The impact of stress on epidermal barrier function: an evidence-based review.

BACKGROUND: The epidermal barrier functions to limit skin infection and inflammation by inhibiting irritant and immunogen invasion. Abundant evidence suggests that psychological stress stemming from crowding, isolation, nicotine smoking, insomnia, mental arithmetic tasks, physical pain, real-life stressors (examinations and marital strain) and lack of positive personality traits may impart both acute and chronic epidermal dysfunction. OBJECTIVES: To review the relationship between stress and epidermal barrier dysfunction. METHODS: A review of the PubMed and Embase databases was conducted to identify all English-language case-control, cross-sectional and randomized control trials that have reported the effect of stress on epidermal barrier function. The authors' conclusions are based on the available evidence from 21 studies that met the inclusion and exclusion criteria. RESULTS: Psychological stressors upregulate the hypothalamic-pituitary-adrenal axis to stimulate local and systemic stress hormone production. This ultimately leads to aberrant barrier dysfunction, characterized by decreased epidermal lipid and structural protein production, decreased stratum corneum hydration and increased transepidermal water loss. CONCLUSIONS: This evidence-based review explores the adverse effects of psychological stressors on epidermal barrier function. Future investigations using more real-life stressors are needed to elucidate further their impact on skin physiology and identify practical stress-relieving therapies that minimize and restore epidermal barrier dysfunction, particularly in at-risk populations. What's already known about this topic? The literature reports the negative effect of stress on prolonged wound healing. Less is known about the relationship between stress and epidermal barrier dysfunction, a chronic, superficial wound involving the upper epidermal layers. What does this study add? Psychological stressors impact epidermal barrier function by activating the hypothalamic-pituitary-adrenal axis to stimulate local and systemic stress hormone production. Stress hormones negatively affect the epidermal barrier by decreasing epidermal lipids and structural proteins, decreasing stratum corneum hydration and increasing transepidermal water loss. Identification of such stressors can promote stress-avoidance and stress-reduction behaviours that protect epidermal barrier function and prevent certain dermatological conditions.

Topical micronutrients in atopic dermatitis-An evidence-based review.

The role of dietary factors is an important and controversial topic in the pathogenesis of atopic dermatitis (AD). Despite the preponderance of consumer products utilizing oral micronutrients supplementation for relief AD symptoms, less attention has been paid on the utility of topical micronutrients, specifically for individuals with AD. We review evidence on topical formulations of vitamins (A, B, C, D, and E) and trace minerals (magnesium, manganese, zinc, and iodine) for treatment of AD. While topical B, C, and E formulations appear to provide some benefit to AD individuals, topical vitamin A has no utility, and topical vitamin D may exacerbate symptoms. Magnesium, zinc, and iodine all appear to improve AD through anti-inflammatory and anti-microbial effects, though future studies must evaluate their use as monotherapy. The exposition of the effects that topical micronutrients have on AD offers an adjuvant treatment modality for this common inflammatory dermatosis.

Neurostimulation for Parkinson's disease with early motor complications.

