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1.
J Hosp Infect ; 114: 10-22, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34301392

RESUMO

BACKGROUND: The measure of disease frequency most widely used to report healthcare-associated infection (HAI) is the point-prevalence survey. Incidence studies are rarely performed due to time and cost constraints; they show which patients are affected by HAI, when and where, and inform planning and design of infection prevention and control (IPC) measures. AIM: To determine the epidemiology of HAI within a general and a teaching hospital in Scotland. METHODS: A prospective observational incidence study was undertaken for one year from April 2018 using data collected as part of the Evaluation of Cost of Nosocomial Infection (ECONI) study. A novel, robust approach was undertaken, using record linkage to national administrative data to provide full admission and discharge information. Cases were recorded if they met international HAI definitions. FINDINGS: Incidence of HAI for the combined hospitals was 250 HAI cases per 100,000 acute occupied bed-days (AOBD). Highest frequency was in urinary tract (51.2 per 100,000 AOBD), bloodstream (44.7), and lower respiratory tract infection (42.2). The most frequently reported organisms were Escherichia coli, Staphylococcus aureus, and norovirus. Incidence of HAI was higher in older people and emergency cases. There was an increase in the rate of HAI in summer months (pneumonia, respiratory, surgical, and gastrointestinal infection) and in winter months norovirus gastrointestinal infection (P < 0.0001). The highest incidence specialties were intensive care, renal medicine, and cardiothoracic surgery. HAI occurred at a median of 9 days (interquartile range: 4-19) after admission. Incidence data were extrapolated to provide an annual national estimate of HAI in NHS Scotland of 7437 (95% confidence interval: 7021-7849) cases. CONCLUSION: This study provides a unique overview of incidence of HAI and identifies the burden of HAI at the national level for the first time. Understanding the incidence in different clinical settings, at different times, will allow targeting of IPC measures to those patients who would benefit the most.


Assuntos
Infecção Hospitalar , Idoso , Estudos de Coortes , Infecção Hospitalar/epidemiologia , Infecção Hospitalar/prevenção & controle , Atenção à Saúde , Hospitais de Ensino , Humanos , Incidência , Controle de Infecções
2.
J Hosp Infect ; 114: 32-42, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34301394

RESUMO

BACKGROUND: Few healthcare-associated infection (HAI) studies focus on risk of HAI at the point of admission. Understanding this will enable planning and management of care with infection prevention at the heart of the patient journey from the point of admission. AIM: To determine intrinsic characteristics of patients at hospital admission and extrinsic events, during the two years preceding admission, that increase risk of developing HAI. METHODS: An incidence survey of adults within two hospitals in NHS Scotland was undertaken for one year in 2018/19 as part of the Evaluation of Cost of Nosocomial Infection (ECONI) study. The primary outcome measure was developing any HAI using recognized case definitions. The cohort was derived from routine hospital episode data and linkage to community dispensed prescribing data. FINDINGS: The risk factors present on admission observed as being the most significant for the acquisition of HAI were: being treated in a teaching hospital, increasing age, comorbidities of cancer, cardiovascular disease, chronic renal failure and diabetes; and emergency admission. Relative risk of developing HAI increased with intensive care unit, high-dependency unit, and surgical specialties, and surgery <30 days before admission and a total length of stay of >30 days in the two years to admission. CONCLUSION: Targeting patients at risk of HAI from the point of admission maximizes the potential for prevention, especially when extrinsic risk factors are known and managed. This study proposes a new approach to infection prevention and control (IPC), identifying those patients at greatest risk of developing a particular type of HAI who might be potential candidates for personalized IPC interventions.


Assuntos
Infecção Hospitalar , Adulto , Infecção Hospitalar/epidemiologia , Infecção Hospitalar/prevenção & controle , Atenção à Saúde , Humanos , Incidência , Controle de Infecções , Unidades de Terapia Intensiva
3.
Neurotox Res ; 34(3): 677-692, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30051419

RESUMO

The reversibility of chemotherapy-induced peripheral neuropathy (CIPN), a disabling and potentially permanent side effect of microtubule-targeting agents (MTAs), is becoming an increasingly important issue as treatment outcomes improve. The molecular mechanisms regulating the variability in time to onset, severity, and time to recovery from CIPN between the common MTAs paclitaxel and eribulin are unknown. Previously (Benbow et al. in Neurotox Res 29:299-313, 2016), we found that after 2 weeks of a maximum tolerated dose (MTD) in mice, paclitaxel treatment resulted in severe reductions in axon area density, higher frequency of myelin abnormalities, and increased numbers of Schwann cell nuclei in sciatic nerves. Biochemically, eribulin induced greater microtubule-stabilizing effects than paclitaxel. Here, we extended these comparative MTD studies to assess the recovery from these short-term effects of paclitaxel, eribulin, and a third MTA, ixabepilone, over the course of 6 months. Paclitaxel induced a persistent reduction in axon area density over the entire 6-month recovery period, unlike ixabepilone- or eribulin-treated animals. The abundance of myelin abnormalities rapidly declined after cessation of all drugs but recovered most slowly after paclitaxel treatment. Paclitaxel- and ixabepilone- but not eribulin-treated animals exhibited increased Schwann cell numbers during the recovery period. Tubulin composition and biochemistry rapidly returned from MTD-induced levels of α-tubulin, acetylated α-tubulin, and end-binding protein 1 to control levels following cessation of drug treatment. Taken together, sciatic nerve axons recovered more rapidly from morphological effects in eribulin- and ixabepilone-treated animals than in paclitaxel-treated animals and drug-induced increases in protein expression levels following paclitaxel and eribulin treatment were relatively transient.


