0110: Exercise stress echocardiography in secondary mitral regurgitation: impact of pulmonary hypertension

BackgroundSecondary mitral regurgitation (MR) is a serious and frequent complication of dilated cardiomyopathy and/or coronary artery disease. The impact of exerxise pulmonary hypertension (ExPHT) on outcome in patients with secondary MR is unknown.Method and resultsAll patients with secondary MR, sinus rhythms, narrow QRS (<120ms) and referred for exercise stress echocardiography with quantifiable exercise systolic pulmonary arterial pressure (SPAP), were included in this study (n=159, 65±11 years, 66% of male). Resting and ExPHT were defined as a systolic pulmonary arterial pressure (SPAP) >50mmHg and >60mmHg, respectively. ExPHT was more frequent than resting PHT (40% vs. 13%, p<0.0001). There was no significant difference between patients with or without ExPHT regarding demographic and clinical data, as well as medication. Using multiple linear regression, exercise SPAP was determined by resting SPAP (β=0.94±0.1, p<0.0001), exercise MR severity (β=0.58±0.1, p<0.0001), and resting e’-wave velocity (β=–1.3±0.4, p=0.004). During a mean follow-up of 35±11 months, 60 major adverse cardiovascular events occured. The incidence of combined cardiac event was significantly higher in patients with ExPHT as compared to those without ExPHT (2-year: 11±3 vs. 28±6%; 4-year: 20±5 vs. 40±7%, p<0.0001). Similarly, patients with ExPHT demonstrated significantly reduced survival (2-year: 88±4 vs. 99±1%; 4-year: 62±8% vs. 94±2%, p<0.0001). In multivariate Cox proportional Hazard model, after adjustment for age, sex, left ventricular volumes, both resting and exercise diastolic function and resting MR severity, ExPHT remains significantly associated with high risk of combined cardiac event (Hazard ratio=3.7, 95% of CI: 1.9-7.2, p<0.0001).ConclusionIn patients with secondary MR, ExPHT may be frequent and mainly determined by resting SPAP, LV diastolic burden markers and exercise MR severity. ExPHT is a powerful predictor of poor outcome and is associated with a 3.7-fold increase in risk of cardiac event. These results further highlight the usefulness of exercise stress echocardiography for the management and the risk stratification of these patients

Comparison of the solophenyl-red polarization method and the immunohistochemical analysis for collagen type III

In the present study, we have compared the staining pattern of the Solophenyl-Red 3 BL-method for the visualization of collagen type III with the immunohistochemical staining in serial sections from 7 skin wounds (wound age 3 days up to 4 weeks) to elucidate the specifity of the histochemical staining method. Large amounts of collagen type III were clearly detectable in the investigated wounds using the immunohistochemical technique. In the sections stained with Solophenyl-Red, however, only 3 out of 7 skin lesions showed a significant positive red staining at the wound margin or in the granulation tissue, while the adjacent normal connective tissue revealed a typical intensive staining. Using polarization microscopy no characteristic bright green fibrils, as reported for collagen type 111, could be seen in the wound areas without positive Solophenyl-Red staining. Since the localization of collagen type III detected by immunohistochemistry and the presumed distribution of this collagen type by the Solophenyl-Red method was not identical, the histochemical polarization method has to be regarded as non-specific for visualization of this collagen type

Context server on a mobile device

Da bi mobilne aplikacije lahko učinkovito nudile vse svoje storitev in jih prilagodile uporabniku, bi morale pri tem uporabiti ves kontekst uporabnika in njegove okolice. V obstoječih raziskavah to nalogo prevzema poseben kontekstni strežnik, ki skrbi za zbiranje podatkov ter posredovanje informacij aplikaciji. V primeru, da bi tak kontekstni strežnik deloval na mobilni napravi, bi bila postopoma odpravljena potreba po omenjenem sistemu. V sklopu naloge smo predlagani model kontekstnega strežnika uspešno implementirali in njegovo delovanje preizkusili s pomočjo kontekstno odvisne aplikacije, ki deluje na principu tekstovne klasifikacije uporabnikovih vnosov v spletnih iskalnikih in njegovi trenutni lokaciji. Aplikaciji omenjenih podatkov ni potrebno zajeti ročno, saj so ti ob pojavitvi novega podatka avtomatično posredovani preko kontekstnega strežnika.In order for mobile applications to efficiently offer all of their services and adjust them according to the end user, they would need to monitor all of his context and surroundings. In the existing researches this is done by a special context server which is responsible for data retrieval and transmission of information application. In the event, when the context server would work on a mobile device, the before mentioned system would gradually not be needed anymore. In the context of the thesis we have successfully implemented the proposed model of context server and tested it with a context application, which operates in the principle of text classification of user entries in the search engines and its current location. The application of this data does not need to be captured manually, since they are automatically transmitted to the server when the new data appears

Comprehensive clinical and molecular analysis of 12 families with type 1 recessive cutis laxa.

