Endovascular repair of abdominal aortic aneurysms: only a mechanical solution for a biological problem?

Endovascular aneurysm repair has matured significantly over the last 20 years and is becoming increasingly popular as a minimally invasive treatment option for patients with abdominal aortic aneurysms (AAA). Long-term durability of this fascinating treatment, however, is in doubt as continuing aneurysmal degeneration of the aortoiliac graft attachment zones is clearly associated with late adverse sequelae. In recent years, our growing understanding of the physiopathology of AAA formation has facilitated scrutiny of various potential drug treatment concepts. In this article we review the mechanical and biological challenges associated with endovascular treatment of infrarenal AAAs and discuss potential approaches to ongoing aneurysmal degeneration, which hampers long-term outcomes of this minimally invasive therapy.

Prospective surveillance of varicella-zoster virus infections in an out-patient setting in Switzerland

Limited data are available on the clinical impact of varicella in the ambulatory setting. Our goal was to determine real-life data on the clinical outcomes, medical management, and resource utilization in patients with varicella in Switzerland, a country without a universal immunization program against varicella. A total of 236 patients (222 = 94% primarily healthy individuals) with a clinical diagnosis of varicella were recruited by pediatricians and general practitioners. Age range of patients was 0-47 years with a median of 5 years. The great majority of patients (179 = 76%) were sequelae. All complications occurred in children under 12 years of age. In conclusion, this study describes the spectrum of varicella in an out-patient setting with a sizeable rate of complications and raises the question of the value of prophylactic immunization.

Long-term follow-up after stroke in childhood

Over the last few years, the importance of paediatric stroke has become more and more evident; however, there is still little known about long-term neurological and especially neuropsychological outcome of these children. By retrospective chart review, questionnaire and clinical examination with structured interview, we analysed initial presentation, aetiology and long-term outcome of children suffering ischaemic childhood stroke between 1985 and 1999. A total of 20 children (13 boys) suffered acute arterial ischaemic events. Aetiology was detected in 14, and suspected in another five. Follow-up after 1-15 years (mean 7 years) was possible for 16 children; two had died and two were lost to follow-up. Only two were completely healthy, five suffered mild, six moderate, and three severe handicap. Eleven children presented with combined neurological and neuropsychological problems. Neurological problems were mild to moderate hemisyndrome in 11, dysphasia, epilepsy and other in six each. Mild to severe neuropsychological problems were detected in 13 children, school problems in eight, attention deficits in nine and behaviour problems in seven, increased fatigability and headache in six each. Recurrence was observed in three children, all due to progressive underlying disease. Outcome was most affected by the presence of combined cortical/subcortical and least affected by subcortical infarction. Epilepsy affected neuropsychological outcome. CONCLUSION: although prognosis of paediatric stroke is better than for adult stroke, neurological and especially neuropsychological long-term problems significantly influence the lives of these children. Careful long-term follow-up to support these children in their school career and integration into professional life is necessary. Future studies should evaluate whether specific treatments during the acute episode could improve outcome for these children.

Impaired verbal memory in Parkinson disease: relationship to prefrontal dysfunction and somatosensory discrimination

OBJECTIVE: To study the neurocognitive profile and its relationship to prefrontal dysfunction in non-demented Parkinson's disease (PD) with deficient haptic perception. METHODS: Twelve right-handed patients with PD and 12 healthy control subjects underwent thorough neuropsychological testing including Rey complex figure, Rey auditory verbal and figural learning test, figural and verbal fluency, and Stroop test. Test scores reflecting significant differences between patients and healthy subjects were correlated with the individual expression coefficients of one principal component, obtained in a principal component analysis of an oxygen-15-labeled water PET study exploring somatosensory discrimination that differentiated between the two groups and involved prefrontal cortices. RESULTS: We found significantly decreased total scores for the verbal learning trials and verbal delayed free recall in PD patients compared with normal volunteers. Further analysis of these parameters using Spearman's ranking correlation showed a significantly negative correlation of deficient verbal recall with expression coefficients of the principal component whose image showed a subcortical-cortical network, including right dorsolateral-prefrontal cortex, in PD patients. CONCLUSION: PD patients with disrupted right dorsolateral prefrontal cortex function and associated diminished somatosensory discrimination are impaired also in verbal memory functions. A negative correlation between delayed verbal free recall and PET activation in a network including the prefrontal cortices suggests that verbal cues and accordingly declarative memory processes may be operative in PD during activities that demand sustained attention such as somatosensory discrimination. Verbal cues may be compensatory in nature and help to non-specifically enhance focused attention in the presence of a functionally disrupted prefrontal cortex.

