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Biomedical subjects

J A Bishop

Publications and source records attributed to J A Bishop.

At least 19 recordsLinked to original sources

The development and evaluation of Student Training, Education and Practice for Dietetics CD-ROM: a computer-assisted instruction programme for dietetic students.

The Student Training, Education and Practice for Dietetics (STEP-DIET) CD-ROM was developed at the University of Surrey to prepare dietetic students for the practical dietetic training component of their Nutrition/Dietetics degree. This study aimed to evaluate student response to the programme and its effectiveness as a teaching tool, based on the evaluation framework of D.L. Kirkpatrick (Evaluating a Course, 2nd edn. London, Kogan Page). Quantitative and qualitative methodologies were employed, with 41 dietetic students, separated by year group, completing questionnaires and taking part in six focus groups, at the University of Surrey. Student attitudes towards the instruction method and the STEP-DIET programme itself were investigated, in conjunction with their perceived learning achievements. Students rated the programme highly in terms of design and content, however, there was a reluctance to accept computer-assisted instruction (CAI) as a sole teaching method. A number of learning achievements relevant to dietetic practice were reported including a perceived increase in ability to conduct a dietetic interview and an increased understanding of the management of Type 2 diabetes. In general students reacted positively to the STEP-DIET programme and it was perceived by students to be effective in preparing them for the practical component of their dietetic training.

Attitude to Computers↗

Promoting healthy diet and exercise patterns amongst primary school children: a qualitative investigation of parental perspectives.

Parents represent a potentially powerful intermediary in behaviour change strategies aimed at improving the lifestyle behaviours of young children. However, to fulfil this role, parents need to have the necessary knowledge and motivation to assimilate dietary guidelines. This study aimed to assess these psychosocial constructs, and subsequent parental receptiveness to nutrition education, through investigation of the barriers and benefits perceived by parents to the provision of a healthy diet and adequate exercise for their children. A qualitative methodology was employed and 41 parents took part in seven focus groups separated by socio-economic status (SES). Across the groups, a combination of reported external barriers and unconscious internal barriers, stemming from high optimistic bias, low perceived control and unrealistic health expectations, were observed. SES differences were suggested in restrictive feeding practices, the responsibility attributed to the school and in the level and format of desired nutrition education. Overall a demand for interventions focusing on behavioural techniques rather than fact transmission was uncovered, in particular the promotion of parental self-awareness to reduce negative influences within the family food environment. Providing realistic definitions of appropriate behaviour and empowering parents to tackle children's weight issues were indicated as important targets for future education programmes.

Attitude to Health↗

Weaning preterm infants: a randomised controlled trial.

OBJECTIVE: To assess the effect on growth and iron status in preterm infants of a specially devised weaning strategy compared with current best practices in infant feeding. The preterm weaning strategy recommended the early onset of weaning and the use of foods with a higher energy and protein content than standard milk formula, and foods that are rich sources of iron and zinc. SUBJECTS AND DESIGN: In a blinded, controlled study, 68 preterm infants (mean (SD) birth weight 1470 (430) g and mean (SD) gestational age 31.3 (2.9) weeks) were randomised to either the preterm weaning strategy group (n = 37) or a current best practice control group (n = 31), from hospital discharge until 1 year gestation corrected age (GCA). MAIN OUTCOME MEASURES: Weight, supine length, occipitofrontal head circumference, and intakes of energy, protein, and minerals were determined at 0, 6, and 12 months GCA. Levels of haemoglobin, serum iron, and serum ferritin were assayed at 0 and 6 months GCA. RESULTS: Significant positive effects of treatment included: greater increase in standard deviation length scores and length growth velocity; increased intake of energy, protein, and carbohydrate at 6 months GCA and iron at 12 months GCA; increased haemoglobin and serum iron levels at 6 months GCA. CONCLUSIONS: The preterm weaning strategy significantly influenced dietary intakes with consequent beneficial effects on growth in length and iron status. This strategy should be adopted as the basis of feeding guidelines for preterm infants after hospital discharge.

Age Factors↗

An investigation into school children's knowledge and awareness of food and nutrition.

