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Biomedical subjects

P Watson

Publications and source records attributed to P Watson.

At least 145 records · Page 8Linked to original sources
PubMed1996

Analysis of mismatch repair genes in hereditary non-polyposis colorectal cancer patients.

Hereditary non-polyposis colorectal cancer (HNPCC) is an autosomal dominant disorder characterized by the early onset of colorectal cancer and linked to germline defects in at least four mismatch repair genes. Although much has been learned about the molecular pathogenesis of this disease, questions related to effective presymptomatic diagnosis are largely unanswered because of its genetic complexity. In this study, we evaluated tumors from 74 HNPCC kindreds for genomic instability characteristic of a mismatch repair deficiency and found such instability in 92% of the kindreds. The entire coding regions of the five known human mismatch repair genes were evaluated in 48 kindreds with instability, and mutations were identified in 70%. This study demonstrates that a combination of techniques can be used to genetically diagnose tumor susceptibility in the majority of HNPCC kindreds and lays the foundation for genetic testing of this relatively common disease.

Base Sequence↗
PubMed1996

Association of HLA-DQA1*0501 with Graves' disease in English Caucasian men and women.

OBJECTIVE: A recent report has demonstrated a stronger association between the HLA-DQA1*0501 allele and Graves' disease in Caucasian men than in women. Our aim was to confirm this association in a larger series of male Caucasian patients. DESIGN: Polymerase chain reaction/sequence specific oligonucleotide probing (PCR/SSOP). PATIENTS: Fifty men and 70 women with Graves' disease were studied as well as a control group consisting of 57 healthy, unrelated men and women. METHODS: Genomic DNA was derived from venous blood samples. Appropriately primed DNA was amplified by PCR and the products were subjected to SSOP. The presence of the allele was demonstrated by enhanced chemiluminescence. RESULTS: A significant association between HLA-DQA1*0501 and Graves' disease was demonstrated among both the men and women as well as in the combined disease cohort, with HLA-DQA1*0501 conferring a greater relative risk than HLA-DR3 in all three groups. This association persisted when the results from the DR3-negative Graves' patients were analysed in isolation. HLA-DQA1*0501 was heterogeneously distributed between the sexes with significantly more female Graves' patients carrying this allele. CONCLUSIONS: There is a significant association between HLA-DQA1*0501 and Graves' disease which may be unrelated to the inheritance of this allele on an extended haplotype with HLA-DR3. In contrast to a recent report, HLA-DQA1*0501 was significantly more prevalent among women with Graves' disease than men.

Alleles↗
PubMed1996

AIDS in Côte d'Ivoire--ten years on.

AIDS is a world-wide health problem with a profile which varies widely. Côte d'Ivoire is one of the hardest hit countries in Africa. Since the declaration of the first cases in 1985, more than 18 600 cases have been diagnosed. Many initiatives have already been undertaken in the context of the government's National Programme Against AIDS, as well as by private institutions and individuals. However, much remains to be done, against heavy odds. Hôpital Protestant de Dabou (HPD) is one of the four major centres dealing with AIDS, and has itself declared more than 3000 cases since 1987. Since 1991 it has had a team dedicated to dealing with the multiple needs of people infected with HIV and their families, and more than 2000 patients have benefited from this support. This paper reports on the experience of this programme and draws lessons for the future.

Acquired Immunodeficiency Syndrome↗
PubMed1996

Response of childhood malaria to chloroquine and Fansidar in an area of intermediate chloroquine resistance in Côte d'Ivoire.

The parasitological, clinical and haematological responses to chloroquine treatment were studied in children during a 28-day follow-up in an area of Côte d'Ivoire with intermediate chloroquine resistance. The parasitological, clinical and haematological responses to Fansidar were also investigated in patients who returned to the health centre within 28 days with symptoms of malaria. Of 82 children aged 0-9 years who completed the study, only 67% were parasite-negative on thick blood film on day 7, which decreased to 21% by day 28. While chloroquine treatment still produced clinical remission at day 7 in 95% of the children, 35% had recurrent fever with concomitant parasitaemia before day 28. All fever cases subsequently treated with Fansidar remained parasite-negative over a period of 28 days. On day 28 the haematocrit levels were higher in those children who responded successfully to treatment with either chloroquine or Fansidar than in the children who were still parasite-positive but without fever (two-tailed t-test, P = 0.02). The rate of resistance to chloroquine was most pronounced among the younger children (< 5 years), 18% of whom showed clinical failure by day 14. This study underlines the importance of monitoring the durability of response to chloroquine treatment for at least 14 days in young children in Côte d'Ivoire.

