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Biomedical subjects

K Wright

Publications and source records attributed to K Wright.

At least 73 records · Page 4Linked to original sources

Ethiodized oil emulsions in hepatic microcirculation: in vivo microscopy in animal models.

RATIONALE AND OBJECTIVES: The authors' purpose was to define the stability and drug-carrying and drug-releasing capacity of ethiodized oil emulsions in the hepatic circulation. METHODS: Emulsions prepared in various ratios of a nonionic contrast material containing doxorubicin to ethiodized oil were injected into the hepatic arteries of normal and tumor-bearing livers in rats or mice. In vivo microscopy was used to observe the dynamic distribution of the emulsions in the hepatic circulation. RESULTS: A solution of less water mixed with more oil formed water-in-oil (w/o) phase emulsions, whereas oil with more water formed oil-in-water (o/w) emulsions. The oil in the emulsions carried the water in the blood circulation. The w/o emulsions exhibited significantly higher carriage capacity and longer release time for the drug solution than did the o/w emulsions (P < .01). CONCLUSION: The delivery of w/o emulsions is superior to that of o/w emulsions. Further studies about preparation methods and delivery capability of emulsions in the liver are warranted.

Animals↗

St. Louis Integrated Immunization Information System.

The immunization rate for St. Louis, Missouri, children age two and younger is only 49 percent, below the statewide rate of 64 percent and far below the estimated national rate of 75 percent. In response to this crisis, the St. Louis Integrated Immunization Information System (SLIIIS) was designed to establish an on-line immunization information system, identify barriers to immunization among health care providers and the client population, and implement methods for removing these barriers. Available to both public and private health care providers, SLIIIS uses a population-based approach to monitoring and improving immunization levels in the Eastern Missouri Region. SLIIIS was initiated by a partnership of an academic center with community agencies and institutions. Review of initial development efforts and system design may be valuable to others involved in creating regionally integrated information systems.

Child, Preschool↗

Psychiatric morbidity in medical and surgical patients evacuated from the Persian Gulf War.

Acute treatment records of all medical and surgical patients evacuated to Walter Reed Army Medical Center in Washington, D.C., from the Persian Gulf theater (N = 161) were examined to better understand the relationship of injury to psychiatric symptoms. A total of 110 (68 percent) sustained a traumatic injury. They were significantly more likely to have an axis I disorder or psychiatric symptoms of concern than participants in the Persian Gulf War who did not sustain traumatic injuries but who were evacuated for medical conditions. The results indicate that traumatically injured veterans are at greater risk of psychiatric symptoms than veterans who are not injured and that they should be referred for psychiatric evaluation.

Adolescent↗

Programme budgeting revisited: special reference to people with learning disabilities.

The recent reorganization of community care in the UK removed many of the perverse incentives identified in the previous system. However, the organization of care for many people is still divided across several agencies in the public and independent sectors. As purchasing and providing agencies in both the National Health Service and local authority personal social services attempt to coordinate policy objectives and the means to achieve them, the total resources available and their allocation across different care groups and among people in the same care groups from a consistent focus of attention. The principles and practice of programme budgeting provide important lessons for planning and monitoring expenditure. This paper rehearses such principles in the specialized area of policies for people with learning disabilities and draws on the experience of mapping expenditure on relevant services in a survey over 10 local authorities in England.

Budgets↗

Psychological distress among informal supporters of frail older people at home and in institutions. The Resource Implications Study Group of the MRC Cognitive Function and Ageing Study.

OBJECTIVE: Investigate presence of psychiatric morbidity in informal carers using 30-item General Health Questionnaire (GHQ) and examine which factors best predict psychiatric morbidity. DESIGN: Two-year longitudinal, panel survey of informal supporters of frail elderly subjects, using semi-structured interview schedules. Subjects were those defined as frail after screening stratified random sample of people aged 65 or over. SETTING: Informal supporters of frail elderly subjects residing in private households or residential or nursing homes in four UK districts. RESPONDENTS: 623 informal supporters of subjects living at home, 129 regular visitors of those in long-term care. MEASURE: 30-item GHQ (cross-sectional analysis). RESULTS: Stepwise multiple regression indicated main predictors of high GHQ scores in key supporters were: subjects had at least three problems of behaviour (b = 1.56, 95% CI 1.25-1.94); supporters had to alter working hours (b = 1.70, 95% CI 1.15-2.51); supporters were female (b =1.26, 95% CI 1.06-1.50). The following variables predicted low GHQ scores: supporters able to leave subject all day (b = 0.71, 95% CI 0.64-0.80); subjects never wandered (b = 0.78, 95% CI 0.62-0.99); supporters were 'other relatives' or friends of subject (b = 0.74, 95% CI 0.59-0.91). For visitors, spouses were most likely to have high GHQ scores (b = 2.46, 95% CI 1.32-4.57). CONCLUSIONS: Results suggest the need for greater collaboration between formal and informal care. Little work has been carried out to ascertain which interventions are most effective in alleviating carer stress: a series of randomized controlled trials to determine long-term effectiveness of various interventions for different groups of carers is required.

