RESUMO
Matrix metalloproteinases (MMPs) play a critical role in cancer pathogenesis, including tumor growth and osteolysis within the bone marrow microenvironment. However, the anti-tumor effects of MMPs are poorly understood, yet have significant implications for the therapeutic potential of targeting MMPs. Host derived MMP-7 has previously been shown to support the growth of bone metastatic breast and prostate cancer. In contrast and underscoring the complexity of MMP biology, here we identified a tumor-suppressive role for host MMP-7 in the progression of multiple myeloma in vivo. An increase in tumor burden and osteolytic bone disease was observed in myeloma-bearing MMP-7 deficient mice, as compared to wild-type controls. We observed that systemic MMP-7 activity was reduced in tumor-bearing mice and, in patients with multiple myeloma this reduced activity was concomitant with increased levels of the endogenous MMP inhibitor, tissue inhibitor of metalloproteinases-1 (TIMP-1). Our studies have identified an unexpected tumour-suppressive role for host-derived MMP-7 in myeloma bone disease in vivo, and highlight the importance of elucidating the effect of individual MMPs in a disease-specific context.
Assuntos
Neoplasias Ósseas/secundário , Metaloproteinase 7 da Matriz/genética , Metaloproteinase 7 da Matriz/metabolismo , Mieloma Múltiplo/patologia , Animais , Neoplasias Ósseas/genética , Neoplasias Ósseas/metabolismo , Neoplasias Ósseas/patologia , Linhagem Celular Tumoral , Sobrevivência Celular , Progressão da Doença , Técnicas de Inativação de Genes , Humanos , Camundongos , Mieloma Múltiplo/genética , Mieloma Múltiplo/metabolismo , Transplante de Neoplasias , Microambiente TumoralRESUMO
UNLABELLED: As annual influenza epidemics continue to cause significant morbidity and economic burden, an understanding of viral persistence and transmission is critical for public health officials and health care workers to better protect patients and their family members from infection. The infectivity and persistence of two influenza A (H1N1) virus strains (A/New Caledonia/20/1999 and A/Brisbane/59/2007) on stainless steel (SS) surfaces were evaluated using three different surface matrices (2% fetal bovine serum, 5 mg/ml mucin, and viral medium) under various absolute humidity conditions (4.1 × 10(5) mPa, 6.5 × 10(5) mPa, 7.1 × 10(5) mPa, 11.4 × 10(5) mPa, 11.2 × 10(5) mPa, and 17.9 × 10(5) mPa) for up to 7 days. Influenza A virus was deposited onto SS coupons (7.07 cm(2)) and recovered by agitation and sonication in viral medium. Viral persistence was quantified using a tissue culture-based enzyme-linked immunosorbent assay (ELISA) to determine the median (50%) tissue culture infective dose (TCID50) of infectious virus per coupon. Overall, both strains of influenza A virus remained infectious on SS coupons, with an approximate 2 log10 loss over 7 days. Factors that influenced viral persistence included absolute humidity, strain-absolute humidity interaction, and time (P ≤ 0.01). Further studies on the transfer of influenza A virus from fomites by hand and the impact of inanimate surface contamination on transmission should be performed, as this study demonstrates prolonged persistence on nonporous surfaces. IMPORTANCE: This study tested the ability of two influenza A (H1N1) virus strains to persist and remain infectious on stainless steel surfaces under various environmental conditions. It demonstrated that influenza A (H1N1) viruses can persist and remain infectious on stainless steel surfaces for 7 days. Additional studies should be conducted to assess the role played by contaminated surfaces in the transmission of influenza A virus.
