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Tolerability, safety and efficacy of conventional amphotericin B administered by 24-hour infusion to lung transplant recipients.

BACKGROUND: Fungal infections cause serious morbidity and mortality in lung transplant recipients. Expensive lipid formulations of amphotericin B (AmB) are generally used because of fear of adverse effects due to concomitant cyclosporine A and other nephrotoxic drugs. However, a 24-hour dosing regimen of AmB may be well tolerated even in these patients. METHODS: In an open pilot study 6 out of 94 lung transplant recipients with invasive or semi-invasive bronchopulmonary azole-resistant candidal infections (3 paraspilosis, 2 glabrata, 1 krusei) were treated for 40 (17-73) days by 24-hour continuous infusions of AmB 1 mg/kg. Additionally, patients received at least 1000 ml of 0.9% saline intravenously per day. Beside cyclosporine A at serum trough levels of 240 (195-273) microg/l, five patients additionally received aminoglycosides for at least 2 weeks, and 4 were treated with ganciclovir. RESULTS: Calculated creatinine clearance decreased from 57 (43-73) ml/min to a nadir of 35 (28-39) and recovered to 52 (33-60) after cessation of therapy. One patient needed temporary haemofiltration for 7 days after 30 days of AmB, most probably because of the use of contrast media in conjunction with furosemide and hypovolaemia. Besides three episodes of mild hypokalaemia no other side effects attributable to AmB were recorded. While in one case an asymptomatic candidal colonisation persisted for 10 months, the other 5 were cured from their infection. CONCLUSION: These preliminary data show that conventional AmB administered by 24-hour infusion is well tolerated, safe, and efficacious in lung transplant recipients receiving cyclosporine A and other nephrotoxic substances.

Adolescent↗

Value of open-lung biopsy in 87 immunocompromised patients with pulmonary infiltrates.

The authors performed a retrospective analysis of 87 consecutive immunocompromised patients who underwent open-lung biopsy at the University of Utah Medical Center, Salt Lake City, Utah, from January 1971 to June 1982. A specific histologic diagnosis was obtained in 62 (71%) of the patients, 33 of whom had infections. Pneumocystis carinii was the most common microbial pathogen (16 patients), but no cases have been observed since 1980 when the routine use of prophylactic trimethoprim/sulfa began. The other specific diagnoses included malignancy or drug-induced lung disease. Specific therapy was available for 52 patients, and in 33 cases, a change in therapy was necessary to treat according to the lung biopsy diagnosis. Forty-one patients received an adequate course of therapy and 27 (66%) of these improved clinically, including 16 of 26 patients with infections, 11 of 14 with malignancies, and 1 of 2 with a vasculitis. Among the subgroup of 33 patients for whom a new, specific therapeutic option was available as a result of the biopsy diagnosis 21 (64%) responded to the treatment. Eleven significant operative complications were encountered, but no deaths were attributable to the biopsy. An open-lung biopsy in immunocompromised patients is a relatively safe, accurate diagnostic procedure which frequently facilitates appropriate therapy and clinical improvement.

Adolescent↗

Magnetic resonance imaging of inflammatory lung disorders: preliminary studies in children.

Magnetic resonance(MR) scans were performed on 14 children with a variety of inflammatory disorders of the lungs. MR successfully identified disease in all of the children and accurately localized the disease within the lung fields. In patients with pneumonia and lung abscesses the acute inflammation was associated with a marked increase in signal intensity on T2 when compared with T1 weighted images. One patient with an inflammatory pseudotumor demonstrated a smaller increase in signal intensity on T2 weighted images than was seen in acute pneumonia. Abscess cavities were well identified along with the wall thickness. In patients with diffuse lung disease (diffuse histoplasmosis, miliary tuberculosis, Letterer-Siwe disease, and allergic alveolitis), each disease appeared different on the MR images. These preliminary studies indicate that magnetic resonance imaging is effective for identifying pulmonary disease in children and may improve the radiologist's ability to differentiate pulmonary disorders.

Adolescent↗

Technique and use of transbronchial biopsy in children and adolescents.

