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1.
Support Care Cancer ; 31(10): 570, 2023 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-37698629

RESUMO

PURPOSE: To describe trends and explore factors associated with quality of life (QoL) and psychological morbidity and assess breast cancer (BC) health service use over a 12-month period for patients joining the supported self-management (SSM)/patient-initiated follow-up (PIFU) pathway. METHODS: Participants completed questionnaires at baseline, 3, 6, 9 and 12 months that measured QoL (FACT-B, EQ 5D-5L), self-efficacy (GSE), psychological morbidity (GHQ-12), roles and responsibilities (PRRS) and service use (cost diary). RESULTS: 99/110 patients completed all timepoints; 32% (35/110) had received chemotherapy. The chemotherapy group had poorer QoL; FACT-B total score mean differences were 8.53 (95% CI: 3.42 to 13.64), 5.38 (95% CI: 0.17 to 10.58) and 8.00 (95% CI: 2.76 to 13.24) at 6, 9 and 12 months, respectively. The odds of psychological morbidity (GHQ12 >4) were 5.5-fold greater for those treated with chemotherapy. Financial and caring burdens (PRRS) were worse for this group (mean difference in change at 9 months 3.25 (95% CI: 0.42 to 6.07)). GSE and GHQ-12 scores impacted FACT-B total scores, indicating QoL decline for those with high baseline psychological morbidity. Chemotherapy patients or those with high psychological morbidity or were unable to carry out normal activities had the highest service costs. Over the 12 months, 68.2% participants phoned/emailed breast care nurses, and 53.3% visited a hospital breast clinician. CONCLUSION: The data suggest that chemotherapy patients and/or those with heightened psychological morbidity might benefit from closer monitoring and/or supportive interventions whilst on the SSM/PIFU pathway. Reduced access due to COVID-19 could have affected service use.


Assuntos
Neoplasias da Mama , COVID-19 , Síndrome Respiratória e Reprodutiva Suína , Autogestão , Suínos , Animais , Humanos , Feminino , Neoplasias da Mama/tratamento farmacológico , Qualidade de Vida
3.
Epidemiol Infect ; 143(6): 1129-38, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25084481

RESUMO

Data were extracted from the case records of UK patients admitted with laboratory-confirmed influenza A(H1N1)pdm09. White and non-White patients were characterized by age, sex, socioeconomic status, pandemic wave and indicators of pre-morbid health status. Logistic regression examined differences by ethnicity in patient characteristics, care pathway and clinical outcomes; multivariable models controlled for potential confounders. Whites (n = 630) and non-Whites (n = 510) differed by age, socioeconomic status, pandemic wave of admission, pregnancy, recorded obesity, previous and current smoking, and presence of chronic obstructive pulmonary disease. After adjustment for a priori confounders non-Whites were less likely to have received pre-admission antibiotics [adjusted odds ratio (aOR) 0·43, 95% confidence interval (CI) 0·28-0·68, P < 0·001) but more likely to receive antiviral drugs as in-patients (aOR 1·53, 95% CI 1·08-2·18, P = 0·018). However, there were no significant differences by ethnicity in delayed admission, severity at presentation for admission, or likelihood of severe outcome.


Assuntos
Etnicidade/estatística & dados numéricos , Vírus da Influenza A Subtipo H1N1 , Influenza Humana/terapia , Adolescente , Adulto , Fatores Etários , Idoso , Criança , Pré-Escolar , Procedimentos Clínicos/estatística & dados numéricos , Feminino , Disparidades em Assistência à Saúde/estatística & dados numéricos , Hospitalização/estatística & dados numéricos , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Avaliação de Resultados da Assistência ao Paciente , Grupos Raciais/estatística & dados numéricos , Fatores Sexuais , Fatores Socioeconômicos , Reino Unido/epidemiologia , Adulto Jovem
4.
J Anim Sci ; 91(10): 5026-36, 2013 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-23942718