BACKGROUND: Subthalamic stimulation reduces motor disability and improves quality of life in patients with advanced Parkinson's disease who have severe levodopa-induced motor complications. We hypothesized that neurostimulation would be beneficial at an earlier stage of Parkinson's disease. METHODS: In this 2-year trial, we randomly assigned 251 patients with Parkinson's disease and early motor complications (mean age, 52 years; mean duration of disease, 7.5 years) to undergo neurostimulation plus medical therapy or medical therapy alone. The primary end point was quality of life, as assessed with the use of the Parkinson's Disease Questionnaire (PDQ-39) summary index (with scores ranging from 0 to 100 and higher scores indicating worse function). Major secondary outcomes included parkinsonian motor disability, activities of daily living, levodopa-induced motor complications (as assessed with the use of the Unified Parkinson's Disease Rating Scale, parts III, II, and IV, respectively), and time with good mobility and no dyskinesia. RESULTS: For the primary outcome of quality of life, the mean score for the neurostimulation group improved by 7.8 points, and that for the medical-therapy group worsened by 0.2 points (between-group difference in mean change from baseline to 2 years, 8.0 points; P=0.002). Neurostimulation was superior to medical therapy with respect to motor disability (P<0.001), activities of daily living (P<0.001), levodopa-induced motor complications (P<0.001), and time with good mobility and no dyskinesia (P=0.01). Serious adverse events occurred in 54.8% of the patients in the neurostimulation group and in 44.1% of those in the medical-therapy group. Serious adverse events related to surgical implantation or the neurostimulation device occurred in 17.7% of patients. An expert panel confirmed that medical therapy was consistent with practice guidelines for 96.8% of the patients in the neurostimulation group and for 94.5% of those in the medical-therapy group. CONCLUSIONS: Subthalamic stimulation was superior to medical therapy in patients with Parkinson's disease and early motor complications. (Funded by the German Ministry of Research and others; EARLYSTIM ClinicalTrials.gov number, NCT00354133.).

Deep brain stimulation of the nucleus basalis of Meynert in Alzheimer's dementia.

Cholinergic neurons of the medial forebrain are considered important contributors to brain plasticity and neuromodulation. A reduction of cholinergic innervation can lead to pathophysiological changes of neurotransmission and is observed in Alzheimer's disease. Here we report on six patients with mild to moderate Alzheimer's disease (AD) treated with bilateral low-frequency deep brain stimulation (DBS) of the nucleus basalis of Meynert (NBM). During a four-week double-blind sham-controlled phase and a subsequent 11-month follow-up open label period, clinical outcome was assessed by neuropsychological examination using the Alzheimer's Disease Assessment Scale-cognitive subscale as the primary outcome measure. Electroencephalography and [(18)F]-fluoro-desoxyglucose positron emission tomography were, besides others, secondary endpoints. On the basis of stable or improved primary outcome parameters twelve months after surgery, four of the six patients were considered responders. No severe or non-transitional side effects related to the stimulation were observed. Taking into account all limitations of a pilot study, we conclude that DBS of the NBM is both technically feasible and well tolerated.

Subjectively perceived personality and mood changes associated with subthalamic stimulation in patients with Parkinson's disease.

BACKGROUND: Clinical and ethical implications of personality and mood changes in Parkinson's disease (PD) patients treated with subthalamic deep brain stimulation (STN-DBS) are under debate. Although subjectively perceived personality changes are often mentioned by patients and caregivers, few empirical studies concerning these changes exist. Therefore, we analysed subjectively perceived personality and mood changes in STN-DBS PD patients. METHOD: In this prospective study of the ELSA-DBS group, 27 PD patients were assessed preoperatively and 1 year after STN-DBS surgery. Two categories, personality and mood changes, were analysed with semi-structured interviews. Patients were grouped into personality change yes/no, as well as positive/negative mood change groups. Caregivers were additionally interviewed about patients' personality changes. Characteristics of each group were assessed with standard neurological and psychiatric measurements. Predictors for changes were analysed. RESULTS: Personality changes were perceived by six of 27 (22%) patients and by 10 of 23 caregivers (44%). The preoperative hypomania trait was a significant predictor for personality change perceived by patients. Of 21 patients, 12 (57%) perceived mood as positively changed. Higher apathy and anxiety ratings were found in the negative change group. CONCLUSIONS: Our results show that a high proportion of PD patients and caregivers perceived personality changes under STN-DBS, emphasizing the relevance of this topic. Mood changed in positive and negative directions. Standard measurement scales failed to adequately reflect personality or mood changes subjectively perceived by patients. A more individualized preoperative screening and preparation for patients and caregivers, as well as postoperative support, could therefore be useful.

Management and outcome of pallidal deep brain stimulation in severe Huntington's disease.

