Structural and electro-anatomical characterization of the equine pulmonary veins: implications for atrial fibrillation.

INTRODUCTION/OBJECTIVES: Spontaneous pulmonary vein (PV) activity triggers atrial fibrillation (AF) in humans. Although AF frequently occurs in horses, the origin remains unknown. This study investigated the structural and electro-anatomical properties of equine PVs to determine the potential presence of an arrhythmogenic substrate. ANIMALS, MATERIALS AND METHODS: Endocardial three-dimensional electro-anatomical mapping (EnSite Precision) using high-density (HD) catheters was performed in 13 sedated horses in sinus rhythm. Left atrium (LA) access was obtained retrogradely through the carotid artery. Post-mortem, tissue was harvested from the LA, right atrium (RA), and PVs for histological characterization and quantification of ion channel expression using immunohistochemical analysis. RESULTS: Geometry, activation maps, and voltage maps of the PVs were created and a median of four ostia were identified. Areas of reduced conduction were found at the veno-atrial junction. The mean myocardial sleeve length varied from 28 ± 13 to 49 ± 22 mm. The PV voltage was 1.2 ± 1.4 mV and lower than the LA (3.4 ± 0.9 mV, P < 0.001). The fibrosis percentage was higher in PV myocardium (26.1 ± 6.6%) than LA (14.5 ± 5.0%, P = 0.003). L-type calcium channel (CaV1.2) expression was higher in PVs than LA (P = 0.001). T-type calcium channels (CaV3.3), connexin-43, ryanodine receptor-2, and small conductance calcium-activated potassium channel-3 was expressed in PVs. CONCLUSIONS: The veno-atrial junction had lower voltages, increased structural heterogeneity and areas of slower conduction. Myocardial sleeves had variable lengths, and a different ion channel expression compared to the atria. Heterogeneous properties of the PVs interacting with the adjacent LA likely provide the milieu for re-entry and AF initiation.

[Work in progress: adaptation of electronic medical records to the requirements of a university eye clinic : Individual extensions of the software "FIDUS" at the Department of Ophthalmology of the Saarland University Medical Center UKS]. / Work in Progress: Anpassung der elektronischen Patientenakte an die Anforderungen einer Universitätsaugenklinik : Individuelle Erweiterungen der Software "FIDUS" an der Klinik für Augenheilkunde am Universitätsklinikum des Saarlandes UKS.

BACKGROUND: The implementation of electronic medical records (EMR) in the Department of Ophthalmology at the Saarland University Medical Center (UKS) in January 2016 was a timely response to growing documentation requirements and rapidly increasing electronic diagnostic data. The software system was primarily developed for private practices and cannot therefore meet the different requirements of various clinics out of the box. The purpose of this study was to identify features of the EMR beyond purely paper replacement that can assist in the clinical workflow and whether these features can be implemented in a running system. METHODS: The EMR was specifically individualized with respect to the work processes and documentation requirements of the Department of Ophthalmology at the UKS. In addition to a seamless integration into the hospital information system (HIS) the modifications included changes in the structure and visual presentation of the EMR as well as functional extensions. An internet-based platform was set up to enable a direct exchange of appointments and patient data with specialist practices. RESULTS: Due to the introduction of a so-called ghost list the position of patients within the hospital who are allocated to a physician, e.g. for diagnostics, can be reconstructed at any point in time. The logging of the individual treatment times enables tracking of patient flow within the clinic and a reduction of waiting times. Existing paper documents particularly for the graphic recording of findings, such as sketches, are digitalized eliminating the need to scan documents. The UKS.AUGEN.NETZ is an internet-based portal to facilitate direct organization of appointments with specialist practitioners and for the exchange of digital examination data and medical correspondence. CONCLUSION: The permanent close cooperation between employees of the Department of Ophthalmology at the UKS and the manufacturer of the software enables a continuous optimization of the EMR in a fully operational clinical workflow. In addition, the web-based interface improves the cooperation between the hospital and private practices.