RESUMO

This survey consisted of data collected from 23 beef harvest plants to document transportation procedures, management practices, and health assessments of market beef and dairy cows and bulls (about n ≅ 7,000 animals). Gooseneck/bumper-pulled trailers were used more often to transport dairy cattle than beef cattle to market whereas tractor-trailers were used more often to transport beef cattle than dairy cattle. All loads (n = 103) met the American Meat Institute Foundation guidelines for spacing. Loads where more than 3% of the cattle slipped during unloading were observed in 27.3% of beef loads and 29.0% of the dairy loads. Beef loads had numerically greater usage of electrical prods (32.4%) versus dairy loads (15.4%) during unloading and were more likely to have a variety of driving aids used more aggressively on them. Fewer cattle had horns, brands, and mud/manure contamination on hides than in the previous survey in 1999. The predominant hide color for beef cows was black (44.2%) whereas the predominant color for dairy cows was the Holstein pattern (92.9%). Fewer cattle displayed evidence of bovine ocular neoplasia (2.9%) than in previous surveys in 1994 (8.5%) and 1999 (4.3%). Knots on live cattle were found less in the round (0.5%) and more in the shoulder region (4.6%) than in 1999 (1.4% and 0.4%, respectively). Dairy cows were more frequently lame in 2007 (48.7%) than 1999 (39.2%) whereas beef cows had numerically less lameness (16.3% vs. 26.6%, respectively). Most beef cows (62.3%) and dairy cows (68.9%) received midpoint body condition scores (3, 4, and 5 for beef; 2 and 3 for dairy). Beef cows had higher numerical percentages of no defects present (72.0%) versus dairy cows (63.0%) when evaluated for a variety of reproductive, health, or management conditions. Continued improvements in several key factors related to transportation, management, and health were observed in this survey, which could result in increased value in market beef and dairy cows and bulls.


Assuntos
Criação de Animais Domésticos , Bem-Estar do Animal , Bovinos/fisiologia , Indústria de Laticínios , Meios de Transporte/normas , Animais , Feminino , Masculino , Estados Unidos
5.
Breast Cancer Res Treat ; 81(2): 117-28, 2003 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-14572154

RESUMO

The protein kinase PKB/Akt plays a pivotal role in promoting cell survival and proliferation. This study investigated the regulation of PKB/Akt activity in breast cancer cells. In primary invasive breast cancers PKB/Akt exhibited elevated phosphorylation at regulatory site Ser473 in 80% of cases, using immunohistochemistry. The degree of phospho-PKB/Akt immunoreactivity was positively correlated with the extent of its nuclear accumulation. Moderate/strong staining was seen in 31% of the samples but was absent in tumour-associated normal breast epithelia. To examine the mechanisms of PKB/Akt activation, we studied its phosphorylation in a panel of breast cancer cell lines. PKB/Akt was constitutively phosphorylated on both regulatory sites (Thr308 and Ser473) in the absence of serum growth factors in 7 of 8 lines but not in two cell lines derived from normal breast epithelia. Further analysis revealed that constitutive PKB/Akt phosphorylation was associated with loss of PTEN phosphatase expression (CAL51, MDA-MB-468, BT549 cells) and constitutive activation of erbB2 (SKBR3, BT474 cells). In two further breast cancer lines (T47D and HS578T) PKB/Akt phosphorylation was dependent upon autocrine factors acting primary through the epidermal growth factor receptor (EGFR) and erbB2. Conditioned medium from HS578T cells stimulated EGFR-dependent PKB/Akt phosphorylation in normal breast cells. These results demonstrate that PKB/Akt is frequently activated in breast cancer through diverse mechanisms, including autocrine signalling via erbB receptors.


Assuntos
Neoplasias da Mama/enzimologia , Proteínas Serina-Treonina Quinases , Proteínas Proto-Oncogênicas/metabolismo , Receptor ErbB-3/metabolismo , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Linhagem Celular Tumoral , Meios de Cultura Livres de Soro , Ativação Enzimática , Feminino , Humanos , Immunoblotting , Imuno-Histoquímica , Fosforilação , Testes de Precipitina , Proteínas Proto-Oncogênicas c-akt
6.
Cancer Lett ; 190(1): 31-6, 2003 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-12536074

RESUMO

Protein kinase B (PKB), a kinase downstream of phosphatidylinositol 3-kinase (PI3-kinase) provides anti-apoptotic and survival signals via phosphorylation of various targets. Inhibiting PI3-kinase with a 12 h exposure to 10 microM LY294002 induces levels of apoptosis of 30.39+/-1.53% in the KB-V1 multidrug resistant (MDR) cell line compared to 4.54+/-1.00% in drug sensitive KB-3-1 cells (P<0.001). This occurred in conjunction with a preferential reduction in activated PKB in MDR cells. These results suggest the PI3-kinase/PKB signalling pathway is important for the survival of MDR cells and inhibition of this pathway results in the selective induction of apoptosis in MDR cells.


