<0.05). C. pneumoniae was greater in the Aortic stenosis group in the calcified and fibrotic regions than in preserved region (P<0.05). CONCLUSION: An association was found between the higher density of C. pneumoniae and fibrosis/calcification in stenotic aortic valves.     

Informal discussions in substance abuse treatment sessions with Spanish-speaking clients

This study investigated the extent to which bilingual counselors initiated informal discussions about topics that were unrelated to the treatment of their monolingual Spanish-speaking Hispanic clients in a National Institute on Drug Abuse Clinical Trial Network protocol examining the effectiveness of motivational enhancement therapy (MET). Session audiotapes were independently rated to assess counselor treatment fidelity and the incidence of informal discussions. Eighty-three percent of the 23 counselors participating in the trial initiated informal discussions at least once in one or more of their sessions. Counselors delivering MET in the trial initiated informal discussion significantly less often than the counselors delivering standard treatment. Counselors delivering standard treatment were likely to talk informally the most when they were ethnically non-Latin. In addition, informal discussion was found to have significant inverse correlations with client motivation to reduce substance use and client retention in treatment. These results suggest that informal discussion may have adverse consequences on Hispanic clients' motivation for change and substance abuse treatment outcomes and that maintaining a more formal relationship in early treatment sessions may work best with Hispanic clients. Careful counselor training and supervision in MET may suppress the tendency of counselors to talk informally in sessions.     

Acceptability and characteristics of 124 human bioequivalence studies with active substances classified according to the Biopharmaceutic Classification System

AIM

The aim of this study was to evaluate the acceptability of 124 bioequivalence (BE) studies with 80 active substances categorized according to the Biopharmaceutics Classification System (BCS) in order to establish if there were different probabilities of proving BE between the different BCS classes.

METHODS

We evaluated the differences between pharmaceutical products with active substances from different BCS classes in terms of acceptability, number of subjects in the study (n), the point estimates, and intra- and inter-subject coefficients of variation data from BE studies with generic products.

RESULTS

Out of 124 BE studies 89 (71.77%) were performed with pharmaceutical products containing active substances classified by the BCS. In all BCS classes there were non-bioequivalent pharmaceutical products: 4 out of 26 (15.38%) in class 1, 14 out of 28 (50%) in class 2, 3 out of 22 (13.63%) in class 3 and 1 out of 13 (7.69%) in class 4. When we removed those pharmaceutical products in which intra-subject variability was higher than predicted (2 in class 1 active substances, 9 in class 2 and 2 in class 3) there were still non-BE pharmaceutical products in classes 1, 2 and 3.

CONCLUSIONS

Comparisons between pharmaceutical products with active substances from the four BCS classes have not allowed us to define differential characteristics of each class in terms of n, inter and intra-subject variability for C_max or AUC. Despite the usually employed test dissolution methodology proposed as quality control, pharmaceutical products with active substances from the four classes of BCS showed non-BE studies.     

Myasthenia gravis and pregnancy: clinical course and management of delivery and the postpartum phase

OBJECTIVES: To study influences of pregnancy on the time-course of myasthenia gravis (MG) and of MG on pregnancy, delivery, postpartum and newborn. METHODS: We retrospectively collected data from 100 women affected with MG, hospitalized between 1994 and 2003 in departments of Neurology of Lille University Hospital. RESULTS: Eighteen patients had a total of 36 pregnancies, occurring 7.2 years on average after MG onset. MG exacerbation occurred in 7 patients (26 percent) during pregnancy and in 4 (14.8 percent) during postpartum. One patient died of acute respiratory failure during postpartum. Delay between the onset of MG and pregnancy was the only variable significantly associated with MG exacerbation: 5.8 years when exacerbation and 9.5 years when no exacerbation (p=0.03). Seven miscarriages, two therapeutic abortions and no death at birth were reported. Levels of anti-acetylcholine receptor antibodies were abnormal in 3 of 27 newborns (11 percent), but only one (3.7 percent) developed seronegative transient neonatal myasthenia gravis. DISCUSSION: During pregnancy, the clinical course of MG is variable but exacerbations were associated with a shorter delay between MG diagnosis and pregnancy. The risk of transient neonatal myasthenia gravis is relatively small but exists even when the parturient has stable MG without elevated levels of anti-acetylcholine receptor antibodies. CONCLUSION: Our study confirms pregnancy is more difficult to manage at the beginning of MG. Given the unpredictable course of MG during pregnancy, we recommend women affected with MG to begin a pregnancy when the disease is stable.     

Genetic prothrombotic risk factors in women with unexplained pregnancy loss

INTRODUCTION: Inherited thrombophilia has been associated with unexplained recurrent pregnancy loss (RPL) and stillbirth. This thrombotic tendency can manifest as thrombotic lesions in the placenta, and may lead to abortion and stillbirth. The aim of our case-control study was to investigate the prevalence of FVL and FII G20210A in women with adverse pregnancy outcome, compared to the prevalence of the same mutations in our health control group. MATERIALS AND METHODS: 102 consecutive women with unexplained pregnancy loss (55 with history of RPL, and 47 with history of stillbirth) were studied for hereditary thrombophilia. The health control group consisted of 217 healthy women from the general population. RESULTS AND CONCLUSIONS: Of the 55 women with recurrent abortions, we found the same prevalence for the FVL and the FII G20210A(9.1%, 5 pts). (p=NS compared to control group). Of the 47 women with stillbirth, 11 (23.4%) had the FVL and 9 (19.1%) had the FII G20210A(p<0.0005 for both mutations). In our experience the prevalence of FVL and the FII G20210Amutations was significantly higher in women with unexplained stillbirth, instead the prevalence of genetic thrombophilia was high but not statistically significant in women with recurrent pregnancy loss.     

The Effects of a 15-Week Exercise Intervention on Fitness and Postural Control in Older Adults

Falls are the leading cause of nonfatal injuries in older adults and often lead to adverse changes in confidence and lifestyle that trigger further declines in postural control. Decreased fitness is associated with poor performance on postural control assessments, especially those that increase task difficulty. The purpose of this study was to analyze the impact of a traditional group fitness class and a Wii fitness exercise program on individual's ability to maintain postural control with an environmental distracter. Eighty-seven community-dwelling seniors were randomized into one of three groups (Control, Wii Fitness, Group Fitness). Interventions were delivered three times per week for 15 weeks. A significant improvement in the Sensory Organization Test (SOT) equilibrium score was seen over time. There was a significant training group by time interaction for 6-minute walk (p?=?0.14, effect size = .776). There was a significant pretest (7.2 ± 1.4) post-test (6.7 ± 1.4) comparison for 8-foot Timed “Up and Go” (p?=?0.017). There was a significant interaction between training groups and time (p?=?0.010) for chair stands. Post hoc tests revealed that equilibrium scores during cognitive distraction (38.1 ± 20.9) were significantly less than both the visual distraction (51.9 ± 20.2) and auditory distraction (49.3 ± 21.1). There were no differences during the increased environmental load testing (p?=?0.686). Results indicated that both intervention programs were successful at improving postural control and fitness.