Assuntos
Microbiologia Ambiental , Vírus da Influenza A Subtipo H1N1/isolamento & purificação , Vírus da Influenza A Subtipo H1N1/fisiologia , Viabilidade Microbiana , Aço Inoxidável , Umidade , Fatores de Tempo , Carga Viral , Cultura de VírusRESUMO
Antibody engineering can tailor the design and activities of therapeutic antibodies for better efficiency or other advantageous clinical properties. Here we report the development of ISB 1442, a fully human bispecific antibody designed to re-establish synthetic immunity in CD38+ hematological malignancies. ISB 1442 consists of two anti-CD38 arms targeting two distinct epitopes that preferentially drive binding to tumor cells and enable avidity-induced blocking of proximal CD47 receptors on the same cell while preventing on-target off-tumor binding on healthy cells. The Fc portion of ISB 1442 is engineered to enhance complement dependent cytotoxicity, antibody dependent cell cytotoxicity and antibody dependent cell phagocytosis. ISB 1442 thus represents a CD47-BsAb combining biparatopic targeting of a tumor associated antigen with engineered enhancement of antibody effector function to overcome potential resistance mechanisms that hamper treatment of myeloma with monospecific anti-CD38 antibodies. ISB 1442 is currently in a Phase I clinical trial in relapsed refractory multiple myeloma.
Assuntos
Anticorpos Biespecíficos , Neoplasias Hematológicas , Mieloma Múltiplo , Humanos , Mieloma Múltiplo/tratamento farmacológico , Antígeno CD47 , Anticorpos Biespecíficos/farmacologia , Anticorpos Biespecíficos/uso terapêutico , Citotoxicidade Celular Dependente de AnticorposRESUMO
In the United States, the 2009 pandemic influenza A (H1N1) virus (pH1N1) infected almost 20% of the population and caused >200,000 hospitalizations and >10,000 deaths from April 2009 to April 2010. On 24 April 2009, the CDC posted interim guidance on infection control measures in health care settings explicitly for pH1N1 and recommended using filtering face respirators (FFRs) when in close contact with a suspected- or confirmed-to-be-infected individual, particularly when performing aerosol-generating procedures. The persistence and infectivity of pH1N1 were evaluated on FFRs, specifically N95 respirators, under various conditions of absolute humidity (AH) (4.1 × 10(5) mPa, 6.5 × 10(5) mPa, and 14.6 × 10(5) mPa), sample matrices (2% fetal bovine serum [FBS], 5 mg/ml mucin, and viral medium), and times (4, 12, 24, 48, 72, and 144 h). pH1N1 was distributed onto N95 coupons (3.8 to 4.2 cm(2)) and extracted by a vortex-centrifugation-filtration process, and the ability of the remaining virus to replicate was quantified using an enzyme-linked immunosorbent assay (ELISA) to determine the log10 concentration of the infectious virus per coupon. Overall, pH1N1 remained infectious for 6 days, with an approximately 1-log10 loss of virus concentrations over this time period. Time and AH both affected virus survival. We found significantly higher (P ≤ 0.01) reductions in virus concentrations at time points beyond 24 to 72 h (-0.52-log10 reduction) and 144 h (-0.74) at AHs of 6.5 × 10(5) mPa (-0.53) and 14.6 × 10(5) mPa (-0.47). This research supports discarding respirators after close contact with a person with suspected or confirmed influenza infection due to the virus's demonstrated ability to persist and remain infectious.