fMRI of Emotion

Recent brain imaging work has expanded our understanding of the mechanisms of perceptual, cognitive, and motor functions in human subjects, but research into the cerebral control of emotional and motivational function is at a much earlier stage. Important concepts and theories of emotion are briefly introduced, as are research designs and multimodal approaches to answering the central questions in the field. We provide a detailed inspection of the methodological and technical challenges in assessing the cerebral correlates of emotional activation, perception, learning, memory, and emotional regulation behavior in healthy humans. fMRI is particularly challenging in structures such as the amygdala as it is affected by susceptibility-related signal loss, image distortion, physiological and motion artifacts and colocalized Resting State Networks (RSNs). We review how these problems can be mitigated by using optimized echo-planar imaging (EPI) parameters, alternative MR sequences, and correction schemes. High-quality data can be acquired rapidly in these problematic regions with gradient compensated multiecho EPI or high resolution EPI with parallel imaging and optimum gradient directions, combined with distortion correction. Although neuroimaging studies of emotion encounter many difficulties regarding the limitations of measurement precision, research design, and strategies of validating neuropsychological emotion constructs, considerable improvement in data quality and sensitivity to subtle effects can be achieved. The methods outlined offer the prospect for fMRI studies of emotion to provide more sensitive, reliable, and representative models of measurement that systematically relate the dynamics of emotional regulation behavior with topographically distinct patterns of activity in the brain. This will provide additional information as an aid to assessment, categorization, and treatment of patients with emotional and personality disorders.

Sleepiness and vigilance tests

Objective assessments of subjective complaints such as sleepiness, tiredness or fatigue using sleepiness and vigilance tests aim to identify its causes and to judge the fitness to drive or to work of the affected person. "Vigilance" comprises wakefulness, alertness and attention and is therefore not merely reciprocal to sleepiness. Since it is a complex phenomenon with several dimensions it is unlikely to be appropriately assessed by one single "vigilance test". One important dimension of vigilance discussed here is wakefulness with its counterpart of overt sleep and the whole spectrum of various levels in between. The transit zone between full wakefulness and overt sleep is mainly characterised by the subjective complaint of sleepiness, which cannot be measured directly. Only the consequences of reduced wakefulness such as a shortened sleep latency, slowed cognitive function and prolonged reaction time can be measured objectively. It is, therefore, more promising to combine a battery of subjective and objective tests to answer a specific question in order to achieve the most appropriate description for a given clinical or medicolegal situation. However even then we must keep in mind that many other important aspects of fitness to drive / fitness to work such as neurological, psychiatric and neuropsychological functions including risk taking behaviour are not covered by vigilance tests. A comprehensive, multidisciplinary approach is essential in such situations.

Relationship between inflammation and cognitive function in obstructive sleep apnea

OBJECTIVES: Obstructive sleep apnea (OSA) can have adverse effects on cognitive functioning, mood, and cardiovascular functioning. OSA brings with it disturbances in sleep architecture, oxygenation, sympathetic nervous system function, and inflammatory processes. It is not clear which of these mechanisms is linked to the decrease in cognitive functioning. This study examined the effect of inflammatory parameters on cognitive dysfunction. MATERIALS AND METHODS: Thirty-nine patients with untreated sleep apnea were evaluated by polysomnography and completed a battery of neuropsychological tests. After the first night of evaluation in the sleep laboratory, blood samples were taken for analysis of interleukin 6, tumor necrosis factor-alpha (TNF-alpha), and soluble TNF receptor 1 (sTNF-R1). RESULTS: sTNF-R1 significantly correlated with cognitive dysfunction. In hierarchical linear regression analysis, measures of obstructive sleep apnea severity explained 5.5% of the variance in cognitive dysfunction (n.s.). After including sTNF-R1, percentage of variance explained by the full model increased more than threefold to 19.6% (F = 2.84, df = 3, 36, p = 0.05). Only sTNF-R1 had a significant individual relationship with cognitive dysfunction (beta = 0.376 t = 2.48, p = 0.02). CONCLUSIONS: sTNF-R1 as a marker of chronic inflammation may be associated with diminished neuropsychological functioning in patients with OSA.

