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Biomedical subjects

P Watson

Publications and source records attributed to P Watson.

At least 109 records · Page 6Linked to original sources
PubMed1998

Hirschsprung disease in MEN 2A: increased spectrum of RET exon 10 genotypes and strong genotype-phenotype correlation.

The RET proto-oncogene encodes a transmembrane receptor with tyrosine kinase activity. Germline mutations in RET are responsible for a number of inherited diseases. These include the dominantly inherited cancer syndromes multiple endocrine neoplasia types 2A and 2B (MEN 2A and MEN 2B) and familial medullary thyroid carcinoma (FMTC), as well as some cases of familial Hirschsprung disease (HSCR1). RET mutations in HSCR1 have been shown to cause a loss of RET function, while the cancer syndromes result in RET oncogenic activation. Occasionally MEN 2A or FMTC occurs in association with HSCR1, albeit with low penetrance. An initial report linked HSCR1 in MEN 2A solely to the C618R and C620R RET mutations. In this study we have analyzed 44 families with MEN 2A. HSCR1 co-segregated with MEN 2A in seven (16%) of the 44 families. The predisposing RET mutation in all seven families had been previously reported in MEN 2A or FMTC and occurred in exon 10 at codons 609, 618 or 620, resulting in C609Y, C618S, C620R or C620W substitution. MEN 2A families with RET exon 10 Cys mutations had a substantially greater risk of developing HSCR1 than those with the more common RET exon 11 Cys634 or exon 14 c804 mutations (P = 0.0005). These findings suggest that expression of HSCR1 in MEN 2A may be peculiar to RET exon 10 Cys mutations . However, HSCR1 in MEN 2A is not exclusive to C618R or C620R RET mutations and can occur with other exon 10 Cys amino acid substitutions. The strong correlation between disease phenotype and position of the MEN 2A RET mutation suggests that oncogenic activation of RET alone is insufficient to account for co-expression of the diseases.

Base Sequence↗
PubMed1998

Managerial partnerships. The wave of the future?

Although managerial partnerships are becoming more common in healthcare organizations, very little is available in the literature regarding a practical, concrete methodology for ensuring success of the relationship. The authors explore the nature of managerial partnerships and the perils and pitfalls of forming these relationships. Experiences from successful and failing partnerships will be used to identify the essential elements of healthy partnerships. Key steps and principles for creating a successful partnership are identified.

Attitude of Health Personnel↗
PubMed1998

A high-resolution microsatellite map of the mouse genome.

The European Collaborative Interspecific Backcross (EUCIB) resource was constructed for the purposes of high-resolution genetic mapping of the mouse genome (). The large Mus spretus/C57BL/6 backcross of 982 progeny has a genetic resolution of 0.3 cM at the 95% confidence level ( approximately 500 kb in the mouse genome). We have used the EUCIB mapping resource to develop a genome-wide high-resolution genetic map incorporating 3368 microsatellites. The microsatellites are distributed among 2302 genetically separated bins with 1.46 markers per bin on average. Average bin separation is 0.61 cM. This high-resolution genetic map will aid the construction of a robust physical map of the mouse genome.

Animals↗
PubMed1998

Somatic hypermutation in autoimmune thyroid disease.

Autoimmune thyroid disease is one of the most common autoimmune diseases. There is typically patient antibody (Ab) reactivity to one or more of the antigens thyroglobulin (Tg), thyroid peroxidase (TPO) and the thyroid simulating hormone receptor (TSHr). With the advent of combinatorial library technology, there has been an enormous increase in the number of sequences from Ab to Tg and TPO. The repertoire of both Tg and TPO Ab is restricted and indicates the importance of somatic hypermutation in the development of the high affinity Ab response. However, there are still too few sequences to determine patterns in which the mutation occurs, which residues are introduced during substitution and how individual substitutions affect the affinity of the Ab. Ab to the TSHr are of far greater pathological significance than those to Tg and TPO, but the current repertoire of Ab to the TSHr has yet to include the high affinity IgG Ab characteristic of patient serum Ab. Instructive analysis of the role of somatic hypermutation in the development of TSHr Ab therefore still awaits the isolation of the pathologically active repertoire. Despite this, the Ab response in thyroid autoimmunity remains one of the best characterised of human autoimmune diseases.