Animals↗
PubMed1996

Musculoskeletal disorders: genitourinary medicine perspective.

The association of musculoskeletal disorders and genitourinary symptoms is reviewed. Reactive arthritis, Sjögren's syndrome and rheumatoid arthritis can present with a variety of genitourinary symptoms. Similarly sexually transmitted diseases including gonorrhoea, syphilis, HIV and other viral infections can affect the musculoskeletal system. Reiter's syndrome may be a consequence of a sexually transmitted infection although its presentation can suggest that also in post-dysenteric cases. The fact that conditions may present to various medical specialties requires doctors outside departments of GUM to allow their patients an opportunity and the time to discuss sexual matters.

Arthritis, Reactive↗
PubMed1996

Triple primer polymerase chain reaction. A new way to quantify truncated mRNA expression.

The most practical method to quantify mRNA expression within small tumor samples is reverse transcription (RT) followed by quantitative polymerase chain reaction (PCR). One approach, known as "competitive RT-PCR" allows absolute quantitation by reference to synthetic RNA standards but is time-consuming and requires multiple manipulations that limit its usefulness as a screening assay. We describe here a new approach to quantify truncated type mRNAs relative to the wild-type transcripts in small amounts of tissue. This technique, called RT-triple primer-PCR, consists of coamplification of wild-type and truncated cDNAs using three primers in the PCR. To validate this approach, a truncated estrogen receptor variant (clone 4) was quantified relative to the wild-type estrogen receptor using plasmid preparations. The ratio of triple primer-PCR products obtained was directly related to the initial ratio of input cDNAs. RT-triple primer-PCR was then used to compare the relative expression of clone 4 mRNA in frozen sections of normal human breast tissue and human breast tumors with characteristics of good prognosis. The statistically significant difference (P = 0.03) observed between normal and tumor tissues suggests that elevated expression of the clone 4 variant may be associated with early steps of tumorigenesis. This technique provides a useful alternative to already described quantitative RT-PCR techniques for the quantification of truncated mRNA within small amounts of biological material.

Base Sequence↗
PubMed1996

Inter-rater reliability of electron beam computed tomography to detect coronary artery calcification.

The electron beam computed tomography (EBCT) provides a safe, rapid, and noninvasive means to detect the presence and quantitate the deposition of calcium in the coronary arteries. To examine the inter-rater reliability of a coronary calcification screen using the EBCT, films from 50 subjects were scored by two technicians. The number, volume, and calcification scores were determined for each artery as well as a total score of coronary calcification. When scan results were interpreted qualitatively (all scores > 10 classified as positive) there was complete agreement between raters in identifying the 22 cases with a positive total scan, and only one instance of discrepancy in identifying positive results for specific arteries. When scores for the 32 cases with non-zero calcium scores were analyzed quantitatively, inter-rater correlation coefficients of 0.98 or higher were observed for the total scan scores and for scores in three of four arteries. In only four cases did the total scan scores from the two raters differ by more than 10%. Therefore, evidence suggests that EBCT films can be reliably scored, enhancing their potential usefulness in the early detection of coronary atherosclerosis.

Adult↗
PubMed1996

Comparison of 10, 20, and 40 level electron beam computed tomography studies for coronary calcium.

