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Biomedical subjects

M Fahey

Publications and source records attributed to M Fahey.

At least 19 recordsLinked to original sources
PubMed2006

NGF receptor TrkAd5: therapeutic agent and drug design target.

Biochemical studies have shown that domain 5 of the TrkA (tropomyosin receptor kinase A) receptor is involved in the binding of NGF (nerve growth factor). Crystallographic studies have confirmed this, demonstrating that one homodimer of NGF binds to two TrkAd5 molecules. TrkAd5 has been made recombinantly in Escherichia coli, purified and shown to bind NGF with picomolar affinity. We have used the co-ordinates of the crystal structure of the NGF-TrkAd5 complex to screen approximately two million compounds in silico for the identification of small molecule agonists/antagonists. Selected hits were shown to be active in an in vitro ligand-binding assay; structure-activity relationships are now being investigated. In addition, TrkAd5 has been shown to be efficacious in preclinical models of inflammatory pain and asthma by the sequestration of excess levels of endogenous NGF, and therefore represents a novel therapeutic agent.

Alzheimer Disease↗
PubMed2004

Growth, behavior, and clinical findings in 27 patients with Kabuki (Niikawa-Kuroki) syndrome.

This study was undertaken to document the phenotype of Kabuki (Niikawa-Kuroki) syndrome in patients from Australia and New Zealand, with particular emphasis on growth patterns, behavior, and relationship between head circumference and intellectual level. Data on 27 children and adults with Kabuki (Niikawa-Kuroki) syndrome from Australia and New Zealand were collected by questionnaire and clinical assessment. The patients ranged in age from 7 months to 36 years with a mean age of 7 years and 2 months. The mean age at diagnosis was 3(5/6) years, but in most cases, the facial phenotype was evident from infancy. The minimum birth prevalence was calculated at 1 in 86,000. Three of our patients died. Parents reported a behavior phenotype characterized by an excellent long-term memory and avoidance of eye contact. No correlation was found between head circumference and severity of intellectual disability. Eight of 14 patients over the age of 5 years were overweight or obese. Six of these eight patients had failure to thrive in infancy. One patient developed insulin-dependent diabetes mellitus in adolescence. Some individuals with Kabuki (Niikawa-Kuroki) syndrome show a characteristic growth profile with failure to thrive in infancy progressing to obesity or overweight in middle childhood or adolescence. A behavior phenotype was noted which requires further investigation. Head size is not a predictor of degree of intellectual disability.

Abnormalities, Multiple↗
PubMed2002

European Prospective Investigation into Cancer and Nutrition (EPIC): study populations and data collection.

The European Prospective Investigation into Cancer and Nutrition (EPIC) is an ongoing multi-centre prospective cohort study designed to investigate the relationship between nutrition and cancer, with the potential for studying other diseases as well. The study currently includes 519 978 participants (366 521 women and 153 457 men, mostly aged 35-70 years) in 23 centres located in 10 European countries, to be followed for cancer incidence and cause-specific mortality for several decades. At enrollment, which took place between 1992 and 2000 at each of the different centres, information was collected through a non-dietary questionnaire on lifestyle variables and through a dietary questionnaire addressing usual diet. Anthropometric measurements were performed and blood samples taken, from which plasma, serum, red cells and buffy coat fractions were separated and aliquoted for long-term storage, mostly in liquid nitrogen. To calibrate dietary measurements, a standardised, computer-assisted 24-hour dietary recall was implemented at each centre on stratified random samples of the participants, for a total of 36 900 subjects. EPIC represents the largest single resource available today world-wide for prospective investigations on the aetiology of cancers (and other diseases) that can integrate questionnaire data on lifestyle and diet, biomarkers of diet and of endogenous metabolism (e.g. hormones and growth factors) and genetic polymorphisms. First results of case-control studies nested within the cohort are expected early in 2003. The present paper provides a description of the EPIC study, with the aim of simplifying reference to it in future papers reporting substantive or methodological studies carried out in the EPIC cohort.

Adult↗
PubMed2002

Diversity of dietary patterns observed in the European Prospective Investigation into Cancer and Nutrition (EPIC) project.

