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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

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↗

Predictors of smoking cessation in adolescents.

OBJECTIVE: To examine factors associated with cessation of smoking in adolescents 12 to 18 years of age who smoke cigarettes. DESIGN AND SETTING: Prospective school-based cohort study of 1384 New Hampshire high school students surveyed at baseline and annually up to 3 subsequent years regarding their substance abuse behaviors, including adolescents who smoked 1 or more cigarettes within the past 30 days at baseline. OUTCOME MEASURES: Cessation behavior was defined by a subsequent response indicating nonsmoking status. We examined associations between smoking cessation and baseline measurements of the level of addiction (cigarette consumption pattern), experience with quitting, intent to quit now and in the future, opinion of adults smoking more than 1 pack of cigarettes per day, social influences to smoke, sex, and psychological attributes. RESULTS: Of 276 adolescents who qualified as cigarette smokers at baseline, 123 (44.6%) were occasional smokers, 65 (23.6%) were daily smokers of 1 to 9 cigarettes, and 88 (31.9%) were daily smokers of 10 or more cigarettes. While 39 (14.1%) had smoked for 1 year or less, 62 (22.5%) had smoked for 6 or more years. Seventy-five (27.2%) reported failed past attempts to quit smoking, 71 (25.7%) reported wanting to quit now, and 50 (18.1%) reported definitely intending to be a nonsmoker in the future. Seventy-nine smokers (28.6%) described themselves as nonsmokers in follow-up surveys. The smoking cessation rate was 46.3% among occasional smokers, 12.3% among daily smokers of 1 to 9 cigarettes, and 6.8% among daily smokers of 10 or more cigarettes. Smoking cessation was associated with occasional smoking status (adjusted odds ratio 6.67 compared with daily smokers of 10 or more cigarettes [95% confidence intervals, 2.26-19.69]), and definite intentions to quit in the future (2.67 [95% confidence intervals, 1.2-5.7]). Most of those with definite intentions to quit in the future were occasional smokers (92.0%). CONCLUSIONS: This study documents cessation of smoking in nearly one third of the adolescent smokers. The cessation rate among daily smokers of 10 or more cigarettes per day is comparable with adult cessation rates. Adolescents who are less addicted, measured by low frequency of cigarette use, are more likely than daily users to quit. In addition, definite intent to quit in the future predicts cessation, but only among occasional smokers. In contrast with adults, experience with quitting was not associated with a higher likelihood of cessation. Pediatricians should focus on keeping occasional smokers from moving into daily smoking status, where nicotine addiction begins to play a prominent role in maintaining the behavior. Further study is needed to guide enhancement of the recruitment of adolescents into cessation, assessment of nicotine dependence in daily adolescent smokers, and appropriate use of nicotine replacement therapy in this group.

Adolescent↗

The prevalence of and risk factors for atopy in early childhood: a whole population birth cohort study.

OBJECTIVES: A birth cohort was followed-up to age 4 years to record the development of allergic disorders and to study the influence of genetic and environmental factors. METHODS: Information on family history and environmental factors was obtained at birth, and serum cord IgE was measured. At age 4 years, 1218 children were reviewed. RESULTS: By age 4 years, 27% of the children had symptoms of allergic disease. Period prevalence of asthma increased from 8.7% in infancy to 14.9% at 4 years. Family history of atopy was the single most important risk factor for atopy in children. Sibling atopy was a stronger predictor of clinical disease than maternal or paternal atopy, whereas paternal atopy, male sex, and high cord IgE were significant for the development of allergen sensitization. Children of asthmatic mothers were three times more likely to have asthma (odds ratio [OR]: 3.0, 95% confidence interval [CI]: 1.6-5.8) and rhinitis (OR: 2.9, CI: 1.1-7.4). Formula feeding before 3 months of age predisposed to asthma at age 4 years (OR: 1.8, CI: 1.2-2.6). The effect of maternal smoking on childhood wheeze seen at 1 and 2 years was lost by age 4, except for a subgroup with negative skin test responses (nonatopic asthma). Less than half (46%) of the infantile wheezers were still wheezing at 4 years of age. CONCLUSION: Family history of atopy remains the most important risk factor for atopy in children, but other markers can be identified with a potential for intervention at an early age.

Animals↗

Role of written advance directives in decision making: insights from qualitative and quantitative data.