There are increasing data to support the use of the electron beam computed tomography (EBCT) scanner for early detection of coronary artery disease (CAD). A negative scan essentially rules out significant disease. How many EBCT 3 mm contiguous slices are needed to cover the coronary circulation? To answer this question, 104 consecutive patients referred for EBCT scan for evaluation of coronary artery calcium (CAC) were asked to participate. The sensitivity and negative predictive value (NPV) of calcium scores for the first 10 slices and first 20 slices, the second 20 slices, and the total scan were recorded. Scores greater than one were regarded as positive. The number of levels required to cover the entire heart was also recorded. Fifty-nine patients (56.7%) had a positive calcium score for the total scan. Of these, 53 were positive for the first 10 slices (sensitivity = 89.8%, NPV 88.2%), and 57 were positive for the first 20 slices (sensitivity = 96.6%, NPV 95.7%). The median number of levels required to cover the entire heart was 34, and 97.2% of cases were covered in 40 or fewer levels. The use of 20 slices for purposes of detecting CAC is a reasonable choice for the C-100 scanners, because this would be accomplished in a breath hold. When the first slice starts at the base of the right pulmonary artery, all patients with CAC were identified. The C-150 scanner with the ability to scan on each heartbeat would increase sensitivity and NPV by acquiring 30 to 40 slices in a single breath hold.

Adult↗
PubMed1996

Factors in stress and burnout among paediatric nurses in a general hospital.

High stress and staff turnover in a multispecialty paediatric area prompted this study that aimed to: 1) measure the burnout level of nurses in a multi-specialty paediatric area 2) identify and validate causes of stress 3) identify new ways of preventing stress on the ward. Fifty-four percent (n = 14) of the paediatric nurses completed a questionnaire booklet that included demographic data, the Maslach Burnout Inventory, the Nursing Situations Questionnaire, the Hopkins Symptom Checklist-21, the Ways of Coping Checklist and open-ended questions about sources of stress and satisfaction at work. Results indicated levels of burnout and distress comparable with larger studies. Conflict with doctors was the major source of stress, followed by workload, inadequate preparation in dealing with the emotional needs of patients and their families and death and dying. Conflict with doctors has not previously been identified as the major source of stress. However, workload and death and dying are commonly identified as sources in the literature. Suggestions for further research and the low response rate are discussed.

Adult↗
PubMed1995

Breast cancer and importance of zygosity determination in triplet sisters.

This study is the first to examine the genetic risk in a breast cancer-prone family wherein two of three triplet sisters and their mother manifested breast cancer. The unaffected triplet, the proband, was found to be monozygotic with her deceased sister through DNA testing of tumor blocks and dizygotic to her living affected sister. Genetic counseling implications are discussed.

Adult↗
PubMed1995

Explaining rising mortality among men in eastern Europe.

Since the mid-1960s, rates of premature mortality have increased among men in all Eastern European countries, giving rise to an East-West health divide. The paper examines the existing data concerning the possible role of levels of smoking, fats consumption and/or environmental factors in explaining this phenomenon. An overview is offered of the key ways in which social experience in Eastern Europe has diverged from that in the West and it is argued that such an overview is pre-requisite for understanding the deteriorating health of men in the East. The importance of the 'incongruity' between aspirations and the means of achieving them is highlighted, as is the centrality of family-based coping strategies. It is argued that the devaluing of the public sphere and valorization of the private domain contribute to the greater health vulnerability of men under in Eastern Europe. The importance of the private sphere is reflected in the fact that the rise of premature male mortality has been overwhelmingly concentrated in the non-married population in the East European countries for which data is currently available.

Adult↗
PubMed1995

Parathyroid hormone restores bone mass and enhances osteoblast insulin-like growth factor I gene expression in ovariectomized rats.

In the osteopenic rat model, estrogen deficiency results in increased bone turnover with net bone loss occurring during cancellous modeling. However, estrogen-deficient rats treated with parathyroid hormone (PTH) experience a net gain of bone tissue due to the anabolic effects of PTH. To evaluate the possibility that local insulinlike growth factor I (IGF-I) production modulates the in vivo balance of bone formation and resorption in ovariectomized (OVX) estrogen-deficient rats and in OVX rats treated with PTH, we have studied the expression of IGF-I mRNA in cancellous bone osteoblasts using in situ hybridization techniques. Three-month-old virgin rats were subjected to sham surgery or OVX. Two weeks later, half the OVX rats began treatment with hPTH(1-34), 5 micrograms/100 g body weight, 5 days/week for 4 weeks. All animals were killed at the same time, providing three groups: sham surgery alone; OVX alone; and OVX + PTH. Bone histomorphometry performed in undecalcified sections of tibial metaphysis confirmed that OVX rats had significantly (p < 0.05) increased bone surface formation rates (BFR/BS, micron 3/micron 2/year) with osteopenia while OVX + PTH rats had increased BFR/BS with increased bone volumes compared to sham animals (p < 0.05). Decalcified tissue from all three groups contained immunoreactive IGF-I. Similar tissue sections were hybridized with an 35S-labeled IGF-I antisense riboprobe. Evaluation of the specific signal over cancellous osteoblasts allowed a relative estimate of IGF-I mRNA transcript abundance in the three groups by counting silver grains per osteoblast, corrected for background activity.(ABSTRACT TRUNCATED AT 250 WORDS)