Adult↗

Tumor necrosis factor-alpha enhances antitumor effects of radiation against glioma xenografts.

Long-term control of high-grade brain tumors is rarely achieved with current therapeutic regimens. The aim of this study was to determine if low doses of tumor necrosis factor-alpha (TNF-alpha) could augment the effects of radiation in a glioma xenograft model and to evaluate hematological and other parameters that might indicate treatment-related toxicity. Nude mice were injected subcutaneously with C6 rat glioma cells and randomized into groups. Two different time-dose protocols were employed using intravenous human recombinant TNF-alpha and radiation beginning within 24 h after tumor cell implantation. The administration of radiation as a single agent slowed tumor progression, whereas TNF-alpha alone had no effect. However, TNF-alpha, especially when given twice per week before radiation for a total of four doses each, significantly increased the efficacy of the radiation. Low leukocyte counts were associated with combination treatment, whereas transforming growth factor-beta 1 levels were depressed in all treated groups. TNF-alpha did not modulate radiation-induced inhibition of C6 cell proliferation in vitro. The data show that TNF-alpha at relatively nontoxic doses can significantly enhance the antitumor effects of radiation against a rapidly growing glioma. This effect was more than additive, because TNF-alpha alone did not slow tumor progression.

Animals↗

Complete analysis of the presenilin 1 gene in early onset Alzheimer's disease.

The presenilin 1 gene has recently been identified as the locus on chromosome 14 which is responsible for a large proportion of early onset, autosomal dominantly inherited Alzheimer's disease (AD). We have elucidated the intron/exon structure of the gene and designed intronic primers to enable direct sequencing of the entire coding region (10 exons) of the presenilin gene in a large number of families. This strategy has enabled us to find a further two novel mutations in the gene. We discuss the distribution of mutations and the proportions of autosomal dominant AD with a mean age of onset below 60 years caused by mutations in this gene.

Alzheimer Disease↗

A further presenilin 1 mutation in the exon 8 cluster in familial Alzheimer's disease.

Recent studies suggest that mutations in the presenilin 1 gene, which encodes a polypeptide predicted to be a multispanning membrane protein, are responsible for the majority of cases of early onset, autosomal dominant Alzheimer's disease. Here we describe a further mutation in the presenilin 1 gene (R269G) in a family with early onset Alzheimer's disease. This mutation is in exon 8 which appears to be a favoured region for pathogenic mutations. In the presenilin protein the region coded for by this exon is likely to comprise a domain located on the membrane surface. We discuss the likely effects of the exon 8 mutations on the structure of the exon and in the pathogenesis of the disease.

Alzheimer Disease↗

Costs of mental illness in Britain.

Cost of illness studies are a growing area of literature without a common methodology and their usefulness has been debated over the years. A short review carried out of the British studies on mental health revealed differences which originate from three main areas: the epidemiological evidence on prevalence, service contact data and the unit costs employed. This paper outlines the differences found in a number of these studies and we develop a worked example using information from the studies to illustrate the issues of concern. We conclude that the area is problematic in two fashions. Firstly, the results are highly sensitive to epidemiological data and assumptions on costs. Secondly, the assumptions on costs and use of services must always be made explicit.

Cost of Illness↗

Rapid recovery of a functional MDR phenotype caused by MRP after a transient exposure to MDR drugs in a revertant human lung cancer cell line.

Prior studies have shown that, in some human tumour cells, increased expression of the multidrug resistance gene MDR1 can be induced in response to certain stress conditions such as a transient exposure to cytotoxic agents. Little is known about the possibility of increasing the expression of the recently cloned multidrug resistance-associated protein (MRP) in response to a transient exposure to cytotoxic drugs. In order to examine this possibility, we have used sensitive assays (RT-PCR, flow cytometry) and the sensitive large cell lung cancer cell line, COR-L23/P, and the revertant line (COR-L23/Rev), generated by growing the doxorubicin-selected, MRP-overexpressing resistant variant COR-L23/R without drug exposure for 24-28 weeks. COR-L23/Rev overexpresses MRP, but to a lesser extent than COR-L23/R. COR-L23/Rev rapidly recovered similar levels of MRP mRNA, protein expression, resistance and drug accumulation deficit as COR-L23/R after a 48-72 h exposure to cytotoxic concentrations of doxorubicin or vincristine but not cisplatin. The increase in MRP mRNA could only be detected 3 to 4 days after the transient exposure to drugs. However, when the parental line, COR-L23/P, was exposed to equitoxic doses of doxorubicin, vincristine or cisplatin, no increase in the levels of MRP mRNA could be observed at higher doses (5- to 10-fold the IC50) of doxorubicin or vincristine (but not of cisplatin), we detected a transient increase in the levels of MDR1 mRNA immediately after short-term exposure. In conclusion, we have shown that a human revertant lung cancer cell line (COR-L23/Rev) has the ability to recover quickly, similar levels of MRP expression and resistance as COR-L23/R after a transient exposure to the MDR-drugs doxorubicin and vincristine.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

An association between precocious puberty and fragile X syndrome?

