Management of hemoptysis in invasive pulmonary aspergillosis

The association between body weight-age and egg weight-age patterns was studied in a segregating population of laying hens belonging to the F3 generation of a Rhode Island Red x White Leghorn reciprocal cross. Body weight and egg weight were expressed as a function of time using the model developed by Weatherup and Foster. Each hen was characterized in terms of its asymptotic body weight (ABW), maturing rate for body weight (MBW), asymptotic egg weight (AEW), and maturing rate for egg weight (MEW) values. Four groups of hens were distinguished by means of a principal component analysis. Birds belonging to Groups 1 and 3 were discriminated for their egg weight-age pattern. Group 1 included hens laying the heaviest eggs (AEW = 66.1 g) at the lowest maturing rate (MEW = 0.922), the inverse being true for birds in Group 3 (AEW = 55.7 g and MEW = 0.737). Birds belonging to Groups 2 and 4 were distinguished for their body weight-age pattern. Hens in Group 2 showed the lowest ABW (1,893 g) and MBW (0.764) whereas the heaviest (ABW = 2,802 g) and less mature (MBW = 0.929) birds were found in Group 4. The results confirm the partial pleiotropic basis of the body weight-egg weight correlation, evincing the feasibility of applying selective pressure not only on each character separately but also on maturing rate independently of asymptotic weight within each trait. This strategy could be implemented using a biological selection index based on principal component analysis equations.     

Role of TNF-alpha in pulmonary host defense in murine invasive aspergillosis

Invasive pulmonary aspergillosis is a common and devastating complication of immunosuppression, whose incidence has increased dramatically in tandem with the increase in the number of immunocompromised patients. Given the role of TNF-alpha in other pulmonary infections, we hypothesized that TNF-alpha is an important proximal signal in murine invasive pulmonary aspergillosis. Intratracheal challenge with Aspergillus fumigatus conidia in both neutropenic (cyclophosphamide-treated) and nonneutropenic BALB/c mice resulted in the time-dependent increase in lung TNF-alpha levels, which correlated with the histologic development of a patchy, peribronchial infiltration of mononuclear and polymorphonuclear cells. Ab-mediated neutralization of TNF-alpha resulted in an increase in mortality in both normal and cyclophosphamide-treated animals, which was associated with increased lung fungal burden as determined by histology and as quantified by chitin content. Depletion of TNF-alpha resulted in a reduced lung neutrophil influx in both normal and cyclophosphamide-treated animals, which occurred in association with a decrease in lung levels of the C-X-C chemokine, macrophage inflammatory protein-2 and the C-C chemokines macrophage inflammatory protein-1alpha and JE. In cyclophosphamide-treated animals, intratracheal administration of a TNF-alpha agonist peptide (TNF70-80) 3 days before, but not concomitant with, the administration of Aspergillus conidia resulted in improved survival from 9% in control mice to 55% in TNF70-80-treated animals. These studies indicate that TNF-alpha is a critical component of innate immunity in both immunocompromised and immunocompetent hosts, and that pretreatment with a TNF-alpha agonist peptide in a compartmentalized fashion can significantly enhance resistance to A. fumigatus in neutropenic animals.     

Changes in the natural history of invasive pulmonary aspergillosis in neutropenic leukemic patients

We describe five patients with acute leukemia who during the period of chemotherapy-induced neutropenia developed invasive pulmonary aspergillosis. Amphotericin B was initiated early in the febrile neutropenic episode at a dose of 1-1.5 mg/kg per day. Four of the five patients had normal chest films at the time amphotericin B was started and only later developed infiltrates, which subsequently progressed to cavitation formation with resolution of the infiltrates around the cavitations. This is compatible with primary aspergilloma or invasive pulmonary aspergillosis. The patients experienced partial (2 patients) or complete resolution (3 patients) of the process, and none died of the fungal infection. In the past, infection with invasive aspergillosis carried a high mortality. We believe that this positive outcome constitutes a change in the natural history of invasive pulmonary aspergillosis in neutropenic patients as a result of the early initiation of high dose amphotericin B. We recommend the early empiric use of amphotericin B therapy in febrile neutropenic patients not responding to broad-spectrum antibiotics, and that the minimal initial dose be 1 mg/kg per day especially in institutions carrying a high incidence of aspergillosis.     

