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1.
BJOG ; 124(4): 641-650, 2017 03.
Artigo em Inglês | MEDLINE | ID: mdl-27726304

RESUMO

OBJECTIVE: To investigate whether simulation-based obstetric team training in a simulation centre improves patient outcome. DESIGN: Multicentre, open, cluster randomised controlled trial. SETTING: Obstetric units in the Netherlands. POPULATION: Women with a singleton pregnancy beyond 24 weeks of gestation. METHODS: Random allocation of obstetric units to a 1-day, multi-professional, simulation-based team training focusing on crew resource management (CRM) in a simulation centre or to no such team training. Intention-to-treat analyses were performed at the cluster level, including a measurement 1 year prior to the intervention. MAIN OUTCOME MEASURES: Primary outcome was a composite outcome of obstetric complications during the first year post-intervention, including low Apgar score, severe postpartum haemorrhage, trauma due to shoulder dystocia, eclampsia and hypoxic-ischaemic encephalopathy. Maternal and perinatal mortality were also registered. RESULTS: Each study group included 12 units with a median unit size of 1224 women, combining for a total of 28 657 women. In total, 471 medical professionals received the training course. The composite outcome of obstetric complications did not differ between study groups [odds ratio (OR) 1.0, 95% confidence interval (CI) 0.80-1.3]. Team training reduced trauma due to shoulder dystocia (OR 0.50, 95% CI 0.25-0.99) and increased invasive treatment for severe postpartum haemorrhage (OR 2.2, 95% CI 1.2-3.9) compared with no intervention. Other outcomes did not differ between study groups. CONCLUSION: A 1-day, off-site, simulation-based team training, focusing on teamwork skills, did not reduce a composite of obstetric complications. TWEETABLE ABSTRACT: 1-day, off-site, simulation-based team training did not reduce a composite of obstetric complications.


Assuntos
Emergências , Equipe de Assistência ao Paciente , Feminino , Humanos , Países Baixos , Mortalidade Perinatal , Hemorragia Pós-Parto , Gravidez
2.
J Clin Microbiol ; 50(12): 3999-4001, 2012 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-23035198

RESUMO

Multilocus sequence typing (MLST) is one of the most reliable methods for typing of Escherichia coli, including extended-spectrum-ß-lactamase-producing E. coli (ESBL-EC). We investigated the performance of a new typing method, SpectraCell RA (River Diagnostics, Madison, WI), in comparison on MLST on a well-defined collection of ESBL-EC isolates obtained from chicken meat and humans. Ninety-two ESBL-EC isolates obtained from meat and 59 ESBL-EC isolates obtained from human rectal swabs and clinical blood cultures were typed using MLST and SpectraCell RA. The sensitivity and specificity of SpectraCell RA were calculated, using MLST as a reference method. Subsequently, the results of SpectraCell RA were used to determine the relatedness of ESBL-EC isolates from chicken and humans. Using MLST as the gold standard, the performance of SpectraCell RA was evaluated for 3 different cutoff values: 0.99975, 0.99955, and 0.99935. Depending on the cutoff value, the sensitivity was mediocre to unacceptably low, with values of 9.4%, 43.9%, and 66.7%, respectively. When sensitivity increased, the specificity decreased rapidly, from 95.6% to 69.8% and 34.4%, respectively. Also, the number of clusters containing both human and meat samples varied from 0 (0.0%) to 14 (38.9%). Our study shows that SpectraCell RA is not a suitable typing method for ESBL-EC when evaluating relationships of ESBL-EC at the population level.


Assuntos
Escherichia coli/classificação , Escherichia coli/genética , Tipagem Molecular/métodos , beta-Lactamases/metabolismo , Animais , Galinhas , Escherichia coli/enzimologia , Escherichia coli/isolamento & purificação , Infecções por Escherichia coli/microbiologia , Humanos , Carne/microbiologia , Epidemiologia Molecular/métodos , Sensibilidade e Especificidade
3.
BJOG ; 119(11): 1387-93, 2012 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-22882714

