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1.
Epidemiol Infect ; 148: e147, 2020 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-32605670

RESUMO

Major surgery carried out in low- and middle-income countries is associated with a high risk of surgical site infections (SSI), but knowledge is limited regarding contributory factors to such infections. This study explores factors related to patients developing an SSI in a teaching hospital in Ghana. A prospective cohort study of patients undergoing abdominal surgical procedures was conducted at Korle Bu Teaching Hospital. Patient characteristics, procedures and environmental characteristics were recorded. A 30-day daily surveillance was used to diagnose SSI, and Poisson regression analysis was used to test for association of SSI and risk factors; survival was determined by proportional hazard regression methods. We included 358 patients of which 58 (16.2%; 95% CI 12.7-20.4%) developed an SSI. The median number of door openings during an operation was 79, with 81% being unnecessary. Door openings greater than 100 during an operation (P = 0.028) significantly increased a patient's risk of developing an SSI. Such patients tended to have an elevated mortality risk (hazard ratio 2.67; 95% CI 0.75-9.45, P = 0.128). We conclude that changing behaviour and practices in operating rooms is a key strategy to reduce SSI risk.


Assuntos
Abdome/cirurgia , Microbiologia do Ar , Infecção da Ferida Cirúrgica/epidemiologia , Infecção da Ferida Cirúrgica/microbiologia , Adulto , Feminino , Gana/epidemiologia , Hospitais de Ensino , Humanos , Masculino , Pessoa de Meia-Idade , Movimento , Salas Cirúrgicas , Estudos Prospectivos , Fatores de Risco
2.
Phys Chem Chem Phys ; 19(7): 5246-5253, 2017 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-28149993

RESUMO

The key challenges for perovskite solar cells include their poor stability and film homogeneity. Studying the degradation and homogeneity of perovskite layers within device structures can be challenging but critical to the understanding of stability and effect of processing in real life conditions. We show that Raman spectroscopy (RS) is a unique and powerful method (simple and fast) to probe the degradation of the perovskite film within the device structure and image perovskite formation. We demonstrate that RS can be used to directly probe chemical (PbI2) and physical (dihydrated phase) degradation of a perovskite film, and estimate the relative amount of the degradation species formed, mapping its distribution with ∼1 µm spatial resolution. This has been applied to mapping a large area perovskite module to characterise the efficacy of PbI2 to perovskite conversion. We also use RS to study the degradation species and kinetics under diverse accelerated degradation conditions (temperature and humidity) in situ. These capabilities are difficult to achieve with other methods, presenting RS as an important tool to gain understanding of the degradation and effect of processing on perovskite-based photovoltaic devices.

3.
Epidemiol Infect ; 144(15): 3288-3299, 2016 11.
Artigo em Inglês | MEDLINE | ID: mdl-27334298

RESUMO

Poultry are possible sources of non-typhoidal Salmonella serovars which may cause foodborne human disease. We conducted a cross-sectional study to determine the prevalence of Salmonella serovars in egg-laying hens and broilers at the farm level and their susceptibility to antimicrobials commonly used in the poultry industry in Ghana. Sampling of faeces by a sock method (n = 75), dust (n = 75), feed (n = 10) and drinking water (n = 10) was performed at 75 commercial egg-laying and broiler farms in two regions of Ghana and skin neck (n = 30) at a local slaughterhouse from broilers representing different flocks. Salmonella was detected in 94/200 (47%) samples with an overall flock prevalence of 44·0%. Sixteen different serovars were identified with S. Kentucky (18·1%), S. Nima (12·8%), S. Muenster (10·6%), S. Enteritidis (10·6%) and S. Virchow (9·6 %) the most prevalent types. The predominant phage type of S. Enteritidis was PT1. All strains were susceptible to cefotaxime, ceftazidime and cefoxitin. Fifty-seven (60·6%) strains were resistant to one or more of the remaining nine antimicrobials tested by disk diffusion, of which 23 (40·4%) showed multi-resistance (resistance to ⩾3 classes of antimicrobials). Of the resistant strains (n = 57), the most significant were to nalidixic acid (89·5%), tetracycline (80·7%), ciprofloxacin (64·9%), sulfamethazole (42·1%), trimethoprim (29·8%) and ampicillin (26·3%). All S. Kentucky strains were resistant to more than two antimicrobials and shared common resistance to nalidixic acid or ciprofloxacin and tetracycline, often in combinations with other antimicrobials. PFGE analysis using XbaI of S. Kentucky demonstrated one dominant clone in the country. In conclusion, poultry produced in Ghana has a high prevalence of multi-resistant Salmonella and the common finding of clonal S. Kentucky in the Kumasi area warrants further investigations into the epidemiology of this serovar. There is an urgent need for surveillance and control programmes on Salmonella and use of antimicrobials in the Ghanaian poultry industry to protect the health of consumers.


