Time courses and quantitative analysis of atrial fibrillation episode number and duration after circular plus linear left atrial lesions: trigger elimination or substrate modification: early or delayed cure?

OBJECTIVES We sought to analyze the time course of atrial fibrillation (AF) episodes before and after circular plus linear left atrial ablation and the percentage of patients with complete freedom from AF after ablation by using serial seven-day electrocardiograms (ECGs). BACKGROUND The curative treatment of AF targets the pathophysiological corner stones of AF (i.e., the initiating triggers and/or the perpetuation of AF). The pathophysiological complexity of both may not result in an "all-or-nothing" response but may modify number and duration of AF episodes. METHODS In patients with highly symptomatic AF, circular plus linear ablation lesions were placed around the left and right pulmonary veins, between the two circles, and from the left circle to the mitral annulus using the electroanatomic mapping system. Repetitive continuous 7-day ECGs administered before and after catheter ablation were used for rhythm follow-up. RESULTS In 100 patients with paroxysmal (n = 80) and persistent (n = 20) AF, relative duration of time spent in AF significantly decreased over time (35 +/- 37% before ablation, 26 +/- 41% directly after ablation, and 10 +/- 22% after 12 months). Freedom from AF stepwise increased in patients with paroxysmal AF and after 12 months measured at 88% or 74% depending on whether 24-h ECG or 7-day ECG was used. Complete pulmonary vein isolation was demonstrated in <20% of the circular lesions. CONCLUSIONS The results obtained in patients with AF treated with circular plus linear left atrial lesions strongly indicate that substrate modification is the main underlying pathophysiologic mechanism and that it results in a delayed cure instead of an immediate cure.

Francisella tularensis infection in a stone marten (Martes foina) without classic pathological lesions consistent with tularemia.

The current report describes the isolation and typing of a strain of Francisella tularensis, the causative agent of tularemia, from the spleen of a stone marten (Martes foina) showing no classic lesions consistent with the disease. The identification of this bacterium, belonging to the World Health Organization risk 3 category and considered to have a low infectious dose, could be performed only because of an ongoing project screening F. tularensis in the environment sensu lato. The findings described herein should alert diagnostic laboratories of the possible presence of F. tularensis in clinical samples in countries where tularemia is endemic even in cases with no consistent anamnesis and from unsuspected animal species.

Cutaneous lesions associated with dual infection caused by canine distemper virus and orthopoxvirus in a domestic cat.

BACKGROUND Within the context of an increased epidemiological pressure caused by canine distemper virus (CDV) in Switzerland together with a potential re-emergence of endemic pathogens such as orthopoxviruses (OPXV), dual infections are possible among susceptible species. OBJECTIVE To describe a case of concurrent CDV and OPXV infection in a cat. ANIMAL A 5-year-old, neutered male cat was presented with erythema, crusts and ulcerations around the left eye. High-grade pruritus and a severe conjunctivitis were also present. METHODS Formalin-fixed skin biopsy samples were obtained from lesional skin. Histopathology, CDV immunohistochemistry and CDV and OPXV RT-PCR were performed. RESULTS Histopathological examination showed severe epidermal necrosis extending to the follicular walls and a dermal infiltration, predominantly eosinophilic. Intranuclear and intracytoplasmic eosinophilic inclusion bodies were visible in the wall of affected hair follicles, with occasional formation of syncytia. The RT-PCR revealed the contextual presence of both CDV and OPXV. Scattered cells stained positive for CDV by immunohistochemistry. CONCLUSION AND DISCUSSION Dual infections with CDV and OPXV, although rare, may occur and represent additional differential diagnoses for ulcerative skin lesions in cats.

Multiple osteosclerotic lesions in an Iron Age skull from Switzerland (320 - 250 BC) - An unusual case

The single Hochdorf burial was found in 1887 during construction work in the Canton of Lucerne, Switzerland. It dates from between 320 and 250 BC. The calvarium, the left half of the pelvis and the left femur were preserved. The finding shows an unusual bony alteration of the skull. The aim of this study was to obtain a differential diagnosis and to examine the skull using various methods. Sex and age were determined anthropologically. Radiological examinations were performed with plain X-ray imaging and a multislice computed tomography (CT) scanner. For histological analysis, samples of the lesion were taken. The pathological processing included staining after fixation, decalcification, and paraffin embedding. Hard-cut sections were also prepared. The individual was female. The age at death was between 30 and 50 years. There is an intensely calcified bone proliferation at the right side of the os frontalis. Plain X-ray and CT imaging showed a large sclerotic lesion in the area of the right temple with a partly bulging appearance. The inner boundary of the lesion shows multi-edged irregularities. There is a diffuse thickening of the right side. In the left skull vault, there is a mix of sclerotic areas and areas which appear to be normal with a clear differentiation between tabula interna, diploë and tabula externa. Histology showed mature organised bone tissue. Radiological and histological findings favour a benign condition. Differential diagnoses comprise osteomas which may occur, for example, in the setting of hereditary adenomatous polyposis coli related to Gardner syndrome.

