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1.
Undersea Hyperb Med ; 47(1): 125-129, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32176953

RESUMO

Hemorrhagic cystitis (HC) after allogeneic hematopoietic stem cell transplantation (AHSCT) in both children and adults has been associated with significant morbidity and mortality. Early HC can occur within 48 hours of completing the chemotherapy conditioning regimen, is usually associated with agents such as cyclophosphamide, and generally resolves promptly. Late HC is commonly associated with BK and other viruses and can prove refractory to antiviral and supportive therapy. There are limited reports of hyperbaric oxygen (HBO2) therapy showing benefit for refractory HC cases. We describe our experience with salvage HBO2 for a 15-year-old male with refractory HC beginning one month post AHSCT and associated with BK virus. Despite supportive therapies including hyperhydration, forced diuresis, transfusions, intravenous and intravesical cidofovir, macroscopic hematuria persisted and resulted in post-obstructive acute renal failure, need for a suprapubic catheter, then bilateral percutaneous nephrostomy tubes. HBO2 was started two months after the AHSCT and one month after detection of BK viremia. In the week prior to starting HBO2 therapy the patient required transfusion with 25 units of red blood cells and seven units of platelets. After HBO2 was started his transfusion requirements progressively decreased, and he had return of renal function. He had no adverse effect from the HBO2. HBO2 therapy could thus be useful in controlling refractory HC after AHSCT.

2.
PLoS Pathog ; 14(1): e1006859, 2018 01.
Artigo em Inglês | MEDLINE | ID: mdl-29357385

RESUMO

Fleas can transmit Yersinia pestis by two mechanisms, early-phase transmission (EPT) and biofilm-dependent transmission (BDT). Transmission efficiency varies among flea species and the results from different studies have not always been consistent. One complicating variable is the species of rodent blood used for the infectious blood meal. To gain insight into the mechanism of EPT and the effect that host blood has on it, fleas were fed bacteremic mouse, rat, guinea pig, or gerbil blood; and the location and characteristics of the infection in the digestive tract and transmissibility of Y. pestis were assessed 1 to 3 days after infection. Surprisingly, 10-28% of two rodent flea species fed bacteremic rat or guinea pig blood refluxed a portion of the infected blood meal into the esophagus within 24 h of feeding. We term this phenomenon post-infection esophageal reflux (PIER). In contrast, PIER was rarely observed in rodent fleas fed bacteremic mouse or gerbil blood. PIER correlated with the accumulation of a dense mixed aggregate of Y. pestis, red blood cell stroma, and oxyhemoglobin crystals that filled the proventriculus. At their next feeding, fleas with PIER were 3-25 times more likely to appear partially blocked, with fresh blood retained within the esophagus, than were fleas without PIER. Three days after feeding on bacteremic rat blood, groups of Oropsylla montana transmitted significantly more CFU than did groups infected using mouse blood, and this enhanced transmission was biofilm-dependent. Our data support a model in which EPT results from regurgitation of Y. pestis from a partially obstructed flea foregut and that EPT and BDT can sometimes temporally overlap. The relative insolubility of the hemoglobin of rats and Sciurids and the slower digestion of their blood appears to promote regurgitative transmission, which may be one reason why these rodents are particularly prominent in plague ecology.


Assuntos
Sangue/microbiologia , Trato Gastrointestinal/microbiologia , Insetos Vetores/microbiologia , Peste/sangue , Peste/transmissão , Sifonápteros/microbiologia , Yersinia pestis/fisiologia , Animais , Trânsito Gastrointestinal/fisiologia , Gerbillinae , Cobaias , Camundongos , Ratos , Fatores de Tempo
3.
Crit Care Med ; 46(1): 85-92, 2018 01.
Artigo em Inglês | MEDLINE | ID: mdl-29088002

