19 research outputs found
Is Sjögren's syndrome a retroviral disease?
Circumstantial evidence suggests that retroviruses play a role in the pathogenesis of Sjögren's syndrome. Such evidence, derived from studies of patients with Sjögren's syndrome, includes the following: the presence of serum antibodies cross-reactive with retroviral Gag proteins; the occurrence of reverse transcriptase activity in salivary glands; the detection of retroviral antigens, retrovirus-like particles, or novel retroviral sequences in salivary glands; the occurrence of Sjögren's syndrome-like illnesses in patients having confirmed systematic infections with retroviruses such as human immunodeficiency virus-1 (HIV-1) and human T lymphotropic virus type 1; and the beneficial effect of anti-retroviral treatment on the occurrence of HIV-1-associated sicca syndrome. Additional evidence is provided by animal models
Pancreatic adenocarcinoma-associated polymyositis treated with corticosteroids along with cancer specific treatment: case report
<p>Abstract</p> <p>Background</p> <p>Adenocarcinoma of the pancreas only rarely is associated with inflammatory myopathy. In this setting, polymyositis may be treated with glucocorticoids in combination with cancer specific treatment.</p> <p>Case presentation</p> <p>We present the case of a 52-year-old man with stage IIA pancreatic tail adenocarcinoma who underwent surgical treatment and six months into therapy with gemcitabine he developed symmetrical, painful, proximal muscle weakness with peripheral oedema. Re-evaluation with imaging modalities, muscle histology and biochemistry conferred the diagnosis of polymyositis associated with pancreatic cancer progression. The patient was treated with glucocorticoids along with gemcitabine and erlotinib which resulted in complete remission within six months. He remained in good health for a further six months on erlotinib maintenance therapy when a new computer tomography scan showed pancreatic cancer relapse and hence prompted 2<sup>nd </sup>line chemotherapy with gemcitabine.</p> <p>Conclusions</p> <p>Polymyositis associated with pancreatic cancer may respond to glucocorticoids along with cancer specific treatment.</p
Treatment of fungal disease in the setting of neutropenia
Invasive fungal infections are important causes of morbidity and
attributable mortality in neutropenic patients with hematological
malignancies, myelodysplasia, and aplastic anemia. Successful risk-based
strategies can be implemented for prophylaxis, empirical therapy, and
preemptive therapy for the prevention and early treatment of invasive
fungal infections in neutropenic hosts. The use of echinocandins for
invasive candidiasis and voriconazole for invasive aspergillosis has
significantly improved outcome. Recent studies demonstrate, however,
that resistant fungal pathogens may emerge during the course of these
antifungal interventions. Although triazole-resistant Candida spp. have
been well described as causes of breakthrough candidemia, other
organisms now pose a similar threat. Such organisms include
echinocandin-resistant Candida glabrata and Candida parapsilosis species
complex. The Mucorales, Fusarium spp., and Scedosporium spp. may emerge
in the setting of voriconazole prophylaxis. The challenges of these
emerging pathogens underscore the need for the development of new
antifungal agents and strategies
Invasive Fungal Infections in Patients with Hematological Malignancies: Emergence of Resistant Pathogens and New Antifungal Therapies
Invasive fungal infections caused by drug-resistant organisms are an emerging threat to heavily immunosuppressed patients with hematological malignancies. Modern early antifungal treatment strategies, such as prophylaxis and empirical and preemptive therapy, result in long-term exposure to antifungal agents, which is a major driving force for the development of resistance. The extended use of central venous catheters, the nonlinear pharmacokinetics of certain antifungal agents, neutropenia, other forms of intense immunosuppression, and drug toxicities are other contributing factors. The widespread use of agricultural and industrial fungicides with similar chemical structures and mechanisms of action has resulted in the development of environmental reservoirs for some drug-resistant fungi, especially azole-resistant Aspergillus species, which have been reported from four continents. The majority of resistant strains have the mutation TR34/L98H, a finding suggesting that the source of