Assuntos
Apoptose , Cromonas/farmacologia , Resistencia a Medicamentos Antineoplásicos , Inibidores Enzimáticos/farmacologia , Morfolinas/farmacologia , Inibidores de Fosfoinositídeo-3 Quinase , Proteínas Serina-Treonina Quinases , Western Blotting , Linhagem Celular , Sobrevivência Celular , Meios de Cultura Livres de Soro/farmacologia , Humanos , Neoplasias/patologia , Fenótipo , Poli(ADP-Ribose) Polimerases/metabolismo , Proteínas Proto-Oncogênicas/metabolismo , Proteínas Proto-Oncogênicas c-akt , RNA Mensageiro/metabolismo , Transdução de Sinais , Fatores de Tempo , Células Tumorais Cultivadas
7.
Eur J Cancer ; 38(1): 194-204, 2002 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-11750850

RESUMO

LS 4477 and LS 4559, two of a series of N-acyl-aminoalkyl phenyl ethers, are rationally designed compounds based on the tubulin binder estramustine. This study investigated their mechanism of action and compared their effectiveness in relation to estramustine in vitro against a panel of human and murine cell lines and in vivo against two murine colon tumour models (MAC). At biologically relevant concentrations, LS 4477 and LS 4559 caused a 59.9 and 56% reduction in tubulin assembly, respectively, compared with a 28.4% reduction in tubulin assembly by estramustine. The analogues were approximately 100 times more potent in chemosensitivity tests in vitro than the parent compound. Both analogues were orally active against the MAC 15A murine tumour model, to a greater extent than estramustine, producing significant growth delays (P<0.01). Significant activity was also shown against the slower growing MAC 26 tumour for LS 4577 (the soluble pro-drug of LS 4559). The results presented in this study suggest these compounds warrant further development with a view to assessing their clinical activity.


Assuntos
Antineoplásicos Alquilantes/uso terapêutico , Neoplasias do Colo/tratamento farmacológico , Estramustina/análogos & derivados , Microtúbulos/metabolismo , Tubulina (Proteína)/metabolismo , Animais , Ligação Competitiva , Colchicina/metabolismo , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Concentração Inibidora 50 , Masculino , Camundongos , Pró-Fármacos , Suínos , Moduladores de Tubulina , Células Tumorais Cultivadas
8.
J Rheumatol ; 28(6): 1385-93, 2001 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-11409135

RESUMO

OBJECTIVE: To address the prevalence and characteristics of nondermatomal somatosensory deficits (NDSD) in subjects with chronic pain in the context of compensation/litigation. METHODS: Data were collected via standardized history, examination, and patient- as well as physician-drawn body maps in a consecutive series of 194 subjects seen for the purpose of an independent medical examination. RESULTS: Forty-nine subjects (25.3%) with primarily widespread pain (often diagnosed as fibromyalgia) presented with hemisensory or quadrotomal deficits to pinprick and other cutaneous stimuli on the side of lateralized pain or worse pain. The NDSD limbs often had impairment of vibration sense (not infrequently associated with "forehead vibration split"), reduced strength, dexterity or movement, and extreme sensitivity to superficial skin palpation or profound insensitivity to deep pain. Spatial, temporal, qualitative, and evolutionary patterns of NDSD emerged associated with cognitive/affective symptoms. NDSD subjects were more often born outside Canada, more likely to be injured at work, present with abnormal pain behavior, and have negative investigations. CONCLUSION: NDSD are a prevalent problem associated with chronic pain. Future research should explore the prevalence of NDSD in other pain populations, the role of personality and related factors, and the underlying biological substrate of these deficits.