Neurodegenerative movement disorders, such as Huntington's disease (HD), have become a promising field for Deep Brain Stimulation (DBS). This study aims to contribute to the establishment of a well-grounded database including both expected and unexpected effects of pallidal DBS in HD, and to discuss the ethical and legal restrictions of DBS in cognitively limited patients. Evaluation of the outcome data indicates that pallidal DBS exerted an independent effect on motor symptoms but probably also on the patient's cognitive and affective state. The cognitive decline, however, that characterizes the late stage of neurodegenerative disorders implicates ethical and legal problems given the patients' inability to give informed consent to DBS.

Stereotactic LINAC radiosurgery for the treatment of brainstem cavernomas.

BACKGROUND: The management of deep-seated cerebral cavernous malformations (CCMs) is still controversial. Although surgery remains the treatment of choice in patients with recurrent hemorrhage, patients with CCMs located in the brainstem are in many cases not eligible for resection due to high procedure-related morbidity and mortality. We evaluated the long-term outcome of LINAC radiosurgery (LINAC-RS) for the treatment of brainstem CCMs. PATIENTS AND METHODS: Between December 1992 and March 2008, 14 patients (6 men, 8 women) harboring brainstem CCMs underwent LINAC-RS. Pretreatment neuroimaging showed no associated developmental venous angiomas (DVAs) in any of our patients. Prior to treatment, all patients suffered at least from one symptomatic hemorrhage (median 1.8, range 1­3). A median follow-up of 7.1 years (range 2.0­16.8 years) could be obtained in 12 patients. We applied a median tumor surface dose of 13.9 Gy (range 11­18 Gy; median tumor volume 1.6 ml, range 0.4­4.3 ml). RESULTS: Following LINAC-RS, neurological outcome improved in 4 (33.3%) and remained unchanged in 8 patients (66.7%). Rebleeding with subsequent transient neurological status deterioration occurred in 4 patients (33.3%), leading to additional surgical resection in 2 patients (16.7%). The corresponding annual hemorrhage rate was 4.8% (4/82.8 patient­years). Adverse radiation effects (ARE, defined by perilesional hyperintensity on T2-weighted MR images) were revealed in 3 patients (25%), leading to transient neurological deficits in 2 patients (16.7%). There were no procedure-related complications leading to either permanent morbidity or mortality. CONCLUSION: Our results support the role of LINAC-RS as an efficient and safe treatment to significantly reduce the annual hemorrhage rate in patients suffering from brainstem CCMs not eligible to microsurgery. Compared with radiosurgery for arteriovenous malformations (AVMs), the intervention-related morbidity is higher.

LINAC-radiosurgery for nonsecreting pituitary adenomas. Long-term results.

BACKGROUND AND PURPOSE: Stereotactic linear accelerator-based radiosurgery (LINAC-RS) is increasingly used for microsurgically inaccessible or recurrent pituitary adenomas. This single-center study evaluates the long-term follow-up after LINAC-RS of nonsecreting pituitary adenomas (NSA). PATIENTS AND METHODS: Between 1992 and August 2008, 65 patients with NSA were treated. Patient treatment and follow-up were conducted according to a prospective protocol. Indications for LINAC-RS were (1) tumor recurrence or (2) residual tumor. Three patients were treated primarily. For analysis of prognostic factors, patients were grouped according to epidemiological or treatment-associated characteristics. RESULTS: A total of 61 patients with a follow-up ≥ 12 months (median 83 months, range 15-186 months, longest follow-up of published radiosurgery series) were evaluated with regard to their clinical, radiological, and endocrinological course. The median tumor volume was 3.5 ml (± 4.3 ml, range 0.3-17.3 ml) treated with a median surface and maximum dose of 13.0 Gy and 29.7 Gy, respectively. Local tumor control was achieved in 98%. One patient died of unrelated cause after 36 months and 1 patient developed a radiation-induced seizure disorder. Visual complications did not occur. In 37 of 41 patients (90.2%), pituitary function remained stable. Maximum dose to the pituitary ≤ 16 Gy and female gender were positive prognostic factors for the preservation of pituitary function. CONCLUSION: LINAC-RS is a minimally invasive, safe, and effective treatment for recurrent NSA or microsurgically inaccessible residual tumor. LINAC-RS yielded a high rate of local long-term tumor control with a small number of radiation-induced side effects.