resistance is the environment. The global emergence of new fungal pathogens with inherent resistance, such as Candida auris, is a new public health threat. The most common mechanism of antifungal drug resistance is the induction of efflux pumps, which decrease intracellular drug concentrations. Overexpression, depletion, and alteration of the drug target are other mechanisms of resistance. Mutations in the ERG11 gene alter the protein structure of C-demethylase, reducing the efficacy of antifungal triazoles. Candida species become echinocandin-resistant by mutations in FKS genes. A shift in the epidemiology of Candida towards resistant non-albicans Candida spp. has emerged among patients with hematological malignancies. There is no definite association between antifungal resistance, as defined by elevated minimum inhibitory concentrations, and clinical outcomes in this population. Detection of genes or mutations conferring resistance with the use of molecular methods may offer better predictive values in certain cases. Treatment options for resistant fungal infections are limited and new drugs with novel mechanisms of actions are needed. Prevention of resistance through antifungal stewardship programs is of paramount importance
Therapy of Mucormycosis
Despite the recent introduction of mold-active agents (posaconazole and isavuconazole), in addition to amphotericin B products, to our armamentarium against mucormycosis, many uncertainties remain for the management of this uncommon opportunistic infection, as there are no data from prospective randomized clinical trials to guide therapy. In this mini-review, we present the current status of treatment options. In view of the heterogeneity of the disease (different types of affected hosts, sites of infection, and infecting Mucorales), mucormycosis management requires an individualized management plan that takes into account the net state of immunosuppression of the host, including comorbidities, certainty of diagnosis, site of infection, and antifungal pharmacological properties
Therapy of Mucormycosis
Despite the recent introduction of mold-active agents (posaconazole and
isavuconazole), in addition to amphotericin B products, to our
armamentarium against mucormycosis, many uncertainties remain for the
management of this uncommon opportunistic infection, as there are no
data from prospective randomized clinical trials to guide therapy. In
this mini-review, we present the current status of treatment options. In
view of the heterogeneity of the disease (different types of affected
hosts, sites of infection, and infecting Mucorales), mucormycosis
management requires an individualized management plan that takes into
account the net state of immunosuppression of the host, including
comorbidities, certainty of diagnosis, site of infection, and antifungal
pharmacological properties
Impaired distensibility of ascending aorta in patients with HIV infection
<p>Abstract</p> <p>Background</p> <p>Our aim was to investigate the aortic distensibility (AD) of the ascending aorta and carotid artery intima-media thickness (c-IMT) in HIV-infected patients compared to healthy controls.</p> <p>Methods</p> <p>One hundred and five HIV-infected patients (86 males [82%], mean age 41 ± 0.92 years), and 124 age and sex matched HIV-1 uninfected controls (104 males [84%], mean age 39.2 ± 1.03 years) were evaluated by high-resolution ultrasonography to determine AD and c-IMT. For all patients and controls clinical and laboratory factors associated with atherosclerosis were recorded.</p> <p>Results</p> <p>HIV- infected patients had reduced AD compared to controls: 2.2 ± 0.01 vs. 2.62 ± 0.01 10<sup>-6</sup> cm<sup>2</sup> dyn<sup>-1</sup>, respectively (p < 0.001). No difference was found in c-IMT between the two groups. In multiadjusted analysis, HIV infection was independently associated with decreased distensibility (beta –0.45, p < 0.001). Analysis among HIV-infected patients showed that patients exposed to HAART had decreased AD compared to HAART-naïve patients [mean (SD): 2.18(0.02) vs. 2.28(0.03) 10<sup>-6</sup> cm<sup>2</sup> dyn<sup>-1</sup>, p = 0.01]. In multiadjusted analysis, increasing age and exposure to HAART were independently associated with decreased AD.</p> <p>Conclusion</p> <p>HIV infection is independently associated with decreased distensibility of the ascending aorta, a marker of subclinical atherosclerosis. Increasing age and duration of exposure to HAART are factors further contributing to decreased AD.</p