With the diet and exercise behaviours of UK school children showing little improvement over recent years, the need for dietary change is clearly indicated. This study aimed to assess the nutritional knowledge and understanding of primary school children in order to identify the most effective format for future nutrition messages. A qualitative methodology was employed and 114 children, aged 7-11 years, took part in 23 focus groups separated by age, gender and socio-economic status (SES). Issues discussed included parental food rules, children's perceptions of 'good' and 'bad' foods, diet-disease links and food groupings. Across the groups restrictive food rules were most frequently reported whilst between groups gender and SES differences were apparent in relation to parental control over food and children's nutritional knowledge. The limitations of the children's cognitive development could be seen in their conceptualization of food groups, where concrete grouping schemes were frequently used, and in the lack of understanding inherent in their food-health or food-nutrient associations. Taste and preference were confirmed as consistent influences in children's food classification. Primary school children may be receptive to food based dietary guidelines based on familiar, concrete food classifications. These should be cognitively appropriate and possibly need to be gender specific.

Child↗

A deep intronic mutation in CDKN2A is associated with disease in a subset of melanoma pedigrees.

Germline mutations of CDKN2A at 9p21 have been shown to predispose to disease in melanoma pedigrees worldwide. However, there remains a significant proportion of melanoma pedigrees with evidence of linkage to 9p21 in which mutations in CDKN2A have not been detected. Investigation of other potential tumour suppressor genes at 9p21 and the promotor of CDKN2A has been unable to explain genetic predisposition to melanoma in these pedigrees. Here we describe a mutation, IVS2-105 A/G, deep in intron 2 of CDKN2A, detected in six English melanoma pedigrees. The mutation creates a false GT splice donor site 105 bases 5' of exon 3 and has been demonstrated to result in aberrant splicing of the mRNA. This is the most common mutation identified in English families to date. The presence of this deep intronic mutation in a relatively large number of kindreds, indicates that it may account for a significant proportion of 9p21-linked melanoma pedigrees with no detectable mutations in the coding region of CDKN2A. In addition, the identification of one deep intronic mutation in CDKN2A indicates the possibility of the existence of other similar splicing mutations located elsewhere in the CDKN2A introns.

Alleles↗

Teaching non-specialist health care professionals how to identify the atypical mole syndrome phenotype: a multinational study.

The atypical mole syndrome (AMS) phenotype is the strongest known risk factor for cutaneous melanoma but recognition of the phenotype has been claimed to be problematic and to require specialist assessment. This study determined the ability of previously unskilled doctors and nurses in five countries to recognize the phenotype after brief training. The system used was the AMS scoring system. This incorporates melanocytic naevus counts, clinical atypia of naevi and distribution of naevi. The agreement in scoring between the dermatologist and trained personnel was determined in 986 patients; overall agreement in diagnosis was 94.5% (kappa 0.70, P < 0.0001). The kappa scores in different countries ranged from 0.65 to 0.77 for individual naevus characteristics, indicative of good agreement. Accurate diagnosis of the atypical mole syndrome phenotype is possible by non-specialists. This has implications for collaborative studies of naevi, for screening and for both primary and secondary prevention of melanoma.

Adolescent↗

Genotype/phenotype and penetrance studies in melanoma families with germline CDKN2A mutations.

Patients with a family history of melanoma are at increased risk of this tumor. Those family members who also have the atypical mole syndrome are commonly targeted for screening in the belief that they are more likely to be mutant gene carriers. We have correlated the atypical mole syndrome phenotype and gene carrier status in five families with germline CDKN2A mutations and shown that family members with the atypical mole syndrome were three times more likely to be mutant gene carriers than their relatives who did not have the atypical mole syndrome (odds ratio 3.4; confidence interval 1.0-11. 1), supporting the view that CDKN2A is nevogenic. Individual characteristics which best predicted mutant gene carrier status were: nevi on the buttocks (odds ratio 4.4; confidence interval 1. 6-12.4), nevi on the feet (odds ratio 4.2; confidence interval 1. 4-12.5), total nevus number being at least 100 (nevi > or = 2 mm in diameter) (odds ratio 3.4; confidence interval 1.0-11.1) and two or more clinically atypical nevi (odds ratio 3.1; confidence interval 1. 1-9.0). Gene carriers were also significantly more likely to have noticeable freckling and possibly also Fitzpatrick skin types 1-3. The overlap between gene carriers and nongene carriers was, however, marked: the atypical mole syndrome did not clearly differentiate mutant gene carriers from those with a normal gene. This study is of significance to clinicians as the clinical practice of using the atypical mole syndrome to identify particular family members for surveillance is shown to be inappropriate. Until formal gene testing is available, all members of families with an excessive number of melanoma cases should be treated as potential mutation carriers at increased risk of melanoma.

