PubMed Health⌕ Search

Biomedical subjects

B Fletcher

Publications and source records attributed to B Fletcher.

At least 19 recordsLinked to original sources
PubMed2001

Population genetic structure of variable drug response.

Geographic patterns of genetic variation, including variation at drug metabolizing enzyme (DME) loci and drug targets, indicate that geographic structuring of inter-individual variation in drug response may occur frequently. This raises two questions: how to represent human population genetic structure in the evaluation of drug safety and efficacy, and how to relate this structure to drug response. We address these by (i) inferring the genetic structure present in a heterogeneous sample and (ii) comparing the distribution of DME variants across the inferred genetic clusters of individuals. We find that commonly used ethnic labels are both insufficient and inaccurate representations of the inferred genetic clusters, and that drug-metabolizing profiles, defined by the distribution of DME variants, differ significantly among the clusters. We note, however, that the complexity of human demographic history means that there is no obvious natural clustering scheme, nor an obvious appropriate degree of resolution. Our comparison of drug-metabolizing profiles across the inferred clusters establishes a framework for assessing the appropriate level of resolution in relating genetic structure to drug response.

Chi-Square Distribution↗
PubMed2000

Treatment refusal/attrition among adults randomly assigned to programs at a drug treatment campus: The New Jersey Substance Abuse Treatment Campus, Seacaucus, NJ.

The New Jersey Substance Abuse Treatment Campus was funded to assess the feasibility of establishing a new model for delivering substance abuse treatment services and to serve as a research laboratory for conducting comparative evaluations of those services. The 350-bed campus was designed to improve treatment effectiveness by providing special services needed by underserved populations, and reduce treatment costs by serving large numbers of clients, centralizing services, and sharing facilities. First-time clients who met preliminary eligibility requirements during phone screening were randomly assigned to therapeutic community and chemical dependency programs. We used data collected on 1,573 adults who were ultimately accepted for admission to analyze treatment refusals and attrition during the 25 days after admission. Only 6.4% of the clients refused admission when informed of their treatment assignment. Planned duration of the residential phase of treatment, gender, and language spoken (English/Spanish) interacted with one another and differentially predicted treatment refusal/attrition. These findings may be useful for understanding treatment refusal and attrition in substance abuse treatment programs.

Adult↗
PubMed2000

Similar-other support for men undergoing coronary artery bypass surgery.

This field experiment examined effects of a support intervention on the physical and mental health of coronary artery bypass graft (CABG) surgery patients. Control participants (N = 90) received usual hospital care; experimental participants (N = 100) also received visits from a "similar other" while in the hospital. Similar others were Veterans Administration veterans who had CABG surgery previously and were trained in simple supportive techniques. Outcomes were assessed prior to surgery and at 1, 6, and 12 months afterwards. Unexpectedly, the intervention generally had no effects on participants' well-being. Further analysis showed that participants who talked often with fellow cardiac patients in the hospital ("de facto similar others") experienced improvements in their physical and emotional well-being over time.

Coronary Artery Bypass↗
PubMed2000

Orthodontic tooth movement after extraction of previously autotransplanted maxillary canines and ridge augmentation.

A case report is detailed in which autotransplanted maxillary canines were removed and the spaces closed. Substantial surrounding bone loss was associated with the upper right canine, and a bone graft was needed to reestablish normal dentoalveolar ridge morphology. Bone was taken from the maxillary tuberosity and placed in the canine extraction site, fixed with a bone screw, and covered with GoreTex. Seven months after placement of the bone graft, the GoreTex and stabilizing screw were removed to allow for consolidation of the bone. The upper left canine and lower second premolars were extracted, and fixed appliances were placed in both arches to align the teeth and close the spaces. Protraction of the upper right first premolar and retraction of the lateral incisor into the graft site were kept slow and constant with continued periodontal assessment. During the space closure, there was some concern that the bone in the graft site might resorb, leaving the teeth with compromised periodontal support. However, no significant periodontal attachment loss occurred despite ongoing concern about the amount of keratinized tissue. Perhaps the relatively slow rate of tooth movement provided for bone to be maintained and recreated ahead of the tooth. Almost complete closure of the upper canine extraction spaces was achieved. The upper premolars were substituted for the maxillary canines, and unfavorable prosthetic options were thus avoided. The lower arch was aligned, and the extraction spaces completely closed.