Assuntos
Vírus da Influenza A Subtipo H1N1/isolamento & purificação , Viabilidade Microbiana , Ventiladores Mecânicos/virologia , Fatores de Tempo , Estados UnidosRESUMO
UNLABELLED: A repeatable and sensitive method to evaluate the effect of three antiseptics and two disinfection techniques on viable micro-organisms on luer-activated catheter needleless connectors (NCs) was developed. NCs were inoculated with Staphylococcus epidermidis or Klebsiella pneumoniae and disinfected with 3·15% chlorhexidine gluconate + 70% isopropanol (CGI), 70% isopropanol (IPA) or 10% PVP povidone-iodine (PI) antiseptic pads using: (i) scrubbing the NC septum and threaded external surfaces or (ii) wiping only the surface of the septum. Treatments were also evaluated against NCs pretreated with human serum and exposed for 18 h to Staph. epidermidis prior to testing. Viable cells were quantified by plate count. The method for inoculation and recovery of luminal micro-organisms was repeatable (SD, 0·31; n = 28). IPA disinfection provided an approximate 3 log10 CFU reduction; CGI and PI provided 3-4 log10 reductions. PI and CGI were more effective than IPA (P < 0·05), but differences between CGI and PI were not significant for either disinfection method. IPA, but not CGI and PI was also less effective (P < 0·05) against NCs inoculated with Kl. pneumoniae than Staph. epidermidis. Pretreatment with serum and prolonged Staph. epidermidis inoculation removed the advantage seen with CGI and PI; log10 reductions were 1·80, 1·73 and 2·50 for CGI, PI and IPA, respectively. PI or CGI may be more effective than IPA for NC disinfection but effectiveness may be reduced on NCs contaminated with blood or serum. SIGNIFICANCE AND IMPACT OF THE STUDY: sensitive and repeatable protocol was developed to evaluate antiseptics for disinfecting catheter needleless connectors (NCs). Povidone-iodine (PI) and chlorhexidine gluconate plus isopropanol (CGI) were more effective than isopropanol (IPA) for reducing Staphylococcus epidermidis contamination of NCs. The effectiveness of PI and CGI was reduced on NCs pre-exposed to human serum and prolonged bacterial inoculation. IPA was also less effective against NCs contaminated with Klebsiella pneumoniae.
Assuntos
Infecções Relacionadas a Cateter/prevenção & controle , Cateteres Venosos Centrais/microbiologia , Desinfetantes/farmacologia , Desinfecção/métodos , Contaminação de Equipamentos/prevenção & controle , Infecções Relacionadas a Cateter/microbiologia , Clorexidina/análogos & derivados , Clorexidina/farmacologia , Desinfecção/instrumentação , Humanos , Klebsiella pneumoniae/efeitos dos fármacos , Povidona-Iodo/farmacologia , Staphylococcus epidermidis/efeitos dos fármacosRESUMO
UNLABELLED: A large-eddy simulation is used to investigate contaminant transport owing to complex human and door motions and vent-system activity in room compartments where a contaminated and clean room are connected by a vestibule. Human and door motions are simulated with an immersed boundary procedure. We demonstrate the details of contaminant transport owing to human- and door-motion-induced wake development during a short-duration event involving the movement of a person (or persons) from a contaminated room, through a vestibule, into a clean room. Parametric studies that capture the effects of human walking pattern, door operation, over-pressure level, and vestibule size are systematically conducted. A faster walking speed results in less mass transport from the contaminated room into the clean room. The net effect of increasing the volume of the vestibule is to reduce the contaminant transport. The results show that swinging-door motion is the dominant transport mechanism and that human-induced wake motion enhances compartment-to-compartment transport. PRACTICAL IMPLICATIONS: The effect of human activity on contaminant transport may be important in design and operation of clean or isolation rooms in chemical or pharmaceutical industries and intensive care units for airborne infectious disease control in a hospital. The present simulations demonstrate details of contaminant transport in such indoor environments during human motion events and show that simulation-based sensitivity analysis can be utilized for the diagnosis of contaminant infiltration and for better environmental protection.
Assuntos
Movimentos do Ar , Poluição do Ar em Ambientes Fechados , Modelos Teóricos , Simulação por Computador , Temperatura Alta , Humanos , CaminhadaRESUMO
BACKGROUND: We describe a minimally invasive, image-guided technique for obstructed hemivagina and ipsilateral renal anomaly (OHVIRA) syndrome complicated by tubo-ovarian abscess (TOA). CASE: A 15-year-old female adolescent with OHVIRA syndrome presented with TOA. Magnetic resonance imaging of the abdomen/pelvis showed a loculated pelvic mass and fluid collection near the obstructed left hemivagina. Tissue quality and ill-defined surgical planes prevented surgical excision. A transabdominal drain was placed via laparoscopic port by Interventional Radiology. She later underwent transvaginal and transabdominal drain placement into the hemivaginal collection using computed tomography and ultrasound guidance, allowing for surgical excision of the vaginal septum, drainage and excision of the TOA, and neosalpingostomy. SUMMARY AND CONCLUSION: Because of the anatomic complexity in OHVIRA syndrome, preoperative minimally invasive techniques with Interventional Radiology collaboration can assist intraoperative anatomic navigation for successful surgical treatment.