RESUMO

OBJECTIVES: We examined the effects of introducing patient-centered structured interdisciplinary bedside rounds in the medical ICU with respect to rounding efficiency, provider satisfaction, and patient/family satisfaction. DESIGN: A prospective, nonblinded, nonrandomized, parallel group study from June 21, 2016, to August 15, 2016. SETTING: The medical ICU at a tertiary care academic medical center. SUBJECTS: A consecutive sample of adult patients, family members, and healthcare providers. The patients and healthcare providers were arbitrarily assigned to either the patient-centered structured interdisciplinary bedside rounds or nonstructured interdisciplinary bedside round care team. INTERVENTIONS: Healthcare providers on the patient-centered structured interdisciplinary bedside rounds team were educated about their respective roles and the information they were expected to discuss on rounds each day. Rounds completion data and satisfaction questionnaires from healthcare providers, patients, and family members were obtained from both patient-centered structured interdisciplinary bedside rounds and nonstructured interdisciplinary bedside round teams. MEASUREMENTS AND MAIN RESULTS: Data were obtained from 367 patient-centered structured interdisciplinary bedside rounds and 298 nonstructured interdisciplinary bedside round patient encounters. Family members were present during 31.1% rounding encounters on the patient-centered structured interdisciplinary bedside rounds team and 10.1% encounters on the nonstructured interdisciplinary bedside round team (p < 0.01). Total rounding and interruption times were significantly shorter on patient-centered structured interdisciplinary bedside rounds compared with nonstructured interdisciplinary bedside round patients, 16.9 ± 10.0 versus 22.4 ± 14.9 and 2.0 ± 2.2 versus 3.9 ± 5.5 minutes, respectively (both p < 0.01). Mechanical ventilation, patient-centered structured interdisciplinary bedside rounds, and attending style independently contributed to the earlier completion of rounds (all p < 0.01). Surveys of 338 healthcare provider encounters on the patient-centered structured interdisciplinary bedside rounds team compared with 301 nonstructured interdisciplinary bedside round encounters showed perceptions of improved communication of patient management plans, increased input from the entire team, and clarity on task assignments (all p < 0.05). The attending physicians provided teaching points on 51.2% of patient-centered structured interdisciplinary bedside rounds compared with 33.9% of nonstructured interdisciplinary bedside round patient encounters (p < 0.01). For the patients and family members surveyed, 38 patient-centered structured interdisciplinary bedside rounds, and 30 nonstructured interdisciplinary bedside round, there were no differences in measures of satisfaction. CONCLUSIONS: Patient-centered structured interdisciplinary bedside rounds provide a venue for increased rounding efficiency, provider satisfaction, and consistent teaching, without impacting patient/family perception.


Assuntos
Unidades de Terapia Intensiva , Comunicação Interdisciplinar , Colaboração Intersetorial , Assistência Centrada no Paciente , Visitas com Preceptor , Centros Médicos Acadêmicos , Adulto , Idoso , Atitude do Pessoal de Saúde , California , Cuidadores , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Satisfação do Paciente , Estudos Prospectivos
4.
Annu Rev Microbiol ; 71: 215-232, 2017 09 08.
Artigo em Inglês | MEDLINE | ID: mdl-28886687

RESUMO

Interest in arthropod-borne pathogens focuses primarily on how they cause disease in humans. How they produce a transmissible infection in their arthropod host is just as critical to their life cycle, however. Yersinia pestis adopts a unique life stage in the digestive tract of its flea vector, characterized by rapid formation of a bacterial biofilm that is enveloped in a complex extracellular polymeric substance. Localization and adherence of the biofilm to the flea foregut is essential for transmission. Here, we review the molecular and genetic mechanisms of these processes and present a comparative evaluation and updated model of two related transmission mechanisms.


Assuntos
Adaptação Biológica , Biofilmes/crescimento & desenvolvimento , Insetos Vetores/microbiologia , Peste/microbiologia , Peste/transmissão , Sifonápteros/microbiologia , Yersinia pestis/fisiologia , Animais , Transmissão de Doença Infecciosa , Trato Gastrointestinal/microbiologia , Yersinia pestis/genética
5.
PLoS Negl Trop Dis ; 11(1): e0005276, 2017 01.
Artigo em Inglês | MEDLINE | ID: mdl-28081130