[Per aspera ad astra: implementation of electronic patient records in a university eye hospital : Experience with FIDUS in the Clinic for Ophthalmology at the Saarland University Medical Center UKS]. / Per aspera ad astra: Einführung einer elektronischen Patientenakte an einer Universitätsaugenklinik : Erfahrungen mit "FIDUS" in der Klinik für Augenheilkunde am Universitätsklinikum des Saarlandes UKS.

BACKGROUND: For more than 60 years patient records of the Department of Ophthalmology at the Saarland Medical Center in Homburg were documented on handwritten paper documents and filed in archives. Increasing requirements for medical documentation, exploding volumes of diagnostic data, overcrowded archives and unavailable files when needed, were the essential rationales for the implementation of an electronic patient archive (EPA). METHODS: The EPA has been specifically adapted to the requirements of the Department of Ophthalmology in order to guarantee a standardized unobstructed documentation and patient care across all sections of the department. Seamless integration into the clinic information system (KIS) and network-compatible diagnostic software were essential as well as a timely digitization of existing paper charts. Decisive factors for using FIDUS (Arztservice Wente GmbH, Darmstadt, Germany) as the EPA software were the visual layout of the EPA, user friendliness and reference installations of the software in other ophthalmology departments. RESULTS: After one and a half years of meticulous preparation with specific adaptations to the requirements of our department, the EPA was finally implemented in January 2016 and since then we have been working on improvements. The EPA software retrieves basic patient data from the KIS and diagnostic data from electronic devices via various interfaces. Expenses for printers could be reduced but computer workplaces had to be expanded or newly created. For previous patients paper files are digitized externally and stored in an electronic archive directly accessible from the EPA. DISCUSSION: Successful reorganization and implementation of electronic documentation during clinical routine is feasible with careful preparation and timely involvement of information technology experts, motivated physicians, nurses, research departments and the administration.

Left Ventricular Function After Prolonged Exercise in Equine Endurance Athletes.

BACKGROUND: Prolonged exercise in human athletes is associated with transient impairment of left ventricular (LV) function, known as cardiac fatigue. Cardiac effects of prolonged exercise in horses remain unknown. OBJECTIVES: To investigate the effects of prolonged exercise on LV systolic and diastolic function in horses. ANIMALS: Twenty-six horses competing in 120-160 km endurance rides. METHODS: Cross-sectional field study. Echocardiography was performed before and after rides, and the following morning, and included two-dimensional echocardiography, anatomical M-mode, pulsed-wave tissue Doppler imaging, and two-dimensional speckle tracking. Correlation between echocardiographic variables and cardiac troponin I was evaluated. RESULTS: Early diastolic myocardial velocities decreased significantly in longitudinal (baseline: -17.4 ± 2.4cm/s; end of ride: -15.8 ± 3.2cm/s (P = .013); morning after: -15.4 ± 3.0cm/s (P = .0033)) and radial directions (-32.8 ± 3.4cm/s; -28.1 ± 5.8cm/s (P < .001); -26.4 ± 5.5cm/s (P < .001)). Early diastolic strain rates decreased significantly in longitudinal (1.58 ± 0.27s(-1) ; 1.45 ± 0.26s(-1) (P = .036); 1.41 ± 0.25s(-1) (P = .013)) and circumferential directions (2.43 ± 0.29s(-1) ; 1.96 ± 0.46s(-1) (P < .001); 2.11 ± 0.32s(-1) (P < .001)). Systolic variables showed ambiguous results. No correlations with serum cardiac troponin I concentrations were evident. CONCLUSIONS AND CLINICAL IMPORTANCE: Prolonged exercise in horses is associated with impaired LV diastolic function. Reduced ventricular filling persisted for 7-21 hours despite normalization of biochemical indicators of hydration status, indicating that the observed changes were not entirely related to altered preload conditions. The clinical relevance of cardiac fatigue in horses remains uncertain.

Antiarrhythmic and electrophysiologic effects of flecainide on acutely induced atrial fibrillation in healthy horses.

