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1.
Intern Med ; 56(6): 707-711, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28321075

RESUMO

Pulmonary mucormycosis (PM) is a life-threatening fungal infection in patients with hematologic malignancies, and early and accurate diagnostic modalities are urgently needed. We conducted a polymerase chain reaction (PCR) assay targeting these fungi in peripheral blood from four patients with hematologic malignancies who were strongly suspected of having PM. In these four patients, the Rhizopus species was identified in two patients, and the Cunninghamella and Absidia species in one each. Based on these molecular findings, all of the patients were successfully treated via targeted therapy with liposomal amphotericin B. In this report, a PCR analysis proved very useful for managing PM in patients with hematologic malignancies.


Assuntos
Anfotericina B/uso terapêutico , Antifúngicos/uso terapêutico , Cunninghamella , Pneumopatias Fúngicas/tratamento farmacológico , Mucormicose/tratamento farmacológico , Adulto , Idoso , Feminino , Neoplasias Hematológicas/complicações , Humanos , Pneumopatias Fúngicas/complicações , Pneumopatias Fúngicas/diagnóstico , Masculino , Pessoa de Meia-Idade , Mucormicose/complicações , Mucormicose/diagnóstico , Reação em Cadeia da Polimerase
2.
Case Rep Oncol Med ; 2016: 7510901, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27195162

RESUMO

Over the past decades, 5-Fluorouracil (5-FU) has been widely used to treat several types of carcinoma, including esophageal squamous cell carcinoma. In addition to its common side effects, including diarrhea, mucositis, neutropenia, and anemia, 5-FU treatment has also been reported to cause hyperammonemia. However, the exact mechanism responsible for 5-FU-induced hyperammonemia remains unknown. We encountered an esophageal carcinoma patient who developed hyperammonemia when receiving 5-FU-containing chemotherapy but did not exhibit any of the other common adverse effects of 5-FU treatment. At the onset of hyperammonemia, laboratory tests revealed high dihydropyrimidine dehydrogenase (DPD) activity and rapid 5-FU clearance. Our findings suggested that 5-FU hypermetabolism may be one of the key mechanisms responsible for hyperammonemia during 5-FU treatment.

3.
Int Cancer Conf J ; 5(2): 113-119, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31149437

RESUMO

We report the case of a 59-year-old man with thymic adenocarcinoma who was treated with colon cancer chemotherapy. He was referred to our hospital for an anterior mediastinal mass and multiple bone metastases that were found by computed tomography. Needle biopsy of the mediastinal tumor revealed a caudal-type homeobox 2 (CDX2)-positive adenocarcinoma. Neither upper nor lower gastrointestinal endoscopic examinations revealed any evidence of a primary tumor. The patient was administered CapeOX (capecitabine and oxaliplatin) and FOLFIRI (fluorouracil, leucovorin and irinotecan)/cetuximab. He died 6 months after diagnosis. Primary thymic adenocarcinoma was confirmed by autopsy. As far as we know, this is the first report in which colon cancer chemotherapy was used to treat CDX2-positive metastatic thymic adenocarcinoma.