RESUMO

BACKGROUND: Transmission of Yersinia pestis by flea bite can occur by two mechanisms. After taking a blood meal from a bacteremic mammal, fleas have the potential to transmit the very next time they feed. This early-phase transmission resembles mechanical transmission in some respects, but the mechanism is unknown. Thereafter, transmission occurs after Yersinia pestis forms a biofilm in the proventricular valve in the flea foregut. The biofilm can impede and sometimes completely block the ingestion of blood, resulting in regurgitative transmission of bacteria into the bite site. In this study, we compared the relative efficiency of the two modes of transmission for Xenopsylla cheopis, a flea known to become completely blocked at a high rate, and Oropsylla montana, a flea that has been considered to rarely develop proventricular blockage. METHODOLOGY/PRINCIPAL FINDINGS: Fleas that took an infectious blood meal containing Y. pestis were maintained and monitored for four weeks for infection and proventricular blockage. The number of Y. pestis transmitted by groups of fleas by the two modes of transmission was also determined. O. montana readily developed complete proventricular blockage, and large numbers of Y. pestis were transmitted by that mechanism both by it and by X. cheopis, a flea known to block at a high rate. In contrast, few bacteria were transmitted in the early phase by either species. CONCLUSIONS: A model system incorporating standardized experimental conditions and viability controls was developed to more reliably compare the infection, proventricular blockage and transmission dynamics of different flea vectors, and was used to resolve a long-standing uncertainty concerning the vector competence of O. montana. Both X. cheopis and O. montana are fully capable of transmitting Y. pestis by the proventricular biofilm-dependent mechanism.


Assuntos
Insetos Vetores/fisiologia , Peste/transmissão , Sifonápteros/fisiologia , Xenopsylla/microbiologia , Yersinia pestis/fisiologia , Animais , Biofilmes , Feminino , Humanos , Insetos Vetores/microbiologia , Masculino , Peste/microbiologia , Sifonápteros/microbiologia , Xenopsylla/fisiologia , Yersinia pestis/genética
6.
PLoS Negl Trop Dis ; 10(2): e0004413, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26829486

RESUMO

BACKGROUND: The cat flea, Ctenocephalides felis, is prevalent worldwide, will parasitize animal reservoirs of plague, and is associated with human habitations in known plague foci. Despite its pervasiveness, limited information is available about the cat flea's competence as a vector for Yersinia pestis. It is generally considered to be a poor vector, based on studies examining early-phase transmission during the first week after infection, but transmission potential by the biofilm-dependent proventricular-blocking mechanism has never been systematically evaluated. In this study, we assessed the vector competence of cat fleas by both mechanisms. Because the feeding behavior of cat fleas differs markedly from important rat flea vectors, we also examined the influence of feeding behavior on transmission dynamics. METHODOLOGY/PRINCIPAL FINDINGS: Groups of cat fleas were infected with Y. pestis and subsequently provided access to sterile blood meals twice-weekly, 5 times per week, or daily for 4 weeks and monitored for infection, the development of proventricular biofilm and blockage, mortality, and the ability to transmit. In cat fleas allowed prolonged, daily access to blood meals, mimicking their natural feeding behavior, Y. pestis did not efficiently colonize the digestive tract and could only be transmitted during the first week after infection. In contrast, cat fleas that were fed intermittently, mimicking the feeding behavior of the efficient vector Xenopsylla cheopis, could become blocked and regularly transmitted Y. pestis for 3-4 weeks by the biofilm-mediated mechanism, but early-phase transmission was not detected. CONCLUSIONS: The normal feeding behavior of C. felis, more than an intrinsic resistance to infection or blockage by Y. pestis, limits its vector competence. Rapid turnover of midgut contents results in bacterial clearance and disruption of biofilm accumulation in the proventriculus. Anatomical features of the cat flea foregut may also restrict transmission by both early-phase and proventricular biofilm-dependent mechanisms.


