Successful therapy with bevacizumab in a case of hereditary hemorrhagic telangiectasia.

Hereditary hemorrhagic telangiectasia (HHT), genetic disorder manifested by uncontrolled multisystem angiogenesis with epistaxis, gastrointestinal bleeding, iron-deficiency anaemia, and arteriovenous malformations (AVM) is often related with increased levels of vascular endothelial growth factor (VEGF). Bevacizumab, a VEGF inhibitor, reduces epistaxis, telangiectasias, and iron-deficiency anaemia. A case of a female patient with HHT and chronic gastrointestinal bleeding is presented. The patient required iron supplementation and multiple blood transfusions. Bevacizumab brought marked symptomatic improvement and allowed for transfusion-independence. It is intended to apply for approval of the indications for bevacizumab administration in HHT as the 'orphan drug'.

[Anakinra treatment in Schnitzler syndrome -  results of the first retrospective multicenter study in six patients from the Czech Republic]. / Lécba anakinrou u Schnitzler syndromu -  výsledky první retrospektivní multicentrické studie sesti pacientu z Ceské republiky.

BACKGROUND: Schnitzler syndrome is a very rare, acquired, autoinflammatory disease of mostly adult onset with characteristic combination of chronic recurrent urticaria and monoclonal immunoglobulin M or G gammopathy predisposing the patients to malignant lymphoproliferation. In this work, we analyzed the results of bio-logical therapy with anakinra on a national level aiming to supply data for effective pharmaco-economic estimates, lay the grounds of nationwide patient registry, raise awareness among professional public and optimize provided health care. PATIENTS AND METHODS: The retrospective study (10/ 2006- 9/ 2013) included six males with definite Schnitzler syndrome verified by the new Strasbourg criteria. All patients were pretreated with antihistamines, nonsteroidal antiinflammatory drugs and glucocorticoids. Four patients underwent two or more treatment lines including intravenous bisphosphonates, 2- chlorodeoxyadenosine (cladribine), interferonα, PUVA photochemotherapy, cyclosporine A, thalidomide, bortezomib, chlorambucil, cyclophosphamide, colchicine and methotrexate. Anakinra monotherapy was initiated in standard dosing (100 mg subcutaneously daily). RESULTS: Complete and partial remissions were achieved in five (83%) and one patients (17%), respectively. Complete remission was characterized by urticaria and pain regression (within hours), normalization of inflammatory markers (with--in days) and bone metabolism improvement assessed by the markers of osteoblastic osteoformation and osteoclastic osteoresorption in one case (within weeks). With normalized inflammatory markers (including interleukin6 and interleukin18), arthralgia and sporadic exacerbations of urticaria and fevers persist in the patient in partial remission with proven Q703K polymorphism in NLRP3 gene. The median treatment followup was 30.5 months (37.2 ± 31.2 (n = 6)). The dosing interval was prolonged in one case of complete remission to 48 hours. No serious adverse reactions occurred during anakinra application. CONCLUSION: In Schnitzler syndrome, anakinra represents an effective, verified and safe medication with potentionally longterm administration not compromising its original efficacy and subjective tolerance. Anakinra, blocking autonomous inflammatory reaction of the organism via interleukin1 pathway, is a generally accepted first line treatment that should be made available in standard dosing for all Schnitzler patients.

Accurate T(1) mapping for oxygen-enhanced MRI in the mouse lung using a segmented inversion-recovery ultrashort echo-time sequence.