RESUMO

OBJECTIVE: To determine whether obstetric team training in a medical simulation centre improves the team performance and utilisation of appropriate medical technical skills of healthcare professionals. DESIGN: Cluster randomised controlled trial. SETTING: The Netherlands. SAMPLE: The obstetric departments of 24 Dutch hospitals. METHODS: The obstetric departments were randomly assigned to a 1-day session of multiprofessional team training in a medical simulation centre or to no such training. Team training was given with high-fidelity mannequins by an obstetrician and a communication expert. More than 6 months following training, two unannounced simulated scenarios were carried out in the delivery rooms of all 24 obstetric departments. The scenarios, comprising a case of shoulder dystocia and a case of amniotic fluid embolism, were videotaped. The team performance and utilisation of appropriate medical skills were evaluated by two independent experts. MAIN OUTCOME MEASURES: Team performance evaluated with the validated Clinical Teamwork Scale (CTS) and the employment of two specific obstetric procedures for the two clinical scenarios in the simulation (delivery of the baby with shoulder dystocia in the maternal all-fours position and conducting a perimortem caesarean section within 5 minutes for the scenario of amniotic fluid embolism). RESULTS: Seventy-four obstetric teams from 12 hospitals in the intervention group underwent teamwork training between November 2009 and July 2010. The teamwork performance in the training group was significantly better in comparison to the nontraining group (median CTS score: 7.5 versus 6.0, respectively; P = 0.014). The use of the predefined obstetric procedures for the two clinical scenarios was also significantly more frequent in the training group compared with the nontraining group (83 versus 46%, respectively; P = 0.009). CONCLUSIONS: Team performance and medical technical skills may be significantly improved after multiprofessional obstetric team training in a medical simulation centre.


Assuntos
Competência Clínica , Educação Médica Continuada , Obstetrícia/educação , Equipe de Assistência ao Paciente , Feminino , Humanos , Países Baixos , Obstetrícia/organização & administração , Simulação de Paciente , Gravidez , Complicações na Gravidez
4.
J Cell Biochem ; 105(4): 1128-38, 2008 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-18819098

RESUMO

The development and maintenance of a healthy skeleton depends on the migration of cells to areas of new bone formation. Osteoblasts, the bone forming cells of the body, mature from mesenchymal stem cells under the influence of bone morphogenetic protein. It is unclear at what developmental stage the osteoblasts start to migrate to their functional location. We have studied migration of immature pre-osteoblasts and of mature osteoblasts in response to Platelet-derived growth factor (PDGF) and sphingosine-1-phosphate (S1P). PDGF is a growth factor involved in bone remodeling and fracture healing whereas S1P is a circulating sphingolipid known to control cell trafficking. Our data indicate that PDGF acts as a chemotactic cue for pre-osteoblasts. In contrast, S1P is a chemorepellent to these cells. Upon Bone Morphogenetic Protein 2-induced conversion to the osteoblast phenotype, the chemotaxis response to PDGF is retained whereas the sensitivity to S1P is lost. By RNA interference and overexpression experiments we showed that the expression level of the S1P2 receptor is the sole determinant controlling responsiveness to S1P. The combined data indicate that migration of osteoblasts is controlled by the balance between PDGF, S1P and the differentiation state of the cells. We propose that this mechanism preserves the osteoprogenitor pool in the bone marrow, only allowing the more differentiated cell to travel to sites of bone formation.


Assuntos
Quimiotaxia/efeitos dos fármacos , Lisofosfolipídeos/farmacologia , Osteoblastos/citologia , Proteínas Proto-Oncogênicas c-sis/farmacologia , Receptores de Lisoesfingolipídeo/fisiologia , Esfingosina/análogos & derivados , Animais , Diferenciação Celular , Células Cultivadas , Humanos , Camundongos , Osteogênese , Proteínas Proto-Oncogênicas c-sis/antagonistas & inibidores , Esfingosina/farmacologia
5.
J Vet Pharmacol Ther ; 31(5): 479-87, 2008 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-19000268

RESUMO

The efficacy of an injectable formulation of florfenicol (300 mg/mL) as metaphylactic control of naturally occurring bovine respiratory disease (BRD) was evaluated in two double-blind randomly controlled field studies on two Dutch veal calf herds (A and B). Cattle aged not older than 3 months and in the direct presence of calves with clinical respiratory disease were randomly allocated to treatment with 40 mg/kg florfenicol subcutaneously (s.c.) a positive control treatment (12.5 mg/kg tilmicosin p.o. twice daily for five consecutive days in herd A, and 12.5 mg/kg doxycycline p.o. twice daily for five consecutive days in herd B), or a negative control (one placebo saline s.c. administration on D0). The predominant respiratory pathogens present in pretreatment respiratory samples from affected animals were Mycoplasma bovis and Pasteurella multocida in outbreaks A and B, respectively. Metaphylactic administration of florfenicol resulted in a statistically significant weight gain, decreased rectal temperature for five consecutive days after treatment and decreased metaphylactic failure percentages compared with both positive and negative control groups. In summary, these studies demonstrated that a single s.c. injection of florfenicol is effective and practical for control of the bacterial component of BRD in veal calves.


