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Biomedical subjects

C Strong

Publications and source records attributed to C Strong.

At least 19 recordsLinked to original sources

An approach to teaching ethical, legal, and psychosocial aspects of gynecologic oncology in a residency program.

An approach to teaching ethical, legal, and psychosocial issues in gynecologic oncology has been integrated into an obstetrics and gynecology residency program. Team-teaching is used, involving gynecologic oncology faculty members and a medical ethicist with experience teaching in the clinical setting of obstetrics and gynecology. The teaching takes place as part of ongoing teaching rounds in the division of gynecologic oncology. Articles from clinical journals are used to inform and stimulate discussion of clinical ethical, legal, and psychosocial issues. Integrating the teaching of ethical and legal aspects of gynecologic oncology into residency education is challenging, given the competing demands on the residents' time and the need for teaching to be clinically relevant. The program described in this article illustrates that such teaching can be carried out in a manner that covers main issues and has practical value for residents.

Curriculum

Identification of mutations in the duplicated region of the polycystic kidney disease 1 gene (PKD1) by a novel approach.

Mutation screening of the major autosomal dominant polycystic kidney disease gene (PKD1) has been complicated by the large transcript size (> 14 kb) and by reiteration of the genomic area encoding 75% of the protein on the same chromosome (the HG loci). The sequence similarity between the PKD1 and HG regions has precluded specific analysis of the duplicated region of PKD1, and consequently all previously described mutations map to the unique 3' region of PKD1. We have now developed a novel anchored reverse-transcription-PCR (RT-PCR) approach to specifically amplify duplicated regions of PKD1, employing one primer situated within the single-copy region and one within the reiterated area. This strategy has been incorporated in a mutation screen of 100 patients for more than half of the PKD1 exons (exons 22-46; 37% of the coding region), including 11 (exons 22-32) within the duplicated gene region, by use of the protein-truncation test (PTT). Sixty of these patients also were screened for missense changes, by use of the nonisotopic RNase cleavage assay (NIRCA), in exons 23-36. Eleven mutations have been identified, six within the duplicated region, and these consist of three stop mutations, three frameshifting deletions of a single nucleotide, two splicing defects, and three possible missense changes. Each mutation was detected in just one family (although one has been described elsewhere); no mutation hot spot was identified. The nature and distribution of mutations, plus the lack of a clear phenotype/genotype correlation, suggest that they may inactivate the molecule. RT-PCR/PTT proved to be a rapid and efficient method to detect PKD1 mutations (differentiating pathogenic changes from polymorphisms), and we recommend this procedure as a firstpass mutation screen in this disorder.

Adult

The moral status of preembryos, embryos, fetuses, and infants.

Some have argued that embryos and fetuses have the moral status of personhood because of certain criteria that are satisfied during gestation. However, these attempts to base personhood during gestation on intrinsic characteristics have uniformly been unsuccessful. Within a secular framework, another approach to establishing a moral standing for embryos and fetuses is to argue that we ought to confer some moral status upon them. There appear to be two main approaches to defending conferred moral standing; namely, consequentialist and contractarian arguments. This article puts forward a consequentialist argument for the conferred moral standing of preembryos, embryos, fetuses, and infants. It states and defends an original version of the commonly-held view that moral standing increases during gestation. It also explores the implications of this viewpoint for several issues: what is involved in showing 'respect' for preembryos; and whether it is permissible to create preembryos solely for research.

Beginning of Human Life

Decision making by parents and healthcare professionals when considering continued care for pediatric patients with cancer.

PURPOSE/OBJECTIVES: To better define the treatment-related decisions considered most difficult by parents of pediatric patients with cancer and the factors that influenced their final decisions. DESIGN: Retrospective-descriptive design. SETTING: Pediatric oncology institution in the mid-southern region on the United States. SAMPLE: 39 parents representing 37 of 83 eligible families, 16 attending physicians, three nurses, and two chaplains. METHODS: Parent participants responded by telephone to six open-ended interview questions and a 15-item questionnaire about factors that were important when making the decision to continue care. Healthcare professionals were interviewed face-to-face. MAIN RESEARCH VARIABLES: Most difficult treatment-related decisions; factors influencing decision making. FINDINGS: Parents reported 15 types of difficult decisions, the majority of which were made late in the course of treatment. Deciding between a phase I drug study or no further treatment (n = 14), maintaining or withdrawing life support (n = 11), and giving more chemotherapy or giving no further treatment (n = 8) were the most frequently reported difficult decisions. Parents rated "recommendations received from healthcare professionals" as the questionnaire factor most important in their decision making, and healthcare professionals rated "discussion with the family of the patient" as the most important factor. CONCLUSION: Parents of children or adolescents with cancer and their healthcare providers face difficult treatment-related decisions, many of which occur late in the course of treatment. Parents and healthcare professionals cite similar factors in their decision making but differ in their ratings of the factors' importance. For parents, the information and recommendations they receive from healthcare professionals figure most frequently and most importantly in their decision making. For healthcare professionals, the certainty that the patient will not get better and discussions with the patient's family figure most importantly in their decision making. Once parents conclude that their child can not get better, they are more likely to choose noncurative options such as choosing no further treatment or withdrawing life support. IMPLICATIONS FOR NURSING PRACTICE: Nurses can help determine what information parents need in their decision making. Particular attention must be given to ways to communicate the likelihood of the their child's survival.