PURPOSE: A segmented inversion-recovery module combined with the 2D ultrashort echo time radial technique is proposed that allows accurate pixel level T(1) mapping of mouse lung in vivo. METHODS: Numerical simulations were performed to estimate T(1) measurement accuracy and precision versus flip angle and signal-to-noise ratio. Phantom measurements were used for protocol validation, where the segmented inversion-recovery ultrashort echo-time sequence was compared with the reference technique (inversion-recovery rapid acquisition with refocused echoes). The in vivo experiments were carried out on free-breathing C57 mice (n = 10), breathing first air and then oxygen. RESULTS: The simulations demonstrated the high potential of the technique for accurate and precise T(1) assessment. Phantom experiments showed good agreement for T(1) values measured with segmented inversion-recovery ultrashort echo-time and the reference technique. The in vivo experiment demonstrated the utility of the technique in oxygen-enhanced assessment, where small T(1) changes were detected with high precision. CONCLUSION: Segmented inversion-recovery ultrashort echo-time provides accurate, high resolution T(1) mapping of the lung parenchyma.

[Pathogenesis, diagnostics and therapy of gout]. / Patogeneze, diagnostika a lécba dny.

Gout refers to heterogeneous group of metabolic diseases characterized by production of deposits of sodium urate crystals in tissues. Gout manifests as acute gouty arthritis with classic clinical picture, or as chronic gouty arthropathy with periarticular and subcutaneous deposits of sodium urate crystals, i.e. tophi. As for kidney, gout is manifested as acute or chronic gouty nephropathy and urolithiasis. These manifestations occur separately or they are combined. Hyperuricemia of primary gout is caused rather by impaired renal secretion than overproduction of uric acid. Secondary hyperuricemia is associated with many pathological conditions; it is also connected with the use of various medicaments. Pathogenesis of gouty arthritis is critically influenced by sodium urate crystals and inflammatory processes they induce. Hyperuricemia is part of metabolic syndrome X which is associated with unanswered question of the relationship between uric acid and atherosclerosis. Although gouty arthritis is the most frequent inflammatory disease of joints in men over 50 years of age, it is often diagnosed and treated inadequately. On that account, the indication of long-term hypouricemic therapy should be always based on the following criteria: secondary causes of hyperuricemia have to be excluded first; frequency of gout attacks and the risk of their recurrence should be taken into consideration; then it is necessary to search for renal manifestations of gout; and last but not least, we should check whether there are any associated diseases classified in metabolic syndrome X.

C1q complement component and -antibodies reflect SLE activity and kidney involvement.

The role of the complement system in the pathogenesis of systemic diseases is very ambivalent. In systemic lupus erythematosus (SLE), many abnormalities in the activation of the complement system have been reported. The most important antibodies formed against the complement system in SLE are the ones associated with the C1q component. The aim of this study was to assess separately the anti-C1q antibodies and C1q component in the serum from 65 patients with SLE, then in individuals with (n=33) and without (n=32) lupus nephritis and with active (n=36) and nonactive (n=29) form of the disease (European Consensus Lupus Activity Measurement, ECLAM>3, ECLAM

[Pre-hospital management of acute coronary syndromes with ST elevation in the Ile-de-France Region: the E-MUST registry]. / Prise en charge préhospitalière des syndromes coronaires aigus ST+ en île-de-France. Le registre E-MUST.

The E-MUST registry gathers patient data from the emergency ambulance service of the IIe-de-France for acute coronary syndromes with ST elevation seen within 24 hours from onset of symptoms. The parameters include the type of emergency phone call, details relative to the different phase of management, decisions of therapeutic strategy concerning pre-hospital thrombolysis or primary angioplasty and the different factors influencing these decisions. From January 2001 to June 2002, the mean delay from the onset of symptoms and the call-out of the emergency ambulance was 67.5 minutes for the 2584 patients studied. In this group, a pre-hospital decision for coronary revascularisation was taken in 84.3% of cases, pre-hospital thrombolyis started 33 minutes after arrival of the ambulance (32.7% of cases) and primary angioplasty carried out 81 minutes after that arrival (51.6% of cases). Decisions for revascularisation were less common in the elderly and those seen over 6 hours after the onset of symptoms. Pre-hospital management allows decisions concerning coronary reperfusion to be taken more often and earlier in patients with acute coronary syndromes.

Osteoprotegerin and bone density.