In Vivo Reflectance Confocal Microscopy: Emerging Role in Noninvasive Diagnosis and Monitoring of Eczematous Dermatoses. / Microscopia confocal de reflectancia in vivo: papel emergente en el diagnóstico no invasivo, así como en el seguimiento de las dermatosis eccematosas.

Dermatologic diagnosis and monitoring have been dependent largely on visual grading. A skin biopsy is performed in case of diagnostic uncertainty, but can be traumatic, and results are delayed due to time for specimen transport and processing. Biopsies also destroy specimens, prohibiting lesion evolution monitoring. In vivo reflectance confocal microscopy (RCM) offers a diagnostic alternative to skin biopsy. RCM captures real-time, high-resolution images, and has been piloted for the evaluation of various dermatologic conditions. Identification of unique RCM features may distinguish dermatoses with similar clinical morphologies. Allergic contact dermatitis (ACD) and irritant contact dermatitis (ICD) are diagnosed by patch testing that currently uses a subjective scoring system. RCM has increasingly been studied for early detection and severity grading of CD. Common RCM features shared by ACD and ICD are stratum corneum disruption, vesicle formation, exocytosis, spongiosis, and parakeratosis. Features unique to ACD are vasodilation, increased epidermal thickness, intercellular edema, and acanthosis. Features unique to ICD are detached corneocytes and targetoid keratinocytes. This review summarizes the use of RCM in evaluating contact eccematous conditions and aims to spark future research and interest in this promising tool.

Deep-brain stimulation: long-term analysis of complications caused by hardware and surgery--experiences from a single centre.

OBJECTIVE: To determine the surgery-related and hardware-related complications of deep-brain stimulation (DBS) at a single centre. METHODS: 262 consecutive patients (472 electrodes) operated for DBS in our department from February 1996 to March 2003 were retrospectively analysed to document acute adverse events (30 days postoperatively). The data of 180 of these patients were additionally revised to assess long-term complications (352 electrodes, mean follow-up 36.3 (SD 20.8) months). RESULTS: The frequency of minor intraoperative complications was 4.2% (11/262 patients). Transient (0.2%) or permanent (0.4%) neurological deficits, and in one case asymptomatic intracranial haemorrhage (0.2%), were registered as acute severe adverse events caused by surgery. Among minor acute complications were subcutaneous bleeding along the extension wire (1.2%) and haematoma at the pulse generator implantation site (1.2%). Skin infection caused by the implanted material was registered in 15 of 262 patients (5.7%). The infection rate during the first observation period was 1.5% (4/262 patients) and the late infection rate was 6.1% (11/180 patients). Partial or complete removal of the stimulation system was necessitated in 12 of 262 (4.6%) patients because of skin infection. During the long-term observation period, hardware-related problems were registered in 25 of 180 (13.9%) patients. CONCLUSIONS: Stereotactic implantation of electrodes for DBS, if performed with multiplanar three-dimensional imaging and advanced treatment planning software, is a safe procedure with no mortality and low morbidity. The main causes for the patients' prolonged hospital stay and repeated surgery were wound infections and hardware-related complications.

Changes in Nutritional Status after Deep Brain Stimulation of the Nucleus Basalis of Meynert in Alzheimer's Disease--Results of a Phase I Study.