Analysis of Variance↗
PubMed1995

Unique and interactive effects of depression, age, socioeconomic advantage, and gender on cognitive performance of normal healthy older people.

A sample of 4,243 residents of Manchester, England and Newcastle-upon-Tyne, England, aged 50 to 93 years, completed the Beck Depression Scale (A.T. Beck, C.H. Ward, M. Mendelson, J. Mock, & J. Erbaugh, 1961) and a battery of 6 different cognitive tests. Beck scores were low, indicating gradations of dysphoria rather than clinical depression. Beck scores did not vary with age but were significantly higher for women than for men and for disadvantaged than for advantaged socioeconomic groups. Measures of fluid, but not of crystallized, ability declined as age increased. Socioeconomic disadvantage was associated with poorer performance on all cognitive tests. Men scored higher on a test of spatial reasoning, and women scored higher on a test of word definition and on 2 tests of verbal memory and learning. However, after variance associated with all these demographic and individual-difference variables was considered, and within a range indicative of dysphoria rather than clinical depression, higher Beck scores were associated with significantly poorer performance on both crystallized and fluid measures of cognitive ability. This association was less marked in women than in men, but age, socioeconomic advantage, and estimated lifetime intellectual ability did not act as protective or risk factors for vulnerability of cognitive processes to dysphoria.

Age Factors↗
PubMed1995

Effect of postmenopausal hormonal replacement therapy on mammographic density and parenchymal pattern.

PURPOSE: To measure changes and predictors of change in mammograms obtained in postmenopausal women undergoing continuous combined hormonal replacement therapy (HRT). MATERIALS AND METHODS: Mammograms of 41 postmenopausal women obtained before and 1 year after the initiation of HRT were evaluated blindly according to the quantitative density percentage method and the Wolfe classification system. RESULTS: Mammographic densities increased compared with baseline values in 73% of subjects (mean increase, 6.7%; 95% confidence interval, 2.5%, 11.0%; P = .003). A shift in Wolfe classification from lower to greater parenchymal density was noted in 24% of subjects (P = .016). Multivariate analysis results indicated that the lower the tissue density percentage before treatment, the greater the increase in density percentage after treatment. CONCLUSION: An increase in mammographic density was demonstrated in most subjects undergoing continuous combined HRT and was most pronounced in subjects with a lower baseline density percentage.

Breast↗
PubMed1995

Choroid plexus electrolytes and ultrastructure following transient forebrain ischemia.

A temporal profile of lateral and fourth ventricle rat choroid plexus (LVCP and 4VCP, respectively) tissue injury and recovery was determined using alterations in K, Na, and H2O content and ultrastructure after 10 min of transient forebrain ischemia (TFI). At 0.5 h postischemia the LVCP displayed a maximum reduction in K content by 32% and a significant increase in Na content by 85% and H2O content by 22%. LVCP tissue K, Na, and H2O content returned to sham values by 24 h postischemia. Ultrastructural changes appeared more severe between 0.5 and 12 h postischemia, whereas by 24 h, normal ultrastructure was restored. Elevations in 4VCP tissue Na (P < 0.05) and H2O content, which were less than those in LVCP, gradually reached a maximum by 24 h compared with sham. No change in 4VCP tissue ultrastructure was observed. These results indicate that the LVCP tissue is more vulnerable than 4VCP in the bilateral carotid artery occlusion model but that it recovers in a timely manner after TFI. Furthermore, the ability of the LVCP tissue to rapidly recover suggests its functional importance in helping to restore brain homeostasis.

Animals↗