Adolescent↗
PubMed1999

Predicting posttreatment cocaine abstinence for first-time admissions and treatment repeaters.

OBJECTIVES: This study examined client and program characteristics that predict posttreatment cocaine abstinence among cocaine abusers with different treatment histories. METHODS: Cocaine abusers (n = 507) treated in 18 residential programs were interviewed at intake and 1-year follow-up as part of the nationwide Drug Abuse Treatment Outcome Study (DATOS). Program directors provided the program-level data in a mail survey. We applied the hierarchical linear modeling approach for the analysis. RESULTS: No prior treatment and longer retention in DATOS programs were positive predictors of posttreatment abstinence. The interactive effect of these 2 variables was also significantly positive. Program that offered legal services and included recovering staff increased their clients' likelihood of cocaine abstinence. Crack use at both the client and program level predicted negative impact. None of the program variables assessed differentially affected the outcomes of first-timers and repeaters. CONCLUSIONS: Although treatment repeaters were relatively difficult to treat, their likelihood of achieving abstinence was similar to that of first-timers if they were retained in treatment for a sufficient time. First-timers and repeaters responded similarly to the treatment program characteristics examined. The treatment and policy implications of these findings are discussed.

Adult↗
PubMed1998

Bcl-xL is expressed in ovarian carcinoma and modulates chemotherapy-induced apoptosis.

OBJECTIVE: To investigate the role of Bcl-xL in resistance to chemotherapy-induced apoptosis in ovarian carcinoma. METHODS: Two human ovarian carcinoma cell lines were used in this study: A2780 and SKOV3. A2780 cells were transfected with human Bcl-xL or control plasmid alone. Expression of Bcl-xL in single cell clones was analyzed by flow cytometry and protein expression was confirmed by Western blot. For in vitro chemotherapy-induced death assays, cisplatin and Taxol were used. The percentage of apoptotic cells was determined by nuclear propidium iodide staining followed by flow cytometric analysis. Human ascites samples were used to make tumor lysates which were then analyzed for expression of Bcl-xL protein by Western blot. RESULTS: A2780 cells express low levels of endogenous Bcl-xL while SKOV3 cells express high amounts as determined by Western blot. In addition, A2780 cells are sensitive to chemotherapy-induced cell death while SKOV3 cells are resistant. To determine if chemoresistance is mediated by expression of Bcl-xL, A2780 cells were transfected with Bcl-xL or control plasmid. Cells were incubated with either cisplatin or Taxol to induce apoptosis. Bcl-xL-expressing cells were highly resistant to cisplatin and Taxol compared with controls (P < 0.05). All samples of malignant ascites analyzed expressed high levels of Bcl-xL on Western blot. CONCLUSIONS: The results of these studies indicate that Bcl-xL is expressed in ovarian carcinoma, and in A2780 cells functions in a manner analogous to Bcl-2 by inhibiting chemotherapy-induced apoptosis. This may have prognostic significance; previous studies have demonstrated that patients with breast cancer that overexpress Bcl-2 have low-grade, hormonally responsive tumors. In ovarian carcinoma, another Bcl-2 family member, Bcl-xL may be responsible for modulating resistance to chemotherapy-induced apoptosis.

Antineoplastic Agents↗
PubMed1998

Investigating the relationship between stress and worker behaviour.