Assuntos
Hipestesia/epidemiologia , Responsabilidade Legal , Dor/epidemiologia , Indenização aos Trabalhadores/legislação & jurisprudência , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , Doença Crônica , Feminino , Humanos , Hipestesia/diagnóstico , Masculino , Pessoa de Meia-Idade , Ontário , Dor/diagnóstico , Prevalência , Distúrbios Somatossensoriais/diagnóstico , Distúrbios Somatossensoriais/epidemiologia , Vibração
9.
Psychoneuroendocrinology ; 26(4): 411-20, 2001 May.
Artigo em Inglês | MEDLINE | ID: mdl-11259860

RESUMO

The aim of this research was study the role of psychosocial factors in exacerbations of asthma in adults induced by upper respiratory tract infections (URTIs). It involved a longitudinal study (one year) of 92 adults with asthma. The volunteers were 27 men and 65 women 19-46 years of age with a mean duration of wheeze of 19 years. The main outcome measure was symptomatic colds producing asthma exacerbations (infections confirmed by laboratory assays and exacerbation of asthma confirmed by objective changes in peak expiratory flow rate). The results showed that about 20% of the sample did not report an episode. This sub-group had a high proportion of males, low negative affectivity scores and consumed more alcohol. When volunteers with at least one episode were considered it was found that those who reported more negative life events and had low levels of social support had more episodes. Smokers were more likely to have to visit their doctor when they developed a cold-induced exacerbation of asthma. Overall, these results show that health-related behaviours, demographic and psychosocial factors influence susceptibility to and severity of exacerbations of asthma by URTIs.


Assuntos
Asma/psicologia , Asma/virologia , Infecções Respiratórias/virologia , Adulto , Consumo de Bebidas Alcoólicas , Asma/complicações , Resfriado Comum/complicações , Resfriado Comum/epidemiologia , Suscetibilidade a Doenças , Feminino , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Infecções Respiratórias/epidemiologia , Fumar/efeitos adversos , Apoio Social , Estresse Psicológico/complicações
10.
J Palliat Care ; 17(3): 173-6, 2001.
Artigo em Inglês | MEDLINE | ID: mdl-11816758

RESUMO

This article examines the imagery and music components of the relaxation program at the Vancouver Centre of the British Columbia Cancer Agency. An outline of the objectives and design of the experiential portion of the sessions is accompanied by a detailed description of the musical elements and influences. Some participant evaluation is also included.


Assuntos
Imagens, Psicoterapia/métodos , Musicoterapia/métodos , Neoplasias/terapia , Terapia de Relaxamento , Humanos , Neoplasias/psicologia
11.
Br J Cancer ; 81(3): 423-30, 1999 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-10507766

RESUMO

This study has compared the preferential killing of three multidrug-resistant (MDR) KB cell lines, KB-C1, KB-A1 and KB-V1 by two inhibitors of glucosylceramide synthase, 1-phenyl-2-decanoylamino-3-morpholino-1-propanol (PDMP) and 1-phenyl-2-hexadecanoylamino-3-pyrrolidino-1-propanol (PPPP), to the killing produced by these compounds in the drug-sensitive cell line, KB-3-1. Both of the inhibitors caused much greater induction of apoptosis in each of the three MDR cell lines than in the drug-sensitive cell line, as judged by morphological assay and confirmed by poly-(ADP-ribose)-polymerase cleavage. The highest level of apoptosis was produced following 24-h exposure to 5 microM PPPP. This treatment produced 75.8 (+/- 7.1)%, 73.6 (+/- 9.8)% and 75.3 (+/- 6.4)% apoptotic cells in the three MDR cell lines respectively, compared to 19.0 (+/- 9.8)% in the drug-sensitive cell line. A reduction in glucosylceramide level following inhibitor treatment occurred in KB-3-1 cells as well as in the MDR cell lines, suggesting that the increased apoptotic response in the MDR cells reflected a different downstream response to changes in the levels of this lipid in these cells compared to that in the drug-sensitive cells. These results suggest that the manipulation of glucosylceramide levels may be a fruitful way of causing the preferential killing of MDR cells in vitro and possibly in vivo.


Assuntos
Apoptose/efeitos dos fármacos , Resistência a Múltiplos Medicamentos , Resistencia a Medicamentos Antineoplásicos , Inibidores Enzimáticos/farmacologia , Glucosilceramidas/metabolismo , Glucosiltransferases/antagonistas & inibidores , Células KB/efeitos dos fármacos , Morfolinas/farmacologia , Proteínas de Neoplasias/antagonistas & inibidores , Propanolaminas/farmacologia , Pirrolidinas/farmacologia , Humanos , Células KB/patologia , Metabolismo dos Lipídeos , Proteínas de Neoplasias/metabolismo , Poli(ADP-Ribose) Polimerases/metabolismo
12.
Epidemiol Infect ; 123(1): 103-8, 1999 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-10487646