4.
Tohoku J Exp Med ; 232(3): 215-22, 2014 03.
Artigo em Inglês | MEDLINE | ID: mdl-24646956

RESUMO

Periodontal disease is a chronic inflammatory disease that results in the breakdown of the tooth-supporting tissues, and can ultimately lead to resorption of the alveolar bone. Recently, several studies have shown a close relationship between increased interleukin-18 (IL-18) levels and the pathogenesis of chronic periodontitis, a major cause of tooth loss. However, it has yet to be shown whether chronic periodontitis results from or causes an increase in IL-18 after bacterial infection. In the present study, we investigated how IL-18 overexpression relates to periodontal disease using IL-18 transgenic (Tg) mice. IL-18Tg and wild-type mice were inoculated intraorally with Porphyromonas (P.) gingivalis, which has been implicated in the etiology of chronic periodontitis. Seventy days after P. gingivalis infection, alveolar bone loss and gingival cytokine levels were assessed using histo-morphological analysis and enzyme-linked immuno-absorbent assay, respectively. Periodontal bone loss was evoked in IL-18Tg mice, but not in wild-type mice. Interestingly, levels of bone-resorptive cytokines, including IL-1α, IL-1ß, tumor necrosis factor-α, and IL-6, were unchanged in the gingival tissues of IL-18Tg mice infected with P. gingivalis, although levels of interferon γ (a proinflammatory T-helper 1 cytokine) decreased. RT-PCR analysis showed elevated expression of mRNAs for receptor activator of nuclear factor kappa-B ligand (a key stimulator of osteoclast development and activation) and CD40 ligand (a marker of T cell activation) in the gingiva of IL-18Tg mice infected with P. gingivalis. We conclude that increased IL-18 in the gingival tissues evokes chronic periodontitis after bacterial infection, presumably via a T cell-mediated pathway.


Assuntos
Infecções Bacterianas/complicações , Infecções Bacterianas/metabolismo , Periodontite Crônica/etiologia , Periodontite Crônica/metabolismo , Gengiva/metabolismo , Interleucina-18/metabolismo , Perda do Osso Alveolar/sangue , Perda do Osso Alveolar/complicações , Perda do Osso Alveolar/microbiologia , Perda do Osso Alveolar/patologia , Animais , Infecções Bacterianas/sangue , Infecções Bacterianas/microbiologia , Biomarcadores/metabolismo , Periodontite Crônica/sangue , Periodontite Crônica/microbiologia , Gengiva/microbiologia , Gengiva/patologia , Interleucina-18/sangue , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Porphyromonas gingivalis/fisiologia , Células Th1/metabolismo , Células Th2/metabolismo , Transgenes
5.
Kansenshogaku Zasshi ; 88(6 Suppl 11): 11-4, 2014 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-25796921

RESUMO

A 69-year-old man, who had been receiving prednisolone for 11 months for treatment of interstitial pneumonia, was diagnosed with acute myeloid leukemia. During induction therapy, he developed severe pneumonia. Although meropenem and micafungin were started, he died of circulatory failure owing to massive gastrointestinal bleeding. Autopsy specimens obtained from the stomach revealed fungal hyphae, which had invaded diffusely into submucosal vessels and caused the massive gastric bleeding. The same hyphae were also observed in both lungs. A diagnosis of disseminated zygomycosis was confirmed by its characteristic histopathological findings. Because zygomycetes are spontaneously resistant to the newer antifungal agents, such as voriconazole or micafungin, it seems likely that the prevalence of zygomycosis as a breakthrough infection may increase in the future. Zygomycosis is a rare, but life-threatening, deep fungal infection that appears in immunologically or metabolically compromised hosts. Its manifestations are clinically similar to those of invasive aspergillosis. In addition to the well-established epidemiology of zygomycosis, this case suggests the following new characteristics. (1) Although the gastrointestinal manifestation of zygomycosis is relatively rare, it is observed more frequently than invasive aspergillosis. (2) Gastrointestinal zygomycosis occasionally leads to the development of necrotic ulcers and may induce hemorrhagic shock.(3) We should be cautious of an occurrence of breakthrough zygomycosis when we use echinocandins for patients with known risk factors, especially steroid use and neutropenia. (4) For patients who are receiving broad-spectrum antibiotics and echinocandins, who are negative for culture studies and aspergillus antigen, and who present with unresolved fever, it is important to make a prompt clinical diagnosis of zygomycosis.

