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Biomedical subjects

P Watson

Publications and source records attributed to P Watson.

At least 73 records · Page 4Linked to original sources
PubMed2000

Pathways to abstinence: two-year follow-up data on 60 abstinent former opiate addicts who had been turned away from treatment.

Structural changes in the organization of drug treatment services in the northwest of England during the early 80s provided a unique opportunity to study a group of opiate addicts who were turned away from treatment. This paper reports on 60 opiate addicts who were abstinent at follow-up (2-3 years after their original referral). For the majority of subjects, any treatment received in the intervening period had been from a range of local, non-specialist treatment providers, including: general practices (n = 24) and local hospitals (n = 32). The subjects had also received assistance from non-statutory agencies (n = 35). Informal sources of support were drawn upon in the form of friends, family, and voluntary agencies. Social acceptance, legal problems, financial difficulties, and imprisonment were frequently cited as motivational factors that led to abstinence. At follow-up, improvements were reported in personal relationships and family circumstances, although there was less progress in relation to employment, finances, and housing. Increased involvement with the criminal justice system was significantly associated with a greater use of treatment services at follow-up. This paper presents the treatment and non-treatment pathways that led to abstinence amongst this group of opiate addicts. It also points to the importance of including non-treatment samples in evaluations of treatment interventions.

Adolescent↗
PubMed2000

Reliability of a measure of post-stroke shoulder pain in patients with and without aphasia and/or unilateral spatial neglect.

OBJECTIVE: To determine the inter/intra-rater reliability of expert physiotherapists (PTs) measuring post-stroke shoulder pain with 100 mm vertical visual analogue scales (VAS; intensity, frequency and affective response) and a categorical site-of-pain scale. DESIGN: Three PTs independently rated subjects (normal clinical procedure but with a standardized starting position) on three days, at the same time of day, during one week in a randomized order determined by a nested latin square. Reliability for VAS scores was determined with the intraclass correlation coefficient (ICC) and for site-of-pain with the kappa statistic (kappa). Acceptable reliability was set at 0.75. The limits of agreement were also calculated. SETTING: Community. SUBJECTS: Thirty-three patients, mean time post stroke 42 months (range 7-360). RESULTS: Mean inter-rater reliability was 0.79 for intensity, 0.75 for frequency and 0.62 for affective response (ICC). The limits of agreement were wide and rater bias was significant for 6/27 ratings. Mean intra-rater reliability was 0.70 for intensity, 0.77 for frequency and 0.69 for affective response (ICC). For site-of-pain inter-rater reliability ranged from 0.156 (kappa) to 0.385 (kappa) and intrarater reliability ranged from 0.300 (kappa) to 0.559 (kappa). CONCLUSIONS: Although inter-rater reliability was acceptable for intensity and frequency there was a consistently large systematic bias between pairs of raters. Agreement might be improved if a standardized assessment procedure was used and/or if training in pain behaviour interpretation was provided.

Aged↗
PubMed2000

Adapting the Rivermead Behavioural Memory Test Extended Version (RBMT-E) for people with restricted mobility.

OBJECTIVES: The study aimed to facilitate use of the RBMT-E with people who have impaired mobility by devising substitute tasks for the route and message subtests that do not require the individual to move around, and by presenting normative data for these substitute tasks. DESIGN: A within-subjects design was used to assess a standardization sample. Participants completed two parallel versions of the tasks in counter-balanced order in two test sessions approximately 1 week apart. METHODS: Substitute versions of the route and message subtests not requiring the individual to move around the test room were devised using commercially available materials. These were administered to participants along with other RBMT-E subtests. Scores for each version were compared for the group as a whole and for subgroups divided according to age, gender and IQ. Based on the results, profile scores were derived for each task using box plot analysis. The participants (N = 111) were part of the standardization sample for the RBMT-E and comprised consecutive series of recruits in two centres, Cambridge (UK) and Sydney (Australia). RESULTS: Normative data are presented in the form of mean scores for the group as a whole, for men and women, for people aged under 30, 30 to 50, and over 50 years, and for people with an IQ of either 90-110 or over 110. Profile score transformations for the substitute tasks are provided. CONCLUSIONS: Where mobility problems preclude the use of the route and message subtests of the RBMT-E, the 'model' tasks described here can be substituted and profile scores calculated. This allows clinicians to obtain a full spectrum of subtest scores for the RBMT-E with mobility-impaired patients, thus allowing the calculation of a total profile score.

Adolescent↗
PubMed2000

Normal emmetropization in infants with spectacle correction for hyperopia.

