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Biomedical subjects

Gregory M Anstead

Publications and source records attributed to Gregory M Anstead.

7 recordsLinked to original sources

Coccidioidomycosis.

The difficulties in managing this potentially horrific disease, with its myriad manifestations, are immense, because host factors dramatically impact outcome. Coccidioidomycosis should warrant great respect among clinicians, because, even with dramatic improvements in therapies, outcomes remain poor. Although there have been outstanding successes with these new therapies, tragic losses after years of immense patient suffering still occur. Coccidioidomycosis is a geographically restricted fungus but is one that inflicts tremendous suffering on affected patients. In addition, because of travel and the influx of susceptible hosts, dramatic increases in patients at risk for infection are seen throughout the southwest United States. The extended-spectrum azoles, such as posaconazole and voriconazole, may prove to be more efficacious in the treatment of coccidioidomycosis than prior agents, including amphotericin B, fluconazole, and itraconazole. Additional resources are needed to conduct randomised, controlled clinical trials for the treatment of this disease.

Antifungal Agents↗

Refractory coccidioidomycosis treated with posaconazole.

BACKGROUND: Disseminated coccidioidomycosis (which is caused by the endemic fungi of the genus Coccidioides) can be a life-threatening systemic fungal infection. Although conventional antifungal therapies have activity against Coccidioides, the disease can be refractory to standard therapies. Drug-associated toxicities also may limit the clinical utility of the standard antifungal drugs. In addition, relapses in patients with disseminated coccidioidomycosis are common, making long-term management of this disease challenging. METHODS: We report the outcomes of 6 patients with coccidioidomycosis who were treated with posaconazole salvage therapy after treatment with conventional antifungal therapies failed to produce sustained clinical improvement. Patients were administered posaconazole oral suspension 800 mg/day in divided doses as part of an open-label clinical trial. A modified version of the Mycoses Study Group Coccidioides scoring system was used to evaluate the burden of disease. Posaconazole therapy resulted in rapid clinical improvements in the signs and symptoms of coccidioidomycosis. RESULTS: At the end of therapy, 5 of 6 patients had successful outcomes. Posaconazole was well tolerated despite long-term administration (1-2 years), and 2 patients continued to receive posaconazole maintenance therapy at the time of writing. CONCLUSIONS: The successful outcomes observed in this case series suggest that posaconazole is an effective therapy for coccidioidomycosis.

Adolescent↗

Jaccoud arthropathy: a rarity in the spectrum of HIV-associated arthropathy.

In studies comparing HIV-infected patients with HIV-negative patients, rheumatic manifestations, including reactive arthritis, psoriatic arthritis, myalgia, tendinitis, fibromyalgia, necrotizing vasculitis, polymyositis, Sjogren syndrome, were shown to occur more frequently in the HIV-positive group. Uncommon clinical features and the demonstration of HIV antigens in the synovial membranes suggest a direct role of HIV in the pathogenesis of HIV-associated rheumatic disease. Jaccoud arthropathy is a nonerosive deforming arthropathy reported to occur in cases of chronic rheumatic fever and systemic lupus erythematosus. Only two cases of HIV-associated Jaccoud arthropathy has been reported in the literature thus far, both in patients with features of reactive arthritis. We report a case of HIV-associated Jaccoud arthropathy in a patient without features of reactive arthropathy.

HIV Infections↗

Recent advances in the treatment of infections due to resistant Staphylococcus aureus.

PURPOSE OF REVIEW: This paper reviews recent data on the treatment of infections caused by drug-resistant Staphylococcus aureus, particularly methicillin-resistant S. aureus (MRSA). This review will focus on new findings reported in the English-language medical literature from June 2003 to September 2004. RECENT FINDINGS: Despite the emergence of resistant and multidrug-resistant S. aureus, we have three effective drugs in clinical use for which little resistance has been observed: quinupristin-dalfopristin, linezolid, and daptomycin. Linezolid looks particularly promising in the treatment of MRSA pneumonia. Daptomycin displays rapid bactericidal activity in vitro, but, so far, clinical trials have only been conducted for the treatment of skin and soft-tissue infections. There are three drugs with broad-spectrum activity against Gram-positive organisms at an advanced stage of testing: two new glycopeptides with potent bacteriocidal activity and long half-lives (oritavancin and dalbavancin), and tigecycline, a minocycline derivative. These drugs have also shown efficacy in the treatment of skin and soft-tissue infections. SUMMARY: The promising data that have emerged in the last year indicate that we may have six available drugs to treat resistant S. aureus infections within the next few years. The next goal is to determine the appropriate indications and cost-effectiveness of each of these drugs in our treatment strategy against S. aureus and other Gram-positive pathogens.

Acetamides↗

Primary esophageal lymphoma: a diagnostic challenge in acquired immunodeficiency syndrome--two case reports and review.

Although extranodal presentation occurs in the majority of cases of acquired immunodeficiency syndrome-associated non-Hodgkin lymphoma, the esophagus is only rarely affected. We discuss two patients with acquired immunodeficiency syndrome who presented with dysphagia and weight loss, who were found to have human immunodeficiency virus-associated primary esophageal lymphoma. Both patients died within a few weeks of diagnosis, reflecting the poor prognosis associated with this malignancy. Primary esophageal lymphoma should be considered in the differential diagnosis in a human immunodeficiency virus-seropositive patient presenting with dysphagia.

Acquired Immunodeficiency Syndrome↗

Reversible dilated cardiomyopathy related to amphotericin B therapy.

We describe a patient who developed dilated cardiomyopathy and clinical congestive heart failure after 2 months of therapy with amphotericin B (AmB) for disseminated coccidioidomycosis. His echocardiographic abnormalities and heart failure resolved after posaconazole was substituted for AmB. It is important to recognize the rare and potentially reversible toxicity of AmB.

Adult↗

Multinutrient undernutrition dysregulates the resident macrophage proinflammatory cytokine network, nuclear factor-kappaB activation, and nitric oxide production.

We have described previously a murine model of multinutrient undernutrition that reproduced the features of moderate human malnutrition and led to increased early dissemination of Leishmania donovani. Peritoneal cells from these malnourished mice produced decreased NO after stimulation with IFN-gamma/LPS. We hypothesized that malnutrition may cause a deficit in NF-kappaB activation, a principal transcription pathway for inducible NO synthase and proinflammatory cytokines. Macrophages from malnourished mice, stimulated with IFN-gamma/LPS, showed increased IL-6 production and decreased IL-10 and TNF-alpha production. Neutralization of TNF-alpha in macrophage cultures from the control mice mimicked the effect of malnutrition on NO and IL-10 production, whereas supplemental TNF-alpha added to cultures of macrophages from malnourished mice increased NO secretion. NF-kappaB nuclear binding activity in macrophages from the malnourished mice was reduced early after stimulation, but increased to supranormal values by 16- or 24-h poststimulation. Blocking NO production in the macrophages from the control mice reproduced the effect of malnutrition on the late activation of NF-kappaB, whereas supplemental NO decreased the late NF-kappaB activation in the malnourished mice. Thus, in macrophages from the malnourished mice, initial deficits in NF-kappaB activity probably lead to decreased TNF-alpha, which results in decreased NO; however, IL-6 is regulated independently from NF-kappaB and TNF-alpha. The late activation of NF-kappaB in the macrophages from malnourished mice is due to absence of negative feedback from NO.

Animals↗