Thoracic endovascular aortic repair: impact of urgency on outcome and quality of life

OBJECTIVES: Endovascular repair of the descending thoracic aorta is a very promising technique in elective and, particularly, emergency situations. This study assessed the impact of urgency of the procedure on outcome and mid-term quality of life in surviving patients. METHODS: Post hoc analysis of prospectively collected data of 58 consecutive patients (January 2001-December 2005) with surgical pathologies of the descending thoracic aorta treated by endovascular means. Six patients were excluded due to recent operations on the ascending aorta before thoracic endovascular repair. The remaining patients (n=52) were 69+/-10 years old, and 43 were men (83%). Twenty-seven had been treated electively, and 25 for emergency indications. Reasons for emergency were acute type B aortic dissections with or without malperfusion syndrome in 14, and aortic ruptures in 11 cases. Follow-up was 29+/-16 months. Endpoints were perioperative and late morbidity and mortality rates and long-term quality of life as assessed by the short form health survey (SF-36) and Hospital Anxiety and Depression Scale questionnaires. RESULTS: Cohorts were comparable regarding age, sex, cardiovascular risk factors, and comorbidities. Perioperative mortality was somewhat higher in emergency cases (12% vs 4%, p=0.34). Paraplegia occurred in one patient in each cohort (4%). Overall quality of life after two and a half years was similar in both treatment cohorts: 72 (58-124) after emergency, and 85 (61-105) after elective endovascular aortic repair (p=0.98). Normal scores range from 85 to 115. Anxiety and depression scores were in the normal range and comparable. CONCLUSIONS: Thoracic endovascular aortic repair is an excellent and safe treatment option for the diseased descending aorta, particularly in emergency situations. Early morbidity and mortality rates can be kept very low. Mid-term quality of life was not affected by the urgency of the procedure. Similarly, mid-term anxiety and depression scores were not increased after emergency situations.

Conventional radiographs to assess femoroacetabular impingement

Femoroacetabular impingement (FAI) is a pathologic condition of the hip joint in young adults that, if untreated, leads to end-stage osteoarthritis. It is characterized by early pathologic contact between primary osseous prominences of the acetabular rim (so-called pincer FAI) and/or the femoral head-neck junction (cam FAI). Conventional radiographs are often considered normal because classic radiographic signs of osteoarthritis are not present initially. The physician should be aware of the radiographic features for both types of impingement to recognize subtle pathologies.

Three-dimensional magnetic resonance observation of cartilage repair tissue (MOCART) score assessed with an isotropic three-dimensional true fast imaging with steady-state precession sequence at 3.0 Tesla

