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Biomedical subjects

M Stevens

Publications and source records attributed to M Stevens.

At least 55 records · Page 3Linked to original sources

A Dutch version of the Social Support for Exercise Behaviors Scale.

We studied the reliability of a Dutch version of the Social Support for Exercise Behaviors Scale, originally developed by Sallis, Grossman, Pinski, Patterson, and Nader, using a sample of 461 older adults between 55 and 65 years of age. Cronbach alpha for the three subscales was calculated, respectively, as .69, .71, and .26, which are lower than the alphas reported in the original study. This may be due to the cultural differences between The Netherlands and the United States and differences between the samples of the two studies.

Adult↗

Description of the SUPPORT intervention. Study to Understand Prognoses and Preferences for Outcomes and Risks of Treatments.

BACKGROUND: The purpose of Study to Understand Prognoses and Preferences for Outcomes and Risks of Treatments (SUPPORT) was to improve outcomes for seriously ill hospitalized adults by improving information and decision-making. The SUPPORT intervention has been characterized only briefly in previous publications. OBJECTIVE: To characterize the intervention in SUPPORT and its implementation. DESIGN: Reports derived from training and administrative materials, quantitative descriptions of implementation activities, and qualitative analysis of narrative reports and focus group participation by the intervention nurses. SETTING AND PATIENTS: SUPPORT enrolled 2652 patients in the intervention arm and 2152 in the control arm of a block-randomized trial of enhanced information, counseling, and support. The patients were hospitalized with one of nine serious illnesses in one of five US teaching hospitals between 1992 and 1994. MEASUREMENTS: (1) Reports on training and supervisory materials; (2) Rates of intervention component completion from contact logs and reports completed by the intervention nurses; and (3) grounded theory analysis of patient narratives, overview questionnaires, and focus group transcripts from the intervention nurses. RESULTS: Prognostic reports were delivered on time to the caregiving team in 83% of cases on Day 3. Reports of surrogate interviews of patient preferences and understanding were delivered on time to the caregiving team in 72% of first week cases. Patients' own reports of preferences were unavailable for 56% of cases in the first week. Overall, 39% of the rest of the patients had their interview information delivered on time to the caregiving team. The SUPPORT intervention nurses averaged 8.5 contacts with patients, 7.6 with surrogates, 3.5 with physicians, and 11.7 with other staff. The intervention nurses felt that they were fully involved in 81% of cases and had a limited role in another 14%. The major issues for patients were: understanding their situation, communication and decision-making, advance planning, do not resuscitate orders, and general support, including support for loss and grieving. The narrative sources showed that the nurses were enthusiastic, dedicated, and strong in their support of the study objectives. They identified various barriers to effectiveness and voiced doubt that the analytic targets would show an effect from the intervention. CONCLUSIONS: The SUPPORT intervention was implemented vigorously and completely.

Adult↗

Distinct roles for STAT1, STAT3, and STAT5 in differentiation gene induction and apoptosis inhibition by interleukin-9.

Interleukin-9 (IL-9) activates three distinct STAT proteins: STAT1, STAT3, and STAT5. This process depends on one tyrosine of the IL-9 receptor, which is necessary for proliferation, gene induction, and inhibition of apoptosis induced by glucocorticoids. By introduction of point mutations in amino acids surrounding this tyrosine, we obtained receptors that activated either STAT5 alone or both STAT1 and STAT3, thus providing us with the possibility to study the respective roles of these factors in the biological activities of IL-9. Both mutant receptors were able to prevent apoptosis, but only the mutant that activated STAT1 and STAT3 was able to support induction of granzyme A and L-selectin. In line with these results, constitutively activated STAT5 blocked glucocorticoid-induced apoptosis. In Ba/F3 cells, significant proliferation and pim-1 induction were observed with both STAT-restricted mutants, though proliferation was lower than with the wild-type receptor. These results suggest that survival and cell growth are redundantly controlled by multiple STAT factors, whereas differentiation gene induction is more specifically correlated with individual STAT activation by IL-9.

Animals↗

Phenotypic variation in hereditary frontotemporal dementia with tau mutations.