Assuntos
Antibacterianos/uso terapêutico , Doenças dos Bovinos/tratamento farmacológico , Surtos de Doenças/veterinária , Infecções por Mycoplasma/veterinária , Mycoplasma bovis/isolamento & purificação , Infecções por Pasteurella/veterinária , Pasteurella multocida/isolamento & purificação , Infecções Respiratórias/veterinária , Tianfenicol/análogos & derivados , Tilosina/análogos & derivados , Animais , Temperatura Corporal , Peso Corporal , Bovinos , Doenças dos Bovinos/epidemiologia , Surtos de Doenças/prevenção & controle , Masculino , Infecções por Mycoplasma/tratamento farmacológico , Mycoplasma bovis/patogenicidade , Países Baixos , Infecções por Pasteurella/tratamento farmacológico , Pasteurella multocida/patogenicidade , Infecções Respiratórias/tratamento farmacológico , Infecções Respiratórias/microbiologia , Tianfenicol/uso terapêutico , Tilosina/uso terapêutico
6.
Cardiovasc Intervent Radiol ; 41(10): 1494-1504, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-29948003

RESUMO

PURPOSE: There is paucity of data on patient-perceived outcomes of bleomycin sclerotherapy for low-flow vascular malformations. In this study, the long-term outcomes of bleomycin sclerotherapy were investigated in terms of quality of life (QoL) and patient-perceived changes in health. MATERIALS AND METHODS: A cohort of Dutch patients with vascular malformations treated with bleomycin sclerotherapy (June 2010-November 2015) completed a questionnaire evaluating disease symptoms, QoL (Short Form 36), patient-perceived change in health status (Global Rating of Change scales) and treatment satisfaction. QoL was assessed for the patient's status before and after treatment and was analyzed relative to an age and sex-matched Dutch reference population. Predictive factors associated with QoL and patient-perceived improvement in overall health status were assessed using multivariable linear and logistic regression analyses, respectively. RESULTS: Seventy-seven patients, with a median follow-up of 22 months, were enrolled. About half of the respondents (49.3%) indicated that they perceived (any form of) improvement in their overall health status. Most often improved were the specific health aspects 'pain' (54.5%) and 'overall severity of symptoms' (57.1%). No factors were significantly predictive for patient-perceived improvement in health with respect to the vascular malformation. Impairment in work- or study-related activities prior to sclerotherapy was found to negatively impact physical QoL at follow-up (p = 0.03). CONCLUSION: Approximately half of patients with low-flow vascular malformations indicate an improvement in overall health status following bleomycin sclerotherapy, particularly concerning pain and severity of symptoms. However, most patients only perceived little to moderate improvement to their health and desire further treatment.


Assuntos
Bleomicina/administração & dosagem , Anormalidades Linfáticas/terapia , Satisfação do Paciente , Qualidade de Vida/psicologia , Escleroterapia/métodos , Malformações Vasculares/terapia , Adulto , Estudos de Coortes , Feminino , Seguimentos , Humanos , Anormalidades Linfáticas/psicologia , Masculino , Pessoa de Meia-Idade , Países Baixos , Prognóstico , Estudos Retrospectivos , Escleroterapia/psicologia , Inquéritos e Questionários , Resultado do Tratamento , Malformações Vasculares/psicologia
7.
Ned Tijdschr Geneeskd ; 161: D1136, 2017.
Artigo em Holandês | MEDLINE | ID: mdl-28351438

RESUMO

A 34-year-old woman presented with abdominal pain, vaginal blood loss and severe shoulder pain. Ultrasound revealed an ectopic pregnancy. The shoulder pain was due to irritation of the diaphragm caused by bleeding from a ruptured fallopian tube into the abdominal cavity.


Assuntos
Gravidez Ectópica/diagnóstico por imagem , Dor Abdominal/diagnóstico , Dor Aguda , Adulto , Feminino , Humanos , Gravidez , Dor de Ombro/diagnóstico , Hemorragia Uterina/diagnóstico
8.
Eur J Obstet Gynecol Reprod Biol ; 216: 79-84, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28738295

