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Biomedical subjects

C Strong

Publications and source records attributed to C Strong.

At least 37 records · Page 2Linked to original sources

Splicing mutations of the polycystic kidney disease 1 (PKD1) gene induced by intronic deletion.

Autosomal dominant polycystic kidney disease (ADPKD) is a common genetic disease which frequently results in renal failure. The major ADPKD gene, polycystic kidney disease 1 (PKD1), has recently been identified. In an attempt to understand better the aetiology of this disorder we have searched for mutations in the PKD1 gene. Analysis of three regions in the 3' part of the gene has revealed two mutations that occur by a novel mechanism. Both mutations are deletions (of 18 or 20 bp) within the same 75 bp intron and although these deletions do not disrupt the splice donor or acceptor sites at the boundary of the intron, they nevertheless result in aberrant splicing. Two different transcripts are produced in each case; one includes the deleted intron while the other has a 66 bp deletion due to activation of a cryptic 5' splice site. No normal product is generated from the deleted gene. Aberrant splicing probably occurs because the deleted intron is too small for spliceosome assembly using the authentic splice sites; this mechanism has previously only been described from in vitro studies of vertebrate genes. A 9 bp direct repeat has been identified within the intron, which probably facilitated deletion by promoting misalignment of sequence. The possible phenotypic implications of producing more than one aberrant PKD1 transcript in these cases are discussed.

Adult↗

Abnormally phosphorylated tau protein in senile dementia of Lewy body type and Alzheimer disease: evidence that the disorders are distinct.

The relationship between Alzheimer disease (AD) and dementia with Lewy bodies (senile dementia Lewy body type, or SDLT) and dementia in Parkinson's disease is unclear. AD pathology is characterised by both amyloid deposition and abnormal phosphorylation of tau in paired helical filaments (PHF-tau). In AD, abnormally phosphorylated PHF-tau is present in neurofibrillary tangles, in neuritic processes of senile plaques, and also in neuropil threads dispersed throughout the cerebral cortex. Cortical homogenates from 12 cases each of AD and SDLT, 13 cases of Parkinson's disease, and 11 normal controls were examined by Western blot analysis with antibodies that detect PHF-tau. No PHF-tau was found in Parkinson's disease or control cortex. No PHF-tau was found in SDLT cases without histological evidence of tangles. PHF-tau was detectable in SDLT cases with a low density of tangles, and large amounts of PHF-tau were present in AD cases. This study demonstrates that abnormally phosphorylated PHF-tau is only present where tangles are found and not in SDLT cases without tangles or with only occasional tangles. It is concluded that Lewy body dementias are distinct at a molecular level from AD.

Aged↗

Dietary intervention in primary care: validity of the DINE method for diet assessment.

Primary health care staff are involved increasingly in the provision of dietary advice for health promotion, often without adequate training in nutrition assessment or counselling. At present no brief diet assessment methods are available which have been validated for this purpose in the UK. We report on the accuracy of the Dietary Instrument for Nutrition Education (DINE) in classifying dietary fat and fibre intakes. This structured questionnaire can be administered and scored in under 10 minutes by primary care staff without specialized nutritional knowledge, and includes a dietary counselling component. The classification of fat and fibre intakes as low, medium or high by the DINE method was compared to that of a detailed 4-day diet record in a population of 206 factory workers. There was exact agreement of categorization for 53% of fat intakes and 52% of fibre intakes, and only 6% of fat intakes and 5% of fibre intakes were grossly misclassified (placed in a high category by one method and a low category by another). Pearson correlation coefficients between the two methods were 0.51 for fat, 0.46 for fibre and 0.43 for the polyunsaturated:saturated fat ratio. The DINE method is a brief and inexpensive tool for diet assessment in primary care health promotion programmes.

Counseling↗

The effectiveness of an intervener model of services for young deaf-blind children.

Project Validation of the Intervener Program (VIP) studied and documented the effectiveness of the Intervener Service Model which provides the services of a paraprofessional (called an intervener) to families of young children who are deaf-blind. The intervener provides auditory, visual, and tactile stimulation for the child and helps the child develop interactive behaviors instead of isolated, defensive, or self-stimulatory behaviors. The intervener also enables the parents to obtain much needed respite. Project VIP obtained abundant quantitative and qualitative data on the effectiveness of the Intervener Service Model. The data strongly support the need for Intervener Services for young children who are deaf-blind and their families.

Blindness↗

Tomorrow's prenatal genetic testing. Should we test for 'minor' diseases?

