A myeloma paraprotein with specificity for platelet glycoprotein IIIa in a patient with a fatal bleeding

Abstract Impaired platelet aggregation, normal shape change, and agglutination and normal ATP secretion and thromboxane synthesis in response to high concentrations of thrombin or arachidonic acid were found in a patient with multiple myeloma and hemorrhagic tendency. The purified IgG1 kappa or its F(ab'}2 fragments induced similar changes when added in vitro to plateletrich plasma from normal subjects. In addition, the paraprotein inhibited adhesion to glass microbeads, fibrin clot retraction, and binding of radiolabeled fibrinogen or von Willebrand factor to platelets exposed to thrombin or arachidonic acid without affecting intraplatelet levels of cAMP. The radiolabeled paraprotein bound to an average of 35,000 sites on normal platelets but it bound to <2,000 sites on the platelets from a patient with Glanzmann's thrombasthenia. Immunoprecipitation studies showed that the platelet antigen identified by the paraprotein was the glycoprotein IlIa. Furthermore, binding of radiolabeled prostaglandin El (PGEI) to resting platelets as well as binding of von Willebrand factor to platelets stimulated with ristocetin were entirely normal in the presence of patient's inhibitor. These studies indicate that bleeding occurring in dysproteinemia may be the result of a specific interaction of monoclonal paraproteins with platelets. In addition, our data support the concept that the interaction of fibrinogen and/or von Willebrand factor with the platelet glycoprotein Ilb-IIla complex is essential for effective hemostasis

Morphology of the toe flexor muscles in older people with toe deformities

Objective: Despite suggestions that atrophied, or weak toe flexor muscles are associated with the formation of toe deformities, there has been little evidence to support this theory. This study aimed to determine whether the size of the toe flexor muscles differed in older people with and without toe deformities. Methods: Forty-four older adults (>60 years) were recruited for the study. Each participant had their feet assessed for the presence of hallux valgus or lesser toe deformities. Intrinsic and extrinsic toe flexor muscles were imaged with an ultrasound system using a standardised protocol. Assessor blinded muscle thickness and cross-sectional area was measured using Image J software. Results: Participants with lesser toe deformities (n=20) were found to have significantly smaller quadratus plantae (p=0.003), flexor digitorum brevis (p=0.013), abductor halluces (p=0.004) and flexor halluces brevis (p=0.005) muscles than the participants without any toe deformities (n=19). Female participants with hallux valgus (n=10) were found to have significantly smaller abductor hallucis (p=0.048) and flexor halluces brevis (p=0.013) muscles than the female participants without any toe deformities (n=10; p<0.05). Conclusion: This is the first study to use ultrasound to investigate the size of the toe flexor muscles in older people with hallux valgus and lesser toe deformities compared to otherwise healthy older adults. The size of the abductor hallucis and flexor hallucis brevis muscles were decreased in participants with hallux valgus whereas the quadratus plantae, flexor digitorum brevis, abductor hallucis and flexor halluces brevis muscles were smaller in those participants with lesser toe deformities

Influence of Antisynthetase Antibodies Specificities on Antisynthetase Syndrome Clinical Spectrum TimeCourse

Introduction: Increased cardiovascular (CV) morbidity and mortality is observed in inflammatory joint diseases (IJDs) such as rheumatoid arthritis, ankylosing spondylitis, and psoriatic arthritis. However, the management of CV disease in these conditions is far from being well established.Areas covered: This review summarizes the main epidemiologic, pathophysiological, and clinical risk factors of CV disease associated with IJDs. Less common aspects on early diagnosis and risk stratification of the CV disease in these conditions are also discussed. In Europe, the most commonly used risk algorithm in patients with IJDs is the modified SCORE index based on the revised recommendations proposed by the EULAR task force in 2017.Expert opinion: Early identification of IJD patients at high risk of CV disease is essential. It should include the use of complementary noninvasive imaging techniques. A multidisciplinary approach aimed to improve heart-healthy habits, including strict control of classic CV risk factors is crucial. Adequate management of the underlying IJD is also of main importance since the reduction of disease activity decreases the risk of CV events. Non-steroidal anti-inflammatory drugs may have a lesser harmful effect in IJD than in the general population, due to their anti-inflammatory effects along with other potential beneficial effects.This research was partially funded by FOREUM—Foundation for Research in Rheumatolog

Sonic hedgehog pathway for the treatment of inflammatory diseases: implications and opportunities for future research

