Variation of the Intercellular Space in the Esophageal Epithelium in Response to Hydrochloridric Acid Infusion in Patients with Erosive Esophagitis

ABSTRACT:

The purpose of this study was to compare esophageal infusion with 0.1 N hydrochloridric acid (HCl) to esophageal infusion with saline in patients presenting with typical gastroesophageal reflux symptoms and erosive esophagitis.

METHODS:

Upper gastrointestinal endoscopy was performed on 44 prospective subjects, 29 of whom were included in the study. Eighteen patients presented with normal esophagi (Control Group “C”), nine of whom were infused with HCl and nine with saline. Eleven patients presented with erosive esophagitis (Lesion Group “L”), five of whom were infused with HCl and six with saline. Biopsies of the esophageal mucosa were collected before and after infusions.

RESULTS:

No statistically significant difference was found between the two types of infusions in terms of the dilation of the intercellular space of the esophageal epithelium, regardless of the status of the patient.

CONCLUSIONS:

Response to HCl infusion cannot be used as a marker for gastroesophageal reflux disease.     

Vacuolating megalencephalic leukoencephalopathy with subcortical cysts: functional studies of novel variants in MLC1

Nine new unrelated patients presenting vacuolating myelinopathy with subcortical cysts were identified and analyzed for variations in the MLC1 gene. We detected 12 mutations (p.Leu37fs, p.Met80Val, p.Leu83Phe, p.Pro92Ser, p.Ser93Leu, p.Ile108fs, p.Gly130Arg, p.Cys171fs, p.Glu202Lys, p.Ser269Tyr, p.Ala275Asn, and p.Leu310_311insLeu) of which nine were novel. In one patient we did not detect mutations. Using a heterologous system, three new missense variants (p.Glu202Lys, p.Ser269Tyr, and p.Ala275Asn) and a single leucine insertion (p.Leu310insLeu)--lying in a stretch of seven leucines--were functionally assayed by determining total protein levels and mutant protein expression at the plasma membrane. No correlation was observed between mutation, clinical features, and plasma membrane expression of mutant protein.     

Laboratory Diagnosis of Human Herpesvirus 8 Infection in Humans

Human herpesvirus 8 (HHV-8) is causally associated with Kaposi's sarcoma, primary effusion lymphoma and multicentric Castleman's disease. Serological and molecular biology assays are used to investigate the biology of this virus in different populations and diseases. Serological assays are mainly used to study the prevalence of the viral infection and to predict the diagnosis of Kaposi's sarcoma and other HHV-8-associated cancers. The appearance of antibodies against lytic antigens precedes the appearance of antibodies against latent antigens, probably explaining the lower sensitivity of assays based on latent HHV-8 antigens. The lack of international reference serum panels is presently the major bottleneck for further progress in the field of HHV-8 serology. Molecular biological assays are an absolute requirement for both the diagnosis and the follow-up of HHV-8 infection. Qualitative methods have been particularly useful to elucidate the mode of transmission and the causal association between HHV-8 and HHV-8-associated diseases. Quantitative methods have become an essential tool to monitor the progression of the infection and the effects of antiviral therapies. This review analyzes the performance of the different serological and molecular biological assays available at present. The main conclusion is that more research is needed to define the most useful laboratory tests for the diagnosis of HHV-8 infection and to establish the clinical role of such tests. Electronic Publication     

Sexual disparities in the incidence and course of SLE and RA

Systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) disproportionately affect females compared to males, with female to male prevalence ratios of 7–9:1 for SLE and 2–3:1 for RA. Interestingly, epidemiologic studies indicate that men that develop SLE may have more morbidity than women, but the same is not true for RA. Given the sex and age bias of SLE and RA, sex hormones may influence the pathogenesis of these diseases. However, the ways in which, and to what degree, sex hormones affect disease incidence and severity remain unclear and is the topic of ongoing research. Recent findings have implicated interactions between sex hormones, the immune system, genetic factors, and epigenetic modifications in influencing SLE and RA disease activity. This article reviews current hypotheses regarding the potential impact of sex hormones and genetics on disease pathogenesis, incidence, and severity of SLE and RA.     