Assuntos
Antibacterianos/farmacologia , Farmacorresistência Bacteriana Múltipla , Doenças das Aves Domésticas/epidemiologia , Salmonelose Animal/epidemiologia , Salmonella/isolamento & purificação , Animais , Galinhas , Estudos Transversais , Eletroforese em Gel de Campo Pulsado/veterinária , Feminino , Gana/epidemiologia , Testes de Sensibilidade Microbiana/veterinária , Doenças das Aves Domésticas/microbiologia , Prevalência , Salmonella/genética , Salmonelose Animal/microbiologia , Sorogrupo
4.
J Hosp Infect ; 104(3): 321-327, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31931045

RESUMO

BACKGROUND: Surveillance systems for surgical site infections (SSIs), as a measure of patient safety, help health institutions devise strategies to reduce or prevent them. No surveillance systems exist to monitor SSIs in Ghana. AIM: To establish a system for monitoring trends and detecting outbreaks in order to create awareness of and control SSIs. METHODS: An active 30-day surveillance was undertaken at the general surgical unit of the Korle Bu Teaching Hospital, from July 1st, 2017 to December 31st, 2018 to identify SSI. It involved a daily inpatient surveillance of patients who had had a surgical procedure, followed by post-discharge surveillance by means of a healthcare personnel-based survey and a patient-based telephone survey. We supplied quarterly feedback of results to surgeons. FINDINGS: Among the 3267 patients included, 331 were identified with an SSI, a 10% incidence risk. Patients who acquired an SSI experienced increased morbidity including nine extra days in hospital and an adjusted relative mortality risk of 2.3 (95% confidence interval: 1.3 - 4.1; P=0.006) compared to patients without SSI. Forty-nine per cent (161/331) of SSIs were diagnosed post discharge using the healthcare personnel-based survey. The patient-based telephone survey contributed 12 additional cases. SSI incidence risk decreased from 12.8% to 7.5% during the study period. CONCLUSION: Post-discharge surveillance is feasible using existing healthcare personnel, and the results highlight the high risk and burden of SSIs in Ghana. A surveillance system with feedback for monitoring SSIs may contribute to reducing SSIs; however, firm conclusions regarding the impact need longer observation time.


Assuntos
Infecção Hospitalar/epidemiologia , Segurança do Paciente , Infecção da Ferida Cirúrgica/epidemiologia , Adolescente , Adulto , Idoso , Criança , Estudos de Coortes , Feminino , Gana , Hospitais de Ensino , Humanos , Masculino , Pessoa de Meia-Idade , Vigilância da População , Estudos Prospectivos , Fatores de Risco , Infecção da Ferida Cirúrgica/prevenção & controle , Adulto Jovem
5.
Science ; 201(4351): 150-1, 1978 Jul 14.
Artigo em Inglês | MEDLINE | ID: mdl-17801831

RESUMO

Variations in the efficiency of convection resulting from its stochastic nature could be manifested as small ( less, similar1 percent) fluctuations in the solar constant. This could result in changes in the earth's climate with time scales of decades to centuries.

6.
Science ; 198(4321): 1035-7, 1977 Dec 09.
Artigo em Inglês | MEDLINE | ID: mdl-17779689

RESUMO

The roughly 25 percent increase in luminosity over the life of the sun shared by many different solar models is shown to be a very general result, independent of the uncertainties suggested by the solar neutrino experiment. Superficially, this leads to a conflict with the climatic history of the earth, and if basic concepts of stellar evolution are not fundamentally in error, compensating effects must have occurred, as first pointed out by Sagan and Mullen. One possible interpretation supported by recent detailed models of the earth's atmosphere is that the greenhouse effect was substantially more important than at present even as recently as 1 billion to 2 billion years ago.