New genetic knowledge will make it possible to test prenatally for a wide range of fetal genetic characteristics. One consequence will be an expansion of potential reasons for selective abortion following prenatal testing. It will likely become possible for patients to request prenatal testing and abortion not only for serious diseases but also relatively mild diseases, late-onset diseases, treatable diseases, elevated risks for common diseases, and eventually nondisease characteristics, such as height and body build. Two main ethical views concerning prenatal testing have been advocated: (1) Prenatal testing should be restricted to the "most severe" disorders, involving profound retardation, severe physical handicaps, or prolonged physical suffering and (2) Patients' requests for prenatal tests should be honored except for diseases considered to be "too minor." At least two additional views can be identified: (3) Physicians should honor requests for prenatal testing for diseases, including relatively minor ones, but not requests pertaining to nondisease characteristics and (4) All requests for prenatal tests should be honored. A difficulty with the first and second views is that they deviate from the norm of nondirectiveness in prenatal testing and counseling. The problems with the fourth view are that it leads to abortions for morally trivial reasons and that attempts to design our children could adversely affect parent-child relationships and exacerbate current social inequities. These considerations support the third view, which holds that the future role of reproductive genetic testing and counseling should be based on the imperfect, but helpful, distinction between disease and nondisease.

Ethics, Medical↗

Should physicians infected with human immunodeficiency virus be allowed to perform surgery?

Practice restrictions on physicians who have the human immunodeficiency virus can significantly interfere with their freedom to practice. Three main ethical views have been advocated concerning such restrictions: (1) infected physicians should be required either to refrain from performing procedures posing any risk of transmission or to reveal their seropositivity to the patient and proceed if consent is obtained; (2) they should not be restricted; (3) they should be restricted from some subset of invasive procedures posing higher risks of transmission. However, the first view overlooks the adverse effects of restrictions and the second view disregards consequences of patient exposure. A shortcoming of the third view is its focus on risks of transmission rather than exposure. An ethical view avoiding these difficulties is the following: Physicians infected with human immunodeficiency virus should be restricted from procedures involving risks of patient exposure great enough to require informed consent. Given current risk estimates, this implies restrictions, at the least, on procedures involving an open wound.

Acquired Immunodeficiency Syndrome↗

A microbiological comparison between acute and complicated appendicitis.

Bacteria recovered from appendiceal specimens from 20 patients with acute appendicitis were compared with those recovered from 19 patients with complicated (gangrenous or perforative) appendicitis. Specimens of both peritoneal fluid and appendiceal tissue from patients with acute appendicitis yielded smaller numbers and fewer species of bacteria in culture than did specimens from patients with more complicated disease (2.3 strains per specimen for the former; 9.9 strains per specimen for the latter). Bacteria were recovered from all 13 cultures of specimens of appendiceal tissue and from 13 of 18 cultures of specimens of peritoneal fluid obtained from patients with gangrenous and perforative appendicitis; however, only eight of 17 cultures of appendiceal specimens and seven of 18 cultures of peritoneal fluid specimens from patients with acute appendicitis yielded bacteria. These findings suggest that some bacteria traverse the intact appendiceal wall prior to perforation and that progressive infection and subsequent tissue damage and necrosis allow larger numbers and varieties of bacteria to move through appendiceal wall tissue and into the peritoneal cavity.

Acute Disease↗

Teachers' perceptions of difficulties in teaching ethics in residencies.

In 1989 the authors surveyed faculty who were teaching medical ethics in residencies in order to obtain information concerning the goals, formats, topics, and settings of such teaching, as well as the difficulties encountered. Of 163 teachers contacted, 94 (58%) responded and 63 (39%), representing 50 institutions, reported participation in formal ethics teaching programs for residents. The 63 teachers reported using a variety of formats, including ethics rounds, lectures, and incorporating ethics teaching into weekly case-management conferences. Frequently mentioned goals of ethics teaching included improving the residents' skills in reasoning about ethical decisions and improving the residents' understanding of the language and concepts of ethics. Thirty-four of the 63 teachers (54%) taught ethics in hospital settings exclusively and 21 (33%) taught both in hospitals and in outpatient clinics or offices. The teachers identified a number of barriers encountered in carrying out such teaching, most of which can be grouped in six categories: (1) time constraints due to residents' heavy schedules; (2) attitudes of residents that pose obstacles; (3) logistical problems associated with teaching in the clinical setting; (4) time demands placed on teachers; (5) lack of reinforcement for teaching ethics from other faculty; and (6) shortcomings in the background and training of faculty for teaching ethics in the clinical setting. The authors conclude that difficulties are commonly encountered and discuss ways to overcome the principal barriers to effective teaching of ethics in the residency years.

Attitude of Health Personnel↗

A conference on ethics for obstetric and gynaecological clerkship students.

Integrating the teaching of medical ethics into medical students' clinical education is challenging, given the competing demands on students' time and the need for teaching to be clinically relevant. This paper describes a model programme for incorporating ethics teaching into the obstetrics and gynaecology clerkship for third-year medical students. The programme is taught by two attending teachers and a medical ethicist with experience teaching in the clinical setting of obstetrics and gynaecology. Objective pretests and posttests showed substantial improvement in students' knowledge, and student feedback has been very positive.

Clinical Clerkship↗

Safe sex and women.

