[ADAPTHERA-Statewide cross-sectoral care network for patients with early rheumatoid arthritis shows sustained remission in standard care]. / ADAPTHERA ­ Landesweit transsektorales Versorgungsnetzwerk für Patienten mit früher rheumatoider Arthritis zeigt anhaltende Remissionen in der Regelversorgung.

BACKGROUND/OBJECTIVE: The majority of patients in Germany miss out on the necessity of early diagnosis and initiation of therapy for rheumatoid arthritis (RA) caused by considerable structural deficits in the health care system. The challenge is to reconcile the individual demand for the best possible therapy result with a sustainable expenditure of resources. METHODS: The cross-sectoral regional care network ADAPTHERA aims to improve early RA diagnosis and treatment in Rhineland-Palatinate. The retrospective triage analyses of suspected early onset RA patients was performed by tracing the selection process of all available enquiries (n = 1045). For analysis of the clinical course of the disease, a subset comprising 143 patients with a minimum observation time of 12 months (5 consecutive visits) was available. Clinical and laboratory parameters were collected quarter yearly, self-administered questionnaires were filled out and the treatment was adapted if necessary. RESULTS: A total of 454 patients were included. The mean waiting time was 23.9 (SD = 18) days. The mean observation period in the subcohort was 29.2 (SD = 12.7) months, with about 50% of the patients presenting within 3 months. Almost 75% of the patients were in remission after 2 years. A sustained remission could be described for 74.8% (6 months) and 53.5% (12 months), respectively. Especially patients with rapid remission induction benefited in terms of longer remissions (p = 0.03). A very early stage of the disease (VERA) was associated with a rarely necessary biologic therapy (p = 0.022). DISCUSSION: The approach of a supply network is not a panacea, but it might improve healthcare for patients with early onset RA. In order to minimize resource utilization, a pinpoint referral and accurate triage of potential cases are crucial.

[The regional network ADAPTHERA : Rheumatology care through coordinated cooperation: comprehensive, trans-sectoral, covering all health insurance. Initial results]. / Das landesweite Netzwerk ADAPTHERA : Erste Ergebnisse einer flächendeckenden, krankenkassenübergreifenden und transsektoralen rheumatologischen Versorgung.

The aim of the rheumatology network ADAPTHERA ("risk-adapted rheumatology therapy") is to achieve a comprehensive improvement in rheumatology care by coordinating treatment in a regional, trans-sectoral network. Accompanying biomedical research projects, training concepts, and the construction of a rheumatology register (gathering data and biomaterials) should furthermore ensure the stable and sustainable optimisation of care. In the pilot phase (2012-2015) the focus of the ADAPTHERA network, required as a "regional key project" within the framework of the Initiative on Health Economy of Rheinland-Palatinate (RL-P), Germany, was placed on the optimisation of the early diagnosis of rheumatoid arthritis, where it is well-known that there is a significant care deficit.Through the intensive, stable, and coordinated cooperation of all health care partners in the field of rheumatology (registered general practitioners and orthopaedic specialists, registered core rheumatologists as well as the Association of Rheumatology of RL-P) a unique regional, comprehensive offer with verifiable care optimisation has been established in RL-P. The network is supported by outstanding collaboration with the Association of Statutory Health Insurance Physicians and the self-help organisation Rheumatology League.The aims that were established at the start of the project will be achieved by the end of the pilot phase:- significant improvement in the early diagnosis of rheumatoid arthritis (an average of 23.7 days until diagnosis by rheumatologists)- access covering all health insurance (regardless of the particular scheme the patients belong to)- comprehensive (verifiable participation of general practitioners from all over RL-P)- data and biomaterials collection, established as a basis for biomarker research, and a rheumatology register for RL-P.

Echocardiographic parameters in healthy young adult Sphynx cats.