Assuntos
Antineoplásicos/toxicidade , Neuropatia Ciática , Animais , Modelos Animais de Doenças , Epotilonas/toxicidade , Feminino , Furanos/toxicidade , Filamentos Intermediários/metabolismo , Cetonas/toxicidade , Camundongos , Camundongos Endogâmicos BALB C , Proteínas Associadas aos Microtúbulos/metabolismo , Bainha de Mielina/efeitos dos fármacos , Bainha de Mielina/patologia , Paclitaxel/toxicidade , Recuperação de Função Fisiológica/efeitos dos fármacos , Recuperação de Função Fisiológica/fisiologia , Proteínas S100/metabolismo , Células de Schwann/efeitos dos fármacos , Células de Schwann/patologia , Neuropatia Ciática/induzido quimicamente , Neuropatia Ciática/metabolismo , Neuropatia Ciática/patologia , Fatores de Tempo , Tubulina (Proteína)/metabolismo
4.
J Cell Sci Ther ; 9(4)2018.
Artigo em Inglês | MEDLINE | ID: mdl-31032145

RESUMO

Pancreatic cancer is one of the most aggressive malignancies with an increase in incidence predicted, particularly in African Americans. Pancreatic cancer is considered a silent disease with poor prognosis and a lack of early biomarkers for detection. Proteomics has been applied in many diseases for identifying or discovering biomarkers. It has long been suggested that chronic pancreatitis may be a risk factor for developing pancreatic cancer. This study identified proteins that are altered in expression in pancreatic cancer and pancreatitis compared to normal using proteomic technology. Proteins were extracted from laser captured micro-dissected tissues and separated in 2-DPAGE and imaged. The protein profiles of pancreatic cancer and pancreatitis are similar but differed with the protein profile of normal adjacent tissues. Representative proteins, overexpressed in tumor and pancreatitis but not normal tissues, were excised from gels, subjected to in-gel digestion, and analyzed by MALDI-TOF mass spectrometry. Proteins identified included transferrin, ER-60 protein, proapolipoprotein, tropomyosin 1, alpha 1 actin precursor, ACTB protein, and gamma 2 propeptide, aldehyde dehydrogenase 1A1, pancreatic lipase and annexin A1. Several proteins, which were shown in pancreatic cancer, were also observed in pancreatitis samples. Understanding the role of these specific proteins and their mechanistic action will give insights into their involvement in pancreatic cancers.

5.
J Helminthol ; 89(1): 68-79, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-24018146

RESUMO

We examined changes to the behaviour of flour beetles, Tribolium confusum, infected with the rodent stomach worm, the spirurid Protospirura muricola, in the context of the 'Behavioural Manipulation Hypothesis'. Trobolium confusum infected with the third-stage infective larvae of P. muricola showed consistently altered patterns of behaviour. Relative to uninfected beetles, over a measured time period, beetles infected with P. muricola were likely to move over a shorter distance, when moving their speed of movement was slower, they were more likely to stay in the illuminated area of their environment, more likely to emerge from darkened areas into the illuminated areas, and their longevity was significantly shortened. The changes in behaviour, as reflected in effects on speed of movement, were only evident among beetles that actually harboured infective cysts and not among those carrying younger infections when the larvae within their haemocoels would have been at an earlier stage of development and not yet capable of infecting the definitive murine hosts. We discuss whether these changes would have made the beetles more susceptible to predation by rodents, and specifically by the omnivorous eastern spiny mouse, Acomys dimidiatus, the natural definitive host of this parasite in Egypt, from where the P. muricola isolate originated, and whether they support the Behavioural Manipulation Hypothesis or reflect parasite-induced pathology.


Assuntos
Spiruroidea/fisiologia , Tribolium/fisiologia , Tribolium/parasitologia , Animais , Comportamento Animal , Feminino , Larva/crescimento & desenvolvimento , Larva/fisiologia , Camundongos/parasitologia , Spiruroidea/crescimento & desenvolvimento
6.
Exp Oncol ; 32(3): 172-80, 2010 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-21403613

RESUMO

One of the major limitations of chemotherapy is that often, over time, tumor cells become either inherently resistant or develop multidrug resistance to the treatment. Another limitation of chemotherapy is toxicity to normal tissues and adverse side effects. The reasons for the failure of some cancers to respond to chemotherapeutic drugs are not clear but have been attributed to alterations in many molecular pathways, which include drug metabolizing enzymes and drug transporter genes. Alterations in the energy-dependent ATP-binding cassette (ABC) transporter genes have been suggested to confer a drug-resistant phenotype by decreasing the intracellular accumulation of chemotherapeutic drugs via efflux mechanisms. In addition, polymorphisms in UDP-glucuronosyltransferases (UGTs) have been reported to correlate with clinical outcome and drug resistance. In this review, we provide an overview of known polymorphisms within UGTs and ABC transporter genes that have been reported to have altered expression and/or activity in breast cancer. Those polymorphic variants that affect the clinical efficacy and confer drug resistance of chemotherapeutic agents, including hormonal therapies, taxanes, anthracyclines, and alkylating agents, in breast cancer.