Several mutations in the tau gene have been found in families with hereditary frontotemporal dementia and parkinsonism linked to chromosome 17q21-22 (FTDP-17). This study is the first attempt to correlate genotype and phenotype in six families with FTDP-17 with mutations in the tau gene (deltaK280, G272V, P301L, and R406W). We have investigated tau pathology in 1 P301L and 1 R406W patient. The R406W family showed a significantly higher age at onset (59.2 +/- 5.5 years) and longer duration of illness (12.7 +/- 1.5 years) than the families with the other mutations. The six families showed considerable variation in clinical presentation, but none of them had early parkinsonism. Mutism developed significantly later in the R406W family than in the other families. Frontotemporal atrophy on neuroimaging in the R406W family was less severe than in the P301L and deltaK280 families. The P301L brain contained many pretangles in the frontal and temporal cortex, and the dentate gyrus of hippocampus, showing three tau bands (64, 68, and 72 kd) of extracted tau from the frontal cortex. The presence of many neurofibrillary tangles, many diffuse and classic neuritic plaques in the temporal and parietal cortex, and the hippocampus of the same P301L brain correlated with the presence of four sarkosyl-insoluble (60, 64, 68, and 72 kd) tau bands. The coexistence of characteristic P301L and Alzheimer pathology in the same brain needs further explanation. The R406W brain showed abundant neurofibrillary tangles in several brain regions, and four tau bands (60, 64, 68, and 72 kd) of extracted tau from these regions. The slower progression of the disease in the R406W family might be explained by the microtubule-binding properties of the mutant protein.

Adult↗

Groningen Active Living Model (GALM): stimulating physical activity in sedentary older adults.

BACKGROUND: A significant number of Dutch older adults can be considered sedentary when it comes to regular participation in leisure-time physical activity. Sedentariness is considered a potential public health burden-all the more reason to develop a strategy for stimulating older adults toward becoming more involved in leisure-time physical activity. The Groningen Active Living Model (GALM) is a behavioral change strategy for stimulating participation in leisure-time physical activity. METHODS: The GALM strategy is based on a process model of behavioral change in which behavioral change is seen as a multidimensional and dynamic process. The strategy has three phases: recruitment, introduction, and follow-up, and lasts 18 months. RESULTS: Preliminary results indicate that, up until the summer of 1998, about 4000 older adults were participating in 76 local GALM projects. Further research will be done to assess the validity of the model and its effects on the leisure-time physical activity pattern, ADL performance, and health in newly active older adults. CONCLUSIONS: The GALM strategy is a feasible strategy for stimulating leisure-time physical activity participation on a large-scale basis. The strategy is being implemented in The Netherlands on a nationwide basis.

Activities of Daily Living↗

Positive and negative outcome expectations of smoking: implications for prevention.

BACKGROUND: To inform the development of messages for tobacco prevention programs, we examined seven positive and five negative outcome expectations of smoking as risk factors for smoking uptake. METHODS: A cross-sectional, self-administered survey of 471 students in grades 6-12 who were never or experimental smokers was performed. Logistic regression was used to examine the relationship between outcome expectations and susceptibility to becoming a smoker in the future, a measure of intent and resistance to peer smoking. RESULTS: A total of 36.1% of the sample was susceptible to smoking. All positive outcome expectations showed a strong and significant association with susceptibility. Students were most likely to be susceptible if they believed they would enjoy smoking (OR = 29.4). Three of the five negative outcome expectations were significantly associated with susceptibility, but the strength of these associations was much lower than that observed for the positive expectations (OR = 0.5 to 0.6). A strong belief in the negative outcomes of smoking did not alter the association between susceptibility and positive outcome expectations. CONCLUSIONS: These findings suggest that teaching adolescents and teens about the negative consequences of smoking is unlikely to change their intent to smoke. Preventive efforts should identify ways to address the positive expectations adolescents have about smoking, possibly by offering alternative means for achieving these outcomes.

Adolescent↗

CYP 3A proteins are expressed in human neutrophils and lymphocytes but are not induced by rifampicin.

Cytochrome P-450 3A (CYP 3A) enzymes, the prominent subfamily in the cytochrome system, are expressed in various extrahepatic tissues. Until now, their expression has been demonstrated in human polymorphic neutrophils (PMNs) but not in lymphocytes using immunohistochemistry and immunoblot analysis. Moreover, their potential modulation has not been determined yet. To study such an expression in different peripheral blood cell populations, rifampicin (600 mg/day during 6 days) was given to 8 healthy subjects. PMNs and lymphocytes were isolated by centrifugation of whole white blood cell fractions using Ficoll gradients before drug administration, immediately after, and 3 days after drug withdrawal. PMN and lymphocyte smears and homogenates were subjected to immunostaining and immunoblotting, respectively, with a mouse monoclonal antibody recognizing all CYP 3A proteins. These proteins were quantified by densitometric analysis. Before and after rifampicin administration, a positive cytoplasmic staining was observed in all PMNs and in about 50% of lymphocytes. CYP 3A expression in lymphocytes was further confirmed by positive immunoblots for lymphocyte homogenates. Neither in PMNs nor in lymphocytes, induction of CYP 3A protein expression was observed after rifampicin treatment despite overall induction of CYP 3A activity assessed by the urinary excretion of 6beta-hydroxycortisol. These results demonstrate that CYP 3A proteins are constitutively expressed not only in PMNs but also in lymphocytes. However, in both cell lineages CYP 3A protein expression was not induced by rifampicin.