BACKGROUND: Only few pharmacologic compounds have been validated for treatment of atrial fibrillation (AF) in horses. Studies investigating the utility and safety of flecainide to treat AF in horses have produced conflicting results, and the antiarrhythmic mechanisms of flecainide are not fully understood. OBJECTIVES: To study the potential of flecainide to terminate acutely induced AF of short duration (≥ 15 minutes), to examine flecainide-induced changes in AF duration and AF vulnerability, and to investigate the in vivo effects of flecainide on right atrial effective refractory period, AF cycle length, and ventricular depolarization and repolarization. ANIMALS: Nine Standardbred horses. Eight received flecainide, 3 were used as time-matched controls, 2 of which also received flecainide. METHODS: Prospective study. The antiarrhythmic and electrophysiologic effects of flecainide were based on 5 parameters: ability to terminate acute pacing-induced AF (≥ 15 minutes), and drug-induced changes in atrial effective refractory period, AF duration, AF vulnerability, and ventricular depolarization and repolarization times. Parameters were assessed at baseline and after flecainide by programmed electrical stimulation methods. RESULTS: Flecainide terminated all acutely induced AF episodes (n = 7); (AF duration, 21 ± 5 minutes) and significantly decreased the AF duration, but neither altered atrial effective refractory period nor AF vulnerability significantly. Ventricular repolarization time was prolonged between 8 and 20 minutes after initiation of flecainide infusion, but no ventricular arrhythmias were detected. CONCLUSIONS AND CLINICAL IMPORTANCE: Flecainide had clear antiarrhythmic properties in terminating acute pacing-induced AF, but showed no protective properties against immediate reinduction of AF. Flecainide caused temporary prolongation in the ventricular repolarization, which may be a proarrhythmic effect.

Increasing incidence of childhood tumours of the central nervous system in Denmark, 1980-1996.

The registered incidence rate of childhood central nervous system (CNS) tumours has increased in several countries. It is uncertain whether these increases are biologically real or owing to improved diagnostic methods. We explored the medical records of 626 CNS tumours diagnosed in Danish children between 1980 and 1996. Population-based registers were used to extract data on mortality and background population. Temporal patterns were analysed by regression techniques. Most tumours were verified by computed tomography (78%) or magnetic resonance imaging (14%). Overall, the incidence rate increased by 2.9% per year (95% confidence interval (CI): 1.3;4.5) and the mortality rate increased by 1.4% per year (95% CI: -0.4;3.3). Among children aged 0-4 years, the survival rate after diagnosis remained almost unchanged, whereas among children aged 5-14 years, the 10-year survival rate improved from 59 to 74%. These data suggest that the incidence rate of CNS tumours among Danish children has truly increased, although alternative explanations cannot be excluded.

High expression of markers of apoptosis in Langerhans cell histiocytosis.

AIMS: Langerhans cell histiocytosis is a rare disease with clonal proliferation of dendritic histiocytes, occurring most frequently in infancy and early childhood. In the localized form (single system), the disease is self-limiting, but in the cases of multisystem disease a third of the patients develop organ dysfunction. In these cases the prognosis is poor. Our objective has been to study the immunohistochemical expression of Fas and Fas-ligand (Fas-L) in order to determine whether the level of expression of these proteins could predict the outcome of the disease. We also wanted to determine the number of apoptotic cells to compare with the expression of Fas and Fas-L. METHODS AND RESULTS: We analysed the expression of Fas and Fas-L in 76 infiltrates from 49 paediatric patients with Langerhans cell histiocytosis. We also compared the results with the expression of the tumour suppressor protein p53 and the number of cells in apoptosis detected with TUNEL. Langerhans cell histiocytosis cells showed strong expression of p53 and in some cases co-expression of Fas and Fas-L. The expression of Fas-L was significantly higher in infiltrates from patients with single-system disease. The actual number of pathological Langerhans cells in apoptosis as estimated by TUNEL was low. CONCLUSIONS: The low number of TUNEL-reactive cells can be explained by the rapid turnover of apoptotic cells in the tissue, not leaving the apoptotic cells long enough in the tissue to be detected. The co-expression of Fas and Fas-L in some Langerhans cells can lead to an autocrine apoptotic shortcut, mediating the death of the double-positive cells. Our findings suggest that apoptosis mediated through the Fas/Fas-L pathway may contribute to the spontaneous regression of lesions in single-system disease. A delicate balance between autocrine death and survival of Langerhans cells may have been disturbed in patients with multisystem lesions.

