RESUMO
With the recent global surge of SARS-CoV-2 Delta variant, there continues to be high demand for COVID-19 diagnostic testing. Abbott ID NOW is a rapid, CLIA-waived, COVID-19 diagnostic test ideally suited for use in urgent care settings or where access to diagnostic testing is limited. In this study we describe the results of rigorous validation of ID NOW and post-implementation study of POC test utilization patterns within community hospitals and clinics. Performance of ID NOW was validated by comparison of the results from 207 consecutive, paired, specimens tested on the ID NOW and on the m2000/Alinity m platforms. Once validated, ID NOW devices were placed for clinical use at four regional hospitals and clinics. We found that the ID NOW and m2000/Alinity m positive and negative percent agreement were 94.5% (95% CI, 85.1% to 98.1%) and 99.3% (95% CI, 96.4% to 99.9%), respectively. As of August 2021, a total of 2,301 tests were performed by ID NOW at individual regional network sites. The population tested consisted of 55.5% White and 42.9% Black patients, with Black patients presenting predominantly in the hospitals, while White patients were more evenly distributed between hospital and clinic sites. Disease prevalence observed among patients tested by ID NOW (12.3%) was aligned with overall prevalence seen at regional sites (11.3%). In summary, the ID NOW test can provide rapid and accurate results in a variety of near-to-patient and POC settings. If used correctly, it could serve as a valuable diagnostic tool to enable equal access to care and improve healthcare delivery within large health network systems.
Assuntos
COVID-19 , SARS-CoV-2 , Humanos , Teste para COVID-19 , COVID-19/diagnóstico , COVID-19/epidemiologia , Técnicas de Laboratório Clínico/métodos , Fluxo de Trabalho , Sensibilidade e Especificidade , Atenção à SaúdeRESUMO
A healthy adult male patient presented himself, 11 days after a fixed orthodontic appliance was placed, with a sudden pink discoloration of the dental crown of tooth 21. The emergency dentist on call diagnosed the discoloration as non-painful peri-apical periodontitis, partly on the basis of a radiograph, and recommended endodontic treatment of tooth 21. Prior to endodontic treatment, the patient was first seen by the orthodontist who had initiated treatment. Tooth 21 was investigated and reacted normally to percussion and palpation but did not react to the cold test. The patient was referred to an endodontist who made the likely diagnosis: 'Transient apical breakdown'. No endodontic treatment was carried out and the orthodontic treatment was not interrupted. Six weeks after the discoloration appeared, visible recovery was evident.
Assuntos
Periodontite Periapical , Descoloração de Dente , Adulto , Dente Pré-Molar , Humanos , Masculino , Descoloração de Dente/diagnóstico , Descoloração de Dente/etiologiaRESUMO
Multidrug-resistant organisms (MDRO) have been developing as an emerging problem in allogeneic hematopoietic cell transplantation (HCT). Since no data are available on the course of MDRO colonization after HCT, we investigated in this retrospective, single-center study, persistence and clearance of MDRO after HCT. From June 2010 to December 2015, 121 consecutive HCT patients were included. Patients received a MDRO screening before conditioning as well as surveillance cultures after HCT. In MDRO-colonized patients, surveillance specimens were taken until MDRO were no longer detectable. Thirty-three patients (27%) were found to be colonized by at least one MDRO at any time point until day 100 post HCT. Day 100 (2-year) non-relapse mortality (NRM) and overall survival (OS) of MDRO-colonized (MDRO+) versus non-colonized (MDRO-) patients were essentially the same. NRM is 15% (21%) versus 15% (24%). Two-year OS is 60 versus 55% for MDRO+ versus MDRO- patients. Out of the 33 MDRO+ patients, 21 cleared the MDRO. Median time to non-detectability of MDRO was 6 months. In 12 patients, the MDRO persisted. There was a significant (p < 0.0001) survival difference between patients who cleared the MDRO versus those with MDRO persistence (2-year OS 80 vs 40%). Except for the length of antibiotic therapy as a potential risk factor for MDRO persistence after HCT, no other conventional factors could be identified. (a) colonization by MDRO per se had no negative impact on the outcome, (b) MDRO can be cleared by the majority of patients after allogeneic HCT, and (c) to increase the probability to clear MDRO, the use of antibiotics in MDRO+ patients should be reviewed critically.