Assuntos
Transportadores de Cassetes de Ligação de ATP/genética , Neoplasias da Mama/tratamento farmacológico , Resistencia a Medicamentos Antineoplásicos , Glucuronosiltransferase/genética , Polimorfismo Genético , Animais , Neoplasias da Mama/genética , Resistência a Múltiplos Medicamentos , Feminino , Humanos
7.
J Anim Sci ; 86(8): 1963-76, 2008 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-18407986

RESUMO

Twenty-four Angus x Hereford crossbred steers (247 kg BW; SE = 2.4 kg) were used in a completely random design to evaluate the effect of energy source and level with or without antibiotic administration on measures of immune function. Steers were fed 1 of 3 dietary treatments: a 70% concentrate diet ad libitum (70AL), a 30% concentrate diet ad libitum (30AL), and a 70% concentrate diet offered in an amount calculated to provide NE(g) intake equal to the 30AL treatment (70RES). Half the steers in each dietary treatment received a s.c. injection of tilmicosin phosphate (ANTI; 1 mL/30 kg of BW); the other half received an equal volume of saline s.c. (SAL). Steers were offered the treatment diets for 28 d before and were administered the ANTI or SAL injections 2 d before indwelling catheters were placed in the jugular vein and 2.0 microg/kg of BW of Escherichia coli lipopolysaccharide (LPS) was administered i.v. Blood serum was collected at 30-min intervals from -2 to 6 h and at 8, 12, 24, 48, and 72 h relative to the LPS challenge. Increased energy intake (70AL) increased (P < or = 0.04) DMI, ADG, and rectal temperature (RT) after the challenge compared with the 70RES treatment. The 30AL treatment increased the maximum concentrations and area under the response curve of the proinflammatory cytokines (PIC) interferon-gamma, tumor necrosis factor-alpha, and IL-6 (P < or = 0.05) compared with the average of the 70AL and 70RES treatments. Decreased energy intake (70RES vs. 70AL) increased IL-6 (P < or = 0.003) but did not significantly increase interferon-gamma and tumor necrosis factor-alpha (P > or = 0.14) after LPS administration. Tilmicosin administration decreased the time to attain maximal RT (P = 0.01) by 1 h without altering the peak RT (P = 0.85), and tilmicosin interacted with energy intake to increase prechallenge PIC in 70RES vs. 70AL (P < or = 0.05). Results indicate that increased PIC response, presumably resulting from a combination of decreased energy intake and from direct effects of roughage, may be a mode of action for the slight decrease in morbidity that often occurs when newly received, stressed calves are fed roughage-based receiving diets. Tilmicosin phosphate might have immunomodulatory capacity beyond its direct effects on pathogenic bacteria, and these effects could interact with dietary energy intake in cattle.


Assuntos
Ração Animal/análise , Antibacterianos/farmacologia , Bovinos/imunologia , Metabolismo Energético/efeitos dos fármacos , Lipopolissacarídeos/toxicidade , Tilosina/análogos & derivados , Proteínas de Fase Aguda/metabolismo , Fenômenos Fisiológicos da Nutrição Animal , Animais , Citocinas/sangue , Dieta/veterinária , Hidrocortisona/sangue , Masculino , Fatores de Tempo , Tilosina/farmacologia
8.
J Laryngol Otol ; 121(12): 1184-8, 2007 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-17445355

RESUMO

INTRODUCTION: Early glottic cancer may be treated with primary radiotherapy or transoral laser microsurgery with comparable survival. The choice of therapy therefore depends on patient preference after discussion of risks, benefits and alternatives. MATERIALS AND METHODS: All previously untreated patients undergoing transoral laser microsurgery for T1 or T2 glottic cancer at St Vincent's Hospital between July 1997 and December 2004 had their staging and demographics recorded. Surgery was categorised according to the European Laryngological Society. A voice recording was made pre-operatively then at 12 weeks post-operatively and scored by two independent speech therapists on the Oates Russell Voice Profile - a scale of zero (normal) to five (severe dysphonia). Follow up was for a minimum of two years. RESULTS AND ANALYSIS: Fifty-three patients with a mean age of 56 were included. The observed survival was T1 89.4 per cent and T2 85.3 per cent after a mean follow up of 47 months. Nineteen patients staged T1 underwent cordectomy. A second procedure was required in 22.2 per cent, however, none required a laryngectomy. Thirty-four patients staged T2 underwent hemilaryngectomy. A second procedure was required in 41.2 per cent including 8.8 per cent requiring salvage laryngectomy. One patient died with unresectable nodal disease. The mean Oates Russell Voice Profile for T1 disease was 2.37 and for T2 2.68 (range 1 to 4) indicating a mild (2) to moderate (3) degree of voice impairment. CONCLUSIONS: Survival outcomes following transoral laser microsurgery are comparable to treatment with radiotherapy. Voice impairment is usually mild to moderate following transoral laser microsurgery for early glottic cancer but overall may be greater than in radiotherapy patients. The repeatability of transoral laser microsurgery may result in a lower laryngectomy rate compared with published series using radiotherapy.


