Case Of Pulmonary Aspergillosis Research Articles

Bronchopulmonary Aspergillosis Associated with Acute Myocardial Infarction in Dog

Background: Fungi of the genus Aspergillus are ubiquitous microorganisms of opportunistic character, of which animals and humans are continually exposed. Are described three main forms of aspergillosis in dogs: nasal, disseminated and bronchopulmonary. This form which is restricted to the lung parenchyma is considered rare in dogs. The aim of this paper is to report a case of pulmonary aspergillosis associated to acute myocardial infarction in a dog, focusing on epidemiological, clinical, pathological and immunohistochemical characteristics. Case: A male dog, 4-year-old, Pinscher, clinically presented dyspnea, anorexia, vomiting, concentrated urine and dark and mollifed faeces. On physical examination, there were congested oral and conjunctival mucosas, dehydration and petechiae in the outer ear. The animal died fve days after the clinical attendance and was sent for necropsy. The macroscopic lesions were restricted to the lung, heart and liver. There were multifocal areas of consolidation in the lung parenchyma and yellowish content in the trachea and bronchi lumen. The heart was rounded and with pale areas in the myocardium. Liver was discreet accentuation of the lobular pattern. Histologically the lesion was characterized by pyogranulomatous and necrotizing bronchopneumonia, multifocal to coalescing, moderate, associated with myriads of intralesional hyphae consistente with Aspergillus spp., associated with acute myocardial infarction. The hyphae weakly stained basophilic by hematoxylin and eosin were strongly impregnated by Grocott’s methenamine silver nitrate and showed strong immunolabelling of the cytoplasm, which were evidenced in brown. There were areas of acute myocardial infarction and hepatocellular degeneration and congestion in the liver, although fungal hyphae were not observed in these tissues. Discussion: The diagnosis of pulmonary aspergillosis was established based on the morphological and tinctorial characteristics of the agent and confrmed by immunohistochemistry. In this case, is not included in the clinical history any conditions that could promote immunosuppression, neither were observed morphological changes in the pathological examination which suggested other intercurrent diseases. It is likely that the dog has been exposed to the inhalation of large amounts of conidia for a long period of time, condition that favors the occurrence of the disease, even in immunocompetent animals. Probably were not evidenced severe respiratory clinical signs, that characterize the pulmonary impairment, due to the shortcourse of the disease. The pyogranulomatous and necrotizing inflammatory reaction is typical of fungal infection and was restricted to the lung parenchyma. The areas of coagulation necrosis observed in the myocardium are probably secondary to vascular injury caused by the fungi, with subsequent thromboembolism, ischemia and infarction. In Brazil, there are few reports of aspergillosis in dogs, have been reported the nasal and systemic forms. In the world literature, there are few reports about this bronchopulmonary form of the disease. Although uncommon, pulmonary aspergillosis should be considered in the differential diagnosis of diseases that affect the lower respiratory tract of dogs, as well as it’s systemic complications resulting from angioinvasive characteristic of the fungus, which in this case was determinant to the death of the animal. Keywords: Aspergillus, fungal disease, respiratory tract

Invasive Fungal Infections After Kidney Transplantation: A Single-center Experience