Assuntos
Farmacorresistência Bacteriana Múltipla , Farmacorresistência Fúngica Múltipla , Transplante de Células-Tronco Hematopoéticas , Staphylococcus aureus Resistente à Meticilina , Infecções por Pneumocystis , Pneumocystis carinii , Infecções Estafilocócicas , Adulto , Idoso , Aloenxertos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Infecções por Pneumocystis/tratamento farmacológico , Infecções por Pneumocystis/epidemiologia , Infecções por Pneumocystis/etiologia , Estudos Retrospectivos , Fatores de Risco , Infecções Estafilocócicas/tratamento farmacológico , Infecções Estafilocócicas/epidemiologia , Infecções Estafilocócicas/etiologiaRESUMO
BACKGROUND/OBJECTIVES: Characterisation of the adipocyte cellular lineage is required for a better understanding of white adipose tissue homoeostasis and expansion. Although several studies have focused on the phenotype of the most immature adipocyte progenitors, very few tools exist to identify committed cells. In haematopoiesis, the CD38 ectoenzyme is largely used to delineate various stages of stem cell lineage commitment. We hypothesise that this marker could be used to identify committed preadipocytes. METHODS: Complementary strategies including flow cytometry, cell-sorting approaches, immunohistochemistry and primary cultures of murine adipose progenitors isolated from different fat pads of control or high-fat diet exposed C57BL/6 J mice were used to determine the molecular expression profile, proliferative and differentiation potentials of adipose progenitors expressing the CD38 molecule. RESULTS: We demonstrate here that a subpopulation of CD45- CD31- CD34+ adipose progenitors express the cell surface protein CD38. Using a cell-sorting approach, we found that native CD45- CD31- CD34+ CD38+ (CD38+) adipose cells expressed lower CD34 mRNA and protein levels and higher levels of adipogenic genes such as Pparg, aP2, Lpl and Cd36 than did the CD45- CD31- CD34+ CD38- (CD38-) population. When cultivated, CD38+ cells displayed reduced proliferative potential, assessed by BrdU incorporation and colony-forming unit assays, and greater adipogenic potential. In vitro, both CD38 mRNA and protein levels were increased during adipogenesis and CD38- cells converted into CD38+ cells when committed to the adipogenic differentiation programme. We also found that obesity development was associated with an increase in the number of CD38+ adipose progenitors, this effect being more pronounced in intra-abdominal than in subcutaneous fat, suggesting a higher rate of adipocyte commitment in visceral depots. CONCLUSIONS: Together, these data demonstrate that CD38 represents a new marker that identifies committed preadipocytes as CD45- CD31- CD34low CD38+ cells.
Assuntos
ADP-Ribosil Ciclase 1/metabolismo , Adipócitos/citologia , Tecido Adiposo Branco/citologia , Diferenciação Celular , Linhagem da Célula , Glicoproteínas de Membrana/metabolismo , Obesidade/metabolismo , Adipócitos/metabolismo , Tecido Adiposo Branco/metabolismo , Animais , Biomarcadores/metabolismo , Células Cultivadas , Dieta Hiperlipídica , Modelos Animais de Doenças , Citometria de Fluxo , Imuno-Histoquímica , Masculino , Síndrome Metabólica/metabolismo , Síndrome Metabólica/fisiopatologia , Camundongos , Camundongos Endogâmicos C57BL , Obesidade/fisiopatologia , Células Estromais/citologiaRESUMO
High mortality rates of invasive fungal disease (IFD), especially invasive aspergillosis (IA), in immunocompromised haematological patients and current diagnostic limitations require improvement of detection of fungal pathogens by defining the optimal use of biomarkers and clinical samples. Concurrent bronchoalveolar lavage (BAL) and peripheral blood samples of 99 haematological patients with suspected IFD were investigated within a multicentre prospective study. Diagnostic performance of a galactomannan (GM) enzyme immune assay (EIA), a 1,3-ß-D-glucan assay (BDG), an Aspergillus PCR, and a multifungal DNA-microarray (Chip) alone or in combination were calculated. IFD were classified as proven (n=3), probable (n=34), possible (n=33), and no IFD (n=29) according to EORTC/MSG criteria. GM, PCR, and Chip showed superior diagnostic performance in BAL than in blood, whereas specificity of BDG in BAL was poor (48% (14/29)). The combination of GM (BAL) with BDG (blood) showed sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and DOR (diagnostic odds ratio) of 92% (34/37), 93% (27/29), 94%, 90%, and 153.0, respectively. Combining GM (BAL) with PCR (BAL) showed convincing diagnostic potential for diagnosing IA with sensitivity, specificity, PPV, NPV, and DOR of 85% (17/20), 97% (28/29), 94%, 90%, and 158.7. Addition of the DNA-microarray resulted in further detection of two mucormycetes infections. In 1 out of 15 Aspergillus DNA-positive samples a triazole resistance-mediating Cyp51A mutation was found. Combination of biomarkers is superior to their sole use in diagnosing IFD, particularly IA. Integrating blood and BAL samples into a diagnostic algorithm is an advantageous approach.
