IntroductionPulmonary tuberculosis (TB) is an infectious disease with high incidence in low-income countries (LICs); it remains one of the infectious diseases with the highest mortality in the world, ...especially in LICs. It is crucial to recognise and diagnose TB as soon as possible, but microbiological tests on sputum are not always sensitive enough. New methods for an early diagnosis of TB are needed. In this study, we will investigate the role of two different tests to detect TB in Ethiopia (where the prevalence of TB is high): molecular search for TB in stool samples with Xpert assay and detection of pulmonary TB signs on chest X-rays with CAD4TB technology.Methods and analysisA prospective diagnostic test accuracy study during TB active contact investigation will be conducted. In the referral hospital in Southwest Shoa Zone, Oromia Region, Ethiopia, patients with pulmonary TB and a sputum sample positive for Mycobacterium tuberculosis and household contacts of at least 4 years of age will be enrolled, with a target sample size of 231 patients. Trained staff will label household contacts as ‘possible TB’ cases or not according to their symptoms; when TB is possible, a stool Xpert and computer-aided detection on chest X-ray will be performed, alongside standard diagnostic methods, assessing the diagnostic accuracy of CAD4TB compared with Xpert MTB/RIF during TB contact investigation and the accuracy of stool Xpert compared with sputum Xpert.Ethics and disseminationThis study has been approved by the Oromia Health Bureau Research Ethics Committee (ref no BFO/MBTFH/1-16/100023). All information obtained will be kept confidential. Selected investigators will have access to data, while international partners will sign a dedicated data protection agreement. Eligible participants will receive brief information about the study before being asked to participate and they will provide written informed consent. Results will be disseminated through peer-reviewed journals.Trial registration numberNCT05818059.
The optimal duration of oral anticoagulant treatment after a first episode of pulmonary embolism remains uncertain.
To evaluate the long-term clinical benefit of extending a 3-month course of oral ...anticoagulant therapy to 6 months (pulmonary embolism associated with temporary risk factors) or to 1 year (idiopathic pulmonary embolism) in patients with a first episode of pulmonary embolism.
Multicenter randomized study with independent, blinded assessment of the outcome events.
19 Italian hospitals.
326 patients who had had 3 months of oral anticoagulant therapy without experiencing recurrence or bleeding.
The primary study outcome was recurrence of symptomatic, objectively confirmed venous thromboembolism.
Among 165 patients assigned to extended anticoagulant therapy, 15 patients (9.1%) had a recurrence of venous thromboembolism (3.1% per patient-year; average follow-up, 34.9 months), as compared with 18 of 161 patients (11.2%) assigned to discontinue treatment (4.1% per patient-year; average follow-up, 32.7 months); the rate ratio was 0.81 (95% CI, 0.42 to 1.56). All but one of the recurrences occurred after anticoagulant treatment was discontinued. Nineteen recurrences (57.6%) were episodes of pulmonary embolism, two of which were fatal. Three major bleeding episodes were observed during extended anticoagulation (1.8%). Among patients with idiopathic venous thromboembolism, 11 of 90 patients assigned to extended anticoagulation and 11 of 91 patients assigned to discontinue treatment experienced a recurrence (relative risk, 0.99 CI, 0.45 to 2.16).
Patients with pulmonary embolism have a substantial risk for recurrence after discontinuation of oral anticoagulation, regardless of treatment duration. Physicians should try to identify patients who are at high risk for recurrent venous thromboembolism and are therefore potential candidates for indefinite oral anticoagulant therapy.
The aim of this study was to determine whether paroxysmal atrial fibrillation (PAF) and/or restoration to sinus rhythm with electric or pharmacologic cardioversion induce modifications to the ...coagulation system. Thirty-five patients with PAF undergoing either electric (n = 11) or pharmacologic (n = 24) cardioversion were studied. Fibrinopeptide A and D -dimer blood samples were taken immediately before and after cardioversion at different intervals. When compared with the control group (n = 70), the precardioversion fibrinopeptide A plasma values were significantly elevated (11.8 vs 2.5 ng/mL). Fibrinopeptide A plasma values were significantly reduced 5 minutes after cardioversion (11.8 vs 5.3 ng/mL) and remained stable throughout the follow-up sequential measurements. D -dimer plasma values were significantly increased (measured at 12 hours and at day 7) in patients who underwent electrical cardioversions only. A positive correlation (R2 = 0.76) was found between the energy delivered for cardioversion to sinus rhythm and D -dimer plasma values on day 7. In patients with PAF, levels of fibrinopeptide A, an indicator of coagulation activation, are elevated and soon reduced by the restoration of sinus rhythm. Electric, but not pharmacologic, cardioversion induces an early activation of the fibrinolytic system. (Am Heart J 2000;140:423-29.)