Genes, p16↗

Melanoma.

Cutaneous melanoma is becoming more common. Although still rarer than some cancers it is important, particularly as it afflicts young adults relatively frequently. Furthermore early detection with resultant better prognosis should be achievable if the public was to become more aware, and if health-care professionals were more familiar with melanoma and the behaviour of normal moles.

Age Distribution↗

Role of GnRH agonists in managing proximal fallopian tube obstruction.

OBJECTIVE: To assess the response of proximal fallopian tube obstruction to a medically induced hypoestrogenic state after control for spasm at the uterotubal ostium. STUDY DESIGN: This was a prospective, randomized, placebo-controlled, pilot study in a tertiary care, university-affiliated infertility practice. Twenty-one infertile women with unilateral or bilateral proximal tubal obstruction previously diagnosed by standard hysterosalpingography or laparoscopic chromotubation were randomized into two groups in a 2:1 design. Group I, 14 patients (27 occluded tubes), was administered a depot preparation of the gonadotropin-releasing hormone (GnRH) agonist leuprolide acetate, 3.75 mg intramuscularly every 28 days. Group II, seven patients (11 occluded tubes), was administered a placebo. Follow-up hysterosalpingography was performed after administration of the antispasmodic glucagon within four weeks of completion of the protocol. RESULTS: Evidence of ovarian suppression was confirmed within four weeks in group I. A trend toward higher posttherapy patency rates was noted in group I (74.7% vs. 40%). The lack of statistical significance may have been a function of sample size. Similarly, spontaneous intrauterine pregnancy rates were also higher in GnRH agonist-treated patients (35.1% vs. 16.6%, P < .05). Tubal patency rates were significantly greater in patients with documented estrogen-sensitive disorders who received the agonist (75% vs. 20%, P < .05) CONCLUSION: Proximal tubal obstruction may be an estrogen-sensitive phenomenon in a subset of infertile patients. The administration of GnRH agonists may successfully overcome this state and result in enhanced conception rates.

Adult↗

Melanoma excision by general practitioners in north-east Thames region, England.

A retrospective study of pathology reports of melanomas excised by general practitioners (GPs) was undertaken in the course of a population-based study of melanoma, with a telephone survey of the current practice of those GPs who had excised melanomas. The objectives of this study were to identify all cases of cutaneous melanoma excised by GPs in the North-East Thames Region between 1989 and 1993, and to review the management of those patients. The main outcome measures of the study were: (i) the patterns of distribution of GP excisions within the region; (ii) the histological subtypes of melanomas excised, the accuracy of the pre-excision clinical diagnosis and the adequacy of treatment of the GP-treated tumours compared with the control group; and (iii) the reported current practice in the management of pigmented skin lesions by the GPs who had excised melanomas. Eight hundred and nineteen melanomas were excised in the region during the study period, of which 59 were excised by GPs. The Breslow thickness of tumours was similar in both GP-excised and non-GP-excised groups. Tumours were more likely to be amelanotic in the GP-excised group (P < 0.001). Incomplete excision was significantly more likely in the GP group (P < 0.001). The GPs made a confident clinical diagnosis of melanoma in only 17% of patients prior to surgery. The reported referral rate to specialists by this subset of GPs of patients with pigmented lesions was low, and at interview half of the GPs reported that they felt confident enough to manage patients with suspected skin cancers on their own. The majority of the GPs did not routinely obtain histological examination of skin lesions they believed to be benign. In conclusion, there are problems with the accuracy of clinical diagnosis and inadequacy of excision of melanomas removed in primary care. In the majority of cases, however, patients were subsequently appropriately treated by referral to specialist units. There was an under-usage of pathological examination of samples by the GPs interviewed.