Adult↗

The relationship between alcohol consumption patterns and injury.

AIMS AND DESIGN: A case-control design was employed to quantify the risk of injury after the recent consumption of alcohol. PARTICIPANTS AND SETTING: A total of 797 cases and 797 controls were interviewed throughout 1997. A response rate of 82% was calculated for eligible cases who were approached by an interviewer. The rate for interviews conducted of all people presenting with an injury during the study period was 67%. Cases were injured patients from a hospital emergency unit. Controls were matched on suburb and were interviewed at home regarding activities leading up to the time of their matched case's injury. MEASUREMENTS: Cases and controls were questioned about the injury event and alcohol and other drug use consumed in the 6 hours prior to the injury. They were also breath-tested and medical records were checked for validation purposes. FINDINGS: Logistic regression analysis produced an odds ratio of 3.4 (95% CI: 1.8-6.4) for the risk of sustaining an injury after consuming more than 60 g of alcohol in a 6-hour period, after controlling for demographic variables. The risk of injury at different levels of alcohol use was substantially higher for females with a significant odds ration of 9.6 at greater than 60 g of alcohol compared to 2.1 for men. CONCLUSIONS: These results need to be interpreted cautiously, but provide additional support that the risk of injury increases with the quantity of alcohol consumed and that the risk of injury is significantly higher for women.

Adolescent↗

Epidemiology of Cryptosporidium parvum in symptomatic paediatric oncology patients.

BACKGROUND: Although Cryptosporidium parvum is known to cause significant morbidity in immunocompromised individuals, including adults with cancer, the epidemiology of this pathogen in paediatric oncology patients is not known. OBJECTIVE: We prospectively investigated the incidence of symptomatic C. parvum infection in children receiving treatment for malignancy. METHODOLOGY: Over a 9 month period, all oncology inpatients with diarrhoea had stool analysis for C. parvum oocysts. The incidence of cryptosporidiosis was also recorded in non-oncology patients who had a stool analysed for C. parvum during the 6 years of the study period. RESULTS: None of the 149 stool samples from 60 oncology patients analysed contained C. parvum oocysts. Thirteen per cent of 173 samples from non-oncology patients were positive for C. parvum oocysts. CONCLUSIONS: In contrast to studies of adult oncology patients, paediatric oncology patients in our institution appear at low risk of cryptosporidiosis.

Animals↗

High prevalence of mutations in the microtubule-associated protein tau in a population study of frontotemporal dementia in the Netherlands.

Mutations in microtubule-associated protein tau recently have been identified in familial cases of frontotemporal dementia (FTD). We report the frequency of tau mutations in a large population-based study of FTD carried out in the Netherlands from January 1994 to June 1998. Thirty-seven patients had >/=1 first-degree relative with dementia. A mutation in the tau gene was found in 17.8% of the group of patients with FTD and in 43% of patients with FTD who also had a positive family history of FTD. Three distinct missense mutations (G272V, P301L, R406W) accounted for 15.6% of the mutations. These three missense mutations, and a single amino acid deletion (DeltaK280) that was detected in one patient, strongly reduce the ability of tau to promote microtubule assembly. We also found an intronic mutation at position +33 after exon 9, which is likely to affect the alternative splicing of tau. Tau mutations are responsible for a large proportion of familial FTD cases; however, there are also families with FTD in which no mutations in tau have been found, which indicates locus and/or allelic heterogeneity. The different tau mutations may result in disturbances in the interactions of the protein tau with microtubules, resulting in hyperphosphorylation of tau protein, assembly into filaments, and subsequent cell death.

Dementia↗

Nine-year follow-up of successful placement of endosseous implants in a mandibular bone graft.

Facial trauma injuries secondary to gunshot wounds present a unique challenge. These wounds are avulsive and typically involve the destruction of soft tissue with bone loss. A technique in bone transplantation is that of particulate cancellous bone and marrow. Initial form and stability can be provided by a titanium mesh tray or reconstruction plates while the graft undergoes maturation and consolidation. Dental implants can then be placed in this grafted site to provide stabilization for a functional and comfortable prosthesis and for the support of the peri-oral soft tissues.

Bone Transplantation↗

Protein 4.1R-deficient mice are viable but have erythroid membrane skeleton abnormalities.

