Surveillance and simulation of bovine spongiform encephalopathy and scrapie in small ruminants in Switzerland

BACKGROUND: After bovine spongiform encephalopathy (BSE) emerged in European cattle livestock in 1986 a fundamental question was whether the agent established also in the small ruminants' population. In Switzerland transmissible spongiform encephalopathies (TSEs) in small ruminants have been monitored since 1990. While in the most recent TSE cases a BSE infection could be excluded, for historical cases techniques to discriminate scrapie from BSE had not been available at the time of diagnosis and thus their status remained unclear. We herein applied state-of-the-art techniques to retrospectively classify these animals and to re-analyze the affected flocks for secondary cases. These results were the basis for models, simulating the course of TSEs over a period of 70 years. The aim was to come to a statistically based overall assessment of the TSE situation in the domestic small ruminant population in Switzerland. RESULTS: In sum 16 TSE cases were identified in small ruminants in Switzerland since 1981, of which eight were atypical and six were classical scrapie. In two animals retrospective analysis did not allow any further classification due to the lack of appropriate tissue samples. We found no evidence for an infection with the BSE agent in the cases under investigation. In none of the affected flocks, secondary cases were identified. A Bayesian prevalence calculation resulted in most likely estimates of one case of BSE, five cases of classical scrapie and 21 cases of atypical scrapie per 100'000 small ruminants. According to our models none of the TSEs is considered to cause a broader epidemic in Switzerland. In a closed population, they are rather expected to fade out in the next decades or, in case of a sporadic origin, may remain at a very low level. CONCLUSIONS: In summary, these data indicate that despite a significant epidemic of BSE in cattle, there is no evidence that BSE established in the small ruminant population in Switzerland. Classical and atypical scrapie both occur at a very low level and are not expected to escalate into an epidemic. In this situation the extent of TSE surveillance in small ruminants requires reevaluation based on cost-benefit analysis.

Development and application of a real-time TaqMan((R)) qPCR assay for detection and quantification of 'Candidatus Mycoplasma haemolamae' in South American camelids

Two alpacas from a herd in southwest Switzerland died for unknown reasons. Necropsy revealed chronic weight loss and pale mucous membranes. Infection with hemotropic mycoplasmas was suspected and subsequently confirmed by molecular methods. In order to investigate the epidemiological situation in this herd, a real-time TaqMan((R)) qPCR assay for the specific detection and quantification of hemoplasma infection in South American camelids was developed. This assay was based on the 16S rRNA gene and amplified 'Candidatus Mycoplasma haemolamae' DNA, but not DNA from other hemoplasmas or non-hemotropic mycoplasma species. The lower detection limit was one copy/PCR, and the amplification efficiency was 97.4%. In 11 out of 24 clinically healthy herd mates of the two infected alpacas, 'Candidatus M. haemolamae' infection was confirmed. No correlation was found between bacterial load and clinical signs or anemia. The assay described herein enables to detect and quantify 'Candidatus M. haemolamae' and may be used in future studies to investigate the prevalence, pathogenesis and treatment follow-up of hemoplasma infections in South American camelids.

Distensibility and diameter of ascending aorta assessed by cardiac magnetic resonance imaging in adults with tetralogy of fallot or complete transposition

Structural abnormalities of the medial aorta have been described for conotruncal defects (e.g., tetralogy of Fallot [TOF] and complete transposition of the great arteries (dextrotransposition [d]-TGA). In TOF, progressive aortic dilation is a frequent finding. In patients with d-TGA with an atrial switch, this problem is less often described. The aim of the present study was to compare the extent of dilative aortopathy and aortic distensibility in adults with an atrial switch procedure (n = 39) to that in adults with repaired TOF (n = 39) and controls (n = 39), using cardiac magnetic resonance imaging. The groups were matched for age and gender. Diameters of the aorta indexed to the body surface area were significantly increased in the patients with d-TGA and TOF compared to that of the controls at the aortic sinus up to the level of the right pulmonary artery. On multivariate testing, the diagnosis of a conotruncal defect (β = 0.260; p = 0.003) and aortic regurgitant fraction (β = 0.405; p <0.001) were independent predictors of an increased aortic sinus diameter. Ascending aorta distensibility was significantly reduced in those with d-TGA and TOF compared to controls: 3.6 (interquartile range 1.5 to 4.4) versus 2.8 (interquartile range 2.0 to 3.7) versus 5.5 (interquartile range 4.8 to 6.9) ×10(-3) mm Hg(-1) (p <0.001). The independent predictors of ascending aorta distensibility were the diagnosis of a conotruncal defect (p <0.001) and age (p = 0.028). In conclusion, intrinsic aortopathy, manifested as increased ascending aortic diameters and reduced ascending aortic distensibility, is not only evident in adults with TOF, but also in adults with d-TGA and an atrial switch procedure. Long-term follow-up is needed to monitor the aortic size in both patient groups.