7.
Science ; 201(4355): 522-5, 1978 Aug 11.
Artigo em Inglês | MEDLINE | ID: mdl-17790439

RESUMO

A statistical analysis of the properties of dense interstellar clouds indicates that the solar system has encountered at least a dozen clouds of sufficient density to cause planets to accumulate nonnegligible amounts of some isotopes. The effect is most pronounced for neon. This mechanism could be responsible for much of the neon in Earth's atmosphere. For Mars, the predicted amount of neon added by cloud encounters greatly exceeds the present abundance.

8.
West Afr J Med ; 28(5): 300-3, 2009.
Artigo em Inglês | MEDLINE | ID: mdl-20383833

RESUMO

BACKGROUND: Nosocomial or hospital acquired infection has been recognized as a serious public health problem in the last twenty years. In most hospitals in Africa-South of the Sahara, although the types of community acquired infections are known, neither the magnitude, nor the common types of nosocomial infections has been documented. OBJECTIVE: This study was carried out to find the prevalence of hospital and community acquired infections in hospitals, and to estimate the overall prevalence of HAI and CAI in Korle Bu Teaching Hospital. METHODS: A one-day prevalence survey of nosocomial and community acquired infection in a tertiary-care hospital in Accra was performed using the 1980 British national protocol and the result was analyzed using computerized gargets. RESULTS: Of the 907 patients on admission (on the day of the study), 61 (6.7%) had hospital-acquired infection and 287 (31.6%) had community acquired infection. The commonest hospital acquired infection was wound infection followed by skin and lower respiratory infections. Of the community infections, the most common cases were lower respiratory and skin infections. Fifty-three percent of all patients were on antimicrobial treatment. Patients on metronidazole were 212 (44%), ampicillin/amoxicillin 199 (41.6%), cloxacillin 163 (34%) and gentamicin 135 (28%). Approximately 20% of patients were on three or more drugs. CONCLUSION: This study has shown that the prevalence of community acquired infections in our hospital is much higher than that from nosocomial infections and that the British national survey protocol can be used in countries with limited resources.


Assuntos
Infecções Comunitárias Adquiridas/epidemiologia , Infecção Hospitalar/epidemiologia , Infecções Comunitárias Adquiridas/prevenção & controle , Infecção Hospitalar/prevenção & controle , Feminino , Gana/epidemiologia , Hospitais de Ensino/estatística & dados numéricos , Humanos , Masculino , Vigilância da População/métodos , Prevalência
9.
J Hosp Infect ; 101(1): 60-68, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29730140

RESUMO

BACKGROUND: There is a paucity of data describing hospital-acquired infections (HAIs) in Africa. OBJECTIVE: To describe the prevalence and distribution of HAIs in acute care hospitals in Ghana. METHODS: Between September and December 2016, point-prevalence surveys were conducted in participating hospitals using protocols of the European Centre for Disease Prevention and Control. Medical records of eligible inpatients at or before 8am on the survey date were reviewed to identify HAIs present at the time of the survey. FINDINGS: Ten hospitals were surveyed, representing 32.9% of all acute care beds in government hospitals. Of 2107 inpatients surveyed, 184 HAIs were identified among 172 patients, corresponding to an overall prevalence of 8.2%. The prevalence values in hospitals ranged from 3.5% to 14.4%, with higher proportions of infections in secondary and tertiary care facilities. The most common HAIs were surgical site infections (32.6%), bloodstream infections (19.5%), urinary tract infections (18.5%) and respiratory tract infections (16.3%). Device-associated infections accounted for 7.1% of HAIs. For 12.5% of HAIs, a micro-organism was reported; the most commonly isolated micro-organism was Escherichia coli. Approximately 61% of all patients surveyed were on antibiotics; 89.5% of patients with an HAI received at least one antimicrobial agent on the survey date. The strongest independent predictors for HAI were the presence of an invasive device before onset of infection and duration of hospital stay. CONCLUSION: A low HAI burden was found compared with findings from other low- and middle-income countries.