Assuntos
Carcinoma de Células Escamosas/cirurgia , Neoplasias Laríngeas/cirurgia , Terapia a Laser/métodos , Distúrbios da Voz/etiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Escamosas/patologia , Métodos Epidemiológicos , Feminino , Glote , Humanos , Neoplasias Laríngeas/patologia , Laringectomia , Terapia a Laser/efeitos adversos , Masculino , Microcirurgia/efeitos adversos , Microcirurgia/métodos , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/cirurgia , Estadiamento de Neoplasias , Reoperação , Resultado do Tratamento
9.
Int J Gynecol Cancer ; 16(6): 1963-72, 2006.
Artigo em Inglês | MEDLINE | ID: mdl-17177833

RESUMO

Epithelial ovarian tumors are the most common subtype of ovarian cancer. In this study, we reveal distinct expression signatures of previously uncharacterized ovarian carcinoma subtypes, including endometrioid component of mixed ovarian tumor and Sertoli-Leydig tumor. Both subtypes were compared to the most common and well-characterized ovarian epithelial carcinoma of the serous type. These comparisons were performed by complementaryDNA (cDNA) microarrays allowing high-fidelity measurements of the expression levels of 39,360 human individual cDNA species representing both known and unknown human genes. Functional analysis of differentially expressed genes in Sertoli-Leydig tumor revealed an upregulation in sonic hedgehog pathway, deregulation of several metabolic pathways especially in amino acid metabolism and overexpression of genes associated with protein synthesis, including ribosomal genes.


Assuntos
Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Neoplasias Ovarianas/genética , Tumor de Células de Sertoli-Leydig/genética , Feminino , Humanos , Análise de Sequência com Séries de Oligonucleotídeos , Neoplasias Ovarianas/classificação , Neoplasias Ovarianas/patologia , RNA Mensageiro/genética , Reprodutibilidade dos Testes , Tumor de Células de Sertoli-Leydig/diagnóstico , Tumor de Células de Sertoli-Leydig/patologia
10.
Cell Biol Toxicol ; 22(2): 73-80, 2006 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-16532285

RESUMO

NAD(P)H:quinone oxidoreductase 1 (NQO1) is elevated in several human tumors. This study was conducted to determine whether increased levels of NQO1 expression also occur in human pancreatic tumor tissue, and to compare expression levels in nontumorous tissue from smokers with those in nonsmokers. The expression of NQO1 was examined in pancreatic tissue samples from 82 human donors. These samples included normal (n = 20), smokers (n = 25), pancreatitis (n = 7), and adenocarcinomas of the pancreas (n = 30). Genotyping for the C609T polymorphism in NQO1 by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis was also performed. Polymorphic variants were confirmed by automatic sequencing. Higher levels of NQO1 expression were demonstrated in pancreatic adenocarcinomas (0.831 +/- 0.021) compared to those in nontumorous tissues from nonsmokers (0.139 +/- 0.024). These high levels were also found in smokers (0.729 +/- 0.167) and in pancreatitis tissues (0.923 +/- 0.184). NQO1 activity was also higher in smokers (2.43 +/- 0.61 nmol/min per mg protein) compared to nonsmokers (0.44 +/- 0.05 nmol/min per mg protein; p < 0.05). No differences were found in genotype distribution and frequencies of the variant alleles between normal and cancer tissues in this relatively small sample pool. Seventy-five percent of the normal pancreatic tissues showed 609(C/C) and 25% 609(C/T). In pancreatic adenocarcinomas the frequency distribution was 65% C/C, 30% C/T and 5% T/T. The increased expression in noncancer pancreatic tissue from smokers and the fact that smoking is a moderate risk factor for pancreatic cancer suggest that NQO1 expression may be a good candidate as a biomarker for pancreatic cancer, especially in risk groups such as smokers.


Assuntos
Adenocarcinoma/enzimologia , Biomarcadores Tumorais/análise , NAD(P)H Desidrogenase (Quinona)/metabolismo , Pâncreas/enzimologia , Neoplasias Pancreáticas/enzimologia , Polimorfismo de Nucleotídeo Único , Fumar/metabolismo , Adenocarcinoma/diagnóstico , Adenocarcinoma/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Sequência de Bases , Estudos de Casos e Controles , Feminino , Predisposição Genética para Doença , Humanos , Masculino , Pessoa de Meia-Idade , Dados de Sequência Molecular , NAD(P)H Desidrogenase (Quinona)/genética , Pâncreas/metabolismo , Neoplasias Pancreáticas/diagnóstico , Neoplasias Pancreáticas/genética , Pancreatite/enzimologia , Fumar/efeitos adversos
11.
Proc Natl Acad Sci U S A ; 98(26): 15203-8, 2001 Dec 18.
Artigo em Inglês | MEDLINE | ID: mdl-11752463