Direct care staff working in six residential group homes for people with intellectual disability were asked to complete a questionnaire which asked for information on levels of stress (anxiety and depression), the types of demand experienced by the staff, the support they received and the constraints they faced at work. Staff were also observed at work using a schedule which detailed who they interacted with, the content and type of interaction, and what activities staff were involved in. Measurement of workers' anxiety and depression levels confirmed management assessments of staff stress levels in the homes: two residential group homes were classified as 'low stress' and four as 'high stress'. A number of differences emerged between the two groups. Staff in the high stress homes reported greater demands and less support than those in the low stress homes. Higher levels of interaction were found between staff and residents in low stress houses, where more of the interaction was given as assistance and positive interactions. However, activities in higher-stress group homes appeared to be more community oriented, with staff spending a much greater amount of time out of the house. The importance of these results for both staff and residents is discussed, and suggestions for further work are made.

Adult↗
PubMed1997

HIV prophylaxis for health care workers.

The US Public Health Service (PHS) published new recommendations for preventing HIV seroconversion in health care workers suffering needle-stick injuries. In response, health care institutions across the United States are updating their internal protocols to meet the currently accepted standard of care in this area. We found the new guidelines lacking in critical definitions necessary to clarify practical applications in specific cases. We also found the recommendations of when to use one, two, or three drugs for post-exposure prophylaxis confusing. We report our university hospital's experience with needle-stick injuries over the past year. We propose modified guidelines that more finely stratify risk categories, define clinical variables which occur in practice, and simplify the algorithm for case management. The cost of managing our cases according to the modified guidelines are compared with management costs using the PHS guidelines. Potential costs of applying the PHS guidelines in our institution ranged from $68,994-$260,544; according to our modified guidelines, costs would range from $19,199-$54,749. We also present an analysis of the number of injured health care workers who need to be treated to prevent one case of seroconversion in the various risk stratifications.

Allied Health Personnel↗
PubMed1996

Air movement around a worker in a low-speed flow field.

A knowledge of the air movement around a worker in a low-speed airflow is important in a number of areas: containment testing of fume cupboards; testing of personal dust samplers; testing of LEV effectiveness; and measurement of worker exposure. Measurements of velocity vectors around the upper torsos of manikins and a human in low-speed airflows have been made using a laser Doppler anemometer. Both heated and unheated manikins, as well as a 'breathing' manikin were used. The results show that quite distinctive flow patterns develop with heated and unheated bodies. Comparison of the flows around two- and three-dimensional manikins with that around a human shows that only a three-dimensional heated manikin gives good results. The unheated breathing manikin gave results which were unrepresentative of the real situation. A suitable manikin for use in sampling or testing in low-speed airflows would have a heated, rounded, three-dimensional body of reasonably human dimensions and would be non-breathing and clothed.

Air Movements↗
PubMed1996

Occupational factors in multiple sclerosis: an analysis of occupational mortality statistics for men and married women in Great Britain.

This paper presents an exploratory study based on occupational mortality statistics for Great Britain. It examines disease concordance between marital partners for multiple sclerosis (MS). Previous studies have revealed that a married woman's life expectancy and her specific cause of death is reliably associated with the occupational mortality of her husband. This relationship exists across a wide range of occupations but is particularly marked in the case of MS. The present study examines the mortality rates for MS for a large number of occupations (taking into account possible sources of statistical bias) and considers the relationship of these findings with existing hypotheses about the aetiology of MS. It is suggested that there should be more consideration of occupational and psychological factors in multicausal explanations of the disease.

Adult↗
PubMed1995

Children's distress during magnetic resonance imaging procedures.