Assuntos
Aspergilose/diagnóstico , Líquido da Lavagem Broncoalveolar/microbiologia , Infecções Fúngicas Invasivas/diagnóstico , Técnicas Microbiológicas/métodos , Técnicas de Diagnóstico Molecular/métodos , Aspergilose/sangue , Aspergillus/efeitos dos fármacos , Aspergillus/genética , Azóis/farmacologia , Galactose/análogos & derivados , Humanos , Infecções Fúngicas Invasivas/sangue , Mananas/análise , Reação em Cadeia da Polimerase Multiplex/métodos , Análise de Sequência com Séries de Oligonucleotídeos/métodos , Estudos Prospectivos , Sensibilidade e Especificidade , beta-Glucanas/análiseAssuntos
Fatores Imunológicos/uso terapêutico , Mutação , Síndromes Mielodisplásicas/tratamento farmacológico , Síndromes Mielodisplásicas/genética , Talidomida/análogos & derivados , Proteína Supressora de Tumor p53/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Deleção Cromossômica , Cromossomos Humanos Par 5/genética , Feminino , Humanos , Lenalidomida , Masculino , Pessoa de Meia-Idade , Prevalência , Estudos Prospectivos , Talidomida/uso terapêuticoAssuntos
Fatores Imunológicos/uso terapêutico , Síndromes Mielodisplásicas/tratamento farmacológico , Talidomida/análogos & derivados , Adulto , Idoso , Idoso de 80 Anos ou mais , Deleção Cromossômica , Cromossomos Humanos Par 5/genética , Feminino , Humanos , Estimativa de Kaplan-Meier , Lenalidomida , Masculino , Pessoa de Meia-Idade , Síndromes Mielodisplásicas/genética , Síndromes Mielodisplásicas/mortalidade , Modelos de Riscos Proporcionais , Estudos Prospectivos , Talidomida/uso terapêutico , Resultado do TratamentoRESUMO
Fluoroquinolone (FQ) and fluconazole prophylaxis is recommended for patients undergoing allogeneic hematopoietic cell transplantation (alloHCT). However, due to an uncertain scientific basis and the increasing emergence of resistant germs, this policy should be questioned. Therefore, FQ and fluconazole prophylaxis was omitted in alloHCT at our center. In this retrospective analysis, all consecutive patients (n = 63) who underwent first alloHCT at our institution from September 2010 to September 2013 were included. Patients neither received FQ nor fluconazole prophylaxis. Day 100 mortality, incidence of febrile neutropenia, bacterial infections, and invasive fungal diseases (IFD) were assessed. Sixteen patients who started conditioning under antimicrobial treatment/prophylaxis due to pre-existing neutropenia (3/16), IFD (12/16), or aortic valve replacement (1/16) were excluded from the analysis. Finally, 47 patients were transplanted without prophylaxis as intended. Day 100 mortality was 9 %. Febrile neutropenia occurred in 62 % (29/47); 17/47 patients (36 %) experienced a blood stream infection (BSI) with detection of Gram-positive bacteria in 14 patients, Gram-negative bacteria in five patients, and candida in one patient, respectively. Coagulase-negative staphylococci were the most frequently isolated Gram-positive bacteria; 12/21 isolated Gram-positive and 3/6 Gram-negative bacteria were FQ resistant. In 21 % (10/47) of the patients, IFD (1x proven, 1x probable, and 8x possible) were diagnosed. To conclude, all three criteria, day 100 mortality, the incidence of IFD, and BSI, are in the range of published data for patients transplanted with FQ and fluconazole prophylaxis. These data demonstrate that alloHCT is feasible without FQ and fluconazole prophylaxis.