OBJECTIVE: The progression of Alzheimer's disease (AD) is associated with impaired nutritional status. New methods, such as deep brain stimulation (DBS), are currently being tested to decrease the progression of AD. DBS is an approved method in the treatment of Parkinson's disease, and its suitability for the treatment of AD patients is currently under experimental investigation. To evaluate the advantages and disadvantages of this new treatment, it is important to assess potential side effects of DBS regarding the nucleus basalis of Meynert; this new treatment is thought to positively affect cognition and might counteract the deterioration of nutritional status and progressive weight loss observed in AD. This study aims to assess the nutritional status of patients with AD before receiving DBS of the nucleus basalis of Meynert and after 1 year, and to analyze potential associations between changes in cognition and nutritional status. DESIGN: A 1-year phase I proof-of-concept study. SETTING: The Department of Psychiatry and Psychotherapy at the University of Cologne. PARTICIPANTS: We assessed a consecutive sample of patients with mild to moderate AD (n=6) who fulfilled the inclusion criteria and provided written informed consent. INTERVENTION: Bilateral low-frequency DBS of the nucleus basalis of Meynert. MEASUREMENTS: Nutritional status was assessed using a modified Mini Nutritional Assessment, bioelectrical impedance analysis, a completed 3-day food diary, and analysis of serum levels of vitamin B12 and folate. RESULTS: With a normal body mass index (BMI) at baseline (mean 23.75 kg/m²) and after 1 year (mean 24.59 kg/m²), all but one patient gained body weight during the period of the pilot study (mean 2.38 kg, 3.81% of body weight). This was reflected in a mainly stable or improved body composition, assessed by bioelectrical impedance analysis, in five of the six patients. Mean energy intake increased from 1534 kcal/day (min 1037, max 2370) at baseline to 1736 kcal/day (min 1010, max 2663) after 1 year, leading to the improved fulfillment of energy needs in four patients. The only nutritional factors that were associated with changes in cognition were vitamin B12 level at baseline (Spearman's rho = 0.943, p = 0.005) and changes in vitamin B12 level (Spearman's rho = -0.829, p = 0.042). CONCLUSION: Patients with AD that received DBS of the nucleus basalis of Meynert demonstrated a mainly stable nutritional status within a 1-year period. Whether DBS is causative regarding these observations must be investigated in additional studies.

The influence of head frame distortions on stereotactic localization and targeting.

A strong attachment of a stereotactic head frame to the patient's skull may cause distortions of the head frame. The aim of this work was to identify possible distortions of the head frame, to measure the degree of distortion occurring in clinical practice and to investigate its influence on stereotactic localization and targeting. A model to describe and quantify the distortion of the Riechert-Mundinger (RM) head frame was developed. Distortions were classified as (a) bending and (b) changes from the circular ring shape. Ring shape changes were derived from stereotactic CT scans and frame bending was determined from intraoperative stereotactic x-ray images of patients with implanted 125I-seeds acting as landmarks. From the examined patient data frame bending was determined to be 0.74 mm+/-0.32 mm and 1.30 mm in maximum. If a CT-localizer with a top ring is used, frame bending has no influence on stereotactic CT-localization. In stereotactic x-ray localization, frame bending leads to an overestimation of the z-coordinate by 0.37 mm+/-0.16 mm on average and by 0.65 mm in maximum. The accuracy of patient positioning in radiosurgery is not affected by frame bending. But in stereotactic surgery with an RM aiming bow trajectory displacements are expected. These displacements were estimated to be 0.36 mm+/-0.16 mm (max. 0.74 mm) at the target point and 0.65 mm+/-0.30 mm (max. 1.31 mm) at the entry point level. Changes from the circularring shape are small and do not compromise the accuracy of stereotactic targeting and localization. The accuracy of CT-localization was found to be close to the resolution limit due to voxel size. Our findings for frame bending of the RM frame could be validated by statistical analysis and by comparison with an independent patient examination. The results depend on the stereotactic system and details of the localizers and instruments and also reflect our clinical practice. Therefore, a generalization is not possible. Preliminary experience with a new MR-compatible RM head frame made of ceramics shows no frame distortions as with the conventional frame made of an Al-Cu-Mg alloy.

MR-guided stereotactic neurosurgery--comparison of fiducial-based and anatomical landmark transformation approaches.