Etiology and pathogenesis of adverse drug reactions

In clinical routine, adverse drug reactions (ADR) are common, and they should be included in the differential diagnosis in all patients undergoing drug treatment. Only part of those ADR are immune-mediated hypersensitivity reactions and thus true drug allergies. Far more common are non-immune-mediated ADR, e.g. due to the pharmacological properties of the drug or to the individual predisposition of the patient (enzymopathies, cytokine dysbalance, mast cell hyperreactivity). In true drug allergiesT cell- and immunoglobulin E (lgE)-mediated reactions dominate the clinical presentation. T cell-mediated ADR usually have a delayed appearance and include skin eruptions in most cases. Nevertheless, it should not be forgotten that they may involve systemic T cell activation and thus take a severe, sometimes lethal turn. Clinical danger signs are involvement of mucosal surfaces, blistering within the exanthematous skin areas and systemic symptoms, e.g. fever or malaise. Drug presentation via antigen-presenting cells to T cells can either involve the classical pathway of haptenization of endogenous proteins or be directly mediated via noncovalent binding to immune receptors (MHC molecules or T cell receptors), the so-called p-i concept. Flare-up reactions during the acute phase of T cell-mediated ADR should not be mistaken for true drug allergies, as they only occur in the setting of a highly activated T cell pool. IgE-mediated ADR are less frequent and involve mast cells and/or basophils as peripheral effector cells. Recent data suggest that certain patients with drug allergy have a preexistent sensitization although they have never been exposed to the culprit drug, probably due to cross-reactivity. Thus, allergic drug reactions on first encounter are possible. In general, the extent of cross-reactivity is higher in IgE-compared to T cell-mediated ADR. Based on a specific ethnic background and only for severe T cell-mediated ADR to certain drugs, a strong HLA association has been established recently.

Wetting and spreading of a surfactant film on solid particles: influence of sharp edges and surface irregularities

In addition to particle size and surface chemistry, the shape of particles plays an important role in their wetting and displacement by the surfactant film in the lung. The role of particle shape was the subject of our investigations using a model system consisting of a modified Langmuir-Wilhelmy surface balance. We measured the influence of sharp edges (lines) and other highly curved surfaces, including sharp corners or spikes, of different particles on the spreading of a dipalmitoylphosphatidyl (DPPC) film. The edges of cylindrical sapphire plates (circular curved edges, 1.65 mm radius) were wetted at a surface tension of 10.7 mJ/m2 (standard error (SE) = 0.45, n = 20) compared with that of 13.8 mJ/m2 (SE = 0.20, n = 20) for cubic sapphire plates (straight linear edges, edge length 3 mm) (p < 0.05). The top surfaces of the sapphire plates (cubic and cylindrical) were wetted at 8.4 mJ/m2 (SE = 0.54, n = 20) and 9.1 mJ/m2 (SE = 0.50, n = 20), respectively, but the difference was not significant (p > 0.05). The surfaces of the plates showed significantly higher resistance to spreading compared to that of the edges, as substantially lower surface tensions were required to initiate wetting (p < 0.05). Similar results were found for talc particles, were the edges of macro- and microcrystalline particles were wetted at 7.2 mJ/m2 (SE = 0.52, n = 20) and 8.2 mJ/m2 (SE = 0.30, n = 20) (p > 0.05), respectively, whereas the surfaces were wetted at 3.8 mJ/m2 (SE = 0.89, n = 20) and 5.8 mJ/m2 (SE = 0.52, n = 20) (p < 0.05), respectively. Further experiments with pollen of malvaceae and maize (spiky and fine knobbly surfaces) were wetted at 10.0 mJ/m2 (SE = 0.52, n = 10) and 22.75 mJ/m2 (SE = 0.81, n = 10), respectively (p < 0.05). These results show that resistance to spreading of a DPPC film on various surfaces is dependent on the extent these surfaces are curved. This is seen with cubic sapphire plates which have at their corners a radius of curvature of about 0.75 microm, spiky malvaceae pollen with an even smaller radius on top of their spikes, or talc with various highly curved surfaces. These highly curved surfaces resisted wetting by the DPPC film to a higher degree than more moderately curved surfaces such as those of cylindrical sapphire plates, maize pollens, or polystyrene spheres, which have a surface free energy similar to that of talc but a smooth surface. The macroscopic plane surfaces of the particles demonstrated the greatest resistance to spreading. This was explained by the extremely fine grooves in the nanometer range, as revealed by electron microscopy. In summary, to understand the effects of airborne particles retained on the surfaces of the respiratory tract, and ultimately their pathological potential, not only the particle size and surface chemistry but also the particle shape should be taken in consideration.