The Sonic hedgehog (Shh) signaling pathway is an essential pathway in the human body that plays an important role in embryogenesis and tissue homeostasis. Aberrant activation of this pathway has been linked to the development of different diseases, ranging from cancer to immune dysregulation and infections.Uncontrolled activation of the pathway through sporadic mutations or other mechanisms is associated with cancer development and progression in various malignancies, such as basal cell carcinoma, medulloblastoma, pancreatic cancer, breast cancer and small-cell lung carcinoma. Targeted inhibition of the pathway components has therefore emerged as an attractive and validated therapeutic strategy for the treatment of a wide range of cancers. Currently, two main components of the pathway, the smoothened receptor and the glioma-associated oncogene homolog transcriptional factors, have been investigated for the development of targeted drugs, leading to the marketing authorization of three smoothened receptor inhibitors for the treatment of basal cell carcinoma and acute myeloid leukemia.The Shh pathway also seems to be involved in regulating the immune response, possibly playing a role in immune system evasions by tumors, development of autoimmune diseases, such as rheumatoid arthritis and Crohn’s disease, airway inflammation, and diseases related to aberrant activation of T-helper 2 cellular response, such as allergy, atopic dermatitis, and asthma.Finally, the Shh pathway is involved in pathogen-mediated infection, including influenza-A and, more recently, SARS-CoV-2 viruses. Therefore, agents that inhibit the Shh signaling pathway might be used to treat pathogenic infections, shifting the therapeutic approach from strain-specific treatments to host-based strategies that target highly conserved host targets

Ossido di zinco: nuovo preparato specifico per cute intollerante

It is well known that irritant contact dermatitis (ICD) may precede or promote allergic contact dermatitis (ACD) as damage to the cutaneous barrier allows the penetration of irritant and allergic substances through the outer layers of skin. Therefore, the most important step in the treatment of eczematous diseases, is to restore the physiological skin barrier function and zinc oxide paste has always been one of the best treatments. The present study was undertaken to assess the efficacy and tolerability of a new water in oil formulation which contains 8% zinc oxide and a very low percentage of additives and nickel, and which has soothing and protective properties. 27 patients (21 females and 6 males), aged between 9 and 75 years (average 37) with different types of dermatitis were included in the study. All patients gave their informed consent and they were asked to apply the topical preparation twice a day for a two-week trial period. At the start (T0) and at the end of the treatment (T1), patients were assessed clinically on a 0-3 arbitrary unit (AU) score scale for objective features (erythema, dryness and desquamation) and on a 0-10 (AU) score scale for subjective features (itching and burning). Moreover, an instrumental estimate of cutaneous hydration (conductivity) was made using the Corneometer CM 800 (Courage & Khazaka). In order to test the tolerability, the product was patch tested as is on the backs of 33 healthy volunteers. All the patients completed the study and the formulation was always tolerated when applied to both affected and normal skin. Our results demonstrated a 64% improvement for erythema, dryness and desquamaton (TO: 3.33 AU; T1: 1.19 AU), 76% for itching and burning (T0: 8.07 AU; T1: 1.96 AU) and 20% for skin hydration (TO: 81.9±21.6 AU; T: 100±19.9 AU). No positive patch test reactions or side effects were observed. The preparation has a very low percentage of preservatives and nickel and is fragrance free. It was tolerated by all and has been found to be effective in decreasing the subjective and objective symptoms of multiple dermatitis related to sensitive skin

Verruche e tatuaggi

I tatuaggi negli ultimi anni sono diventati una pratica sempre più diffusa, specialmente dopo lo sviluppo della rimozione dei tatuaggi con il laser. Di conseguenza le reazioni cutanee che si verificano in risposta ai tatuaggi sono sempre più frequenti. In letteratura sono stati distinti tre grandi gruppi di reazioni cutanee osservate in seguito a tatuaggi: allergiche/granulomatose/lichenoidi, da inoculazione/infezione e da lesioni insorte in sede. Il semplice traumatismo meccanico del tatuaggio può inoltre scatenare la manifestazione clinica di malattie cutanee concomitanti (fenomeno di Köbner). Riportiamo il caso di un paziente di sesso maschile di 27 anni giunto alla nostra osservazione per la comparsa di verruche volgari comuni lungo tutto il margine del tatuaggio

Prolonged Activated Partial Thromboplastin Time: Difficulties in Discriminating Coexistent Factor VIII inhibitor and Lupus Anticoagulant

To review the diagnostic difficulties of a prolonged activated partial thromboplastin time (aPTT) when 2 inhibitors with opposite clinical presentations coexist, we searched MEDLINE from January 1970 to November 2013 using acquired, factor VIII (FVIII), factor IX, hemophilia A and B, inhibitor, lupus anticoagulant (LA), antiphospholipid, anticardiolipin, anti-b2-glycoprotein I, antibodies, syndrome, bleeding, and thrombosis. We identified 13 articles for a total of 15 cases of possible coexistence of FVIII inhibitor and LA. The presenting clinical manifestation was thrombosis in 6 cases and bleeding in 9 cases. Activated partial thromboplastin time was the presenting laboratory abnormality in all cases, and first-line investigations suggested the coexistence of LA and acquired FVIII inhibitor. None of the articles addressed the diagnostic accuracy of the screening tests by performing ‘‘second line’’ assays. We reviewed the diagnostic pitfalls of the cases under study and provide some guidance for alternative tests when facing a prolonged aPTT that may have a double meaning