The safety and efficacy of MenoTreat, a new balloon device for thermal endometrial ablation.

BACKGROUND: An evaluation of the performance and safety of the prototype of a new device, MemoTreat (Atos Medical) for thermal endometrial balloon ablation in patients with menorrhagia. The evaluation was performed at four Swedish hospitals. METHODS: In total 51 consecutive, premenopausal patients, suffering from menorrhagia due to benign causes and not responding to conventional treatment, were treated between March 1997 and March 1998. The treatment entailed heated (85 degrees C) sterile saline circulated in a uterine balloon at a treatment pressure of 200 mmHg for 11 minutes. The procedure was performed mainly under general anesthesia and no pre-treatment endometrial thinning was performed. A validated pictorial assessment technique was used to evaluate changes in menstrual blood loss before and after treatment. Changes in quality of life and severity of dysmenorrhea were also evaluated. Data analysis was based on the 'intention to treat' method. RESULTS: The success rate in terms of a 50% reduction in menstrual bleeding was 84.3% at 6 months after treatment. Five patients became amenorrheic. The quality of life assessment showed substantial improvement and the severity of dysmenorrhea was markedly reduced. No intra-operative treatment complications occurred and the post-treatment morbidity was similar to that reported for other similar treatment methods. CONCLUSIONS: MenoTreat significantly reduced menstrual bleeding in menorrhagic patients, with a concomitant improvement in quality of life. The findings in this study resulted in a redesigned device with a thinner balloon catheter, improved cervical protection and treatment temperatures kept at a constant level.

Manual acupuncture reduces hyperemesis gravidarum: a placebo-controlled, randomized, single-blind, crossover study.

Hyperemesis gravidarum, severe vomiting, develops in about 1-2% of all pregnancies. Acupuncture on the point PC6 above the wrist on the palmar side has been found to prevent some types of nausea and vomiting. The purpose of the present study was to see if acupuncture, in addition to standard treatment, could hasten the improvement of hyperemesis gravidarum. Thirty-three women with hyperemesis were evaluated in a randomized, single-blind, crossover comparison of two methods of acupuncture, active (deep) PC6 acupuncture or placebo (superficial) acupuncture. The women estimated their degree of nausea on a visual analogue scale (VAS). The daily number of emesis episodes were documented. Crossover analyses showed that there was a significantly faster reduction of nausea VAS and more women who stopped vomiting after active acupuncture than after placebo acupuncture. This study suggests that active PC6 acupuncture, in combination with standard treatment, could make women with hyperemesis gravidarum better faster than placebo acupuncture.

21. Increased FDG uptake in Childhood CNS Tumors is Associated with Tumor Malignancy.

Background: In adults PET scanning of CNS tumors with the tracer FDG (18F-flourodeoxyglucose) can provide information about the degree of malignancy, tumor extent, and dissemination. FDG PET can also be able to assess tumor response to therapy and to differentiate recurrence from necrosis. Although CNS tumors are the most common solid tumor in childhood, so far only few PET-studies have been reported. Pre-operative assessment of malignancy would facilitate surgical planning and the use of pre-operative chemotherapy.Materials and Methods: 21 children with CNS tumors were referred to clinical FDG PET prior to therapy (M/F = 12/9, median age: 9 (range 0-16)), (4 PNET/medulloblastomas; 1 gr. III ependymoma, 16 benign tumors)). Image processing included co-registration with MRI and image fusion. The FDG uptake in the tumors was ranked 0-5 by a hotspot/cortex-ratio by two observers independently. The FDG uptake in grey and white matter was used as reference for the grading system with FDG uptakes defined as 4 and 2 respectively.Results: 15 of 16 patients with tumors WHO gr. I-II had FDG-uptake of 1-2, and all 5 patients with tumors WHO gr. III-IV had FDG-uptake of 3-4. A WHO gr. I papilloma, known to have a high metabolism caused by high mitochondrial activity, had FDG uptake of 5. Except for this tumor, the FDG uptake was positively correlated with tumor malignancy. MRI/PET co-registration and image fusion increased the specificity of tumor location, as well as of tumor extent, and of heterogeneity (e.g., areas of necrosis).Conclusion: FDG PET with MRI/PET co-registration and image fusion could be an important adjunct in the diagnostic work up of pediatric CNS tumors, and could help define patients eligible for pre-operative chemotherapy.