RESUMO

Does the effect of one-day simulation team training in obstetric emergencies decline within one year? A post-hoc analysis of a multicentre cluster randomised controlled trial. J van de Ven, AF Fransen, E Schuit, PJ van Runnard Heimel, BW Mol, SG Oei OBJECTIVE: To investigate whether the effect of a one-day simulation-based obstetric team training on patient outcome changes over time. STUDY DESIGN: Post-hoc analysis of a multicentre, open, randomised controlled trial that evaluated team training in obstetrics (TOSTI study).We studied women with a singleton pregnancy beyond 24 weeks of gestation in 24 obstetric units. Included obstetric units were randomised to either a one-day, multi-professional simulation-based team training focusing on crew resource management in a medical simulation centre (12 units) or to no team training (12 units). We assessed whether outcomes differed between both groups in each of the first four quarters following the team training and compared the effect of team training over quarters. Primary outcome was a composite outcome of low Apgar score, severe postpartum haemorrhage, trauma due to shoulder dystocia, eclampsia and hypoxic-ischemic encephalopathy. RESULTS: During a one year period after the team training the rate of obstetric complications, both on the composite level and the individual component level, did not differ between any of the quarters. For trauma due to shoulder dystocia team training led to a significant decrease in the first quarter (0.06% versus 0.26%, OR 0.19, 95% CI 0.03 to 0.98) but in the subsequent quarters no significant reductions were observed. Similar results were found for invasive treatment for severe postpartum haemorrhage where a significant increase was only seen in the first quarter (0.4% versus 0.03%, OR 19, 95% CI 2.5-147), and not thereafter. CONCLUSION: The beneficial effect of a one-day, simulation-based, multiprofessional, obstetric team training seems to decline after three months. If team training is further evaluated or implemented, repetitive training sessions every three months seem therefore recommended.


Assuntos
Competência Clínica , Emergências , Obstetrícia/educação , Equipe de Assistência ao Paciente , Treinamento por Simulação , Adulto , Feminino , Humanos , Tocologia/educação , Gravidez
9.
Eur J Obstet Gynecol Reprod Biol ; 216: 130-137, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28763738

RESUMO

OBJECTIVE: Team training is frequently applied in obstetrics. We aimed to evaluate the cost-effectiveness of obstetric multi-professional team training in a medical simulation centre. STUDY DESIGN: We performed a model-based cost-effectiveness analysis to evaluate four strategies for obstetric team training from a hospital perspective (no training, training without on-site repetition and training with 6 month or 3-6-9 month repetition). Data were retrieved from the TOSTI study, a randomised controlled trial evaluating team training in a medical simulation centre. We calculated the incremental cost-effectiveness ratio (ICER), which represent the costs to prevent the adverse outcome, here (1) the composite outcome of obstetric complications and (2) specifically neonatal trauma due to shoulder dystocia. RESULTS: Mean costs of a one-day multi-professional team training in a medical simulation centre were €25,546 to train all personnel of one hospital. A single training in a medical simulation centre was less effective and more costly compared to strategies that included repetition training. Compared to no training, the ICERs to prevent a composite outcome of obstetric complications were €3432 for a single repetition training course on-site six months after the initial training and €5115 for a three monthly repetition training course on-site after the initial training during one year. When we considered neonatal trauma due to shoulder dystocia, a three monthly repetition training course on-site after the initial training had an ICER of €22,878. CONCLUSION: Multi-professional team training in a medical simulation centre is cost-effective in a scenario where repetition training sessions are performed on-site.


Assuntos
Competência Clínica , Emergências , Obstetrícia/educação , Equipe de Assistência ao Paciente , Treinamento por Simulação/economia , Análise Custo-Benefício , Feminino , Humanos , Gravidez
10.
Cancer Res ; 57(11): 2109-11, 1997 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-9187104

RESUMO

In about one-third of advanced breast cancers, estrogen deprivation causes tumor regression. Estrogen concentrations in tumor tissue seem to depend largely on local production. The aromatase enzyme complex is thought to be the key enzyme in this respect. In the present study, the effect of the new third-generation nonsteroidal aromatase inhibitor vorozole (Rivizor) on tumor tissue aromatase activity and estrogen concentrations was evaluated. During 7 days preceding mastectomy, 11 postmenopausal breast cancer patients were treated with 2.5 mg of vorozole once daily. Eight patients could be evaluated. Intratumoral aromatase activity and estrone and estradiol levels were measured and compared to the values of nine untreated postmenopausal breast cancer patients. In treated patients, median tissue aromatase activity was 89% lower than that in controls (P < 0.001). Similarly, median tissue estrone and estradiol concentrations were 64 and 80% lower, respectively, in treated patients (P = 0.001 and P < 0.05, respectively). These results support the hypothesis that depleting the tumor of estrogens, thus impairing estrogenic stimulation, is an important mechanism in the antitumor activity of aromatase inhibitors.