A diverse family of protein 4.1R isoforms is encoded by a complex gene on human chromosome 1. Although the prototypical 80-kDa 4.1R in mature erythrocytes is a key component of the erythroid membrane skeleton that regulates erythrocyte morphology and mechanical stability, little is known about 4.1R function in nucleated cells. Using gene knockout technology, we have generated mice with complete deficiency of all 4.1R protein isoforms. These 4.1R-null mice were viable, with moderate hemolytic anemia but no gross abnormalities. Erythrocytes from these mice exhibited abnormal morphology, lowered membrane stability, and reduced expression of other skeletal proteins including spectrin and ankyrin, suggesting that loss of 4. 1R compromises membrane skeleton assembly in erythroid progenitors. Platelet morphology and function were essentially normal, indicating that 4.1R deficiency may have less impact on other hematopoietic lineages. Nonerythroid 4.1R expression patterns, viewed using histochemical staining for lacZ reporter activity incorporated into the targeted gene, revealed focal expression in specific neurons in the brain and in select cells of other major organs, challenging the view that 4.1R expression is widespread among nonerythroid cells. The 4.1R knockout mice represent a valuable animal model for exploring 4.1R function in nonerythroid cells and for determining pathophysiological sequelae to 4.1R deficiency.

Animals↗

High-dose melphalan with autologous stem-cell rescue in metastatic rhabdomyosarcoma.

PURPOSE: The European Collaborative MMT4-91 trial was conducted as a prospective nonrandomized study to evaluate the potential benefit of high-dose melphalan as consolidation of first complete remission in children with stage IV rhabdomyosarcoma. PATIENTS AND METHODS: Fifty-two patients in complete remission after six courses of chemotherapy received "megatherapy": 42 received melphalan alone, whereas 10 received melphalan in combination with etoposide, carboplatin/etoposide, or thiotepa/busulfan and etoposide. The outcome of this group of patients was compared with that observed in 44 patients who were also in complete remission after six courses of identical chemotherapy (plus surgery or radiotherapy) but went on to receive a total of up to 12 courses of conventional chemotherapy (four cycles). No differences were found between the two groups regarding clinical characteristics, chemotherapy received before complete remission, or response to chemotherapy. In particular, there was no significant difference between the groups for site of primary tumor, histologic subtype, age at presentation, presence of bone or bone marrow metastases, or number of metastases. RESULTS: The 3-year event-free survival (EFS) and overall survival (OS) rates were 29.7% and 40%, respectively, for those receiving high-dose melphalan or other multiagent high-dose regimens and 19.2% and 27.7%, respectively, for those receiving standard chemotherapy. The difference was not statistically significant (P =.3 and P =.2 for EFS and OS, respectively). There was a significant prolongation in the time from the last day of high-dose chemotherapy or the end of chemotherapy cycle 4 to the time of relapse in those receiving megatherapy (168 days for patients receiving megatherapy v 104 days for those receiving standard therapy; P =.05). CONCLUSION: The addition of a high-dose alkylating agent to consolidation therapy may have prolonged progression-free survival in this poor-risk patient group, but it did not significantly improve the ultimate outcome.

Adolescent↗

Outbreak of hepatitis A in Rotterdam associated with visits to 'darkrooms' in gay bars.

An unexpectedly large number of hepatitis A virus (HAV) infections were notified among homosexual men in Rotterdam in the first five months of 1998. A case control study was conducted to investigate the hypothesis that this outbreak was associated with sexual practices and to collect information with which to focus preventive activities. Notified cases and controls selected from male members of a gay sports club completed anonymous questionnaires about known risk factors for HAV infection and sexual behaviour. Single variable analysis showed that HAV infection was associated with sexual contact with anonymous sex partners (odds ratio (OR) 4.6; 95% confidence interval (CI) 1.0-23.2) and with visits to 'darkrooms' in gay bars (OR 6.2; 95% CI 1.5-26.8). A negative association with travel abroad to western countries was observed (OR 0.4; 95% CI 0.1-1.3). The associations with visits to darkrooms (OR = 9.2; 95% CI 1.6-52.4) and travel abroad to western countries (OR 0.1; 95% CI 0.02-0.9) remained significant in a multivariable logistic regression analysis. This risk group was targeted for health education and vaccination and darkroom owners were advised to provide hygiene facilities.

Adult↗

Association of missense and 5'-splice-site mutations in tau with the inherited dementia FTDP-17.

Thirteen families have been described with an autosomal dominantly inherited dementia named frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP-17), historically termed Pick's disease. Most FTDP-17 cases show neuronal and/or glial inclusions that stain positively with antibodies raised against the microtubule-associated protein Tau, although the Tau pathology varies considerably in both its quantity (or severity) and characteristics. Previous studies have mapped the FTDP-17 locus to a 2-centimorgan region on chromosome 17q21.11; the tau gene also lies within this region. We have now sequenced tau in FTDP-17 families and identified three missense mutations (G272V, P301L and R406W) and three mutations in the 5' splice site of exon 10. The splice-site mutations all destabilize a potential stem-loop structure which is probably involved in regulating the alternative splicing of exon10. This causes more frequent usage of the 5' splice site and an increased proportion of tau transcripts that include exon 10. The increase in exon 10+ messenger RNA will increase the proportion of Tau containing four microtubule-binding repeats, which is consistent with the neuropathology described in several families with FTDP-17.

Alternative Splicing↗