Assuntos
Abscesso , Cirurgia Assistida por Computador , Abscesso/diagnóstico por imagem , Abscesso/cirurgia , Adolescente , Drenagem , Feminino , Humanos , Útero , Vagina/diagnóstico por imagem , Vagina/cirurgiaRESUMO
The aim of this study was to identify risk factors associated with PFS in patients with Ewing sarcoma undergoing ASCT; 116 patients underwent ASCT in 1989-2000 and reported to the Center for International Blood and Marrow Transplant Research. Eighty patients (69%) received ASCT as first-line therapy and 36 (31%), for recurrent disease. Risk factors affecting ASCT were analyzed with use of the Cox regression method. Metastatic disease at diagnosis, recurrence prior to ASCT and performance score <90 were associated with higher rates of disease recurrence/progression. Five-year probabilities of PFS in patients with localized and metastatic disease at diagnosis who received ASCT as first-line therapy were 49% (95% CI 30-69) and 34% (95% CI 22-47) respectively. The 5-year probability of PFS in patients with localized disease at diagnosis, and received ASCT after recurrence was 14% (95% CI 3-30). PFS rates after ASCT are comparable to published rates in patients with similar disease characteristics treated with conventional chemotherapy, surgery and irradiation suggesting a limited role for ASCT in these patients. Therefore, ASCT if considered should be for high-risk patients in the setting of carefully controlled clinical trials.
Assuntos
Agonistas Mieloablativos/uso terapêutico , Sarcoma de Ewing/terapia , Transplante de Células-Tronco/métodos , Adolescente , Adulto , Criança , Terapia Combinada , Progressão da Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Sarcoma de Ewing/mortalidade , Sarcoma de Ewing/secundário , Análise de Sobrevida , Transplante AutólogoRESUMO
This paper reports on a retrospective study of the antibody responses to structural and non-structural proteins of FMD virus O Taiwan 97 in six pig herds in Taiwan in the year after the 1997 Taiwanese FMD outbreak. All herds were vaccinated against FMD after the outbreak as part of the countrywide control program. Three of the herds had confirmed FMD infections (herds N, O and P) and three herds remained non-infected (herds K, L and M). The serum neutralizing antibody titers and the non-structural protein ELISA (NSP) antibody responses in sows and 1-month-old pigs in the infected herds were higher than in the non-infected herds, but over time a number of positive NSP reactors were detected. From the serological studies and the herd monitoring and investigations it was considered that the FMD NSP positive reactors may not have constituted a true reservoir of FMD virus infection especially in herds where susceptible pigs were no longer present post-exposure or post-vaccination. Pigs vaccinated with an unpurified FMD type O vaccines being used at that time also showed false positive responses for NSP antibodies.