RESUMO

We used hierarchical clustering to examine gene expression profiles generated by serial analysis of gene expression (SAGE) in a total of nine normal lung epithelial cells and non-small cell lung cancers. Separation of normal and tumor, as well as histopathological subtypes, was evident by using the 3,921 most abundant transcript tags. This distinction remained when only 115 highly differentially expressed tags were used. Furthermore, these 115 transcript tags clustered into groups suggestive of the unique biological and pathological features of the different tissues examined. Adenocarcinomas were characterized by high-level expression of small airway-associated or immunologically related proteins, whereas squamous cell carcinomas overexpressed genes involved in cellular detoxification or antioxidation. The messages of two p53-regulated genes, p21(WAF1/CIP1) and 14-3-3final sigma, were consistently underexpressed in the adenocarcinomas, suggesting that the p53 pathway itself might be compromised in this cancer type. Gene expression patterns observed by SAGE were consistent with results obtained by quantitative real-time PCR or cDNA array analyses by using a total of 43 lung tumor and normal samples. Thus, although derived from only a few tissue libraries, gene expression profiles obtained by using SAGE most likely represent an unbiased yet distinctive molecular signature for the most common forms of human lung cancer.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/genética , Perfilação da Expressão Gênica , Neoplasias Pulmonares/genética , Sequência de Bases , DNA Complementar , Humanos , Análise de Sequência com Séries de Oligonucleotídeos , Reação em Cadeia da Polimerase
12.
Ophthalmology ; 108(11): 2088-98; quiz 2099-100, 2121, 2001 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-11713084

RESUMO

PURPOSE: To provide evidence-based clinical recommendations for treatment options and future prospects for the management of common malignant eyelid tumors, including global ratings for the strength of published evidence supporting them. CLINICAL RELEVANCE: Approximately 5% to 10% of all skin cancers occur in the eyelid. Incidence studies indicate that basal cell carcinoma is the most frequent malignant eyelid tumor, followed by squamous cell carcinoma, sebaceous gland carcinoma, and malignant melanoma. Many therapeutic methods have been suggested to combat the morbidity and mortality associated with these lesions. LITERATURE REVIEWED: A MEDLINE and PubMed literature search (1966-1999) was conducted for English language abstracts and appropriate (selected) full-text references retrieved regarding treatment of malignant eyelid tumors. These sources then were used to prepare recommendations for patient care. Each recommendation was rated according to: (1) its importance in the care process and (2) the strength of evidence supporting the given recommendation. RESULTS: All recommendations were rated as level A (very important to patient-care outcome). For basal cell carcinoma, squamous cell carcinoma, and sebaceous gland carcinoma, the published evidence supporting two recommendations (Mohs' micrographic surgery or excision with frozen-section control) were graded as I (providing strong evidence in support of a recommendation). For sebaceous gland carcinoma, the recommendations also included conjunctival map biopsies. The published evidence supporting all other recommendations for these three eyelid tumors were graded II (substantial evidence in support of a recommendation), primarily because of the small numbers of patients in each clinical study. For malignant melanoma, the recommendation for therapy (i.e., excision with variable margins depending on tumor thickness) was based on published papers individually variably rated as I, II, and III, reflecting ongoing debate as to the best method of therapy. CONCLUSIONS: Published reports regarding the treatment of malignant eyelid tumors include a myriad of treatment options. The strongest evidence favors complete surgical removal using histologic controls for verifying tumor-free margins of excision.


Assuntos
Adenocarcinoma Sebáceo/cirurgia , Carcinoma Basocelular/cirurgia , Carcinoma de Células Escamosas/cirurgia , Neoplasias Palpebrais/cirurgia , Melanoma/cirurgia , Neoplasias das Glândulas Sebáceas/cirurgia , Adenocarcinoma Sebáceo/patologia , Carcinoma Basocelular/patologia , Carcinoma de Células Escamosas/patologia , Medicina Baseada em Evidências , Neoplasias Palpebrais/patologia , Previsões , Humanos , Melanoma/patologia , Neoplasias das Glândulas Sebáceas/patologia
13.
Life Sci ; 69(7): 839-45, 2001 Jul 06.
Artigo em Inglês | MEDLINE | ID: mdl-11487095

RESUMO

Human cytochrome P4501A2 (CYP1A2) is involved in the metabolism of a large number of common drugs and is responsible for the metabolic activation of numerous promutagens and procarcinogens. Large interindividual differences exist in the expression of this enzyme. This variability has important implications for drug efficacy and cancer susceptibility. In this sudy, the methylation status of the CCGG site (bp -2759) located adjacent to an AP-1 site in the 5'-flanking region of the CYP1A2 gene was assessed in liver samples from a pool of 55 human donors. DNA methylation is an important epigenetic mechanism controlling gene expression and may be one of the molecular mechanisms underlying the interindividual variation. Analysis was conducted using Hpa II digestion and PCR. Results showed that individual samples varied in the methylation status at this site. The site was found to be hypermethylated in approximately 60% of the samples. To compare methylation status with level of CYP1A2 expression, results were analyzed by median test. In 44% of the samples with expression levels above the median the CCGG site was hypermethylated. However, for those samples with levels below the median hypermethylation of the site was found in 73% of the samples. The difference was statistically significant (p<0.05). These findings indicate that CpG methylation may be involved in controlling the expression of CYP1A2, with hypermethylation reducing expression. Moreover, this approach can be useful in assessing the role of site-specific DNA methylation in interindividual variation of CYP1A2. Analysis of other CpG sites in potentially important regulatory elements of the CYP1A2 gene will continue.