Assuntos
Ctenocephalides/microbiologia , Ctenocephalides/fisiologia , Insetos Vetores/microbiologia , Insetos Vetores/fisiologia , Peste/transmissão , Yersinia pestis/fisiologia , Animais , Comportamento Alimentar , Feminino , Trato Gastrointestinal/microbiologia , Humanos , Masculino , Peste/microbiologia , Ovinos
7.
PLoS One ; 10(7): e0133318, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26177454

RESUMO

Yersinia pestis, the causative agent of bubonic and pneumonic plague, is typically a zoonotic vector-borne disease of wild rodents. Bacterial biofilm formation in the proventriculus of the flea contributes to chronic infection of fleas and facilitates efficient disease transmission. However prior to biofilm formation, ingested bacteria must survive within the flea midgut, and yet little is known about vector-pathogen interactions that are required for flea gut colonization. Here we establish a Drosophila melanogaster model system to gain insight into Y. pestis colonization of the insect vector. We show that Y. pestis establishes a stable infection in the anterior midgut of fly larvae, and we used this model system to study the roles of genes involved in biofilm production and/or resistance to gut immunity stressors. We find that PhoP and GmhA both contribute to colonization and resistance to antimicrobial peptides in flies, and furthermore, the data suggest biofilm formation may afford protection against antimicrobial peptides. Production of reactive oxygen species in the fly gut, as in fleas, also serves to limit bacterial infection, and OxyR mediates Y. pestis survival in both insect models. Overall, our data establish the fruit fly as an informative model to elucidate the relationship between Y. pestis and its flea vector.


Assuntos
Sistema Digestório/imunologia , Sistema Digestório/microbiologia , Resistência à Doença/imunologia , Drosophila melanogaster/imunologia , Drosophila melanogaster/microbiologia , Imunidade Inata , Yersinia pestis/fisiologia , Animais , Peptídeos Catiônicos Antimicrobianos/biossíntese , Biofilmes , Contagem de Colônia Microbiana , Sistema Digestório/parasitologia , Drosophila melanogaster/parasitologia , Larva/microbiologia , Larva/parasitologia , Mutação/genética , Espécies Reativas de Oxigênio/metabolismo , Sifonápteros/fisiologia
8.
mBio ; 4(6): e00837-13, 2013 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-24194541

RESUMO

Vector-borne infections begin in the dermis when a pathogen is introduced by an arthropod during a blood meal. Several barriers separate an invading pathogen from its replicative niche, including phagocytic cells in the dermis that activate immunity by engulfing would-be pathogens and migrating to the lymph node. In addition, neutrophils circulating in the blood are rapidly recruited when the dermal barriers are penetrated. For flea-borne disease, no insect-encoded immune-suppressive molecules have yet been described that might influence the establishment of infection, leaving the bacteria on their own to defend against the mammalian immune system. Shortly after a flea transmits Yersinia pestis to a mammalian host, the bacteria are transported to the lymph node, where they grow logarithmically and later spread systemically. Even a single cell of Y. pestis can initiate a lethal case of plague. In their article, J. G. Shannon et al. [mBio 4(5):e00170-13, 2013, doi:10.1128/mBio.00170-13] used intravital microscopy to visualize trafficking of Y. pestis in transgenic mice in vivo, which allowed them to examine interactions between bacteria and specific immune cells. Bacteria appeared to preferentially interact with neutrophils but had no detectable interactions with dendritic cells. These findings suggest that Y. pestis infection of neutrophils not only prevents their activation but may even result in their return to circulation and migration to distal sites.


Assuntos
Neutrófilos/imunologia , Peste/imunologia , Peste/microbiologia , Pele/imunologia , Yersinia pestis/imunologia , Animais , Feminino , Humanos
9.
PLoS One ; 6(3): e17352, 2011 Mar 02.
Artigo em Inglês | MEDLINE | ID: mdl-21399698

RESUMO

Molecular studies of bacterial virulence are enhanced by expression of recombinant DNA during infection to allow complementation of mutants and expression of reporter proteins in vivo. For highly pathogenic bacteria, such as Yersinia pestis, these studies are currently limited because deliberate introduction of antibiotic resistance is restricted to those few which are not human treatment options. In this work, we report the development of alternatives to antibiotics as tools for host-pathogen research during Yersinia pestis infections focusing on the diaminopimelic acid (DAP) pathway, a requirement for cell wall synthesis in eubacteria. We generated a mutation in the dapA-nlpB(dapX) operon of Yersinia pestis KIM D27 and CO92 which eliminated the expression of both genes. The resulting strains were auxotrophic for diaminopimelic acid and this phenotype was complemented in trans by expressing dapA in single and multi-copy. In vivo, we found that plasmids derived from the p15a replicon were cured without selection, while selection for DAP enhanced stability without detectable loss of any of the three resident virulence plasmids. The dapAX mutation rendered Y. pestis avirulent in mouse models of bubonic and septicemic plague which could be complemented when dapAX was inserted in single or multi-copy, restoring development of disease that was indistinguishable from the wild type parent strain. We further identified a high level, constitutive promoter in Y. pestis that could be used to drive expression of fluorescent reporters in dapAX strains that had minimal impact to virulence in mouse models while enabling sensitive detection of bacteria during infection. Thus, diaminopimelic acid selection for single or multi-copy genetic systems in Yersinia pestis offers an improved alternative to antibiotics for in vivo studies that causes minimal disruption to virulence.