IntroductionInvasive fungal infections (IFI) affecting transplant recipients are associated with increased mortality and graft dysfunction. ObjectiveDescribe the frequency, clinical features, and outcomes of IFI (except pneumocystis infection) in kidney transplant recipients. MethodSingle-center descriptive study including every kidney transplant recipient with a culture-proven or probable IFI between 2003 and 2013, according to the EORTC-MSG criteria. ResultsWe identified 45 IFI. There were 13 cases of invasive candidiasis (C. albicans: 6 and non–C. albicans candidial spp.: 7), 11 cases of pulmonary aspergillosis (A. fumigatus: 9 and A. flavus: 2); 11 cases of subcutaneous mycosis (Alternaria spp.: 9, Paecilomyces spp.: 1, and Pseudallescheria spp.: 1); 7 cases of cryptococcosis; 2 cases of pneumonia by non-Aspergillus molds (Mucor spp.: 1 and Cunninghamella spp.: 1); and 1 case of Geotrichum capitatum pneumonia. All patients were recipients from deceased donors. Six cases occurred in the first 3 months post-transplant, 15 cases between the third and twelfth months, and 21 cases after the twelfth month. Treatment options were fluconazole for Candida infections, voriconazole or caspofungin for aspergillosis, liposomal amphotericin for cryptococcosis, and itraconazole plus excision or cryotherapy for subcutaneous mycosis. Fifteen patients died (33%). Mortality rates were 15% for invasive candidiasis, 45% for aspergillosis, 71% for cryptococcosis, 100% for non-Aspergillus molds and G. capitatum pneumonia, and 0% for subcutaneous mycosis. Six patients who survived (14%) started regular hemodialysis. ConclusionIFI still have a high mortality and morbidity in kidney transplant recipients, as verified in this report. We reinforce the need for a high index of suspicion and prompt treatment.

Calcium oxalate in the sputum may aid in the diagnosis of pulmonary aspergillosis: A report of two cases

We present two cases of pulmonary aspergillosis in which calcium oxalate crystals in the sputum proved to be a useful diagnostic clue. In case 1, Aspergillus hyphae was not identified; however, calcium oxalate crystals were present, and chronic necrotizing pulmonary aspergillosis was diagnosed. In case 2, calcium oxalate was detected and Aspergillus fumigatus was identified later. Thus, the presence of calcium oxalate in the sputum may be an important indicator for an A. fumigatus infection.

Comparison of the Count Regression Models in Evaluation of the Effects of Hazelnut Harvest Season Variations on Pulmonary Aspergillus

Pulmonary aspergillosis has recently emerged as a worldwide health care problem especially in patients with underlying lung disease. The objective of this study was to compare the Poisson and COM-Poisson regression models and to find the best fitted model for determining the effect of hazelnut harvest season on pulmoner aspergillosis. The data obtained from the state hospital of our cityin the time period of two years, from September, 2012 to August, 2014. A retrospective study was conducted. Respiratory specimens which showed repeated isolation of Aspergillus were included in the study however only one of the samples was analysed. Cases were classified according to revised definitions given by European Organization for Research and Treatment of Cancer/Invasive Mycosis Study Consensus Group (EORT/MSG). Culture positive 36 patients were detected from 3457 patients. Poisson and Conway-Maxwell- Poisson (COM-Poisson) regression models were compared to determine the best fitted model for identifying the number of new pulmonary aspergillosis cases in hazelnut harvest season. To describe the best fitted model of count data, dispersion, deviance and Akaike Information Criteria (AIC) test statistics were used. Based on statistical test for dispersion, the under-dispersion was found non-significant. This results clearly indicate that Poisson regression model is more approtiate for pulmonary aspergillosis data when compared to COM-Poisson regression model. Deviance and AIC values also confirm this result. Poisson regression model and COM- Poisson regression model were compared with statistical tests. According to statistical tests Poisson regression model was found to be the best fit model for pulmonary aspergillosis data.

Apergillosis Pulmonar (Información de dos casos)

Informamos acerca de dos casos de aspergillosis pulmonar encontrados en el Sanatorio de Bravo Chico, uno de ellos en un caso de autopsia y el otro en una pieza quirúrgica pulmonar.

Aspergillosis in a rescued Himalayan griffon vultureGyps himalayenensis: A case study

A rare case of pulmonary aspergillosis was documented in a Himalayan griffon vulture with characteristic gross and histopathological lesions in lung and air sacs. Gross changes were observed in lungs and air sacs with yellowish white nodules of 0.5–3mm in diameter including thickening of air sacs. Histopathologically, multifocal caseous necrotic areas, inflammatory cellular infiltrations, presence of fungal hyphae and fibrous tissue proliferation in lungs and air sacs were observed. The characteristic hyphae of Aspergillus spp. were demonstrated in the nodules of lung in histopathological sections stained by Gridley's and H & E staining method.