Steroid-induced invasive aspergillosis with thyroid gland abscess and positive blood cultures

Demonstration of quality health care includes documentation of outcomes of care. Surveillance is a comprehensive method of measuring outcomes and related processes of care, analyzing the data, and providing information to members of the health care team to assist in improving those outcomes. Surveillance is an essential component of effective clinical programs designed to reduce the frequency of adverse events such as infection or injury.     

Anatomo-clinical correlation. A case of invasive pulmonary aspergillosis]

This report describes a case of invasive pulmonary aspergillosis affecting a young female patient who had benefited from a liver transplantation for a fulminant hepatic failure. Infections following liver transplantation can happen but in this case the short delay to the fatal outcome is unusual (6 days). Corticotherapy given prior to transplantation could have impaired the immune system. The authors discuss the infections due to Aspergillus species and particularly invasive pulmonary aspergillosis.     

Cytokine- and T helper-dependent lung mucosal immunity in mice with invasive pulmonary aspergillosis

The role of cytokine- and T helper (Th)-dependent lung mucosal antifungal immunity in murine invasive pulmonary aspergillosis (IPA) was investigated. Intact or leukopenic DBA/2 mice were resistant or highly susceptible, respectively, to infection caused by multiple intranasal injections of viable Aspergillus fumigatus conidia. Resistance was associated with unimpaired innate antifungal activity of pulmonary phagocytic cells, concomitant with high-level production of tumor necrosis factor (TNF)-alpha and interleukin (IL)-12 and the presence of interstitial lymphocytes producing interferon-gamma and IL-2. Conversely, production of TNF-alpha and IL-12 was down-regulated in highly susceptible mice, which also had defective innate antifungal immunity and high-level production of IL-4 and IL-10 by lung lymphocytes. Resistance was increased in susceptible mice upon local IL-4 or IL-10 neutralization or IL-12 administration. These results indicate that, similar to observations in mice with disseminated aspergillosis, innate and Th1-dependent immunity play an essential role in host defense against IPA.     

血清半乳甘露聚糖检测对血液病患者侵袭性曲霉菌感染早期诊断的价值

目的 评价血清半乳甘露聚糖(GM)检测对血液病患者侵袭性曲霉菌(IA)感染早期诊断的价值.方法 前瞻性采用酶联免疫吸附试验(ELISA)每周2次测定患者的GM水平,并计算该诊断试验的各项评价指标.结果 共有来自92例患者的113例次感染进入研究,检测血清标本472份,以确诊IA感染和临床诊断IA感染为真阳性组,排除IA感染为真阴性组,0.7为阈值,连续2次GM结果阳性为真阳性,该诊断试验的敏感度为83.3%,特异度为91.1%,阳性预测值为78.9%,阴性预测值为93.1%.GM阳性结果较痰培养阳性时间提前4 d(1～7 d),比影像学改变提早7 d(1～14 d),较抗真菌治疗提前6 d(1～15 d).结论 通过ELISA方法进行血清GM检测可以快速、灵敏的为早期诊断IA感染提供有力证据.     

Treatment of invasive aspergillosis: relation of early diagnosis and treatment to response

Aspergillus infections in patients with cancer are difficult to diagnose, and such diagnoses are frequently made at necropsy. Earlier therapy has been proposed to provide better response. We reviewed 17 consecutive patients with documented aspergillosis to determine the impact of earlier diagnosis and prompt treatment with amphotericin B. Sixteen had hematologic malignancies, and all had marked granulocytopenia. Six were diagnosed and treated within 96 h of the appearance of infiltrates. Three of these six had complete resolution of all signs and symptoms of aspergillus infection. The other three had a partial response to therapy despite continued granulocytopenia. All 11 patients in whom antifungal therapy was either delayed (six) or not given (five) for at least 2 weeks after the infiltrate was present diet with progressive aspergillosis aggressive diagnostic methods to establish the diagnosis of aspergillosis are warranted so that antifungal therapy can be started early, which may then be successful in resolving these potentially fatal infections.     