6.
Acute Med Surg ; 1(2): 109-114, 2014 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29930832

RESUMO

CASE: Alcoholic ketoacidosis (AKA) usually occurs in patients with a history of prolonged alcohol abuse and recent binge drinking followed by abrupt cessation of alcohol consumption. OUTCOME: A 61-year-old man was brought to our emergency department. He had a history of eating barbecued beef with beer the previous night. He had unexplained hypoglycemia with high anion gap metabolic acidosis and fatty liver, and we strongly suspected AKA. After hydration with saline solution, dextrose, and thiamine, given i.v., his metabolic acidosis rapidly improved. A history of alcohol abuse and high serum ß-hydroxybutyrate concentration were subsequently confirmed, and the diagnosis of AKA was finally made. CONCLUSION: Our case suggests that a high-fat meal can induce AKA without abrupt cessation of alcohol consumption and that AKA should be considered when encountering patients with unexplained high anion gap metabolic acidosis with hypoglycemia and fatty liver, even if the past history of alcohol abuse is unknown.

7.
Gan To Kagaku Ryoho ; 40(9): 1237-40, 2013 Sep.
Artigo em Japonês | MEDLINE | ID: mdl-24047788

RESUMO

A 52-year-old woman had a primary neuroendocrine tumor, Grade 2(NET G2)with multiple liver metastases and a mesenteric tumor. Since no drugs were approved for NET at that time in Japan, we treated her with sunitinib after approval by the Ethics Committee of Mie University Hospital and obtaining informed consent. Sunitinib was administered at a daily dose of 37.5mg/day, but the dose was reduced to 12.5mg/day because of thrombocytopenia(G3)and neutropenia(G3). CT revealed stable disease after 3 months of treatment, but disease progression was observed after 11 months. The non-hematological toxicity was hypertension(G3), which was controlled with antihypertensive agents. Although there are no previous reports of the treatment of well-differentiated NET with sunitinib in Japan, sunitinib may be effective against this disease.


Assuntos
Antineoplásicos/uso terapêutico , Indóis/uso terapêutico , Neoplasias Primárias Desconhecidas/tratamento farmacológico , Tumores Neuroendócrinos/tratamento farmacológico , Pirróis/uso terapêutico , Diferenciação Celular , Progressão da Doença , Feminino , Humanos , Pessoa de Meia-Idade , Tumores Neuroendócrinos/patologia , Sunitinibe
8.
Intern Med ; 52(5): 611-5, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23448774

RESUMO

We herein report the case of a 77-year-old woman who developed acute thrombocytopenia during the 23rd cycle of modified FOLFOX therapy. She developed a hypersensitivity reaction with nasal bleeding. The chemotherapy infusion was immediately discontinued. The patient's symptoms resolved with discontinuation of chemotherapy and the administration of supportive therapy. A complete blood count showed severe thrombocytopenia, and oxaliplatin-induced thrombocytopenia was diagnosed. The patient was admitted to the hospital, and the thrombocytopenia was corrected with a platelet transfusion followed by prednisolone. She was discharged after one week without requiring additional platelet transfusions. With the widespread use of oxaliplatin, the risk of oxaliplatin-induced acute thrombocytopenia should be considered an acute onset hematological emergency.


Assuntos
Antineoplásicos/efeitos adversos , Compostos Organoplatínicos/efeitos adversos , Trombocitopenia/induzido quimicamente , Trombocitopenia/diagnóstico , Doença Aguda , Idoso , Feminino , Humanos , Oxaliplatina
9.
Eur J Haematol ; 90(4): 331-9, 2013 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-23360173