Assuntos
Infecção Hospitalar/epidemiologia , Infecções Respiratórias/epidemiologia , Sepse/epidemiologia , Infecção da Ferida Cirúrgica/epidemiologia , Infecções Urinárias/epidemiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Estudos Transversais , Escherichia coli/isolamento & purificação , Feminino , Gana/epidemiologia , Hospitais Públicos , Humanos , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Adulto Jovem
10.
Curr Biol ; 8(24): 1331-4, 1998 Dec 03.
Artigo em Inglês | MEDLINE | ID: mdl-9843689

RESUMO

Anoikis is a form of programmed cell death induced in normal epithelial cells by detachment from the extracellular matrix [1] [2] [3]. In epithelial cells of the intestine and other organs, activated rasinduces resistance to anoikis [3] [4], but the actual molecular effectors directly involved in the apoptotic machinery that execute or block anoikis have not yet been identified. Bak, a pro-apoptotic member of the Bcl-2 family, is downregulated in a high proportion of colorectal tumours [5]. In addition, Bak is an important regulator of apoptosis in normal intestinal epithelial cells [6] [7]. Here, we show that activated rasinduces the downregulation of Bak in rat and human intestinal epithelial cells. This ras-induced downregulation of Bak expression could be suppressed by an inhibitor of phosphatidylinositol (PI) 3-kinase, an enzyme already implicated in ras-induced resistance to anoikis [8]. Ectopic expression of Bak in ras-transformed rat intestinal epithelial IEC-18 cells inhibited ras-induced resistance to anoikis and significantly reduced their tumorigenicity. We conclude, therefore, that the ability of rasto downregulate Bak, and the consequent resistance to anoikis, are essential components of the transforming capacity of this oncogene in intestinal epithelial cells.


Assuntos
Apoptose/genética , Apoptose/fisiologia , Transformação Celular Neoplásica/genética , Transformação Celular Neoplásica/metabolismo , Genes ras , Mucosa Intestinal/metabolismo , Intestinos/citologia , Proteínas de Membrana/genética , Proteínas de Membrana/fisiologia , Animais , Cromonas/farmacologia , Células Clonais , Regulação para Baixo , Inibidores Enzimáticos/farmacologia , Células Epiteliais/metabolismo , Humanos , Morfolinas/farmacologia , Inibidores de Fosfoinositídeo-3 Quinase , Ratos , Transfecção , Proteína Killer-Antagonista Homóloga a bcl-2
11.
J Clin Invest ; 82(1): 145-53, 1988 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-3392204

RESUMO

The presence of serum antibodies to the diol-epoxide DNA adducts of representative polycyclic aromatic hydrocarbons (PAH), chrysene, benz[a]anthracene and benzo[a]pyrene, was determined by ELISA using serum samples obtained from normal healthy individuals. Antibodies that reacted against PAH adducted-DNA, but not against PAH-adducted protein, were found in the serum of approximately 40% of the test individuals. Specificity analysis of the antibodies demonstrated that serological cross-reactions between the benzo[a]pyrene and the chrysene diol-epoxide adducts were present. Similar cross-reactivity between the benz[a]anthracene and the chrysene adducts was observed. Sera containing antibodies that were apparently specific for each of the three PAH-DNA adducts were also identified. The presence of antibodies to PAH-DNA adducts indicates both past exposure to these carcinogenic PAH and their metabolic activation to the DNA damaging metabolites. These antibodies may prove to be useful in both retrospective and prospective epidemiological studies of various diseases associated with PAH exposure.


Assuntos
Anticorpos/análise , Benzo(a)pireno , Carcinógenos Ambientais , Adutos de DNA , DNA , Compostos Policíclicos/imunologia , Adulto , Fatores Etários , Idoso , Especificidade de Anticorpos , Reações Antígeno-Anticorpo , Benzo(a)Antracenos/imunologia , Benzopirenos/imunologia , Sítios de Ligação de Anticorpos , Crisenos/imunologia , DNA/imunologia , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores Sexuais , Fumar/imunologia
12.
East Afr Med J ; 84(3): 136-40, 2007 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-17600983