Assuntos
Citocromo P-450 CYP1A2/genética , Citocromo P-450 CYP1A2/metabolismo , Metilação de DNA , Regulação Enzimológica da Expressão Gênica , Fígado/enzimologia , DNA/análise , Primers do DNA/química , Humanos , Mutação Puntual , Polimorfismo Genético , RNA/análise , Reação em Cadeia da Polimerase Via Transcriptase Reversa
14.
Ophthalmic Plast Reconstr Surg ; 17(3): 161-8, 2001 May.
Artigo em Inglês | MEDLINE | ID: mdl-11388380

RESUMO

PURPOSE: To describe a novel surgical technique for lower eyelid ectropion repair that avoids canthotomy and cantholysis and can be used in combination with external levator repair and/or in combination with blepharoplasty. METHODS: A retrospective analysis of lower eyelid procedures with the use of the canthus-sparing technique between January 1, 1998, and December 31, 1999, was performed. The canthus-sparing approach was used in 198 eyelid procedures for the correction of lower eyelid ectropion. Seventy-four (37.4%) procedures involved the correction of lower eyelid ectropion alone and 25 (12.6%) procedures involved the correction of lower eyelid ectropion during upper eyelid small-incision external levator repair. In these cases, an incision was made lateral to the lateral canthus and a periosteal flap was created at the lateral orbital rim. The inferior crus of the lateral canthal tendon was then attached to this full-thickness elevated periosteum. Twenty (10.1%) procedures involved the correction of ectropion during upper blepharoplasty and 79 (39.9%) procedures involved the correction of ectropion during combined upper eyelid ptosis repair and blepharoplasty. In these cases, the inferior crus of the lateral canthal tendon was attached to a periosteal flap created through the lateral portion of the blepharoplasty incision. RESULTS: The mean age of patients undergoing ectropion repair was 74.3+/-9.3 years (range, 42-93 years). The average duration of symptoms (most commonly tearing and/or ocular irritation) was 20+/-14 months (range, 3-84 months). Recurrences of lower eyelid ectropion or symptoms occurred in 4 (2%) eyelids. The average follow-up interval was 54+/-65 days (range, 3-330 days). CONCLUSIONS: The canthus-sparing approach to ectropion repair promotes a secure adhesion to the lateral orbital wall with minimal violation of normal anatomic structures and relations. It is time-efficient and reduces postoperative morbidity.


Assuntos
Blefaroplastia/métodos , Ectrópio/cirurgia , Pálpebras/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Procedimentos Cirúrgicos Minimamente Invasivos , Músculos Oculomotores/cirurgia , Estudos Retrospectivos , Técnicas de Sutura
15.
Biochemistry ; 40(18): 5382-91, 2001 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-11331001

RESUMO

The leukocyte adhesion molecule L-selectin mediates lymphocyte homing to secondary lymphoid organs and to certain sites of inflammation. The cognate ligands for L-selectin possess the unusual sulfated tetrasaccharide epitope 6-sulfo sialyl Lewis x (Siaalpha2-->3Galbeta1-->4[Fucalpha1-->3][SO(3)-->6]GlcNAc). Sulfation of GlcNAc within sialyl Lewis x is a crucial modification for L-selectin binding, and thus, the underlying sulfotransferase may be a key modulator of lymphocyte trafficking. Four recently discovered GlcNAc-6-sulfotransferases are the first candidate contributors to the biosynthesis of 6-sulfo sLex in the context of L-selectin ligands. Here we report the in vitro activity of the four GlcNAc-6-sulfotransferases on a panel of synthetic oligosaccharide substrates that comprise structural motifs derived from sialyl Lewis x. Each enzyme preferred a terminal GlcNAc residue, and was impeded by the addition of a beta1,4-linked Gal residue (i.e., terminal LacNAc). Surprisingly, for three of the enzymes, significant activity was observed with sialylated LacNAc, and two of the enzymes were capable of detectable sulfation of GlcNAc in the context of sialyl Lewis x. On the basis of these results, we propose possible pathways for 6-sulfo sialyl Lewis x biosynthesis and suggest that sulfation may be an early committed step.