Assuntos
Fluconazol , Fluoroquinolonas , Transplante de Células-Tronco Hematopoéticas/métodos , Profilaxia Pré-Exposição , Condicionamento Pré-Transplante , Adulto , Idoso , Feminino , Fluconazol/administração & dosagem , Fluoroquinolonas/administração & dosagem , Humanos , Leucemia/diagnóstico , Leucemia/terapia , Masculino , Pessoa de Meia-Idade , Síndromes Mielodisplásicas/diagnóstico , Síndromes Mielodisplásicas/terapia , Estudos Retrospectivos , Transplante Homólogo/métodos , Adulto JovemAssuntos
Transfusão de Sangue , Eritropoetina/uso terapêutico , Ácidos Hidroxâmicos/uso terapêutico , Indóis/uso terapêutico , Síndromes Mielodisplásicas/tratamento farmacológico , Administração Oral , Eritropoetina/administração & dosagem , Humanos , Ácidos Hidroxâmicos/administração & dosagem , Indóis/administração & dosagem , PanobinostatRESUMO
The majority of patients with myelodysplastic syndrome (MDS) present with anemia and will become dependent on regular transfusions of packed red blood cells (PRBC) with the risk of iron overload (IOL). Liver iron content best reflects the total body iron content, and measurement of liver iron concentration (LIC) by MRI is a validated tool for detection, but data in MDS is rather limited. Here we present the results of a multi-center trial evaluating the efficacy and safety of deferasirox (DFX) in low and intermediate-1 risk MDS patients with transfusion-dependent IOL. Three patients with transfusion frequency of > 4 units PRBC per month were initially treated with 30 mg/kg/day while in 46 patients with a lower transfusion burden deferasirox was initiated at 20 mg/kg/day, due to patient related reasons one patient received DFX in a dose of 6 mg/kg/day only. LIC was measured by MRI at baseline and end of study using the method by St. Pierre et al. The intention to treat population consisted of 50 MDS patients (28 male; 22 female) with a median age of 69 years who were treated with DFX for a median duration of 354 days. Mean daily dose of DFX was 19 mg/kg/day. Median serum ferritin level (SF) at baseline was 2,447 ng/mL and decreased to 1,685 ng/mL (reduction by 31 %) at end of study (p = 0.01). In 7 (13 %) patients the initially chosen dose had to be increased due to unsatisfactory efficacy of chelation therapy. For 21 patients, LIC measurement by liver MRI was performed at baseline and for 19 of these patients at the end of study: mean LIC decreased significantly from 16,8 mg/g dry tissue weight (± 8.3 mg/g dry tissue weight) at study entry to 10,8 mg/g dry tissue weight (± 10.4 mg/g dry tissue weight) at end of study (p = 0.01). Of all patients exposed to the study drug (n = 54), 28 (52 %) did not complete the 12 month study period most commonly due to AEs in 28 % (n = 15) and abnormal laboratory values in 7 % (n = 4), respectively. The most common adverse events (≥ 10 % of all patients) with suspected drug relationship were diarrhea (n = 25, 46 %), nausea (n = 13, 24 %), upper abdominal pain (n = 8, 15 %), serum creatinine increase (n = 16, 30 %) and rash (n = 5, 9 %). Adverse events making dose adjustments or interruption of study drug necessary occurred in 33 patients (61 %). Hematologic improvement according to IWG criteria (2006) was observed in 6 patients (11 %). Initiation of treatment of IOL with DFX depending on the transfusion burden yields sufficient reduction of excess iron indicated by serum ferritin levels and most importantly by liver MRI. The safety profile of DFX was comparable to previous observations.