Hemispheric lateralization patterns and psychotic experiences in healthy subjects

The hypothesis that psychotic experiences in healthy subjects are associated with a dysfunction of the right hemisphere is supported by some, but not all, available studies. Differences in gender composition of study samples may explain in part the divergent findings. The present study was carried out in 42 healthy, right-handed university students. Scores on the Schizophrenia and Paranoia scales of the Minnesota Multidimensional Personality Inventory-2 were used in correlation analyses and to define a High- and a Low-Psychotic group. Brain Electrical Microstates and Low Resolution Electromagnetic Tomography (LORETA) source analyses of the auditory P300 (P3a and P3b) components of the event-related potential, as well as a battery of neuropsychological tests, were used to assess hemispheric functioning. Scores on the Paranoia scale were positively associated with a leftward shift of the P3a topographic descriptors in females but not in males. When comparing High-Psychotic and Low-Psychotic females, a leftward shift of P3a descriptors and an increased cortical activation in left fronto-temporal areas were observed in the High-Psychotic group. Our results demonstrated gender-related differences in the pattern of hemispheric imbalance associated with psychotic experiences in healthy subjects.

Faces and emotions: brain electric field sources during covert emotional processing

Covert brain activity related to task-free, spontaneous (i.e. unrequested), emotional evaluation of human face images was analysed in 27-channel averaged event-related potential (ERP) map series recorded from 18 healthy subjects while observing random sequences of face images without further instructions. After recording, subjects self-rated each face image on a scale from “liked” to “disliked”. These ratings were used to dichotomize the face images into the affective evaluation categories of “liked” and “disliked” for each subject and the subjects into the affective attitudes of “philanthropists” and “misanthropists” (depending on their mean rating across images). Event-related map series were averaged for “liked” and “disliked” face images and for “philanthropists” and “misanthropists”. The spatial configuration (landscape) of the electric field maps was assessed numerically by the electric gravity center, a conservative estimate of the mean location of all intracerebral, active, electric sources. Differences in electric gravity center location indicate activity of different neuronal populations. The electric gravity center locations of all event-related maps were averaged over the entire stimulus-on time (450 ms). The mean electric gravity center for disliked faces was located (significant across subjects) more to the right and somewhat more posterior than for liked faces. Similar differences were found between the mean electric gravity centers of misanthropists (more right and posterior) and philanthropists. Our neurophysiological findings are in line with neuropsychological findings, revealing visual emotional processing to depend on affective evaluation category and affective attitude, and extending the conclusions to a paradigm without directed task.

Influence of postnatally administered glucocorticoids on rat lung growth

Postnatal formation of alveoli can be largely prevented by glucocorticoid treatment, which accelerates alveolar wall thinning and inhibits outgrowth of new interalveolar septa. Since a double capillary network is a prerequisite for interalveolar wall formation, we hypothesized that glucocorticoid treatment inhibited alveolar formation, indirectly, by inducing precocious microvascular maturation. Between 4 and 60 days we followed up qualitatively and quantitatively the effects of 2 weeks (days 2-15) of daily Decadron (Dexamethasone phosphate) injections on the lung structure. Glucocorticoid induced only small changes in body weight or lung volume. However, during the first 2 weeks, it accelerated alveolar wall thinning and microvascular maturation and partly suppressed the outgrowth of new interalveolar septa. In Decadron-treated rats, the interstitial tissue mass was significantly reduced during the first 2 weeks, and a larger alveolar surface area was endowed with a capillary monolayer on days 10 and 13. One week after drug withdrawal, the trend towards precocious maturation of the lung was reversed. Lipofibroblasts reappeared, and inter-airspace septa regressed towards a more immature state. We found indications of a second burst of alveolization by resumption of secondary septa formation. The late sequelae of Decadron treatment (day 60) were manifested as an 'emphysematous' condition of the lungs, with larger and fewer airspaces, the delayed alveolization being insufficient to compensate for the initial deficit.