RESUMO

In a prospective study of community-dwelling people 60-90 years of age, we examined the coverage of influenza vaccine during 1992-3 and 1993-4, the efficacy of vaccination in reducing serologically-confirmed clinical episodes of influenza A during 1993, and the effect of cigarette smoking. During 1992 and 1993, influenza vaccine was given to 106/215 (49%) and 120/204 (59%) people with risk conditions, and 84/225 (37%) and 103/235 (44%) without risk conditions. Influenza vaccination and general practitioner consultations during 1992 were independent predictors of vaccination in 1993, but current smoking was a negative predictor. Of 209 unimmunized people, 8/35 (23%) smokers had clinical influenza as compared with 11/174 (6%) non-smokers (OR 4.4, 95% CI 1.6 to 11.9). Of 371 non-smokers, 1/197 (0.5%) vaccinees had influenza as compared with 11/174 (6%) non-vaccinees (OR 0.075, 95% CI 0.587 to 0.009). No cases of influenza occurred among 21 current smokers who were vaccinated.


Assuntos
Vírus da Influenza A/imunologia , Vacinas contra Influenza , Influenza Humana/epidemiologia , Influenza Humana/prevenção & controle , Fumar/efeitos adversos , Idoso , Idoso de 80 Anos ou mais , Inglaterra/epidemiologia , Feminino , Habitação para Idosos , Humanos , Vírus da Influenza A/isolamento & purificação , Vacinas contra Influenza/normas , Influenza Humana/sangue , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores de Risco , Vacinação/estatística & dados numéricos
13.
J Hand Surg Br ; 24(3): 263-6, 1999 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-10433432

RESUMO

The outcome in patients having surgery to the hand was assessed subjectively using a questionnaire that covered activities of daily living (ADL), hand pain and psychological well-being. The questionnaires were completed on average 6.9 months preoperatively and 20.6 months postoperatively by 15 patients with osteoarthritis undergoing trapeziectomy and 25 patients with rheumatoid arthritis undergoing Swanson arthroplasties of the metacarpophalangeal joints. Surgery resulted in significant improvements in reported ADL and hand pain, in both groups. Improvement in perception of hand function and health was only seen in the osteoarthritic group. There was no improvement in arthritis activity, mood or quality of life in either group. These results confirm that surgery for arthritis of the hand relieves pain and improves ADL. However, it has a greater effect in patients with localized osteoarthritis than in those with rheumatoid arthritis.


Assuntos
Atividades Cotidianas/classificação , Artrite Reumatoide/cirurgia , Artroplastia/reabilitação , Osteoartrite/cirurgia , Complicações Pós-Operatórias/reabilitação , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Articulação Metacarpofalângica/cirurgia , Pessoa de Meia-Idade , Estudos Prospectivos
14.
Vet Ophthalmol ; 2(2): 87-96, 1999.
Artigo em Inglês | MEDLINE | ID: mdl-11397248

RESUMO

The purpose of this study was to assess the feasibility and reproducibility of color Doppler imaging (CDI) of the vasculature of the normal canine orbit and eye. Eight normal Beagles were evaluated by Doppler imaging. The goals of the study were to determine the location, spectral waveform morphology, specific blood velocity parameters, and reproducibility for the ophthalmic and orbital vessels most frequently identified in the normal dog. Vessels identified a majority of the time (> 50%) included: external ophthalmic artery, dorsal external ophthalmic vein, ventral external ophthalmic vein, internal ophthalmic artery, anterior ciliary artery and vein, short and long posterior ciliary arteries, primary retinal arteries, and vortex veins. Other vessels imaged less frequently included: external ethmoidal artery (50%), and primary retinal veins (25%). For each blood vessel the time averaged velocity, peak systolic velocity, minimum diastolic velocity, pulsatility index, and resistive index were determined. The ophthalmic and orbital vessels have unique spectral waveforms and velocities which serve as a basis for identification. Reproducibility of the most commonly imaged vessels of the canine eye and orbit with Doppler imaging was high (< 10% variation). Doppler imaging has the potential for determining noninvasively and consecutively the blood velocity parameters found in orbital and ocular diseases, including orbital inflammations and neoplasms; intraocular inflammations and neoplasms; vascular diseases including systemic vascular disease (hypertension), vasculopathies, and anemia; the glaucomas; and documentable follow-up after medical and/or surgical treatment of these diseases.