Chronic bovine besnoitiosis: intra-organ parasite distribution, parasite loads and parasite-associated lesions in subclinical cases.

Bovine besnoitiosis caused by Besnoitia besnoiti is a chronic and debilitating disease. The most characteristic clinical signs of chronic besnoitiosis are visible tissue cysts in the scleral conjunctiva and the vagina, thickened skin and a generally poor body condition. However, many seropositive animals remain subclinically infected, and the role that these animals may play in spreading the disease is not known. The aim of the present study was to assess the intra-organ parasite distribution, the parasite load and the parasite-associated lesions in seropositive but subclinically infected animals. These animals were seropositive at the time of several consecutive samplings, had visible tissue cysts in the past and, at time of slaughter, had detectable specific anti-Besnoitia spp. antibody levels, but they did not show evident clinical signs at culling. Thus, histopathological, immunohistochemical and molecular analyses of several samples from the respiratory tract, reproductive tract, other internal organs and skin from six cows were performed. The tissue cysts were located primarily in the upper respiratory tract, i.e., in the rhinarium and larynx/pharynx (four cows), followed by the distal genital tract (vulva/vagina) and the skin of the neck (three and two cows, respectively, out of the four cows with cysts in the respiratory tract). We were unable to detect any parasites in the two remaining cows. Cysts were associated with a significant non-purulent inflammatory infiltrate consisting predominantly of T lymphocytes and activated monocytes/macrophages in two cows. The parasite burden, estimated by quantitative real-time PCR, was very low. It is noteworthy that the only animal that showed a recent increase in the antibody titre had the highest parasite burden and the most conspicuous inflammatory reaction against the cysts. In conclusion, although these cows no longer displayed any visible signs of besnoitiosis, they remained infected. Therefore, cows without visible signs of disease may still be able to transmit the parasite.

Differential Effects on Survival, Humoral Immune Responses and Brain Lesions in Inbred BALB/C, CBA/CA, and C57BL/6 Mice Experimentally Infected with Neospora caninum Tachyzoites

C57BL/6, BALB/c, and CBA/Ca mouse strains with different MHC-I haplotypes were compared with respect to susceptibility to Neospora caninum infection. Groups of 5 mice received , , or tachyzoites of the NC-Liverpool isolate by intraperitoneal injection and were observed for disease symptoms. Humoral responses, splenocyte interferon-γ (IFN-γ) production, cerebral parasite loads, and histopathology were evaluated at human end points or the latest at 34 days postinfection (PI). The mortality rates in C57BL/6 mice were the highest, and relatively high levels of IgG1 antibodies were detected in those mice surviving till 34 days PI. In lymphocyte proliferation assays, spleen cells from C57BL6 mice stimulated with N. caninum antigen extract exhibited large variations in IFN-γ production. In BALB/c mice mortality was 0% at the lowest and 100% at the highest infection dose. Serologically they responded with high levels of both IgG2a and IgG1 subclasses, and lymphocyte proliferation assays of surviving mice yielded lower IFN-γ levels. CBA/Ca mice were the most resistant, with no animal succumbing to infection at a dose of and tachyzoites, but 100% mortality at tachyzoites. High IgG2a levels as well as increased IFN-γ in lymphocyte proliferation assays were measured in CBA/Ca mice infected with tachyzoites.

Epidemiologic survey in Swiss group-housed breeding rabbits: extent of lesions and potential risk factors

In Switzerland, group-housing for breeding rabbit does is not explicitly required by law, but label programmes, as well as the general public and animal welfare groups, are advocating it. Although group-housing is of great benefit to the gregariously living rabbits, the establishment of a social hierarchy within the group might lead to stress and lesions. In the present epidemiological study, lesions were scored twice on 30% of the breeding does on all 28 commercial Swiss farms with group-housed breeding does. Additionally, a detailed questionnaire was filled out with all producers to determine risk factors potentially associated with lesions. Data were analysed using hierarchical proportional odds models. About 33% of the does examined had lesions, including wounds that were almost healed and small scratches. Severe lesions were counted on 9% of the animals. Differences between seasons in lesions score were identified, with the extent of lesions being higher in summer than in spring. Fewer lesions occurred on farms on which mastitis was more common. More lesions were found on farms where the does were isolated between littering and artificial insemination than on farms without isolation. According to the producers, most of the aggression occurred directly after the isolation phase when the does were regrouped again. We conclude that lesions in group-housed breeding does might be reduced by appropriate reproductive management.