The objective of this retrospective study is to determine normal reference values for 2-Dimension (2D) and Motion-mode (M-mode) echocardiographic parameters in nonsedated healthy young adult Sphynx cats and to compare them to those of the domestic shorthair (DSH). 131 Sphynx cats underwent cardiac screening prior to breeding. The control group consisted of 30 healthy adult domestic cats. A complete cardiac ultrasound was performed on all cats using right parasternal long and short axis views. There were few echocardiographic parameters in the Sphynx that differed from those of the healthy DSH. Only the left atrial (LA) dimension in 2D and M-mode, the left atrial/aortic (LA/Ao) ratio and the internal dimension of the left ventricle in systole (LVIDs) measured with M-mode were different. In conclusion, although the heart of Sphynx cat can often have a particular 2-D echocardiographic appearance, the M-mode cardiac dimensions are similar to those of the DSH.

[Prevalence of heart murmurs, aortic and pulmonic stenosis in boxers presented for pre-breeding exams in Switzerland]. / Prävalenz von Herzgeräuschen, Aorten- und Pulmonalstenosen bei Zuchtuntersuchungen von Boxern in der Schweiz.

Boxer are predisposed to subaortic (SAS) and pulmonic stenosis (PS). To decrease the prevalence, pre-breeding cardiologic exams were performed in the last years. In our study the results of 309 pre-breeding exams of boxers presented between 1999 and 2008 were evaluated retrospectively. The overall prevalence of heart murmurs was 26.5 %. A SAS was diagnosed in 25 (8.1 %) and a PS in 10 (3.3 %) dogs. A combination of both defects was found in 7 (2.3 %) Boxers. Animals with a heart murmur of at least grade 3/6 had a significantly higher peak aortic flow velocity (VmaxAo) than animals without or only soft heart murmurs. Over the study period both the frequency of heart murmurs and diagnosis of SAS and PS decreased.

Phenotypes and echocardiographic characteristics of a European population of domestic shorthair cats with idiopathic hypertrophic cardiomyopathy.

111 Domestic Shorthair cats with idiopathic hypertrophic cardiomyopathy were reviewed retrospectively. Two-dimensional echocardiography was used to classify cases in 6 established phenotypes. Hypertrophy was diffuse in 61 % of cats and involved major portions of the ventricular septum and the left ventricular free wall (phenotype D). In the remaining cats, distribution of hypertrophy was more segmental and was identified on the papillary muscles exclusively (phenotype A, 6 %), on the anterior and basal portion of the ventricular septum (phenotype B, 12 %), on the entire septum (phenotype C, 14 %), or on the left ventricular free wall (phenotype E, 7 %). Echocardiographic characteristics and clinical findings were determined for each phenotype to study the correlation between distribution of hypertrophy and clinical implications. 31 cats demonstrated systolic anterior motion of the mitral valve, 75 % of them belonged to phenotype C of hypertrophy. Left ventricular-outflow turbulences were identified more frequently with patterns of hypertrophy involving the ventricular septum (65.5 %), while prevalence of mitral regurgitation was higher when hypertrophy included the papillary muscles (phenotypes A and E, 85 % and 87 %, respectively). Left atrial dilatation occurred more frequently when hypertrophy was diffuse or confined to the left ventricular free wall (61 % of cats with phenotype D or E) rather than to the ventricular septum (31 % of cats with phenotype B or C).

Telomere length analysis in monocytes and lymphocytes from patients with systemic lupus erythematosus using multi-color flow-FISH.

In order to analyse telomere length in subsets of human peripheral blood lymphocytes and monocytes, we modified a recently developed multicolor flow- fluorescent in situ hybridization (FISH) methodology that combines flow-FISH and antibody staining for cell surface antigens. We analysed telomere length of peripheral blood mononuclear cells in a group of 22 patients with systemic lupus erythematosus (SLE) and 20 age-matched healthy donors. We found that neither CD4+, CD8+, CD19+ cells nor CD14+ monocytes have significantly shorter telomeres compared with their healthy counterparts. On the basis of these findings, we then used monocyte telomere length as internal reference in order to control for intra-individual variability in telomere length. By using this approach, we could demonstrate significant telomere shortening in all three lymphocyte subsets (in all cases P < 0.05) compared with monocytes. However, these differences did not vary significantly between SLE patients and controls. In summary, telomere lengths in subpopulations of hematopoietic cells can be monitored in patients with SLE using multicolor flow-FISH. While confirming data by other groups on telomere length in lymphocyte subpopulations, our data argue against an increased proliferation rate of peripheral blood monocytes reflected by accelerated telomere shortening in patients with SLE.