Aim of study was determine if a correlation exists between bone mass density and concentration of osteoprotegerin. We examined the group of 199 patients of mean age of 63 years. Of the group under study, 31 patients had normal bone density (T score > -1 and < 1) and 168 probands had osteopenia or osteoporosis (T < -1). Persons with normal BMD values had median values of OPG 60.8 ng/l, while patients with reduced bone density had median values of 73 ng/l OPG. Cut-off for reduction of bone density was 128 ng/l OPG. We demonstrated that OPG concentrations vary inversely with bone density values (correlation coefficient -0.31). These results suggest that determination of OPG could allow discrimination of individuals with normal bone density and those with reduced bone density.

Determination of leptin receptor in the serum and relations to laboratory and anthropological parameters in patients with atherosclerotic complications.

Leptin receptors are supposed to have signal effects and are located in most tissues in the organism but we failed to find literary data on concentration (measurement) of leptin receptors in the system circulation. We examined by the method of randomized selection the group of 20 patients with manifested atherosclerosis in whom BMI was calculated. Then we analyzed concentration of leptin receptor (double sandwich ELISA, standard recombinant human leptin), leptin, glucose, insulin, proinsulin, CRP and uric acid in the serum. The control group consisted of 103 probands without signs of atherosclerosis or other manifested diseases. The control group was subjected to determination of BMI, leptin and leptin receptor in the serum. Concentration of leptin receptor does not differ significantly between the patients with atherosclerosis and normal population. Probands with atherosclerosis showed a very close negative correlation between concentration of leptin receptor and leptinemia which is absent in normal population.

Femtosecond infrared spectroscopy of reaction centers from Rhodobacter sphaeroides between 1000 and 1800 cm-1.

Time-resolved pump-and-probe experiments of reaction centers of the purple bacterium Rhodobacter sphaeroides (R26) in the mid-IR region between 1000 and 1800 cm-1 are recorded with a time resolution of 300-400 fs. The difference spectra of the states P*, P+HA-, and P+QA- with respect to the ground state P predominantly reflect changes of the special pair. They show positive and negative bands due to changes of distinct vibrational modes superimposed on a broad background of enhanced absorption. A number of certain bands can be assigned to the special pair P, to the bacteriopheophytin HA, and to the quinone QA. The temporal evolution of the IR absorbance changes is well described by the time constants known from femtosecond spectroscopy of the electronic states. Differences occur only at very early times, which are indicative of fast vibrational relaxation with a time constant of a few hundred femtoseconds.

[Elastic recoil pressure in radiation induced injury of the lung]. / Cisnienie skoku sprezystego w popromiennym uszkodzeniu pluc.

The study was carried out on 34 females, age range 31-62 years, mean 46 years. It was conducted in the early phase, 3 months after introduction of the radiotherapy with X-rays. The results were compared with the initial values measured immediately after surgical removal of the tumour. The irradiation dose was 40 Gy to the sternum area and 35 Gy to the middle part of the axilla. Volume and capacity indices, bronchial resistance, small airway function parameters and mechanical properties of the lungs were studied. In the group of younger females (age < 46 years) a significant increase of the retraction index was noted (RC = P.TLC: TLC) following radiotherapy and a coexistent decrease of thoracic gas volume (TGV). In the whole group 13 patients reacted to radiotherapy with a left shift of the V/Pel curve, demonstrating an increase of elastic recoil. This group of patients also showed a marked decrease of TGV. These observations demonstrate that in a part of the patients treated with X radiotherapy a new equilibrium instated between elastic recoil pressure and lung capacity.

Highly sensitive multichannel spectrometer for subpicosecond spectroscopy in the midinfrared.

A spectrometer system is presented for time-resolved probing in the midinfrared between 5 and 11 microm with a temporal resolution of better than 400 fs. Multichannel detection with HgCdTe detector arrays consisting of ten elements in combination with a high repetition rate permits one to record weak absorbance changes with an accuracy of 0.1 mOD.