Search PubMed⌕ Search

Biomedical subjects

W Burke

Publications and source records attributed to W Burke.

At least 55 records · Page 3Linked to original sources
PubMed1999

Psychophysical observations concerned with a foveal lesion (macular hole).

A not uncommon occurrence in elderly people is the development of a 'macular hole' but very few psychophysical observations have been made in such cases. I describe here some distortions of image experienced when I view objects with my right eye which has a macular hole. Objects are distorted by being shrunk towards the fovea. Thus, a disc retains its shape but becomes smaller whereas lines are broken or bent. By analogy with animal experiments it is suggested that the perceptual changes are due to physiological changes in the visual cortex.

Humans↗
PubMed1999

Velocity response profiles of collicular neurons: parallel and convergent visual information channels.

We have recorded from single neurons in the retinorecipient layers of the superior colliculus of the cat. We distinguished several functionally distinct groups of collicular neurons on the basis of their velocity response profiles to photic stimuli. The first group was constituted by cells responding only to photic stimuli moving at slow-to-moderate velocities across their receptive fields (presumably receiving strong excitatory W-type input but not, or only subthreshold, Y-type input). These cells were recorded throughout the stratum griseum superficiale and stratum opticum and constituted 50% of our sample. The second group of cells exhibited excitatory responses only at moderate and fast velocities (presumably receiving excitatory Y-type but not W-type input). These cells constituted only about 7% of the sample and were located principally in the lower stratum griseum superficiale. The third group of cells was constituted by cells excited over the entire range of velocities tested (1-2000 /s) and presumably received substantial excitatory input from both W- and Y-channels. These cells constituted almost 26% of our sample and were located in the lower stratum griseum superficiale, stratum opticum and the upper part of the stratum griseum intermediale. Overall, cells receiving excitatory Y-type input, i.e. the sum of group two and group three cells, constituted about a third of the sample and their excitatory discharge fields were significantly larger than those of cells receiving only W-type input. A fourth distinct group of collicular neurons was also constituted by cells responding over a wide range of stimulus velocities. These cells were excited by slowly moving stimuli, while fast-moving photic stimuli evoked purely suppressive responses. The excitatory discharge fields of these cells (presumably, indicating the spatial extent of the W-input) were located within much larger inhibitory fields, the extent of which presumably indicates the spatial extent of the Y-input. These low-velocity-excitatory/high-velocity-suppressive cells were recorded from the stratum griseum superficiale, stratum opticum and stratum griseum intermediale and constituted about 17% of the sample. The existence of low-velocity-excitatory/high-velocity-suppressive cells in the mammalian colliculus has not been previously reported. Low-velocity-excitatory/high-velocity-suppressive cells might play an important role in activating "fixation/orientation" and "saccade" premotor neurons recorded by others in the intermediate and deep collicular layers. Overall, in the majority (57%) of collicular neurons in our sample there was no indication of a convergence of W- and Y-information channels. However, in a substantial minority of collicular cells (about 43% of the sample) there was clear evidence of such convergence and about 40% of these (low-velocity-excitatory/high-velocity-suppressive cells) appear to receive excitatory input from the W-channel and inhibitory input from the Y-channel.

Animals↗
PubMed1999

Screening for hemochromatosis. A public health perspective.

CONTEXT: The discovery of the HFE gene in 1996 has introduced DNA testing as a possible tool for screening and diagnosis of hemochromatosis and increased interest in the disorder. Population screening using transferrin saturation has been advocated by experts to permit early detection and treatment with phlebotomy before the onset of clinical disease. METHODS: Based on a literature review, we consider the relative risks and merits of two screening tests as part of a broader look at the evidence required for the recommendation of universal screening for hemochromatosis. RESULTS: Several questions must be answered before universal screening can be recommended. Uncertainties remain about the penetrance and preventable disease burden, laboratory standardization, and optimal strategies to minimize potential risks of screening for hemochromatosis. CONCLUSIONS: As a common genetic disorder with simple, effective therapy, hemochromatosis offers a model for other genetically influenced chronic diseases that some day may have interventions to improve prognosis. Resolution of questions related to prevention of chronic diseases from hemochromatosis, therefore, will have broad usefulness in the future.