Comparison of different radiography systems in an experimental study for detection of forearm fractures and evaluation of the Müller-AO and Frykman classification for distal radius fractures

OBJECTIVES: We sought to compare the diagnostic performance of screen-film radiography, storage-phosphor radiography, and a flat-panel detector system in detecting forearm fractures and to classify distal radius fractures according to the Müller-AO and Frykman classifications compared with the true extent, depicted by anatomic preparation. MATERIALS AND METHODS: A total of 71 cadaver arms were fractured in a material testing machine creating different fractures of the radius and ulna as well as of the carpal bones. Radiographs of the complete forearm were evaluated by 3 radiologists, and anatomic preparation was used as standard of reference in a receiver operating curve analysis. RESULTS: The highest diagnostic performance was obtained for the detection of distal radius fractures with area under the receiver operating curve (AUC) values of 0.959 for screen-film radiography, 0.966 for storage-phosphor radiography, and 0.971 for the flat-panel detector system (P > 0.05). Exact classification was slightly better for the Frykman (kappa values of 0.457-0.478) compared with the Müller-AO classification (kappa values of 0.404-0.447), but agreement can be considered as moderate for both classifications. CONCLUSIONS: The 3 imaging systems showed a comparable diagnostic performance in detecting forearm fractures. A high diagnostic performance was demonstrated for distal radius fractures and conventional radiography can be routinely performed for fracture detection. However, compared with anatomic preparation, depiction of the true extent of distal radius fractures was limited and the severity of distal radius fractures tends to be underestimated.

Proposed minimal standards for the description of genera, species and subspecies of the Pasteurellaceae

Principles and guidelines are presented to ensure a solid scientific standard of papers dealing with the taxonomy of taxa of Pasteurellaceae Pohl 1981. The classification of the Pasteurellaceae is in principle based on a polyphasic approach. DNA sequencing of certain genes is very important for defining the borders of a taxon. However, the characteristics that are common to all members of the taxon and which might be helpful for separating it from related taxa must also be identified. Descriptions have to be based on as many strains as possible (inclusion of at least five strains is highly desirable), representing different sources with respect to geography and ecology, to allow proper characterization both phenotypically and genotypically, to establish the extent of diversity of the cluster to be named. A genus must be monophyletic based on 16S rRNA gene sequence-based phylogenetic analysis. Only in very rare cases is it acceptable that monophyly can not be achieved by 16S rRNA gene sequence comparison. Recently, the monophyly of genera has been confirmed by sequence comparison of housekeeping genes. In principle, a new genus should be recognized by a distinct phenotype, and characters that separate the new genus from its neighbours should be given clearly. Due to the overall importance of accurate classification of species, at least two genotypic methods are needed to show coherence and for separation at the species level. The main criterion for the classification of a novel species is that it forms a monophyletic group based on 16S rRNA gene sequence-based phylogenetic analysis. However, some groups might also include closely related species. In these cases, more sensitive tools for genetic recognition of species should be applied, such as DNA-DNA hybridizations. The comparison of housekeeping gene sequences has recently been used for genotypic definition of species. In order to separate species, phenotypic characters must also be identified to recognize them, and at least two phenotypic differences from existing species should be identified if possible. We recommend the use of the subspecies category only for subgroups associated with disease or similar biological characteristics. At the subspecies level, the genotypic groups must always be nested within the boundaries of an existing species. Phenotypic cohesion must be documented at the subspecies level and separation between subspecies and related species must be fully documented, as well as association with particular disease and host. An overview of methods previously used to characterize isolates of the Pasteurellaceae has been given. Genotypic and phenotypic methods are separated in relation to tests for investigating diversity and cohesion and to separate taxa at the level of genus as well as species and subspecies.

