RESUMO
BACKGROUND: Surgical antimicrobial prophylaxis (SAP) is one of the major purposes of antimicrobial use. AIM: To determine the adherence to the Japanese SAP guidelines in Japanese university hospitals. METHODS: This was a retrospective cohort study including 15 general hospitals and one dental university hospital. Up to three cases of 18 designated surgeries were evaluated regarding adherence to Japanese SAP guidelines: selection of antibiotics, timing of administration, re-dosing intervals, and duration of SAP. When all items were appropriate, surgery was defined as 'appropriate'. FINDINGS: In total, 688 cases (22-45 cases per surgery) were included. The overall appropriateness was 46.8% (322/688), and the appropriateness of each surgery ranged from 8.0% (2/25, cardiac implantable electronic device implantation) to 92.1% (35/38, distal gastrectomy). The appropriateness of each item was as follows: pre/intraoperative selections, 78.5% (540/688); timing of administrations, 96.0% (630/656); re-dosing intervals, 91.6% (601/656); postoperative selection, 78.9% (543/688); and duration of SAP, 61.4% (423/688). The overall appropriateness of hospitals ranged from 17.6% (9/51) to 73.3% (33/45). The common reasons for inappropriateness were the longer duration (38.5%, 265/688) and choice of antibiotics with a non-optimal antimicrobial spectrum before/during, and after surgery (19.0%, 131/688 and 16.9%, 116/688, respectively), compared to the guideline. CONCLUSIONS: Adherence to the guidelines differed greatly between the surgeries and hospitals. Large-scale multi-centre surveillance of SAP in Japanese hospitals is necessary to identify inappropriate surgeries, factors related to the appropriateness, and incidences of surgical site infections.
Assuntos
Anti-Infecciosos , Antibioticoprofilaxia , Humanos , Estudos Retrospectivos , Hospitais Universitários , Japão , Fidelidade a Diretrizes , Antibacterianos/uso terapêutico , Infecção da Ferida Cirúrgica/epidemiologia , Infecção da Ferida Cirúrgica/prevenção & controle , Infecção da Ferida Cirúrgica/tratamento farmacológico , Anti-Infecciosos/uso terapêuticoRESUMO
BACKGROUND: Intestinal microbial ecology is actively regulated by Paneth cell-derived antimicrobial peptides, α-defensins. Graft-versus-host disease (GVHD) is a major complication of allogeneic hematopoietic stem cell transplantation (SCT). We previously demonstrated that Paneth cells are targeted by GVHD, and their expression of antimicrobial peptide α-defensins is impaired, leading to a loss of physiological diversity among the microflora and development of bloodstream infection. Herein, we evaluated whether fecal levels of α-defensins could be surrogate marker of intestinal dysbiosis. METHODS: We directly measured α-defensin cryptdin-1 (Crp1) in fecal pellets of mice with GVHD by using a novel enzyme-linked immunosorbent assay. RESULTS: Fecal levels of Crp1 were significantly decreased in mice with GVHD but unchanged in mice without GVHD after SCT. These were correlated with intestinal flora diversity. CONCLUSION: We demonstrate a link between reduced secretion of Paneth cell α-defensins and dysbiosis of intestinal flora in GVHD. Fecal levels of α-defensins could be surrogate markers for intestinal microbial homeostasis.
Assuntos
Disbiose/metabolismo , Fezes/química , Doença Enxerto-Hospedeiro/metabolismo , Proteínas com Domínio LIM/metabolismo , Proteínas Nucleares/metabolismo , Celulas de Paneth/metabolismo , alfa-Defensinas/metabolismo , Animais , Biomarcadores/metabolismo , Disbiose/microbiologia , Ensaio de Imunoadsorção Enzimática , Fezes/microbiologia , Feminino , Microbioma Gastrointestinal , Transplante de Células-Tronco Hematopoéticas , Mucosa Intestinal/metabolismo , Intestinos/microbiologia , Camundongos , Camundongos Endogâmicos C57BL , Transplante HomólogoRESUMO
There is increasing interest in the role of T cell exhaustion and it is well known that the natural history of chronic hepatitis C virus infection (HCV) is modulated by CD8(+) T cell immunobiology. There are many pathways that alter the presence of exhaustive T cells and, in particular, they are functionally impaired by inhibitory receptors, such as programmed death-1 (PD-1) and T cell immunoglobulin and mucin domain-containing protein 3 (Tim-3). We obtained spleen, liver and peripheral blood (before and after splenectomy) lymphoid cells from 25 patients with HCV-related cirrhosis undergoing liver transplantation for end-stage disease or splenectomy for portal hypertension. In all samples we performed an extensive phenotypic study of exhaustion markers [PD-1, Tim-3, interferon (IFN)-γ) and their ligands (PD-L1, PD-L2, galectin-9] in CD8(+) T cell subpopulations (both total and HCV-specific) and in antigen-presenting cells (APC; monocytes and dendritic cells). In the spleen, total and HCV-specific CD8(+) T cells demonstrated enhanced markers of exhaustion, predominantly in the effector memory subpopulation. Similarly, splenic APC over-expressed inhibitory receptor ligands when compared to peripheral blood. Finally, when peripheral blood CD8(+) T cells were compared before and after splenectomy, markers of exhaustion were reduced in splenic CD8(+) T cells and APC. Our data in HCV-related cirrhosis suggest that CD8(+) T cells in the spleen manifest a significantly higher exhaustion compared to peripheral blood and may thus contribute to the failure to control HCV. Counteracting this process may contribute to inducing an effective immune response to HCV.