OBJECTIVE: To describe the diversity in dietary patterns existing across centres/regions participating in the European Prospective Investigation into Cancer and Nutrition (EPIC). DESIGN AND SETTING: Single 24-hour dietary recall measurements were obtained by means of standardised face-to-face interviews using the EPIC-SOFT software. These have been used to present a graphic multi-dimensional comparison of the adjusted mean consumption of 22 food groups. SUBJECTS: In total, 35 955 men and women, aged 35-74 years, participating in the EPIC nested calibration study. RESULTS: Although wide differences were observed across centres, the countries participating in EPIC are characterised by specific dietary patterns. Overall, Italy and Greece have a dietary pattern characterised by plant foods (except potatoes) and a lower consumption of animal and processed foods, compared with the other EPIC countries. France and particularly Spain have more heterogeneous dietary patterns, with a relatively high consumption of both plant foods and animal products. Apart from characteristics specific to vegetarian groups, the UK 'health-conscious' group shares with the UK general population a relatively high consumption of tea, sauces, cakes, soft drinks (women), margarine and butter. In contrast, the diet in the Nordic countries, The Netherlands, Germany and the UK general population is relatively high in potatoes and animal, processed and sweetened/refined foods, with proportions varying across countries/centres. In these countries, consumption of vegetables and fruit is similar to, or below, the overall EPIC means, and is low for legumes and vegetable oils. Overall, dietary patterns were similar for men and women, although there were large gender differences for certain food groups. CONCLUSIONS: There are considerable differences in food group consumption and dietary patterns among the EPIC study populations. This large heterogeneity should be an advantage when investigating the relationship between diet and cancer and formulating new aetiological hypotheses related to dietary patterns and disease.

Adult↗
PubMed2001

Decreased expression of TGF-beta cell surface receptors during progression of human oral squamous cell carcinoma.

This study examined the immunocytochemical expression of the transforming growth factor-beta (TGF-beta) isoforms TGF-beta1, TGF-beta2, and TGF-beta3, together with the TGF-beta cell surface receptors TbetaR-I and TbetaR-II, in patient-matched tissue pairs of normal human oral epithelium, primary squamous cell carcinomas, and metastatic lymph node tumour deposits. There were no significant differences in the intensity of TGF-beta isoform specific staining between the normal oral epithelium, the primary tumours, and the lymph node metastases. By contrast, there was significantly less TbetaR-II in the metastases than in the primary tumour and between the primary tumour and the normal oral epithelium. Similar trends were evident with TbetaR-I, but not at a statistically significant level. This study also examined the structure of TbetaR-I and TbetaR-II in normal human oral keratinocytes in vitro and in 14 human oral carcinoma cell lines with known responses to TGF-beta1. No structural abnormalities of TbetaR-II were present in the normal keratinocytes or in 13 of 14 malignant cell lines; in one line, there were both normal and mutant forms of TbetaR-II, the latter being in the form of a frameshift mutation with the insertion of a single adenine base (bases 709-718, codons 125-128), predicting a truncated receptor having no kinase domain. No defects were present in TbetaR-I. The structures of TbetaR-I and TbetaR-II did not correlate with growth inhibition by TGF-beta1. The data suggest that decreased expression of TGF-beta receptors, rather than structural defects of these genes, may be important in oral epithelial tumour progression. In order to examine the functional significance of a specific decrease in TbetaR-II expression, a dominant-negative TbetaR-II construct (dnTbetaR-II) was transfected into a human oral carcinoma cell line with a normal TGF-beta receptor profile and known to be markedly inhibited by TGF-beta1. In those clones that overexpressed the dnTbetaR-II, growth inhibition and Smad binding activity were decreased, whilst the regulation of Fra-1 and collagenase-1 remained unchanged following treatment with TGF-beta1. The results demonstrate that a decrease in TbetaR-II relative to TbetaR-I leads to selective gene regulation with loss of growth inhibition but continued transcription of AP-1-dependent genes that are involved in the regulation of the extracellular matrix.