PURPOSE: The development of emmetropic refraction is known to be under visual control. Does partial spectacle correction of infants' refractive errors, which has been shown to have beneficial effects in reducing strabismus and amblyopia, impede emmetropization? The purpose of the present study was to perform the first longitudinal controlled trial to investigate this question in human subjects. METHODS: Children identified as having significant hyperopia in a population screening program at age 8 to 9 months were assigned to treated (partial spectacle correction) or untreated groups. A control group of infants with no significant refractive errors at screening was also recruited. Measurements of retinoscopic refraction under cycloplegia were taken at 4- to 6-month intervals up to the age of 36 months, and changes in refraction of 148 subjects were analyzed longitudinally. RESULTS: Refractive error decreased toward low hyperopic values between 9 and 36 months in both hyperopic groups. By 36 months, this reduction of hyperopia showed no overall difference between children who were treated with partial spectacle correction and those who were not. Despite the improvement, both hyperopic groups' mean refractive error at 36 months remained higher than that of the control group. When infants in all three groups were considered together, the rate of reduction of refractive error was, on average, a linear function of the initial level of hyperopia. CONCLUSIONS: The benefits of spectacle correction for infants with hyperopia can be achieved without impairing the normal developmental regulation of refraction.

Accommodation, Ocular↗
PubMed1999

Clinical impact of molecular genetic diagnosis, genetic counseling, and management of hereditary cancer. Part I: Studies of cancer in families.

Hereditary cancer represents approximately 5-10% of the total cancer burden and may account for 60,000 to 120,000 new cancer occurrences this year in the United States. New developments in molecular genetics and the cloning of cancer-prone genes have intensely fueled interest in dealing with hereditary forms of cancer. The authors provide an algorithm that depicts the process for the identification, study, and DNA-based genetic counseling of families being investigated under a research proposal at the Hereditary Cancer Institute of Creighton University School of Medicine. They have studied 56 hereditary nonpolyposis colorectal carcinoma families; in 18 of them, associated genomic mutations have been identified in affected members. DNA-based genetic counseling has been provided for seven of these families. The authors have also evaluated 131 hereditary breast-ovarian carcinoma families. BRCA1 and BRCA2 mutation searches have been performed for 76 of these families; BRCA1 mutations were found in 38 families and BRCA2 mutations in 9. The study of cancer-prone families is a powerful approach to cancer control, particularly when the germ-line mutation is identified in the family and individuals at high risk can be tested, once they provide informed consent, and receive DNA-based genetic counseling. Discovery of the germ-line mutation for cancer proneness provides an unparalleled opportunity to predict patients' life-time risk for cancer of specific anatomic sites, inclusive of a pattern of multiple primaries. Surveillance and management protocols, when melded to the particular syndrome's natural history, can be life-saving.

Clinical Protocols↗
PubMed1999

Clinical impact of molecular genetic diagnosis, genetic counseling, and management of hereditary cancer. Part II: Hereditary nonpolyposis colorectal carcinoma as a model.

Hereditary nonpolyposis colorectal carcinoma (HNPCC) is the most common hereditary form of colorectal carcinoma (CRC) and may account for 5-10% of the total CRC burden. The discovery of DNA mismatch repair (MMR) genes, inclusive of hMSH2, hMLH1, hPMS2, and hMSH6, has enabled the identification of who has and who does not have inordinately increased susceptibility to CRC as well as a litany of extracolonic cancers. Mutation testing has focused on hMSH2 and hMLH1, the most common mutations in HNPCC. The protocol for DNA testing and DNA-based genetic counseling is described in Part I of this study. One hundred ninety-nine bloodline relatives were tested and counseled from five hMLH1 and two hMSH2 families. Their major reason for seeking genetic counseling and DNA testing was to inform their children and other loved ones of their mutation status. Those who sought counseling overestimated their risk for inheriting the mutation and showed a high rate of interest in prophylactic surgery, and many were greatly concerned about insurance discrimination. Knowledge about HNPCC, its molecular genetic diagnosis, surveillance and management opportunities, and genetic counseling implications are still emerging, all in the face of a greater need for physician education regarding all facets of hereditary cancer.

Adaptor Proteins, Signal Transducing↗
PubMed1999

Suppression of ING1 expression in sporadic breast cancer.