Assuntos
Linfócitos T CD8-Positivos/imunologia , Linfócitos T CD8-Positivos/patologia , Hepatite C Crônica/imunologia , Hepatite C Crônica/patologia , Idoso , Células Apresentadoras de Antígenos/imunologia , Células Apresentadoras de Antígenos/patologia , Células Apresentadoras de Antígenos/virologia , Biomarcadores/sangue , Biomarcadores/metabolismo , Linfócitos T CD8-Positivos/virologia , Feminino , Receptor Celular 2 do Vírus da Hepatite A , Hepatite C Crônica/sangue , Humanos , Cirrose Hepática/sangue , Cirrose Hepática/imunologia , Cirrose Hepática/patologia , Masculino , Proteínas de Membrana/biossíntese , Proteínas de Membrana/sangue , Pessoa de Meia-Idade , Receptor de Morte Celular Programada 1/biossíntese , Receptor de Morte Celular Programada 1/sangue , Baço/imunologia , Baço/patologia , Baço/virologia , Esplenectomia , Trombocitopenia/complicações , Trombocitopenia/imunologia , Trombocitopenia/patologiaAssuntos
Transplante de Células-Tronco de Sangue do Cordão Umbilical , Leucemia Mieloide Aguda/complicações , Leucemia Mieloide Aguda/terapia , Mucormicose/etiologia , Mucormicose/terapia , Anfotericina B/uso terapêutico , Antifúngicos/uso terapêutico , Feminino , Humanos , Pessoa de Meia-Idade , Mucormicose/tratamento farmacológico , Mucormicose/microbiologia , Resultado do TratamentoRESUMO
Here we report the case of a 43-year-old Japanese woman with acute myelogenous leukemia who underwent 2 unrelated cord blood transplantations (UCBT), terminating in fatal disseminated tuberculosis (TB). The patient did not achieve remission despite intensive chemotherapy, and subsequently underwent UCBT with a standard conditioning regimen. However, engraftment was not achieved. Fifty days after the first UCBT, the patient underwent a second UCBT with a reduced-intensity conditioning regimen. She developed a pre-engraftment immune reaction, which responded well to prednisolone, and engraftment was documented. However, 50 days after the second UCBT, the patient presented with high fever and developed pneumonia despite antibiotic and antifungal treatments. Thereafter, Mycobacterium tuberculosis was detected in blood cultures and specimens of bronchoalveolar lavage, thus indicating disseminated TB. Despite anti-tuberculous treatment, she died on day 85. TB should always be considered as a possible diagnosis when treating febrile immunocompromised patients.
Assuntos
Bacteriemia/microbiologia , Transplante de Células-Tronco de Sangue do Cordão Umbilical/efeitos adversos , Leucemia Mieloide Aguda/terapia , Mycobacterium tuberculosis/isolamento & purificação , Tuberculose Pulmonar/microbiologia , Adulto , Antituberculosos/uso terapêutico , Bacteriemia/tratamento farmacológico , Evolução Fatal , Feminino , Humanos , Tuberculose Pulmonar/tratamento farmacológicoRESUMO
The ability to gain entry and resist the antimicrobial intracellular environment of mammalian cells is an essential virulence property of Mycobacterium tuberculosis. A purified recombinant protein expressed by a 1362 bp locus (mce1) in the M. tuberculosis genome promoted uptake into HeLa cells of polystyrene latex microspheres coated with the protein. N-terminus deletion constructs of Mce1 identified a domain located between amino acid positions 106 and 163 that was needed for this cell uptake activity. Mce1 contained hydrophobic stretches at the N-terminus predictive of a signal sequence, and colloidal gold immunoelectron microscopy indicated that the corresponding native protein is expressed on the surface of the M. tuberculosis organism. The complete M. tuberculosis genome sequence revealed that it contained four homologues of mce (mce1, mce2, mce3, mce4) and that they were all located within operons composed of genes arranged similarly at different locations in the chromosome. Recombinant Mce2, which had the highest level of identity (67%) to Mce1, was unable to promote the association of microspheres with HeLa cells. Although the exact function of Mce1 is still unknown, it appears to serve as an effector molecule expressed on the surface of M. tuberculosis that is capable of eliciting plasma membrane perturbations in non-phagocytic mammalian cells.