We investigated the epidemiology of pediatric anxiety and distress associated with magnetic resonance imaging procedures (MRIPs). Scores on the State-Trait Anxiety Inventory (Spielberger, Gorsuch, Lushene, Vagg, & Jacobs, 1983) and the State-Trait Anxiety Inventory for Children (Spielberger, Edwards, Lushene, Montuori, & Platzek, 1973), and subjective ratings of distress associated with MRIP were obtained from 55 pediatric oncology patients and their parents. Approximately 30% of children and their parents reported that MRIP produced significant distress. However, parents' ratings of their child's distress were significantly higher than children's self-ratings, and agreement between child and parent pairs was poor. Insertion of an intravenous line was identified as the most aversive component of MRIP by both parents (55%) and children (38%). The selective application of cognitive-behavioral interventions for noninvasive diagnostic procedures is suggested.

Adolescent↗
PubMed1995

Allogeneic BMT from a donor with fragile X syndrome: cytogenetic and molecular evaluation.

We report the first case of engraftment of bone marrow collected from a donor with Fragile X syndrome with subsequent cytogenetic and molecular evaluation. Engraftment was prompt and stable. Whilst the Fragile X abnormality could be detected initially by molecular techniques in the peripheral blood, it could not be detected cytogenetically while the patient was receiving CsA.

Adult↗
PubMed1992

Prevalence of spinal pain among the staff of a district health authority.

Being aware of the many neck and back problems which occur among staff, the departments of Occupational Medicine and Physiotherapy initiated a study to ascertain the scale of the problem among employees of the district health authority. A questionnaire was sent to a 10 per cent sample, stratified by occupation, of the 16,000 employees of a district health authority of which 84 per cent (1363) responded. Over half of all respondents had had a significant degree of spinal pain in the past year, mainly located in the back. In over half of those with pain, their discomfort had been significant enough to interfere with sport, work and sleep. Over one-quarter said they had taken time off work for spinal pain in the past five years. Nearly half of respondents under 25 years of age had some degree of spinal pain. Although a very small group, ambulance workers appear to have the greatest problems. Staff involved in lifting equipment and manual work had a lower prevalence of spinal pain than nurses or ambulance workers, but were more likely to have severe pain for which analgesics were taken. Nurses had a prevalence rate of 60 per cent, but less than one third had frequent or severe pain. Based upon this information an application has been made to implement a programme to reduce both the number of injuries and the severity of those that occur.

Adult↗
PubMed1992

Ifosfamide plus etoposide in newly diagnosed Ewing's sarcoma of bone.

PURPOSE: We assessed the activity of ifosfamide plus etoposide against newly diagnosed Ewing's sarcoma of bone by administering this drug pair before standard induction therapy (the upfront window approach). PATIENTS AND METHODS: Twenty-six children and adolescents with newly diagnosed, previously untreated Ewing's sarcoma of bone were enrolled onto this pilot study (EW-87). Eighteen were at a higher risk of treatment failure, with a primary tumor size of more than 8 cm or metastases at diagnosis. Window therapy with ifosfamide (1.6 g/m2/d with mesna uroprotection) and etoposide (100 mg/m2/d) was given in three 5-day cycles at 21-day intervals. Responses were evaluated clinically and radiologically. Subsequent induction therapy comprised three cycles of cyclophosphamide and doxorubicin. Radiation therapy was the primary local control modality; surgery was limited to biopsy or resection of expendable bones. After the local control phase, alternating courses of vincristine plus dactinomycin, ifosfamide plus etoposide, and cyclophosphamide plus doxorubicin were given as maintenance therapy. RESULTS: There were four complete responses and 21 partial responses to ifosfamide/etoposide window therapy (overall response rate 96%; 95% confidence interval [CI], 80% to 99%). Disease progression was observed in four patients during the cyclophosphamide/doxorubicin phase. Chemotherapy was well tolerated; only 16% (20 of 125) of all ifosfamide/etoposide window and maintenance cycles resulted in hospitalization for fever and neutropenia. Two patients developed chemotherapy-induced cystitis. CONCLUSIONS: The combination of ifosfamide and etoposide is highly active against previously untreated Ewing's sarcoma and generally is well tolerated. The ultimate impact of these two agents on outcome will be determined in randomized multicenter studies.

Adolescent↗