RESUMO

OBJECTIVES: Invasive fungal diseases (IFDs) are life-threatening events in patients with haematologic disorders, and the spectrum of the aetiological pathogens continues to expand. This study aimed to evaluate the clinical utility of a panfungal polymerase chain reaction (PCR) assay for the management of IFDs in such patients. METHODS: We prospectively analysed 273 consecutive blood samples from 64 risk episodes in 51 patients with haematologic disorders at high risk for IFD who were treated at our hospital between April 2007 and October 2010. RESULTS: PCR-positive results were obtained in 18 of 64 risk episodes (35.3%). IFD was documented in 14 episodes (21.9%, 9 probable IFDs and 5 possible IFDs) according to the revised criteria of the European Organization for Research and Treatment of Cancer/Mycoses Study Group. PCR was positive in all of these 14 episodes, and in 4 of the 50 episodes with no IFD category. Sensitivity, specificity, positive predictive value, and negative predictive value of our assay were 100%, 92%, 78% and 100% respectively. A considerable number of fungi (44.4%) that are less common than Aspergillus and Candida species were positive by PCR. Molecular diagnoses of Cunninghamella species, Aspergillus ustus, Fusarium species, Scedosporium apiospermum, Rhodotorula species and Rhizopus species were beneficial in selecting suitable treatments. CONCLUSIONS: Our panfungal PCR approach allows for the highly sensitive and specific detection and identification of a wide spectrum of fungal pathogens, which provides indispensable information for managing IFDs, especially refractory or breakthrough IFDs during antifungal therapy in high-risk patients with haematologic disorders.


Assuntos
Doenças Hematológicas/complicações , Doenças Hematológicas/microbiologia , Micoses/diagnóstico , Micoses/etiologia , Reação em Cadeia da Polimerase/métodos , Adolescente , Adulto , Idoso , Sequência de Bases , DNA Fúngico/genética , DNA Fúngico/isolamento & purificação , Feminino , Fungemia/diagnóstico , Fungemia/etiologia , Fungemia/microbiologia , Humanos , Técnicas Imunoenzimáticas , Masculino , Pessoa de Meia-Idade , Micoses/microbiologia , Valor Preditivo dos Testes , Estudos Prospectivos , Fatores de Risco , Especificidade da Espécie , Adulto Jovem
10.
PLoS One ; 7(4): e34951, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22545094

RESUMO

BACKGROUND: Gene expression profiling of peripheral blood mononuclear cells (PBMCs) is a powerful tool for the identification of surrogate markers involved in disease processes. The hypothesis tested in this study was that chronic exposure of PBMCs to a hypertensive environment in remodeled pulmonary vessels would be reflected by specific transcriptional changes in these cells. METHODOLOGY/PRINCIPAL FINDINGS: The transcript profiles of PBMCs from 30 idiopathic pulmonary arterial hypertension patients (IPAH), 19 patients with systemic sclerosis without pulmonary hypertension (SSc), 42 scleroderma-associated pulmonary arterial hypertensio patients (SSc-PAH), and 8 patients with SSc complicated by interstitial lung disease and pulmonary hypertension (SSc-PH-ILD) were compared to the gene expression profiles of PBMCs from 41 healthy individuals. Multiple gene expression signatures were identified which could distinguish various disease groups from controls. One of these signatures, specific for erythrocyte maturation, is enriched specifically in patients with PH. This association was validated in multiple published datasets. The erythropoiesis signature was strongly correlated with hemodynamic measures of increasing disease severity in IPAH patients. No significant correlation of the same type was noted for SSc-PAH patients, this despite a clear signature enrichment within this group overall. These findings suggest an association of the erythropoiesis signature in PBMCs from patients with PH with a variable presentation among different subtypes of disease. CONCLUSIONS/SIGNIFICANCE: In PH, the expansion of immature red blood cell precursors may constitute a response to the increasingly hypoxic conditions prevalent in this syndrome. A correlation of this erythrocyte signature with more severe hypertension cases may provide an important biomarker of disease progression.


