Mucosal loss with increased expression of IL-6, IL-8, and COX-2 in a formula-feeding only neonatal rat model of necrotizing enterocolitis

Introduction

The aim of our study is to establish a reliable neonatal rat model by formula feeding only for evaluation of early surgical intervention on the course of experimental necrotizing enterocolitis (NEC).

Material and methods

Newborn Sprague–Dawley rats were divided into 50 breast-fed (group 1) and 38 formula fed (Similac/Esbilac, group 2) animals. The pups were sacrificed on the 4th, 5th, and 6th day of life and the terminal intestine examined for macroscopic and histologic changes as well as cytokine expression.

Results

The histological mucosal damage was significantly higher of group 2 compared to group 1. The area of the vital mucosa of group 2 was significantly (58.57%, p < 0.001) lower compared to group 1 (75.12%). The mRNA expression of the inflammatory cytokines IL-6, IL-8 and COX-2 was significantly 2-, 5- and 10-fold increased in group 2 compared to group 1.

Discussion

Formula fed newborn rats displayed an inflammatory enterocolitis similar to human NEC. Our study demonstrates a significant loss of mucosa in animals with NEC having increased expression levels of IL-6, IL-8 and COX-2. Mucosal loss appears to be a distinct feature of experimental NEC and has to be correlated with the human disease.     

Environmental mercury exposure,semen quality and reproductive hormones in Greenlandic Inuit and European men: a cross-sectional study

Several animal studies indicate that mercury is a male reproductive toxicant, but human studies are few and contradictory. We examined semen characteristics and serum levels of reproductive hormones in relation to environmental exposure to mercury. Blood and semen samples were collected from 529 male partners of pregnant women living in Greenland, Poland and Ukraine between May 2002 and February 2004. The median concentration of the total content of mercury in whole blood was 9.2 ng ml⁻¹ in Greenland (0.2–385.8 ng ml⁻¹), 1.0 ng ml⁻¹ in Poland (0.2–6.4 ng ml⁻¹) and 1.0 ng ml⁻¹ in Ukraine (0.2–4.9 ng ml⁻¹). We found a significantly positive association between the blood levels of mercury and serum concentration of inhibin B in men from Greenland (β=0.074, 95% confidence interval (CI)=0.021 to 0.126) and in an analysis including men from all three regions (β=0.067, 95% CI=0.024 to 0.110). The association may be due to beneficial effects of polyunsaturated fatty acids (PUFAs), which are contained in seafood and fish. No significant association (P>0.05) was found between blood concentrations of mercury and any of the other measured semen characteristics (semen volume, total sperm count, sperm concentration, morphology and motility) and reproductive hormones (free androgen index (FAI), follicle-stimulating hormone (FSH), luteinizing hormone (LH), testosterone and LH×testosterone) in any region. In conclusion, the findings do not provide evidence that environmental mercury exposure in Greenlandic and European men with median whole blood concentration up to 10 ng ml⁻¹ has adverse effects on biomarkers of male reproductive health.     

P300 in obsessive–compulsive disorder: Source localization and the effects of treatment

Converging evidence suggests that frontostriatal abnormalities underlie OCD symptoms. The event-related potential P300 is generated along a widely distributed network involving several of the areas implicated in OCD. P300 abnormalities reported in patients with OCD suggest increased activity in these areas. The aim of the present study was to investigate this assumption in unmedicated patients with OCD, and to assess the effects of OCD treatment on P300 brain activity patterns. Seventy-one unmedicated patients with a DSM-IV diagnosis of OCD and 71 age- and gender-matched healthy control subjects participated in the study. The P300 was obtained through 32-channel EEG during an auditory oddball paradigm. Forty-three patients underwent a second EEG assessment after treatment with sertraline and behavioural therapy. Low-resolution electromagnetic tomography (LORETA) was used to localize the sources of brain electrical activity. Results: Increased P300-related activity was observed predominantly in the left orbitofrontal cortex, but also in left prefrontal, parietal and temporal areas, in patients compared to controls at baseline. After treatment, reduction of left middle frontal cortex hyperactivity was observed in patients. Conclusions: Findings of increased activity in frontoparietal areas in patients are consistent with several previous studies. Importantly, OCD treatment led to reduction of hyperactivity in the left middle frontal cortex, an area associated with context processing and uncertainty that might be important for the emergence of OCD symptoms. Thus, the present study is the first to show an association between P300 abnormalities and activity in brain regions postulated to be involved in the pathophysiology of OCD.     