Assuntos
Benzoatos/uso terapêutico , Terapia por Quelação , Quelantes de Ferro/uso terapêutico , Sobrecarga de Ferro/tratamento farmacológico , Síndromes Mielodisplásicas/terapia , Reação Transfusional , Triazóis/uso terapêutico , Administração Oral , Adulto , Idoso , Idoso de 80 Anos ou mais , Benzoatos/administração & dosagem , Benzoatos/efeitos adversos , Terapia por Quelação/efeitos adversos , Creatinina/sangue , Deferasirox , Toxidermias/etiologia , Feminino , Ferritinas/sangue , Gastroenteropatias/induzido quimicamente , Humanos , Ferro/análise , Quelantes de Ferro/administração & dosagem , Quelantes de Ferro/efeitos adversos , Sobrecarga de Ferro/etiologia , Fígado/química , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Síndromes Mielodisplásicas/epidemiologia , Risco , Resultado do Tratamento , Triazóis/administração & dosagem , Triazóis/efeitos adversosAssuntos
Transfusão de Sangue , Transplante de Medula Óssea , Síndromes Mielodisplásicas/terapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/uso terapêutico , Azacitidina/uso terapêutico , Terapia por Quelação , Deleção Cromossômica , Cromossomos Humanos Par 5/genética , Feminino , Humanos , Sobrecarga de Ferro/etiologia , Sobrecarga de Ferro/terapia , Lenalidomida , Leucemia Mieloide Aguda/diagnóstico , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/terapia , Assistência de Longa Duração , Masculino , Pessoa de Meia-Idade , Síndromes Mielodisplásicas/diagnóstico , Síndromes Mielodisplásicas/genética , Cuidados Paliativos , Talidomida/análogos & derivados , Talidomida/uso terapêuticoRESUMO
OBJECTIVE: To test the hypothesis that in young, normotensive obese subjects, physical activity at a fixed, moderate workload, causes a more pronounced hypertensive effect than in lean subjects. PATIENTS AND METHODS: 24 subjects (12 with BMI >30 kg/m(2), 12 with BMI <25 kg/m(2)), underwent a moderate-intensity physical activity protocol (cycling at 100 W). Blood pressure and oxygen consumption were monitored continuously. RESULTS: In the obese subjects, physical activity caused a more pronounced increase in both systolic blood pressure (increase of 40.4 +/- 15.3 mmHg vs 21.2 +/- 10.2 mmHg in lean subjects; p=0.001) and diastolic blood pressure (17.5 +/- 17.9 mmHg vs 3.2 +/- 8.1 mmHg in lean subjects; p=0.02). In regression analyses, these differences were only partly explained by small differences in resting blood pressure. CONCLUSION: Healthy obese subjects show an enhanced prohypertensive response of both systolic and diastolic blood pressure to moderate-intensity physical activity.
Assuntos
Pressão Sanguínea , Exercício Físico/fisiologia , Hipertensão/etiologia , Atividade Motora/fisiologia , Obesidade/complicações , Adulto , Índice de Massa Corporal , Estudos de Casos e Controles , Terapia por Exercício , Feminino , Hemodinâmica , Humanos , Hipertensão/prevenção & controle , Masculino , Análise Multivariada , Obesidade/fisiopatologia , Consumo de Oxigênio , Análise de Regressão , Inquéritos e QuestionáriosRESUMO
OBJECTIVE: To investigate the marked increase noted over an 8-month period in the number of Legionella pneumophila isolates recovered from bronchoalveolar lavage fluid specimens obtained during bronchoscopy in our healthcare system. SETTING: Bronchoscopy suite that serves a 580-bed tertiary care center and a large, multisite, faculty practice plan with approximately 2 million outpatient visits per year. METHODS: Cultures of environmental specimens from the bronchoscopy suite were performed, including samples from the air and water filters, bronchoscopes, and the ice machine, with the aim of identifying Legionella species. Specimens were filtered and acid-treated and then inoculated on buffered charcoal yeast extract agar. Serogrouping was performed on all isolates recovered from patient and environmental samples. RESULTS: All L. pneumophila isolates recovered from patients were serogroup 8, a serogroup that is not usually recovered in our facility. An epidemiologic investigation of the bronchoscopy suite revealed the ice machine to be contaminated with L. pneumophila serogroup 8. Patients were exposed to the organism as a result of a recently adopted practice in the bronchoscopy suite that involved directly immersing uncapped syringes of sterile saline in contaminated ice baths during the procedures. At least 1 patient was ill as a result of the pseudo-outbreak. Molecular typing of isolates recovered from patient and environmental samples revealed that the isolates were indistinguishable. CONCLUSIONS: Extensive cleaning of the ice machine and replacement of the machine's water filter ended the pseudo-outbreak. This episode emphasizes the importance of using aseptic technique when performing invasive procedures, such as bronchoscopies. It also demonstrates the importance of reviewing procedures in all patient areas to ensure compliance with facility policies for providing a safe patient environment.