RESUMO

BACKGROUND: Most neonatal deaths in developing countries are caused by infections, birth asphyxia and prematurity. Even though most of these deaths occur at home, newborns admitted to hospital neonatal units have a high risk of contracting fatal multi-drug resistant infections. OBJECTIVE: To compare the type of bacteria and the pattern of antimicrobial susceptibility of organisms causing neonatal infections in 2001/02 with 1991/92 in the same neonatal unit. DESIGN: We reviewed the hospital records of newborns admitted to the neonatal unit in 2001/02 that had positive blood cultures and compared the findings with similar work done 1991/92. SETTING: Neonatal Unit, Korle Bu Teaching Hospital, Ghana. RESULTS: Gram negative organisms (predominantly Enterobacter, Klebsiella and Acinetobacter) remained the predominant cause of neonatal infection. There was a reduction in the proportion of gram negative bacteraemia [70.9% in 1991/92 vs. 54.2% in 2001/02 (p<0.001)] due to the increased prevalence of coagulase negative staphylococcus (31.9% in 2001/02 vs. 0% in 1991/92) as a cause of neonatal bacteraemia ten years later. In 1991/92 as 2001/02 all bacterial isolates showed less than 40% susceptibility to ampicillin. The susceptibility of Klebsiella and Enterobacter to commonly used aminoglycosides and cephalosporins had decreased from over 80% in 1991/92 to less than 35% in 2001/02. CONCLUSION: Bacterial causes of neonatal infections change over time and antimicrobial resistance is a major cause for concern in neonatal units in resource-poor hospitals. Improving infection control practices and instituting systems to monitor antimicrobial use and resistance will compliment community efforts to reduce neonatal mortality.


Assuntos
Infecções Bacterianas/microbiologia , Bactérias Gram-Negativas/isolamento & purificação , Bactérias Gram-Positivas/isolamento & purificação , Infecções Bacterianas/epidemiologia , Gana/epidemiologia , Hospitais de Ensino , Humanos , Recém-Nascido
13.
West Afr J Med ; 26(2): 131-3, 2007.
Artigo em Inglês | MEDLINE | ID: mdl-17939315

RESUMO

BACKGROUND: The level of drug resistance in mycobacterial isolates from previously treated cases in Ghana is not known although drug resistant tuberculosis threatens efforts to control the disease. OBJECTIVE: To identify and determine the susceptibility of mycobacterial isolates from tuberculosis cases with clinical treatment failure. METHODS: This prospective survey was undertaken at the Chest Clinic of Korle Bu Teaching Hospital in Accra, Ghana. The participants were twenty-eight cases referred to the hospital with clinical treatment failure. Two sputum specimens from each case were stained by Ziehl-Neelsen method, cultured, identified and sensitivity tests performed by the proportion method. RESULTS: Eighteen isolates of mycobacteria were identified from 28 failed treatment cases. Five were atypical mycobacteria. Approximately fifty percent (13/28) of cases had Mycobacterium tuberculosis, 5(18%) had atypical mycobacteria, 7(25%) had pure fungal growth and 3(11% 8) had no growth. Fifteen isolates were resistant to two or more drugs, of which 6 were resistant to all four drugs tested. CONCLUSION: Continuous drug resistance monitoring must be instituted as part of the tuberculosis control programme.


Assuntos
Suscetibilidade a Doenças , Farmacorresistência Bacteriana , Mycobacterium/efeitos dos fármacos , Falha de Tratamento , Tuberculose Pulmonar/microbiologia , Antibacterianos/farmacologia , Feminino , Gana , Inquéritos Epidemiológicos , Hospitais de Ensino , Humanos , Masculino , Mycobacterium/isolamento & purificação , Estudos Prospectivos , Escarro
14.
Cancer Res ; 46(11): 5842-50, 1986 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-3019539

RESUMO

A partially transformed cell line (NRK-PT14) was isolated from normal rat kidney (NRK) cells. Like NRK cells, NRK-PT14 cells required epidermal growth factor for anchorage-independent growth, but lost the additional requirement for exogenous type beta transforming growth factor (TGF-beta). Compared to NRK cells, NRK-PT14 cells did not secrete elevated levels of TGF-beta, but exhibited an altered response to this growth factor. Monolayer growth of NRK cells in a serum-free medium was inhibited by TGF-beta, whereas growth of NRK-PT14 cells was stimulated by TGF-beta. In addition, TGF-beta stimulated epidermal growth factor binding to high affinity sites in NRK cells, but decreased epidermal growth factor binding to NRK-PT14 cells during growth of the cells in serum-free medium. These qualitative changes in the response to TGF-beta may be representative of an intermediate stage in the spontaneous transformation of NRK cells.