Adolescent

Assessment of nutritional status in dialysis patients.

Malnutrition is common in patients treated with maintenance dialysis and appears to influence mortality in these patients. Thus, assessment of the nutritional status of dialysis patients is important if one is to make appropriate treatment interventions. This article describes the various parameters used in assessing the nutritional status of patients treated by hemodialysis and continuous ambulatory peritoneal dialysis. The usefulness of these parameters, as well as the pitfalls in their interpretation, are also reviewed.

Humans

Screening the 3' region of the polycystic kidney disease 1 (PKD1) gene reveals six novel mutations.

Recently, the gene for the most common form of autosomal dominant polycystic kidney disease (ADPKD), PKD1 (polycystic kidney disease 1), has been fully characterized and shown to encode an integral membrane protein, polycystin, involved in cell-cell and/or cell-matrix interactions. Study of the PKD1 gene has been complicated because most of the gene lies in a genomic region reiterated several times elsewhere on the same chromosome, and consequently only seven mutations have been described so far. Here we report a systematic screen covering approximately 80% of the approximately 2.75 kb of translated transcript that is encoded by single-copy DNA. We have identified and characterized six novel mutations that, together with the previously described changes, amount to a detection rate of 10%-15% in the population studied. The newly described mutations are two deletions, an insertion of a T-nucleotide causing a frame shift, two single-base-pair substitutions resulting in premature stop codons, and a G-->C transversion that may be a missense mutation. These results have important implications for genetic diagnosis of PKD1 because they indicate that the majority of mutations lie within the duplicated area, which is difficult to study. The regions of polycystin removed in each mutation so far described are assessed for their functional significance; an area disrupted by two new small in-frame changes is highlighted. PKD1 mutations are contrasted with those in the PKD1/TSC2 contiguous-gene syndrome, and the likely mutational mechanism in PKD1 is considered.

Alternative Splicing

Difficulty accepting lifestyle limitations after the abrupt onset of end-stage renal disease.

Adjustment to the lifestyle changes imposed by end-stage renal disease is particularly difficult when the onset is abrupt and unheralded. A case of atheroembolism is presented in which living situation, dietary compliance, and family involvement are particularly problematic for the dialysis staff. Discussion by team members focuses on the evolution of a reasonable disposition through diligence and persistence, recognizing the need to compromise medical indications with individual lifestyle and available family support.

Adaptation, Psychological

Bacteriology of skin and soft-tissue infections: comparison of infections in intravenous drug users and individuals with no history of intravenous drug use.

The bacteriology of cutaneous or subcutaneous abscesses (86 specimens) among intravenous drug users (IVDUs) was compared with the bacteriology of abscesses (74 specimens) in patients with no history of intravenous drug use (non-IVDUs). The IVDU abscesses yielded 173 aerobes and 131 anaerobes. Staphylococcus aureus was the most common aerobe isolated (50% of specimens yielded this isolate), followed by "Streptococcus milleri" (46%). The commonly encountered anaerobes were Fusobacterium nucleatum (17%), pigmented Prevotella species (22%), Peptostreptococcus micros (17%), Actinomyces odontolyticus (15%), and Veillonella species (13%). The non-IVDU isolates included 116 aerobes and 106 anaerobes. S. aureus was isolated from 53% of these specimens, followed by coagulase-negative staphylococci (19%), "S. milleri" (19%), and Streptococcus pyogenes (16%). The main groups of anaerobes were Peptostreptococcus species (35%), Bacteroides species (19%), and gram-positive bacilli (31%). Overall, 67% of the IVDU isolates were of oral origin, compared with 25% of the non-IVDU isolates. Of the specimens from IVDUs and non-IVDUs, 48% and 67%, respectively, yielded only aerobes, and 2% and 4%, respectively, yielded only anaerobes. Sixty-four percent of the patients had one or more beta-lactamase-producing organisms.

Abscess

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