Adult↗
PubMed2001

Use and costs of ambulatory care services among Medicare enrollees with schizophrenia.

OBJECTIVE: The objective of this study was to identify predictors of the use and cost of ambulatory care services among Medicare recipients with schizophrenia. METHODS: The design was a cross-sectional analysis of Medicare claims in 1991. The study subjects were a 5 percent random sample of all persons in the United States who had at least one Medicare service claim in 1991 and who were diagnosed as having schizophrenia in any care setting. Outcome measures included use and cost of any ambulatory care service, individual therapy, psychiatric somatotherapy, group therapy, or family therapy. RESULTS: For nearly 25 percent of the total sample of 12,440, no claims were filed for ambulatory care services in 1991. The mean+/-SD number of ambulatory care visits during the year was 7.9+/-21. The most frequently used type of therapy was individual therapy (5+/-14 visits). The mean+/-SD yearly cost of care for persons who received ambulatory care services was $470+/-$1,028. Among persons under 65 years of age, Caucasians were about 1.5 times as likely as African Americans to have received an ambulatory care service and 1.3 times as likely to have received individual therapy. Persons who were 65 or older were less likely to have received any service. Among service recipients, costs of care were lower for African Americans and for older people. CONCLUSIONS: The use of Medicare-funded ambulatory care services by persons with schizophrenia varied by race and age. Further investigation is required to determine whether subgroups of individuals who do not have additional insurance coverage or access to services are receiving substandard care.

Aged↗
PubMed2000

Autoantibodies against the processed ectodomain of collagen XVII (BPAG2, BP180) define a canine homologue of linear IgA disease of humans.

Linear IgA disease (LAD) is an acquired autoimmune subepidermal blistering dermatosis that affects human children and adults. In contrast to bullous pemphigoid, in which autoantibodies recognize transmembrane type XVII collagen (BP180, BPAG2), LAD is associated with skin-fixed and circulating IgA autoantibodies that target LAD-1, the processed extracellular form of type XVII collagen. An immunologic homologue of LAD in humans was identified in two dogs according to the following criteria: 1) erosive, ulcerative, and crusted lesions seen on the face, in the oral cavity, and on the extremities, 2) dermoepidermal clefting present in the basement membrane lamina lucida without inflammation or with mild neutrophilic infiltration, 3) basement membrane-fixed IgG and/or IgA antibodies, and 4) circulating IgA and IgG autoantibodies that target the 120-kd soluble protein LAD-1. The present study establishes unequivocally the existence of a naturally occurring canine model of LAD of humans.

Animals↗
PubMed1999

Novel feline autoimmune blistering disease resembling bullous pemphigoid in humans: IgG autoantibodies target the NC16A ectodomain of type XVII collagen (BP180/BPAG2).

In humans and dogs, bullous pemphigoid (BP) is an autoimmune blistering disease associated with the production of basement membrane autoantibodies that target the 180-kd type XVII collagen (BP180, BPAG2) and/or the 230-kd plakin epidermal isoform BPAG1e (BP230). In two adult cats, an acquired dermatosis and stomatitis was diagnosed as BP subsequent to the fulfillment of the following criteria: 1) presence of cutaneous vesicles, erosions, and ulcers; 2) histologic demonstration of subepidermal vesiculation with inflammatory cells, including eosinophils; 3) in vivo deposition of IgG autoantibodies at the epidermal basement membrane zone; and 4) serum IgG autoantibodies targeting a 180-kd epidermal protein identified as type XVII collagen. In both cats, the antigenic epitopes targeted by IgG autoantibodies were shown to be situated in the NC16A ectodomain of type XVII collagen, a situation similar to that of humans and dogs with BP. Feline BP therefore can be considered a clinical, histopathologic, and immunologic homologue of BP in humans and dogs.

Animals↗
PubMed1997

Comparative analysis of transforming growth factor-beta isoforms 1-3 in human and rabbit dentine matrices.