Ambulatory Surgical Procedures↗

Demographic change and income inequality in the United States, 1976-1989.

"The U.S. economy experienced significant increases in the degree of income inequality over the past two decades.... In this paper we consider the effects of race, age, female headship, and college education on the distribution of family income by developing a multivariate methodology that allows us to gauge the influence of one factor while holding other determinants of family incomes constant. Over the period studied we find that race had only a minor effect on the overall size distribution of income. Age had a somewhat greater effect than race. In contrast, the impact of female heads and college education were quite substantial. The multivariate estimates reveal that the effects of female heads and college education both increase the Gini to a much greater extent than the progressivity of federal income taxes decreases it. The effects of college education and female headed families on inequality have grown larger across time, while the influence of age has declined. We find that the effects of race on inequality have changed little over the 1976 to 1989 period."

Age Factors↗

Risk of cutaneous melanoma in relation to the numbers, types and sites of naevi: a case-control study.

The atypical mole syndrome (AMS) phenotype, characterised by a large number of common naevi as well as atypical naevi, has been described in families with a genetic susceptibility to melanoma. However, the importance of this phenotype for melanoma in the general population has not been conclusively determined. This study was designed to examine the types and distribution of naevi as well as the prevalence of the AMS phenotype in melanoma patients in England compared with controls. A total of 426 cutaneous melanoma cases (61% of all incident cases) aged 16-75 years were recruited between 1989 and 1993 from the north-east Thames region of the UK and 416 controls from the same age group were recruited over the same period and from the same region. Each subject answered a questionnaire covering demographic details, sun exposure history and other risk factors and underwent a skin examination with total body naevus count performed by a dermatologist. The AMS phenotype was defined using a scoring system. Atypical naevi gave the highest relative risk for cutaneous melanoma, with an odds ratio (OR) of 28.7 (P < 0.0001) for four or more atypical naevi compared with none. Many common naevi were also an important risk factor: the OR for 100 or more naevi 2 mm or above in diameter compared with 0-4 naevi was 7.7 (P < 0.0001). Melanoma was also associated with naevi on sun-exposed sites but also with naevi on non-sun-exposed sites such as the dorsum of the feet, buttocks and anterior scalp. Sixteen per cent of the cases had the AMS phenotype compared with 2% of the controls (OR 10.4, P < 0.0001). The AMS phenotype was more common in males than females (P = 0.008). The odds ratio for the presence of the AMS phenotype was dependent on age, with an odds ratio of 16.1 (95% CI 4.6-57.5) for the presence of the AMS phenotype if aged less than 40 compared with an odds ratio of 6.9 (95% CI 2.9-16.6) if aged 40 or more. The AMS phenotype was strongly predictive of an increased risk of melanoma outside the familial context.

Adolescent↗

Interferon system defects in human malignant melanoma.

We have examined the ability of melanoma cell lines and normal human melanocytes, which have demonstrable intact IFN genes, to secrete both IFN-alpha and IFN-beta in response to induction with virus. Normal melanocytes were found to secrete both IFN-alpha and IFN-beta after virus induction. In contrast, although all but one of the melanoma lines tested were capable of secreting IFN-beta, none were capable of IFN-alpha secretion. This phenomenon was not due to defects in either translation of IFN-alpha mRNA or secretion of IFN-alpha proteins, since transfection of melanoma lines with a constitutive IFN-alpha 2b expression vector resulted in the secretion of high levels of IFN. On further examination, this inability to express natural IFN-alpha appeared to be due to a defect in activation of the IFN-alpha promoters, since constructs containing the IFN-alpha promotor were completely unresponsive to viral infection in melanoma cells but inducible in melanocytes. These results show that there is a specific disruption of IFN-alpha gene activation rather than IFN-beta in melanoma lines and suggest that this is due to disruption of a trans-acting IFN-alpha gene transcription factor. Disruption of this factor and its consequences may be important in the development of malignant melanoma.