Cost of Illness↗
PubMed1999

Screening for hereditary hemochromatosis: are DNA-based tests the answer?

Universal screening for hereditary hemochromatosis (HH) has been proposed by many experts, with understandable enthusiasm: HH can cause fatal complications, which are preventable with early treatment. The disorder involves excess iron accumulation that can result in tissue iron overload, with secondary cirrhosis, diabetes, heart failure, impotence and arthritis. These complications are preceded by years of iron accumulation, and most are believed to be preventable by removal of excess iron by phlebotomy. Thus, early identification and treatment - the quintessential functions of health screening - seem to make sense for HH. However, the available screening tests are imperfect. While they can identify many persons at increased risk from HH, the proportion that will develop serious clinical manifestations related to iron overload is not known with certainty. DNA-based tests do not provide a simple resolution to these questions.

Genetic Testing↗
PubMed1999

Attitudes and interest in genetic testing for breast and ovarian cancer susceptibility in diverse groups of women in western Washington.

OBJECTIVES: This paper examines the knowledge, opinions, and predictors of interest in genetic testing for breast cancer risk in a demographically diverse group of women in western Washington who participated in a randomized controlled trial (RCT) of breast cancer risk counseling methods. MATERIALS AND METHODS: Four groups of women were surveyed, all with some family history of breast cancer: (a) 307 white women; (b) 36 African-American women; (c) 87 lesbian/bisexual women; and (d) 113 Ashkenazi Jewish women. As part of the baseline questionnaire for the RCT, participants were asked about their familiarity with genetic testing for breast cancer risk, their interest in such testing and opinions of it, and actions they anticipated based on test results. RESULTS: Women in all four groups favored ready access to testing, believed the decision to be tested should be a personal choice, believed that genetic test results should stay confidential, and were not greatly concerned that this might not be possible. Women anticipated using such genetic test results to increase the frequency of various breast cancer screening methods (in all four groups, > 69% would increase mammogram frequency, > 85% would increase clinician exam, and > 92% would increase breast self exam). Women overwhelmingly rejected prophylactic surgery as a preventive measure (in all > 80% probably or definitely would not consider it). Significant predictors of interest in genetic testing for cancer risk included perceived risk, cancer worry, and beliefs about access to testing. CONCLUSIONS: These data will be of interest to health care providers, payers, public health professionals, legislators, and others as they consider issues associated with population testing for susceptibility to common diseases such as breast cancer.

Adult↗
PubMed1999

Participation in breast cancer risk counseling among women with a family history.

Recent scientific breakthroughs in the genetics of breast cancer may have had effects on women's perceptions of risk and subsequent worry about breast cancer. Here, we present the rates of interest in counseling among women identified from diverse sources, their levels of cancer worry and perceived risk, and predictors of their agreement to participate in breast cancer risk counseling. Women were identified through breast cancer cases and through media offers. They completed a telephone survey and were ultimately either entered or not entered into a counseling trial. Overall, almost half (46%) of cases who were approached responded to the contact letter asking for information about potentially interested relatives. A total of 588 women responded to the brief media solicitations over a 15-week period. Participants recruited from media contacts reported slightly but significantly higher levels of worry about getting cancer, compared to case-recruited participants. Cancer worry negatively and significantly predicted entry into the counseling project. The results presented here may have implications for recruiting women in the general population with a family history of breast cancer for counseling about their risk for the disease.

Adolescent↗
PubMed1998

Iron overload, public health, and genetics: evaluating the evidence for hemochromatosis screening.

Population screening for hemochromatosis done by using the transferrin saturation test has been advocated by experts to permit the initiation of therapeutic phlebotomy before the onset of clinical disease. The discovery of a gene associated with hemochromatosis has made DNA testing another option for screening and diagnosis. In this paper, U.S. Preventive Services Task Force criteria are used to evaluate the evidence for the usefulness of population screening done by using iron measures or genetic testing. Published clinical research offers little evidence to suggest that population screening for hemochromatosis done by using genetic testing improves clinical outcomes. Although one recently discovered mutation, C282Y, accounts for 60% to 92% of cases of the disease in series of patients with hemochromatosis, uncertainties remain about the clinical penetrance of various genotypes; the accuracy of genetic testing; and the ethical, legal, and social effects of genetic testing. Before population screening for hemochromatosis done by using transferrin saturation testing can be recommended, laboratory standardization needs to be addressed and questions about risk for clinical disease in asymptomatic persons with mutations or early biochemical expression of disease require resolution. Evidence from case series suggests that hemochromatosis may be associated with liver cancer, other liver disease, diabetes, bradyarrhythmias, and arthritis. In all studies but one, however, estimation of the magnitude and significance of this risk is limited by lack of adequate comparison groups. The need for population data to answer questions about penetrance among asymptomatic persons should not impede efforts to increase the detection and treatment of hemochromatosis in persons found to have elevated iron measures a family history of hemochromatosis, or consistent early signs and symptoms of the disease.