Dysfunctions within limbic–motor networks in amyotrophic lateral sclerosis

Previous studies have shown that affective symptoms are part of the clinical picture in amyotrophic lateral sclerosis (ALS), the most common motor neuron disorder in elderly people. Diffuse neurodegeneration of limbic regions (e.g., prefrontal cortex [PFC], amygdala) was demonstrated in ALS post-mortem, although the mechanisms of emotional dysregulation in ALS in vivo remain unclear. Using functional imaging, we assessed the brain responses to emotional faces in 11 cognitively unimpaired ALS patients and 12 healthy controls (HCs). We tested whether regional activities and connectivity patterns in the limbic system differed between ALS patients and HCs and whether the variability in clinical measures modulated the neuroimaging data. Relative to HCs, ALS patients displayed greater activation in a series of PFC areas and altered left amygdala–PFC connectivity. Anxiety modulated the right amygdala–PFC connectivity in HCs but not in ALS patients. Reduced right premotor cortex activity and altered left amygdala–supplementary motor area connectivity were associated with longer disease duration and greater disease severity, respectively. Our findings demonstrate dysfunctions of the limbic system in ALS patients at early stages of the disease, and extend our knowledge about the interplay between emotional brain areas and the regions traditionally implicated in motor control.     

The strength of primary care in Europe: an international comparative study

Background

A suitable definition of primary care to capture the variety of prevailing international organisation and service-delivery models is lacking.

Aim

Evaluation of strength of primary care in Europe.

Design and setting

International comparative cross-sectional study performed in 2009–2010, involving 27 EU member states, plus Iceland, Norway, Switzerland, and Turkey.

Method

Outcome measures covered three dimensions of primary care structure: primary care governance, economic conditions of primary care, and primary care workforce development; and four dimensions of primary care service-delivery process: accessibility, comprehensiveness, continuity, and coordination of primary care. The primary care dimensions were operationalised by a total of 77 indicators for which data were collected in 31 countries. Data sources included national and international literature, governmental publications, statistical databases, and experts’ consultations.

Results

Countries with relatively strong primary care are Belgium, Denmark, Estonia, Finland, Lithuania, the Netherlands, Portugal, Slovenia, Spain, and the UK. Countries either have many primary care policies and regulations in place, combined with good financial coverage and resources, and adequate primary care workforce conditions, or have consistently only few of these primary care structures in place. There is no correlation between the access, continuity, coordination, and comprehensiveness of primary care of countries.

Conclusion

Variation is shown in the strength of primary care across Europe, indicating a discrepancy in the responsibility given to primary care in national and international policy initiatives and the needed investments in primary care to solve, for example, future shortages of workforce. Countries are consistent in their primary care focus on all important structure dimensions. Countries need to improve their primary care information infrastructure to facilitate primary care performance management.     

Plasma levels of matrix metalloproteinase‐9 in chronic urticaria patients correlate with disease severity and C‐reactive protein but not with circulating histamine‐releasing factors

Background Matrix metalloproteinase‐9 (MMP‐9) is an endopeptidase produced by many inflammatory cells that has been found in increased amounts in plasma from patients with chronic urticaria (CU). Objective To evaluate plasma levels of MMP‐9 and its tissue inhibitor of metalloproteinase‐1 (TIMP‐1) in CU patients in relation with disease severity, C‐reactive protein (CRP) and circulating histamine‐releasing factors. Methods Fifty‐two consecutive CU patients were included in the study and disease activity was graded from 0 to 3. Plasma MMP‐9, TIMP‐1 and CRP levels were measured by enzyme immunoassays. Circulating histamine‐releasing factors were assessed using in vivo (autologous serum skin test) and in vitro (basophil histamine release) tests. Seven CU patients were studied both during active disease and during remission. Thirty healthy subjects were used as normal controls. Results Plasma levels of MMP‐9, TIMP‐1 and CRP were significantly higher in CU patients than in healthy controls (P=0.0001, 0.003 and 0.005, respectively) and a trend towards a higher MMP‐9/TIMP‐1 molar ratio was found (P=0.051). A significant correlation was found between plasma MMP‐9 levels and urticaria severity score (r=0.48, P<0.0001). CRP levels correlated with MMP‐9 levels (r=0.37, P=0.008) and CU severity score (r=0.52, P=0.0001), but not with TIMP‐1 (r=0.13) concentrations. MMP‐9, TIMP‐1 and CRP plasma levels and MMP‐9/TIMP‐1 molar ratio did not differ in patients either with or without an evidence of circulating histamine‐releasing factors. Seven patients evaluated during remission showed a significant reduction of MMP‐9 and CRP plasma levels. Conclusion Plasma levels of MMP‐9 and its inhibitor TIMP‐1 are increased in CU patients. MMP‐9 levels are associated with disease severity and CRP levels, but not with skin reactivity to autologous serum and with circulating histamine‐releasing factors. These findings suggest that in CU there is an ongoing inflammatory process independent of the presence of circulating histamine‐releasing factors.     