Since July 1988, a total of 92 transbronchial biopsies (TBB) have been performed in 18 patients (aged 3-16 years). Twelve patients (67%) were heart-lung transplant (HLT) recipients undergoing surveillance for pulmonary graft rejection and infection. The remainder included immunocompromised patients at risk of opportunistic infections (n = 4), patients with fibrosing alveolitis (n = 1) and a collagen vascular disorder with suspected lung involvement (n = 1). TBB was performed through either a fiberoptic (n = 50) or a rigid (n = 41) bronchoscope, all under general anesthesia. On one occasion a cardiac bioptome was used through an endotracheal stent. The sensitivity of TBB for diagnosing acute and chronic rejection in HLT patients was 88% and 60%, respectively (specificity, 91% and 100%). Definitive diagnoses were made in 4 (67%) of the non-HLT group. Bronchoalveolar lavage (BAL) was performed during each procedure for microbiological and cytological examination. Thirty-four pathogenic organisms including Pseudomonas aeruginosa (16/34), Staphylococcus aureus (8/34), and Candida albicans (5/34) were isolated from BAL culture. Complications included pneumothorax (8%), transient pyrexia (7%), and dyspnea (2%).

Acquired Immunodeficiency Syndrome↗

Pulmonary aspergillosis masquerading as progressive post-transplant lymphoma.

We report a patient with post-transplant lymphoma who was treated by renal allograft nephrectomy, discontinuation of immuno-suppressive therapy, and initiation of acyclovir administration. Despite these measures he appeared to have progressive lymphoma. Had a biopsy and cultures not been done, the diagnosis of aspergillosis would have been missed and the patient might have been treated with chemotherapy, with a potentially lethal outcome. Data from the Cincinnati Transplant Tumor Registry indicate that of 662 patients treated for posttransplant lymphoma, 277 patients died of cancer and 137 died of other causes, of which infection was a major factor. This case emphasizes the importance of proper work-up of patients with apparently progressive lymphomas.

Adolescent↗

The gamut of progressive pulmonary paracoccidioidomycosis.

Paracoccidioidomycosis is an important Latin American endemy. The lung is the portal of entrance of the infection and the lesions are confined to this organ in, at least, 30 per cent of the progressive cases. Twelve case histories of patients with the progressive pulmonary form are presented in order to illustrate the repetitious clinical manifestations but the large variety of radiological presentations. The mycologic diagnosis is also emphasized.

Adult↗

Diagnosis of bronchopulmonary infections by quantification of microflora.

The quantification of bacteria and fungi in sputum or bronchoaspirate is of clinical value for the diagnosis of respiratory tract infections. We have developed an easy method to count the micro-organisms in patients with respiratory tract infections. This consists of the quantification of micro-organisms by subsequent streakings of a calibrated loop on agar. The correlation between microbiological quantitative data and the clinical status of patients with lower respiratory tract infections is discussed. The data seem to indicate that certain bacteria present in sputum or bronchoaspirate above a certain concentration may be responsible for lower respiratory tract infections. In patients with immunological disorders or chronic pathologies even lower concentrations of micro-organisms in bronchial secretions probably are enough to cause infections. The advantage of this counting method of the microbic species from the respiratory tract consists of their quantification: thus we can attribute an etiological role to a high concentration of the germs, while micro-organisms at low concentrations are probably contaminants. By this method isolated colonies are obtained after 12-18 hours. The bacterial quantification, by respiratory samples examination of the same patient in the following days, allows us to evaluate the efficacy of antibacterial therapy, producing a reduction of bacterial concentration.

Acquired Immunodeficiency Syndrome↗

Multifocal thoracic actinomycosis simulating lymphoma.

Thoracic actinomycosis is rare in the pediatric age group. We report the unusual case of a 10-year-old girl who presented with prolonged fever and weight loss with a neck mass and multiple pulmonary nodules resembling lymphoma. Open lung biopsy confirmed the diagnosis of actinomycosis and the symptoms and signs improved after treatment with cephalosporin. The pathogenesis and radiographic manifestations are briefly discussed.

Actinomycosis↗

Arterial embolization to preoperatively manage pulmonary disease associated with inflammation.

Preoperative arterial embolization is used in pulmonary disease to reduce intraoperative blood loss resulting from exposure of extensive adherent pleura due to repeated inflammation. Between January 1996 and February 2001, 5 patients underwent surgery with this procedure. Underlying diseases were 3 cases of aspergilloma and 1 each of chronic expanding hematoma and lung cancer. All embolization was permanent, involving coil insertion. Surgical treatment was successful in all 5 patients without mortality. Such preoperative management proved useful in reducing intraoperative blood loss in hypervascular collateral feeding vessels in the area of resection or decortication.

Aged↗

Resected early lung cancer with pulmonary aspergilloma.