Assuntos
Células Eritroides/metabolismo , Hipertensão Pulmonar/genética , Leucócitos Mononucleares/metabolismo , Transcriptoma , Adulto , Idoso , Feminino , Regulação da Expressão Gênica , Hemodinâmica , Humanos , Hipertensão Pulmonar/fisiopatologia , Leucócitos Mononucleares/patologia , Pulmão/metabolismo , Pulmão/fisiopatologia , Masculino , Pessoa de Meia-Idade
11.
Int J Infect Dis ; 16(1): e2-e4, 2012 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-22071235

RESUMO

The detection of serum 1,3-ß-d-glucan (BDG) has been reported to be useful for the diagnosis and therapeutic monitoring of various invasive fungal infections. Although Trichosporon fungemia is increasingly recognized as a fatal mycosis in immunocompromised patients, the utility of this assay for Trichosporon fungemia is still unknown. In our experience (28 cases), the level of BDG rose in about half of the patients with hematologic disorders who developed Trichosporon fungemia. Among them, early death from this infection was more frequently seen in BDG-negative patients than in BDG-positive patients. In addition, overall survival was also significantly worse in BDG-negative patients than in BDG-positive patients. There were no significant differences between these two patient groups in terms of clinical background. Unlike for other invasive fungal infections, elevation of BDG level may indicate a paradoxical sign for Trichosporon fungemia in patients with hematologic disorders.


Assuntos
Fungemia/diagnóstico , Doenças Hematológicas/diagnóstico , Trichosporon/patogenicidade , beta-Glucanas/sangue , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Anfotericina B/uso terapêutico , Antifúngicos/uso terapêutico , Equinocandinas/uso terapêutico , Feminino , Fluconazol/uso terapêutico , Fungemia/tratamento farmacológico , Fungemia/microbiologia , Doenças Hematológicas/tratamento farmacológico , Humanos , Hospedeiro Imunocomprometido , Lipopeptídeos/uso terapêutico , Masculino , Micafungina , Miconazol/uso terapêutico , Pessoa de Meia-Idade , Proteoglicanas , Estudos Retrospectivos , Resultado do Tratamento , Trichosporon/efeitos dos fármacos , Adulto Jovem
12.
Microbiol Immunol ; 55(1): 66-70, 2011 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-21175776

RESUMO

Candida species were detected and identified in samples from the buccal mucosa, dorsal surface of the tongue and supragingival plaque of subjects with oral lichen planus (OLP). The Candida in the samples were cultured on selection agars, and identified by sequence analyses of 18S, 5.8S and 25/28S rRNA. The isolation frequency of Candida was higher in subjects with OLP than in those with healthy oral mucosa. Non-C. albicans were only isolated from people with OLP. These results support the notion that subjects with OLP are more likely to have oral colonization with Candida, and that non-C. albicans are specifically present in subjects with this condition.


Assuntos
Candida/isolamento & purificação , Líquen Plano Bucal/microbiologia , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
13.
J Clin Microbiol ; 48(6): 2030-6, 2010 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-20392911

RESUMO

This study aimed to assess the clinical utility of PCR for the analysis of bacteria and fungi from blood for the management of febrile neutropenic patients with hematologic malignancies. Using a PCR system able to detect a broad range of bacteria and fungi, we conducted a prospective pilot study of periodic analyses of blood from patients following intensive chemotherapy. When fever occurred, it was treated with empirical antibiotic therapy, basically without knowledge of the PCR results. In 23 febrile episodes during the neutropenic period, bacteria were detected by PCR in 11 cases, while the same species were identified by blood culture in 3 cases. In 10 out of 11 PCR-positive cases, fever could be managed by empirical therapy. In the empirical-therapy-resistant case, the identification of Stenotrophomonas maltophilia by PCR led to improvement of fever. No fungi were detected by PCR in febrile cases, while Aspergillus fumigatus was detected in one afebrile patient, several days before a clinical diagnosis was made. In subsequent sporadic PCR analyses in 15 cases of febrile neutropenia, bacteria were detected by both PCR and blood culture in 7 cases and by PCR alone in 6. Fungi were not detected. While fever was improved by empirical therapy in 12 out of the 13 PCR-positive cases, the identification of Pseudomonas aeruginosa by PCR in one therapy-resistant case contributed to the successful treatment of persistent fever. Our results indicate that PCR analysis of bacteria from blood provides essential information for managing empirical-therapy-resistant febrile neutropenia.