Fatal Invasive Aspergillosis in Acute Lymphoblastic Leukemia Patient

Invasive aspergillosis (IA) is one of the most common fungal infections in immunocompromised patients. Is an air-borne disease and the majority of patients develop pneumonia or sinusitis. However central nervous system (CNS) aspergillosis may also occur. Infections by Aspergillus fumigatus are most prevalent although in recent years, non-fumigatus Aspergillus species such as A. flavus has become common as causal agents this mycosis. The major risk factors associated include neutropenia, hematological malignancy,andtransplantation of hematopoietic stem cells and solid organs. Therefore, here we report a fatal case of pulmonary aspergillosis and CNS due Aspergillus flavus in neutropenic patient with acute lymphoblastic leukemia. The diagnosis of pulmonary infection was based in the isolation of A. flavus in tracheal secretions associated with the pulmonary infiltration detected in the Chest X-ray. Because of the thrombocytopenia the CNS aspergillosis was diagnosed only by brain magnetic resonance imaging. This case underscores the Importance of IA as a serious disease and late diagnosis leading to a poor prognosis with fatal course due to worsening clinical.

Spontaneous pneumothorax associated withAspergillusbronchopneumonia in a dog

AbstractObjectiveTo describe a case of pulmonary aspergillosis in a previously healthy dog that manifested as a spontaneous pneumothorax.Case SummaryA 3‐year‐old neutered male mixed‐breed dog was presented with inappetence and respiratory distress. Thoracic radiography revealed a right‐sided pneumothorax. Following stabilization, thoracic computed tomography found 1 large and many small pulmonary blebs in the right caudal lung lobe. The dog underwent a right lateral thoracotomy, identifying numerous emphysematous regions in the right middle lung lobe, and a right middle lung lobectomy was performed. Histopathologic examination of the resected lung lobe revealed severe, diffuse bronchopneumonia with necrotizing pleuritis and the presence of fungal organisms strongly suggestive ofAspergillussp. Surgical removal of the affected lung lobe and continued medical treatment with itraconazole resolved the dog's clinical signs.New Information ProvidedThis report describes the successful surgical and medical management ofAspergillusbronchopneumonia in a dog presenting with spontaneous pneumothorax.

Pulmonary aspergillosis: Atypical presentation in immunocompetent individuals

Aspergillosis, an opportunistic infection, is a major cause of morbidity and mortality in immunocompromised patients. But, Aspergillus is also known to cause Pulmonary aspergillosis in immunocompetent host too. Only few cases have been reported in literature of Aspergillosis in Immunocompetent individuals so far. Here, we report 4 different cases of Pulmonary Aspergillosis , who have presented with acute symptoms.The possibility of pulmonary mycosis needs to be considered in patients with acute pulmonary symptoms like breathlessness , hemoptysis, etc with signs of infection even in immunocompetent individuals, without underlying pulmonary disease.

Clinico-Microbiological Profile of Chronic Pulmonary Aspergillosis from a Tertiary Care Centre in Southern India

Pulmonary aspergillosis is commonly seen in immunocompromised individuals. A significant rise has been seen in these cases in the past decade, owing to growing number of patients with impaired immune status. This study includes the detailed clinical and microbiological profiles of all the culture positive cases of pulmonary aspergillosis, detected in three years, from Jan 2008-Dec 2010, at our tertiary care centre. A hospital based observational and retrospective study was conducted to study the clinico-microbiological characteristics of patients with pulmonary aspergillosis. Respiratory specimens which showed repeated isolation of Aspergillus were included in the study. Demographic details, clinical findings and predisposing factors were noted down for all the patients. Treatment of patients with antifungal agents and their responses to treatment were also documented. There were 22 patients with male to female ratio of 1.2:1 and mean age of 52.5 years. The most common underlying lung disease was presence of bronchial asthma in 27.3% (6/22) cases. Many patients (40.9%; 9/22) were on steroid treatment. Cough with expectoration was the most common symptom observed in 72.7% (16/22) cases. Microbiologically, microscopy showed positivity for the presence of gram positive, acutely branched, fungal hyphae, suggestive of Aspergillus, in all the cases. Aspergillus fumigatus was the predominant species that was isolated in 40.9% (9/22) cases. All the diagnosed patients were given either oral itraconazole or intravenous amphotericin B. A clinical improvement was observed in 72.5% (16/22) cases, but 27.3% (6/22) patients died. Pulmonary aspergillosis presents with non-specific clinical and radiological findings. An early suspicion and diagnosis is essential, especially in patients with underlying lung disease, to prevent dissemination and invasion.