Assuntos
Surtos de Doenças/veterinária , Febre Aftosa/imunologia , Doenças dos Suínos/imunologia , Animais , Anticorpos Antivirais , Antígenos Virais , Febre Aftosa/epidemiologia , Estudos Retrospectivos , Suínos , Doenças dos Suínos/epidemiologia , Taiwan/epidemiologia , Vacinas Virais/imunologiaRESUMO
UNLABELLED: An immersed boundary method for particulate flow in an Eulerian framework is utilized to examine the effects of complex human motion on the transport of trace contaminants. The moving human object is rendered as a level set in the computational domain, and realistic human walking motion is implemented using a human kinematics model. A large eddy simulation (LES) technique is used to simulate the fluid and particle dynamics induced by human activity. Parametric studies are conducted within a Room-Room and a Room-Hall configuration, each separated by an open doorway. The effects of the average walking speed, initial proximity from the doorway, and the initial mass loading on room-to-room contaminant transport are examined. The rate of mass transport increases as the walking speed increases, but the total amount of material transported is more influenced by the initial proximity of the human from the doorway. The Room-Hall simulations show that the human wake transports material over a distance of about 8 m. Time-dependent data extracted from the simulations is used to develop a room-averaged zonal model for contaminant transport due to human walking motion. The model shows good agreement with the LES results. PRACTICAL IMPLICATIONS: The effect of human activity on contaminant transport may be important in applications such as clean or isolation room design for biochemical production lines, in airborne infection control, and in entry/exit into collective protection or decontamination systems. The large eddy simulations (LES) performed in this work allow precise capturing of the local wakes generated by time-dependent human motion and thus provide a means of quantifying contaminant transport due to wake effects. The LES database can be used to develop zonal models for the bulk effects of human-induced contaminant transport. These may be incorporated into multi-zone infiltration models for use in threat-response and exposure mitigation studies.
Assuntos
Movimentos do Ar , Poluentes Atmosféricos/química , Poluição do Ar em Ambientes Fechados/análise , Modelos Teóricos , Material Particulado/química , Poluentes Atmosféricos/análise , Simulação por Computador , Convecção , Arquitetura de Instituições de Saúde , Humanos , Material Particulado/análise , Análise de Regressão , CaminhadaRESUMO
Three commercialized ELISA kits for the detection of antibodies to the non-structural proteins (NSPs) of FMD virus were compared, using sera from uninfected, vaccinated, challenged and naturally infected pigs. The kinetics of the antibody response to NSPs was compared on sequential serum samples in swine from challenge studies and outbreaks. The results showed that ELISA A (UBI) and ELISA B (CEDI) had better sensitivity than that of the 3ABC recombinant protein-based ELISA C (Chekit). The peak for detection of antibodies to NSPs in ELISA C was significantly delayed in sera from natural infection and challenged swine as compared to the ELISA A and B. The sensitivity of the three ELISAs gradually declined during the 6-month post-infection as antibodies to NSP decline. ELISA kits A and B detected NSP antibody in 50% of challenged pigs by the 9-10th-day and 7-8th-day post-challenge, respectively. ELISA B and C had better specificity than ELISA A on sequential serum samples obtained from swine immunized with a type O FMD vaccine commercially available in Taiwan. Antibody to NSPs before vaccination was not detected in swine not exposed to FMD virus, however, antibody to NSPs was found in sera of some pigs after vaccination. All assays had significantly lower specificity when testing sera from repeatedly vaccinated sows and finishers in 1997 that were tested after the 1997 FMD outbreak. However, when testing sera from repeatedly vaccinated sows or finishers in 2003-2004, the specificity for ELISAs A, B and C were significantly better than those in 1997. This effect was less marked for ELISA A. The ELISA B was the best test in terms of the highest sensitivity and specificity and the lowest reactivity with residual NSP in vaccinates.