Assuntos
Antineoplásicos/uso terapêutico , Neoplasias da Mama/metabolismo , Triazóis/uso terapêutico , Idoso , Aromatase/análise , Aromatase/efeitos dos fármacos , Aromatase/metabolismo , Neoplasias da Mama/tratamento farmacológico , Estradiol/análise , Estradiol/metabolismo , Estrogênios/análise , Estrogênios/metabolismo , Estrona/análise , Estrona/metabolismo , Feminino , Humanos , Pessoa de Meia-Idade
11.
Cancer Res ; 57(7): 1238-40, 1997 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-9102205

RESUMO

Mutations with clear "UVB fingerprints" have been observed in the p53 gene of human nonmelanoma skin tumors and of experimentally UVB-induced murine skin tumors. Although UVA (315-400 nm) radiation is also a complete carcinogen, its contribution to sunlight-induced mutagenesis remains poorly characterized. There is experimental evidence that the production of reactive oxygen species plays a more dominant role with long-wave UVA than with UVB radiation. We have induced skin tumors (n = 42) in hairless SKH:HR1 mice (n = 14) by daily exposure to long-wave UVA (365-nm) radiation. The incidence of p53 alterations in these tumors is low compared to UVB-induced tumors; positive staining for the p53 protein was observed in only 50% of the tumors, and less than 15% of the tumors showed a mutation in one of the exons 5, 7, or 8 of the p53 gene. The pattern of p53 staining was more irregular and less dense compared to UVB, and the mutations (all C-->T) were mainly (six of seven) located at codon 267. Besides a general p53 hotspot, this codon is also the main hotspot for UVB-induced skin tumors in these mice. No mutations specific for UVA, ie., mutations specific for reactive oxygen species, could be detected.


Assuntos
Genes p53 , Mutação , Neoplasias Induzidas por Radiação , Neoplasias Cutâneas/genética , Raios Ultravioleta , Animais , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/metabolismo , Análise Mutacional de DNA , Feminino , Genes p53/efeitos da radiação , Imuno-Histoquímica , Masculino , Camundongos , Camundongos Endogâmicos , Papiloma/genética , Papiloma/metabolismo , Neoplasias Cutâneas/etiologia
12.
Endocrinology ; 143(10): 4048-55, 2002 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-12239116

RESUMO

To assess whether growth plate-specific production of sex steroids is possible, we have surveyed the presence of several key-enzymes involved in androgen and estrogen metabolism in the tibial growth plate of female and male rats during development. Using in situ hybridization, mRNAs of aromatase p450, type I and II 17beta-hydroxysteroid dehydrogenase (HSD), steroid sulfatase (STS), and 5alpha-reductase were detected in proliferating and hypertrophic chondrocytes of the growth plate. The former three were strongly up-regulated around sexual maturation (7 wk), whereas the latter two were expressed at a relatively constant level during development. These data were supported by measuring aromatase, type I 17beta-HSD, and STS enzyme activities in chondrocytes collected from tibial growth plates at 1 and 7 wk of age. Of the enzymes studied, there were minor differences between the sexes in aromatase and 5alpha-reductase expression only. In conclusion, our findings clearly indicate the presence of various enzymes involved in sex steroid metabolism in the tibial growth plate, especially in sexually maturing rats, a timepoint at which sex steroids have major effects on longitudinal growth. Our data suggest that intracrinology in the rat growth plate can occur and may be a major source of local sex steroid delivery.


Assuntos
Hormônios Esteroides Gonadais/metabolismo , Lâmina de Crescimento/metabolismo , Tíbia/metabolismo , 17-Hidroxiesteroide Desidrogenases/genética , 17-Hidroxiesteroide Desidrogenases/metabolismo , Envelhecimento/metabolismo , Animais , Aromatase/genética , Aromatase/metabolismo , Arilsulfatases/genética , Arilsulfatases/metabolismo , Feminino , Hibridização In Situ , Masculino , RNA Mensageiro , Ratos , Ratos Wistar , Esteril-Sulfatase
13.
J Steroid Biochem Mol Biol ; 81(3): 237-47, 2002 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-12163135