INTRODUCTION: Cartilage defects are common pathologies and surgical cartilage repair shows promising results. In its postoperative evaluation, the magnetic resonance observation of cartilage repair tissue (MOCART) score, using different variables to describe the constitution of the cartilage repair tissue and the surrounding structures, is widely used. High-field magnetic resonance imaging (MRI) and 3-dimensional (3D) isotropic sequences may combine ideal preconditions to enhance the diagnostic performance of cartilage imaging.Aim of this study was to introduce an improved 3D MOCART score using the possibilities of an isotropic 3D true fast imaging with steady-state precession (True-FISP) sequence in the postoperative evaluation of patients after matrix-associated autologous chondrocyte transplantation (MACT) as well as to compare the results to the conventional 2D MOCART score using standard MR sequences. MATERIAL AND METHODS: The study had approval by the local ethics commission. One hundred consecutive MR scans in 60 patients at standard follow-up intervals of 1, 3, 6, 12, 24, and 60 months after MACT of the knee joint were prospectively included. The mean follow-up interval of this cross-sectional evaluation was 21.4 +/- 20.6 months; the mean age of the patients was 35.8 +/- 9.4 years. MRI was performed at a 3.0 Tesla unit. All variables of the standard 2D MOCART score where part of the new 3D MOCART score. Furthermore, additional variables and options were included with the aims to use the capabilities of isotropic MRI, to include the results of recent studies, and to adapt to the needs of patients and physician in a clinical routine examination. A proton-density turbo spin-echo sequence, a T2-weighted dual fast spin-echo (dual-FSE) sequence, and a T1-weighted turbo inversion recovery magnitude (TIRM) sequence were used to assess the standard 2D MOCART score; an isotropic 3D-TrueFISP sequence was prepared to evaluate the new 3D MOCART score. All 9 variables of the 2D MOCART score were compared with the corresponding variables obtained by the 3D MOCART score using the Pearson correlation coefficient; additionally the subjective quality and possible artifacts of the MR sequences were analyzed. RESULTS: The correlation between the standard 2D MOCART score and the new 3D MOCART showed for the 8 variables "defect fill," "cartilage interface," "surface," "adhesions," "structure," "signal intensity," "subchondral lamina," and "effusion"-a highly significant (P < 0.001) correlation with a Pearson coefficient between 0.566 and 0.932. The variable "bone marrow edema" correlated significantly (P < 0.05; Pearson coefficient: 0.257). The subjective quality of the 3 standard MR sequences was comparable to the isotropic 3D-TrueFISP sequence. Artifacts were more frequently visible within the 3D-TrueFISP sequence. CONCLUSION: In the clinical routine follow-up after cartilage repair, the 3D MOCART score, assessed by only 1 high-resolution isotropic MR sequence, provides comparable information than the standard 2D MOCART score. Hence, the new 3D MOCART score has the potential to combine the information of the standard 2D MOCART score with the possible advantages of isotropic 3D MRI at high-field. A clear limitation of the 3D-TrueFISP sequence was the high number of artifacts. Future studies have to prove the clinical benefits of a 3D MOCART score.

Life and death partners: apoptosis, autophagy and the cross-talk between them

It is not surprising that the demise of a cell is a complex well-controlled process. Apoptosis, the first genetically programmed death process identified, has been extensively studied and its contribution to the pathogenesis of disease well documented. Yet, apoptosis does not function alone to determine a cell's fate. More recently, autophagy, a process in which de novo-formed membrane-enclosed vesicles engulf and consume cellular components, has been shown to engage in a complex interplay with apoptosis. In some cellular settings, it can serve as a cell survival pathway, suppressing apoptosis, and in others, it can lead to death itself, either in collaboration with apoptosis or as a back-up mechanism when the former is defective. The molecular regulators of both pathways are inter-connected; numerous death stimuli are capable of activating either pathway, and both pathways share several genes that are critical for their respective execution. The cross-talk between apoptosis and autophagy is therefore quite complex, and sometimes contradictory, but surely critical to the overall fate of the cell. Furthermore, the cross-talk is a key factor in the outcome of death-related pathologies such as cancer, its development and treatment.

[Implantation: physiology, pathology and therapeutic options in disorders of implantation]

So far, implantation is a poorly understood process, which involves several paradoxical cell-biological mechanisms. First, 50% of the embryo is paternal and immunologically foreign material, and second, both the endometrium and embryo are covered by epithelial tissue to prevent cellular fusion. The adhesion and invasion of the blastocyst require an accurate coordination of embryonic and endometrial physiology and the modulation of maternal immune tolerance. Endometrial function plays an important role in assisted reproduction. Pathologies such as fibroids, hydrosalpinges, endometriosis and the polycystic ovary syndrome have a significant negative impact on implantation but can be treated in most cases. Therapeutic strategies to improve endometrial and embryonic function in recurrent implantation disorders are however still controversially discussed.

Integration of electrical neuroimaging with other functional imaging methods

Integrating evidence from different imaging modalities is important to overcome specific limitations of any given imaging method, such as insensitivity of the EEG to unsynchronized neural events, or the lack of fMRI sensitivity to events of low metabolic demand. Processes that are visible in one modality may be related in a nontrivial way to other processes visible in another modality and insight may only be obtained by integrating both methods through a common analysis. For example, brain activity at rest seems to be at least partly determined by an interaction of cortical rhythms (visible to EEG but not to fMRI) with sub-cortical activity (visible to fMRI, but usually not to EEG without averaging). A combination of EEG and fMRI data during rest may thus be more informative than the sum of two separate analyses in both modalities. Integration is also an important source of converging evidence about specific aspects and general principles of neural functions and their dysfunctions in certain pathologies. This is because not only electrical, but also energetic, biochemical, hemodynamic and metabolic processes characterize neural states and functions, and because brain structure provides crucial constraints upon neural functions. Focusing on multimodal integration of functional data should not distract from the privileged status of the electric field as the primary direct, noninvasive real-time measure of neural transmission. The preceding chapters illustrate how electrical neuroimaging has turned scalp EEG into an imaging modality which directly captures the full temporal dynamics of neural activity in the brain.