Health risk appraisal in older people 3: prevalence, impact, and context of pain and their implications for GPs

BACKGROUND: Pain is a common experience in later life. There is conflicting evidence of the prevalence, impact, and context of pain in older people. GPs are criticised for underestimating and under-treating pain. AIM: To assess the extent to which older people experience pain, and to explore relationships between self-reported pain and functional ability and depression. DESIGN OF STUDY: Secondary analysis of baseline data from a randomised controlled trial of health risk appraisal. SETTING: A total of 1090 community-dwelling non-disabled people aged 65 years and over were included in the study from three group practices in suburban London. METHOD: Main outcome measures were pain in the last 4 weeks and the impact of pain, measured using the 24-item Geriatric Pain Measure; depression symptoms captured using the 5-item Mental Health Inventory; social relationships measured using the 6-item Lubben Social Network Scale; Basic and Instrumental Activities of Daily Living and self-reported symptoms. RESULTS: Forty-five per cent of women and 34% of men reported pain in the previous 4 weeks. Pain experience appeared to be less in the 'oldest old': 27.5% of those aged 85 years and over reported pain compared with 38-53% of the 'younger old'. Those with arthritis were four times more likely to report pain. Pain had a profound impact on activities of daily living, but most of those reporting pain described their health as good or excellent. Although there was a significant association between the experience of pain and depressed mood, the majority of those reporting pain did not have depressed mood. CONCLUSION: A multidimensional approach to assessing pain is appropriate. Primary care practitioners should also assess the impact of pain on activities of daily living.

Neurokinin-2 receptor levels correlate with intensity, frequency, and duration of pain in chronic pancreatitis

OBJECTIVE: Generation and maintenance of pain in chronic pancreatitis (CP) have been shown to be partially attributable to neuroimmune interactions, which involve neuropeptides such as substance P (SP). So far, expression of SP receptors NK-2R, NK-3R, the SP-encoding gene preprotachykinin A (PPT-A), and the SP degradation enzyme neutral endopeptidase (NEP) and their relation to pain in CP have not been determined. METHODS: Tissue samples from patients with CP (n = 25) and from healthy donors (n = 20) were analyzed for PPT-A, NK-2R, NK-3R, and NEP expression using quantitative RT-PCR. NEP protein levels were examined by immunoblot analysis and its localization was determined using immunohistochemistry. A scoring system was used to grade the extent of fibrosis on hematoxylin and eosin- and Masson-Trichrome-stained sections. Messenger RNA levels and the extent of pain were analyzed for correlations. RESULTS: In CP tissues, NK-2R and PPT-A expression was increased, whereas NK-3R and NEP mRNA levels were comparable with normal pancreas. Overexpression of NK-2R was related to the intensity, frequency, and duration of pain in CP patients. NK-1R and NEP expression was significantly related to the extent of fibrosis. CONCLUSIONS: Expression of NK-2R and PPT-A is increased in CP and is associated with pain. Failure to up-regulate NEP may contribute to the disruption of the neuropeptides loop balance in CP and thus may exacerbate the severe pain syndrome.

New evidence for involvement of the entorhinal region in schizophrenia: a combined MRI volumetric and DTI study

Postmortem examinations and magnetic resonance imaging (MRI) studies suggest involvement of the entorhinal cortex (EC) in schizophrenic psychoses. However, the extent and nature of the possible pathogenetical process underlying the observed alterations of this limbic key region for processing of multimodal sensory information remains unclear. Three-dimensional high-resolution MRI volumetry and evaluation of the regional diffusional anisotropy based on diffusion tensor imaging (DTI) were performed on the EC of 15 paranoid schizophrenic patients and 15 closely matched control subjects. In schizophrenic patients, EC volumes showed a slight, but not significant, decrease. However, the anisotropy values, expressed as inter-voxel coherences (COH), were found to be significantly decreased by 17.9% (right side) and 12.5% (left side), respectively, in schizophrenics. Reduction of entorhinal diffusional anisotropy can be hypothesized to be functionally related to disturbances in the perforant path, the principal efferent EC fiber tract supplying the limbic system with neuronal input from multimodal association centers. Combinations of different MRI modalities are a promising approach for the detection and characterization of subtle brain tissue alterations.

