Is there a crossroad between infections,genetics, and Henoch–Schönlein purpura?

Henoch–Schönlein purpura is the most common systemic vasculitis in childhood, characterized by the presence of immunoglobulin A deposits in the small vessels of skin, gastrointestinal tube, joints and kidneys. Although there have been great efforts made in elucidating its pathogenic mechanisms, Henoch–Schönlein purpura etiology remains unknown: the basic scene comes across an abnormal inflammatory process deriving from immune reactions to various antigenic stimuli, which might be bacterial, viral, or parasitic agents, in a genetically prone individual. Then, a peculiar immune complex deposition in the vascular walls and overproduction of different proinflammatory molecules elicit different clinical signs, which might be differentiated according to either a specific trigger or a specific genetic make-up. The aim of this review is to make a critical appraisal of the last 15 years' medical literature concerning the relationship between infections, genetics, and Henoch–Schönlein purpura in pediatrics.     

The role of small intestinal bacterial overgrowth in Parkinson's disease

Parkinson's disease is associated with gastrointestinal motility abnormalities favoring the occurrence of local infections. The aim of this study was to investigate whether small intestinal bacterial overgrowth contributes to the pathophysiology of motor fluctuations. Thirty‐three patients and 30 controls underwent glucose, lactulose, and urea breath tests to detect small intestinal bacterial overgrowth and Helicobacter pylori infection. Patients also underwent ultrasonography to evaluate gastric emptying. The clinical status and plasma concentration of levodopa were assessed after an acute drug challenge with a standard dose of levodopa, and motor complications were assessed by Unified Parkinson's Disease Rating Scale–IV and by 1‐week diaries of motor conditions. Patients with small intestinal bacterial overgrowth were treated with rifaximin and were clinically and instrumentally reevaluated 1 and 6 months later. The prevalence of small intestinal bacterial overgrowth was significantly higher in patients than in controls (54.5% vs. 20.0%; P = .01), whereas the prevalence of Helicobacter pylori infection was not (33.3% vs. 26.7%). Compared with patients without any infection, the prevalence of unpredictable fluctuations was significantly higher in patients with both infections (8.3% vs. 87.5%; P = .008). Gastric half‐emptying time was significantly longer in patients than in healthy controls but did not differ in patients based on their infective status. Compared with patients without isolated small intestinal bacterial overgrowth, patients with isolated small intestinal bacterial overgrowth had longer off time daily and more episodes of delayed‐on and no‐on. The eradication of small intestinal bacterial overgrowth resulted in improvement in motor fluctuations without affecting the pharmacokinetics of levodopa. The relapse rate of small intestinal bacterial overgrowth at 6 months was 43%. © 2013 Movement Disorder Society     

MYH9-related disease: Five novel mutations expanding the spectrum of causative mutations and confirming genotype/phenotype correlations

MYH9-related disease (MYH9-RD) is a rare autosomal dominant syndromic disorder caused by mutations in MYH9, the gene encoding for the heavy chain of non-muscle myosin IIA (myosin-9). MYH9-RD is characterized by congenital macrothrombocytopenia and typical inclusion bodies in neutrophils associated with a variable risk of developing sensorineural deafness, presenile cataract, and/or progressive nephropathy. The spectrum of mutations responsible for MYH9-RD is limited. We report five families, each with a novel MYH9 mutation. Two mutations, p.Val34Gly and p.Arg702Ser, affect the motor domain of myosin-9, whereas the other three, p.Met847_Glu853dup, p.Lys1048_Glu1054del, and p.Asp1447Tyr, hit the coiled-coil tail domain of the protein. The motor domain mutations were associated with more severe clinical phenotypes than those in the tail domain.     

Unemployment as a Risk Factor for Completed Suicide: A Psychological Autopsy Study

This study adopts a psychological autopsy method to compare (1) unemployed suicides, (2) other suicides who were either employed or not in the labor force, and (3) psychiatric outpatients without any prior suicidal behavior. A total of 245 consecutive suicides from Province of Parma (Italy) with recorded employment status were included in the analysis. The control group included 41 psychiatric outpatients aged 18 to 64 years, who had not engaged in any previous suicidal act, and who were unemployed. The unemployed suicides had a risk 17 times higher to have had financial problems in the last 12 months (95% confidence interval [CI]: 2.0/149.5; p < 0.01) than other suicides. Unemployed suicides (compared to living unemployed controls) were 10 times more likely to have had poor social support (95% CI: 1.7/56.1; p < 0.01), 16 times more likely to have had any stressful life events in the past 12 months (95% CI: 2.5/103.9; p < 0.01), and 22 times more likely to have a diagnosis of borderline personality disorder (95% CI: 2.4/203.2; p < 0.01). New suicide prevention strategies for those who are facing job loss need to focus on social support and personality disorders, as well as hopelessness and despair.     