Previous studies have implicated transforming growth factor-beta (s)(TGF-beta) in both development. Here TGF-beta isoforms in dentine extracellular matrix were analysed because these molecules may participate in dental issue repair. EDTA-soluble and collagenase-released fractions were isolated from human crown and root and rabbit incisor dentine samples and analysed for TGF-beta isoforms. TGF-beta(1) was the major isoform detected in all samples and the only isoform detected in human dentine samples. TGF-beta(2) was detected only in the collagenase-released fraction of rabbit incisor dentine and was present at low levels. TGF-beta(3) was detected in both EDTA-soluble and collagenase-released fractions of rabbit dentine. Greater levels of the TGF-beta(1) isoform were detected in the rabbit than human dentine samples and some differences in distribution amongst the two tissue fractions were observed between these species. The presence of these isoforms of TGF-beta in dentine may provide a reservoir of growth factor in the matrix that could participate in processes leading to tissue repair after injury.

Animals↗
PubMed1996

Two women and their mothers: on the internalization and development of mother-daughter relationships.

This is a report from a 30-year followup study conducted by a member of Margaret Mahler's original separation-individuation research team. Based on a series of unstructured, clinical interviews with the original subjects and psychological testing of the subjects and their mothers, two mother-daughter pairs are compared from the perspective of the meaning of each daughter to her mother, how that meaning influenced the separation-individuation process, and how it influenced the unfolding of each daughter's life as a woman. Because the mother-child pairs were observed several times a week by both participant and nonparticipant observers beginning during the preverbal period, this study offers a unique opportunity to examine the influence of the earliest interactions on adult life.

Adolescent↗
PubMed1995

Meta-analytic methods for diagnostic test accuracy.

Meta-analyses of diagnostic test accuracy are uncommon and often based on separate pooling of sensitivity and specificity, which can lead to biased estimates. Recently, several appropriate methods have been developed for meta-analysing diagnostic test data from primary studies. Primary studies usually only provide binary test data, for which Moses et al. have developed a method to estimate Summary Receiver Operating Characteristic Curves, thereby taking account of possible test threshold differences between studies. Several methods are also available for analysing multicategory and continuous test data. The usefulness of applying these methods is constrained by publication bias and the generally poor quality of primary studies of diagnostic test accuracy. Meta-analysts need to highlight important defects in quality and how they affect summary estimates to ensure that better primary studies are available for meta-analysis in the future.

Bias↗
PubMed1992

Evaluating social work discharge planning services for elderly people: access, complexity, and outcome.

The discharge planning role of hospital social workers has become increasingly important in services to elderly people. This article examines three issues: (1) the extent to which elderly people most in need receive social work services, (2) the extent to which the discharge planning performed is a professional task, and (3) the effectiveness of discharge planning for those who return to their homes after hospitalization. The study focused on 1,100 elderly patients from five Baltimore hospitals. Data were gathered from their social workers, from the patients themselves (by phone after discharge), and from medical records. Results show that only a minority of elderly patients who return to the community after hospitalization receive social work services while in the hospital but that those who do are likely to have posthospital needs. In most cases, the discharge planning uses professional skills, but 28 percent of cases are fairly routine. Finally, social work services were effective in reducing the level of unmet needs in the areas of nursing, medication, and physical therapy.

Aged↗
PubMed1992

Impact of hospital discharge planning on meeting patient needs after returning home.

This study examines the contribution of hospital discharge planning in meeting the needs of patients for care after their return home. A random sample of 919 admissions (age 60 and over) to five hospitals was studied to obtain information on characteristics of discharge planning during the patients' hospital stay. Specifically, information was obtained on the involvement of a designated professional for managing and coordinating the discharge plan, and the extent to which the planning was interdisciplinary. Patient interviews conducted two weeks after discharge provided information on needs for care related to: (1) treatment, (2) activity limitations, and (3) other self-sufficiency limitations. Patients were asked about their need for care in these three areas and about whether or not these needs were being met. Overall, 97 percent reported one or more needs for care and 33 percent reported that at least one of these needs was not being met. Findings show that the involvement of a discharge planning case manager is related to a significant reduction in unmet treatment needs, but not to reductions in activity limitation, other self-sufficiency needs, or overall needs. No significant effects of interdisciplinary planning were identified. These findings suggest that treatment-related benefits result when a case manager has specific responsibility for the discharge planning of elderly patients returning home after hospitalization. These results provide insights into what is being achieved through current discharge planning practices. The meeting of specific patient needs through enhanced discharge planning may save future costs by reducing the rates of complications and hospital readmissions in an era of prospective payment, thus potentially offsetting the increased costs involved in planning and coordinating postdischarge care for older adults.