Assuntos
Surtos de Doenças , Contaminação de Equipamentos , Gelo , Legionella pneumophila/isolamento & purificação , Doença dos Legionários/epidemiologia , Adulto , Idoso , Líquido da Lavagem Broncoalveolar/microbiologia , Broncoscópios , Infecção Hospitalar/epidemiologia , Infecção Hospitalar/microbiologia , Infecção Hospitalar/transmissão , Reservatórios de Doenças , Feminino , Humanos , Legionella pneumophila/classificação , Legionella pneumophila/genética , Doença dos Legionários/microbiologia , Doença dos Legionários/transmissão , Masculino , Pessoa de Meia-Idade , Sorotipagem , Microbiologia da ÁguaRESUMO
We report a case of rhino-orbital zygomycosis in a 43-year-old male with well-controlled diabetes mellitus. The patient initially received liposomal amphotericin B, but the infection continued to progress, so posaconazole treatment was begun and eventually led to the cure of his infection. The causative agent was identified as Apophysomyces elegans, an emerging cause of zygomycosis in immunocompetent hosts.
Assuntos
Dermatomicoses/tratamento farmacológico , Dermatomicoses/microbiologia , Fungos/isolamento & purificação , Triazóis/uso terapêutico , Zigomicose/tratamento farmacológico , Zigomicose/microbiologia , Adulto , Antifúngicos/uso terapêutico , Dermatomicoses/cirurgia , Diabetes Mellitus , Humanos , Masculino , Zigomicose/cirurgiaRESUMO
PURPOSE: The new malononitrilamide FK778 is currently being evaluated as an immunosuppressant for organ transplantation. Its main mechanism is inhibition of a pivotal enzyme of pyrimidine biosynthesis. This report revealed new mechanisms of action on different cell types involved in acute and chronic allograft rejection. METHODS: Purified Brown-Norway rat aortic endothelial cell (EC) cultures were pretreated with several concentrations of FK778. Endothelial adhesion molecule expression (ICAM-1/VCAM-1) stimulated with TNF-alpha was quantified by immunofluorescence. Purified Lewis rat lymphocytes (LC) incubated with FK778 were stimulated via TCR/CD28 signals, and CD25 expression was quantified using FACS analysis. Uridine addition was used in all assays to reverse the pyrimidine synthesis blockade. Lymphocyte-EC interaction was assessed by micromanipulator-assisted single-cell adhesion assays. Finally, smooth muscle cell (SMC) proliferation and migration was analyzed. Uridine addition was used in all assays to reverse the pyrimidine synthesis blockade. RESULTS: TNF-alpha stimulation and TCR/CD28 co-stimulation significantly increased EC ICAM-1/VCAM-1-expression and LC CD25 surface expression, respectively. These effects were dose-dependently inhibited by FK778 and were not reversed by the addition of uridine. FK778 dose-dependently attenuated LC adhesion to allogeneic EC. The dose-dependent inhibition of SMC proliferation by FK778 was abolished by uridine addition, whereas the inhibitory effect on SMC migration was not affected by uridine supplementation. CONCLUSIONS: FK778 directly reduced endothelial adhesion molecule up-regulation, inhibited lymphocyte activation, and attenuated lymphocyte-endothelium interactions, critical early steps in graft rejection. These effects were separate from the blockade of pyrimidine synthesis. The antiproliferative potency of FK778 on SMC may be an important mechanism to inhibit the fibroproliferative lesions of chronic organ rejection.