Assuntos
Ácido Diaminopimélico/metabolismo , Técnicas Genéticas , Seleção Genética , Yersinia pestis/genética , Yersinia pestis/patogenicidade , Animais , Modelos Animais de Doenças , Espaço Extracelular/microbiologia , Fluorescência , Dosagem de Genes/genética , Genes Bacterianos/genética , Teste de Complementação Genética , Humanos , Espaço Intracelular/microbiologia , Proteínas Luminescentes , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Mutagênese Insercional/genética , Óperon/genética , Peste/microbiologia , Plasmídeos/genética , Regiões Promotoras Genéticas/genética , Virulência/genética , Yersinia pestis/crescimento & desenvolvimento
10.
Shock ; 35(4): 360-6, 2011 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-21068697

RESUMO

Patients who present to the emergency department (ED) with return of spontaneous circulation after cardiac arrest generally have poor outcomes. Guidelines for treatment can be complicated and difficult to implement. This study examined the feasibility of implementing a care bundle including therapeutic hypothermia (TH) and early hemodynamic optimization for comatose patients with return of spontaneous circulation after out-of-hospital cardiac arrest. The study included patients over a 2-year period in the ED and intensive care unit of an academic tertiary-care medical center. The first year (prebundle) provided a historical control, followed by a prospective observational period of bundle implementation during the second year. The bundle elements included (a) TH initiated; (b) central venous pressure/central venous oxygen saturation monitoring in 2 h; (c) target temperature in 4 h; (d) central venous pressure greater than 12 mmHg in 6 h; (e) MAP greater than 65 mmHg in 6 h; (f) central venous oxygen saturation greater than 70% in 6 h; (g) TH maintained for 24 h; and (h) decreasing lactate in 24 h. Fifty-five patients were enrolled, 26 patients in the prebundle phase and 29 patients in the bundle phase. Seventy-seven percent of bundle elements were completed during the bundle phase. In-hospital mortality in bundle compared with prebundle patients was 55.2% vs. 69.2% (P = 0.29). In the bundle patients, those patients who received all elements of the care bundle had mortality 33.3% compared with 60.9% in those receiving some of the bundle elements (P = 0.22). Bundle patients tended to achieve good neurologic outcome compared with prebundle patients, Cerebral Performance Category 1 or 2 in 31 vs. 12% patients, respectively (P = 0.08). Our study demonstrated that a post-cardiac arrest care bundle that incorporates TH and early hemodynamic optimization can be implemented in the ED and intensive care unit collaboratively and can achieve similar clinical benefits compared with those observed in previous clinical trials.


Assuntos
Coma/fisiopatologia , Coma/terapia , Parada Cardíaca/fisiopatologia , Hipotermia Induzida/métodos , Idoso , Feminino , Hemodinâmica , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos
11.
World J Gastroenterol ; 12(33): 5306-10, 2006 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-16981259