Assuntos
Selectina L/metabolismo , Antígenos do Grupo Sanguíneo de Lewis , Oligossacarídeos/biossíntese , Sequência de Aminoácidos , Animais , Células COS , Sequência de Carboidratos , Vetores Genéticos/síntese química , Humanos , Antígenos do Grupo Sanguíneo de Lewis/biossíntese , Antígenos do Grupo Sanguíneo de Lewis/metabolismo , Antígenos CD15/biossíntese , Antígenos CD15/metabolismo , Ligantes , Dados de Sequência Molecular , Oligossacarídeos/genética , Oligossacarídeos/metabolismo , Ratos , Homologia de Sequência de Aminoácidos , Antígeno Sialil Lewis X , Especificidade por Substrato/genética , Sulfotransferases/biossíntese , Sulfotransferases/genética , Sulfotransferases/metabolismo , Carboidrato Sulfotransferases
16.
Am J Ophthalmol ; 131(2): 161-6, 2001 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-11228290

RESUMO

PURPOSE: To estimate the cumulative probability of Nd:YAG laser posterior capsulotomy after cataract extraction in a geographically defined population. METHODS: Rochester Epidemiology Project databases were used to identify retrospectively all Nd:YAG laser posterior capsulotomies performed on Olmsted County, Minnesota, residents who had previously undergone cataract extraction between 1988 and 1996, inclusive. Demographic data and potential risk factors for laser, including age, sex, surgical technique, year of surgery, and intraocular lens material, were obtained by chart review or by retrieval from computer databases. The cumulative probability of Nd:YAG laser posterior capsulotomy was calculated by Kaplan-Meier estimates, and risk factors were analyzed using the Cox proportional hazards model. RESULTS: A total of 925 Nd:YAG laser posterior capsulotomies were identified after 3541 cataract extractions in 2718 patients. The cumulative probability of Nd:YAG laser posterior capsulotomy after cataract surgery was 6% (95% confidence interval = 5% to 7%) at 1 year, increasing to 38% (35% to 40%) at 9 years. Young age at the time of surgery (P =.02), polymethylmethacrylate intraocular lens material (P <.001), earlier year of surgery (P <.001), and extracapsular extraction (in comparison with phacoemulsification, P <.001) were found to increase significantly the risk of subsequent Nd:YAG laser posterior capsulotomy. Women tended to have a greater probability of Nd:YAG laser posterior capsulotomy (P =.17), but this difference was not statistically significant. CONCLUSIONS: Nd:YAG laser posterior capsulotomy was common after cataract surgery but infrequent during the first postoperative year. Prolonged follow-up is necessary in investigations of the effects of new cataract surgery technologies on the probability of capsulotomy.


Assuntos
Extração de Catarata/efeitos adversos , Terapia a Laser/estatística & dados numéricos , Cápsula do Cristalino/cirurgia , Complicações Pós-Operatórias/cirurgia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Implante de Lente Intraocular , Masculino , Pessoa de Meia-Idade , Minnesota/epidemiologia , Polimetil Metacrilato , Complicações Pós-Operatórias/epidemiologia , Probabilidade , Estudos Retrospectivos , Fatores de Risco
17.
Ophthalmic Plast Reconstr Surg ; 17(6): 404-11, 2001 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-11766019

RESUMO

PURPOSE: To describe the gross and microscopic anatomy of the depressor supercilii muscle and to discuss its cosmetic implications. METHODS: The depressor supercilii muscle was studied in detail with the use of gross anatomic dissections carried out on eight sides of four fresh cadaver heads and ten sides of five preserved cadaver heads. Histological analysis was performed on parasagittal sections of one side of a preserved cadaver head. Measurements were taken on cadaver specimens to determine the insertion point of the depressor supercilii muscle on the undersurface of the skin. RESULTS: The depressor supercilii muscle is distinct from the corrugator supercilii muscle and the medial head of the orbital portion of the orbicularis oculi muscle. The depressor supercilii muscle was noted to be superior in orientation and redder in color than the orbicularis oculi muscle. The depressor supercilii muscle arose from the frontal process of the maxilla approximately 1 cm above the medial canthal tendon and appeared to originate from two distinct heads in most specimens, a novel finding. In specimens containing two heads of the depressor supercilii muscle, the angular vessels passed between the two muscle heads. In specimens containing one muscle head, the angular vessels were found anterior to the muscle. The insertion of the depressor supercilii muscle in the dermis lay approximately 13 to 14 mm superior to the medial canthal tendon. CONCLUSIONS: The origin, insertion, and anatomy of the depressor supercilii muscle help it to act as a depressor of the eyebrow. Histologically, the depressor supercilii muscle arises distinctly from bone and has a unique insertion. The depressor supercilii muscle appears to be distinct from the corrugator supercilii and the orbicularis oculi muscles.


Assuntos
Sobrancelhas/anatomia & histologia , Músculos Faciais/anatomia & histologia , Toxinas Botulínicas Tipo A/uso terapêutico , Pálpebras/anatomia & histologia , Músculos Faciais/inervação , Testa/anatomia & histologia , Humanos , Fármacos Neuromusculares/uso terapêutico , Músculos Oculomotores/anatomia & histologia , Ritidoplastia
18.
Biochim Biophys Acta ; 1497(3): 279-88, 2000 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-10996652