Prevalence of heart disease in symptomatic cats: an overview from 1998 to 2005.

A total of 408 cats with various cardiovascular problems has been presented to two investigational clinics during the last 8 years. The number of yearly examinations has steadily increased during this period. Definitive cardiovascular disease was diagnosed in 287 cats, whereby hypertrophic cardiomyopathy (HCM) was the most common diagnosis with 67.6%. Congenital cardiovascular malformations were found in 11.8% of the cases. Ventricular septal defect (VSD) was the most frequent anomaly, in contrast to previously published studies. The ECG was found to be relatively non-specific and insensitive for the diagnosis of heart disease: Its usefulness lies in the recognition and diagnosis of cardiac arrhythmias. The radiographically recognized changes were also non-specific for certain heart diseases. Radiographs of the thorax are especially useful in the evaluation of cardiomegaly, and secondary signs of congestion.

Echocardiographic screening of purebred cats: an overview from 2002 to 2005.

During the last 3 years, a total of 144 cats underwent echocardiographic screening at two investigational clinics before being admitted for breeding. The number of cats presented for that purpose has constantly increased. 8.3% of cats were diagnosed as having hypertrophic cardiomyopathy and 6.9% were diagnosed as suspicious. Male cats were more affected than females (9.4% vs 7.7%). In 4.2 of all presented cats, a congenital cardiac malformation was recognised, most often tricuspid valve dysplasia.

Autologous stem cell transplantation of treatment-resistant systemic vasculitis--a single center experience and review of the literature.

AIMS: Autologous peripheral blood stem cell transplantation (autoPBSCT) is increasingly and successfully applied to patients with treatment-resistant autoimmune diseases, mainly multiple sclerosis and systemic sclerosis, but also juvenile idiopathic arthritis and systemic lupus erythematosus. We intended to analyze the effects of autoPBSCT in patients with treatment-resistant systemic vasculitis by analyzing the outcome of 4 patients from our own hospital, and comparing them to cases reported in the literature. METHODS: 4 patients with treatment-resistant vasculitis (Wegener granulomatosis, Churg Strauss syndrome, Takayasu arteritis and relapsing polychondritis) received an autologous PBSCT. Stem cell mobilization was performed with cyclophosphamide (CY) and G-CSF, stem cells were purged by positively selecting CD34+ stem cells over a CliniMacs device, and the conditioning was performed with high dose CY and anti-thymocyte globulin (ATG). RESULTS: AutoPBSCT was well tolerated in all 4 patients. The patient with WG achieved complete remission although cANCA persisted, the other patients are in good partial remissions and respond to maintenance treatments which had been ineffective before PBSCT (CSA, azathioprin). Glucocorticosteroids (GC) could be reduced to a maximum of 10 mg in all patients. Shortly after the procedure, reactivation of viruses from the herpes family occurred in 3 of the patients and had to be treated. In the data base, 25 patients transplanted for severe systemic vasculitis are registered, in the literature, 6 additional vasculitis patients remitting after autoPBSCT are reported. CONCLUSIONS: Autologous PBSCT is feasible and effective in severe, treatment-resistant forms of systemic vasculitis. Data are sparse, further prospective studies are needed. These should also aim at evaluating more optimal regimens for conditioning and purging during PBSCT, as in most of the vasculitis patients reported until now, mostly good partial remissions, but less complete remissions were achieved.

