Search

Essentials Genetic predisposition to acquired thrombotic thrombocytopenic purpura (aTTP) is mainly unknown. Genetic risk factors for aTTP were studied by Immunochip analysis and replication study. Human leukocyte antigen (HLA) variant rs6903608 conferred a 2.5-fold higher risk of developing aTTP. rs6903608 and HLA-DQB1*05:03 may explain most of the HLA association signal in aTTP. Click to hear Dr Cataland's presentation on acquired thrombotic thrombocytopenic purpura. Summary: Background Acquired thrombotic thrombocytopenic purpura (TTP) is a rare, life-threatening thrombotic microangiopathy associated with the development of autoantibodies against the von Willebrand factor-cleaving protease ADAMTS-13. Similarly to what has been found for other autoimmune disorders, there is evidence of a genetic contribution, including the association of the human leukocyte antigen (HLA) class II complex with disease risk. Objective To identify novel genetic risk factors in acquired TTP. Patients/Methods We undertook a case–control genetic association study in 190 European-origin TTP patients and 1255 Italian healthy controls by using the Illumina Immunochip. Replication analysis in 88 Italian cases and 456 controls was performed with single-nucleotide polymorphism (SNP) TaqMan assays. Results and conclusion We identified one common variant (rs6903608) located within the HLA class II locus that was independently associated with acquired TTP at genome-wide significance and conferred a 2.6-fold increased risk of developing a TTP episode (95% confidence interval [CI] 2.02–3.27, P = 1.64 × 10−14). We also found five non-HLA variants mapping to chromosomes 2, 6, 8 and X that were suggestively associated with the disease: rs9490550, rs115265285, rs5927472, rs7823314, and rs1334768 (nominal P-values ranging from 1.59 × 10−5 to 7.60 × 10-5). Replication analysis confirmed the association of HLA variant rs6903608 with acquired TTP (pooled P = 3.95 × 10-19). Imputation of classic HLA genes followed by stepwise conditional analysis revealed that the combination of rs6903608 and HLA-DQB1*05:03 may explain most of the HLA association signal in acquired TTP. Our results refined the association of the HLA class II locus with acquired TTP, confirming its importance in the etiology of this autoimmune disease.

PRESENTATION FOREWORD 1. INTRODUCTION TO THE CONCEPT OF HAZARD AND RISK 1.1 FORECASTING, HAZARD, AND RISKS RELATED TO NATURAL PHENOMENA 1.2 FORECASTING NATURAL PHENOMENA FOR EMERGENCY MANAGEMENT 1.3 A KNOWLEDGE BASE AND THE DIFFUSION OF KNOWLEDGE AS SUPPORTS FOR THE ASSESSMENT OF HAZARD AND RISK 1.4 GLOSSARY 2. THE ASSESSMENT OF HAZARD AND RISK 2.1 METEOROLOGICAL PHENOMENA 2.2 THE LARGE ALPINE LANDSLIDES 2.3 ROCK FALLS 2.4 SHALLOW LANDSLIDES 2.5 TORRENTIAL PROCESSES 2.6 AVALANCHES 2.7 RIVER FLOODING 3. FORECASTING AND WARNING 3 FORECASTING AND ALERTS 3.1 METEOROLOGICAL FORECASTING 3.2 INDICATORS OF RAINFALL HAZARD 3.3 TOWARDS A DIFFERENT APPROACH TO FORECASTING METHODS 3.4 FORECASTING FLOODS 3.5 FORECASTING LANDSLIDES 4. THE UNCERTAINTY OF FORECASTING AND ASSESSMENT METHODS 4.1 THE UNCERTAINTY OF FORECASTING METHODS 4.2 THE CASE OF THE SCRIVIA RIVER ON SEPTEMBER 15-16, 2004 4.3 THE DEBRIS FLOW OF THE RIO FREJUS (BARDONECCHIA) - AUGUST 6, 2004 5 GENERAL CONCLUSIONS

International audience; In the case of large unstable mountain slopes, the spatial repartition of the saturated zones influence the pressure repartitions in the massif and the slope stability. This contribution proposes an evaluation of water origin and pressure transit time of groundwater flows from hydrochemical and isotopic measurements. The objective is to propose a conceptual model of the groundwater flows and a location of the saturated zones in the slope. The interpretation of time measurements of water pressure in the collapsed zone highlights (i) an evolution of flows with deformation that induces a damaging of the rock properties and (ii) the necessity to connect hydrogeological conditions and geological background in a dynamical system to analyse the pore pressure in the fractured collapsed zone