Assuntos
Endotélio Vascular/fisiologia , Isoxazóis/farmacologia , Alcinos , Animais , Antígenos CD28/imunologia , Adesão Celular/efeitos dos fármacos , Adesão Celular/fisiologia , Endotélio Vascular/efeitos dos fármacos , Citometria de Fluxo , Ativação Linfocitária/efeitos dos fármacos , Linfócitos/efeitos dos fármacos , Linfócitos/imunologia , Nitrilas , Ratos , Ratos Endogâmicos BN , Ratos Endogâmicos Lew , Receptores de Antígenos de Linfócitos T/imunologia , Fator de Necrose Tumoral alfa/imunologia , Uridina/farmacologiaRESUMO
With reference to radiosurgery of the liver, we describe techniques designed to solve the methodological problem of striking targets subject to respiratory motion with the necessary precision. Implanting a gold marker in the vicinity of the liver tumor was the first step in ensuring the reproducibility of the isocenter's position. An 18-karat gold rod measuring 1.9 x 3 mm was implanted approximately 2 cm from the edge of the tumor as this was displayed in the spiral, thin-slice CT with contrast media. Both the implantation of the marker and the required, CT-controlled biopsy of the liver tumor can be achieved simultaneously with the same puncture needle. The efficiency of high-frequency jet ventilation (HFJV) in neutralizing the targeted organ's respiratory motion during stereotactic single-dose irradiation was evaluated. The procedure was carried out on ten patients without any complications. In the time between treatment planning and irradiation (3 days), no significant marker migration was observable. In all cases, the gold marker (volume: 7.5 mm(3)) was readily observable in the treatment beam using portal imaging. HFJV provided reliable immobilization. The liver motion in each anesthetized patient was limited to under 3.0 mm in all directions. Thus, the correct field settings and target reproducibility were able to be analyzed and documented during the irradiation. The combination of marker and HFJV enables the determination of stereotactic coordinates directly related to the liver itself and, in this way, stereotactic radiation treatment of liver tumors is freed from the uncertainties involved in orientation to bony landmarks, in respiratory motion, and in changes of position in the stereotactic body frame. The method is feasible and can improve the accuracy of stereotactic body radiation therapy.
Assuntos
Ouro , Ventilação em Jatos de Alta Frequência , Neoplasias Hepáticas/cirurgia , Radiocirurgia/métodos , Humanos , Imobilização , Neoplasias Hepáticas/diagnóstico por imagem , Tomografia Computadorizada por Raios XRESUMO
We describe a case of Acanthamoeba encephalitis in a 45-year-old Caucasian male with acute myelogenous leukemia, who was 140 days status post partially mismatched related donor peripheral blood stem cell transplant. The patient had been transplanted with a highly T-cell-depleted graft, and was not taking any immunosuppressive drugs, and had no history of graft-versus-host disease. He complained of nausea, vomiting, and occasional episodes of confusion; he also had a chronic cough since transplantation. Physical examination was unremarkable except for orthostatic hypotension. Neurologic examination was within normal limits. Laboratory values including electrolytes, white blood cells and platelet counts were normal. Computed tomographic scan of the brain showed a pansinusitis and a hyperdense lesion along the corona radiata suggestive of a fungal abscess. Magnetic resonance imaging showed multifocal areas with mass effect in the posterior fossa and parietal and occipital lobes. The patient had worsening respiratory failure and died three days after admission. At autopsy, specific immunofluorescent staining identified Acanthamoeba castellani in the brain and lungs.