Amino Acid Sequence↗
PubMed1998

The value of the Rivermead Behavioural Memory Test (Children's Version) in an epidemiological study of older adults with Down syndrome.

The Rivermead Behavioural Memory Test for Children (RBMT-C) was used to assess a population-based sample of 74 people with Down syndrome (DS) aged 30 years and over (range 30-65 years) living in the Cambridge health district. Given the high age-specific risk of Alzheimer-like neuropathology in people with DS, the aim of this study was to determine whether this test provided a suitable measure of memory function in an older population of adults with DS who were at the age of risk for Alzheimer's disease. We also investigated whether there was a significant difference in everyday memory performance between different age, gender and day-centre groups. The level of learning disability in our sample ranged from mild, through severe to profound. Individuals with severe or profound learning disability were virtually untestable on this and other cognitive tests, but for the remaining two-thirds of the group, the RBMT-C could be used to assess memory function. Significant differences in memory function were found between younger (30-44 years) and older (45+ years) participants. Performance also varied between groups (e.g. from different day centres), illustrating the importance of population-based samples when determining the value of such tests. Ongoing longitudinal studies are required to establish the extent to which the RBMT-C is useful in assessing change in retrospective and prospective memory.

Adult↗
PubMed1998

Blood cultures positive for coagulase-negative staphylococci: antisepsis, pseudobacteremia, and therapy of patients.

A blood culture cohort study investigating issues related to isolation of coagulase-negative staphylococci (CoNS) and other skin microflora is reported. Data were collected over 12 weeks to determine the incidence of significant CoNS bacteremia versus that of pseudobacteremia (contaminants) and to evaluate drug therapy in patients with cultures positive for CoNS. In addition, the effectiveness of 0.2% chlorine peroxide as a bactericidal disinfectant was compared to that of 10% providone iodine. A total of 3,276 cultures of blood from 1,433 patients were evaluated in the study. Eighty-nine cultures were positive for skin flora, with 81 of 89 (91%) involving CoNS. The incidence of significant CoNS bacteremia was 20 of 81 (24.7%), that of indeterminate bacteremia was 10 of 81 (12.3%), and that of contamination was 59 of 81 (72.8%). The incidence of significant bacteremia involving CoNS was double the 10 to 12% rate based on previous estimations at our institutions. In tests with the two bactericidal disinfectants, 22 of 1,639 cultures (1.3%) in the chlorine peroxide group versus 37 of 1,637 (2.3%) in the providone iodine group were considered contaminated (P = 0.065). Rates of contamination for venipuncture versus catheter collection were not significantly different (P = 0.46). The overall contamination rate was 59 of 3,276 (1.8%), which is consistent with the lower end of published quality assurance benchmark standards. The low rate was believed to be due to the professional phlebotomy staff in our institutions. There was excellent agreement between retrospective analysis by reviewers, when formal criteria were used, and the attending physicians' intuitive clinical impressions in the classification of significant bloodstream infections (100% agreement) or contamination (95% agreement). However, physicians still used antimicrobial agents to treat nearly one-half of the patients with contaminated blood cultures, with vancomycin being misused in 34% of patients. In addition, 10% of patients with significant bacteremia were treated with inappropriate agents. There were no significant adverse events or prolonged hospital stays due to the unnecessary use of vancomycin; however, the additional costs of treating patients whose cultures contained CoNS contaminants was estimated to be $1,000 per patient. Measures to limit the unnecessary use of vancomycin (and other agents) are important.

Adult↗
PubMed1998

Catching goldfish: quality in qualitative research.