OBJECTIVE: To understand the role of written advance directives (ADs) in medical decision making through examination of qualitative and quantitative data sources. We specifically wanted to address whether physicians unilaterally disregard advance directives. DESIGN: Block randomized controlled trial to improve decision making and outcomes of seriously ill patients. SETTING: Five academic medical centers. PATIENTS: Fourteen hospitalized, seriously ill adults were randomized to receive an intervention of patient-specific information on prognoses and specially trained nurse to facilitate decision making. To be included in this analysis, patients reported having an AD and also met one of these criteria of severity: were comatose, had objective estimate of prognosis for surviving 2 months of 40% or less, or died during this hospital admission. MEASUREMENTS AND MAIN RESULTS: Quantitative data sources consisted of medical record review and interviews with the patient (when possible), surrogate, and responsible physician about prognosis, symptoms, preferences, and decision making. Qualitative data consisted of narratives by the nurse responsible for counseling and facilitating decision making. Each element of the quantitative database was reviewed, and a timeline of communication and decision making was constructed. Qualitative data were analyzed using grounded theory and narrative summary analysis. We compared and contrasted qualitative and quantitative data to better understand the role of ADs in decision making. In each case, the patient had a period of diminished capacity in which ADs should have been invoked. Advance directives played an important role in decision making of 5 of 14 cases, but even in those cases, life-sustaining treatment was stopped only when the patient was "absolutely, hopelessly ill." In two of these cases, the family member wrongly reported that the patient had an AD, and in the remaining seven cases, ADs had a limited role. The limited role could not be traced to a single explanation. Rather, a complex interaction of several factors was identified: patients were not considered hopelessly ill, so the directive was never seen as applicable and a transition in the goals of care did not occur; family members or the designated surrogate were not available, were ineffectual, or were overwhelmed; or the content of the AD was vague, or not applicable to the clinical situation, and the intent in completing the AD was never clarified. A physician did not unilaterally disregard a patient's preference in any of the cases. Two factors that enhanced the role of the AD were an available surrogate who was able to advocate for the patient and open communication between the physician and the surrogate in which the patient's prognosis was reconsidered. CONCLUSIONS: Our findings indicate that physicians are not unilaterally disregarding patients' ADs. Despite the patients' serious illnesses, family members and physicians did not see them as "absolutely, hopelessly ill." Hence, ADs were not considered applicable to the majority of these cases. Cases in which ADs had an impact evidenced open negotiation with a surrogate that yielded a transition in the goals of care.

Adult↗

Experiences of mothers in five countries whose child died of cancer.

Although increasing attention is being focused on the emotional aspects of caring for dying children and their families, few research reports concentrate on the experiences of mothers, particularly in different countries. This article describes the findings of an exploratory, descriptive study that investigated the experiences of mothers from five different countries who each had a child die from cancer in the past 6 months. Principal investigators, members of the International Work Group on Death, Dying, and Bereavement, conducted semistructured interviews with 21 mothers in their own countries. No culturally related differences were noted among mothers, and the mothers' recall of their experiences are more similar than different. All mothers, irrespective of country, described similar reactions to the diagnosis, management of the end-stage illness, and challenge of coping with bereavement. Lessons learned from this project provide suggestions for future research across countries.

Adolescent↗

Use of dialectical behavior therapy in a partial hospital program for women with borderline personality disorder.

Dialectical behavior therapy, an outpatient psychosocial treatment for chronically suicidal women with borderline personality disorder, has been adapted for use in a partial hospital program for women. Patients attend the program for a minimum of five days of individual and group therapy, and full census is 12 women. About 65 percent of participants meet at least three criteria for borderline personality disorder, and most have suicidal and self-injurious behavior. Their comorbid diagnoses include trauma-related diagnoses and anxiety disorders, severe eating disorders, substance abuse, and depression. The partial hospital program is linked to an aftercare program offering six months of outpatient skills training based on dialectical behavior therapy. Both programs focus on teaching patients four skills: mindfulness (attention to one's experience), interpersonal effectiveness, emotional regulation, and distress tolerance. Two years of operation of the women's partial hospital program provides promising anecdotal evidence that dialectical behavioral therapy, an outpatient approach, can be effectively modified for partial hospital settings and a more diverse population.

Adult↗

Familial aggregation in frontotemporal dementia.