Implicit task sequence learning in patients with Parkinson's disease, frontal lesions and amnesia: The critical role of fronto–striatal loops

The purpose of this study was to investigate the role of the fronto–striatal system for implicit task sequence learning. We tested performance of patients with compromised functioning of the fronto–striatal loops, that is, patients with Parkinson's disease and patients with lesions in the ventromedial or dorsolateral prefrontal cortex. We also tested amnesic patients with lesions either to the basal forebrain/orbitofrontal cortex or to thalamic/medio-temporal regions. We used a task sequence learning paradigm involving the presentation of a sequence of categorical binary-choice decision tasks. After several blocks of training, the sequence, hidden in the order of tasks, was replaced by a pseudo-random sequence. Learning (i.e., sensitivity to the ordering) was assessed by measuring whether this change disrupted performance. Although all the patients were able to perform the decision tasks quite easily, those with lesions to the fronto–striatal loops (i.e., patients with Parkinson's disease, with lesions in the ventromedial or dorsolateral prefrontal cortex and those amnesic patients with lesions to the basal forebrain/orbitofrontal cortex) did not show any evidence of implicit task sequence learning. In contrast, those amnesic patients with lesions to thalamic/medio-temporal regions showed intact sequence learning. Together, these results indicate that the integrity of the fronto–striatal system is a prerequisite for implicit task sequence learning.

Lameness and foot lesions in Swiss dairy cows: I. Prevalence.

Prevalences of foot lesions and lameness were recorded in 1'449 Swiss dairy cows during routine claw-trimming on 78 farms from June 2010 until February 2011. Lameness was present in 14.8 % of cows and on 80.8 % of investigated farms. Highest prevalences were seen for widened white line (80.7 %/100 %), signalling foot lesion (65.6 %/98.7 %), heel-horn erosion (34.2 %/88.5 %), digital dermatitis complex (29.1 %/73.1 %), severe hemorrhages (27.9 %/87.2 %), and Rusterholz' sole ulcers (11.5 %/74.4 %) at cow and herd level, respectively. Lower prevalences were found for subclinical laminitis (5.4 %/47.4 %), chronic laminitis (3.3 %/25.6 %), white line disease (4.7 %/42.3 %), double soles (2.6 %/33.3 %), interdigital hyperplasia (3.1 %/33.3 %), sole ulcers (0.4 %/6.4 %), toe infections caused by faulty claw-trimming (3.9 %/39.7 %) and by injury (0.1 %/2.6 %), deep lacerations (0.4 %/6.4 %), and interdigital phlegmona (0.1 %/1.3 %). Lameness and foot lesions were shown to represent important health problems of dairy cows under the conditions of the typical grass-based production system in Switzerland. Digital dermatitis has developed to the most relevant foot disease with a high impact on welfare of Swiss dairy cows within the past 10 years.

Lameness and foot lesions in Swiss dairy cows: II. Risk factors.

The objective of this study was to evaluate risk factors associated with foot lesions and lameness in Swiss dairy cows. Potential risk factors were recorded by means of examination of 1'449 Swiss cows and the management systems of 78 farms during routine claw-trimming, and during personal interviews with the associated farmers. Statistical analysis of animal-based and herd level risk factors were performed using multivariate logistic regression models. The risk of being lame was increased in cows affected by digital dermatitis complex, heel-horn erosion, interdigital hyperplasia, Rusterholz' sole ulcer, deep laceration, double sole and severe hemorrhages. Cleanliness, BCS, affection with other foot lesions, breed, importance of claw health to the farmer, frequency of routine claw-trimming, producing according to the guidelines of the welfare label program RAUS, and silage feeding were shown to be associated with the occurrence of some of the evaluated foot lesions and lameness. The identified risk factors may help to improve management and the situation of lameness and claw health in dairy cows in Switzerland and other alpine areas with similar housing and pasturing systems.

Apoptosis in Bovine viral diarrhea virus (BVDV)-induced mucosal disease lesions: a histological, immunohistological, and virological investigation

Cattle persistently infected with a noncytopathic Bovine viral diarrhea virus (BVDV) are at risk of developing fatal "mucosal disease" (MD). The authors investigated the role of various apoptosis pathways in the pathogenesis of lesions in animals suffering from MD. Therefore, they compared the expression of caspase-3, caspase-8, caspase-9, and Bcl-2L1 (Bcl-x) in tissues of 6 BVDV-free control animals, 7 persistently infected (PI) animals that showed no signs of MD (non-MD PI animals), and 11 animals with MD and correlated the staining with the localization of mucosal lesions. Caspase-3 and -9 staining were markedly stronger in MD cases and were associated with mucosal lesions, even though non-MD PI animals and negative controls also expressed caspase-9. Conversely, caspase-8 was not elevated in any of the animals analyzed. Interestingly, Bcl-x also colocalized with mucosal lesions in the MD cases. However, Bcl-x was similarly expressed in tissues from all 3 groups, and thus, its role in apoptosis needs to be clarified. This study clearly illustrates ex vivo that the activation of the intrinsic, but not the extrinsic, apoptosis pathway is a key element in the pathogenesis of MD lesions observed in cattle persistently infected with BVDV. However, whether direct induction of apoptosis in infected cells or indirect effects induced by the virus are responsible for the lesions observed remains to be established.