Exposure margin in skeletal radiography and its effect on tube tilt compensation.

OBJECTIVE: To examine the rationale for and necessity of adjusting the film focal distance when X-ray angulation is employed during a radiographic study, and to determine the sensitivity of human interpreters to overall differences in film density and the correlation, if any, with digital analysis of radiographic films. DESIGN AND SETTING: The study was performed in the radiology department at Logan College of Chiropractic in St. Louis, Missouri. A standard X-ray phantom of the hand and wrist and several aluminum step wedges were exposed from 10% to 250% of baseline exposure intensity using equipment commonly found in a field doctor's practice. EVALUATION: The films were independently rated for overall image quality on a visual analog scale by five board-certified chiropractice radiologists. The films were also digitized, and selected regions analyzed on a computer. RESULTS: The panel of radiologists was able to consistently grade exposure intensity differences of approximately 10% relative change between films. The perceived density was directly proportional to the logarithm of the exposure intensity, as would be predicted from theoretical film response characteristics. The range of "acceptable" image quality was determined to lie between -40% and +60% of the baseline technique. CONCLUSIONS: This study validated the empirically derived tube tilt correction factor of 1 in of vertical adjustment per 5 degrees of tube angulation for tube tilts greater than or equal to 20 degrees. Underexposure impaired the interpretation of radiographs more than overexposure. Experienced human observers were able to reliably discriminate exposure differences on the order of 10% relative change when presented with complex grey-scale images, such as plain film radiographs.

Cranio-orbital teratoma.

A new-born baby presented with a large, rapidly growing tumour. The tumour involved the right orbit, the anterior half of the right intracranial space and extended through the skull of the temporal region. The proptotic eye ruptured due to exposure. The tumour was extirpated when the patient was 12 days old. A large recurrence was extirpated two months later. The tumour was firmly bound to the medial aspect of the superior orbital fissure which probably was the location of origin of the tumour. Based on the size of the intracranial-and the orbital part of the tumour, it was classified as a secondary orbital teratoma. The tumour was macroscopically composed of cystic and solid areas. Microscopically it was seen to be a benign teratoma with tissue from all three germinal layers.

[Langerhans-cell histiocytosis (histiocytosis X) in children]. / Langerhans-cellehistiocytosis (histiocytosis X) hos børn.

Langerhans cell histiocytosis (LCH), formerly histiocytosis X, is a rare disorder of unknown aetiology and pathogenesis which is characterized by clinical heterogeneity and an unpredictable course. LCH is considered to be a reactive, proliferative disease. The pathognomonic cell in the lesion has been shown to be identical or very similar to the Langerhans cell. Immunophenotyping studies have shown the cell to be CD1a (OKT-6), S-100 protein, HLA-DR, and CD4 positive; ultrastructurally, the presence of intracytoplasmic Birbeck granules is the hallmark of the entity. The lesions may be localized or generalized. Due to the lack of an accepted classification system for the stage of the disease and its rarity, very few comparative therapy studies have been carried out. Recently, the Histiocyte Society has suggested diagnostic criteria for LCH, and established a program of initial evaluation of the patient in order to start controlled treatment trials. Traditionally, chemotherapy has been preferred with a trend over time towards a more conservative approach. The rate of sequelae is high and connected to a chronic course of recurrent multiosseous disease. Case fatality is strongly associated to development of organ dysfunction seen in disseminated disease, which is especially seen at low age (< 2 years) of onset.

