Coronary artery disease is common in asymptomatic patients with signs of myocardial ischemia

BACKGROUND: The incidence of coronary artery disease (CAD) in totally asymptomatic patients with myocardial ischemia during stress testing is unknown. METHODS: 54 patients with asymptomatic myocardial ischemia participated in the Swiss Interventional Study on Silent Ischemia type I (SWISSI I). Asymptomatic myocardial ischemia was verified by bicycle ergometry and stress imaging (echocardiography or scintigraphy). Findings from coronary angiographies in the course of the study constituted the main outcome. RESULTS: Of the 54 study participants, 29 patients (53.7%) underwent coronary angiography. CAD was found in 27 of 29 patients (93.1%). In those 27 patients with CAD, 9 patients (33.3%) suffered from single vessel disease, 9 patients (33.3%) from two vessel disease, and 9 patients (33.3%) from triple vessel disease. Two patients showed left main coronary artery stenosis. CONCLUSION: This study shows a high incidence of relevant CAD among totally asymptomatic patients with myocardial ischemia during stress testing. Previously healthy subjects with exercise-induced ST-segment depression at check-up examinations, even if asymptomatic, should have further diagnostic evaluation.

[Tritrichomonas fetus: a new intestinal parasite in Swiss cats]

Recent reports identified Tritrichomonas fetus, the causative agent of bovine trichomonosis, in cats with large-bowel diarrhea in the US. Between July 2007 and August 2008, a total of 105 Swiss cats were tested for T. fetus with the InPouchTM culture system and/or PCR, whereof 27 (26%) yielded positive results. All positive cats were pedigree cats, whereof 22 (81%) were less than 1 year of age (median 5 months). 25 (93%) of these cats lived in multi-cat households, and all but one were kept indoor. The clinical picture was dominated by large bowel diarrhea with increased frequency of defecation and fresh blood and mucus. Furthermore, inflamed anus and fecal incontinence was common. 52% of the T. fetus-positive cats were tested positive for Giardia before, but the treatment with fenbendazole or metronidazole only temporarily alleviated the clinical signs. The treatment with 30 mg/kg of ronidazole q12h p.o. was successful in all but 1 cat with only minor transient adverse effects in 3 cats. In conclusion, T. fetus has to be considered an important causative agent of large bowel diarrhea in cats in Switzerland, especially in young indoor pedigree cats.

Neospora caninum and bone marrow-derived dendritic cells: parasite survival, proliferation, and induction of cytokine expression

Dendritic cells (DCs) represent the first line defence of the innate immune system following infection with pathogens. We exploratively addressed invasion and survival ability of Neospora caninum, a parasite causing abortion in cattle, in mouse bone marrow DCs (BMDCs), and respective cytokine expression patterns. Immature BMDCs were exposed to viable (untreated) and nonviable parasites that had been inactivated by different means. Invasion and/or internalization, as well as intracellular survival and proliferation of tachyzoites were determined by NcGRA2-RT-PCR and transmission electron microscopy (TEM). Cytokine expression was evaluated by reverse transcription (RT)-PCR and cytokine ELISA. Transmission electron microscopy of DCs stimulated with untreated viable parasites revealed that N. caninum was able to invade and proliferate within BMDCs. This was confirmed by NcGRA2-RT-PCR. On the other hand, no viable parasite organisms were revealed by TEM when exposing BMDCs to inactivated parasites (nonviability demonstrated by NcGRA2-RT-PCR). Cytokine expression analysis (as assessed by both RT-PCR and ELISA) demonstrated that both viable and nonviable parasites stimulated mBMDCs to express IL-12p40, IL-10 and TNF-alpha, whereas IL-4 RNA expression was not detected. Thus, exposure of mBMDCs to both viable and nonviable parasites results in the expression of cytokines that are relevant for a mixed Th1/Th2 immune response.