15.
BMJ ; 315(7115): 1060-4, 1997 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-9366736

RESUMO

OBJECTIVE: To evaluate the disease burden of upper respiratory infections in elderly people living at home. DESIGN: Prospective surveillance of elderly people. INTERVENTION: None. SETTING: Leicestershire, England SUBJECTS: 533 subjects 60 to 90 years of age. MAIN OUTCOME MEASURES: Pathogens, symptoms, restriction of activity, duration of illness, medical consultations, interval between onset of illness and medical consultation, antibiotic use, admission to hospital, and death. RESULTS: 231 pathogens were identified for 211 (43%) of 497 episodes for which diagnostic specimens were available: 121 (52%) were rhinoviruses, 59 (26%) were coronaviruses, 22 (9.5%) were influenza A or B, 17 (7%) were respiratory syncytial virus, 7 (3%) were parainfluenza viruses, and 3 (1%) were Chlamydia species; an adenovirus and Mycoplasma pneumoniae caused one infection each. Infections occurred at a rate of 1.2 episodes per person per annum (95% confidence interval 1.0 to 1.7; range 0-10) and were clinically indistinguishable. Lower respiratory tract symptoms complicated 65% of upper respiratory infections and increased the medical consultation rate 2.4-fold (chi 2 test P < 0.001). The median interval between onset of illness and medical consultation was 3 days for influenza and 5 days for other infections. Rhinoviruses caused the greatest disease burden overall followed by episodes of unknown aetiology, coronaviruses, influenza A and B, and respiratory syncytial virus. CONCLUSIONS: Respiratory viruses cause substantial morbidity in elderly people. Although respiratory syncytial virus and influenza cause considerable individual morbidity, the burden of disease from rhinovirus infections and infections of unknown aetiology seems greater overall. The interval between onset of illness and consultation together with diagnostic difficulties raises concern regarding the role of antiviral drugs in treating influenza.


Assuntos
Infecções Respiratórias/epidemiologia , Viroses/epidemiologia , Idoso , Idoso de 80 Anos ou mais , Antibacterianos/uso terapêutico , Efeitos Psicossociais da Doença , Inglaterra/epidemiologia , Feminino , Hospitalização , Humanos , Masculino , Pessoa de Meia-Idade , Aceitação pelo Paciente de Cuidados de Saúde , Estudos Prospectivos , Infecções Respiratórias/tratamento farmacológico , Infecções Respiratórias/virologia , Viroses/complicações
16.
Eur J Cancer ; 33(8): 1291-8, 1997 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-9301458

RESUMO

Paclitaxel is a chemotherapeutic drug which has clinical activity against several solid tumours including ovarian and metastatic breast cancers. Despite extensive preclinical evaluation in several experimental models, no studies have determined the effect of taxol on multicellular spheroids, a model which closely mimics the microregions of solid tumours. MCF-7 human breast carcinoma spheroids were significantly less sensitive than monolayers with IC50 values of 14.33 +/- 4.51 microM and 0.15 +/- 0.09 microM, respectively, following a 1 h drug exposure. Similarly, DLD-1 human colon carcinoma spheroids were also more resistant (IC50 = 33.0 +/- 8.89 microM) than monolayers (IC50 = 0.36 +/- 0.14 microM) following a 1 h drug exposure. Paclitaxel was unable to penetrate DLD-1 multicell layers (22 microns in thickness), suggesting that suboptimal drug exposures to paclitaxel occur in cells which reside some distance away from the surface of the spheroid. In the case of DLD-1 spheroids, extending the exposure time to 24 h whilst maintaining the same overall concentration x time (C x T) drug exposure parameters, resulted in greater cell kill (C x T required to kill 50% of cells = 13.67 +/- 3.21 microM/h) compared with 1 h drug exposures (C x T required to kill 50% of cells = 33.00 +/- 8.89 microM/h). Similar results were obtained with MCF-7 spheroids. In monolayers cultures, dose-response curves contained a marked plateau phase (a characteristic feature of cell cycle phase specific drug) and in the case of MCF-7 cells, cell kill was proportional to T as opposed to C x T. These results support the use of prolonged infusions of paclitaxel in the clinic, as extending the duration of drug exposure not only allows more cells to enter sensitive phases of the cell cycle, but would also allow paclitaxel more time to penetrate into avascular regions of solid tumours. It is likely that paclitaxel will only be effective against cells which reside close to tumour blood vessels and combination therapy with bioreductive drugs (such as tirapazamine) may produce synergistic effects in vivo.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Neoplasias da Mama/tratamento farmacológico , Neoplasias do Colo/tratamento farmacológico , Paclitaxel/farmacologia , Esferoides Celulares/efeitos dos fármacos , Antineoplásicos Fitogênicos/farmacocinética , Neoplasias da Mama/patologia , Sobrevivência Celular/efeitos dos fármacos , Neoplasias do Colo/patologia , Relação Dose-Resposta a Droga , Esquema de Medicação , Feminino , Humanos , Paclitaxel/farmacocinética , Esferoides Celulares/metabolismo , Células Tumorais Cultivadas/efeitos dos fármacos
17.
BMJ ; 313(7065): 1119-23, 1996 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-8916700