OBJECTIVE AND BACKGROUND: Frontotemporal dementia (FTD) is a common, non-Alzheimer's dementia. Its familial occurrence has been reported, but the frequency of positive family history is unknown. METHODS: We carried out a nationwide genetic-epidemiologic study of FTD in the Dutch population of 15 million people. The family history of dementia was analyzed in 74 FTD patients and 561 age- and gender-matched control subjects. RESULTS: We found one or more first-degree relatives with dementia before age 80 in 38% (28 of 74) of FTD patients, but only in 15% (84 of 561) of control subjects. Ten percent of FTD patients had two or more first-degree relatives with dementia compared with 0.9% of the control subjects. Seven percent of FTD patients showed the ApoE4E4 genotype versus 2.3% of the control subjects. The first-degree relatives of FTD had a risk of 22% for dementia before age 80 compared with 11% in relatives of control subjects. The age of onset of dementia in affected first-degree relatives of FTD patients (60.9+/-10.6 years) was significantly lower than among affected relatives of control subjects (72.3+/-8.5 years). The first-degree relatives of FTD patients were 3.5 times (95% CI, 2.4 to 5.2) more at risk for developing dementia before age 80 than relatives of control subjects. The hazard ratio in the subgroup with unknown linkage to chromosome 17 was 2.4 (95% CI, 1.5 to 3.7). CONCLUSION: This study documents the importance of genetic factors in a proportion of FTD patients with the age at onset of dementia in first-degree relatives being 11 years earlier than in the general population.

Adult↗

A community-based randomized trial encouraging sun protection for children.

OBJECTIVE: We evaluated the impact of an intervention promoting sun protection behavior among children 2 to 11 years of age through schools and day care centers, primary care practices, and recreation areas. METHODS: Ten towns in New Hampshire were paired, then assigned randomly to intervention or control status. The multicomponent SunSafe intervention was provided to children and caregivers through primary care practices, day care centers, schools, and beach recreation areas. Training support and materials were provided by the SunSafe project, but project staff had no direct contact with children or parents in providing the intervention. All intervention components promoted the same message: avoid the sun between 11 AM and 3 PM, cover up using hats and protective clothing, use sun block with a sun protection factor >/=15, and encourage sun protection among family and friends. The impact of the intervention was determined by observing children's sun protection behavior at the beach during baseline compared with 1 year later. The primary outcomes of interest were changes in the proportion of children per town using at least some sun protection and changes in the proportion of children fully protected. Children were clustered by town, with the town thus being the unit of analysis. The primary care practice component included one practice meeting for clinicians and staff at which project staff presented background on skin cancer and how to promote its prevention; a sun protection office system manual based on our previous work, which provided specific direction on how to share responsibility among office staff and clinicians in carrying out routines that promote sun protection; and educational posters, pamphlets, and self-adhesive reminder notes designed to enhance sun protection counseling. SunSafe removable tattoos and stickers were offered to children at well-child and illness visits during the summer months. Schools each received three project staff visits: a brief visit with the principal to describe the intervention and to answer questions; an in-service program to educate teachers about skin cancer and to introduce curricular materials; and help with one parent outreach program. Larger day care centers each received one project staff visit. An additional six smaller day care centers received curricular materials through the mail but no visits. Two similar sets of curricular materials were used, one for grade schools and the other for preschools and day care centers. Both emphasized the importance of sun protection rather than the danger of skin cancer. Materials emphasized dynamic activities modeled after the "Slip, Slop, Slap" and "SunSmart" programs and included new material developed to suit regional needs. Both manuals offered structured plans but also provided a variety of activities from which teachers could choose. Teachers agreed to devote a minimum of two class periods to these materials. For recreation areas, lifeguards in each of the intervention communities attended an in-service meeting, during which background about skin cancer prevention was presented by project staff. The project also provided displays about the ultraviolet (UV) light index and about sun protection to be posted at each beach. Subsequently, project staff called beach staff in each community each morning with the predicted UV index for the day to post on the display. Educational pamphlets about the UV index and free sun-block samples were available to beachgoers through the lifeguards. One brief follow-up visit by project staff was made to each beach area to provide reinforcement. RESULTS: We observed 1930 children. Use of some sunscreen on at least one body area increased in all 5 intervention towns compared with paired control towns. In intervention towns, this mean proportion increased from 0.56 of those observed at baseline to 0.76 of those observed postintervention, with a minimal increase among control town children. (ABSTRACT TRUNCATED

Child↗