Proliferative kidney disease in rainbow trout: time- and temperature-related renal pathology and parasite distribution

Proliferative kidney disease is a parasitic infection of salmonid fishes caused by Tetracapsuloides bryosalmonae. The main target organ of the parasite in the fish is the kidney. To investigate the influence of water temperature on the disease in fish, rainbow trout Oncorhynchus mykiss infected with T bryosalmonae were kept at 12 degrees C and 18 degrees C. The number of parasites, the type and degree of lesions in the kidney and the mortality rate was evaluated from infection until full development of disease. While mortality stayed low at 12 degrees C, it reached 77% at 18 degrees C. At 12 degrees C, pathological lesions were dominated by a multifocal proliferative and granulomatous interstitial nephritis. This was accompanied by low numbers of T. bryosalmonae, mainly located in the interstitial lesions. With progression of the disease, small numbers of parasites appeared in the excretory tubuli, and parasite DNA was detected in the urine. Parasite degeneration in the interstitium was observed at late stages of the disease. At 18 degrees C, pathological lesions in kidneys were more severe and more widely distributed, and accompanied by significantly higher parasite numbers. Distribution of parasites in the renal compartments, onset of parasite degeneration and time course of appearance of parasite DNA in urine were not clearly different from the 12 degrees C group. These findings indicate that higher mortality at 18 degrees C compared to 12 degrees C is associated with an enhanced severity of renal pathology and increased parasite numbers.

Occurrence, quantification, and genotyping of Mycoplasma conjunctivae in wild Caprinae with and without infectious keratoconjunctivitis

Mycoplasma conjunctivae, the causative agent of infectious keratoconjunctivitis (IKC), was recently detected in asymptomatic Alpine ibex (Capra ibex ibex). This suggested that an external source of infection may not be required for an IKC outbreak in wildlife but might be initiated by healthy carriers, which contradicted previous serologic investigations in chamois. Our aims were to 1) assess the prevalence of M. conjunctivae among asymptomatic ibex and Alpine chamois (Rupicapra rupicapra rupicapra) and its frequency in IKC-affected animals, 2) determine mycoplasma loads in different disease stages, and 3) characterize the M. conjunctivae strains involved. Eye swabs from 654 asymptomatic and 204 symptomatic animals were collected in diverse Swiss regions between 2008 and 2010, and tested by TaqMan real-time PCR. Data analysis was performed considering various patterns of IKC occurrence in the respective sampling regions. Strains from 24 animals were compared by cluster analysis. Prevalence of M. conjunctivae was 5.6% (95% confidence interval [CI]: 3.7-8.1%) in asymptomatic ibex and 5.8% (CI: 3.0-9.9%) in asymptomatic chamois, with significant differences between years and regions in both species. Detection frequency in symptomatic animals was significantly higher during IKC outbreaks than in nonepidemic situations (i.e., regular but low incidence or sporadic occurrence). Mycoplasma load was significantly lower in eyes from healthy carriers and animals with mild signs than from animals with moderate and severe signs. Although some strains were found in both asymptomatic and diseased animals of the same species, others apparently differed in their pathogenic potential depending on the infected species. Overall, we found a widespread occurrence of M. conjunctivae in wild Caprinae with and without IKC signs. Our results confirm the central role of M. conjunctivae in outbreaks but suggest that other infectious agents may be involved in IKC cases in nonepidemic situations. Additionally, presence and severity of signs are related to the quantity of M. conjunctivae in the eyes rather than to the strain. We propose that individual or environmental factors influence the clinical expression of the disease and that persistence of M. conjunctivae in populations of wild Caprinae cannot be excluded.

Is the development of infectious keratoconjunctivitis in Alpine ibex and Alpine chamois influenced by topographic features?

Infectious keratoconjunctivitis (IKC) caused by Mycoplasma conjunctivae is a widespread ocular affection of free-ranging Caprinae in the Alpine arc. Along with host and pathogen characteristics, it has been hypothesized that environmental factors such as UV light are involved in the onset and course of the disease. This study aimed at evaluating the role of topographic features as predisposing or aggravating factors for IKC in Alpine chamois (Rupicapra rupicapra rupicapra) and Alpine ibex (Capra ibex ibex). Geospatial analysis was performed to assess the effect of aspect (northness) and elevation on the severity of the disease as well as on the mycoplasmal load in the eyes of affected animals, using data from 723 ibex and chamois (583 healthy animals, 105 IKC-affected animals, and 35 asymptomatic carriers of M. conjunctivae), all sampled in the Swiss Alps between 2008 and 2010. An influence of northness was not found, except that ibex with moderate and severe signs of IKC seem to prefer more north-oriented slopes than individuals without corneal lesions, possibly hinting at a sunlight sensitivity consequent to the disease. In contrast, results suggest that elevation influences the disease course in both ibex and chamois, which could be due to altitude-associated environmental conditions such as UV radiation, cold, and dryness. The results of this study support the hypothesis that environmental factors may play a role in the pathogenesis of IKC.