Effectiveness and cost-effectiveness of traditional and new partner notification technologies for curable sexually transmitted infections: observational study, systematic reviews and mathematical modelling

BACKGROUND Partner notification is essential to the comprehensive case management of sexually transmitted infections. Systematic reviews and mathematical modelling can be used to synthesise information about the effects of new interventions to enhance the outcomes of partner notification. OBJECTIVE To study the effectiveness and cost-effectiveness of traditional and new partner notification technologies for curable sexually transmitted infections (STIs). DESIGN Secondary data analysis of clinical audit data; systematic reviews of randomised controlled trials (MEDLINE, EMBASE and Cochrane Central Register of Controlled Trials) published from 1 January 1966 to 31 August 2012 and of studies of health-related quality of life (HRQL) [MEDLINE, EMBASE, ISI Web of Knowledge, NHS Economic Evaluation Database (NHS EED), Database of Abstracts of Reviews of Effects (DARE) and Health Technology Assessment (HTA)] published from 1 January 1980 to 31 December 2011; static models of clinical effectiveness and cost-effectiveness; and dynamic modelling studies to improve parameter estimation and examine effectiveness. SETTING General population and genitourinary medicine clinic attenders. PARTICIPANTS Heterosexual women and men. INTERVENTIONS Traditional partner notification by patient or provider referral, and new partner notification by expedited partner therapy (EPT) or its UK equivalent, accelerated partner therapy (APT). MAIN OUTCOME MEASURES Population prevalence; index case reinfection; and partners treated per index case. RESULTS Enhanced partner therapy reduced reinfection in index cases with curable STIs more than simple patient referral [risk ratio (RR) 0.71; 95% confidence interval (CI) 0.56 to 0.89]. There are no randomised trials of APT. The median number of partners treated for chlamydia per index case in UK clinics was 0.60. The number of partners needed to treat to interrupt transmission of chlamydia was lower for casual than for regular partners. In dynamic model simulations, > 10% of partners are chlamydia positive with look-back periods of up to 18 months. In the presence of a chlamydia screening programme that reduces population prevalence, treatment of current partners achieves most of the additional reduction in prevalence attributable to partner notification. Dynamic model simulations show that cotesting and treatment for chlamydia and gonorrhoea reduce the prevalence of both STIs. APT has a limited additional effect on prevalence but reduces the rate of index case reinfection. Published quality-adjusted life-year (QALY) weights were of insufficient quality to be used in a cost-effectiveness study of partner notification in this project. Using an intermediate outcome of cost per infection diagnosed, doubling the efficacy of partner notification from 0.4 to 0.8 partners treated per index case was more cost-effective than increasing chlamydia screening coverage. CONCLUSIONS There is evidence to support the improved clinical effectiveness of EPT in reducing index case reinfection. In a general heterosexual population, partner notification identifies new infected cases but the impact on chlamydia prevalence is limited. Partner notification to notify casual partners might have a greater impact than for regular partners in genitourinary clinic populations. Recommendations for future research are (1) to conduct randomised controlled trials using biological outcomes of the effectiveness of APT and of methods to increase testing for human immunodeficiency virus (HIV) and STIs after APT; (2) collection of HRQL data should be a priority to determine QALYs associated with the sequelae of curable STIs; and (3) standardised parameter sets for curable STIs should be developed for mathematical models of STI transmission that are used for policy-making. FUNDING The National Institute for Health Research Health Technology Assessment programme.

Patients with oral tumors. Part 1: Prosthetic rehabilitation following tumor resection. Resection prosthetics: surgery, implants and prosthetic treatment

The present study reports on the surgical and prosthodontic rehabilitation of 46 patients, 31 male and 15 female, after resection of oral tumors. The treatment was carried out from 2004 to 2007 at the Department of Prosthodontics, University of Bern, with a follow-up time of 3 to 6 years. The average age at diagnosis was 54 years. 76% of all tumors were squamous cell carcinoma, followed by adenocarcinoma. Resection of the tumors including soft and/or hard tissues was performed in all patients. 80% of them additionally underwent radiotherapy and 40% chemotherapy. A full block resection of the mandible was perfomed in 23 patients, and in 10 patients, the tumor resection resulted in an oronasal communication. 29 patients underwent grafting procedures, mostly consisting of a free fibula flap transplant. To enhance the prosthetic treatment outcome and improve the prosthesis stability, a total of 114 implants were placed. However, 14 implants were not loaded because they failed during the healing period or the patient could not complete the final treatment with the prostheses. The survival rate of the implants reached 84.2% after 4 to 5 years. Many patients were only partially dentate before the tumors were detected, and further teeth had to be extracted in the course of the tumor therapy. Altogether, 31 jaws became or remained edentulous. Implants provide stability and may facilitate the adaptation to the denture, but their survival rate was compromised. Mostly, patients were fitted with removable prostheses with obturators in the maxilla and implant-supported complete dentures with bars in the mandible. Although sequelae of tumor resection are similar in many patients, the individual intermaxillary relations, facial morphology and functional capacity vary significantly. Thus, individual management is required for prosthetic rehabilitation.