[On quality of life after surgical therapy of oral cancer - a retrospective multi-center study: the connection between dedentition, denture, quality of life, and dysphagia, and the resulting rehabilitation schemes]

PURPOSE: The surgical treatment of oral cancer results in functional and aesthetical impairments. Patients' quality of life is considerably impaired by oral symptoms resulting from therapy of oral cancer. In many cases the inevitable resection of the tumor, as well as the adjuvant radiochemotherapy will cause the destruction of physiologically and anatomically important structures. One focus of research was the specific rehabilitation of dental loss by functional dentures. Another was the course of 19 impairments (comprehension of speech for unknown others, comprehension of speech for familiar others, eating/swallowing, mobility of the tongue, opening range of the mouth, mobility of lower jaw, mobility of neck, mobility of arms and shoulders, sense of taste, sense of smell, appearance, strength, appetite, respiration, pain, swelling, xerostomia, halitosis). METHODS: Commissioned by the German, Austrian and Swiss cooperative group on tumors of the maxillofacial region (DOSAK), data were collected in 3.894 questionnaires at 43 hospitals in Germany, Austria and Switzerland. The catalogue comprised 147 items in 9 chapters. At the end of the enquiry, 1.761 anonymous questionnaires were returned by 38 hospitals. 1.652 of these could be evaluated regarding the question. RESULTS: The sum score of the 19 impairments was highly increased immediately after the operation and recovered over the next 6 months, without, however, reaching the pre-surgery level. Of 1.652 patients, only 35% did not lose any teeth during therapy. 23% lost up to 5, 17% up to 10 teeth. A quarter of the patients lost more than 10 teeth. The more teeth were lost, the greater the decline of quality of life (p < or = 0.001), although this could be allayed by the functionality of the dentures (p < or = 0.001). There is a reciprocal dependence between the functionality of dental prosthetics and impairment by eating/swallowing (p < or = 0.001). CONCLUSIONS: Patients' quality of life after radical surgery of a carcinoma of the oral cavity depends not only on the functionality of dentures and the specificity of rehabilitation, but also from the initial findings, the extent and location of the resection, the chosen therapy, the general circumstances of the patient's life as well as their strategies of coping. These factors, however, unlike those of functionality of dental prosthesis and rehabilitation, are not modifiable.

Aortic root replacement does not affect outcome and quality of life

BACKGROUND: Different studies have analyzed the potential impact of the underlying pathologic process and the use of deep hypothermic circulatory arrest on outcome and quality of life after surgery on the thoracic aorta. The aim of this study is to analyze the impact of different surgical procedures on outcome and quality of life. METHODS: Between June 2001 and December 2003, 244 patients underwent surgery for various diseases of the ascending aorta with or without involvement of the aortic valve or root. They were divided according to the operative procedure: 76 patients (31.2%) underwent isolated replacement of the ascending aorta, 42 patients (17.2%) received separate aortic valve replacement and supracoronary replacement of the ascending aorta, 86 patients (35.2%) received a mechanical composite graft, and 40 patients (16.4%) received a biologic composite graft. All in-hospital data were assessed, and a follow-up was performed in all survivors after 26.6 +/- 8.8 months, focusing on outcome and quality of life (SF-36). RESULTS: Overall in-hospital mortality was 6.1%, and late mortality was 5.7%, with no significant difference between groups. Independent of the surgical technique and the extent of surgery, there was no difference in quality of life between the surgical collective and an age-matched and sex-matched standard population. CONCLUSIONS: Operations of the ascending aorta and aortic valve are very safe, with low in-hospital mortality and favorable midterm outcome regarding late mortality and morbidity. Quality of life after operations of the ascending aorta and aortic valve is equal to a standard population and is not affected by the surgical procedure. Liberal use of aortic root replacement is therefore justified to radically treat the diseased aortic segment.