Depiction of small veins draining into the vein of galen using preoperative 3-dimensional navigation in living patients

OBJECTIVE: The purpose of this study was to delineate the anatomy of the precentral cerebellar vein, superior vermian vein, and internal occipital vein using reconstructions of computed tomographic and magnetic resonance imaging scans with navigation software. These data were compared with previous anatomic and angiographic findings to show the resolution and accuracy of the system. METHODS: We retrospectively reviewed 100 patients with intracranial pathologies (50 computed tomographic scans with contrast and 50 magnetic resonance imaging scans with gadolinium) using a neuronavigation workstation for 3-dimensional reconstruction. Particular attention was paid to depiction of the precentral cerebellar vein, superior vermian vein, and internal occipital vein. The data were reviewed and analyzed. RESULTS: The precentral cerebellar vein, superior vermian vein, and its tributary, the supraculminate vein, were depicted in 52 (52%) patients. The internal occipital vein was delineated on 99 (49.5%) sides and joined the basal vein and vein of Galen in 39 (39.4%) and 60 (60.6%) hemispheres, respectively. Comparing these results with previous angiographic studies, the ability of the neuronavigation system for depicting these vessels is similar to that of digital subtraction angiography. CONCLUSION: This study illustrates the possibility of depicting the small vessels draining into the pineal region venous complex using 3-dimensional neuronavigation with an accuracy comparable to that of digital subtraction angiography. This tool provides important information for both surgical planning and intraoperative orientation.

Selecting control genes for RT-QPCR using public microarray data

BACKGROUND: Gene expression analysis has emerged as a major biological research area, with real-time quantitative reverse transcription PCR (RT-QPCR) being one of the most accurate and widely used techniques for expression profiling of selected genes. In order to obtain results that are comparable across assays, a stable normalization strategy is required. In general, the normalization of PCR measurements between different samples uses one to several control genes (e.g. housekeeping genes), from which a baseline reference level is constructed. Thus, the choice of the control genes is of utmost importance, yet there is not a generally accepted standard technique for screening a large number of candidates and identifying the best ones. RESULTS: We propose a novel approach for scoring and ranking candidate genes for their suitability as control genes. Our approach relies on publicly available microarray data and allows the combination of multiple data sets originating from different platforms and/or representing different pathologies. The use of microarray data allows the screening of tens of thousands of genes, producing very comprehensive lists of candidates. We also provide two lists of candidate control genes: one which is breast cancer-specific and one with more general applicability. Two genes from the breast cancer list which had not been previously used as control genes are identified and validated by RT-QPCR. Open source R functions are available at http://www.isrec.isb-sib.ch/~vpopovic/research/ CONCLUSION: We proposed a new method for identifying candidate control genes for RT-QPCR which was able to rank thousands of genes according to some predefined suitability criteria and we applied it to the case of breast cancer. We also empirically showed that translating the results from microarray to PCR platform was achievable.

Doxycycline-controlled splicing modulation by regulated antisense U7 snRNA expression cassettes

Many diseases affect pre-mRNA splicing, and alternative splicing is a major source of proteome diversity and an important mechanism for modulating gene expression. The ability to regulate a specific splicing event is therefore desirable; for example, to understand splicing-associated pathologies. We have developed methods based on modified U7 snRNAs, which allow us to induce efficient skipping or inclusion of selected exons. Here, we have adapted these U7 tools to a regulatable system that relies on a doxycycline-sensitive version of the Kruppel-associated box (KRAB)/KAP1 transcriptional silencing. Co-transduction of target cells with two lentiviral vectors, one carrying the KRAB protein and the other the regulatable U7 cassette, allows a tight regulation of the modified U7 snRNA. No leakage is observed in the repressed state, whereas full induction can be obtained with doxycycline in ng ml(-1) concentrations. Only a few days are necessary for a full switch, and the induction/repression can be repeated over several cycles without noticeable loss of control. Importantly, the U7 expression correlates with splicing correction, as shown for the skipping of an aberrant beta-globin exon created by a thalassaemic mutation and the promotion of exon 7 inclusion in the human SMN2 gene, an important therapeutic target for spinal muscular atrophy.