RESUMO

AIM: To investigate the role of MHC class II in the modulation of gastric epithelial cell apoptosis induced by H pylori infection. METHODS: After stimulating a human gastric epithelial cell line with bacteria or agonist antibodies specific for MHC class II and CD95, the quantitation of apoptotic and anti-apoptotic events, including caspase activation, BCL-2 activation, and FADD recruitment, was performed with a fluorometric assay, a cytometric bead array, and confocal microscopy, respectively. RESULTS: Pretreatment of N87 cells with the anti-MHC class II IgM antibody RFD1 resulted in a reduction in global caspase activation at 24 h of H pylori infection. When caspase 3 activation was specifically measured, crosslinking of MHC class II resulted in a marked reduced caspase activation, while simple ligation of MHC class II did not. Crosslinking of MHC class II also resulted in an increased activation of the anti-apoptosis molecule BCL-2 compared to simple ligation. Confocal microscope analysis demonstrated that the pretreatment of gastric epithelial cells with a crosslinking anti-MHC class II IgM blocked the recruitment of FADD to the cell surface. CONCLUSION: The results presented here demonstrate that the ability of MHC class II to modulate gastric epithelial apoptosis is at least partially dependent on its crosslinking. Furthermore, while previous research has demonstrated that MHC class II signaling can be pro-apoptotic during extended ligation, we have shown that the crosslinking of this molecule has anti-apoptotic effects during the earlier time points of H pylori infection. This effect is possibly mediated by the ability of MHC class II to modulate the activation of the pro-apoptotic receptor Fas by blocking the recruitment of the accessory molecule FADD, and this delay in apoptosis induction could allow for prolonged cytokine secretion by H pylori-infected gastric epithelial cells.


Assuntos
Apoptose , Epitélio/metabolismo , Epitélio/microbiologia , Mucosa Gástrica/metabolismo , Mucosa Gástrica/microbiologia , Genes MHC da Classe II , Infecções por Helicobacter/metabolismo , Helicobacter pylori/metabolismo , Antígenos de Histocompatibilidade Classe II/metabolismo , Caspase 3/metabolismo , Caspases/metabolismo , Linhagem Celular , Linhagem Celular Tumoral , Fragmentação do DNA , Ativação Enzimática , Humanos , Microscopia Confocal , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Receptor fas/biossíntese
12.
World J Gastroenterol ; 12(29): 4689-93, 2006 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-16937440

RESUMO

AIM: To investigate the role of MHC class II in the modulation of gastric epithelial cell apoptosis induced by H pylori infection. METHODS: After stimulating a human gastric epithelial cell line with bacteria or agonist antibodies specific for MHC class II and CD95, the quantitation of apoptotic and anti-apoptotic events, including caspase activation, BCL-2 activation, and FADD recruitment, was performed with a fluorometric assay, a cytometric bead array, and confocal microscopy, respectively. RESULTS: Pretreatment of N87 cells with the anti-MHC class II IgM antibody RFD1 resulted in a reduction in global caspase activation at 24 h of H pylori infection. When caspase 3 activation was specifically measured, crosslinking of MHC class II resulted in markedly reduced caspase activation, while simple ligation of MHC class II did not. Crosslinking of MHC class II also resulted in an increased activation of the anti-apoptosis molecule BCL-2 compared to simple ligation. Confocal microscope analysis demonstrated that the pretreatment of gastric epithelial cells with a crosslinking anti-MHC class II IgM blocked the recruitment of FADD to the cell surface. CONCLUSION: The ability of MHC class II to modulate gastric epithelial apoptosis is at least partially dependent on its crosslinking. The crosslinking of this molecule has anti-apoptotic effects during the earlier time points of H pylori infection. This effect is possibly mediated by the ability of MHC class II to modulate the activation of the pro-apoptotic receptor Fas by blocking the recruitment of the accessory molecule FADD, and this delay in apoptosis induction could allow for prolonged cytokine secretion by H pylori-infected gastric epithelial cells.


Assuntos
Apoptose/fisiologia , Infecções por Helicobacter/fisiopatologia , Helicobacter pylori/imunologia , Antígenos de Histocompatibilidade Classe II/fisiologia , Estômago/microbiologia , Estômago/patologia , Proteínas Adaptadoras de Transdução de Sinal/fisiologia , Anticorpos/imunologia , Anticorpos/farmacologia , Caspase 3 , Caspases/fisiologia , Linhagem Celular , Ativação Enzimática/fisiologia , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/microbiologia , Células Epiteliais/patologia , Proteína de Domínio de Morte Associada a Fas , Infecções por Helicobacter/imunologia , Infecções por Helicobacter/patologia , Antígenos de Histocompatibilidade Classe II/imunologia , Humanos , Proteínas Proto-Oncogênicas c-bcl-2/fisiologia , Estômago/efeitos dos fármacos , Estômago/fisiopatologia , Receptor fas/imunologia , Receptor fas/fisiologia
13.
Am J Crit Care ; 14(5): 370-6, 2005 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-16120888