Down regulation of the ING1 candidate tumour suppressor promotes growth in soft agar and focus formation in vitro and tumour formation in vivo. ING1 encodes a nuclear, cell cycle-regulated protein, overexpression of which efficiently blocks cell growth and is capable of inducing apoptosis in different experimental systems. Here we present the first report of ING1 mutation and expression analysis in a total of 452 cancer samples. One germline missense alteration and three germline silent alterations were detected in 377 primary breast cancers while marked (2 - 10-fold) decreases in ING1 mRNA expression were seen in 44% of primary breast cancers and in ten of ten breast cancer cell lines examined. Furthermore, the majority of breast cancers (58%) showing decreased ING1 expression had metastasized to regional lymph nodes whereas only 9% of cancers with elevated ING1 expression, compared to adjacent normal tissues, were metastatic. Thus, ING1 mutation is very rare in breast or ovarian cancers, however, repression of ING1 expression frequently accompanies tumour development of breast cancer.

Adult↗
PubMed1999

Breast cancer risk after bilateral prophylactic oophorectomy in BRCA1 mutation carriers.

BACKGROUND: The availability of genetic testing for inherited mutations in the BRCA1 gene provides potentially valuable information to women at high risk of breast or ovarian cancer; however, carriers of BRCA1 mutations have few clinical management options to reduce their cancer risk. Decreases in ovarian hormone exposure following bilateral prophylactic oophorectomy (i.e., surgical removal of the ovaries) may alter cancer risk in BRCA1 mutation carriers. This study was undertaken to evaluate whether bilateral prophylactic oophorectomy is associated with a reduction in breast cancer risk in BRCA1 mutation carriers. METHODS: We studied a cohort of women with disease-associated germline BRCA1 mutations who were assembled from five North American centers. Surgery subjects (n = 43) included women with BRCA1 mutations who underwent bilateral prophylactic oophorectomy but had no history of breast or ovarian cancer and had not had a prophylactic mastectomy. Control subjects included women with BRCA1 mutations who had no history of oophorectomy and no history of breast or ovarian cancer (n = 79). Control subjects were matched to the surgery subjects according to center and year of birth. RESULTS: We found a statistically significant reduction in breast cancer risk after bilateral prophylactic oophorectomy, with an adjusted hazard ratio (HR) of 0.53 (95% confidence interval [CI] = 0.33-0.84). This risk reduction was even greater in women who were followed 5-10 (HR = 0. 28; 95% CI = 0.08-0.94) or at least 10 (HR = 0.33; 95% CI = 0.12-0.91) years after surgery. Use of hormone replacement therapy did not negate the reduction in breast cancer risk after surgery. CONCLUSIONS: Bilateral prophylactic oophorectomy is associated with a reduced breast cancer risk in women who carry a BRCA1 mutation. The likely mechanism is reduction of ovarian hormone exposure. These findings have implications for the management of breast cancer risk in women who carry BRCA1 mutations.

Age Factors↗
PubMed1999

Microsatellite instability and expression of MLH1 and MSH2 in normal and malignant endometrial and ovarian epithelium in hereditary nonpolyposis colorectal cancer family members.

Mismatch repair deficiency is a characteristic molecular finding in hereditary nonpolyposis colorectal cancer (HNPCC), and has been demonstrated in both colorectal cancers and benign adenomas. Endometrial and ovarian cancers are common extracolonic tumors in this syndrome; however, few studies have investigated whether genetic changes occur in histologically normal endometrial and ovarian epithelia from HNPCC family members. If early genetic changes exist, they might be used as molecular markers to detect susceptibility to endometrial and ovarian cancers. In this study, we analyzed microsatellite instability (MSI) and MLH1 and MSH2 immunohistochemical expression in 20 histologically normal epithelia (12 endometrial and 8 ovarian) and 8 cancers (4 endometrial and 4 ovarian) obtained from 20 individuals representing 7 unrelated HNPCC families. While MSI was observed in endometrial (75%) and ovarian (100%) cancers, no case was determined to exhibit MSI in histologically normal epithelia of the endometrium or ovary. Similarly, in immunohistochemical expressions for MLH1 and MSH2, histologically normal epithelia had no genetic changes predisposing to malignancy. In cancer cases, a correlation existed between the expression of MLH1 and MSH2, the presence of germline mutations in the hMLH1 and hMSH2 genes, and the presence of tumor MSI. These data suggest that MSI and MLH1 and MSH2 expression are not useful biomarkers for the early detection of endometrial and ovarian malignancy in cancer-unaffected HNPCC germline mutation carriers. Further studies of other genetic changes in normal and premalignant precursor lesions are needed.