Activities of Daily Living↗
PubMed1992

Osteosarcoma of the pelvis. A clinical and histopathological study of twenty-five patients.

Twenty-five patients who had an osteosarcoma of the pelvis were treated at the University of Florida between 1967 and 1990. Two of these patients had underlying Paget disease, and five had received previous radiation therapy to the pelvis. Common problems in this series of patients included delays and errors in establishment of the diagnosis, underestimation of the extent of the tumor on the radiographic staging studies, histopathological findings of local extension next to and into pelvic structures, widespread invasion into major pelvic veins, and microscopic foci of tumor in otherwise normal tissue. These problems led to difficulty in gaining local control of the tumor with any type of operative procedure. Of the eighteen patients who had a resection, only four had a contamination-free wide margin, and a local recurrence developed in thirteen. Only one patient, who had no evidence of disease eleven years after treatment, was alive at the time of writing. Because of the tendency for venous invasion, the radiographic staging studies should include a thorough evaluation of the blood vessels adjacent to the tumor.

Adolescent↗
PubMed1990

Acute hospital costs of pediatric trauma in the United States: how much and who pays?

National estimates of the numbers and expenditures associated with hospitalization due to injury among children (aged 0 to 14) were derived using data from the 1984, 1985, and 1986 National Hospital Discharge Surveys (NHDS) and the 1980 National Medical Care Utilization and Expenditures Study (NMCUES). In this report, age- and sex-specific estimates of the numbers of hospital admissions and expenditures are reported for subgroup of patients defined by external cause of the injury and by nature and severity of the injury. In 1985, over 266,000 children sustained a traumatic injury resulting in hospitalization (rate of 51 per 10,000 children). Expenditures totaled nearly $1 billion. Over 80% of the hospitalizations and two thirds of total expenditures were for minor (Maximum AIS = 1.2) trauma. Moderate (Maximum AIS = 3) and severe (Maximum AIS = 4,5) trauma accounted for 18% and 2% of admissions and 31% and 8% of expenditures, respectively. Falls ranked first in expenditures and admissions (36% of the total). Motor vehicle-related injuries accounted for 19% of trauma admissions and 24% of expenditures. Other less common causes included bicycle injuries, penetrating injuries and injuries caused by the child being hit by an object or person. An estimated 28% of the total hospital charges were paid for by public sources (15% from federal government programs, 13% from state and local programs). An additional 63% of total expenditures were paid for by private sources, with the remaining 9% considered uninsured care.(ABSTRACT TRUNCATED AT 250 WORDS)

Accidental Falls↗
PubMed1990

Effectiveness of a hospital-based cooperative care model on patients' functional status and utilization.

The primary objective of this study was to test the hypothesis that inpatient care which emphasized structured, patient education, self-care and social support from a care partner (the Cooperative Care Program) is a cost-effective alternative to the more expensive staff-intensive, traditional hospital care; and that such care can be substituted without resulting in poorer outcomes with regard to subsequent health status or use of services. The effects of this program on patient and physician acceptance, patient knowledge and treatment and health status, were evaluated by means of an experimental design with comparable groups of patients assigned to experimental (cooperative care) or control (usual hospitalization) group status. Follow-up analyses of both groups of patients for a 12-month time period concluded that there were comparable and equally positive post-hospitalization experiences, with greater than 90% of both groups of patients functioning well with respect to a series of measures of functional status. There was no evidence that Cooperative Care patients were re-hospitalized more often or needed more emergency, home care or other types of services. There was, on the other hand, evidence of the positive effect on patient understanding, adherence to treatment, satisfaction, and self-management.

Female↗