Assuntos
Acanthamoeba/isolamento & purificação , Amebíase/etiologia , Encefalite/etiologia , Transplante de Células-Tronco de Sangue Periférico/efeitos adversos , Amebíase/diagnóstico , Animais , Encefalite/diagnóstico , Teste de Histocompatibilidade , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
BACKGROUND: The analysis of early and late postoperative results after tracheostomy in children. METHODS: A 6 year, prospective, observational cohort study was undertaken in 14 children of mean age 4 years 7 months (range 0.03 month-15 years) at the Department of Otorhinolaryngology, University of Ulm. Children were included if they had at least two follow-up examinations postoperatively because of local disorders in wound healing of the tracheostoma. Etiologic factors, the type of tracheotomy, the size and type of the tracheostomy tube, primary and secondary local disorders in wound healing of the tracheostoma, and the clinical follow-up were analyzed. RESULTS: Formation of granulation tissue and tracheal stenosis were the most observed local disorders. In five patients, the tracheal stenosis was located below the stoma, in one patient also above the stoma. A stenosis of the stoma was found in two patients. One patient died because of a tracheoinnominate artery fistula. In 10 patients problems in swallowing and recurrent aspiration of saliva was observed early postoperatively. CONCLUSIONS: The tracheotomy in childhood is often related with late wound healing disorders. An association of wound healing disorders with a feasible lethal outcome is rarely found. Local formation of granulation tissue renders decannulation more difficult. The choice of a correctly fitting tracheostomy tube and special care of the tracheostoma in long-term cannulated children has to be emphasized.
Assuntos
Traqueostomia/efeitos adversos , Cicatrização , Adolescente , Fatores Etários , Criança , Pré-Escolar , Cicatriz/etiologia , Feminino , Seguimentos , Tecido de Granulação , Humanos , Lactente , Recém-Nascido , Masculino , Estudos Prospectivos , Fatores Sexuais , Fatores de Tempo , Estenose Traqueal/etiologiaRESUMO
Mono(ADP-ribosyl)transferases regulate the function of target proteins by attaching ADP-ribose to specific amino acid residues in their target proteins. The purpose of this study was to determine the structure, chromosomal localization, and expression profile of the gene for mouse ecto-ADP-ribosyltransferase ART5. Southern blot analyses indicate that Art5 is a single copy gene which maps to mouse chromosome 7 at offset 49.6 cM in close proximity to the Art1, Art2a and Art2b genes. Northern blot and RT-PCR analyses demonstrate prominent expression of Art5 in testis, and lower levels in cardiac and skeletal muscle. Sequence analyses reveal that the Art5 gene encompasses six exons spanning 8 kb of genomic DNA. The 5' end of the Art5 gene overlaps with that of the Art1 gene. A single long exon encodes the predicted ART5 catalytic domain. Separate exons encode the N-terminal leader peptide and a hydrophilic C-terminal extension. Sequencing of RT-PCR products and ESTs identified six splice variants. The deduced amino acid sequence of ART5 shows 87% sequence identity to its orthologue from the human, and 37 and 32% identity to its murine paralogues ART1 and ART2. Unlike ART1 and ART2, ART5 lacks a glycosylphosphatidylinositol-anchor signal sequence and is predicted to be a secretory enzyme. This prediction was confirmed by transfecting an Art5 cDNA expression construct into Sf9 insect cells. The secreted epitope-tagged ART5 protein resembled rat ART2 in exhibiting potent NAD-glycohydrolase activity. This study provides important experimental tools to further elucidate the function of ART5.
Assuntos
ADP Ribose Transferases/genética , Genes/genética , Sequência de Aminoácidos , Animais , Sequência de Bases , Northern Blotting , Linhagem Celular , Mapeamento Cromossômico , DNA/química , DNA/genética , DNA Complementar/química , DNA Complementar/genética , Éxons , Feminino , Expressão Gênica , Íntrons , Isoenzimas/genética , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos , Dados de Sequência Molecular , Muridae , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Alinhamento de Sequência , Análise de Sequência de DNA , Homologia de Sequência de Aminoácidos , Distribuição TecidualRESUMO
ADP-ribosyltransferases (ADPRTs) form an interesting class of enzymes with well-established roles as potent bacterial toxins and metabolic regulators. ADPRTs catalyze the transfer of the ADP-ribose moiety from NAD(+) onto specific substrates including proteins. ADP-ribosylation usually inactivates the function of the target. ADPRTs have become adapted to function in extra- and intracellular settings. Regulation of ADPRT activity can be mediated by ligand binding to associated regulatory domains, proteolytic cleavage, disulphide bond reduction, and association with other proteins. Crystallisation has revealed a conserved core set of elements that define an unusual minimal scaffold of the catalytic domain with remarkably plastic sequence requirements--only a single glutamic acid residue critical to catalytic activity is invariant. These inherent properties of ADPRTs suggest that the ADPRT catalytic fold is an attractive, malleable subject for protein design.