Adaptor Proteins, Signal Transducing↗
PubMed1999

Refined mapping of the region of loss of heterozygosity on the long arm of chromosome 7 in human breast cancer defines the location of a second tumor suppressor gene at 7q22 in the region of the CUTL1 gene.

In breast cancer, loss of heterozygosity (LOH) has been described on the long arm of chromosome 7, at band q31, suggesting the presence of a tumor suppressor gene in this region. In this study, we have identified a second region of LOH on 7q, at band 7q22. Deletion of genetic material at 7q22 was found in all tumor types and grades and was associated with increased tumor size. The region of LOH at 7q22 in every case included one or more of three polymorphic markers that are located within the CUTL1 gene. LOH of 7q22 has also been documented in the case of human uterine leiomyomas (Zeng et al., 1997; Ishwad et al., 1997). Interestingly, in both leiomyomas and mammary tumors induced in transgenic mice expressing the Polyomavirus (PyV) large T (LT) antigen, immunocomplexes of CUTL1 and PyV LT antigen were detected (Webster et al., 1998). Altogether, genetic data in human breast cancer and biochemical analyses in breast tumors from transgenic mice suggest that CUTL1 is a candidate tumor suppressor gene.

Breast Neoplasms↗
PubMed1999

Sips, Sops, and SPIs but not stn influence Salmonella enteropathogenesis.

The virulence factors influencing Salmonella-induced enteropathogenesis remain poorly characterised. The interactions of different serotypes of Salmonella with bovine ileal mucosa have been characterised in the ligated ileal loop model. In a quantitative intestinal invasion assay Salmonella dublin, S. choleraesuis, S. gallinarum, and S. abortusovis strains were all recovered from ileal mucosa, either with or without Peyer's patches in similar numbers. This observation suggests that the magnitude and route of intestinal invasion does not mediate Salmonella serotype host specificity. Despite being equally invasive there was a clear hierarchy in the enteropathogenicity of these serotypes. The magnitude of the enteropathogenic responses did not correlate to serotype host specificity. These observations implicate undefined serotype specific factors in influencing enteropathogenicity independently of intestinal invasion. Disruption of genes in Salmonella Pathogenicity Island (SPI) 1 of S. typhimurium and S. dublin blocked the secretion of Salmonella Invasion Proteins (Sips) and Salmonella Outer Proteins (Sops). These mutants were significantly less invasive and enteropathogenic then the wild type strain in ligated ileal loops. Disruption of sopB and sopD significantly reduced enteropathogenesis, but without influencing intestinal invasion. These two genes appear to act in concert. Surprisingly, disruption of stn, the Salmonella enterotoxin gene cloned on the basis of its homology to cholera toxin, did not influence enteropathogenesis. SopB was mapped to the 20 centisome of S. typhimurium and is flanked by 5 genes that are organised in a manner typical of a pathogenicity island, which we have termed SPI-5. Mutation of the other genes in SPI-5 also attenuated enteropathogenesis but not virulence for mice, suggesting SPI-5 is a key locus specifically influencing Salmonella enteropathogenesis.

Animals↗
PubMed1999

Colorectal cancer in hereditary breast cancer kindreds.

PURPOSE: This study compared characteristics of colorectal cancer between families with dominant breast cancer inheritance and the general population. The cumulative incidence of colorectal cancer was also studied in genetically determined breast cancer syndrome subjects with BRCA1 and BRCA2 mutations and compared with the general population. METHODS: Subjects included 42 patients with colorectal cancer from 32 clinically determined hereditary breast cancer kindreds based on the autosomal dominant inheritance of breast cancers and early age of onset. The general population colorectal cancer cohort was composed of 755 patients from a tumor registry. Lifetime risk of colorectal cancer was determined in 164 BRCA1 and 88 BRCA2 gene mutation carriers and compared with the general population. Mean age of colorectal cancer onset, anatomic site distribution, histologic stage at presentation, and five year stage-stratified survival rates were compared between clinically determined hereditary breast cancer family members and the general population. RESULTS: The lifetime risk of colorectal cancer in male BRCA1 and BRCA2 mutation carriers was 5.6 percent, which was not different from 6 percent in males from the general population. Likewise, the lifetime colorectal cancer risk in female BRCA1 and BRCA2 mutation carriers was 3.2 percent, which was not different from 5.9 percent in females from the general population. Mean age of onset +/- standard error for patients with colorectal cancer was 60 +/- 2 years for hereditary breast cancer kindreds compared with 67 +/- 0.4 years for the general population (P = 0.0004). Colorectal cancer site distribution did not vary between hereditary breast cancer and the general population. Overall colorectal cancer stage distribution was significantly different, with more Stage I and fewer Stage IV cancers in subjects with hereditary breast cancer compared with the general population (P = 0.01). Overall five year stage-stratified colorectal cancer survival rate +/- standard error was 66 +/- 8 percent for hereditary breast cancer kindreds and 46 +/- 2 percent for the general population (P = 0.023). CONCLUSION: Lifetime cumulative colorectal cancer incidence in subjects with BRCA1 and BRCA2 gene mutations was not different from the general population. However, significant differences in colorectal cancer were noted between hereditary breast cancer family members and the general population. Hereditary breast cancer-associated colorectal cancer had an earlier age of onset, lower tumor stage, and better survival rate than the general population. Except for age of onset, colorectal cancer in hereditary breast cancer kindreds exhibited more favorable characteristics than colorectal cancer in the general population.