Impaired pancreatic polypeptide response to a meal in type 1 diabetic patients: vagal neuropathy or islet cell dysfunction?

The pancreatic polypeptide (PP) response to a mixed meal was investigated in seven insulin-dependent diabetics without measurable signs of diabetic autonomic neuropathy, and in seven healthy subjects. Since acute changes in metabolic regulation might influence the meal-induced PP response, the insulin-dependent diabetic patients were studied during normo- and hyperglycemic experimental conditions at blood glucose levels of 5 and 15 mmol/l, respectively. The PP response was identical on the two occasions, the response being significantly smaller than in the healthy subjects. Thus, PP response is independent of short-term changes in metabolic control. Since the response was attenuated in the insulin-dependent diabetic patients, who had no otherwise measurable signs of neuropathy, the PP response to a meal could be a sensitive indicator of dysfunction of the reflex arc controlling PP secretion in insulin-dependent diabetic patients. Alternatively, the reduction in PP secretion in these patients reflects dysfunction of the PP secreting cells of the pancreas. Iv injection of cholecystokinin-8 elicited a small but significant increase in PP concentrations, while iv secretin did not increase PP concentrations at all in healthy subjects. These stimuli are therefore less suitable in the assessment of vagal neuropathy.

Tumours classified as "malignant histiocytosis" in children are T-cell neoplasms.

During the last five years increasing evidence has accumulated that many tumours classified as 'histiocytic' in the past do not originate from macrophages, but from transformed (or anaplastic) large lymphoid cells. Most of these studies have focused upon adult neoplasms. Knowledge concerning the lineage of 'histiocytic' tumours in the paediatric age group is more limited. In this study we have examined the clinical, morphological and immunophenotypical features of six childhood malignancies originally diagnosed as being of histiocytic origin. Three patients showed an aggressive course with involvement of internal organs and very short survival times. Two patients were brought into remission: one is alive without active disease after seven years; the other died after seven years due to treatment-related cardiomyopathy. The remaining patient had a protracted course for two and a half years, but subsequently deteriorated and died three years after diagnosis. The histomorphological features in five cases were those of anaplastic large cell lymphomas. The remaining case consisted of pleomorphic (rather than anaplastic) large lymphoid cells. In all cases the immunophenotypical examination showed features characteristic of activated T lymphocytes. All cases were positive for Ki-1 (CD30), and three were positive for epithelial membrane antigen (EMA). Histiocyte-associated markers were positive in residual reactive macrophages, but nowhere could unequivocal positivity for macrophage-associated markers be seen in the neoplastic cells. It is concluded that most childhood malignancies in the past classified as 'histiocytic' are examples of anaplastic large cell (Ki-1) lymphomas of T-cell type and that true histiocytic malignancies are exceedingly rare in the paediatric age group.

Flow cytometric DNA analysis of lesions from 18 children with langerhans cell histiocytosis (histiocytosis x).

The DNA content in 26 formalin-fixed, paraffin-embedded histologic specimens from 18 children with Langerhans cell histiocytosis (LCH) was analyzed by flow cytometry. In two cases, the propidium iodide fluorescence histograms showed small (5 and 3% of the analyzed nuclei) but significant aneuploid subpopulations with DNA indices of approximately 1.5. This was confirmed by analysis of unfixed, frozen material in one patient. Both patients had disseminated disease without organ dysfunction and were treated with prednisone. Currently, they are without signs of disease activity after 1 and 10 years. DNA histograms were normal from a patient who died from disseminated disease and from two patients with disseminated disease who experienced several relapses and various chemotherapeutical regimens. The histograms were also normal in lesions from four patients with unifocal bone involvement. Our results show that DNA aneuploidy occurs in LCH lesions in the pediatric age group. Further investigation is necessary to reveal whether DNA aneuploidy is restricted to disseminated LCH or its presence has any value in predicting the course and outcome of the disease.