Outcome of ICU treatment in invasive aspergillosis

OBJECTIVE: To assess the outcome of intensive care treatment in invasive aspergillosis. DESIGN: Retrospective study. SETTING: University Hospital, Medical Intensive Care Unit (ICU). PATIENTS: Twenty-five patients with invasive aspergillosis who were admitted to the medical ICU in a 5 1/2 year period. Twenty-two had received high-dose chemotherapy for (mainly hematologic) malignancies, one had been treated with cyclosporine and prednisolone for systemic lupus erythematosus, one with high-dose methylprednisolone for polyarteritis nodosa and one had an ARDS after near-drowning. MEASUREMENTS AND RESULTS: The medical records were reviewed for patient and disease characteristics, outcome, reasons for admission to the ICU, supportive care and antifungal therapy as well as for the results of cultures and autopsy. Out of 25 patients, a definite ante mortem diagnosis could be established in seven. When autopsied patients were included, a total of 15 suffered from proven invasive aspergillosis. Although standard antifungal treatment and maximal available supportive care were given, 23 of 25 patients (92%) died after a mean of 15 (1-51) days in the ICU. Both patients who recovered had received high-dose chemotherapy for hematologic malignancy and showed bone marrow recovery and/or had a localized pulmonary infection. CONCLUSIONS: In patients with highly suspected or proven invasive aspergillosis, admission to an ICU and mechanical ventilation should be considered in cases of localized infection and obvious signs of hematologic recovery. In most other circumstances ICU admission for mechanical ventilation does not seem to improve survival.     

The alkaline protease of Aspergillus fumigatus is not a virulence determinant in two murine models of invasive pulmonary aspergillosis

Little is known of the pathophysiology of invasive pulmonary aspergillosis (IPA), an opportunistic fungal infection usually caused by Aspergillus fumigatus. It has been suggested that the ability of the fungus to degrade elastin may aid its invasion and growth in lung tissue. We have described previously the construction of a strain of A. fumigatus in which the gene encoding an alkaline protease, AFAlp, had been disrupted (C.M. Tang, J. Cohen, and D.W. Holden, Mol. Microbiol. 6:1663-1671, 1992); this mutant is deficient in extracellular proteolytic and elastinolytic activity over a broad pH range. In this study, we compared the pathogenicity of this and another AFAlp disruptant with their isogenic, elastase-producing parental strains in two murine models of IPA. In both models, animals were inoculated via the respiratory tract. In the first model, the inoculum was delivered as airborne conidia and animals developed signs of respiratory distress within 2 to 4 days. In the second model, conidia were administered intranasally as a suspension and the disease developed over a 2-week period. No difference was observed between the wild-type and AFAlp disruptants in terms of mortality, and elastin breakdown was detected in lung tissue from animals inoculated with all four strains. We conclude that AFAlp is not a virulence determinant in these models of IPA.     

Surgical treatment of pulmonary aspergillosis

There is controversy about the optimal treatment for pulmonary aspergillosis. Eight patients with pulmonary aspergilloma underwent surgical treatment. Three patients had tuberculosis, one Sj?gren syndrome, one aortitis syndrome, one malignant lymphoma. Lobectomy was performed in five patients, segmentectomy in three patients. All patients are alive and have no recurrence. We have obtained excellent results from surgery and advocate early surgery for localized lesions to prevent life-threatening hemoptysis. This will allow patients to continue with further treatment for the underlying disease. We encountered a granulocytopenic patient with rapidly progressive aspergillus infection resulting in occlusion of main pulmonary artery leading to death. Surgical intervention could not prevent this fatal outcome. The selection of the patients with diffuse lesions should be made carefully.     

PCR-ELISA for the early diagnosis of invasive pulmonary aspergillus infection in neutropenic patients

This paper outlines criteria which allow the clinician to identify endodontically treated teeth that can be restored with a high level of predictability. The intent of the article is not to preclude the restoration of teeth that do not meet these criteria; it is to provide a science-based approach for identifying those teeth with a high probability of long-term success upon restoration. For an endodontically treated tooth not requiring a post, the requirements are for biologic width + ferrule length, (i.e. 4.5 mm of supra-bony solid tooth--dentin a minimum of 1 mm thick after preparation). A tooth requiring a post needs, in addition, enough root length to allow a 4 mm apical seal and a post length--apical to the crown margin, equal to the length of the crown. It is essential to assess the functional loads to which the restored tooth would be subjected. Teeth that are endodontically treated, or are likely to be in future, should be avoided as abutments supporting precision attachment RPDs, distal extension RPDs or cantilever FPDs.     