Pulmonary aspergillosis and lung cancer rarely occur simultaneously. We report a 66-year-old man with a round shadow in the thin-wall cavity of the right upper lobe. Radiological findings and transbronchial biopsy revealed squamous cell carcinoma complicated by aspergilloma at the site. Right upper lobectomy suggested that early lung cancer arose from preexisting lung scars containing an aspergilloma.

Aged↗

[Radiologic diagnosis of lung tuberculosis].

The radiologic knowledge of tuberculosis-associated lung disease is an essential tool in the clinical diagnosis of tuberculosis. Chest radiography is the primary imaging method, but the importance of CT is still increasing, as CT is more sensitive in the detection of cavitation, of hilar and mediastinal lymphadenopathie, of endobronchial spread and of complications in the course of the disease. In addition, CT has been proven as a valuable technique in the assessment of tuberculosis activity, especially in patients where M. tuberculosis has not been detected in the sputum or in patients with multidrug-resistant tuberculosis. Depending on the immune status of the patient, the morphologic spectrum of tuberculosis is quite variable. Early diagnosis of tuberculosis is essential to prevent further spread of the disease.

Adult↗

Correlation between high-resolution computed tomographic, magnetic resonance and pathological findings in cases with non-cancerous but suspicious lung nodules.

Computed tomography scans, including thin-section high-resolution computed tomography (HRCT), occasionally fail to differentiate between small non-cancerous nodules from lung cancers. We describe nine such lesions ( < 20 mm in diameter) initially identified through our screening program for lung cancer using CT scanning. Pathological diagnoses included nodular fibrosis (n = 4), granuloma (n = 1), cryptococcoma (n = 1), localised organising pneumonia (n = 1), inflammatory pseudo-tumour (n = 1) and sclerosing haemangioma (n = 1). High-resolution CT findings, together with MRI findings with contrast-enhanced dynamic studies, were retrospectively evaluated. Additional cases should be identified and radiologically characterised in order to reduce the number of non-cancerous tumours that are treated by unnecessary surgery.

Aged↗

Aspergillus infection of the respiratory tract after lung transplantation: chest radiographic and CT findings.

The objective of our study was to assess radiographic and CT findings in lung transplant patients with evidence of Aspergillus colonization or infection of the airways and correlate the findings with clinical, laboratory, bronchoalveolar lavage, biopsy and autopsy findings. The records of 189 patients who had undergone lung transplantation were retrospectively reviewed for evidence of Aspergillus colonization or infection of the airways. Aspergillus was demonstrated by culture or microscopy of sputum or bronchoalveolar lavage fluid or histologically from lung biopsies or postmortem studies in 44 patients (23 %). Notes and radiographs were available for analysis in 30 patients. In 12 of the 30 patients (40 %) chest radiographs remained normal. In 11 of 18 patients with abnormal radiographs pulmonary abnormalities were attributed to invasive pulmonary aspergillosis (IPA) in the absence of other causes for pulmonary abnormalities (8 patients) or because of histological demonstration of IPA (3 patients). In these 11 patients initial radiographic abnormalities were focal areas of patchy consolidation (8 patients), ill-defined pulmonary nodules (2 patients) or a combination of both (1 patient). In some of the lesions cavitation was demonstrated subsequently. At CT a "halo" of decreased density was demonstrated in some of the nodules and lesion morphology and location were shown more precisely. Demonstration of Aspergillus from the respiratory tract after lung transplantation does not necessarily reflect IPA but may represent colonization of the airways or semi-invasive aspergillosis. The findings in patients with IPA did not differ from those described in the literature in other immunocompromised patients, suggesting that surgical disruption of lymphatic drainage and nervous supply or effects of preservation and transport of the transplant lung do not affect the radiographic appearances.

Adult↗

The role of the Aspergillus fumigatus areA gene in invasive pulmonary aspergillosis.

The areA gene of Aspergillus nidulans is a positive-acting transcriptional factor required for the expression of genes involved in the utilization of a broad range of nitrogen sources other than ammonium and glutamine. We have investigated the role in pathogenesis of the corresponding gene (AfareA) of Aspergillus fumigatus, a causative agent of invasive pulmonary aspergillosis. Stable and unstable AfareA- strains were constructed and tested for altered virulence in mice on the basis of host survival, mixed infection experiments and genetic reversion studies. These showed that the AfareA gene contributes to, but is not essential for, virulence. Strains carrying extragenic mutations that partially suppress the AfareA- phenotype for growth on different nitrogen sources were tested for altered virulence in mixed infection studies. One of these was found to be more virulent than the parental AfareA- strain.

Animals↗