Cortical sources of resting state electroencephalographic alpha rhythms deteriorate across time in subjects with amnesic mild cognitive impairment

Cortical sources of resting state electroencephalographic (EEG) rhythms are abnormal in subjects with mild cognitive impairment (MCI). Here, we tested the hypothesis that these sources in amnesic MCI subjects further deteriorate over 1 year. To this aim, the resting state eyes-closed EEG data were recorded in 54 MCI subjects at baseline (Mini Mental State Examination I = 26.9; standard error [SE], 0.2) and at approximately 1-year follow-up (13.8 months; SE, 0.5; Mini Mental State Examination II = 25.8; SE, 0.2). As a control, EEG recordings were also performed in 45 normal elderly and in 50 mild Alzheimer's disease subjects. EEG rhythms of interest were delta (2–4 Hz), theta (4–8 Hz), alpha1 (8–10.5 Hz), alpha2 (10.5–13 Hz), beta1 (13–20 Hz), and beta2 (20–30 Hz). Cortical EEG sources were estimated using low-resolution brain electromagnetic tomography. Compared with the normal elderly and mild Alzheimer's disease subjects, the MCI subjects were characterized by an intermediate power of posterior alpha1 sources. In the MCI subjects, the follow-up EEG recordings showed a decreased power of posterior alpha1 and alpha2 sources. These results suggest that the resting state EEG alpha sources were sensitive—at least at the group level—to the cognitive decline occurring in the amnesic MCI group over 1 year, and might represent cost-effective, noninvasive and widely available markers to follow amnesic MCI populations in large clinical trials.     

Occurrence of Spontaneous Periodontal Disease in the SAMP1/YitFc Murine Model of Crohn Disease

Background: Oral involvement is often associated with inflammatory bowel disease (IBD). Recent evidence suggests a high incidence of periodontal disease in patients with Crohn disease (CD). To the best of the authors’ knowledge, no animal model of IBD that displays associated periodontal disease was reported previously. The aim of this study is to investigate the occurrence and progression of periodontal disease in SAMP1/YitFc (SAMP) mice that spontaneously develop a CD‐like ileitis. In addition, the temporal correlation between the onset and progression of periodontal disease and the onset of ileitis in SAMP mice was studied. Methods: At different time points, SAMP and parental AKR/J (AKR) control mice were sacrificed, and mandibles were prepared for stereomicroscopy and histology. Terminal ilea were collected for histologic assessment of inflammation score. Periodontal status, i.e., alveolar bone loss (ABL) and alveolar bone crest, was examined by stereomicroscopy and histomorphometry, respectively. Results: ABL increased in both strains with age. SAMP mice showed greater ABL compared with AKR mice by 12 weeks of age, with maximal differences observed at 27 weeks of age. AKR control mice did not show the same severity of periodontal disease. Interestingly, a strong positive correlation was found between ileitis severity and ABL in SAMP mice, independent of age. Conclusions: The present results demonstrate the occurrence of periodontal disease in a mouse model of progressive CD‐like ileitis. In addition, the severity of periodontitis strongly correlated with the severity of ileitis, independent of age, suggesting that common pathogenic mechanisms, such as abnormal immune response and dysbiosis, may be shared between these two phenotypes.     

Effectiveness of systemic amoxicillin/metronidazole as adjunctive therapy to scaling and root planing in the treatment of chronic periodontitis: a systematic review and meta-analysis

Background: The combination of Amoxicillin and metronidazole (AMX/MET) as an adjunctive treatment to scaling root planing (SRP) has been proposed for the treatment of chronic periodontitis; however, its effectiveness and clinical safety remain to be defined. The purpose of the present meta-analysis is to assess the effectiveness of SRP + AMX/MET compared to SRP alone. Methods: An electronic search of eight databases from their earliest records through October 8, 2011 and a hand search of international dental journals for the last 15 years were conducted. Gain in clinical attachment level (CAL), reduction in probing depth (PD), secondary outcomes, and adverse events were analyzed. A random-effect model was used to pool the extracted data. The weighted mean difference (WMD) with 95% confidence interval (CI) was calculated for continuous outcomes; heterogeneity was assessed with the Cochrane χ(2) and I(2) tests. The level of significance was set at P <0.05. Results: After the selection process, four randomized clinical trials were included. Results of the meta-analysis showed significant CAL gain (WMD = 0.21; 95% CI = 0.02 to 0.4; P <0.05) and PD reduction (WMD = 0.43; 95% CI = 0.24 to 0.63; P <0.05) in favor of SRP + AMX/MET. No significant differences were found for bleeding on probing (WMD = 10.77; 95% CI = -3.43 to 24.97; P >0.05) or suppuration (WMD = 1.77; 95% CI = -1.7 to 5.24; P >0.05). Conclusion: The findings of this meta-analysis seem to support the effectiveness of SRP + AMX/MET; however, future studies are needed to confirm these results.     