Assuntos
Anticorpos Antivirais/biossíntese , Ensaio de Imunoadsorção Enzimática/veterinária , Vírus da Febre Aftosa/imunologia , Febre Aftosa/diagnóstico , Doenças dos Suínos/diagnóstico , Proteínas não Estruturais Virais/imunologia , Animais , Anticorpos Antivirais/sangue , Ensaio de Imunoadsorção Enzimática/normas , Febre Aftosa/sangue , Febre Aftosa/virologia , Kit de Reagentes para Diagnóstico/veterinária , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Suínos , Doenças dos Suínos/sangue , Doenças dos Suínos/virologia , Taiwan , Vacinas ViraisRESUMO
Approximately 75% of breast cancers express estrogen receptor α (ERα) and depend on estrogen signals for continued growth. Aromatase inhibitors (AIs) prevent estrogen production and inhibit ER signaling, resulting in decreased cancer recurrence and mortality. Advanced tumors treated with AIs almost always develop resistance to these drugs via the upregulation of alternative growth signals. The mechanisms that drive this resistance-especially epigenetic events that alter gene expression-are, however, not well understood. Genome-wide DNA methylation and expression analysis of cell line models of acquired AI resistance indicated that prostaglandin E2 receptor 4 (PTGER4) is upregulated after demethylation in resistant cells. Knockdown and inhibitor studies demonstrate that PTGER4 is essential for estrogen-independent growth. Our exploratory analysis of downstream signaling indicates that PTGER4 likely promotes AI resistance via ligand-independent activation of the ERα-cofactor CARM1. We believe that we have discovered a novel epigenetic mechanism for altering cell signaling and acquiring endocrine therapy resistance. Our findings indicate that PTGER4 is a potential drug target in AI-resistant cancers. In addition, the epigenetic component of PTGER4 regulation suggests that further study of PTGER4 may yield valuable insights into how DNA methylation-targeted diagnoses and treatments can improve AI-resistant breast cancer treatment.
Assuntos
Neoplasias da Mama/genética , Resistencia a Medicamentos Antineoplásicos/genética , Epigênese Genética , Receptores de Prostaglandina E Subtipo EP4/genética , Antineoplásicos/uso terapêutico , Inibidores da Aromatase/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Proliferação de Células , Metilação de DNA , DNA de Neoplasias/metabolismo , Receptor alfa de Estrogênio/metabolismo , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Células MCF-7 , Proteína-Arginina N-Metiltransferases/metabolismo , Receptores de Prostaglandina E Subtipo EP4/metabolismo , Transdução de SinaisRESUMO
Matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MS) has been explored widely for DNA sequencing. The major requirement for this method is that the DNA sequencing fragments must be free from alkaline and alkaline earth salts as well as other contaminants for accurately measuring the masses of the DNA fragments. We report here the development of a novel MS DNA sequencing method that generates Sanger-sequencing fragments in one tube using biotinylated dideoxynucleotides. The DNA sequencing fragments that carry a biotin at the 3'-end are made free from salts and other components in the sequencing reaction by capture with streptavidin-coated magnetic beads. Only correctly terminated biotinylated DNA fragments are subsequently released and loaded onto a mass spectrometer to obtain accurate DNA sequencing data. Compared with gel electrophoresis-based sequencing systems, MS produces a very high resolution of DNA-sequencing fragments, fast separation on microsecond time scales, and completely eliminates the compressions associated with gel electrophoresis. The high resolution of MS allows accurate mutation and heterozygote detection. This optimized solid-phase DNA-sequencing chemistry plus future improvements in detector sensitivity for large DNA fragments in MS instrumentation will further improve MS for DNA sequencing.
Assuntos
Biotinilação , DNA/análise , DNA/genética , Didesoxinucleosídeos/metabolismo , Análise de Sequência de DNA/métodos , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz , Sequência de Bases , Biotina/metabolismo , Didesoxinucleosídeos/química , Heterozigoto , Microesferas , Dados de Sequência Molecular , Mutação/genética , Polimorfismo Genético/genética , Sensibilidade e Especificidade , Estreptavidina/metabolismo , Moldes GenéticosRESUMO
The glycosyltransferase complex from Streptococcus mutans can be resolved by polyacrylamide gel electrophoresis following treatment with Tween 80. The enzyme complex was treated with Tween 80 and electrophoresis was performed in the presence of Tween 80. Discrete bands of glycosyltransferase activity were observed when the gels were incubated in buffered sucrose. The enzyme aggregation that occurs with the exocellular glycosyltransferase may involve lipophilic interactions that are disrupted by the Tween 80.
