摘要:

Scedosporium apiospermum(Sca) is a ubiquitous filamentous fungus capable of causing invasive disease. We reviewed our electronic microbiology records and the English-language literature. Between 1976 and December 1999 we identified 23 solid organ transplant recipients with Sca infection, 7 of which occurred between December 1987 and December 1999 at our institution. Overall incidence was 1 per 1,000 patients, with a trend of higher incidence in patients receiving lung transplants compared with other transplant organs (p = 0.06). The 23 patients included liver (4), kidney (8), heart (8), lung (2), and heart/lung (1) recipients. Male to female ratio was 19:4, and the mean age was 46 ± 12 (SD) years. Fungal infection was diag-nosed at a median of 4 months (range, 0.4–156 mo) after transplant. The clinical presentation included disseminated disease (8), skin lesions (3), lung disease (5), endophthalmitis (1), meningitis (1), brain abscess with or without extension to eye (3), fungal mycotic aneurysm (1), and sinusitis (1). Seven (30%) patients had intravascular infection, and 11 (48%) patients had central nervous system involvement. Antifungal therapy was accompanied by surgical debridement in 9 cases. Three additional patients were found to have airway colonization only and received itraconazole prophylaxis, without evidence of disease. Of 22 patients with known outcome, 16 (72.7%) died. Five of 6 patients who survived had localized infections: skin lesions (n = 3), sinus fungus ball (n = 1), and solitary lung nodule (n = 1). All patients with disseminated disease and 10 of 11 patients with central nervous system disease died. An exception was 1 patient with a brain abscess, successfully treated with voriconazole and surgical drainage.Sca infection is rare but is associated with high mortality. Early diagnosis by culture is important because Sca is resistant to amphotericin B, routinely used in the empiric therapy of invasive fungal infections. Treatment with the combination of an antifungal and surgery may have a better outcome. Voriconazole promises to be an effective antifungal agent. Cultures positive for Sca should not be ignored, and long-term antifungal prophylaxis in candidates and transplant recipients should be considered.

ISSN:0025-7974    

出版商:OVID    

年代:2002

数据来源: OVID

摘要:

The present report describes and expands the clinical and genetic spectrum of the autoinflammatory disorder, tumor necrosis factor (TNF) receptor-associated periodic syndrome (TRAPS). A total of 20 mutations have been identified since our initial discovery of 6 missense mutations in TNF receptor super family 1A (TNFRSF1A) in 1999. Eighteen of the mutations result in amino acid substitutions within the first 2 cysteine-rich domains (CRDs) of the extracellular portion of the receptor. A single splicing mutation also affects the first CRD by causing the insertion of 4 amino acids. Haplotype analysis of the most commonly occurring and ethnically heterogeneous mutation, R92Q, demonstrates an ancient founder; however, analysis of the T50M mutation, another commonly occurring mutation in Irish and Scottish families, does not, suggesting that T50M is a recurring mutation. Mutations that result in cysteine substitutions demonstrate a higher penetrance of the clinical phenotype (93% versus 82% for noncysteine residue substitutions), and also increase the probability of developing life-threatening amyloidosis (24% versus 2% for noncysteine residue substitutions).Retrospective and prospective evaluation of more than 50 patients, representing 10 of the 20 known mutations, allows us to expand and better define the clinical spectrum of TRAPS. Recurrent episodes of fever, myalgia, rash, abdominal pain, and conjunctivitis that often last longer than 5 days are the most characteristic clinical features of TRAPS.Defective shedding of TNFRSF1A can only partially explain the pathophysiologic mechanism of TRAPS, since some mutations have normal shedding. Consequently, other mechanisms may be mediating the observed phenotype. We are currently investigating other possible mechanisms using stable and transiently transfected cell systems in vitro, as well as developing a knockin mouse model.Preliminary data suggest that etanercept may be effective in decreasing the severity, duration, and frequency of symptoms in TRAPS patients. Additionally, it provides a viable therapeutic alternative to glucocorticoid therapy, which has numerous serious, long-term adverse effects. Two clinical trials are being conducted to evaluate the efficacy of etanercept in decreasing the frequency and severity of symptoms in TRAPS.Lastly, we have summarized data that R92Q and P46L, and probably as yet undiscovered substitutions, represent very low penetrance mutations that may play a much larger role in more broadly defined inflammatory diseases such as rheumatoid arthritis. Our laboratories are currently undertaking both clinical and basic research studies to define the role of these mutations in more common inflammatory diseases.