RESUMO

Tibolone (Org OD14) is a synthetic steroid used for post-menopausal hormone replacement therapy (HRT). Since HRT might increase breast cancer risk, it is important to determine the possible effects of tibolone on breast tissues. Tibolone and its metabolites Org 4094, Org 30126 and Org OM38 have been reported to inhibit estrone sulfatase activity in MCF-7 and T47D breast cancer cell lines, which suggest beneficial effects on hormone dependent breast cancer by reducing local production of free estrogens. Breast adipose stromal cells (ASCs) contain aromatase activity-an obligatory step in the biosynthesis of estrogens-and possibly contain sulfatase activity. We investigated the effects of tibolone, its metabolites and the pure progestin Org 2058 on PGE(2)-stimulated aromatase activity and on sulfatase activity in human ASC primary cultures and on sulfatase activity in MCF-7 and T47D cell lines. In MCF-7, tibolone and metabolites, but not Org 2058, were found to inhibit sulfatase activity. In T47D, tibolone inhibited sulfatase only at 10(-6)M, although weakly. ASC had high sulfatase activity, which was inhibited by 10(-6)M of tibolone, Org 4094 and Org 30126, but not by Org OM38 or Org 2058. Surprisingly, aromatase activity in ASC was increased by both tibolone and Org 2058 at 10(-6)M. As ligand binding assay results and immunohistochemistry indicated the absence of progesterone and estrogen receptors in ASC, these effects on aromatase and sulfatase activity in ASC likely take place by other routes. Because tibolone and its metabolites inhibit sulfatase activity, and because tibolone only increases aromatase activity at a high concentration, we conclude that effects of tibolone on the breast are probably safe.


Assuntos
Tecido Adiposo/citologia , Aromatase/metabolismo , Neoplasias da Mama/patologia , Mama/citologia , Moduladores de Receptor Estrogênico/farmacologia , Norpregnenos/farmacologia , Sulfatases/metabolismo , 17-Hidroxiesteroide Desidrogenases/metabolismo , Mama/patologia , Relação Dose-Resposta a Droga , Estradiol/metabolismo , Moduladores de Receptor Estrogênico/metabolismo , Estrogênios/metabolismo , Humanos , Imuno-Histoquímica , Ligantes , Modelos Químicos , Norpregnenos/metabolismo , Ligação Proteica , Receptores de Progesterona , Células Estromais/enzimologia , Células Tumorais Cultivadas
14.
J Steroid Biochem Mol Biol ; 69(1-6): 293-7, 1999.
Artigo em Inglês | MEDLINE | ID: mdl-10419005

RESUMO

Breast cancer tissue is an endocrine organ and particularly the estrogen biosynthetic properties of this tissue have been well studied. The concentration of estradiol in breast cancer tissue from postmenopausal patients is considerably higher than that in the circulation and appears to depend largely on local production. Androgenic precursor steroids are abundantly present, but estrogen storage pools like fatty acid derivatives appear to be less important than initially thought. New, potent and highly specific aromatase inhibitors effectively inhibit peripheral conversion of androgens to estrogens (Cancer Res. 53: 4563, 1993) as well as intratumour aromatase, median aromatase activity being 89% lower in the tissue from patients pretreated with aromatase inhibitor 7 days prior to surgery (P < 0.001). Also the intratissue concentrations of estrogens were decreased (64% and 80% reduction, respectively for estrone and estradiol; P = 0.001 and <0.05; Cancer Res. 57: 2109, 1997). These results illustrate that intratissue estrogen biosynthesis is effectively inhibited by the new generation of aromatase inhibitors. The pathophysiological consequences of this finding are currently under study.


Assuntos
Neoplasias da Mama/metabolismo , Estrogênios/metabolismo , Humanos
15.
J Steroid Biochem Mol Biol ; 79(1-5): 41-7, 2001 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-11850206

RESUMO

We have investigated aromatase and the inducible cyclooxygenase COX-2 expression using immunocytochemistry in tumors of a series of patients with advanced breast cancer treated with aromatase inhibitors. Aromatase was expressed in 58/102 breast cancers. This is similar to the percentage previously reported for aromatase activity. Interestingly, aromatase was expressed in a variety of cell types, including tumor, stromal, adipose, and endothelial cells. Since prostaglandin E2 is known to regulate aromatase gene expression and is the product of COX-2, an enzyme frequently overexpressed in tumors, immunocytochemistry was performed on the tissue sections using a polyclonal antibody to COX-2. Aromatase was strongly correlated (P<0.001) with COX-2 expression. These results suggest that PGE2 produced by COX-2 in the tumor may be important in stimulating estrogen synthesis in the tumor and surrounding tissue. No correlation was observed between aromatase or COX-2 expression and the response of the patients to aromatase inhibitor treatment. However, only 13 patients responded. Nine of these patients were aromatase positive. Although similar to responses in other studies, this low response rate to second line treatment suggests that tumors of most patients were no longer sensitive to the effects of estrogen. Recent clinical studies suggest that greater responses occur when aromatase inhibitors are used as first line treatment. In the intratumoral aromatase mouse model, expression of aromatase in tumors is highly correlated with increased tumor growth. First line treatment with letrozole was effective in all animals treated and was more effective than tamoxifen in suppressing tumor growth. Letrozole was also effective in tumors failing to respond to tamoxifen, consistent with clinical findings. In addition, the duration of response was significantly longer with the aromatase inhibitor than with tamoxifen, suggesting that aromatase inhibitors may offer better control of tumor growth than this antiestrogen.