Assuntos
Transformação Celular Neoplásica/fisiopatologia , Fator de Crescimento Epidérmico/farmacologia , Peptídeos/farmacologia , Animais , Ciclo Celular/efeitos dos fármacos , Linhagem Celular , Meios de Cultura , Receptores ErbB/fisiologia , Camundongos , Camundongos Nus , Neoplasias Experimentais/fisiopatologia , Peptídeos/metabolismo , Ratos , Vírus do Sarcoma Murino , Fatores de Crescimento Transformadores
15.
Cancer Res ; 46(8): 4178-83, 1986 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-3731085

RESUMO

Workers in coke oven plants have a higher incidence of lung cancer than the general population. They are exposed to a variety of chemicals, in particular the polycyclic aromatic hydrocarbons (PAH), including benzo(a)pyrene. To evaluate the genotoxic effects of PAH exposure, air samples and urine samples were analyzed for PAH by capillary gas chromatography and high-performance liquid chromatography, respectively. Since benzo(a)pyrene is activated to 7 beta,8 alpha-dihydroxy-(9 alpha,10 alpha)-epoxy-7,8,9,10-tetrahydrobenzo(a)pyrene (BPDE) and binds to DNA, we have used ultrasensitive enzymatic radioimmunoassay and synchronous fluorescence spectrophotometry to measure BPDE-DNA adducts in lymphocyte DNA. The results show that workers were exposed to high concentrations of atmospheric PAH. However, the mean PAH exposure levels are reduced 60% when the workers wore masks during work. When compared to exposure levels, the urinary excretion of PAH was relatively low. Approximately one-third of the workers had detectable putative BPDE-DNA adducts in lymphocytes by ultrasensitive enzymatic radioimmunoassay, and 10% of the samples had emission peaks at 379 nm by synchronous fluorescence spectrophotometry. The four most positive samples were the same in both of the assays. Antibodies to an epitope(s) on BPDE-DNA were found in the sera of approximately one-third of the workers. Detection of DNA adducts and antibodies to these adducts are internal indicators of exposure to benzo(a)pyrene.


Assuntos
7,8-Di-Hidro-7,8-Di-Hidroxibenzo(a)pireno 9,10-óxido , Poluentes Ocupacionais do Ar/toxicidade , Anticorpos/análise , Benzopirenos/análise , Carcinógenos Ambientais/urina , Carvão Mineral , Adutos de DNA , DNA/análise , Linfócitos/análise , Compostos Policíclicos/urina , Benzopirenos/imunologia , DNA/imunologia , Exposição Ambiental , Humanos , Compostos Policíclicos/toxicidade , Radioimunoensaio , Fumar , Espectrometria de Fluorescência
16.
Cancer Res ; 49(14): 3884-90, 1989 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-2786745

RESUMO

The tumorigenic NRK-PT14 cell line requires exogenous epidermal growth factor (EGF), but has lost the requirement for transforming growth factor beta (TGF-beta) for anchorage-independent growth, compared to normal rat kidney (NRK) cells. Development of an optimized serum-free medium for the growth of these cells revealed that NRK-PT14 cells also exhibit a qualitatively altered sensitivity to exogenous type 1 TGF-beta, compared to NRK cells. EGF-induced serum-free monolayer growth of NRK-PT14 cells was stimulated 2-fold by TGF-beta under conditions where growth of NRK cells was inhibited by 67%. TGF-beta only stimulated the growth of NRK-PT14 cells when EGF was present and when EGF was added before TGF-beta. In addition, the stimulation of EGF-induced NRK-PT14 cell growth by TGF-beta was associated with a specific, reversible loss of the high-affinity subpopulation of EGF receptors from the surface of these cells. Treatment of NRK cells with TGF-beta resulted in an increase in this EGF receptor population. Finally, EGF-induced anchorage-independent growth of NRK-PT14 cells was shown to be dependent on secreted TGF-beta, demonstrating an autocrine role for TGF-beta in the transformed phenotype of these cells. Autocrine transformation of NRK-PT14 cells by TGF-beta may result directly from the acquisition of an altered (positive) sensitivity to this growth factor.