[Large vessel vasculitis as cause of fever of unknown origin (FUO) or systemic inflammation. Diagnosis using 18-F-fluor-2-deoxy-D-glucose positron emission tomography ((18)F-FDG-PET)]. / Vaskulitiden der grossen Gefässe als Ursache eines Fiebers unklarer Genese (FUO) oder unklarer Entzündungskonstellationen Diagnostik mittels 18-F-Fluor-2-deoxy-D-Glukose Positronen-Emissionstomographie (18F-FDG-PET).

BACKGROUND: Diagnosis and treatment of FUO or systemic inflammation with unknown reason are still a great challenge for the treating physician. We used (18)F-FDG-PET for further diagnostic work in patients in whom a diagnosis could not be established despite intensive diagnostic efforts. METHODS/RESULTS: We studied nine patients with (18)F-FDG-PET. Two female patients with known Takayasu's arteritis but undefined disease activity, and seven patients with the clinical suspicion of an underlying large vessel vasculitis. The diagnosis of active vasculitis could be confirmed by the PET-results in eight patients. Active vasculitis could be nearly ruled out in one. The diagnoses could be confirmed by follow-up visits. CONCLUSION: (18)F-FDG-PET is a useful diagnostic tool in patients with unclear systemic inflammation and FUO. Especially when large vessel vasculitis is suspected, further diagnostic work by PET seems to be of benefit. Furthermore, it offers the opportunity to evaluate disease activity and to check which vessels are involved.

Plexogenic pulmonary arteriopathy in a Pembroke Welsh corgi.

A 21-month-old, male Pembroke Welsh corgi was referred for investigation of respiratory distress and progressive lethargy. Cardiac evaluation revealed a grade 4 pansystolic murmur over the left and right heart base. A heart murmur, dyspnoea, cyanosis, prolonged capillary refill time and ascites led to the tentative diagnosis of a cardiac malformation with a right-to-left shunt, with likely additional pulmonary disease. Pulmonary hypertension became evident during echocardiography, when the estimated systolic pulmonary artery pressure was over 70 mmHg. Angiography revealed abnormal pulmonary vascular markings consistent with pulmonary hypertension and a small right-to-left shunting patent ductus arteriosus (PDA). The diagnosis of PDA was confirmed at postmortem examination. Histology of the pulmonary arteries showed lesions of plexogenic pulmonary arteriopathy. The question of whether both conditions were separate or part of the same clinical syndrome is discussed in this report.

Efficacy and tolerability of intravenous tropisetron in the treatment of fibromyalgia.

OBJECTIVE: To determine the efficacy of a serotonin receptor (5-HT(3)) antagonist in the treatment of fibromyalgia (FM) in a prospective, randomized, double-blind, placebo-controlled, multicentre trial. METHODS: Twenty-one female patients (age 21-63 years) with FM according to the American College of Rheumatology classification criteria for FM were assigned randomly to either a placebo group or to receive a daily intravenous bolus injection of 5 mg tropisetron for 5 days. RESULTS: In patients receiving tropisetron, the visual analogue scale (VAS) score for pain decreased by 28.9 compared with a decrease of 6.8 in the placebo group [probability (p)=0.063; effect size: 0.794]. Similar results were obtained using a body diagram pain score as a secondary efficacy parameter: mean pain reduction was 27.2 in the tropisetron group, versus 2.8 in the placebo group (p=0.038; effect size: 0.902). CONCLUSION: 5-HT(3) receptor antagonists provide significant pain relief for a group of FM patients.

Takayasu's arteritis secondary to myelodysplasia as a predictor of poor outcome: two case reports.

We present two patients with myelodysplasia in association with Takayasu's arteritis (TA). In both patients intensive immunosuppressive treatment could not control the vascular inflammation. Subsequently both patients developed myelodysplasia, rapidly progressing to secondary acute myelogenous leukaemia. One patient had a peripheral blood stem cell transplant from a compatible sibling donor, but died of refractory leukaemia 5 months later. The other patient died of fungal sepsis. These are the first two patients reported to have TA associated with myelodysplasia/secondary leukaemia.