This paper reviews the contribution of qualitative methods to health services research (HSR) and discusses some of the issues involved in recognizing quality in such work. The place of qualitative work is first defined by reference to Archie Cochrane's agenda for HSR and the limitations of the recent focus on randomized trials as the standard method. Health care practice involves large elements of improvisation which cannot be captured by evidence-based approaches. Qualitative methods offer ways of understanding this improvisation and of identifying more efficient and effective practices, as well as considering the traditional topics of equity and humanity. The methodological procedures of qualitative work reflect a long-established inductive tradition in scientific practice. The logic of grounded theory provides a contemporary specification. In its application, it is quite different from the methodological anarchy of postmodernism. The use of qualitative research and the theoretically stated generalizations which arise from it inform reflective work by health service managers, planners and clinicians.

Evidence-Based Medicine↗
PubMed1998

Population-based study of the prevalence and presentation of dementia in adults with Down's syndrome.

BACKGROUND: The reported prevalence rates of dementia in people with Down's syndrome have varied considerably across studies. The aim of this study was to investigate the extent of clinical change with age using an established diagnostic instrument in an unbiased, population-based sample of older people with Down's syndrome. METHOD: Changes in memory, personality, general mental functioning and daily living skills were assessed using a modified version of the informant interview of the Cambridge Examination for Mental Disorders of the Elderly (CAMDEX). RESULTS: Age-specific prevalence rates of dementia varied according to the diagnostic criteria used. Using CAMDEX criteria for Alzheimer's disease, prevalence rates increased from 3.4 to 10.3 to 40% in the 30-39, 40-49 and 50-59 age group, respectively. CONCLUSIONS: Overall, the age-related pattern of presentation and dementia diagnoses differs from that seen in the general elderly population. However, age-specific prevalence rates of Alzheimer's disease were similar but 30-40 years earlier in life.

Adult↗
PubMed1997

A descriptive study of BRCA1 testing and reactions to disclosure of test results.

BACKGROUND: The identification of the BRCA1 gene is a powerful tool for predicting a patient's lifetime risk for carcinoma of the breast and ovary when she has hereditary breast/ovarian carcinoma (HBOC) syndrome. The process of BRCA1 testing and genetic counseling and participants' reactions to test results, are described. METHODS: Education about the natural history of HBOC syndrome and the pros and cons of genetic testing was provided to 14 HBOC families comprised of 2549 bloodline relatives. Of these, 388 underwent DNA testing. After informed consent was given by participants, formal linkage analysis and gene mutation studies were performed on the families. Qualitative data on intentions and emotional reactions were collected by physicians/counselors during the genetic counseling sessions. RESULTS: Of those tested, 181 received their results after further genetic counseling. Seventy-eight of them were positive and 100 were negative for BRCA1 gene mutation. Three had ambiguous findings. The most common reasons given for seeking DNA testing were concern about risk to children and concern about surveillance and prevention. Prophylactic mastectomy was considered by 35% of women who tested positive, whereas prophylactic oophorectomy was considered an important option by 76%. Twenty-five percent of both BRCA1 positive and negative individuals were concerned about discrimination by insurance companies. Eighty percent of those who tested negative reported emotional relief, whereas over one-third of those who tested positive reported sadness, anger, or guilt. CONCLUSIONS: DNA testing of patients with HBOC syndrome must be performed in the context of genetic counseling. The authors' results demonstrate the many complex clinical and nonclinical issues that are important in this process.

Adult↗
PubMed1997

A comparison of two pertussis epidemics in Auckland.