Base Sequence↗

Risk of ocular melanoma in relation to cutaneous and iris naevi.

A case-control study was set up to assess the risk of eye melanoma in relation to the number and type of cutaneous melanocytic naevi and pigmented lesions of the iris. Cases comprised 211 unselected ocular melanoma patients attending the Ocular Oncology Clinic at Moorfields Eye Hospital, London, during November 1990 to October 1991 and diagnosed after August 1986. Hospital and general practice controls (416) were recruited in the North East Thames Region of the UK. Cutaneous naevi greater than or equal to 2 mm in diameter were counted on the skin. Clinically atypical and congenital naevi were recorded separately. Pigmented lesions of the iris were counted. The relative risk for ocular melanoma increased with numbers of atypical naevi and numbers of common naevi. Ten percent of cases but 3% of controls had at least 100 naevi of 2 mm or greater diameter. Seven percent of cases and 0.4% of controls had 4 or more atypical naevi. Pigmented lesions of the iris were significantly more common in cases than controls. Nine percent of cases had the Atypical Mole syndrome (AMS) phenotype compared with 1% of controls. Six cases had concurrent cutaneous melanoma primaries. We conclude that atypical and iris naevi are important risk factors for eye melanoma and that patients with eye melanoma are at increased risk of cutaneous melanoma. Dermatological examination for the AMS phenotype and cutaneous melanoma should be recommended in eye melanoma patients with large numbers of pigmented lesions of the skin or family history of melanoma.

Adolescent↗

Generation and selection of monoclonal antibodies, single-chain Fv and antibody fusion phage specific for human melanoma-associated antigens.

A panel of 13 murine monoclonal antibodies (mAbs) recognizing antigens on human melanoma cells but not on melanocytes was generated. Two mAbs (LHM3 and LHM5) stained sections of melanoma but not normal tissues. mAbs LHM2 and LHM8 stained only a minority of normal tissues. The mAbs differed further in their staining patterns on melanoma cell lines HMB2, DX3 and SK23 in FACS. The mAbs recognize antigens of 34, 38, 57, 94, 190-200 and > 200 kD. One mAb each bound to each of the antigens HLA DR (LHM4) and high molecular weight proteoglycan (LHM2). The high molecular weight proteoglycan-specific mAb was used to construct a single-chain Fv (scFv) antibody fragment and an antibody fusion phage in Escherichia coli. Both the scFv and the fusion phage were shown to bind specifically to melanoma cells. A method for the selection of melanoma cell-binding phages from phage libraries is described.

Animals↗

Retinoblastoma, melanoma and the atypical mole syndrome.

Retinoblastoma patients and their relatives appear to have an increased risk of other cancers, especially melanoma, which represents 7% of second primaries in retinoblastoma survivors. Individuals belonging to families with the atypical mole syndrome (another family cancer syndrome with a genetic susceptibility to melanoma) have a recognizable phenotype, with many atypical melanocytic naevi. We report two families in which both retinoblastoma and melanoma occurred. It is of interest that in these families atypical melanocytic naevi were also demonstrated.

Adult↗

Genetic heterogeneity in familial malignant melanoma.

Following reports of linkage to chromosome 9p in families with malignant melanoma, we have been studying a series of UK families. Six families were selected with three or more cases of malignant melanoma. We have used a total of twelve markers mapping in the interval 9p13-p23 and constructed a set of haplotypes to study the inheritance of the disease chromosome. Of the six families, three were consistent with linkage to the short arm of 9, although their limited size precluded confirmation of linkage. One family was clearly unlinked, one family was either unlinked, or contains a sporadic case, or delimits the location of the melanoma gene, and one family was essentially uninformative. This is strong evidence for genetic heterogeneity in families with the malignant melanoma phenotype. We have also sequenced exon 2 of the recently identified candidate tumour suppressor gene, p16, in six individuals and found no evidence for germline mutations in this region of the p16 gene in our families with inherited malignant melanoma.

Adolescent↗