“In-house” pharmacological management for computed tomography coronary angiography: heart rate reduction, timing and safety of different drugs used during patient preparation

We retrospectively evaluated the effect, timing and safety of different pharmacological strategies during 64-slice CT coronary angiography (CT-CA). From the institutional database of CT-CA we enrolled 560 consecutive patients with suspected coronary artery disease. The type of drug preparation (group 1 = no treatment; group 2 = oral metoprolol; group 3 = other; group 4?=?intravenous (IV) atenolol; group 5?=?IV atenolol + nitrates; NR = non-responders), timing, and adverse effects were recorded. Heart rate (HR) during different preparation phases was recorded. Four adverse effects were recorded, none of which was attributable to pharmacological treatment. In all groups, except group 1, the HR on arrival was significantly reduced by the pharmacological treatment (p?<?0.01). Group 4 showed the best (?16?±?8 bpm) HR reduction. There was no significant effect on HR due to nitrates (p?=?0.49), while a slight increase due to contrast material was noted (p?<?0.05). Average time required for preparation was 44?±?25 min. Groups 4 and 5 showed the most effective timing (8?±?9 min and 8?±?8 min, respectively; p?<?0.01). Pharmacological preparation in patients undergoing CT-CA is safe and effective. Best results in terms of HR reduction and fast preparation are obtained with IV administration of beta-blockers.     

Multi-View Ensemble Classification of Brain Connectivity Images for Neurodegeneration Type Discrimination

Brain connectivity analyses using voxels as features are not robust enough for single-patient classification because of the inter-subject anatomical and functional variability. To construct more robust features, voxels can be aggregated into clusters that are maximally coherent across subjects. Moreover, combining multi-modal neuroimaging and multi-view data integration techniques allows generating multiple independent connectivity features for the same patient. Structural and functional connectivity features were extracted from multi-modal MRI images with a clustering technique, and used for the multi-view classification of different phenotypes of neurodegeneration by an ensemble learning method (random forest). Two different multi-view models (intermediate and late data integration) were trained on, and tested for the classification of, individual whole-brain default-mode network (DMN) and fractional anisotropy (FA) maps, from 41 amyotrophic lateral sclerosis (ALS) patients, 37 Parkinson’s disease (PD) patients and 43 healthy control (HC) subjects. Both multi-view data models exhibited ensemble classification accuracies significantly above chance. In ALS patients, multi-view models exhibited the best performances (intermediate: 82.9%, late: 80.5% correct classification) and were more discriminative than each single-view model. In PD patients and controls, multi-view models’ performances were lower (PD: 59.5%, 62.2%; HC: 56.8%, 59.1%) but higher than at least one single-view model. Training the models only on patients, produced more than 85% patients correctly discriminated as ALS or PD type and maximal performances for multi-view models. These results highlight the potentials of mining complementary information from the integration of multiple data views in the classification of connectivity patterns from multi-modal brain images in the study of neurodegenerative diseases.     

Subcortical motor plasticity in patients with sporadic ALS: An fMRI study

OBJECTIVE: To address the potential contribution of subcortical brain regions in the functional reorganization of the motor system in patients with sporadic ALS (sALS) and to investigate whether functional changes in brain activity are different in sALS patients with predominant upper motor neuron (UMN) or lower motor neuron (LMN) dysfunction. METHODS: We studied 16 patients with sALS and 13 healthy controls, using BOLD-fMRI, while they performed a simple visually paced motor task. Seven patients had definite clinical UMN signs while nine patients had prevalent clinical and electrophysiological LMN involvement. fMRI data were analyzed with Brain Voyager QX. RESULTS: Task-related functional changes were identified in motor cortical regions in both patients and healthy controls. Direct group comparisons revealed relatively decreased BOLD fMRI responses in left sensorimotor cortex, lateral premotor area, supplementary motor area and right posterior parietal cortex (p < 0.05 corrected) and relatively increased responses in the left anterior putamen (p < 0.001 uncorrected) in sALS patients. Additional analyses between the two patients subgroups demonstrated significant BOLD fMRI response differences in the anterior cingulate cortex and right caudate nucleus (p < 0.001 uncorrected) with more robust activation of these areas in patients with greater UMN burden. Importantly, there were no significant differences in performance of the motor task between sALS patients and controls as well as between sALS patient subgroups. CONCLUSIONS: Our data demonstrate a different BOLD fMRI pattern between our sALS patients and healthy controls even during simple motor behavior. Furthermore, patients with sALS and greater UMN involvement show a different reorganization of the motor system compared to sALS patients with greater LMN dysfunction.