An Autopsy Case of Pulmonary Aspergillosis with Fungus Ball Formation in an Artificial Aortic Graft

A 38-year-old man with Marfan syndrome underwent an aortic replacement with an artificial aortic valve at 27 years of age and an aortic graft at 31 years of age. In 2011, he was diagnosed as having chronic necrotizing pulmonary aspergillosis (CNPA). He developed a fever and an increased sputum volume and was admitted to the hospital in 2012. Contrast-enhanced CT showed an irregularly shaped nonenhanced structure in the aortic graft. He died on hospital day 31. From the autopsy findings, we speculated that an infiltration by the CNPA lesion into a pulmonary vein was followed by the hematogenous formation of a fungus ball in the aortic graft.

Spirohexalines, new inhibitors of bacterial undecaprenyl pyrophosphate synthase, produced by Penicillium brasilianum FKI-3368

An enzyme assay for bacterial undecaprenyl pyrophosphate (UPP) synthase was performed to screen microbial culture broths for inhibitors of UPP synthase. During the course of this screening program, an EtOH extract of a rice culture of Penicillium brasilianum FKI-3368 was found to inhibit UPP synthase activity. From activity-guided purification, a new compound-designated spirohexaline was isolated together with the structurally related and known viridicatumtoxin by ethyl acetate extraction silica gel and octadecylsilane column chromatographies and high-performance liquid chromatography. The structure of spirohexaline was elucidated by spectroscopic analysis, including NMR. Spirohexaline and viridicatumtoxin have a common hexacycline structure produced by fusion of a tetracycline-type ring with a spiro-type ring. They inhibited UPP synthase activity with IC₅₀ values of 9.0 and 4.0 μM, respectively.

空洞性腫瘤を呈し肺真菌感染を伴った肺腺癌の1切除例

空洞性腫瘤を呈し肺真菌感染を伴った肺腺癌の1切除例

Retrospective Review of Invasive Fungal Disease in a Cohort of Patients with Acute Leukemia