Assuntos
Proteínas de Bactérias/fisiologia , Mycobacterium tuberculosis/fisiologia , Anticorpos Antibacterianos/imunologia , Proteínas de Bactérias/genética , Proteínas de Bactérias/imunologia , Membrana Celular/microbiologia , Membrana Celular/ultraestrutura , Escherichia coli , Genes Bacterianos , Células HeLa , Humanos , Immunoblotting , Microscopia Imunoeletrônica , Microesferas , Mycobacterium tuberculosis/genética , Mycobacterium tuberculosis/imunologia , Mycobacterium tuberculosis/ultraestrutura , Fases de Leitura Aberta , Óperon , Proteínas Recombinantes/metabolismoAssuntos
Infecções Bacterianas/tratamento farmacológico , Ceftizoxima/análogos & derivados , Cefalosporinas/administração & dosagem , Pró-Fármacos/administração & dosagem , Infecções Respiratórias/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Ceftizoxima/administração & dosagem , Ceftizoxima/efeitos adversos , Cefalosporinas/efeitos adversos , Esquema de Medicação , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pró-Fármacos/efeitos adversos , Cefpodoxima ProxetilAssuntos
Anti-Infecciosos/uso terapêutico , Ofloxacino/uso terapêutico , Infecções Respiratórias/tratamento farmacológico , Anti-Infecciosos/administração & dosagem , Anti-Infecciosos/efeitos adversos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Ofloxacino/administração & dosagem , Ofloxacino/efeitos adversos , Infecções Respiratórias/microbiologiaRESUMO
The direct effects of human granulocyte colony-stimulating factor (hG-CSF) on mature polymorphonuclear neutrophils (PMNs) in vitro were studied with regard to chemotaxis, superoxide production, and phagocytosis and microbicidal activity against the following viable microorganisms: Staphylococcus aureus, serum-resistant Pseudomonas aeruginosa, and Candida albicans. Recombinant hG-CSF (rhG-CSF) acted as a chemoattractant for human PMNs in a dose-dependent manner. The chemotactic response of PMNs to N-formyl-methionyl-leucyl-phenylalanine (FMLP) was not enhanced by rhG-CSF at any of the concentrations used. rhG-CSF did not induce the generation of superoxide by itself. However, rhG-CSF was able to prime human PMNs and to enhance O2- release stimulated by FMLP in a dose-dependent manner. rhg-CSF did not enhance phagocytosis or killing of the three species of microorganisms by normal PMNs. With PMNs obtained from patients who had hematological disorders or solid tumors, no enhancement of the microbicidal activity was observed in most cases. Microbial killing mediated by PMNs depended on the ratio of PMNs to target organisms. We concluded from these facts that the most important effect of rhG-CSF was to increase the number of the peripheral PMNs and not to enhance the functions of mature PMNs.
Assuntos
Atividade Bactericida do Sangue/efeitos dos fármacos , Fator Estimulador de Colônias de Granulócitos/farmacologia , Neutrófilos/imunologia , Fagocitose/efeitos dos fármacos , Candida albicans/imunologia , Quimiotaxia/imunologia , Humanos , Hospedeiro Imunocomprometido/imunologia , Ativação de Neutrófilo/imunologia , Neutrófilos/citologia , Neutrófilos/microbiologia , Pseudomonas aeruginosa/imunologia , Proteínas Recombinantes/farmacologia , Staphylococcus aureus/imunologia , Superóxidos/imunologia , Superóxidos/metabolismoRESUMO
We examined the clinical records of patients from whom S. milleri was isolated at Kyushu University Hospital from January 1987 through December 1988. Sixty-one patients were treated in 64 episodes with drainage or antibiotics. Oral and nasopharyngeal infections were observed in 27 cases, intrathoracic infections in 13, urogenital infections in 8, intraabdominal infections in 6 and skin and subcutaneous infections in 6. Except for acute bronchitis and urogenital infections, all of them were suppurative. As to underlying diseases, 21 patients had malignancies and 6 had diabetes mellitus. Leukocytopenia was not observed in any of the patients. S. milleri can be eradicated by treatment but it is sometimes replaced by other organisms. However, considering its tendency to cause suppurative infections, its pathogenic significance should be taken into account and patients should undergo surgical drainage combined with antibiotic therapy.