CT radiation dose for computer-assisted endoscopic sinus surgery: dose survey and determination of dose-reduction limits

BACKGROUND AND PURPOSE: Computer-assisted navigation is increasingly used in functional endoscopic sinus surgery (FESS) to prevent injury to vital structures, necessitating preparative CT and, thus, radiation exposure. The purpose of our study was to investigate currently used radiation doses for CT in computer-assisted navigation in sinus surgery (CAS-CT) and to assess minimal doses required. MATERIALS AND METHODS: A questionnaire inquiring about dose parameters used for CAS-CT was sent to 30 radiologic institutions. The feasibility of low-dose registration was tested with a phantom. The influence of CAS-CT dose on technical accuracy and on the practical performance of 5 ear, nose, and throat (ENT) surgeons was evaluated with cadaver heads. RESULTS: The questionnaire response rate was 63%. Variation between minimal and maximal dose used for CAS-CT was 18-fold. Phantom registration was possible with doses as low as 1.1 mGy. No dose dependence on technical accuracy was found. ENT surgeons were able to identify anatomic landmarks on scans with a dose as low as 3.1 mGy. CONCLUSIONS: The vast dose difference between institutions mirrors different attitudes toward image quality and radiation-protection issues rather than being technically founded, and many patients undergo CAS-CT at higher doses than necessary. The only limit for dose reduction in CT for computer-assisted endoscopic sinus surgery is the ENT surgeon's ability to cope with impaired image quality, whereas there is no technically justified lower dose limit. We recommend, generally, doses used for the typical diagnostic low-dose sinus CT (120 kV/20-50 mAs). When no diagnostic image quality is needed, even a reduction down to a third is possible.

Acute Stroke: Present and Future of Catheter-Based Interventions

Acute ischemic stroke is a major cause of morbidity and mortality in industrialized nations. The sequel of stroke ranges from mild to severe disability and even death. Since the impairment may be permanent, the costs to society from work incapacity and the need for long-term care can be high. Additionally, the burden of suffering associated with the disease may have devastating effects on individuals and families.Following the occlusion of a cerebral vessel, the full extent of the infarction may not become clinically and radiologically apparent until days after. By then, the surrounding watershed zone, or penumbra, either survives or succumbs to necrosis over time. The natural history of this "tissue at risk" is determined by two factors: the collateralization from other vascular territories and the possible occurrence of spontaneous recanalization of the occluded vessel. The current treatment options for acute ischemic stroke are aiming at an early and sustained restoration of flow to the penumbra. The effect of the treatment is therefore time-dependent and the neurologic outcome is a function of the time span between onset of symptoms and recanalization therapy as well as of the recanalization rate associated with a specific treatment.This report summarizes the results of the major trials on catheter-based interventions, either using thrombolytic drugs or novel mechanical approaches being developed to treat patients with acute ischemic stroke.

Effects of diabetes mellitus on periodontal and peri-implant conditions: update on associations and risks

OBJECTIVES: To review the evidence for the association between diabetes and periodontal and peri-implant conditions and the impact of periodontal therapy in subjects with diabetes. MATERIAL AND METHODS: A search of MEDLINE-PubMed was performed up to and including December 2007. The search was limited to clinical studies published in English. Publications on animal studies were excluded. The selection criteria included all levels of available evidence. RESULTS: Evidence on the association between diabetes and periodontitis supports the concept of increased severity but not extent of periodontitis in subjects with poorly controlled diabetes. Subjects with controlled diabetes do not show an increase in extent and severity of periodontitis. Periodontitis is associated with poor glycaemic control and diabetes-related complications. It is inconclusive that periodontal therapy with or without the use of antibiotics results in improvements of glycaemic control and of markers of systemic inflammation. Evidence is lacking to indicate that implant therapy in subjects with diabetes yields long-term outcomes comparable with those of non-diabetic subjects. CONCLUSIONS: Poorly controlled diabetes may be considered a risk factor for increased severity of periodontitis. The effects of periodontal therapy on glycaemic control and systemic inflammation is not proven beyond doubt and need to be confirmed in large-scale randomized-controlled clinical trials.