Abstract 4265 Background:Invasive fungal disease (IFD) is a significant cause of morbidity and mortality in patients with acute leukemia (AL). Fluconazole has an established role for prophylaxis in the setting of allogeneic hematopoietic stem cell transplant (AHSCT), and possibly in the setting of acute leukemia. More recently, posaconazole has been shown to reduce the incidence of IFD and mortality in AHSCT recipients, and in patients undergoing chemotherapy for acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS). However, with increasing use of broader-spectrum antifungal agents, there are concerns regarding breakthrough infections with resistant organisms. Objectives:The first goal of this study is to define the epidemiology of IFD in all patients with acute leukemia, treated at one academic center (The Ottawa Hospital). The second goal is to identify risk factors, which could stratify patients into a very high risk category for the development of IFD. We hope to identify a subset of patients who would benefit from prophylaxis with broader-spectrum antifungal agents. Methods:We performed a retrospective study of adult patients with acute leukemia (including AML, acute lymphoblastic leukemia (ALL), high-grade MDS and blast-phase CML) treated at our institution between May 2009 and April 2011. Patients at all stages of treatment were included. All patients treated with antifungal agents were identified through our pharmacy database. Computerized medical records were reviewed for baseline demographics (age, gender, occupation, diagnosis, days of neutropenia and comorbidities), as well as treatment-related variables (chemotherapy regimen, conditioning regimen, date of AHSCT, response to treatment and presence of GVHD). Imaging, microbiology and biopsy results were also collected. Proven and probable IFD were defined as per the 2008 EORTC/MSG revised criteria. Patient characteristics were compared using Fisher's exact test. Results:We identified 89 inpatient encounters. Primary diagnosis was AML in 58, high-grade MDS in 15, ALL in 12, blast-phase CML in 3 and PCL in 1 patient. 42 patients were undergoing induction chemotherapy and 10 were undergoing consolidation. 30 patients were post-AHSCT. Contrary to prior studies, all patients were on fluconazole prophylaxis. Out of these 89 encounters, 8 patients (9%) were diagnosed with proven or probable IFD, 12 (13%) met criteria for possible IFD, and the rest (69/89 or 78%) did not meet criteria for IFD. There were 5 probable cases of pulmonary aspergillosis, 1 proven case of hepatic aspergillosis, and 2 proven cases of zygomycosis (1 disseminated and 1 CNS).In terms of risk factors, in our initial analysis, median age was higher in patients with IFD than in patients without (62 vs. 57), though this difference did not reach statistical significance (p = 0.46). There was no difference in the development of IFD based on gender, occupation, days of neutropenia or comorbidities. Although this did not reach statistical significance, almost all patients with IFD had an underlying diagnosis of AML (7/8). In addition, no patients were diagnosed with IFD during consolidation therapy. This is consistent with prior studies. We were not able to assess transplant-related variables, given that only one IFD was diagnosed in a post-AHSCT patient.Overall mortality at 30 days post-admission was significantly higher in the IFD group (6/8 vs. 28/81, p = 0.05). However, only 1 death was directly attributable to the IFD. Otherwise, 3/8 patients with IFD died of refractory leukemia (1 post-AHSCT), 1/8 died of leukemia, 1/8 died of multiorgan failure (not clearly related to IFD), 1/8 survived hepatic aspergillosis and 1/8 survived disseminated mucormycosis. Conclusions:Though limited by sample size, our study indicates that older patients, patients with AML, patients undergoing induction chemotherapy and patients with refractory leukemia may be at highest risk for IFD. In addition, in our cohort, almost all patients with IFD died of their underlying leukemia, while being treated for IFD. It is not clear at this time, but suggestive, that the diagnosis of IFD delayed or interfered with the ongoing treatment plan for some of these patients, possibly contributing to their treatment failure. Therefore, the use of novel antifungal agents would be favored in this group to avoid interruption of leukemia treatment. Further study of this group is currently underway. Disclosures:No relevant conflicts of interest to declare.