Assuntos
Divisão Celular/efeitos dos fármacos , Transformação Celular Neoplásica , Receptores ErbB/metabolismo , Fatores de Crescimento Transformadores/farmacologia , Animais , Linhagem Celular , Meios de Cultura , Fator de Crescimento Epidérmico/metabolismo , Fator de Crescimento Epidérmico/farmacologia , Rim , Cinética , Ratos
17.
Cancer Res ; 60(11): 2964-72, 2000 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-10850444

RESUMO

OC144-093 is a novel substituted diarylimidazole (Mr 495) generated using the OntoBLOCK system, a solid-phase combinatorial chemistry technology, in combination with high-throughput cell-based screening. OC144-093 reversed multidrug resistance (MDR) to doxorubicin, paclitaxel, and vinblastine in human lymphoma, breast, ovarian, uterine, and colorectal carcinoma cell lines expressing P-glycoprotein (P-gp) with an average EC50 of 0.032 microM. Inhibition of MDR by OC144-093 was reversible, but the effect persisted for at least 12 h after removal of compound from the culture medium. OC144-093 had no effect on the response to cytotoxic agents by cells in vitro lacking P-gp expression or expressing a multidrug resistance-associated protein (MRP-1). OC144-093 was not cytotoxic by itself against 15 normal, nontransformed, or tumor cell lines, regardless of P-gp status, with an average cytostatic IC50 of >60 microM. OC144-093 blocked the binding of [3H]azidopine to P-gp and inhibited P-gp ATPase activity. The compound was >50% p.o. bioavailable in rodents and dogs and did not alter the plasma pharmacokinetics of i.v.-administered paclitaxel. OC144-093 increased the life span of doxorubicin-treated mice engrafted with MDR P388 leukemia cells by >100% and significantly enhanced the in vivo antitumor activity of paclitaxel in MDR human breast and colon carcinoma xenograft models, without a significant increase in doxorubicin or paclitaxel toxicity. The results demonstrate that OC144-093 is an orally active, potent, and nontoxic inhibitor of P-gp-mediated multidrug resistance that exhibits all of the desired properties for treatment of P-gp-mediated MDR, as well as for prevention of MDR prior to selection and/or induction of refractory disease.


Assuntos
Membro 1 da Subfamília B de Cassetes de Ligação de ATP/antagonistas & inibidores , Resistência a Múltiplos Medicamentos , Imidazóis/farmacologia , Adenosina Trifosfatases/metabolismo , Animais , Antineoplásicos/farmacologia , Antineoplásicos Fitogênicos/farmacologia , Divisão Celular/efeitos dos fármacos , Cães , Relação Dose-Resposta a Droga , Doxorrubicina/farmacologia , Resistencia a Medicamentos Antineoplásicos , Feminino , Humanos , Imidazóis/química , Concentração Inibidora 50 , Cinética , Camundongos , Camundongos SCID , Paclitaxel/farmacologia , Ratos , Fatores de Tempo , Células Tumorais Cultivadas , Vimblastina/farmacologia
18.
J Infect Prev ; 17(4): 179-184, 2016 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-28989477

RESUMO

INTRODUCTION: Antimicrobial resistance (AMR) represents a growing threat to public health, with the potential to reverse many of the gains made in modern medicine. AMR is contributed to by both inappropriate choice of antibiotics and inappropriate antibiotic course durations. OBJECTIVES: The objective of this audit was to determine if the introduction of antimicrobial prescribing electronic prompts in an electronic patient record had a positive impact on antimicrobial stewardship. METHODS: The audit examined the proportion of antibiotic prescriptions within a critical care unit in which both a valid stop date and indication were recorded. The audit was repeated on two occasions: first, after an education programme, and second, after the introduction of an electronic prompt within the patients' electronic patient record. RESULTS: Chi-square analyses indicated that significant improvements in both the recording of indications (χ²(4) = 39.69, P <0.0001) and stop-dates (χ²(4) = 42.10, P <0.0001) occurred across the three audits. CONCLUSION: We conclude that the novel use of daily electronic prompts has a positive impact on antimicrobial stewardship.