Assuntos
Hexosiltransferases/isolamento & purificação , Streptococcus/enzimologia , Eletroforese em Gel de Poliacrilamida , Polissorbatos , Especificidade da EspécieRESUMO
The purpose of this report is to describe the tolerability and activity of the combination of high-dose cytosine arabinoside (Ara-C) given at the maximum tolerated dose of 36 g/m2, together with high doses of etoposide in relapsed and refractory childhood acute leukemias. Eighteen children with relapsed or refractory acute leukemia were treated with Ara-C 3 g/m2 every 12 h on days 1-6, followed by etoposide 400 mg/m2 on days 7-9 (HDAC/VP-16). Eight children with refractory disease received HDAC/VP-16 as salvage induction therapy after failing conventional induction regimens; four of five refractory ANLL patients (80%) had a complete response (CR) after HDAC/VP-16 therapy. Ten patients received HDAC/VP-16 as post-remission intensification therapy; five patients (four ANLL, one relapsed ALL) remain in second CR at 56, 26, 9, 5 and 2 months. Toxicities were primarily hematologic and dermatologic. Seven patients (39%) developed bacterial or fungal infections; four patients developed grade 3 or 4 acral erythema. No patient died of therapy-related toxicity. The combination of 36 g/m2 cytosine arabinoside and 1200 mg/m2 etoposide is an effective regimen for children with relapsed or refractory acute nonlymphocytic leukemia, with tolerable toxicities; the absence of anthracyclines makes this regimen suitable for patients who have previously received maximal doses of anthracyclines or who have evidence of cardiac dysfunction. Further evaluation of this regimen in acute nonlymphocytic leukemia is presently being investigated.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Leucemia Mieloide/tratamento farmacológico , Doença Aguda , Adolescente , Antraciclinas , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Doenças da Medula Óssea/induzido quimicamente , Criança , Pré-Escolar , Contraindicações , Citarabina/administração & dosagem , Citarabina/efeitos adversos , Etoposídeo/administração & dosagem , Etoposídeo/efeitos adversos , Feminino , Humanos , Lactente , Infecções/etiologia , Leucemia Mieloide/mortalidade , Masculino , Terapia de Salvação , Resultado do TratamentoRESUMO
Forty-two infants of HIV-seropositive women were evaluated to determine the value of polymerase chain reaction (PCR) in the early detection of HIV infection. All infants less than 6 months old had a simultaneous PCR and culture for HIV. There was an 88% concordance between the two techniques. PCR results showed an excellent correlation with clinical outcome; no PCR-negative patient has subsequently been found to be infected. Occasional false-positive or equivocal PCR results did occur. There was one false-negative culture. PCR is a rapid and sensitive diagnostic test for the early diagnosis of HIV infection in infants at risk, but at present it should be performed in conjunction with other diagnostic tests and good clinical follow-up.
Assuntos
Infecções por HIV/diagnóstico , Soropositividade para HIV/complicações , Reação em Cadeia da Polimerase/métodos , Complicações Infecciosas na Gravidez , Adulto , Feminino , HIV/isolamento & purificação , Infecções por HIV/microbiologia , Humanos , Lactente , Recém-Nascido , GravidezRESUMO
We describe the annual incidence of primary bloodstream infection (BSI) associated with Candida albicans and common non-albicans species of Candida among patients in intensive care units that participated in the National Nosocomial Infections Surveillance system from 1 January 1989 through 31 December 1999. During the study period, there was a significant decrease in the incidence of C. albicans BSI (P<.001) and a significant increase in the incidence of Candida glabrata BSI (P=.05).