AIM: To determine if the addition of the 6 week dose of pertussis vaccine in 1984 was associated with any change in the hospitalisation rate for children with pertussis and the higher hospitalisation rates for Maori and Pacific Islander children with pertussis. METHODS DESIGN: Population based study of pertussis hospitalisations using a retrospective chart review of hospitalisation data for children during the 1991 epidemic, which was compared to previously published data from the 1982 epidemic. SETTING: Princess Mary and Middlemore hospitals, Auckland. SUBJECTS: Children aged 0-14 years resident in metropolitan Auckland and hospitalised in Auckland during 1982 or 1991 with pertussis. MEASUREMENTS: Hospitalisation rates were calculated as number of children with a discharge diagnosis of pertussis per 1000 children aged 0-14 years based on 1981 and 1991 census data. 1982 data were converted to person-years as published report was for an 8 month period. Hospitalisation rates were compared as a relative risk (RR) of hospitalisation in 1991 versus 1982. RESULTS: There were 84 cases during 8 months in 1982 and 66 cases in 1991. Rates of hospitalisation by ethnic group; in 1982 were 0.24 Other/European (OE), 1.98 Maori (M), 1.37 Pacific Islander (PI); and in 1991 were 0.22 OE, 0.51 M, 0.40 PI. Compared to 1982 the relative risk of hospitalisation in 1991 adjusted for ethnicity was 0.43 (CI 0.33, 0.58, p < 0.0001). Compared to 1982 there was a significant reduction in the hospitalisation rate in 1991 for M (RR = 0.26, CI 0.16, 0.43, p < 0.0001); and PI children (RR = 0.29, CI 0.16, 0.54, p < 0.0001); but not for OE children (RR = 0.91, 95% CI 0.57, 1.46, p = 0.70). CONCLUSIONS: There was a significant reduction in the rate of hospitalisation for pertussis in 1991 compared to 1982. This reduction in hospitalisation rate was due to a reduction in rates for Maori and Pacific Islander children.

Adolescent↗
PubMed1997

Information needs and decisional preferences in women with breast cancer.

OBJECTIVE: To determine the degree of involvement women with breast cancer wanted in medical decision making, extent to which they believed they had achieved their preferred level of involvement, and types of information they judged to be most important. DESIGN AND SETTING: Cross-sectional survey at 2 tertiary oncology referral clinics and 2 community hospital oncology clinics in Winnipeg, Manitoba. PATIENTS: Consecutive sample of 1012 women with a confirmed diagnosis of breast cancer who were scheduled for a visit at 1 of 4 hospital oncology clinics. MAIN OUTCOME MEASURES: The following measures were used: (1) Preferences about various levels of participation in treatment decision making; (2) the extent to which subjects believed they had achieved their preferred levels of involvement in decision making; and (3) priority needs for information and how these needs differed by selected sociodemographic, disease, and treatment variables. RESULTS: A total of 22% of women wanted to select their own cancer treatment, 44% wanted to select their treatment collaboratively with their physicians, and 34% wanted to delegate this responsibility to their physicians. Only 42% of women believed they had achieved their preferred level of control in decision making. The 2 most highly ranked types of information were related to knowing about chances of cure and spread of disease. Women younger than 50 years rated information about physical and sexual attractiveness as more important than did older women (P<.001); women older than 70 years rated information about self-care as more important than did younger women (P=.002); and women who had a positive family history of breast cancer rated information about family risk as more important than did other women (P=.03). CONCLUSIONS: The substantial discrepancy between women's preferred and attained levels of involvement in treatment decision making suggests that systematic approaches to assess and respond to women's desired level of participation in treatment decision making need to be evaluated. Priorities for information identified in this study provide an empirical basis to guide communication with women seeking care for breast cancer.

Adult↗
PubMed1997

The additive intraocular pressure-lowering effect of latanoprost in combined therapy with other ocular hypotensive agents.

Latanoprost, a prostaglandin F2 alpha analogue prodrug, has been shown to be an effective ocular hypotensive agent when used alone on ocular hypertensive or open angle glaucoma patients. In various studies, the ocular hypotensive effects of latanoprost have also been evaluated when used in addition to, or in combination with, other ocular hypotensive agents. Latanoprost produces an additional reduction of intraocular pressure (IOP) when used in combination with timolol, pilocarpine, acetazolamide and dipivefrin. These represent four different classes of glaucoma drugs-beta-adrenergic antagonists, cholinergic agonists, carbonic anhydrase inhibitors, and adrenergic agonists-all of which reduce the IOP by different mechanisms (reduction of aqueous humor production, increased outflow facility, or by a mixed effect on aqueous humor dynamics). All the available evidence shows that latanoprost produces a clinically significant additive ocular hypotensive effect when used in combination with any currently available ocular hypotensive agent.

Acetazolamide↗