Adult↗
PubMed1999

NCL-CD10-270: a new monoclonal antibody recognizing CD10 in paraffin-embedded tissue.

CD10 (CALLA) antigen is expressed in a wide variety of epithelial and nonepithelial tissues, but its most significant application is in the diagnosis and classification of certain types of malignant lymphoma and leukemia. CD10 is expressed in a high percentage of cases of acute lymphoblastic leukemia (ALL), follicular lymphoma, Burkitt's lymphoma, and some hematopoietic tumors. Although the antigen is not lineage specific, CD10 expression is widely used to define subgroups within B-ALL and is a useful tool for detecting the presence of leukemic blasts in the bloodstream. Currently available monoclonal antibodies to CD10 have been found to be effective only in fresh-frozen tissue and for techniques such as flow cytometry. We have used a recombinant protein corresponding to the whole of CD10 to generate a monoclonal antibody that is effective in paraffin-embedded tissue sections. We have used this antibody to assay for the presence of CD10 on a range of normal and pathological tissues. Strong staining was seen in lymphoid germinal centers, renal tubules, glomeruli, syncytiotrophoblast, hepatic parenchymal canaliculi, B-lineage ALL, follicle center cell lymphoma, and a proportion of cases of large-B-cell lymphoma. We believe that this antibody will be of value in the characterization of malignant lymphoma, in particular the differential diagnosis of small-B-cell lymphoma and subtyping of lymphoblastic leukemia, as well as the investigation of the significance of expression of CD10 in other normal and pathological tissues.

Animals↗
PubMed1999

Are long hours and hard work detrimental to end-clerkship examination scores?

BACKGROUND: Third-year medical students' complaints focus on the number of hours worked and subsequent lack of study time among three general surgery blocks. We hypothesize that this difference between the surgical blocks does not adversely influence student examination scores. METHODS: Student scores for the academic years 1996-97 to 1997-98 for the National Board of Medical Examiners (NBME) surgery subtests were compiled. A comparison of two "slow" general surgery blocks (B/C) with one "busy" block (A) was made using a two-tailed t test. A multiple regression analysis was also employed. Finally, United States Medical Licensing Examination (USMLE) part I scores were used to determine equivalency of groups. RESULTS: No significant difference existed between block A and blocks B/C in USMLE part I and NBME (P = 0.35 and 0.16 respectively). However, USMLE and rotation sequence influenced NBME scores (P < 0.001). CONCLUSION: The data suggest that no difference exists in examination scores between students assigned to a busy general surgery block versus those students assigned to slow blocks.

Clinical Clerkship↗
PubMed1999

An update on DNA-based BRCA1/BRCA2 genetic counseling in hereditary breast cancer.

The identification of BRCA1 and BRCA2 mutations has enabled physicians to identify persons at high risk for carcinoma of the breast and ovary in hereditary breast-ovarian cancer (HBOC) families. Many physicians have limited knowledge about the effective translation of these new discoveries into clinical practice settings. This problem is further confounded by the limited number of genetic counselors who have experience with cancer genetics. Genetic counseling about DNA test results was provided to 420 patients from 37 HBC/HBOC families. Descriptive data were collected and recorded about their responses to questions posed immediately before and after test results were disclosed. Findings disclosed a significant tendency of patients to overestimate rather than underestimate their risk (P < .001) prior to receiving results. The chief reason for declining to receive results was fear of insurance discrimination. The primary reason that patients sought test results was for their children. Most women reported that, if testing identified them as mutation carriers, they would consider lifetime surveillance and prophylactic surgery. Responses to DNA test results were varied and often unpredictable. Counseling by an appropriately educated and skilled professional is essential to assist people in making decisions regarding testing and health management.

Adult↗