Arrhythmogenic Right Ventricular Cardiomyopathy (ARVC) in a Boxer.

ABSTRAST: A 3-year-old boxer bitch was evaluated for syncope and exercise intolerance. Physical examination revealed tachypnea, tachyarrhythmia and pulse deficit. Echocardiography demonstrated right atrial dilatation, thinning and hypokinesis of the right ventricular wall and normal contractility of the left ventricle. Three months after the first onset of clinical symptoms, the dog developed signs of congestive right heart failure despite treatment, and euthanasia was performed because of refractory ascites. The diagnosis of arrhythmogenic right ventricular cardiomyopathy (ARVC) was reached based of the clinical evolution of rapid progressive right ventricular heart failure and the particular form of isolated right atrial and right ventricular alterations without any echographic abnormalities of the pulmonic and tricuspid valves. Definitive confirmation was made by necropsy. In contrast to boxer type dilated cardiomyopathy (BDCM), dilatation occurred primary on the right atrium and ventricle and the right ventricular wall was thinner in subtricuspidal, apical and infundibular locations, similar to the "triangle of dysplasia" of human patient with ARVC. Histological lesions showed myocyte atrophy and replacement with adipose and fibrous tissue extended from the epicardium toward the endocardium in the right ventricle (RV) and right atrium (RA). In contrast to BDCM, where the lesions are multifocal, they take here the form of waves, with a large base against the epicardium and a spike towards the endocardium, known as lesions with a wave-front pattern, which are typical of ARVC. This report with supraventricular arrhythmias and echographic location in the RA and RV supports the hypothesis that ARVC is a progressive disease which may also have left ventricular free wall involvement if the patient lives long enough.

Atrioventricular Canal Defect (incomplete form of endocardial cushion defect) and Ostium Secundum Type Interatrial Septal defect in a dog.

A four-year-old German shepherd mixed-breed dog was presented with an asymptomatic heart murmur. An atrial septal defect associated with tricuspid and mitral dysplasia (atrioventricular canal defect) was diagnosed. The pulmonary to systemic blood flow ratio was in the range of 2.5:1 (Qp:Qs ratio). Echocardiography and flow pattern across the valves as well as the direction of the shunt allows a better description of the physiopathological consequences of this rare congenital heart disease. Additionally, an Ostium Secundum Type interatrial septum defect was found at necropsy.

[Tricuspid valve dysplasia in fifteen dogs]. / Trikuspidaldysplasie bei fünfzehn Hunden.

Clinical findings in fifteen dogs with tricuspid valve dysplasia are described. Thirteen dogs had loud systolic heart murmurs. Eleven of them hat a palpable precordial thrill over the same location. In 14 dogs, right heart enlargement was suspected on thoracic radiographs and electrocardiography. Right atrial dilation was seen echocardiographically in all dogs. Fourteen dogs had additional right ventricular dilatation, some with hypertrophy as well. Doppler echocardiography revealed tricuspid valve regurgitation. Seven dogs remained free of clinical symptoms to date. If symptoms of decompensation develop with tricuspid dysplasia, diuretics, ACE inhibitors and eventually positive inotrope drugs are indicated. Antiarrhythmic drugs may become necessary in cases of supraventricular tachyarrhythmias.

Guidelines for the echocardiographic studies of suspected subaortic and pulmonic stenosis.