Orphan Care in Russia

Current public opinion about the residential care system in contemporary Russia is extremely negative. A majority of Russians, both citizens and professionals, consider that family placement is the best arrangement for orphaned children. The year 2007 was announced as the Year of the Child in Russia. The majority of officials interpreted it as the year of de-institutionalization of the residential care system for children in Russia. De-institutionalization is mostly identified as reform focused on family placement instead of placement in institutions. Vladimir Fridlyanov, the executive director of the Ministry of Science and Education, announced in May, 2007 that the government is going to transfer 120,000 children from institutions into families every year from 2007 until 2010 and reduce the number of residential care institutions by one-third (Nesterova 2007). But the likelihood of family placement is small, with the exception of the adoption of infants without serious pathologies, and the attempts of precipitant de-institutionalization (when children’s homes are closed and children are distributed among families) have failed (children were returned into children homes). According to the opinion of the Ministry, the key obstacle to effective de-institutionalization is the lack of professionals in adoption and foster care (Vazhdaeva 2006).

Screening Swiss water bodies for potentially pathogenic free-living amoebae

Free-ling amoebae (FLA) including Acanthamoeba spp., Naegleria fowleri, Balamuthia mandrillaris and Sappinia pedata, can cause opportunistic infections leading to severe brain pathologies. Human infections with pathogenic FLA have been increasingly documented in many countries. In Switzerland, thus far, the occurrence and distribution of potentially pathogenic FLA has not been investigated. Swiss water biotopes, including swimming pools, lakes, rivers and ponds, have now been screened for the presence of FLA, and assessment of their pathogenicity potential for a mammalian host has been undertaken. Thus, a total of 17 isolates were recovered by in vitro cultivation from these different aquatic sources. Characterization by sequence analysis of Acanthamoeba spp.-specific and 'FLA-specific PCR products amplified from 18s rDNA based on morphological traits, thermotolerance, and cytotoxicity towards murine fibroblasts yielded the following findings: Echinamoeba cf. exundans (3 isolates), Hartmannella spp. (3), Vannella spp. (4), Protacanthamoebica cf. bohemica (1), Acanthamoeba cf. castellanii (1) and Naegleria spp. (5). B. mandrillaris and N. fowleri did not range amongst these isolates. None of the isolates exhibited pronounced cytotoxicity and all failed to grow at 42 degrees C; therefore, they do not present any potential for CNS pathogenicity for humans.

Facts and myths regarding the maxillary midline frenum and its treatment: a systematic review of the literature

OBJECTIVE To systematically review the current literature on the maxillary midline frenum and associated conditions and complications, as well as the recommended treatment options. METHOD AND MATERIALS A detailed MEDLINE database search was carried out to provide evidence about the epidemiology, associated pathologies, and treatment options regarding the maxillary frenum. Of the 206 initially identified articles, 48 met the inclusion criteria. RESULTS The maxillary frenum is highly associated with a number of syndromes and developmental abnormalities. A hypertrophic frenum may be involved in the etiology of the midline diastema. There is also a tendency by orthodontists to suggest posttreatment removal of the frenum (frenectomy). Studies on the cause of gingival recession due to the maxillary frenum are inconclusive. An injured frenum in combination with other traumas and doubtful history might point to child abuse. The involvement of hyperplastic frena in the pathogenesis of peri-implant diseases remains uncertain. There seems to be a clinical interest regarding lasers for surgery for treatment of maxillary frena. The superiority of laser treatment in relation to conventional surgical methods has not yet been demonstrated in the literature. CONCLUSION A maxillary frenum is a clinical symptom in numerous syndromic conditions and plays a role in the development of the median midline diastema. Nevertheless, the contribution to gingival recession and peri-implant diseases in the region of the maxillary incisors is rather controversial. Laser techniques are reported as the method of choice for the surgical removal of frena; however, this needs to be substantiated by appropriate prospective controlled studies.