Pisa syndrome in Parkinson’s disease: an electrophysiological and imaging study

The pathophysiology of postural abnormalities in patients with Parkinson’s disease is poorly understood. In the present study, 13 patients with Pisa syndrome (PS) underwent EMG study of paraspinal lumbar (L2–L4) and thoracic (T8–T10) muscles, and of non-paraspinal muscles. Patients also underwent a whole spine X-ray and an MRI assessment of paraspinal muscles (L1–S1). The EMG evaluation disclosed two main patterns: patients with pattern I (n = 6, hyperactivity of lumbar paraspinals ipsilateral to the trunk leaning side) or pattern II (n = 7: hyperactivity of lumbar paraspinals contralateral to the trunk leaning side. In pattern I, half the patients also had ipsilateral hyperactivity of the thoracic paraspinals, the other half had contralateral thoracic hyperactivity; in pattern II, thoracic paraspinal hyperactivity was contralateral in all patients (like the lumbar paraspinal hyperactivity). Non-paraspinal muscles were hyperactive ipsilaterally in four of six patients with pattern I and in all patients with pattern II. The MRI showed mild muscular atrophy with fatty degeneration in patients with pattern I, whereas in pattern II patients this was greater and prevalent on paraspinal lumbar muscles ipsilateral to the leaning side. The present data support the hypothesis that two main patterns of muscular activation are associated with PS. In both patterns, hyperactivity of contralateral paraspinal muscles is probably compensatory for the trunk leaning.     

Four-year follow-up of a controlled memory training study in closed head injured patients

Abstract

In a controlled group study Berg, Koning-Haanstra, and Deelman (1991) compared the effects of memory strategy training with the effects of drill and practice training and no treatment in severely head injured patients. Four months after training the group in the strategy condition performed significantly better on three memory tests than the patient groups in the other two conditions. Four years following this last evaluation, 31 of the 38 patients from the original training study were retested on the same memory tests. Thirteen normal subjects, who had already served as normal controls in the training study, were also retested. In contrast to the results four years earlier, memory performance was the same for all three patient groups. The level of performance of the patients was still well below the level of the normal controls. One reason for the disappearance of the advantage of the strategy group over the other two patient groups, was the drop-out of patients with relatively poor memory scores on the previous evaluation. A second reason was the improvement in memory performance relative to the previous evaluation found in the drill and practice and the no-treatment groups.     

Influence of ANKK1 and DRD2 polymorphisms in response to haloperidol

The present study explores whether ankyrin repeat and kinase domain containing 1 (ANKK1) and dopamine receptor D2 (DRD2) variants could predict efficacy and tolerability of haloperidol in the treatment of psychotic patients. We also attempted to replicate findings in a group of schizophrenic patients from the Clinical Antipsychotic Trials in Intervention Effectiveness (CATIE) study. Eighty-eight acutely psychotic patients were genotyped for 9 ANKK1 and 27 DRD2 SNPs. Treatment efficacy and tolerability were assessed using the Positive and Negative Symptoms Scale and the Udvalg for Kliniske Undersogelser side effects rating scales, respectively. Multivariate analyses were employed to test possible influences of single-nucleotide polymorphisms on clinical and safety variables. Analysis of haplotypes was also performed. Outcomes in the replication sample were response versus nonresponse and the presence versus absence of motor side effects at 1 month of treatment. rs2242592 within ANKK1 gene and rs1124493 within DRD2 gene were associated with clinical improvement (p = 0.008 and p = 0.001, respectively). Results were confirmed in the allelic analysis. Three haplotype blocks, one among ANKK1 and two among DRD2 gene were associated with better clinical improvement. Our results were not replicated in the CATIE sample, although rs11604671, which is in strong linkage disequilibrium with rs2242592, was associated with response in the replication sample. Our findings support a possible role of ANKK1 and DRD2 variability on haloperidol efficacy. However, due to the discrepancies between the results in the two samples, our results need further validation.     

MAOA and MAOB polymorphisms and anger-related traits in suicidal participants and controls

MAOA and, to a lesser extent, MAOB polymorphisms have been related to aggression traits and suicidality. We aimed to investigate the role of MAOA and MAOB in suicidal versus non-suicidal participants and interactions between genetic variation and suicidal status on aggression and anger-related traits. The sample was composed of three groups: one group of suicide attempters (n = 171, males 35.1 %), one group of suicide completers (n = 90, males 57.8 %) and a healthy control group (n = 317, males 43.8 %). We examined the following markers: MAOA rs909525, rs6323, and rs2064070, and MAOB rs1799836. Anger traits were measured with the state-trait anger expression inventory (STAXI) and aggression traits with the questionnaire for measuring factors of aggression (FAF). Associations were separately examined for males and females. Variation in the three MAOA variants was associated with higher levels of anger expressed outwards (STAXI “anger-out” subscale) in male suicidal patients compared to controls (p < 0.001). In females, the C allele of rs6323 showed higher scores on the same subscale (“anger out”) (p = 0.002). Allele frequencies of the MAOA rs909525 were associated with suicidality (p < 0.007). Our findings show an association between genetic variation in three polymorphisms of the MAOA and anger traits in suicidal males and one replication for the functional variant rs6323 in females. This relationship was stronger than a direct genetic association with suicide status. Future studies incorporating endophenotypic measures of anger and aggression in suicidal participants are warranted.     

