Using a novel pharmacological tool with (125)I-echistatin to detect integrins on the cell, we have observed that cardiac fibroblasts harbor five different RGD-binding integrins: alpha(8)beta(1), alpha(3)beta(1), alpha(5)beta(1), alpha(v)beta(1), and alpha(v)beta(3). Stimulation of cardiac fibroblasts by angiotensin II (ANG II) or transforming growth factor-beta1 (TGF-beta1) resulted in an increase of protein and heightening by 50% of the receptor density of alpha(8)beta(1)-integrin. The effect of ANG II was blocked by an AT(1), but not an AT(2), receptor antagonist, or by an anti-TGF-beta1 antibody. ANG II and TGF-beta1 increased fibronectin secretion, smooth muscle alpha-actin synthesis, and formation of actin stress fibers and enhanced attachment of fibroblasts to a fibronectin matrix. The alpha(8)- and beta(1)-subunits were colocalized by immunocytochemistry with vinculin or beta(3)-integrin at focal adhesion sites. These results indicate that alpha(8)beta(1)-integrin is an abundant integrin on rat cardiac fibroblasts. Its positive modulation by ANG II and TGF-beta1 in a myofibroblast-like phenotype suggests the involvement of alpha(8)beta(1)-integrin in extracellular matrix protein deposition and cardiac fibroblast adhesion.
Sarcoidosis is a granulomatous disease with various extrapulmonary manifestations. We describe a 51-year-old African American woman with a history of cutaneous sarcoidosis admitted with bicytopenia. Suspicion for systemic sarcoidosis was established after contrastenhanced computerized tomography of the chest, abdomen and pelvis showed a pulmonary nodule, diffuse lymphadenopathy and hepatosplenomegaly. Cytopenias in sarcoidosis, when present, may reflect bone marrow infiltration. Hence, biopsy was obtained and bone marrow sarcoidosis was diagnosed. This manifestation, in spite of ethnic and gender predilection, is rarely seen. As with other forms of sarcoidosis, treatment comprises of corticosteroids.
Four months after receiving an orthotopic liver transplant, a 51-year-old man was admitted for progressive liver failure and severe hepatocellular necrosis thought to be due to tacrolimus. During his hospitalization he experienced bloodstream infections including fungemia due to Trichosporon mucoides and prolonged undulating fever despite antifungal and antibacterial treatment. He underwent removal of the allograft and implantation of another liver. Fever continued postoperatively until therapy with posaconazole was initiated. Initiation of posaconazole led to clinical improvement until the patient's demise from bacteremic vancomycin-resistant enterococcal peritonitis. Trichosporonosis appears to be an emerging fungal infection among immunocompromised individuals (including both hematological and solid organ transplant recipients). T. mucoides is a rare cause of systemic infection. When it occurs, trichosporonosis usually is associated with hematological malignancies and, to the best of our knowledge, has not been previously reported in a liver transplant recipient. The optimal treatment is not well defined. We report here the first case using posaconazole for treatment of trichosporonosis in a liver transplant recipient caused by T. mucoides.
Background: COVID-19 convalescent plasma (CCP) represents an appealing approach to the treatment of patients with infections due to SARS-CoV-2. We endeavored to quickly establish a sustainable CCP transfusion program for a regional network of health care facilities. Study design and methods: A regional collaborative group was activated to address the issues necessary to implementing a CCP transfusion program and making the program sustainable. A wide range of health care providers including physicians (critical care, infectious disease, transfusion medicine), nurses, pharmacists, laboratorians, and information technology (IT) specialists were required to make the program a success. Results: The CCP implementation team initially consisted of four members but quickly grew to a group of nearly 20 participants based on different issues related to program implementation. Overall, six major implementation "themes" were addressed: (a) registration of individual hospitals and principal investigators with a national investigational new drug research protocol; (b) collaboration with a regional blood donor center; (c) targeted recruitment of convalesced donors; (d) IT issues related to all aspects of CCP ordering, distribution, and transfusion; (e) prioritization of patients to receive CCP; and (f) evaluation of CCP products including antibody characteristics and patient response to therapy. Conclusion: Within 4 weeks of initiation, CCP was successfully transfused at multiple hospitals in our regional health care delivery system. A program infrastructure was established that will make this program sustainable into the future. This approach has broader implications for the success of multiinstitutional programs requiring rapid implementation. SARS-CoV-2 is a novel coronavirus and is the etiologic agent of COVID-19. 1 It is a single-stranded RNA virus that was first identified in Wuhan, China, in December 2019. Although brought under control locally, the virus Abbreviations: CCP, COVID-19 convalescent plasma; IND, investigational new drug; IT, information technology; MVRBC,
Infection with the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may lead to a disease spectrum named COVID-19, including a severe form of pneumonia characterized by an intense inflammatory response similar to acute respiratory distress syndrome. Current management guidelines in pregnancy have been limited. In the setting of severe COVID-19 in pregnancy, including in the periviability period, combination multitargeted therapy should be strongly considered. We report a case of severe COVID-19 pneumonia in a periviable pregnancy treated with concurrent combination of remdesivir, corticosteroids, and convalescent plasma therapy, leading to rapid maternal pulmonary improvement.
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