19.
Clin Cancer Res ; 3(12 Pt 1): 2355-62, 1997 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-9815634

RESUMO

The clinical and immunological effects of a vaccine consisting of CTP37, a synthetic peptide corresponding to the COOH-terminal peptide (CTP) of beta-human chorionic gonadotropin (beta-hCG) conjugated to diphtheria toxoid, combined with CRL 1005, a novel synthetic nonionic block copolymer adjuvant, were examined. Twenty-one patients with metastatic, nontrophoblastic cancers received up to four immunizations by i.m. injection of a fixed dose of CTP37 and escalating doses of CRL 1005. Doses of CRL 1005 adjuvant as high as 75 mg were administered with 1 mg of CTP37 without evidence of significant local or systemic toxicity. Immunizations resulted in the production of IgG antibody to beta-hCG. CRL 1005 doses of 3-25 mg appeared to be optimal for antibody induction. Immunizations also resulted in increases in the cellular response of peripheral blood mononuclear cells (PBMCs) to the unconjugated CTP, hCG, and diphtheria toxoid. Responding PBMCs specifically secreted the TH1-associated cytokines IFN-gamma and interleukin (IL)-2 as well as the TH2-associated IL-5 and IL-10. Increased expression of IFN gamma and IL-5 mRNAs by PBMCs 4 h after immunization was also observed. CRL 1005 administered with CTP37 in aqueous solution is well tolerated. The CTP37-CRL 1005 subunit vaccine has the capacity to stimulate potentially beneficial humoral and cellular immune responses in patients with advanced cancer.


Assuntos
Adjuvantes Imunológicos/uso terapêutico , Gonadotropina Coriônica Humana Subunidade beta/uso terapêutico , Neoplasias/terapia , Poliéster Sulfúrico de Pentosana/farmacocinética , Adjuvantes Imunológicos/administração & dosagem , Adjuvantes Imunológicos/toxicidade , Adulto , Idoso , Formação de Anticorpos , Gonadotropina Coriônica , Gonadotropina Coriônica Humana Subunidade beta/administração & dosagem , Gonadotropina Coriônica Humana Subunidade beta/efeitos adversos , Toxoide Diftérico/administração & dosagem , Toxoide Diftérico/uso terapêutico , Feminino , Humanos , Hipersensibilidade Tardia , Imunidade Celular , Imunoglobulina G/sangue , Interferon gama/genética , Interleucina-2/genética , Interleucina-5/genética , Masculino , Pessoa de Meia-Idade , Neoplasias/imunologia , Poliéster Sulfúrico de Pentosana/administração & dosagem , Polímeros , Soluções , Células Th1/imunologia
20.
West Afr J Med ; 24(3): 219-22, 2005.
Artigo em Inglês | MEDLINE | ID: mdl-16276698

RESUMO

OBJECTIVE: To determine the vaginal flora of first time urban Family Planning clients at Korle-Bu Teaching Hospital and to assess its implications for the contraceptive choices made. DESIGN: A cross sectional study. METHODS: A standardized questionnaire surveying the sociodemographic characteristics and the choice of Family Planning method was administered to 100 clients at the Korle Bu Teaching Hospital between March and September 2001. High vaginal and endocervical swabs were also taken during the inspection of the vagina and cervix using a sterile bivalve speculum. The specimens were transported in Amies transport medium to the Microbiology laboratory for processing. RESULTS: The age range of the clients was 19-48 years with a modal age of 28 years. Ninety-six percent of them were married while 86% lived in urban slums. Sixty-three percent were sure of their last menstrual period. Potential pathogens were isolated from culture in 56% of the clients. Organisms causing bacterial vaginosis were the most prevalent in their genital tract. The intrauterine contraceptive device (IUCD) was the most common Family Planning method chosen, followed by the Norplant and the Depo-Provera injections. Potential pathogens were isolated from culture in 50% of those who chose the IUCD. CONCLUSION: Potential pathogens were isolated from culture in 56% of these first-time clients and organisms causing bacterial vaginosis were the most prevalent in the genital tract. It is suggested that Family Planning clients who screened positive for potential pathogens and opt for the IUCD should be considered for prophylactic antibiotics at insertion.


Assuntos
Instituições de Assistência Ambulatorial/estatística & dados numéricos , Saúde da População Urbana , Vagina/microbiologia , Vaginose Bacteriana/diagnóstico , Adulto , Contagem de Colônia Microbiana , Anticoncepção/métodos , Estudos Transversais , Feminino , Gana , Hospitais de Ensino , Humanos , Pessoa de Meia-Idade , Inquéritos e Questionários , Esfregaço Vaginal , Vaginose Bacteriana/microbiologia
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