Assuntos
Infecções Bacterianas/diagnóstico , Sangue/microbiologia , Febre de Causa Desconhecida/etiologia , Micoses/diagnóstico , Neutropenia/imunologia , Reação em Cadeia da Polimerase/métodos , Adulto , Idoso , Animais , Antibacterianos/uso terapêutico , Antineoplásicos/efeitos adversos , Antineoplásicos/uso terapêutico , Bactérias/classificação , Bactérias/genética , Bactérias/isolamento & purificação , Infecções Bacterianas/tratamento farmacológico , Infecções Bacterianas/microbiologia , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Feminino , Fungos/genética , Fungos/isolamento & purificação , Neoplasias Hematológicas/complicações , Neoplasias Hematológicas/tratamento farmacológico , Humanos , Masculino , Pessoa de Meia-Idade , Micoses/microbiologia , Neutropenia/induzido quimicamente , Resultado do Tratamento , Adulto Jovem
15.
Eur J Haematol ; 84(5): 441-7, 2010 May.
Artigo em Inglês | MEDLINE | ID: mdl-20059528

RESUMO

OBJECTIVE: Invasive Trichosporon infection has been increasingly recognized in patients with hematologic malignancies. Our study aims to clarify the clinical characteristics of this disease and factors influencing patient prognosis. PATIENTS AND METHODS: We retrospectively analyzed 33 cases of Trichosporon fungemia (TF) in patients with hematologic malignancies treated at our collaborating five hospitals in Japan between 1992 and 2007. RESULTS: The majority of these patients had acute leukemia (82%), neutropenia (85%), and a history of intensive chemotherapy (91%). TF occurred as a breakthrough infection during antifungal therapy in 30 patients (91%), 18 of whom were receiving micafungin. The surveillance cultures of most patients were negative for Trichosporon. Only a few patients exhibited elevated levels of 1,3-beta-d-glucan before positive blood culture. Twenty-five patients (76%) died of this infection. The resolution of infection was associated with neutrophil recovery (P = 0.0001), absence of hyperglycemia (P = 0.023), and azole inclusive therapy (P = 0.031). Survival was significantly longer in patients receiving antifungal therapies containing azole than in those who did not receive azole (P = 0.0034). CONCLUSIONS: At present, the diagnosis of invasive trichosporonosis depends on blood culture studies, and the mortality of this disease is high; however, azole therapy and control of blood glucose level, together with hematopoietic recovery could help in improving the clinical outcome. When we use antifungals lacking anti-Trichosporon activity, sufficient care should be taken to prevent the development of breakthrough trichosporonosis.


Assuntos
Neoplasias Hematológicas/complicações , Micoses/mortalidade , Trichosporon/isolamento & purificação , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Antifúngicos/uso terapêutico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Micoses/complicações , Micoses/tratamento farmacológico , Micoses/prevenção & controle , Estudos Retrospectivos , Adulto Jovem
17.
J Infect Chemother ; 15(1): 42-5, 2009 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-19280300

RESUMO

A 69-year-old man, who had been receiving prednisolone for 11 months for treatment of interstitial pneumonia, was diagnosed with acute myeloid leukemia. During induction therapy, he developed severe pneumonia. Although meropenem and micafungin were started, he died of circulatory failure owing to massive gastrointestinal bleeding. Autopsy specimens obtained from the stomach revealed fungal hyphae, which had invaded diffusely into submucosal vessels and caused the massive gastric bleeding. The same hyphae were also observed in both lungs. A diagnosis of disseminated zygomycosis was confirmed by its characteristic histopathological findings. Because zygomycetes are spontaneously resistant to the newer antifungal agents, such as voriconazole or micafungin, it seems likely that the prevalence of zygomycosis as a breakthrough infection may increase in the future. Zygomycosis is a rare, but life-threatening, deep fungal infection that appears in immunologically or metabolically compromised hosts. Its manifestations are clinically similar to those of invasive aspergillosis. In addition to the well-established epidemiology of zygomycosis, this case suggests the following new characteristics. (1) Although the gastrointestinal manifestation of zygomycosis is relatively rare, it is observed more frequently than invasive aspergillosis. (2) Gastrointestinal zygomycosis occasionally leads to the development of necrotic ulcers and may induce hemorrhagic shock.(3) We should be cautious of an occurrence of breakthrough zygomycosis when we use echinocandins for patients with known risk factors, especially steroid use and neutropenia. (4) For patients who are receiving broad-spectrum antibiotics and echinocandins, who are negative for culture studies and aspergillus antigen, and who present with unresolved fever, it is important to make a prompt clinical diagnosis of zygomycosis.