Hemochromatosis↗
PubMed1998

Hereditary hemochromatosis: gene discovery and its implications for population-based screening.

OBJECTIVE: To evaluate the role of genetic testing in screening for hereditary hemochromatosis to help guide clinicians, policymakers, and researchers. PARTICIPANTS: An expert panel was convened on March 3, 1997, by the Centers for Disease Control and Prevention (CDC) and the National Human Genome Research Institute (NHGRI), with expertise in epidemiology, genetics, hepatology, iron overload disorders, molecular biology, public health, and the ethical, legal, and social implications surrounding the discovery and use of genetic information. EVIDENCE: The group reviewed evidence regarding the clinical presentation, natural history, and genetics of hemochromatosis, including current data on the candidate gene for hemochromatosis (HFE) and on the ethical and health policy implications of genetic testing for this disorder. CONSENSUS PROCESS: Consensus was achieved by group discussion confirmed by a voice vote. A draft of the consensus statement was prepared by a writing committee and subsequently reviewed and revised by all members of the expert group over a 1-year period. CONCLUSIONS: Genetic testing is not recommended at this time in population-based screening for hereditary hemochromatosis, due to uncertainties about prevalence and penetrance of HFE mutations and the optimal care of asymptomatic people carrying HFE mutations. In addition, use of a genetic screening test raises concerns regarding possible stigmatization and discrimination. Tests for HFE mutations may play a role in confirming the diagnosis of hereditary hemochromatosis in persons with elevated serum iron measures, but even this use is limited by uncertainty about genotype-phenotype correlations. To address these questions, the expert group accorded high priority to population-based research to define the prevalence of HFE mutations, age and sex-related penetrance of different HFE genotypes, interactions between HFE genotypes and environmental modifiers, and psychosocial outcomes of genetic screening for hemochromatosis.

Female↗
PubMed1998

A novel substance associated with gallamine-induced myoclonus.

If gallamine or d-tubocurarine gains access to the central nervous system it produces a myoclonus, a synchronized jerking of many skeletal muscles. Each jerk is accompanied by a slow wave in the inferior olive. The jerking continues for 24 h or more after the gallamine or d-tubocurarine can no longer be detected in the CSF. We report here that a novel substance appears in the CSF and persists for a long period of time, possibly as long as the twitching. This substance is not corticotrophin-releasing factor (CRF) nor does CRF or harmaline (a substance causing a tremor by an action on the inferior olive) lead to the appearance of the novel substance. At present the nature of this substance is not known.

Animals↗
PubMed1998

Testing for inherited susceptibility to breast cancer: a survey of informed consent forms for BRCA1 and BRCA2 mutation testing.

The identification of genetic mutations linked to breast cancer has made it possible to test for the genetic predisposition to this disease. However, though this test may provide certain benefits, there are also potential risks involved with the testing process, including social and economic considerations. In light of these potential risks, we sought to determine what information individuals are receiving in the informed decision making process. To learn the minimal amount of information the actual testees receive, we obtained 10 informed consent forms from seven different testing facilities. These testing centers include the major sources of BRCA1 and BRCA2 mutation testing in the United States at this time. We analyzed the content of these forms by developing content categories and scoring them appropriately. We found all ten forms discussed in varying ways and to varying degrees the purpose of genetic testing, limitations of the test, implications of both positive and negative results, and confidentiality procedures; most, but not all, addressed various psychological and insurance risks. Overall, the forms demonstrated substantial variation in content and organization, underlining the need for more discussion and research on the purpose, nature, and effectiveness of informed consent forms for this type of genetic test.