Assuntos
Candida/isolamento & purificação , Candidíase/epidemiologia , Infecção Hospitalar/epidemiologia , Adulto , Candidíase/microbiologia , Infecção Hospitalar/microbiologia , Feminino , Humanos , Unidades de Terapia Intensiva , Masculino , Pessoa de Meia-Idade , Estados Unidos/epidemiologiaRESUMO
The National Nosocomial Infections Surveillance (NNIS) System is an ongoing collaborative surveillance system among the Centers for Disease Control (CDC) and United States hospitals to obtain national data on nosocomial infections. This system provides comparative data for hospitals and can be used to identify changes in infection sites, risk factors, and pathogens, and develop efficient surveillance methods. Data are collected prospectively using four surveillance components: hospital-wide, intensive care unit, high-risk nursery, and surgical patient. The limitations of NNIS data include the variability in case-finding methods, infrequency or unavailability of culturing, and lack of consistent methods for post-discharge surveillance. Future plans include more routine feedback of data, studies on the validity of NNIS data, new components, a NNIS consultant group, and more rapid data exchange with NNIS hospitals. Increasing the number of NNIS hospitals and cooperating with other agencies to exchange data may allow NNIS data to be used better for generating benchmark nosocomial infection rates. The NNIS system will continue to evolve as it seeks to find more effective and efficient ways to measure the nosocomial infection experience and assess the influence of patient risk, changes in the delivery of hospital care, and changes in infection control practices on these measures.
Assuntos
Centers for Disease Control and Prevention, U.S. , Infecção Hospitalar/epidemiologia , Coleta de Dados , Humanos , Estados UnidosRESUMO
To perform a valid comparison of rates among surgeons, among hospitals, or across time, surgical wound infection (SWI) rates must account for the variation in patients' underlying severity of illness and other important risk factors. From January 1987 through December 1990, 44 National Nosocomial Infections Surveillance System hospitals reported data collected under the detailed option of the surgical patient surveillance component protocol, which includes definitions of eligible patients, operations, and nosocomial infections. Pooled mean SWI rates (number of infections per 100 operations) within each of the categories of the traditional wound classification system were 2.1, 3.3, 6.4, and 7.1, respectively. A risk index was developed to predict a surgical patient's risk of acquiring an SWI. The risk index score, ranging from 0 to 3, is the number of risk factors present among the following: (1) a patient with an American Society of Anesthesiologists preoperative assessment score of 3, 4, or 5, (2) an operation classified as contaminated or dirty-infected, and (3) an operation lasting over T hours, where T depends upon the operative procedure being performed. The SWI rates for patients with scores of 0, 1, 2, and 3 were 1.5, 2.9, 6.8, and 13.0, respectively. The risk index is a significantly better predictor of SWI risk than the traditional wound classification system and performs well across a broad range of operative procedures.
Assuntos
Procedimentos Cirúrgicos Operatórios , Infecção da Ferida Cirúrgica/epidemiologia , Centers for Disease Control and Prevention, U.S. , Humanos , Procedimentos Cirúrgicos Operatórios/estatística & dados numéricos , Infecção da Ferida Cirúrgica/classificação , Estados UnidosRESUMO
To determine which intensive care unit (ICU) infection rate may be best for interhospital and intrahospital comparisons and to assess the influence of invasive devices and type of ICU on infection rates, we analyzed data from the National Nosocomial Infections Surveillance System. From October 1986 to December 1990, 79 hospitals reported 2,334 hospital-months of data from 196 hospital units. The median overall infection rate was 9.2 infections per 100 patients. However, this infection rate had a strong positive correlation with average length of ICU stay (r = 0.60, p less than 0.0001). When patient-days was used in the denominator, the median overall nosocomial infection rate was 23.7 infections per 1,000 patient-days. Although there was a marked reduction in the correlation with average length of stay, this rate had a strong positive correlation with device utilization (r = 0.59, p less than 0.0001). To attempt to control for average length of stay and device utilization, we examined device-associated nosocomial infection rates. Central line-associated bloodstream infection rates, catheter-associated urinary tract infection rates, and ventilator-associated pneumonia rates varied by ICU type. The distributions of device-associated infection rates were different between some ICU types and were not different between others (coronary and medical ICUs or medical-surgical and surgical ICUs). Comparison of device-associated infection rates and overall device utilization identified hospital units with outlier infection rates or device utilization. These data show that: (1) choice of denominator is critical when calculating ICU infection rates; (2) device-associated infection rates vary by ICU type; and (3) intrahospital and interhospital comparison of ICU infection rates may best be made by comparing ICU-type specific, device-associated infection rates.