Assuntos
Aromatase/metabolismo , Neoplasias da Mama/enzimologia , Isoenzimas/metabolismo , Prostaglandina-Endoperóxido Sintases/metabolismo , Adipócitos/enzimologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Animais , Inibidores da Aromatase , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Ciclo-Oxigenase 2 , Dinoprostona/metabolismo , Endotélio/enzimologia , Inibidores Enzimáticos/uso terapêutico , Células Epiteliais/enzimologia , Moduladores de Receptor Estrogênico/uso terapêutico , Estrogênios/biossíntese , Feminino , Humanos , Imuno-Histoquímica , Letrozol , Neoplasias Mamárias Experimentais/tratamento farmacológico , Neoplasias Mamárias Experimentais/enzimologia , Neoplasias Mamárias Experimentais/patologia , Proteínas de Membrana , Camundongos , Camundongos Endogâmicos BALB C , Pessoa de Meia-Idade , Neoplasias Hormônio-Dependentes/tratamento farmacológico , Neoplasias Hormônio-Dependentes/enzimologia , Nitrilas/uso terapêutico , Células Estromais/enzimologia , Tamoxifeno/uso terapêutico , Triazóis/uso terapêutico
16.
Clin Microbiol Infect ; 6(6): 308-15, 2000 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-11168139

RESUMO

OBJECTIVE: To follow the evolution of capsular types and resistance of Streptococcus pneumoniae, isolated from deep sites. METHODS: More than 100 Belgian laboratories permanently collect S. pneumoniae strains isolated from puncture specimens (blood, cerebrospinal fluid, middle ear fluid, etc.) and forward them to the reference center in Leuven, in order to determine the capsular serogroups and types (SGTs) and their resistance. RESULTS: From 1994 to 1998, the 5486 S. pneumoniae strains examined belonged to 39 of the 46 currently identified SGTs. The 10 most frequent SGTs accounted for 78.9% of the isolates, and 97% of all isolates belonged to SGTs included in the 23-valent vaccine. Overall mortality of patients with pneumococcal bacteremia or meningitis was 9.7%, and 23.8% in patients over 80 years. From 1994 to 1998, resistance to penicillin (P) increased from 7.6% to 14.2%, to tetracycline (T) from 14.9% to 28.0%, and to erythromycin (E) from 22.9% to 31%. Triple resistance (PTE) increased from 0.9% in 1994 to 6.6% in 1998. Five SGTs (6, 9, 14, 19 and 23) accounted for 50% of the isolates, but for > 90% of the penicillin-resistant or erythromycin-resistant isolates. CONCLUSIONS: Resistance of S. pneumoniae to penicillin, erythromycin and tetracycline is steadily increasing and is concentrated in five serotypes included in the 23-valent pneumococcal vaccine. Increasing resistance and high mortality of invasive infections are an incentive to vaccinate vulnerable groups.


Assuntos
Resistência Microbiana a Medicamentos , Streptococcus pneumoniae/classificação , Adolescente , Adulto , Bélgica , Criança , Pré-Escolar , Humanos , Lactente , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Infecções Pneumocócicas/mortalidade , Sorotipagem , Streptococcus pneumoniae/efeitos dos fármacos , Streptococcus pneumoniae/isolamento & purificação
17.
Breast ; 10(2): 91-9, 2001 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-14965567

RESUMO

The cytochrome P-450 enzyme complex aromatase is the rate-limiting step in the production of oestrogens. It catalyses the conversion of androgens to oestrogens. In the treatment of hormone-dependent breast cancer in postmenopausal women, aromatase is the target for treatment with aromatase inhibitors. Recently registered aromatase inhibitors like anastrozole, letrozole and exemestane have proven to be effective therapy for advanced breast cancer in postmenopausal patients failing to respond to treatment with tamoxifen. Intratumoural aromatase activity has predictive value for response to treatment with aromatase inhibitors. Attempts are being made to find an immunohistochemical technique to determine aromatase in tumour tissue, which may serve as a predictive factor. In situ oestrogen synthesis through local aromatase activity in the tumour and adjacent tissue is probably a very important growth-stimulating system in hormone-dependent breast cancer. This synthesis can be blocked with aromatase inhibitors. The regulation of aromatase activity and the cell types that contribute to this process are the subject of extensive research. There seems to be a complex interaction between malignant cells and adjacent cells in which factors such as IL-6 and its soluble receptor, TNF-alpha and prostaglandin E2 play an important role in stimulating aromatase activity.