121 Incidental extra-cardiac findings on clinical cmr; a comparison of 3 haste techniques

Introduction Cardiac magnetic resonance (CMR) is an increasingly important imaging modality, which by necessity incorporates a large field of view. Both “localiser” and multiple slice half-fourier spin echo (eg, HASTE) sequences provide coverage of the thorax and upper abdomen. Such imaging may reveal hitherto unexpected incidental extra-cardiac findings (IEF). First we sought to assess the frequency of IEF found on clinically indicated CMR scans. Second we compared the 3 clinically used HASTE acquisition protocols in this context. Lastly we determined the impact of the 3 different protocols on acquisition time and image quality. Methods Three subsequent groups of 238 patients (714 patients in total), all referred for clinically indicated CMR, were scanned with either breath-hold (BH) HASTE (Group 1), free breathing (FB) HASTE (Group 2) or diaphragmatic navigated (NAV) HASTE (Group 3). Additionally “localiser” sequences performed in 3 orthogonal planes were analysed. All 714 clinical reports were reviewed regarding the presence of IEF. These were categorised as either minor, or major if recommendations for further investigation, follow-up, and/or clinical correlation were made. Finally, to determine the impact of each HASTE protocol on acquisition time and image quality, an additional cohort of 15 patients underwent 3 protocols back to back in a random fashion. The length of each acquisition was timed and image quality was reviewed and scored externally. Results A total of 180 IEF were found in 162 (22.7%) out of 714 patients. There was no significant difference in frequency of IEF between the 3 HASTE groups. Out of 180 IEF, 88 were considered minor and 92 major findings. Of the latter, 8 (1.1%) were considered highly significant. These included one bronchoalveolar carcinoma stage 1B requiring lobectomy, 2 cases of florid sarcoidosis in patients presenting with VT and “structurally normal hearts” on echocardiography, one case of pulmonary aspergillosis, 2 cases of advanced pulmonary fibrosis, one ascending thoracic aortic aneurysm and a case of iatrogenic liver haemorrhage following placement of a pericardial drain. FB HASTE acquisition (69±2.5 s) was significantly faster than BH (105±3.8 s) and NAV (121±2.7 s), p Conclusion Overall, IEF are common and lead to follow on investigations in a substantial minority of cases. However, the overall incidence of highly significant findings in the current study was low (∼1%). There was no difference in the frequency of incidental extra-cardiac findings between the 3 HASTE protocols. While the free breathing HASTE technique is statistically significantly faster than breath hold and navigated HASTE, the absolute time saving is small and probably out-weighted by lesser image quality.

Cytarabine and Etoposide (CYVE) as First-Line Therapy for Primary Central Nervous System Lymphoma

AbstractAbstract 4895 Background:The treatment of primary central nervous system lymphoma (PCNSL) is characterized by high rates of toxicity and intracranial relapse despite initial response. High-dose methotrexate (HD-MTX), with or without cranial irradiation, has become the standard of care; combining this with other chemotherapeutic agents has improved complete remission rates but at the expense of increased treatment-related adverse events, particularly haematologic and neurologic toxicity. Cytarabine has been used in combination with etoposide (CYVE) as a salvage therapy for patients who have been refractory to or relapsed after HD-MTX-based regimens (Soussain C et al, J. Clin. Oncol. 