RESUMO

OBJECTIVE: To assess the role of rhinoviruses in elderly people living in the community. DESIGN: Prospective community based surveillance of elderly people, without intervention. Subjects were telephoned weekly to identify symptomatic upper respiratory tract infections. Symptoms and impact of illnesses were monitored, and specimens were collected for diagnostic serology and human rhinovirus polymerase chain reaction. SETTING: Leicestershire, England. SUBJECTS: 533 subjects aged 60 to 90. MAIN OUTCOME MEASURES: Symptoms, restriction of activity, medical consultations, and antibiotic use during 96 rhinovirus infections. Adjusted odds ratios for lower respiratory syndromes with respect to smoking and health status. RESULTS: A viral cause was established in 211 (43%) of 497 respiratory illnesses; rhinoviruses were identified in 121 (24%) and as single pathogens in 107. The median duration of the first or only rhinovirus infection in the 96 people with 107 rhinovirus infections was 16 days; 18 of the 96 patients were confined to bed and 25 were unable to cope with routine household activities. Overall, 60 patients with rhinovirus infections had lower respiratory tract syndromes; 41 patients consulted their doctor, 31 of them (76%) receiving antibiotics. One patient died. Logistic regression analysis showed that chronic medical conditions increased the estimated probability of lower respiratory rhinovirus illness by 40% (95% confidence interval 17% to 68%) and smoking by 47% (14% to 90%). There were almost six times as many symptomatic rhinovirus infections as influenza A and B infections. CONCLUSIONS: Rhinoviruses are an important cause of debility and lower respiratory illness among elderly people in the community. Chronic ill health and smoking increase the likelihood of lower respiratory complications from such infections. The overall burden of rhinovirus infections in elderly people may approach that of influenza.


Assuntos
Infecções por Picornaviridae/epidemiologia , Infecções Respiratórias/virologia , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Inglaterra/epidemiologia , Ensaio de Imunoadsorção Enzimática , Humanos , Pessoa de Meia-Idade , Infecções por Picornaviridae/complicações , Estudos Prospectivos , Rhinovirus/isolamento & purificação , Fatores de Risco
18.
Thorax ; 51(11): 1115-22, 1996 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-8958895

RESUMO

BACKGROUND: The polymerase chain reaction has improved the detection of picornaviruses and rhinoviruses and our understanding of their role in reversible airways disease. The effects of colds on lower respiratory morbidity and bacterial colonisation in cystic fibrosis remain uncertain. METHODS: Children with cystic fibrosis were evaluated regularly in the clinic and the parents notified the investigators when their child developed a cold. Nasopharyngeal specimens were collected at the start of the infection for polymerase chain reaction, bacteriology was also undertaken and again three weeks later, and pulmonary function was measured in children aged > or = 6 years at four day intervals for three weeks. The effects of colds on rate of progression of cystic fibrosis were assessed by pulmonary function, Shwachman scores, and radiology. RESULTS: Thirty eight children suffered 147 colds over 17 months. Picornaviruses were detected in 51 (43%) of 119 nasopharyngeal specimens, and 21 of the 51 were further identified as rhinoviruses. Pulmonary dysfunction was similar following picornavirus and non-picornavirus infections; the mean change from baseline in forced expiratory volume in one second (FEV1) was -16.5% and -10.3% at 1-4 days and 21-24 days, respectively, after onset of a cold. Children who experienced more colds than average had evidence of disease progression with reduction in Shwachman score, increasing Chrispin-Norman score, and greater deterioration in FEV1 per annum. Ten of 12 new bacterial infections were associated with a cold. CONCLUSIONS: Picornavirus and non-picornavirus colds are associated with pulmonary function abnormalities and disease progression in patients with cystic fibrosis, and predispose to secondary bacterial infection and colonisation.