BRCA1 Protein↗
PubMed1998

Excitatory convergence of Y and non-Y channels onto single neurons in the anterior ectosylvian visual area of the cat.

Numerous functional and hodological studies of the anterior ectosylvian visual area (AEV) of the cerebral cortex of the cat suggest that this area plays an important role in processing information about visual motion. In the present study, in cats with selective conduction block of Y fibres in one optic nerve, we have examined the extent of the excitatory convergence of Y (presumed 'motion channel') and non-Y information channels on single neurons in AEV, as well as the contribution of the Y channel to the receptive field properties of AEV neurons. While in normal cats all neurons recorded from AEV were binocular, i.e. could be photically activated via either eye, in cats with selective conduction block of Y fibres in one optic nerve, a significant proportion (about 15%) of AEV cells could be photically activated only via the normal eye. In comparison to those in normal cats, the peak discharge rates of AEV neurons in the Y-blocked cats were drastically reduced not only when photic stimuli were presented via the Y-blocked eye, but also when they were presented via the normal eye. Selective block of Y input also resulted in a significant shift in velocity preferences towards the lower velocities. However, the direction selectivity indices of AEV neurons were not affected by selective Y block. Thus: (i) the responses of AEV neurons to a high velocity of motion are dependent on the integrity of the Y input; (ii) the 'spontaneous' (i.e. not photically evoked) discharges of Y retinal ganglion cells exert a facilitatory influence on the responses of AEV cells to photic stimuli; (iii) although the responses of AEV neurons are dominated by the Y inputs, AEV neurons also receive significant non-Y excitatory inputs; and (iv) the strong direction selectivity revealed in most AEV neurons does not dependent on the integrity of Y input.

Animals↗
PubMed1998

What influences career choices among graduates of a primary care training program?

OBJECTIVE: To identify factors that influence primary care residents to become generalists or specialists. DESIGN: Structured survey and interview. SETTING: A large university-based, internal medicine residency program in primary care. PARTICIPANTS: Of 92 residency graduates who completed training between 1979 and 1993, 88 (96%) participated. MAIN RESULTS: Although 82% of the participating graduates reported themselves very committed to primary care at the beginning of residency, only 68% pursued generalist careers. Factors influencing career choice that were more important to generalists than specialists included breadth of knowledge used in primary care practice (p = .04), breadth of clinical problems in practice (p = .001), and opportunity for continuity of care (p = .01). Although salary was rated "not important," 50% of generalists and specialists advocated increased salaries for generalists as a way to increase interest in primary care. Other promoting factors included mentors, increased prestige for generalists, community-based training, lifestyle changes, and decreased paperwork. Seventy-three percent of participants felt it was easier to be a specialist than a generalist. CONCLUSIONS: A substantial minority of primary care residents pursue specialty careers. To produce more generalists, graduates recommend addressing income inequities, providing generalist role models, increasing community-based teaching, and increasing prestige for generalists.

Career Choice↗
PubMed1998

Hemochromatosis: genetics helps to define a multifactorial disease.

Hereditary hemochromatosis (HH) is a common autosomal recessive disorder that can result in iron overload and a wide range of clinical complications, including hepatic cirrhosis, diabetes mellitus, hypopituitarism, hypogonadism, arthritis, and cardiomyopathy. People with HH can be detected at an asymptomatic stage of the disease by abnormalities in serum iron measures. Early detection is desirable, because periodic phlebotomy provides effective treatment for iron overload and may prevent complications of the disorder. The natural history of HH is poorly understood, however, and the proportion of people detected by screening who will develop serious complications of HH is unknown. The genetics of HH may help to resolve these questions. The gene, HFE, and two mutations, C282Y and H63D, have been identified: the C282Y mutation has a higher penetrance than the H63D mutation, and appears to result in a greater loss of HFE protein function. Most people with HH are C282Y homozygotes, a small proportion are compound heterozygotes or H63D homozygotes, and some have no identifiable HFE mutation or are HFE heterozygotes, suggesting that additional mutations associated with HH are yet to be found. Gender and environmental agents, such as alcohol and dietary iron, influence phenotypic expression of HH. The severity of HH is thus determined by an interaction between genotype and modifying factors. HFE mutations also appear to increase the likelihood of iron overload in inherited anemias and to promote the clinical manifestations of porphyria cutanea tarda. HH is an important paradigm for medical genetics because it offers an opportunity to explore the complexity of gene gene and gene environment interactions.