For application in magnetic resonance (MR) guided stereotactic neurosurgery, two methods for transformation of MR-image coordinates in stereotactic, frame-based coordinates exist: the direct stereotactic fiducial-based transformation method and the indirect anatomical landmark method. In contrast to direct stereotactic MR transformation, indirect transformation is based on anatomical landmark coregistration of stereotactic computerized tomography and non-stereotactic MR images. In a patient study, both transformation methods have been investigated with visual inspection and mutual information analysis. Comparison was done for our standard imaging protocol, including t2-weighted spin-echo as well as contrast enhanced t1-weighted gradient-echo imaging. For t2-weighted spin-echo imaging, both methods showed almost similar and satisfying performance with a small, but significant advantage for fiducial-based transformation. In contrast, for t1-weighted gradient-echo imaging with more geometric distortions due to field inhomogenities and gradient nonlinearity than t2-weighted spin-echo imaging, mainly caused by a reduced bandwidth per pixel, anatomical landmark transformation delivered markedly better results. Here, fiducial-based transformation yielded results which are intolerable for stereotactic neurosurgery. Mean Euclidian distances between both transformation methods were 0.96 mm for t2-weighted spin-echo and 1.67 mm for t1-weighted gradient-echo imaging. Maximum deviations were 1.72 mm and 3.06 mm, respectively.

[Primary intracranial germinoma. Problems in determining the diagnosis exemplified by 4 cases]. / Das primäre intrakranielle Germinom. Probleme der Diagnosefindung am Beispiel von vier Fällen.

Primary intracranial germinoma is a possible cause of "idiopathic" diabetes insipidus in childhood and adolescence. The histopathologic appearance can be similar to inflammation, and may delay the final diagnosis. Further diagnostic difficulties are demonstrated by the use of anamnestic and clinical data as well as diagnostic imaging findings in four children with histologically proven primary intracranial germinoma.

Development and characterization of paromomycin-resistant Leishmania donovani promastigotes.

Paromomycin is an antileishmanial chemotherapeutic agent. Leishmania donovani promastigotes resistant to 800 microM of paromomycin were selected by increasing drug pressure and cloned. These promastigotes did not acquire multidrug resistance. Paromomycin resistance was stable in the absence of the drug in the culture. It remained stable also in amastigotes isolated after a passage in mice. Furthermore the resistant parasites were still infective to macrophages in vitro and for mice in vivo. A sensitive method to detect and to quantify intracellular paromomycin by HPLC was developed and allowed to show that the main mechanism of resistance seems to be due to decreased drug uptake probably as a consequence of altered membrane composition.

[Right tracheal bronchus associated with tuberculosis pneumonia. A case report]. / Bronche trachéale droite associée à une lobite segmentaire tuberculeuse. A propos d'un cas.

Right tracheal bronchus is a rare almost always asymptotic congenital malformation. We report a case of right tracheal bronchus associated with pneumonia tuberculosis of the apical segment of the upper right lobe. We describe the characteristic of this malformation and stress the role of computed tomography scan to detect these anomalies.

[Acute traumatic thoracic aortic rupture in double localisation]. / Rupture aiguë post-traumatique de l'aorte thoracique en double foyer.

PURPOSE: Traumatic thoracic aortic rupture are commonly localised in one site essentially in the aortic isthmus but multiple localisation are not uncommon. The authors reported the case of a young man who had a double localisation of RTA after a violent car accident. CASE REPORT: A 23-year-old man had a violent car crush involving sudden deceleration. He had multiple injuries essentially: a traumatic thoracic injury with acute posttraumatic aortic rupture in double localization, in the isthmus and in the descending thoracic aorta. He underwent thoracic endovascular aortic repair (TEVAR) with the use of stent graft three weeks after his car accident. The endovascular treatment was successful and no case of perigraft leakage has been detected during a meaning follow-up of five months. CONCLUSION: The systematic analysis of the whole thoracic aortic vessel is crucial to not misdiagnose eventual multiple aortic rupture.