2001; Soussain C et al, J. Clin. Oncol. 2008). In these studies, cytarabine was given as an infusion at a dose of 50mg/m2/d over 12 hours on days 1–5, and at a dose of 2g/m2/d over 3 hours on days 2–5 with etoposide at 200mg/m2/d on days 2–5. Both responders and non-responders were eligible to proceed to autologous stem cell transplant (autoSCT) using a conditioning regimen of thiotepa 250mg/m2/d on days -9 to -7, busulfan 10mg/kg total dose po or 8mg/kg total dose iv over days -6 to -4, and cyclophosphamide 60 mg/m2/d on days -3 to -2. Median OS was 58.6 months in patients able to undergo autoSCT, but with significant neurotoxicity that may have been related in part to prior therapies. Methods and Results:Given its excellent CNS penetration, CYVE may be an effective regimen in previously untreated patients, with lower risk of neurotoxicity. We have used CYVE as a first-line therapy for patients with PCNSL who are potentially eligible for subsequent autoSCT. Between January 1, 2005 and December 31, 2009, 7 patients with a diagnosis of PCNSL were treated with first-line CYVE using the regimen described above. All were HIV negative, showed no disease outside of the CNS on bone marrow biopsy and staging CT or PET scan, and had biopsy-proven PCNSL with diffuse large B-cell histology. Median age was 55 (42-61) with 4 female and 3 male patients. Median International Extranodal Lymphoma Study Group Prognostic Index score was 2 (0-2), although in actuality may have been higher, as 4 patients were not able to undergo lumbar puncture at diagnosis. ECOG status was < 2 in 3 patients, ≥ 2 in 3 patients, and not documented in 1 case. Patients received a median of 2 cycles of CYVE (1-3), with 2 receiving concurrent rituximab and the 1 patient with intra-ocular lymphoma receiving post-adjuvant orbital radiation. No cranial radiation was administered. Five patients achieved CR and proceeded to autoSCT. Two patients had a PR but later died of progressive disease at day +48 and day +117, respectively. In both cases, however, the patients were suspected of having disease long before they were treated with CYVE. The first had presented 3 years prior to the diagnosis with a solitary brain lesion that resolved with decadron monotherapy before pathologic documentation. The second had had a brain biopsy that failed to show malignant disease 4 months before the PCNSL diagnosis was confirmed and treatment initiated. Median OS and PFS for the group have not yet been reached with mean follow-up of 657 days. Among the 5 patients who achieved CR, all patients remain alive in CR with a mean follow-up of 841 days (320-1262 days), or 28 months. Toxicities included at least 1 episode of febrile neutropenia in all 7 patients, 2 possible but unconfirmed cases of pulmonary aspergillosis, 2 cases of drug-induced hepatitis (with ALT > 3x ULN), 1 case of toxic epidermal necrolysis secondary to imipenem use during an episode of febrile neutropenia, 1 small bowel obstruction requiring surgical intervention, and 1 case of late grade 2 neurotoxicity presenting 3 years after treatment. Conclusions:In this small cohort of patients, first-line CYVE has shown to be highly effective (ORR 100%, CR 71%) with minimal long-term toxicity compared to that which is seen using it as a salvage therapy. When followed by autoSCT, long-term survival with preserved quality of life may be possible. A prospective study would be necessary to confirm these initial results in practice. Disclosures:No relevant conflicts of interest to declare.