RESUMO

This study was undertaken to begin to elucidate the mechanisms by which cytokines influence intracellular iron homeostasis. Intracellular iron homeostasis is maintained by the coordinated regulation of ferritin and transferrin receptor synthesis. The synthesis of these proteins is coordinated by cytoplasmic iron regulatory proteins (IRP), which bind to iron responsive elements (IRE) on their mRNAs. We evaluated the effects of interleukin-1beta (IL-1beta) on iron metabolism in human astrocytoma cells (SW1088). Exposure to IL-1beta for 16 h increased binding of the IRPs to the IRE and also increased ferritin synthesis. Using the iron sensitive dye calcein, we determined that the intracellular labile iron pool increased within 4 h of IL-1beta exposure and continued to increase for 8 h, returning to normal by 16 h. We propose that the cytokine induced increase in the labile iron pool stimulates ferritin synthesis resulting in a subsequent decrease in the labile iron pool. The decrease in the labile iron pool is consistent with the increase in IRE/IRP interaction measured at 16 h. These results indicate that cytokines can influence the labile iron pool and the post-transcriptional regulatory mechanism for maintaining iron homeostasis. These results contribute to understanding the response of ferritin to inflammation by suggesting ferritin synthesis may reflect changes in the labile iron pool. The approach used in this study may provide a model system for studying relations between the labile iron pool and proteins responsible for maintaining intracellular homeostasis


Assuntos
Ferritinas/biossíntese , Interleucina-1/farmacologia , Proteínas Ferro-Enxofre/metabolismo , Ferro/análise , Proteínas de Ligação a RNA/metabolismo , Aconitato Hidratase/metabolismo , Western Blotting , Citoplasma/metabolismo , Fluorometria , Homeostase , Humanos , Interleucina-1/antagonistas & inibidores , Quelantes de Ferro/farmacologia , Proteínas Reguladoras de Ferro , Ligação Proteica , Fatores de Tempo , Transcrição Gênica , Células Tumorais Cultivadas
19.
J Econ Entomol ; 93(4): 1300-7, 2000 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-10985046

RESUMO

Feeding behavior of third-instar bollworm, Helicoverpa zea (Boddie), and tobacco budworm, Heliothis virescens (F.), was observed in pure and mixed stands of nontransgenic and transgenic cotton (BTK), Gossypium hirsutum L., expressing an insecticidal protein CryIA(c) from a bacterium, Bacillus thuringiensis Berliner subsp. kurstaki. Five plant stands composed of BTK and non-BTK plants were evaluated; two pure stands and three mixed stands. Percentage ratios of BTK to non-BTK plants in the stands were 100:0, 75:25, 50:50, 25:75 and 0:100, respectively. In all stands with BTK plants, fewer bollworm and tobacco budworm larvae were found on BTK plants than non-BTK plants 24 h after infestation with third instars. At 48 h, significantly fewer tobacco budworm larvae, but not fewer bollworm larvae, were found on BTK plants. However, the number of larvae of either insect did not increase on non-BTK plants compared with the initial infestation density of three larvae per plant. The number of obacco budworm injured flower buds, and capsules was lower in all plant stands containing BTK plants compared with the pure stand of non-BTK at 48 h after infestation. Higher numbers of larvae on non-BTK plants were possibly the result of larval intoxication, reduced feeding, and increased plant abandonment and death on BTK plants rather than a classical feeding preference. Unexpectedly, the number of flower buds and capsules injured by bollworm and tobacco budworm when averaged per plant for all plants in a stand, differed little among the 75:25, 50:50 and 25:75 plant mixtures. These data suggest that larvae of both species frequently moved among plants, feeding indiscriminately on BTK and non-BTK plants.


Assuntos
Bacillus thuringiensis , Proteínas de Bactérias/fisiologia , Toxinas Bacterianas , Endotoxinas/fisiologia , Comportamento Alimentar , Inseticidas , Mariposas/fisiologia , Controle Biológico de Vetores , Animais , Toxinas de Bacillus thuringiensis , Proteínas de Bactérias/genética , Toxinas Bacterianas/genética , Endotoxinas/genética , Expressão Gênica , Gossypium , Proteínas Hemolisinas , Larva , Controle Biológico de Vetores/métodos , Plantas Geneticamente Modificadas
20.
Dermatol Surg ; 26(8): 793-7, 2000 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-10940068

RESUMO

BACKGROUND: Atrophic scars of the forehead can result from various pathologic processes including morphea en coup de sabre as well as trauma. A variety of surgical techniques can be used to correct these atrophic scars. OBJECTIVE: Soft tissue augmentation for correction of atrophic scars of the forehead using en bloc autologous dermal fat graft. METHODS: Use of en bloc autologous dermal fat graft harvested from the hip and inserted into a pocket created under the atrophic scar in two patients with depressed scars of the forehead. RESULTS: Overcorrection of the scars with en bloc autologous dermal fat grafts resulted in the treated areas becoming level with the adjacent skin within 3 months. Follow-up for a period of 12 months showed a perfectly level and stable graft with no further resorption. CONCLUSION: En bloc autologous dermal fat grafting appears to be a safe technique that provides excellent cosmetic results for the correction of small to medium depressed scars of the forehead.


Assuntos
Tecido Adiposo/transplante , Cicatriz/cirurgia , Testa/lesões , Testa/cirurgia , Esclerodermia Localizada/cirurgia , Adulto , Feminino , Humanos , Pessoa de Meia-Idade , Transplante de Tecidos
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