Measurement of serum triiodothyronine (T3), thyroxine (T4), free triiodothyronine (FT3), free thyroxine (FT4), thyroxine-binding-globulin (TGB), antithyroglobulin antibodies (anti-hTg), thyroid 131I uptake and scanning was performed on 12 patients during the early phase of subacute thyroiditis. Serum thyrotropin (TSH) was measured during baseline conditions and following administration of synthetic thyrotropin-releasing-hormone (TRH). The stimulation with exogenous TSH was performed on 7 subjects. 131I uptake was depressed in all patients including those with solitary nodules. Free and total hormone concentrations were elevated in the three cases with diffuse gland involvement, whereas an increase of T3 alone was present in 3 patients with unilobar involvement. In the latter group and in the 2 patients with a nodular form T4, FT3 and FT4 levels were within normal limits. Interruption of the pituitary-thyroid feed-back mechanism with absence of thyrotropin response to TRH occurred in 11 patients, independent of whether thyroid hormone concentrations were elevated or normal. In one patient only with unilateral involvement, TSH responsiveness to TRH was normal while 131I uptake was not raised by exogenous TSH, indicating diffuse cellular damage. The normal values of FT3 and FT4 found in patients with normal T3 and T4 levels seem to exclude the possibility that the free hormones are responsible for the interrupted feed-back which represents the main cause of suppressed iodine uptake. However, it is possible that the pituitary-thyroid axis is responding to transient or light increases of free and total T3 and T4 still within their 'normal range'.

The effects of left ventricular hypertrophy (LVH) on systolic function were studied by echocardiography in 61 hypertensive patients. LV mass index (LVMI) and relative wall thickness (h/r ratio) were used together as LVH indices, and three patterns of LV adaptation to the pressure overload were observed: 13 patients had normal LVMI and h/r ratio (no LVH); 32 patients had increased h/r ratio, with normal or increased LVMI (concentric LVH); 16 patients had increased LVMI and normal h/r ratio (eccentric LVH). Cuff arterial pressure was lower in patients without LVH than in those with LVH, but both LVH indices correlated weakly with systolic, diastolic, and mean blood pressure (r = 0.22 to 0.33). Eccentric LVH showed peculiar hemodynamics, characterized by high cardiac output (CO) and normal total peripheral resistance (TPR), whereas CO was normal and TPR moderately and severely increased in patients without LVH and with concentric LVH, respectively. In the group without LVH, peak systolic stress (PSS) and systolic blood pressure/end-systolic volume index (SBP/Ves) were increased, whereas end-diastolic diameter (EDD), end-systolic stress (ESS), and fractional shortening (FS) were normal; thus, the ejective performance was preserved by increased contractility. The group with concentric LVH had normal PSS, ESS, EDD, and FS and increased SBP/Ves, showing that systolic function was normal or supernormal in the presence of adequate LVH. The group with eccentric LVH had increased PSS, ESS, and EDD, whereas FS and SBP/Ves were both normal; thus, the ejective performance was preserved--in spite of an inadequate LVH and increased afterload--through the action of preload reserve.(ABSTRACT TRUNCATED AT 250 WORDS)

10 patients with clinical and histopathological evidence of Kaposi’s sarcoma were evaluated with 99Tcm-pertechnetate and 67Ga-citrate scintigraphs. Combined studies using these radionuclides are useful aids in investigating, detecting and following-up Kaposi’s sarcoma and any associated lymphoma or other malignancies.

Serum tissue polypeptide antigen (TPA) was measured by RIA in 151 female patients who had had mastectomies for breast cancer, in 30 patients with benign breast disease, and in 30 normal controls. The marker was elevated in 52 neoplastic patients (25 with metastases) and in six cases of benign breast disease. At the time of our observation 15 cancer patients were at stage I, 53 at stage II, 48 at stage III, and 35 at stage IV, the prevalence of high TPA values significantly correlated with staging gradually increasing from 0 to 71.4% from stage I to IV. In patients with breast cancer TPA was significantly higher in the subgroup with metastatic disease compared to patients with apparently inactive disease. Nineteen patients without (group A) and 35 with metastases (group B) were monitored with serial measurements of TPA for 8-24 months. Group B was receiving either hormone or chemotherapy. In 10 group A patients TPA was either higher or rose 1-7 months prior to the clinical detection of metastases. Twenty-two patients from Group B had disease progression: In 20 of them TPA rose further. The remaining 13 patients had an apparent disease regression, and in 11 instances TPA either fell or remained normal. Thus TPA can detect early recurrence of breast cancer before clinical and instrumental methods; moreover, it might prove important in evaluating tumor response to treatment and in follow-up of patients with metastatic disease. Finally, serial measurements of TPA could identify previous false-positive results, thus improving the specificity of the test.

PEPI (pre-ejection period index), QS2I (total electromechanical systolic index), LVETI (left ventricular ejection time index), and PEP/LVET ratio were measured in 35 thyrotoxic patients. None of the patients had clinical evidence of heart disease nor received drugs which might have affected the systolic time intervals. the hyperthyroid subjects showed significant shortening of PEPI and significant reduction of PEP/LVET, which returned within normal limits when the patients became euthyroid during treatment. No correlation could be found between T3, T4, FTI and PEPI or PEP/LVET. However, serial measurements indicated that the fall toward the normal range of PEPI parallelled that of T3; the latter is considered the most important index of thyroid function. Our study suggests that PEPI and PEP/LVET ratio may be of great usefulness in detecting hemodynamic alterations in subjects with uncomplicated hyperthyroidism. Moreover, these methods may facilitate the diagnosis in unusual types of hyperthyroidism occurring in the absence of clinical signs of toxicosis. In addition, PEPI and PEP/LVET appear to be useful in detecting T3 toxicosis. Finally, serial controls of PEPI could represent a useful index to monitor the response to therapy.