イトラコナゾールカプセルの吸収における黒酢の効果についての検討

Itraconazole (ITCZ), a useful oral drug effective against Aspergillus, is reported to cause insufficient blood concentration through unstable enteral absorption. Hypoacidic gastic conditions have been reported to reduce absorption, whereas acidic drinks promote it. We present a case of pulmonary aspergillosis in a subject administered ITCZ with black vinegar, a popular health food in Japan. The 59-year-old man showed high blood concentrations of ITCZ, resulting in good Aspergillosis control. To confirm the efficacy in black vinegar on absorbing ITCZ, we administered ITCZ capsules with and without black vinegar to 10 healthy adults after preparation with a proton pump inhibitor to decrease gastric acidity, and measured blood concentrations of ITCZ and the metabolite OH-ITCZ. Administration of this combination increased ITCZ and OH-ITCZ Cmax significantly. For patients who produce too little gastric juice, black vinegar could thus serve to promote ITCZ capsule absorption.

Rituximab Increases Response to ESHAP in Relapsed, Refractory, and Transformed Aggressive B-Cell Lymphoma.

Background: Patients with relapsed or refractory aggressive B-cell lymphoma, or transformed indolent lymphoma can achieve long-term survival with high dose therapy and autologous stem cell transplant (HDT/ASCT), provided their disease is sensitive to salvage chemotherapy. Unfortunately, approximately 50% of patients are insensitive to standard salvage regimens.Objectives: This trial investigated whether adding Rituximab to ESHAP (etoposide, solumedrol, cytosine arabinoside, cisplatin) induction improved chemosensitivity. The primary outcome was overall response rate (CR + CRu + PR) to R-ESHAP. Secondary outcomes were toxicity, ability to undergo ASCT, progression free survival (PFS) and overall survival (OS).Methods: The protocol was approved by the local ethics review board and all patients provided informed consent. Eligible patients received ESHAP every 28 days with GCSF support until < 15% bone marrow involvement was achieved (2–4 cycles). Rituximab was given weekly x 8 weeks concurrent with the first 2 cycles of ESHAP. GCSF mobilized stems cells were collected on day 10–11 of cycle 1 or 2.Results: The trial was stopped early after the complete response (CR) rate at a planned interim analysis exceeded 40% (a pre-specified criteria for stopping the trial). Final results of 26 patients are presented. Median age was 55.5 years (range 42–64). Twelve patients had relapsed aggressive lymphoma, 2 had refractory disease and 12 had transformed indolent lymphoma. Twenty-two of 26 patients were stage III/IV. The overall response rate to R-ESHAP was 92% (95% CI 82% to 100%). Twelve patients (46%; 95% CI 27% to 65%) had a CR or unconfirmed CR. Grade 3–4 thrombocytopenia, neutropenia, and anemia occurred in 57%, 40%, and 15% of R-ESHAP cycles respectively. Grade 3–4 infections complicated 7% of cycles. Median follow-up was 17 months (range 2.9 to 43.2) from enrollment. Twenty-three of 26 patients (88%) were transplanted. Notable post-transplant toxicity included 5 cases of herpes zoster, 2 cases of bacterial pneumonia, 1 case of pulmonary aspergillosis, and 1 fatal case of pneumocystis carnii pneumonia (PCP). Three patients did not proceed to HDT/ASCT; 2 were refractory to R-ESHAP and 1 died of a myocardial infarction after induction chemotherapy but prior to ASCT. Fifteen of 23 patients who received ASCT remain in remission, 6 have relapsed. Seven patients have died, 4 of progressive disease, 1 of myocardial infarction, 1 of PCP, and 1 of accelerated Parkinson's Disease. Median PFS and median OS have not yet been reached.Conclusions: In this single-arm, phase II study of relapsed or refractory aggressive B-cell lymphoma and transformed indolent B-cell lymphoma, R-ESHAP induction therapy resulted in a very high ORR (92%) and enabled a large percentage of patients (88%) to proceed to HDT/ASCT. Toxicity of the R-ESHAP regimen was acceptable, and its efficacy compared favorably with other salvage regimens reported in the literature, including R-ICE.

慢性型肺アスペルギルス症の臨床的検討およびエラスターゼ阻害物質の検討

We studied the clinical features of 59 chronic pulmonary aspergillosis cases (aspergilloma, chronic necrotizing pulmonary aspergillosis) which we experienced in our hospital. To diagnose this disease, X-rays, sputum culture and serologic tests were mainly examined, X-ray findings were a fungus ball type in 47% of cases and thickened wall of a cavity type in 32%. Positive sputum culture found was A. fumigatus 78%, A. niger 13% and A. flavus 2%. Positive rates of serologic tests showed precipitating antibody 81% and antigen 11%; 39% of beta-D glucan exceeded the reference value. As clinical symptoms, bloody sputum and hemoptysis were found at high frequency. Antifungal agents were administered intravenously or topically for treatment, primarily AMPH-B, ITCZ and MCFG. As adjuvant therapy, we administered Ulinastatin which is an elastase inhibitor for use against hemoptysis, and we performed steroid combination for cases considered to be associated with allergy. In all of 6 cases of chronic necrotizing pulmonary aspergillosis which were administered MCFG, X-ray findings improved. A pathogenic factor, elastase was isolated from Aspergillus spp., and we also found the elastase inhibitor from this series. Five of 12 strains of A. fumigatus, and one of 2 strains of A. flavus expressed elastase inhibitory activity when we screened for the culture supernatant of various Aspergillus spp. of a clinical isolate. Elastase inhibitory activity from A. niger was very weak. Culture supernatants from 5 strains of A. fumigatus and one strain of A. flavus were stable for a fever, and human leucocyte elastase was inhibited, but these did not inhibit porcine pancreas elastase. We are aiming at clinical application and plan to continue further study.

Epidural mass due to Aspergillus flavus causing spinal cord compression - A case report and brief update

Aspergillus infection of the central nervous system (CNS) is an uncommon disease. Most of the reported cases are of sinocranial spread and cases with contiguous spread to spinal cord from lung and other organs are uncommon. A case of pulmonary aspergillosis with extension to thoracic vertebrae forming a paraspinal mass resulting in neurological deficit due to Aspergillus flavus, is reported. The 43 year old patient did not have any obvious predisposing condition. He presented with loss of motor function and succumbed to the infection despite operative intervention and antifungal therapy. A brief update on CNS aspergillosis is presented along with detailed clinical, radiological and laboratory work up of the patient.