Assuntos
Infecções Estreptocócicas/microbiologia , Streptococcus/isolamento & purificação , Humanos , Doenças Nasofaríngeas/microbiologia , Infecções Respiratórias/microbiologia , Estudos Retrospectivos , Dermatopatias Infecciosas/microbiologia , Infecções Estreptocócicas/fisiopatologia , Infecções Estreptocócicas/terapiaRESUMO
We have developed a new method to isolate Pneumocystis carinii trophozoites from experimental rat bronchoalveolar lavage specimens by using a Percoll discontinuous gradient and have identified the circulating antigens in experimental rat P. carinii pneumonia. The antigenic components of the trophozoites were compared with those of cysts by immunoblotting. A major immunoreactive band of 90,000 Da and some others of lower molecular mass were found in trophozoites. On the other hand, bands of 110,000, 50,000, and 45,000 Da were observed in cysts. The band of 50,000 Da was not identified when antitrophozoite rabbit serum preabsorbed with P. carinii-infected rat serum was used for immunoblotting. These results suggest that the molecule of 50,000 Da is the major circulating antigen in P. carinii-infected rats.
Assuntos
Antígenos de Fungos/sangue , Pneumocystis/isolamento & purificação , Pneumonia por Pneumocystis/microbiologia , Animais , Antígenos de Fungos/química , Western Blotting , Estudos de Avaliação como Assunto , Masculino , Peso Molecular , Micologia/métodos , Pneumocystis/crescimento & desenvolvimento , Pneumocystis/imunologia , Ratos , Ratos Wistar , Coloração e RotulagemRESUMO
Wilson's disease associated with hepatic failure is not common and the underlying mechanism triggering the event is not known at present. We treated a 28-year-old Japanese woman with Wilson's disease who developed hepatic failure associated with hemolytic crisis just after delivery. She was diagnosed as having Wilson's disease at 12 years of age, at which time she started taking D-penicillamine. She had previously delivered two children without difficulty. When she found out she was pregnant this time, she stopped taking D-penicillamine in contrast to taking it faithfully during her first two pregnancies. On the day of delivery of her full-term baby, jaundice developed accompanied with severe hemolytic crisis. Plasma exchanges and blood transfusion were performed and D-penicillamine administration was started again. She gradually recovered and apparently was following a good clinical course. However, on day 30 the second hemolytic crisis occurred and subsequent liver failure led her to death on day 50. At autopsy her liver was cirrhotic and showed massive necrosis. Prophylactic oral administration of D-penicillamine and careful observation are therefore recommended to prevent hemolytic crisis during the perinatal period.
Assuntos
Degeneração Hepatolenticular/complicações , Hepatopatias/etiologia , Fígado/patologia , Transtornos Puerperais/etiologia , Adulto , Anemia Hemolítica/etiologia , Feminino , Degeneração Hepatolenticular/tratamento farmacológico , Humanos , Hepatopatias/patologia , Penicilamina/uso terapêutico , Gravidez , Transtornos Puerperais/patologiaRESUMO
The effects of recombinant murine granulocyte-macrophage colony-stimulating factor (rmGM-CSF) against Pseudomonas aeruginosa infection in ICR mice were investigated. Mice were treated with cyclophosphamide (CPA) and were then injected intraperitoneally with rmGM-CSF three times daily, beginning on the day after CPA treatment, for 7 days. The number of peripheral blood leukocytes in both CPA- and rmGM-CSF-treated mice and control CPA-treated mice reached a nadir on day 4, when P. aeruginosa was injected intraperitoneally. The administration of rmGM-CSF significantly increased the proportion of survivors among mice infected with a lethal dose of P. aeruginosa. This effect was further analyzed by monitoring sequential changes in leukocyte count and bacterial growth in various organs. The number of bacteria in the peritoneal cavities, peripheral blood samples, and livers of GM-CSF-treated mice decreased to an undetectable level after a transient increase, and the number was significantly lower than that in control mice. In GM-CSF-treated mice, the neutrophil levels in peripheral blood started to increase 5 days after CPA administration and were consistently higher than those in controls. Furthermore, the neutrophils in GM-CSF-treated mice were more mature morphologically. Thus, the prophylactic effect of rmGM-CSF against P. aeruginosa infection may result from a rapid recovery of myelopoiesis and a partial enhancement of mature neutrophil function.