Assuntos
Antifúngicos/uso terapêutico , Equinocandinas/uso terapêutico , Gastroenteropatias/complicações , Hemorragia Gastrointestinal/etiologia , Leucemia Mieloide Aguda/complicações , Lipopeptídeos/uso terapêutico , Zigomicose/complicações , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Evolução Fatal , Gastroenteropatias/tratamento farmacológico , Gastroenteropatias/microbiologia , Gastroenteropatias/patologia , Humanos , Hospedeiro Imunocomprometido , Leucemia Mieloide Aguda/diagnóstico , Leucemia Mieloide Aguda/tratamento farmacológico , Masculino , Micafungina , Estômago/patologia , Zigomicose/tratamento farmacológico , Zigomicose/microbiologia , Zigomicose/patologia
18.
J Infect Chemother ; 14(4): 311-4, 2008 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-18709536

RESUMO

A 67-year-old woman with systemic lupus erythematosus (SLE) was admitted to our hospital because of lupus nephritis. Methylprednisolone minipulse therapy dramatically reduced her proteinuria; however; she then complained of general fatigue with low-grade fever. Radiological and culture studies revealed no infectious focus, but she was treated with meropenem and micafungin, considering her immunosuppressive state. Cytomegalovirus antigenemia was later determined and ganciclovir was added. She became afebrile, but complained of nausea and headache, and disorientation, without meningeal signs. Because a brain computed tomography (CT) scan showed no abnormality, we initially suspected some kind of drug interaction. Despite the discontinuation of all drugs, however, she still suffered from disturbance of consciousness. A lumbar puncture revealed yeast cells stained by India ink. A diagnosis of cryptococcal meningitis was confirmed. Though fluconazole and meropenem were administered, the patient died. Autopsy findings revealed disseminated cryptococcosis concomitant with pulmonary aspergillosis. Micafungin is a recently approved echinocandin-class antifungal agent that is now widely used in Japan because of its minimal toxicity and broadspectrum activity. However, such echinocandins have limited activity against a number of fungi. Indeed, breakthrough trichosporonosis is becoming a significant problem in patients with hematological malignancies who are receiving echinocandins. To the best of our knowledge, breakthrough cryptococcosis, as seen in our patient, has not been reported previously in patients who were receiving micafungin as an empiric antifungal therapy. This case highlights that cryptococcosis should be kept in mind as a possible breakthrough infection during the administration of echinocandins, especially in patients with cellular immunodeficiency.


Assuntos
Antifúngicos/uso terapêutico , Farmacorresistência Fúngica , Equinocandinas/uso terapêutico , Lipoproteínas/uso terapêutico , Lúpus Eritematoso Sistêmico/microbiologia , Idoso , Evolução Fatal , Feminino , Humanos , Lipopeptídeos , Pneumopatias Fúngicas/tratamento farmacológico , Pneumopatias Fúngicas/patologia , Meningite Criptocócica/tratamento farmacológico , Meningite Criptocócica/patologia , Micafungina
19.
J Immunol ; 181(4): 2898-906, 2008 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-18684981