The influence of muscle strength on the gait profile score (GPS) across different patients

BACKGROUND Muscle strength greatly influences gait kinematics. The question was whether this association is similar in different diseases. METHODS Data from instrumented gait analysis of 716 patients were retrospectively assessed. The effect of muscle strength on gait deviations, namely the gait profile score (GPS) was evaluated by means of generalised least square models. This was executed for seven different patient groups. The groups were formed according to the type of disease: orthopaedic/neurologic, uni-/bilateral affection, and flaccid/spastic muscles. RESULTS Muscle strength had a negative effect on GPS values, which did not significantly differ amongst the different patient groups. However, an offset of the GPS regression line was found, which was mostly dependent on the basic disease. Surprisingly, spastic patients, who have reduced strength and additionally spasticity in clinical examination, and flaccid neurologic patients showed the same offset. Patients with additional lack of trunk control (Tetraplegia) showed the largest offset. CONCLUSION Gait kinematics grossly depend on muscle strength. This was seen in patients with very different pathologies. Nevertheless, optimal correction of biomechanics and muscle strength may still not lead to a normal gait, especially in that of neurologic patients. The basic disease itself has an additional effect on gait deviations expressed as a GPS-offset of the linear regression line.

Little-known Swiss contributions to the description, diagnosis, and surgery of lumbar disc disease before the Mixter and Barr era

The understanding of lumbar spine pathologies made substantial progress at the turn of the twentieth century. The authors review the original publication of Otto Veraguth in 1929 reporting on the successful resection of a herniated lumbar disc, published exclusively in the German language. His early report is put into the historical context, and its impact on the understanding of pathologies of the intervertebral disc (IVD) is estimated. The Swiss surgeon and Nobel Prize laureate Emil Theodor Kocher was among the first physicians to describe the traumatic rupture of the IVD in 1896. As early as 1909 Oppenheim and Krause published 2 case reports on surgery for a herniated lumbar disc. Goldthwait was the first physician to delineate the etiopathogenes is between annulus rupture, symptoms of sciatica, and neurological signs in his publication of 1911. Further publications by Middleton and Teacher in 1911 and Schmorl in 1929 added to the understanding of lumbar spinal pathologies. In 1929, the Swiss neurologist Veraguth (surgery performed by Hans Brun) and the American neurosurgeon Walter Edward Dandy both published their early experiences with the surgical therapy of a herniated lumbar disc. Veraguth's contribution, however, has not been appreciated internationally to date. The causal relationship between lumbar disc pathology and sciatica remained uncertain for some years to come. The causal relationship was not confirmed until Mixter and Barr's landmark paper in 1934 describing the association of sciatica and lumbar disc herniation, after which the surgical treatment became increasingly popular. Veraguth was among the first physicians to report on the clinical course of a patient with successful resection of a herniated lumbar disc. His observations should be acknowledged in view of the limited experience and literature on this ailment at that time.

[Cone beam computed tomography in endodontics: a review for daily clinical practice]

Since the introduction of cone beam computed tomography (CBCT), this 3-dimensional diagnostic imaging technique has been established in a growing number of fields in dental medicine. It has become an important tool for both diagnosis and treatment planning, and is also able to support endodontic treatments. However, the higher effective dose of ionizing radiation compared to conventional 2-dimensional radiographs is not justifiable in every case. CBCT allows for a more precise diagnosis of periapical lesions, root fractures as well as external and internal resorptions. Concerning the utility of CBCT in treatment planning decisions, the gain of information through 3-dimensional imaging for any of these pathologies has to be evaluated carefully on an individual basis. Moreover, radioopaque materials such as root canal filling and posts often create artefacts, which may compromise diagnosis. The aim of this review is to summarize the possibilities and limits of CBCT imaging in endodontology as well as introduce guidelines for daily clinical practice. Furthermore, the article presents possible therapeutic advantages of preexisting CBCT scans for root canal treatments.