18.
J Behav Ther Exp Psychiatry ; 32(2): 73-90, 2001 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-11764063

RESUMO

On-line therapy offers many advantages over face-to-face settings. Interapy includes psycho-education, screening, effect measures and protocol-driven treatment via the Internet for clients. The present paper reports the results of a controlled trial on the Interapy treatment of posttraumatic stress and grief in students, gaining course credits. The participants in the experimental condition (n = 13) improved significantly than the participants in the waiting-list control condition (n = 12), on trauma-related symptoms and general psychopathology. The effect sizes were large. Eighty percent of the treated participants showed clinically significant improvement after treatment. The possibilities for future research with Interapy, including studies into moderating variables, are discussed.


Assuntos
Internet , Psicoterapia/instrumentação , Transtornos de Estresse Pós-Traumáticos/terapia , Adolescente , Adulto , Feminino , Seguimentos , Humanos , Masculino , Terapia Assistida por Computador/métodos
19.
J Telemed Telecare ; 6(1): 15-21, 2000.
Artigo em Inglês | MEDLINE | ID: mdl-10824385

RESUMO

An Internet system was developed for assessing psychopathology, for on-line, protocol-driven cognitive-behavioural psychological treatment and for measuring the effects of treatment. The system focused on the treatment of post-traumatic stress. The treatment comprised 10 writing sessions (45 min each) over five weeks. Participants were assessed on-line before treatment, after treatment and after six-week follow-up. After treatment the participants had improved significantly in terms of post-traumatic stress symptoms (P < 0.005) and general psychological functioning (P < 0.005), and this was sustained during the follow-up. Nineteen of the 20 participants were clinically recovered after treatment. Reduction in post-traumatic stress symptoms compared favourably to changes in control and experimental groups in trials of similar but face-to-face treatment.


Assuntos
Internet , Psicoterapia/métodos , Consulta Remota/métodos , Transtornos de Estresse Pós-Traumáticos/terapia , Adulto , Análise de Variância , Feminino , Humanos , Masculino , Avaliação de Programas e Projetos de Saúde , Consulta Remota/organização & administração , Inquéritos e Questionários , Resultado do Tratamento
20.
Obstet Gynecol ; 115(5): 1021-1031, 2010 May.
Artigo em Inglês | MEDLINE | ID: mdl-20410778

RESUMO

OBJECTIVE: To perform a systematic review of the literature on the effectiveness of multidisciplinary teamwork training in a simulation setting for the reduction of medical adverse outcomes in obstetric emergency situations. DATA SOURCES: We searched Medline, Embase, and the Cochrane Library from inception to June 2009. The search strategy contained medical subject heading terms ("patient care team" and "patient simulation" and "obstetrics" or "gynecology" and "education" or "teaching") and additional text words ("teamwork," "simulation," "training"). METHODS OF STUDY SELECTION: Studies describing and evaluating teamwork training programs with simulation models for labor ward staff in acute obstetric emergencies were selected. The search revealed 97 articles. TABULATION, INTEGRATION, AND RESULTS: All studies were assessed independently by two reviewers for methodological quality using the quality assessment of diagnostic accuracy studies (QUADAS) criteria. Only eight articles assessed the effect of teamwork training in a simulation setting. Four of them were randomized controlled trials and four were cohort studies. The only study that reported on perinatal outcome showed an improvement in terms of 5-minute Apgar score and hypoxic-ischemic encephalopathy. The seven other studies showed that teamwork training in a simulation setting resulted in improvement of knowledge, practical skills, communication, and team performance in acute obstetric situations. Training in a simulation center did not further improve outcome compared with training in a local hospital. CONCLUSION: Introduction of multidisciplinary teamwork training with integrated acute obstetric training interventions in a simulation setting is potentially effective in the prevention of errors, thus improving patient safety in acute obstetric emergencies. Studies on its effectiveness and cost-effectiveness are needed before team training can be implemented on broad scale.


Assuntos
Equipe de Assistência ao Paciente , Complicações na Gravidez/terapia , Resultado da Gravidez , Emergências/enfermagem , Tratamento de Emergência , Feminino , Humanos , Trabalho de Parto , Pesquisa em Educação em Enfermagem , Enfermagem Obstétrica/educação , Gravidez , Complicações na Gravidez/enfermagem , Pesquisa Qualitativa , Ensino/métodos
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