Genetic Testing↗
PubMed1997

Recommendations for follow-up care of individuals with an inherited predisposition to cancer. II. BRCA1 and BRCA2. Cancer Genetics Studies Consortium.

OBJECTIVE: To provide recommendations for cancer surveillance and risk reduction for individuals carrying mutations in the BRCA1 or BRCA2 genes. PARTICIPANTS: A task force with expertise in medical genetics, oncology, primary care, gastroenterology, and epidemiology convened by the Cancer Genetics Studies Consortium (CGSC), organized by National Human Genome Research Institute (previously the National Center for Human Genome Research). EVIDENCE: Studies evaluating cancer risk, surveillance, and risk reduction in individuals genetically susceptible to breast and ovarian cancer were identified using MEDLINE (National Library of Medicine) and from bibliographies of articles thus identified. Indexing terms used were "genetics" in combination with "breast cancer," "ovarian cancer," and "screening," or "surveillance" in combination with "cancer family" and "BRCA1" and "BRCA2." For studies evaluating specific interventions, quality of evidence was assessed using criteria of the US Preventive Services Task Force. CONSENSUS PROCESS: The task force developed recommendations through discussions over a 14-month period. CONCLUSIONS: Efficacy of cancer surveillance or other measures to reduce risk in individuals who carry cancer-predisposing mutations is unknown. Based on expert opinion concerning presumptive benefit, early breast cancer and ovarian cancer screening are recommended for individuals with BRCA1 mutations and early breast cancer screening for those with BRCA2 mutations. No recommendation is made for or against prophylactic surgery (eg, mastectomy, oophorectomy); these surgeries are an option for mutation carriers, but evidence of benefit is lacking, and case reports have documented the occurrence of cancer following prophylactic surgery. It is recommended that individuals considering genetic testing be counseled regarding the unknown efficacy of measures to reduce risk and that care for individuals with cancer-predisposing mutations be provided whenever possible within the context of research protocols designed to evaluate clinical outcomes.

Antineoplastic Agents, Hormonal↗
PubMed1997

Recommendations for follow-up care of individuals with an inherited predisposition to cancer. I. Hereditary nonpolyposis colon cancer. Cancer Genetics Studies Consortium.

OBJECTIVE: To provide recommendations for cancer surveillance and risk reduction for individuals carrying mutations associated with hereditary nonpolyposis colon cancer (HNPCC). PARTICIPANTS: A task force with expertise in medical genetics, oncology, primary care, gastroenterology, and epidemiology convened by the Cancer Genetics Studies Consortium (CGSC), organized by the National Human Genome Research Institute (previously the National Center for Human Genome Research). EVIDENCE: Studies evaluating cancer risk, surveillance, and risk reduction in individuals genetically susceptible to colon cancer were identified using MEDLINE and bibliographies of articles thus identified. Indexing terms used were "genetics" in combination with "colon cancer," and "screening" in combination with "cancer family" and "HNPCC." For studies evaluating specific interventions, quality of evidence was assessed using criteria of the US Preventive Services Task Force. CONSENSUS PROCESS: The task force developed recommendations through discussions over a 14-month period. CONCLUSIONS: Efficacy of cancer surveillance or other measures to reduce risk in individuals who carry cancer-predisposing mutations is unknown. Based on observational studies, colonoscopy every 1 to 3 years starting at age 25 years is recommended for individuals known to have HNPCC-associated mutations. Endometrial cancer screening is also recommended, based on expert opinion concerning presumptive benefit. No recommendation is made for or against prophylactic surgery (ie, colectomy, hysterectomy); these surgeries are an option for mutation carriers, but evidence of benefit is lacking. It is recommended that individuals considering genetic testing be counseled regarding the unknown efficacy of measures to reduce risk and that care for individuals with cancer-predisposing mutations be provided whenever possible within the context of research protocols designed to evaluate clinical outcomes.

Adaptor Proteins, Signal Transducing↗