RESUMO

BACKGROUND: Critically ill postsurgical patients fare better with intensive control of blood glucose level. The link between glucose control and outcome is less well studied for medical intensive care patients. Whether intensive glucose control requires additional staffing is unclear. OBJECTIVES: To compare intensive glucose control with modified conventional control in the medical intensive care unit and to assess compliance with glucose targets, incidence of hypoglycemia, and staffing adequacy. METHODS: Medical intensive care patients who had been receiving mechanical ventilation for less than 24 hours were randomized to intensive or modified conventional protocols for glucose control. Nurses were trained before participating in the study and were interviewed after its completion. RESULTS: Five subjects were randomized to each protocol. Mean blood glucose levels were 5.8 (SD 1.5) mmol/L (105.3 [SD 26.3] mg/dL) for the intensive group and 9.8 (SD 2.5) mmol/L (177.4 [SD 45.5] mg/dL) for the modified conventional group (P < .001). Fifty percent of glucose levels met target values in the intensive group, and 72% of glucose levels met target values in the modified conventional group (P < .001). Severe hypoglycemia (glucose <2.2 mmol/L [<40 mg/dL]) occurred rarely and without complication. Nurses suggested protocols might be improved by using smaller steps in adjusting insulin dosage and reported that simultaneously caring for more than 1 study subject was taxing. CONCLUSIONS: Target levels for blood glucose were achieved with both protocols. Severe hypoglycemia was rare and uncomplicated regardless of type of glucose control. Additional staffing may be needed for intensive glucose control.


Assuntos
Glicemia/análise , Estado Terminal/terapia , Hipoglicemiantes/administração & dosagem , Insulina/administração & dosagem , Adulto , Idoso , Protocolos Clínicos , Cuidados Críticos/métodos , Feminino , Humanos , Hiperglicemia/tratamento farmacológico , Hipoglicemiantes/uso terapêutico , Insulina/uso terapêutico , Sistemas de Infusão de Insulina , Masculino , Pessoa de Meia-Idade , Projetos Piloto
14.
J Histochem Cytochem ; 53(12): 1481-9, 2005 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-15923369

RESUMO

CD74 is known as the major histocompatibility complex (MHC) class II-associated invariant chain (Ii) that regulates the cell biology and functions of MHC class II molecules. Class II MHC and Ii expression was believed to be restricted to classical antigen-presenting cells (APC); however, during inflammation, other cell types, including mucosal epithelial cells, have also been reported to express class II MHC molecules. Given the importance of Ii in the biology of class II MHC, we sought to examine the expression of Ii by gastric epithelial cells (GEC) to determine whether class II MHC molecules in these nonconventional APC cells were under the control of Ii and to further support the role that these cells may play in local immune and inflammatory responses during Helicobacter pylori infection. Thus we examined the expression of Ii on GEC from human biopsy samples and then confirmed this observation using independent methods on several GEC lines. The mRNA for Ii was detected by RT-PCR, and the various protein isoforms were also detected. Interestingly, these cells have a high level expression of surface Ii, which is polarized to the apical surface. These studies are the first to demonstrate the constitutive expression of Ii by human GEC.


Assuntos
Células Apresentadoras de Antígenos/metabolismo , Antígenos CD/biossíntese , Antígenos de Diferenciação de Linfócitos B/biossíntese , Células Epiteliais/metabolismo , Mucosa Gástrica/metabolismo , Antígenos de Histocompatibilidade Classe II/biossíntese , Antígenos CD/genética , Antígenos de Diferenciação de Linfócitos B/genética , Linhagem Celular , Mucosa Gástrica/citologia , Gastrite/metabolismo , Gastrite/microbiologia , Infecções por Helicobacter/metabolismo , Helicobacter pylori , Antígenos de Histocompatibilidade Classe II/genética , Humanos , Isoformas de Proteínas/biossíntese , Isoformas de Proteínas/genética , RNA Mensageiro/biossíntese , Reação em Cadeia da Polimerase Via Transcriptase Reversa
15.
Infect Immun ; 73(5): 2736-43, 2005 May.
Artigo em Inglês | MEDLINE | ID: mdl-15845476