Mental health treatment seeking among patients with OCD: impact of age of onset

Background

Several studies have described the deficits in the health care provided to persons with obsessive–compulsive disorder (OCD), however, without making any distinction between psychiatric–psychotherapeutic professionals and general practitioners or other professionals. Also, the relation between subjectively defined early signs of the disorder, diagnosis and utilization of professional help has not yet been investigated systematically. The present study addresses these questions, using a self-rating questionnaire for patients with OCD (questionnaire on the utilization of professional help by patients with OCD).

Methods

Eighty-eight patients with OCD, who came to our University Hospital Outpatient Clinic for obsessive–compulsive disorders in Leipzig, participated in the study. The questionnaire, which had been developed specially for this survey, asked study participants to remember when they had first perceived signs of their disorder and their first-time utilization of professional help.

Results

Patients with OCD and early onset of disorder sought professional help later than did patients with later onset of disorder. When professional help was utilized, it took 2 years on average before the diagnosis was made. Patients with OCD first consulted a psychiatrist or psychotherapist and not the general practitioner as their first professional contact person.

Conclusion

First signs in the early stages of OCD, particularly with an onset in childhood and adolescence have to be diagnosed at an earlier stage for appropriate treatment. Psychiatrists and psychotherapists, not primarily general practitioners, have a particularly high demand for further education about early diagnosis and treatment of OCD.     

Prognostic impact of incomplete surgical clearance of radioiodine sensitive local lymph node metastases diagnosed by post-operative <Superscript>124</Superscript>I-NaI-PET/CT in patients with papillary thyroid cancer

Purpose

Nodal involvement is an independent risk factor of recurrence in papillary thyroid cancer (PTC). Neither the international guidelines nor the recently introduced ongoing risk adaptation concept consider the extent of initial surgical clearance of radioiodine sensitive lymph node metastases in their stratification systems. We investigated the prognostic relevance of incomplete initial surgical clearance in patients with purely lymphogeneous metastatic PTC (pN1 M0) despite successful radioiodine therapy. Accurate assessment of pre-ablative nodal status was attempted using PET/CT studies with both ¹²⁴I-NaI and ¹⁸F-FDG along with high-resolution cervical ultrasound.

Methods

Sixty-five patients with histologically diagnosed lymph node metastases (pN1 M0) were retrospectively analyzed. Patients with iodine-negative lymph node metastases diagnosed by ¹⁸F-FDG PET/CT or distant metastases were excluded from the analysis. The association of disease recurrence with the pre-ablative nodal status, as well as other baseline characteristics, were examined applying nonparametric tests for independent samples and multiple regression analysis. Patients with persistent lymph node metastases in ¹²⁴I-NaI PET/CT were further divided according to the additional presence or absence of FDG-uptake in ¹⁸F-FDG PET/CT. Survival analyses were performed using Kaplan–Meier curves and the Cox proportional hazards model for uni- and multivariate analyses to assess the influence of prognostic factors on progression free survival (PFS).

Results

Incomplete metastatic lymph node resection captured by ¹²⁴I-NaI PET/CT (n?=?33) was an independent risk factor for recurrence (61 % vs 25 %, p?=?0.006) and shorter PFS (46 months vs not reached, HR 4.0 [95 %-CI, 1.7–9.2], p?=?0.001). Ultrasound could detect lymph node metastases only in 19/33 patients (58 %). Among patients with positive nodal status, FDG-avidity of metastatic iodine positive lymph nodes worsened the outcome (16 vs 69 months, p?=?0.047). From all other investigated factors including age, N-stage (N1a vs N1b), and T-Stage (T4 vs T1-3), only large tumor size (pT4) had a significant impact on PFS (HR 2.9 [95 %-CI, 1.3–6.4], p?=?0.007).

Conclusions

Incomplete initial surgical clearance of lymph node metastases even after successful radioiodine therapy may increase the chances of recurrence and is an independent risk factor for impaired survival of patients with PTC. Pre-ablative (dual tracer PET/CT) imaging with ¹²⁴I-Na and ¹⁸F provides a prognostic tool for these patients and may considerably complement the current risk stratification systems.