Bilirubin and phthalein dyes are taken up by the liver via a carrier-mediated mechanism operated at least in part by bilitranslocase (BTL). Because they also undergo renal transport, the presence and ...function of BTL was investigated in rat renal tubular plasma membrane vesicles. Transport of sulfobromophthalein (BSP) was enriched in basolateral domain of plasma membrane and followed the distribution pattern of Na(+)-K(+)-ATPase but not of gamma-glutamyltransferase. BSP uptake was inhibited by addition of monospecific antibodies raised against hepatic BTL. As in liver vesicles, BSP transport was electrogenic, being greatly accelerated by addition of valinomycin in presence of an inwardly directed K+ gradient. Apparent Km of BSP transport was 17 +/- 2 microM (n = 3 expts), one order of magnitude higher than that measured in liver; however, Vmax was similar to that described in liver vesicles (429 +/- 18 nmol BSP.mg protein-1.min-1, n = 3 expts). Competitive inhibition was observed with both unconjugated bilirubin (Ki, 2.9 +/- 0.2 microM) and rifamycin SV (Ki, 76 +/- 10 microM), known competitors for hepatic BTL-mediated transport of BSP. Immunoblotting studies with anti-BTL monospecific antibodies revealed presence of a single positive band only in basolateral-enriched membrane fraction; its apparent molecular mass was 37 kDa, virtually identical to that of hepatic protein. Immunohistochemistry confined presence of BTL to renal proximal tubules (RPT) We conclude that BTL is present in basolateral plasma membrane of RPT cells. Lower affinity of renal, compared with hepatic protein, for substrates might explain the marginal role of kidney in plasma clearance of bilirubin and cholephilic dyes.
Epomediol (EPO) is a synthetic terpenoid compound shown to be active in increasing bile flow and some enzymatic activities of liver plasma membranes in the rat. The possible effect of EPO treatment ...in the ethinyl-estradiol (EE) induced cholestasis in the rat was investigated by measuring the hepatic transport of sulfobromophthalein (BSP) (plasma clearance and biliary secretion) and bile flow. Liver plasma membrane fluidity was also determined by the steady state fluorescence polarization (P) of diphenylhexatriene (DPH). EE administration (5 mg/kg s.c. for 5 days) was followed by a significant, comparable reduction (P less than 0.001) in BSP plasma clearance and biliary excretion and in bile flow. Intraperitoneal administration of EPO (100 mg/kg) to EE-treated rats restored both parameters of BSP transport, as well as bile flow, to control values. Liver plasma membrane fluidity was markedly (P less than 0.01) decreased by EE administration with a concomitant reduction (P less than 0.01) in Na+/K+-ATPase activity. EPO administration significantly increased membrane fluidity to values higher either to cholestatic (P less than 0.05) or control (P less than 0.05) animals. On the contrary, EPO did not influence Na+/K+-ATPase activity in either EE-treated or control animals. These data indicate that EPO fully reverses the impairments of BSP transport and bile flow induced by EE, possibly by reversing the decrease in liver plasma membrane fluidity induced by the synthetic estrogen. On the contrary, the EE-mediated decrease in Na+/K+-ATPase activity was not reversed by EPO.
Bilitranslocase, the protein responsible for the anion translocation at the sinusoidal plasma membrane level in liver, was shown to be able to reconstitute the transport of sulfobromophthalein in ...liposomes in the past. The protein preparation used in those experiments consisted of two subunits of 35.5 and 37 kDa. The isolated 37 kDA protein, when inserted in erythrocyte membrane vesicles, confers to the particles the ability to carry out an electrogenic transport of sulfobromophthalein. The effect is specific and can be inhibited by monospecific polyclonal antibodies raised against the protein. In may be concluded that the 37 kDa protein band, present in previous preparations of bilitranslocase, is not only a necessary but also a sufficient component of the transport system for bilirubin and functional analogues.
Allergic contact dermatitis (ACD) is a common inflammatory skin disease caused by delayed hypersensitivity to chemical and biotic contact allergens. ACD significantly affects the patients' quality of ...life negatively impacting both occupational and non-occupational settings. Patch testing is the gold standard diagnostic in vivo test to precise the ACD etiology and to correctly perform prevention. According to the Italian Medicines Agency (AIFA) legislative decree no. 178 of 29
May 1991, allergens are defined as medicines and therefore they are subject to strict regulation. In 2017, AIFA (decree no. 2130/2017) started a procedure to regulate contact allergens on the Italian market and actually the contact allergens temporarily authorized are reported in AIFA decree no. 98/2022, valid until November 2023. The availability on the market of contact allergens to diagnose ACD and continuous updating on the basis of new epidemiological trends are mandatory, jointly with the continuous update of the baseline and integrative series for patch testing. For this reason, the scientific community represented in Italy by the Skin Allergies Study Group of SIDeMaST (Italian Society of Dermatology and Venereology) and SIDAPA (Italian Society of Allergological, Occupational and Environmental Dermatology) are constantly working, in close relationship with the European scientific communities with large expertise in this important sector of the modern Dermatology. Herein, we report the setting up of regulatory legislation by AIFA and the new Italian Adult Baseline Series for patch testing.
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