RESUMO

The pathogenesis associated with Helicobacter pylori infection requires consistent contact with the gastric epithelium. Although several cell surface receptors have been suggested to play a role in adhesion, the bacterium-host interactions that elicit host responses are not well defined. This study investigated the interaction of H. pylori with the class II major histocompatibility complex (MHC)-associated invariant chain (Ii; CD74), which was found to be highly expressed by gastric epithelial cells. Bacterial binding was increased when CD74 surface expression was increased by gamma interferon (IFN-gamma) treatment or by fibroblast cells transfected with CD74, while binding was decreased by CD74 blocking antibodies, enzyme cleavage of CD74, and CD74-coated bacteria. H. pylori was also shown to bind directly to affinity-purified CD74 in the absence of class II MHC. Cross-linking of CD74 and the engagement of CD74 were verified to stimulate IL-8 production by unrelated cell lines expressing CD74 in the absence of class II MHC. Increased CD74 expression by cells increased IL-8 production in response to H. pylori, and agents that block CD74 decreased these responses. The binding of H. pylori to CD74 presents a novel insight into an initial interaction of H. pylori with the gastric epithelium that leads to upregulation of inflammatory responses.


Assuntos
Antígenos de Diferenciação de Linfócitos B/metabolismo , Células Epiteliais/microbiologia , Mucosa Gástrica/microbiologia , Helicobacter pylori/imunologia , Helicobacter pylori/patogenicidade , Antígenos de Histocompatibilidade Classe II/metabolismo , Interleucina-8/biossíntese , Antígenos de Diferenciação de Linfócitos B/genética , Aderência Bacteriana , Linhagem Celular , Fibroblastos , Mucosa Gástrica/citologia , Helicobacter pylori/metabolismo , Antígenos de Histocompatibilidade Classe II/genética , Humanos , Transfecção , Regulação para Cima
16.
J Reprod Med ; 47(7): 591-6, 2002 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-12170540

RESUMO

BACKGROUND: In contrast to the frequent occurrence of localized herpes simplex virus (HSV) infections during pregnancy, disseminated disease has rarely been reported. CASE: A 21-year-old woman in the 27th week of gestation developed a catastrophic illness characterized by fever, progressive pneumonia, respiratory failure, leukopenia, disseminated intravascular coagulation (DIC), anicteric hepatitis, septic shock and acute renal failure. Initial studies for an infectious etiology were negative. In spite of empiric broad-spectrum antimicrobial therapy, her condition continued to deteriorate. Sparse vesicular skin lesions suggestive of HSV infection subsequently appeared. Despite initiation of acyclovir therapy, the patient died. HSV type 2 was cultured from a skin vesicle, and at autopsy there was extensive necrosis of the liver and lung with immunohistochemical stains positive for HSV antigen. CONCLUSION: In the third trimester of pregnancy, HSV can occasionally disseminate in immunocompetent women. A clinical syndrome of unexplained fever, pneumonia, anicteric hepatitis, leukopenia and DIC without mucocutaneous lesions should prompt investigation and possible treatment for disseminated HSV infection.


Assuntos
Herpes Simples/diagnóstico , Complicações Infecciosas na Gravidez/diagnóstico , Viremia/diagnóstico , Aciclovir/uso terapêutico , Adulto , Antígenos Virais/isolamento & purificação , Antivirais/uso terapêutico , Diagnóstico Diferencial , Coagulação Intravascular Disseminada/etiologia , Evolução Fatal , Feminino , Herpes Simples/complicações , Herpes Simples/tratamento farmacológico , Herpesvirus Humano 2/imunologia , Herpesvirus Humano 2/isolamento & purificação , Humanos , Imuno-Histoquímica , Gravidez , Complicações Infecciosas na Gravidez/tratamento farmacológico , Terceiro Trimestre da Gravidez , Viremia/complicações , Viremia/tratamento farmacológico
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