Prevalence of cam and pincer-type deformities on hip MRI in an asymptomatic young Swiss female population: a cross-sectional study

OBJECTIVES Femoroacetabular impingement is proposed to cause early osteoarthritis (OA) in the non-dysplastic hip. We previously reported on the prevalence of femoral deformities in a young asymptomatic male population. The aim of this study was to determine the prevalence of both femoral and acetabular types of impingement in young females. METHODS We conducted a population-based cross-sectional study of asymptomatic young females. All participants completed a set of questionnaires and underwent clinical examination of the hip. A random sample was subsequently invited to obtain magnetic resonance images (MRI) of the hip. All MRIs were read for cam-type deformities, increased acetabular depths, labral lesions, and impingement pits. Prevalence estimates of cam-type deformities and increased acetabular depths were estimated, and relationships between deformities and signs of joint damage were examined using logistic regression models. RESULTS The study included 283 subjects, and 80 asymptomatic females with a mean age of 19.3 years attended MRI. Fifteen showed some evidence of cam-type deformities, but none were scored to be definite. The overall prevalence was therefore 0% [95% confidence interval (95% CI) 0-5%]. The prevalence of increased acetabular depth was 10% (95% CI 5-19). No association was found between increased acetabular depth and decreased internal rotation of the hip. Increased acetabular depth was not associated with signs of labral damage. CONCLUSIONS Definite cam-type deformities in women are rare compared to men, whereas the prevalence of increased acetabular depth is higher, suggesting that femoroacetabular impingement has different gender-related biomechanical mechanisms.

Assay of β-hematin formation by malaria parasite

Novel leads are urgently required for designing antimalarials due to the reduced efficacy of presently available drugs. The malaria parasite has a unique reaction of heme polymerization, which has attracted much attention in the recent past as a target for the design of antimalarial drugs. The process is hampered by non-availability of a proper assay method. Currently available methods are cumbersome and require advanced instrumentation or radioactive substrates. Here, we are describing an assay for hemozoin formation that is simple and reproducible. This assay has routinely been used by us for the identification of potential compounds with antimalarial activity.

Artemisinin, an endoperoxide antimalarial, disrupts the hemoglobin catabolism and heme detoxification systems in malarial parasite

Endoperoxide antimalarials based on the ancient Chinese drug Qinghaosu (artemisinin) are currently our major hope in the fight against drug-resistant malaria. Rational drug design based on artemisinin and its analogues is slow as the mechanism of action of these antimalarials is not clear. Here we report that these drugs, at least in part, exert their effect by interfering with the plasmodial hemoglobin catabolic pathway and inhibition of heme polymerization. In an in vitro experiment we observed inhibition of digestive vacuole proteolytic activity of malarial parasite by artemisinin. These observations were further confirmed by ex vivo experiments showing accumulation of hemoglobin in the parasites treated with artemisinin, suggesting inhibition of hemoglobin degradation. We found artemisinin to be a potent inhibitor of heme polymerization activity mediated by Plasmodium yoelii lysates as well as Plasmodium falciparum histidine-rich protein II. Interaction of artemisinin with the purified malarial hemozoin in vitro resulted in the concentration-dependent breakdown of the malaria pigment. Our results presented here may explain the selective and rapid toxicity of these drugs on mature, hemozoin-containing, stages of malarial parasite. Since artemisinin and its analogues appear to have similar molecular targets as chloroquine despite having different structures, they can potentially bypass the quinoline resistance machinery of the malarial parasite, which causes sublethal accumulation of these drugs in resistant strains.

Genetic of catecholaminergic polymorphic ventricular tachycardia: basic concepts.

Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a cardiac channelopathy characterized by altered intracellular calcium handling resulting in ventricular arrhythmias and high risk of cardiac sudden death in young cases with normal structural hearts. Patients present with exertional syncope and the trademark dysrhythmia is polymorphic and/or bidirectional ventricular tachycardia during exercise or adrenergic stimulation. Early detection of CPVT is crucial because opportune medical intervention prevents sudden cardiac death. Mutations in the ryanodine receptor RYR2 explain nearly 70% of the CPVT cases and cause the autosomic dominant form of the disease. Mutations in calsequestrin 2 causes a recessive form and explain less than 5% of all cases. Genetic screening in CPVT, besides providing early detection of asymptomatic carriers at risk, has provided important insights in the mechanism underlying the disease. Mutational analysis of RYR2 has been a challenge due to the large size of the gene, 105 exons encoded for 4,967 amino-acids. In this review we analyze general concepts of the disease, differential diagnosis and strategies for genetic screening.