SCH56592 treatment of murine invasive aspergillosis

We analyzed the clinical presentation of 800 severe malaria cases six months to 15 years of age (mean +/- SD = 4.3 +/- 3.0) recruited at the pediatric ward of the Ouagadougou University Hospital, and at the Sourou and Nayala District Hospitals in Burkina Faso. Inclusion criteria followed the World Health Organization (WHO) definition of severe and complicated malaria. The children were treated according to WHO guidelines with a complete regimen of drugs that were provided free of charge as part of the study. The case fatality rate of each sign and symptom of severe malaria was calculated on the 686 children whose outcomes were known. A total of 95 patients (13.8%) died while in the hospital; the mean +/- SD age of these children was 3.2 +/- 2.1 years. The age distribution and the clinical patterns of severe malaria was compared in patients from the urban areas of Ouagadougou characterized by relatively low transmission, and from rural areas where the mean inoculation rates are at least 20-fold higher. The mean +/- SD age of the urban and rural patients was 4.8 +/- 3.0 and 2.2 +/- 1.9 years, respectively (P < 0.001). The prevalence of coma was higher in the urban subsample (53.6% versus 28.9%; P < 0.001) while that of severe anemia (hemoglobin < 5 g/dL) was higher in rural patients (47.4% versus 14.8%; P < 0.001). Our data, in line with previous results obtained comparing rural areas characterized by different inoculation rates, show that the epidemiologic context influences the clinical presentation of severe malaria.     

Sequestration of the alveolar bone by invasive aspergillosis in acute myeloid leukemia

Compared to non-invasive aspergillosis, invasive aspergillosis in the region of the mouth, jaw and face has rarely been reported. It occurs particularly often in the presence of haematological oncological illness. The case of a patient suffering from acute myeloid leukemia is described; he contracted invasive aspergillosis of the lungs and the alveolar processes in the course of chemotherapeutic treatment. All the alveolar processes in the region of the premolars and molars were demarcated and had to be removed by sequestrectomy. The therapy of invasive aspergillosis should be carried out within the framework of intensive interdisciplinary treatment. In addition to systemic and local antimycotic therapy, the debridement of necrotic hard and soft tissue was necessary.     

Comparison of an enzyme immunoassay and a latex agglutination system for the diagnosis of invasive aspergillosis in bone marrow transplant recipients

The performance of two Aspergillus antigenemia systems, the sandwich enzyme-linked immunosorbent assay (ELISA), Platelia Aspergillus test, and the latex agglutination (LA), Pastorex Aspergillus test, in the diagnosis of invasive aspergillosis were compared by testing 364 serum samples from 22 bone marrow transplant (BMT) recipients. Sensitivity and specificity for the ELISA test were 60% and 82% respectively, vs 40% and 94% for the LA test. In the two patients found positive with both methods, the ELISA test became positive earlier than the LA test or remained positive after the LA test had become negative. These results encourage further evaluation of the Platelia Aspergillus test, to assess its role in the management of invasive aspergillosis in BMT patients.     

The problem of allergic pulmonary aspergillosis in children in light of personal observations

67 children (age range 4-17 years) with severe asthma were examined for the presence of allergic pulmonary aspergillosis 28 of these underwent long term steroid therapy. The following parameters were analysed: medical history, clinical state, chest radiograms, microbiological examination of the sputum, precipitating IgG antibodies, skin prick tests with aspergillus, level of specific IgE antibodies. The authors did not find any single child that met the diagnostical criteria of allergic pulmonary aspergillosis. Only in 4 serum specific IgE antibodies were found but the precipitin and skin prick tests were negative. The children did not present typical clinical symptoms of pulmonary allergic aspergillosis. It seems worthwhile to re-examine these children in a few years.     