Laser-evoked potentials as a novel tool for sensibility assessment following inferior pedicle breast reduction

Background

Nipple-areola complex numbness is common following breast reduction with most techniques. The aim of our study was to objectively quantify specific sensory outcomes before and after inferior pedicle breast reduction with two combined neurophysiological methods: dermatomal somatosensory evoked potentials (D-SEPs) and laser-evocated potentials (LEPs).

Methods

Patients’ subjective breast sensation was assessed preoperatively and postoperatively by accurate clinical examinations. Thirty patients underwent quantitative measurements preoperatively and at 3 and 6 months following inferior pedicle breast reduction to assess tactile and vibratory sensitivity (D-SEP recordings) and painful and thermic sensitivity (LEP recordings).

Results

The collected data did not reveal significant differences in D-SEP latencies or amplitudes between preoperative and postoperative evaluations following inferior pedicle breast reduction. However, LEP data showed significant alterations in latency and amplitude in accordance with clinical examinations.

Conclusions

This study provides the basis for a new approach to selectively investigate painful and thermic sensitivity, which is necessary to find the best technique to preserve breast sensitivity. This study also provides the first objective neurophysiologic evidence of breast sensitivity modifications and introduces a new technique that provides a simple, inexpensive, and dependable investigative tool for breast sensitivity assessment in breast surgery. Level of Evidence: Level III, diagnostic study     

Fecal calprotectin and alpha-1 antitrypsin predict severity and response to corticosteroids in gastrointestinal graft-versus-host disease

Diagnosis of gastrointestinal GVHD (GI-GVHD) is based on clinical symptoms and histologic findings. No biomarkers predicting responses to treatment are routinely available even though 30% to 50% of patients will not respond to corticosteroids. In this study, we aimed to evaluate fecal calprotectin, α-1-antitrypsin (α(1)-AT), and elastase at the time of first symptoms as diagnostic and prognostic tools for GI-GVHD in 72 consecutive patients, of whom 51 developed GI-GVHD. The prognostic value of markers was evaluated by their association with complete response (CR) and steroid-resistant (SR) GVHD. Calprotectin and α(1)-AT concentrations increased with GI-GVHD initial stages but patients with initial stage 1 GI-GVHD had similar marker levels to patients without GI-GVHD, so sensitivity to diagnose GI-GVHD was weak. In contrast, calprotectin and α(1)-AT were predictors for SR-GVHD and CR. Multiple regression modeling identified calprotectin and α(1)-AT concentration as independently predicting SR-GVHD together with initial stage > 2 GI-GVHD. Our results showed that fecal calprotectin and α(1)-AT levels at the time of diagnosis are predictive for responses to treatment but are not diagnostic markers for initial stage 1 to 3 GI-GVHD.     

Nerve growth factor regulates axial rotation during early stages of chick embryo development

Nerve growth factor (NGF) was discovered because of its neurotrophic actions on sympathetic and sensory neurons in the developing chicken embryo. NGF was subsequently found to influence and regulate the function of many neuronal and non neuronal cells in adult organisms. Little is known, however, about the possible actions of NGF during early embryonic stages. However, mRNAs encoding for NGF and its receptors TrkA and p75(NTR) are expressed at very early stages of avian embryo development, before the nervous system is formed. The question, therefore, arises as to what might be the functions of NGF in early chicken embryo development, before its well-established actions on the developing sympathetic and sensory neurons. To investigate possible roles of NGF in the earliest stages of development, stage HH 11-12 chicken embryos were injected with an anti-NGF antibody (mAb αD11) that binds mature NGF with high affinity. Treatment with anti-NGF, but not with a control antibody, led to a dose-dependent inversion of the direction of axial rotation. This effect of altered rotation after anti NGF injection was associated with an increased cell death in somites. Concurrently, a microarray mRNA expression analysis revealed that NGF neutralization affects the expression of genes linked to the regulation of development or cell proliferation. These results reveal a role for NGF in early chicken embryo development and, in particular, in the regulation of somite survival and axial rotation, a crucial developmental process linked to left-right asymmetry specification.