INTRODUCTION: Subaortic stenosis (SAS) and pulmonic stenosis (PS) are, with PDA, the most common canine congenital heart defects in almost all epidemiological studies or frequency tabulations of the various European countries and the United States. As dog breeder's associations of highly affected breeds such as Boxers and Newfoundlands are attempting to screen breeding stock clinically as well as echocardiographically and are trying to eliminate these defects through the exclusion of affected individuals from breeding programs, it behooves the group of veterinary cardiologists and echocardiographers engaged in these screening programs to use a standardized approach to the echocardiographic examination procedure. This should warrant obtaining comparable studies with little interobserver variability due to the data acquisition procedure. Such uniformly acquired studies would also be easier to review by a board of experts, should this become necessary in the future. The recommendations stated below are valid for the examinations of dogs as well as cats. The present article represents the combined professional opinions of Drs. Bussadori, Le Bobinnec, Amberger and Lombard. REQUIRED EQUIPMENT: Any commercial echocardiographic unit with 2.5 to 7.5 MHz sector transducers is suitable for imaging. Transducers with small "footprints" (contact surface) are easier to couple to the chest wall in small patients with narrow intercostal spaces. A so-called cardiac package is also required and provides the software for standardized M-mode, 2D- and Doppler measurements. An ECG-tracing must be included on all recordings. It is mandatory to record clear and artifact-free imaging sequences of adequate length of each required view and of each Doppler measurement on a videotape or digital archive system, with proper patient identification, for later retrieval and documentation. For the Doppler measurements, pulsed wave (PW) and continuous wave (CW) capabilities are required. Color flow Doppler (CFD) is a useful option and allows the rapid documentation and localization of turbulent blood flow, thereby facilitating the placement of the PWD- and CWD- cursors for spectral display and peak velocity measurements. It is however a costly option and not essential for the documentation of neither SAS or PS. SEDATION: The authors highly recommend against tranquilization of the patients, as blood flow velocities are affected by most sedatives. Even if the blood pressure measured under sedation is in the normal range, this does not warrant truly non-influenced blood flow velocity values.

Effects of benazepril in the treatment of feline hypertrophic cardiomyopathy Results of a prospective, open-label, multicenter clinical trial.

OBJECTIVES: To evaluate the efficacy of benazepril on clinical signs and echocardiographic parameters in cats with primary hypertrophic cardiomyopathy (HCM). BACKGROUND: ACE-inhibitors have positive effects in man with HCM, and contribute to a reduction of myocardial hypertrophy. Addition of an ACE-inhibitor to the standard treatment of HCM in cats may have beneficial effects. METHODS: A total of 32 cats which were either asymptomatic or in stabilised congestive heart failure (ISACHC* class Ib, II or IIIa) were included in a one-year, prospective, open-label, clinical trial in 5 centres in Switzerland. 28 of these cats were allocated to one of two treatment groups: 1) standard therapy (ST) alone (n=9), consisting of a long-acting formulation of diltiazem (6-9 mg/kg sid) and optional acetylsalicylic acid (50 mg twice weekly, or 2) the same ST plus benazepril (0.33 - 0.75 mg/kg sid, n=19). RESULTS: Cats treated with benazepril showed a statistically significant decrease (mean +/- SEM, 0.11 +/- 0.03 mm/month, p = 0.002) in the left ventricular wall thickness (LVWD) from baseline, while no change (increase of 0.02 +/- 0.04 mm/month, p=0.66) was observed in cats on ST alone. Differences in LVWD between the two groups reached statistical significance (p=0.02). Benazepril treated cats showed more improvement in clinical signs (20-53%) than cats receiving ST alone (0-20%) but differences between the groups were not statistically significant (p>0.1). No change in septal thickness (IVSD) or left atrial to aortic root ratio (LA/Ao) was observed in either group. CONCLUSIONS: Benazepril had some beneficial effects on clinical signs and cardiac remodelling in cats with HCM and was well tolerated. These results, however, need to be confirmed in additional controlled studies. * ISACHC classification is described in the previous paper (Bench-study).

[A case of interatrial communication in a dog]. / Un case de communication interatriale (CIA) chez le chien.

A 4 month old female German Shepherd was presented for the work-up of a heart murmur that has been detected by the referring veterinarian. Clinical examination and thoracic radiography showed an enlargement of the right ventricle, and an increased pulmonary perfusion. Echocardiography showed an interatrial communication (atrial septum defect), and colour Doppler allowed the confirmation of a left to right shunt. The article discusses the diagnostic possibilities of this rare congenital cardiac malformation in the dog.