Virulence of Aspergillus fumigatus double mutants lacking restriction and an alkaline protease in a low-dose model of invasive pulmonary aspergillosis

To investigate the pathogenicity of Aspergillus fumigatus mutants lacking putative virulence factors, we have developed a new murine model of invasive pulmonary aspergillosis based on neutropenia, the major factor predisposing patients to this infection. Mice were treated with cyclophosphamide and inoculated by the intranasal route with 5 x 10(3) conidia, a significant reduction from inoculum levels used in previous models. Evidence for the production of the extracellular alkaline protease (Alp) in lung tissue was obtained by using a fungal transformant harboring an alp::lacZ reporter gene fusion. The pathogenicities of single mutant strains lacking either Alp or the ribotoxin restrictocin and of a double mutant strain lacking both proteins were assessed in this infection model. There were no significant differences between the mutant and the wild-type strains in terms of mortality or histological-features. Inoculations with mixtures of conidia showed that the double mutant strain is slightly less virulent than the wild-type strain. We conclude that Alp and restrictocin are not important virulence determinants in pulmonary infection.     

The role of bronchial biopsy and washing in the diagnosis of allergic bronchopulmonary aspergillosis

A polymorphism in the angiotensin I-converting enzyme (ACE) gene has been associated with cerebrovascular diseases as a new potent risk factor. The purpose of this study was to investigate an association of the gene polymorphism with intracranial saccural aneurysmal patients. The study population consisted of 83 aneurysmal patients (age range 41-85 years) (the AN group) and 104 matched control subjects (age range 30-81 years) (the Control group). For detection of the ACE gene polymorphism, the standard PCR method was performed by using genomic DNA isolated from peripheral blood leukocytes. The PCR products were a 490-bp in the presence of the insertion (I) and a 190-bp fragment in the absence of the insertion (D). The ACE gene polymorphism was classified into three genotypes: I/I genotype (a 490-bp band); D/D genotype (a 190-bp band); or I/D genotype (both a 490-bp and a 190-bp band). The number of subjects with I/I, I/D, and D/D genotypes was 38, 40, and 5 in the AN group and 43, 45, and 16 in the Control group, respectively. The frequency of the D/D genotype in the AN group was significantly lower (5/83 = 0.06) than that in the Control group (16/104 = 0.15) (chi 2 = 4.06; p = 0.044). There was no significant difference between the genotype sof hypertensive patients and normotensive patients in the AN group. Thus, this present study suggests that genetic heterogeneity of the ACE gene may be correlated with the etiology of intracranial aneurysms.     

Invasive pulmonary aspergillosis in an apparently nonimmunocompromised host

Invasive aspergillosis generally occurs in patients with hematologic malignancies, neutropenia or other severe derangements of host defense. An adult patient without such a predisposition, and without a previous history of susceptibility to infections, had rapidly progressive respiratory failure associated with repeated growth of Aspergillus fumigatus on culture of sputum and bronchoscopy specimens. At autopsy he proved to have invasive pulmonary aspergillosis.     

Surgical therapy for pulmonary aspergillosis in immunocompromised patients

OBJECTIVE: The objective of our study was to compare child abuse detection using screen-film radiographs and their digitized images displayed on a computer workstation. MATERIALS AND METHODS: Skeletal surveys of 20 consecutive child abuse patients whose abuse was clinically proven by a combination of history, physical and radiographic findings, and social work history, and 20 consecutive control subjects were evaluated. Three radiologists rated both the screen-film radiographs (400-speed, double-emulsion film) and their digitized images displayed on a workstation (2K x 2K resolution) using a six-point ordinal scale for suspicion of child abuse, fracture detection, and image quality. The rating response was analyzed using multiobserver-multicase receiver operating characteristic analysis of variance. The McNemar test was used to evaluate differences between imaging techniques and between diagnoses made using each imaging technique and clinically proven child abuse. RESULTS: The area under the receiver operating characteristic curve for screen-film radiographs was 0.934+/-0.025 and for digitized images was 0.922+/-0.013. This difference was not significant (p = .658); however, two observers significantly underestimated the child abuse diagnosis with digitized images (p = .02). In a review of the false-negative child abuse diagnoses, observers failed to recognize characteristic metaphyseal fractures (10 observations) and rib fractures (five observations) on digitized images that had been recognized on screen-film radiographs. Mean image quality was rated significantly lower (p < .0001) and interpretation time was significantly longer (75 sec; p < .001) for the digitized images than for screen-film radiographs. CONCLUSION: The characteristic types of fractures that were not identified on the digitized images, lower image quality, and longer interpretation time raise concern that digitized images may not be adequate for interpretation of suspected child abuse.