OBJECTIVE: Sexual behaviour, condom use, HIV knowledge and anxiety for women were examined to understand the range of sexual behaviours, predictors of safer sex and the extent of relapse. DESIGN: A cross sectional sample of women STD clinic attenders completed interviews and questionnaires. SETTING: Central London STD Clinic. SUBJECTS: 153 women drawn from consecutive attenders at a sexually transmitted disease (STD) clinic in inner London. RESULTS: A quarter of the sample had never responded to safe sex and a further 14% had been unable to maintain it over time. Anxiety and knowledge did not differ between safe and relapsed groups, but self efficacy and cognitive variables did. Those who maintained safe sex had significantly less sex. Ten percent of the sample had unprotected anal intercourse. Most women saw themselves in longer term relationships, yet a quarter had sex outside of the relationship and a fifth stated that their partners also did. HIV information gathering was passive and 74% felt they could not protect themselves against infection. High concern over HIV was monitored. Condom uptake was low and non-existent for anal intercourse. 25% had undergone HIV testing. These women did not differ significantly in terms of their behaviour from the untested women. CONCLUSIONS: HIV risks for women are a source of anxiety and tailored intervention is needed to reduce risk and promote dialogue and negotiation.

Acquired Immunodeficiency Syndrome↗

Fetal tissue transplantation: can it be morally insulated from abortion?

Ethical controversy over transplantation of human fetal tissue has arisen because the source of tissue is induced abortions. Opposition to such transplants has been based on various arguments, including the following: rightful informed consent cannot be obtained for use of fetal tissue from induced abortions, and fetal tissue transplantation might result in an increase in the number of abortions. These arguments were not accepted by the National Institutes of Health (NIH) Human Fetal Tissue Transplantation Research Panel. The majority opinion of the panel stated that abortion and fetal tissue use are entirely separate issues, and that tissue use is ethically acceptable because it can be morally insulated from the issue of abortion. In support of this view, panel members and others have replied to the arguments put forward by opponents of fetal tissue use. However, replies to the two arguments mentioned above have been unsatisfactory, and the shortcomings of those replies are identified herein. Examination of the arguments pro and con suggests that fetal tissue use cannot be completely insulated from the issue of abortion. Thus, in seeking an ethical justification for fetal tissue transplantation we must consider reasons other than those put forward by the NIH panel. In this paper it is argued that whatever wrong is involved in using fetal tissue from induced abortions must be balanced against the benefits for patients, and it is on this basis that fetal tissue transplantation can be ethically justified.

Abortion, Induced↗

Court-ordered treatment in obstetrics: the ethical views and legal framework.

Four main ethical views have been put forward concerning court-ordered treatment of mentally competent pregnant women for fetal indications: 1) Such treatment is never justifiable; 2) it is justifiable provided it poses no health risks for the woman, minimally invades her bodily integrity, and would clearly prevent substantial harm to the fetus; 3) it is justifiable provided the maternal risks are low, there is a substantial likelihood that the fetus will suffer irrevocable harm without the intervention, and the treatment will likely be effective; and 4) it is justifiable provided the risks to the woman are ones she should reasonably accept, the fetal risks of treatment are minimal, and the potential fetal benefit is substantial. However, the first two views are too rigid to adequately handle the variety of clinical situations in which maternal treatment refusal can occur, and recent legal decisions have ruled out the other views. The ethics of court-ordered treatment are often discussed as though the only interests involved are those of the pregnant woman and fetus, but other important interests may be relevant. An ethical view that avoids these difficulties and takes better account of the complexity of the issues is as follows: Such treatment is justifiable in rare, exceptional circumstances provided it poses insignificant or no health risks to the woman or would promote her interests in life or health and there are compelling reasons to override her autonomy.

Ethics, Medical↗

Regional localization of polymorphic markers on chromosome 10 by physical and genetic mapping.

The human vimentin gene and a random DNA segment (D10S39) were mapped to the short arm of human chromosome 10 by linkage analysis. A panel of somatic cell hybrids and monosomy cell-lines, which divide chromosome 10 into seven regions, was used to localize 10 polymorphic markers on this chromosome. The physical map locations obtained correlate well with linkage maps of chromosome 10. Two markers which have been shown to be closely linked to the gene for multiple endocrine neoplasia type 2A map distal to a translocation breakpoint in band 10q11.2.

Animals↗

Stimulation of plasma renin activity by captopril in renovascular hypertensive conscious dogs.

The increase in plasma renin activity induced by captopril is used in the clinical evaluation of renovascular hypertensive patients. This increase in plasma renin activity could result from either the concomitant fall in systemic pressure or other effects of captopril, such as the removal of an angiotensin II inhibitory effect on renin release, the increased production of bradykinin or prostaglandins, etc. To examine the effect captopril has on plasma renin activity, independent of changes in systemic pressure, captopril (5, 10 and 50 micrograms/kg iv) was administered to conscious dogs before and following the development of 1 clip-2 kidney Goldblatt hypertension. Plasma renin activity, under normal conditions remained unchanged, while during hypertension it increased 2.0, 2.8 and 3.5 fold respectively in response to the three doses of captopril. These results suggest that the development of renovascular hypertension sensitized the kidney to release renin when challenged by captopril and that the effect is independent of changes in systemic pressure.

Animals↗