Prediction of outcome in patients with low-grade squamous intraepithelial lesions by fluorescence in situ hybridization analysis of human papillomavirus, TERC, and MYC

BACKGROUND Cytology is an excellent method with which to diagnose preinvasive lesions of the uterine cervix, but it suffers from limited specificity for clinically significant lesions. Supplementary methods might predict the natural course of the detected lesions. The objective of the current study was to test whether a multicolor fluorescence in situ hybridization (FISH) assay might help to stratify abnormal results of Papanicolaou tests. METHODS A total of 219 liquid-based cytology specimens of low-grade squamous intraepithelial lesions (LSIL), 49 atypical squamous cells of undetermined significance (ASCUS) specimens, 52 high-grade squamous intraepithelial lesion (HSIL) specimens, and 50 normal samples were assessed by FISH with probes for the human papillomavirus (HPV), MYC, and telomerase RNA component (TERC). Subtyping of HPV by polymerase chain reaction (PCR) was performed in a subset of cases (n=206). RESULTS There was a significant correlation found between HPV detection by FISH and PCR (P<.0001). In patients with LSILs, the presence of HPV detected by FISH was significantly associated with disease progression (P<.0001). An increased MYC and/or TERC gene copy number (>2 signals in>10% of cells) prevailed in 43% of ASCUS specimens and was more frequent in HSIL (85%) than in LSIL (33%) (HSIL vs LSIL: P<.0001). Increased TERC gene copy number was significantly correlated with progression of LSIL (P<.01; odds ratio, 7.44; area under the receiver operating characteristic curve, 0.73; positive predictive value, 0.30; negative predictive value, 0.94) CONCLUSIONS: The detection of HPV by FISH analysis is feasible in liquid-based cytology and is significantly correlated with HPV analysis by PCR. The analysis of TERC gene copy number may be useful for risk stratification in patients with LSIL.

Comparison of freehand-navigated and aiming device-navigated targeting of liver lesions

BACKGROUND Accurate needle placement is crucial for the success of percutaneous radiological needle interventions. We compared three guiding methods using an optical-based navigation system: freehand, using a stereotactic aiming device and active depth control, and using a stereotactic aiming device and passive depth control. METHODS For each method, 25 punctures were performed on a non-rigid phantom. Five 1 mm metal screws were used as targets. Time requirements were recorded, and target positioning errors (TPE) were measured on control scans as the distance between needle tip and target. RESULTS Time requirements were reduced using the aiming device and passive depth control. The Euclidian TPE was similar for each method (4.6 ± 1.2-4.9 ± 1.7 mm). However, the lateral component was significantly lower when an aiming device was used (2.3 ± 1.3-2.8 ± 1.6 mm with an aiming device vs 4.2 ± 2.0 mm without). DISCUSSION Using an aiming device may increase the lateral accuracy of navigated needle insertion.

Augmented environments for the targeting of hepatic lesions during image-guided robotic liver surgery

BACKGROUND Stereotactic navigation technology can enhance guidance during surgery and enable the precise reproduction of planned surgical strategies. Currently, specific systems (such as the CAS-One system) are available for instrument guidance in open liver surgery. This study aims to evaluate the implementation of such a system for the targeting of hepatic tumors during robotic liver surgery. MATERIAL AND METHODS Optical tracking references were attached to one of the robotic instruments and to the robotic endoscopic camera. After instrument and video calibration and patient-to-image registration, a virtual model of the tracked instrument and the available three-dimensional images of the liver were displayed directly within the robotic console, superimposed onto the endoscopic video image. An additional superimposed targeting viewer allowed for the visualization of the target tumor, relative to the tip of the instrument, for an assessment of the distance between the tumor and the tool for the realization of safe resection margins. RESULTS Two cirrhotic patients underwent robotic navigated atypical hepatic resections for hepatocellular carcinoma. The augmented endoscopic view allowed for the definition of an accurate resection margin around the tumor. The overlay of reconstructed three-dimensional models was also used during parenchymal transection for the identification of vascular and biliary structures. Operative times were 240 min in the first case and 300 min in the second. There were no intraoperative complications. CONCLUSIONS The da Vinci Surgical System provided an excellent platform for image-guided liver surgery with a stable optic and instrumentation. Robotic image guidance might improve the surgeon's orientation during the operation and increase accuracy in tumor resection. Further developments of this technological combination are needed to deal with organ deformation during surgery.