RESUMO

IL-18 is a proinflammatory cytokine and plays an important pathogenic role in inflammatory and autoimmune disorders. IL-17 is also a proinflammatory cytokine and IL-17-secreting Th17 cells are involved in autoimmunity. However, the pathological roles of IL-18 and Th17 cells in Sjögren's syndrome (SS) remain to be elucidated. This study showed that the expression of IL-18 was detected in acinar cells, intraducts, and CD68(+) macrophages in salivary glands of SS patients, but not in those of healthy subjects or patients with chronic graft-vs-host disease, by immunohistochemistry, and immunoblot analysis revealed that 24-kDa precursor form of IL-18 (proIL-18) and 18-kDa mature IL-18 were detected in SS salivary glands. The majority of the infiltrating cells in the salivary glands of SS patients were CD4(+) T cells, and CD8(+) T cells were infiltrated to a lesser extent. The predominant expression of IL-17 was found in infiltrating CD4(+) T cells, whereas a small number of infiltrating CD8(+) T cells expressed IL-17. Human salivary gland HSY and acinar AZA3 cells constitutively expressed proIL-18 and caspase-1, and a calcium ionophore A23187 induced the secretion of IL-18 from the cells. HSY and AZA3 cells expressed IL-18R and IL-17R on the cell surface, and IL-18 amplified the secretion of IL-6 and IL-8 that were induced by low amounts of IL-17. Primary salivary gland cells from normal subjects partially confirmed these findings. These results suggest that IL-18 and Th17 cells detected in the salivary glands in SS patients are associated with the pathogenesis of SS in the salivary glands.


Assuntos
Citocinas/metabolismo , Mediadores da Inflamação/metabolismo , Interleucina-17/biossíntese , Interleucina-18/biossíntese , Glândulas Salivares Menores/imunologia , Glândulas Salivares Menores/metabolismo , Síndrome de Sjogren/imunologia , Subpopulações de Linfócitos T/imunologia , Adulto , Linhagem Celular Tumoral , Movimento Celular/imunologia , Células Cultivadas , Humanos , Interleucina-17/metabolismo , Interleucina-17/fisiologia , Interleucina-18/metabolismo , Interleucina-18/fisiologia , Glândulas Salivares Menores/patologia , Síndrome de Sjogren/metabolismo , Subpopulações de Linfócitos T/metabolismo , Subpopulações de Linfócitos T/patologia
20.
Rinsho Ketsueki ; 49(5): 340-3, 2008 May.
Artigo em Japonês | MEDLINE | ID: mdl-18572812

RESUMO

A 66year-old man with sustained fever was diagnosed as having acute myeloid leukemia with multilineage dysplasia. Induction therapy with etoposide and AraC was initiated, but was ineffective. Although fever had persisted for more than a few days, there was no evidence of any infection on radiological examination or culture studies. The patient was disorientated and demonstrated personality change. After a severe convulsive seizure, the patient died. Autopsy findings showed that the leukemic cells had permeated the Virchow Robin space, but without a mass lesion in the cerebral parenchyma. He was diagnosed as having had central nervous system leukemia (CNSL) that provoked sustained fever, consciousness disturbance and convulsive seizure. These findings suggested that the Virchow Robin space plays a particular role in the development of CNSL. Even with repeated cerebrospinal fluid examinations and radiological tests, we were unable to correctly diagnose CNSL before death, which may indicate the intractability of diagnosing CNSL spread along the Virchow Robin space. This case provides useful information about the pathophysiology and diagnosis of CNSL.


Assuntos
Neoplasias do Sistema Nervoso Central/patologia , Ventrículos Cerebrais/patologia , Leucemia Mieloide Aguda/patologia , Idoso , Neoplasias do Sistema Nervoso Central/complicações , Neoplasias do Sistema Nervoso Central/diagnóstico , Transtornos da Consciência/etiologia , Evolução Fatal , Febre/etiologia , Humanos , Leucemia Mieloide Aguda/complicações , Leucemia Mieloide Aguda/diagnóstico , Masculino , Invasividade Neoplásica , Convulsões/etiologia
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