STUDY OBJECTIVE: To determine the FMR1 gene status in a 10-year, 10-month-old girl with a history of precocious puberty and a family history of fragile X syndrome. DESIGN: Case report. SETTING: The outpatient facility of the Division of Adolescent Medicine and the Division of Genetic and Metabolic Disorders at Children's Hospital of Michigan and the Medical Genetics and Birth Defects Center of Henry Ford Hospital, Detroit, Michigan. PARTICIPANT: A 10-year, 10-month-old girl with a history of precocious puberty. INTERVENTION: Evaluation for menorraghia, DNA extraction, and fragile X gene analysis of blood samples from the patient and her mother. MAIN OUTCOME MEASURES: Identification of a full mutation in the FMR1 gene. RESULTS: Southern blot analysis of the FMR1 gene identified a full mutation in the daughter with approximately 750 repeats of the CGG sequence. Methylation studies showed that the full mutation was completely methylated. FMR1 DNA studies on her mother identified a premutation of approximately 100 repeats. CONCLUSIONS: This report identifies a young girl with a history of precocious puberty and fragile X syndrome. It is also the first report of molecular genetic FMR1 studies in a female with precocious puberty. A possible association between the two conditions is suggested and warrants further investigation.

Blotting, Southern↗

Cranial base tumor visualization through high-performance computing.

Tumors of the skull base in general are considered among the more difficult head and neck pathological entities to treat surgically; some surgeons, in fact, consider lesions in this area inoperable. The most appropriate and safest surgical approach to lesions of the anterior and lateral skull base can be devised only with accurate and precise pre-operative assessment. The literature demonstrates the constant evolution of and search for more efficient less invasive, and safe surgical approaches to this region. With the development of a more exact three-dimensional, interactive anatomical "road map" for each patient's disease and anatomy, the skull base surgeon can not only achieve a more accurate pre-operative assessment leading to a less invasive and less morbid approach, but also can continue to develop and refine new approaches without fear of actual morbidity and mortality. An interdisciplinary team approach, the advent and continued development of faster high performance computers, and the development of new and innovative rendering algorithms can lead to surgical simulation. A prototype of an interactive system has been developed. The system will be iteratively modified through a stepwise evaluation of its clinical usefulness by continually reassessing the system with clinical trials. The current state of the system and the potential benefits are presented.

Brain Mapping↗

The effects of cytokines and growth factors on osteoblastic cells.

In this short review, some regulatory mechanisms that are involved in the control of normal bone formation are proposed, based on several in vivo and in vitro models our group has utilized recently to study osteoblast differentiation and mineralized bone matrix formation. Of course, these proposals must be assessed in the light of the limitations of the models, which probably represent a simplification of the complex and different ways in which normal mammalian bone is formed at different sites. Nevertheless, it is likely that the same general types of control mechanisms are active in each of the different types of bone formation. In adult humans, bone formation predominantly occurs by remodeling, the process by which bone which has recently been resorbed by osteoclasts is replaced by teams of osteoblasts. Other types of bone formation such as endochondral bone formation and appositional bone formation are also important, particularly during growth and adolescence. The end results of each of these processes are the same, namely a complex mineralized proteinaceous bone matrix. These processes are modulated by systemic hormonal influences, which are particularly important with respect to pituitary hormones and sex steroids during growth and adolescence, and by local cellular microenvironmental differences. The former will not be discussed here. Rather, we will concentrate on the local events and factors which are likely involved in the bone formation process occurring during normal bone remodeling.

Adult↗

Communication aids for the speech impaired. Cost and quality-of-life outcomes of assessment programs provided by specialist Communication Aids Centers in the United Kingdom.

An evaluation was conducted of the approaches, costs, and quality-of-life outcomes associated with communication aid assessment programs for the speech-impaired provided by specialist Communication Aids Centres (CACs) in the United Kingdom. The average costs of CAC assessment programs was 410 pounds per client, which is not excessive. There was evidence of moderate quality-of-life benefits from clients' use of the recommended aids.

Adolescent↗

You can tell by the nose--judging sex from an isolated facial feature.

Measurements taken from the nose are among the most important physical variables which discriminate statistically between male and female faces, yet several investigators have claimed that it is difficult to judge sex on the basis of noses presented in isolation. Previous work on the isolated nose has, however, involved the use of frontal views only, which may have obscured important physical differences between the noses of males and females. An investigation of the accuracy of judgments of the sex of isolated noses observed in frontal, profile, and three-quarter views by male and female subjects is reported. Judgment of sex was performed significantly more accurately than chance in all cases except for frontal views of female noses, where judgment was significantly less accurate than chance. Analysis of variance demonstrated a significant interaction of sex of nose and view of nose, such that male noses were identified better in frontal and in profile views, but female noses better in the three-quarter view. It is suggested that one possible reason for the seemingly contradictory role of the nose in previous studies of sex judgment is that all noses look more male in frontal views. For a nose to be perceived as female, its distinctive shape must be made available to the perceiver; this is most likely from the three-quarter view.

Adolescent↗