ISSN:0025-7974    

出版商:OVID    

年代:2002

数据来源: OVID

摘要:

A prospective long-term study was conducted of 235 young to middle-aged women with past histories of and/or active infections of the urinary tract. The present report defines certain characteristics of the population and of the 1,018 confirmed infections of the urinary tract that occurred during observation periods ranging from 1.1 to 19.4 years (mean, 7.4 yr). The population could be divided into 3 groups: women with confirmed infections who did (Group 1, n = 19) or did not (Group 2, n = 191) receive courses of antimicrobial prophylaxis and those who did not have confirmed infections (Group 3, n = 25). The 3 groups differed significantly only in their mean infection rates per year (3.1, 0.8, and 0.0, respectively). The number of infections among individual women ranged from 0 to 42. The patterns of recurrent infections among individual women ranged widely and were not predictable. Clusters of infections occurred in 45.7% of the women and ranged in size from 2 to 12 infections per cluster.The proportions of different infecting organisms and clinical syndromes were similar to those reported by others.Escherichia coliaccounted for the great majority of infections. Eighty-five percent of the isolates ofE. colitested were serologically classified. A total of 50 different O groups were identified. Three (O4, O6, and O75) of the 131 potential O groups accounted for 49% of the isolates that could be classified. In each of the 4 clinical syndromes, these same 3 O groups were also the most frequently identified. The ability to classify serologically the infecting isolates ofE. colipermitted a more complete definition of the complexity of patterns of recurrent infections among individual women. The findings in the present study are compared with those in the literature.

ISSN:0025-7974    

出版商:OVID    

年代:2002

数据来源: OVID

摘要:

Nocardiosis (NOC) is an important cause of infection in immunocompromised patients. However, large series in patients with cancer have not been described. We review the records of patients with cancer and NOC who were evaluated at The University of Texas M. D. Anderson Cancer Center, Houston, Texas, between 1988 and 2001, and we describe the incidence, microbiologic and clinical characteristics, treatment, and outcome of NOC in this population. Forty-two patients with a total of 43 episodes of NOC were identified (incidence of 60 cases of NOC per 100,000 admissions). Twenty-seven patients (64%) had hematologic malignancies. In 13 patients, NOC complicated bone marrow transplantation. Neutropenia was observed in 4 (10%) of 40 episodes with information available, and lymphopenia in 20 (50%) of 40 episodes. Patients had received steroids for 25 episodes (58%) and had received chemotherapy for 10 episodes (23%) within 30 days before the onset of NOC. Nine episodes of breakthrough NOC were identified in 7 (23%) of the 40 patients with information available. Pulmonary NOC was seen in 30 (70%) of 43 cases; soft-tissue NOC in 7 (16%); central venous catheter-related nocardemia in 3 (7%); and disseminated NOC, central nervous system NOC, and a perinephric abscess each in 1 (2%). Twenty-three percent of patients with pulmonary NOC had an acute presentation.Nocardia asteroidescomplex was the most common causative species (77%). Therapy for NOC was mainly concurrent trimethoprim/ sulfamethoxazole and either a tetracycline or a beta-lactam. The median duration of treatment was 113 days (range, 10–600 d). Nine (60%) of 15 patients with outcome data died from NOC.NOC, although infrequent, is an important cause of morbidity and mortality in patients with cancer. It has pleomorphic manifestations, and it can be seen as a breakthrough infection. The present study confirms that timely diagnosis, the site of NOC, the type ofNocardia, the presence of comorbidities, and cytomegalovirus coinfection influence the outcome of patients with cancer and NOC.

ISSN:0025-7974    

出版商:OVID    

年代:2002

数据来源: OVID

摘要:

We review the clinical and histologic features of 17 patients with cryoglobulinemia and renal disease. Most cases were associated with evidence of hepatitis C virus (HCV), although a significant minority had no evidence of HCV. The most common histologic pattern for renal involvement was membranoproliferative glomerulonephritis, which was seen in both HCVpositive and HVC-negative patients.Clinical presentation was variable, including nephrotic syndrome, unexplained elevations of serum creatinine, acute renal failure, or extrarenal manifestations. All patients had type II or type III cryoglobulins and all had low serum complements at presentation. Liver function abnormalities in HCV-positive patients were mild. No clinical or laboratory features beyond hepatitis serologies were helpful in distinguishing between HCV-positive and HCV-negative patients.All but 1 HCV-positive patient were treated with interferon (IFN) in either standard or high dosage, and this treatment was largely ineffective. Five of 11 HCV-positive patients progressed to renal failure. HCV patients treated with cyclophosphamide did not develop active liver disease. In all HCV-negative patients, renal function stabilized or improved, and 5 of 6 were treated with cyclophosphamide. In our series, there is limited experience with IFNribavirin therapy, which was not well tolerated.Renal cryoglobulinemia is an uncommon illness of diverse etiologies and clinical presentations. Morphologic presentation is also varied. IFN alone is often inadequate therapy for HCV-associated cryoglobulinemia. Experience with IFN-ribavirin in this entity is limited, but has shown promise in hepatic disease and has shown efficacy in HCV-associated cryoglobulinemia. Cyclophosphamide is the treatment of choice for HCV-negative patients and can be used safely in most HCV-positive patients if they fail IFN or IFN-ribavirin therapy, or if they require more aggressive therapy during periods of rapid clinical progression.

ISSN:0025-7974    

出版商:OVID    

年代:2002

数据来源: OVID