Assuntos
Fatores Estimuladores de Colônias/uso terapêutico , Substâncias de Crescimento/uso terapêutico , Leucopenia/terapia , Infecções por Pseudomonas/prevenção & controle , Animais , Líquido Ascítico/patologia , Ciclofosfamida/administração & dosagem , Feminino , Fator Estimulador de Colônias de Granulócitos e Macrófagos , Cinética , Contagem de Leucócitos/efeitos dos fármacos , Leucopenia/sangue , Leucopenia/induzido quimicamente , Camundongos , Camundongos Endogâmicos ICR , Infecções por Pseudomonas/sangue , Infecções por Pseudomonas/mortalidade , Proteínas Recombinantes/uso terapêuticoRESUMO
The properties of internal-surface reversed-phase silica packings developed for use in high-performance liquid chromatography, were investigated with regard to the effects of mobile phase conditions (pH, ionic strength, nature and concentration of organic modifiers, ion-pairing agent and surfactant) on the retention of some selected compounds having different polarities. The results indicated that pi-electron interactions play the main role in solute retention, although it is weaker than that on phenylsilica supports, and that weak cation-exchange properties exert a secondary effect on the retention of ionic solutes. The ion-pairing effect was found to be markedly weakened in mobile phases containing an anionic counter ion. In contrast, the addition of a surfactant (SDS) caused a marked increase in the retention of certain drugs at low pH and expanded the pH range of the mobile phase applicable to plasma samples. Based on these findings, the separation and recovery of several drugs (probenecid, lidocaine, cefpiramide and cefaclor) from human plasma were investigated, with emphasis on their protein bindings. The contour chromatogram of human plasma is also demonstrated in relation to the selection of the detection wavelength.
Assuntos
Preparações Farmacêuticas/sangue , Proteínas Sanguíneas/análise , Cromatografia Líquida de Alta Pressão , Humanos , Concentração de Íons de Hidrogênio , Indicadores e Reagentes , Dióxido de Silício , Dodecilsulfato de Sódio , Propriedades de Superfície , TensoativosRESUMO
The protective mechanism of polyamines against acidified ethanol-induced gastric damage was studied. Their oral administration prevented the formation of gastric mucosal lesions induced by 90% ethanol in 150 mM HCl in a dose-dependent manner, with the order of the protective potency being spermine greater than spermidine greater than putrescine. The acidified ethanol-induced lesions were accompanied by a concomitant increase in gastric mucosal lipid peroxide levels, but spermine in a protective dose could prevent the increment of lipid peroxides. Polyamines, in a concentration-dependent fashion, inhibited the reduction of nitroblue tetrazolium by superoxide anion radicals generated in vitro in the xanthine-xanthine oxidase system and the lipid peroxidation in vitro induced by ferrous ion in the porcine gastric mucosal homogenate. The order of the superoxide scavenging potency and the inhibitory potency of iron-induced lipid peroxidation by polyamines corresponded to the order to the protective potency against acidified ethanol-induced gastric lesions. The present results suggest that cytoprotection by polyamines may be responsible for their antiperoxidative activities.
Assuntos
Etanol/toxicidade , Mucosa Gástrica/efeitos dos fármacos , Putrescina/administração & dosagem , Espermidina/administração & dosagem , Espermina/administração & dosagem , Administração Oral , Animais , Mucosa Gástrica/metabolismo , Mucosa Gástrica/patologia , Ácido Clorídrico , Ferro/farmacologia , Peróxidos Lipídicos/metabolismo , Masculino , Ratos , Ratos Endogâmicos , Compostos de Sulfidrila/metabolismo , Superóxidos/metabolismo , Suínos , Fatores de TempoRESUMO
Gastric antral lesions were produced with hemorrhages by vascular ligation-induced ischemia in the prepyloric regions in rats. Additional treatments with intraluminal acid application and indomethacin markedly aggravated the lesions. Histological examination showed that the incidence of ulcers which penetrated the muscularis mucosae was nearly 100% upon treatment with a combination of acid, indomethacin and ischemia. This model provides a useful tool for studying gastric ulcer etiology.