Effects of neonatal high-dose short-term glucocorticoid treatment on the lung: a morphologic and morphometric study in the rat

Glucocorticoids are often applied in neonatology and perinatology to fight the problems of respiratory distress and chronic lung disease. There are, however, many controversies regarding the adverse side effects and long-term clinical benefits of this therapeutic approach. In rats, glucocorticoids are known to seriously impair the formation of alveoli when applied during the first two postnatal weeks even at very low dosage. The current study investigates short-term and long-term glucocorticoid effects on the rat lung by means of morphologic and morphometric observations at light and electron microscopic levels. Application of a high-dosage protocol for only few days resulted in a marked acceleration of lung development with a precocious microvascular maturation resulting in single capillary network septa in the first 4 postnatal days. By postnatal d 10, the lung morphologic phenotype showed a step back in the maturational state, with an increased number of septa with double capillary layer, followed by an exceptional second round of the alveolarization process. As a result of this process, there was an almost complete recovery in the parenchymal lung structure by postnatal d 36, and by d 60, there were virtually no qualitative or quantitative differences between experimental and control rats. These findings indicate that both dosage and duration of glucocorticoid therapy in the early postnatal period are very critical with respect to lung development and maturation and that a careful therapeutic strategy can minimize late sequelae of treatment.

Chirurgische Maßnahmen zur Wiederherstellung der Körperform und -kontur nach massiver Gewichtsreduktion

The consequences of massive weight loss through bariatric procedures as well as diet are overall positive. However, the sequelae of massive weight loss present themselves as soft tissue redundancies in the areas of the lower abdomen, upper thigh, upper arm and breast as well as face and neck. This condition presents significant mechanical, physical and social day-to-day limitations for the quality of life of these patients. Surgical techniques are indicated for the reconstruction of the body shape and therapy of the above named problems and the coexistent psychosocial component. These surgical techniques involve dermolipectomies in different body areas and can lead to significant improvement. In view of the worldwide increase of adipositas and the increasing need for bariatric surgery, a parallel increase in demand for such reconstructive post-bariatric interventions can be foreseen. Early and precise information is crucial for the patients before engaging in weight reduction, as is the coverage of the costs of the resulting secondary reconstructive body contouring interventions by the insurance companies.

Subclinical thyroid dysfunction and cognitive decline in old age

BACKGROUND Subclinical thyroid dysfunction has been implicated as a risk factor for cognitive decline in old age, but results are inconsistent. We investigated the association between subclinical thyroid dysfunction and cognitive decline in the PROspective Study of Pravastatin in the Elderly at Risk (PROSPER). METHODS Prospective longitudinal study of men and women aged 70-82 years with pre-existing vascular disease or more than one risk factor to develop this condition (N = 5,154). Participants taking antithyroid medications, thyroid hormone supplementation and/or amiodarone were excluded. Thyroid function was measured at baseline: subclinical hyper- and hypothyroidism were defined as thyroid stimulating hormones (TSH) <0.45 mU/L or >4.50 mU/L respectively, with normal levels of free thyroxine (FT4). Cognitive performance was tested at baseline and at four subsequent time points during a mean follow-up of 3 years, using five neuropsychological performance tests. RESULTS Subclinical hyperthyroidism and hypothyroidism were found in 65 and 161 participants, respectively. We found no consistent association of subclinical hyper- or hypothyroidism with altered cognitive performance compared to euthyroid participants on the individual cognitive tests. Similarly, there was no association with rate of cognitive decline during follow-up. CONCLUSION We found no consistent evidence that subclinical hyper- or hypothyroidism contribute to cognitive impairment or decline in old age. Although our data are not in support of treatment of subclinical thyroid dysfunction to prevent cognitive dysfunction in later life, only large randomized controlled trials can provide definitive evidence.