Autosomal recessive cutis laxa type I (ARCL type I) is characterized by generalized cutis laxa with pulmonary emphysema and/or vascular complications. Rarely, mutations can be identified in FBLN4 or FBLN5. Recently, LTBP4 mutations have been implicated in a similar phenotype. Studying FBLN4, FBLN5, and LTBP4 in 12 families with ARCL type I, we found bi-allelic FBLN5 mutations in two probands, whereas nine probands harbored biallelic mutations in LTBP4. FBLN5 and LTBP4 mutations cause a very similar phenotype associated with severe pulmonary emphysema, in the absence of vascular tortuosity or aneurysms. Gastrointestinal and genitourinary tract involvement seems to be more severe in patients with LTBP4 mutations. Functional studies showed that most premature termination mutations in LTBP4 result in severely reduced mRNA and protein levels. This correlated with increased transforming growth factor-beta (TGFβ) activity. However, one mutation, c.4127dupC, escaped nonsense-mediated decay. The corresponding mutant protein (p.Arg1377Alafs(*) 27) showed reduced colocalization with fibronectin, leading to an abnormal morphology of microfibrils in fibroblast cultures, while retaining normal TGFβ activity. We conclude that LTBP4 mutations cause disease through both loss of function and gain of function mechanisms

Therapeutic decision-making for patients with fluctuating mitral regurgitation

Mitral regurgitation (MR) is a common, progressive, and difficult-to-manage disease. MR is dynamic in nature, with physiological fluctuations occurring in response to various stimuli such as exercise and ischaemia, which can precipitate the development of symptoms and subsequent cardiac events. In both chronic primary and secondary MR, the dynamic behaviour of MR can be reliably examined during stress echocardiography. Dynamic fluctuation of MR can also have prognostic value; patients with a marked increase in regurgitant volume or who exhibit increased systolic pulmonary artery pressure during exercise have lower symptom-free survival than those who do not experience significant changes in MR and systolic pulmonary artery pressure during exercise. Identifying patients who have dynamic MR, and understanding the mechanisms underlying the condition, can potentially influence revascularization strategies (such as the surgical restoration of coronary blood flow) and interventional treatment (including cardiac resynchronization therapy and new approaches targeted to the mitral valve)

Localized primary renal aspergillosis in a diabetic patient following lithotripsy – a case report

<p>Abstract</p> <p>Background</p> <p>Primary renal aspergillosis is rare in diabetic patients. Diagnosis of localized primary renal <it>Aspergillus </it>infection in diabetic patients requires careful investigations due to its benign presentation and lack of associated systemic clinical features. There is also paucity of information on the role of conservative treatment of such localized infection with antifungal agents only. Here, we describe a case of localized renal aspergillosis in a type 2 diabetic patient with a brief review of literature.</p> <p>Case presentation</p> <p>We describe a case of unilateral renal aspergillosis following intracorporeal pneumatic lithotripsy (ICPL) in a type 2 diabetic man. The patient presented with mild pain in the left lumbar region and periodic expulsion of whitish soft masses per urethra, which yielded growth of <it>Aspergillus fumigatus</it>. He was treated initially with amphotericin B; however, it was stopped after 2 weeks, as he could not tolerate the drug. Subsequently, he was successfully treated with oral itraconazole.</p> <p>Conclusion</p> <p>Localized renal aspergillosis may be suspected in diabetic patients having history of urinary tract instrumentation, mild lumbar pain, passage of suspicious masses in urine and persistent pyuria. Examination of the suspicious substances expelled per urethra is essential for diagnosis as routine multiple urine analysis may yield negative results. Conservative treatment with oral itraconazole alone is effective in cases with incomplete obstruction.</p

Solvent effects in permeation assessed in vivo by skin surface biopsy

BACKGROUND: Transdermal drug delivery has become an important means of drug administration. It presents numerous advantages but it is still limited by the small number of drugs with a suitable profile. The use of solvents that affect the skin barrier function is one of the classic strategies of penetration enhancement. Some of these solvents have well characterised actions on the stratum corneum, but the majority are still selected using empirical criteria. The objective of this work was to conduct a systematic study on the ability to affect skin permeation of solvents commonly used in transdermal formulations. An innovative methodology in this area was employed, consisting of the combination of skin surface biopsy with colorimetry. METHODS: The study compared in vivo differences in the permeation of a hydrophilic (methylene blue) and a lipophilic (Sudan III) dye, after treatment of the skin with different vehicles. Consecutive skin surface biopsies of each site were taken and the cumulative amounts of the dyes in the stripped stratum corneum were measured by reflectance colourimetry. RESULTS: Results indicate that the amount of methylene blue present in the stratum corneum varied significantly with different skin pre-treatments. Some solvents provided a 1.5 fold penetration enhancement but others decreased by almost half the permeation of the dye. The permeation of Sudan III was less significantly affected by solvent pre-treatment. CONCLUSIONS: This study has only superficially explored the potential of the combination of skin surface biopsy and colourimetry, but the encouraging results obtained confirm that the methodology can be extended to the study of more complex formulations

Comparison of the musculoskeletal forelimb anatomy of the Saimaa (Pusa hispida saimensis) and Baltic ringed seals (Pusa hispida botnica)

Peer reviewe

Characterization of the Fungal Microbiota (Mycobiome) in Healthy and Dandruff-Afflicted Human Scalps

The human scalp harbors a vast community of microbial mutualists, the composition of which is difficult to elucidate as many of the microorganisms are not culturable using current culture techniques. Dandruff, a common scalp disorder, is known as a causative factor of a mild seborrheic dermatitis as well as pityriasis versicolor, seborrheic dermatitis, and atopic dermatitis. Lipophilic yeast Malassezia is widely accepted to play a role in dandruff, but relatively few comprehensive studies have been reported. In order to investigate fungal biota and genetic resources of dandruff, we amplified the 26S rRNA gene from samples of healthy scalps and dandruff-afflicted scalps. The sequences were analyzed by a high throughput method using a GS-FLX 454 pyrosequencer. Of the 74,811 total sequence reads, Basidiomycota (Filobasidium spp.) was the most common phylum associated with dandruff. In contrast, Ascomycota (Acremonium spp.) was common in the healthy scalps. Our results elucidate the distribution of fungal communities associated with dandruff and provide new avenues for the potential prevention and treatment of dandruff