Assuntos
Fibrose Cística/complicações , Infecções Oportunistas/complicações , Infecções Respiratórias/complicações , Adolescente , Infecções Bacterianas/complicações , Criança , Pré-Escolar , Resfriado Comum/complicações , Fibrose Cística/fisiopatologia , Progressão da Doença , Feminino , Volume Expiratório Forçado , Humanos , Lactente , Masculino , Infecções por Picornaviridae/complicações , Capacidade Vital
19.
Ugeskr Laeger ; 157(6): 724-7, 1995 Feb 06.
Artigo em Dinamarquês | MEDLINE | ID: mdl-7701630

RESUMO

Ecstasy (3,4-methylenedioxymethamphetamine) is a popular recreational drug, a "designer drug", which has been developed from the basic structure in amphetamine. Ecstasy has now reached the illegal drug market in Denmark via the US, Great Britain and Sweden. The drug is related to a certain youth culture from which it is estimated that many drug abusers have been recruited. The desired effects of ecstasy, namely enhanced openness, awareness and empathy, have previously been used in various therapeutic connections. In later years the drug has led to abuse which, in connection with certain cultural behaviour patterns (for example in discotheques), can cause dangerous psychiatric as well as somatic effects. The undesirable psychiatric effects range from fear through depression to actual psychoses, and the somatic effects vary from symptoms of increased sympathetic activity to malignant hyperthermia, disseminated intravascular coagulation, rhabdomyolysis, renal failure, and lethal hepatotoxicity. The last mentioned symptoms occur in connection with prolonged physical activities such as exhausting dancing sessions. The article discusses the available treatments for conditions of abuse and stresses the need for prophylactic efforts in the form of information and awareness of the problem.


Assuntos
Encefalopatias/induzido quimicamente , Transtornos Mentais/induzido quimicamente , N-Metil-3,4-Metilenodioxianfetamina/efeitos adversos , Transtornos Relacionados ao Uso de Substâncias , Encefalopatias/tratamento farmacológico , Alucinógenos/efeitos adversos , Humanos , Transtornos Mentais/tratamento farmacológico , N-Metil-3,4-Metilenodioxianfetamina/farmacologia , Transtornos Relacionados ao Uso de Substâncias/complicações , Transtornos Relacionados ao Uso de Substâncias/tratamento farmacológico , Transtornos Relacionados ao Uso de Substâncias/psicologia
20.
Arch Dis Child ; 70(2): 84-9, 1994 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-8129449

RESUMO

All newborn infants in East Anglia are screened for cystic fibrosis by blood immunoreactive trypsin assay at 7 days. Thirty eight infants with cystic fibrosis were randomised to treatment with either continuous oral flucloxacillin 250 mg/day (group P, n = 18) or with episodic antimicrobials as clinically indicated (group E, n = 20). Their progress was monitored from diagnosis to 24 months by a nurse coordinator who visited all infants regularly, at home and in hospital, to collect anthropometric, dietary, clinical, and microbiological data. Mean (range) age of confirmation of diagnosis was 5.7 weeks (1-14 weeks). There was no significant difference in birth weight, genotype, immunoreactive trypsin concentration, neonatal history, symptoms at diagnosis, pancreatic enzyme supplementation, or parental smoking history between the groups. Infants in group E had more frequent cough and a greater number of Staphylococcus aureus isolates than infants in group P. More infants of group E were admitted to hospital, had higher admission rates during the second year (19 v 5), for longer periods (6.4 v 2.2 days), despite receiving more than double the number of courses of antibiotics than group P infants (in addition to flucloxacillin). Continuous prophylactic flucloxacillin from early diagnosis of cystic fibrosis is associated with improved clinical progress during the first two years of life.


Assuntos
Infecções Bacterianas/prevenção & controle , Fibrose Cística/microbiologia , Floxacilina/uso terapêutico , Estatura/efeitos dos fármacos , Esquema de Medicação , Fezes/microbiologia , Feminino , Seguimentos , Hospitalização , Humanos , Recém-Nascido , Masculino , Prognóstico , Estudos Prospectivos , Sistema Respiratório/microbiologia , Aumento de Peso/efeitos dos fármacos
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