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Biomedical subjects

C Grady

Publications and source records attributed to C Grady.

At least 37 records · Page 2Linked to original sources
PubMed1994

HIV preventive vaccine research: selected ethical issues.

This paper explores three selected issues which present ethical challenges unique to the development and testing of preventive HIV vaccines. The issues are: when to move forward with large scale efficacy testing of vaccines, how to incorporate behavioral interventions into the study of vaccine efficacy, and how to plan for and mitigate social harms associated with participation in an HIV vaccine trial. Careful and ongoing consideration must be given to the ethical implications of these decisions. Proposed solutions include planning for a more complex prevention trial which would integrate the evaluation of behavioral interventions and vaccine efficacy; scrupulous attention to the process of individual informed consent and community participation; and serious and deliberate attempts to plan for, educate about, and minimize the social harms.

Acquired Immunodeficiency Syndrome↗
PubMed1994

Role of endothelium-derived nitric oxide in stimulation of Na(+)-K(+)-ATPase activity by endothelin in rabbit aorta.

An endothelium-derived factor with the properties of nitric oxide (NO) has recently been implicated in the regulation of basal Na(+)-K(+)-adenosinetriphosphatase (ATPase) activity in vascular smooth muscle. To determine whether this factor also plays a role in the stimulation of ouabain-sensitive (OS) 86Rb uptake by specific agonists, studies were carried out using rabbit aortic rings. In endothelium-intact rings incubated for 3 h with Krebs-Henseleit solution containing 5.5 mM glucose, endothelin (ET) caused a concentration-dependent increase in OS 86Rb uptake (maximal increase = 205%, with 100 nM ET). Incubation with phenylephrine (Phe; 0.1 and 1 microM) or phorbol 12,13-dibutyrate (PDBu; 0.1 microM), under the same conditions, increased OS 86Rb uptake by 128, 144, and 140%, respectively. Removal of endothelium before incubation decreased the ability of ET to stimulate OS 86Rb uptake by 38-45%, but it did not diminish the stimulation of OS 86Rb uptake by Phe or PDBu. An increase in the concentration of glucose from 5.5 to 44 mM diminished ET-stimulated OS 86Rb uptake by 50% in endothelium-intact rings but had no effect on Phe- or PDBu-induced increases in OS 86Rb uptake. Addition of the NO synthase inhibitor NG-monomethyl-L-arginine (L-NMMA; 0.3 mM) to the medium decreased ET-stimulated OS 86Rb uptake by 40%. Guanosine 3',5'-cyclic monophophate (cGMP) formation in endothelium-intact rings was also increased (65%) by ET but not by Phe or PDBu. The increase in cGMP by ET was totally inhibited by L-NMMA or endothelium denudation.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Stimulation of vascular Na(+)-K(+)-ATPase activity by nitric oxide: a cGMP-independent effect.

An endothelium-derived factor with the properties of nitric oxide (NO) has been implicated in the regulation of Na(+)-K(+)-adenosinetriphosphatase (ATPase) activity in vascular smooth muscle. To examine this phenomenon further and to explore its modulation by guanosine 3',5'-cyclic monophosphate (cGMP), studies were carried out in the isolated rabbit aorta. Incubation of endothelium-denuded rings with NO (1 microM) or sodium nitroprusside (SNP, 10 microM) caused a time-dependent increase in ouabain-sensitive (OS) 86Rb uptake with the maximal stimulation (approximately 170%) seen after 20 min. In contrast, increases in cGMP concentration caused by NO and SNP (40- and 20-fold increases, respectively) were transient, with peak values observed after 2 min and significantly lower values by 10 min. The ability of NO or SNP to increase OS Rb uptake in endothelium-denuded rings was not mimicked by incubation with 8-bromo- or dibutyryl-cGMP or increases in cGMP caused by treatment with the phosphodiesterase inhibitor isobutylmethylxanthine. Depletion of intracellular cGMP levels by the guanylate cyclase inhibitor LY83583 also did not alter OS Rb uptake. SNP-stimulated OS Rb uptake was not inhibited by LY83583 in endothelium-denuded rings; however, it was completely prevented by the Na(+)-H+ exchange inhibitors amiloride and ethylisopropylamiloride. The results suggest that NO stimulates Na(+)-K(+)-ATPase activity in rabbit aorta by a mechanism independent of its ability to increase the intracellular cGMP concentration. They also suggest that NO may stimulate Na(+)-K(+)-ATPase activity secondary to increases in Na(+)-H+ exchange.

Amiloride↗
PubMed1994

Reduction of functional neuronal connectivity in long-term treated hypertension.

BACKGROUND AND PURPOSE: Anatomic imaging of patients with chronic well-treated hypertension has demonstrated dilatation of the lateral cerebral ventricles and left brain atrophy, whereas positron emission tomography has shown only subtle reductions in regional cerebral metabolic rates for glucose in some subcortical nuclei. To further explore the implications of the imaging changes, an analytic technique designed to determine functional neuronal connectivity between regions of interest (ROIs) was applied to the data on regional cerebral metabolic rates for glucose to determine if and where in the brain reduction of functional neuronal connectivity occurred. METHODS: Glucose metabolism was measured by positron emission tomography in 17 older men (age, 68 +/- 8 years) with well-controlled, noncomplicated hypertension of at least 10 years' duration and in 25 age- and sex-matched healthy control subjects. A significant correlation difference analysis was performed to determine which ROI pairs had reduced correlation coefficients (reduced functional neuronal connectivity). The vascular pattern of the reduction was determined after allocating the ROIs to their appropriate vascular territories. RESULTS: Compared with the control subjects, hypertensive patients had reduced correlation coefficients in cortical territories of the internal carotid arteries but not of the vertebrobasilar arteries. The border zone supplied by the middle and anterior cerebral arteries was most affected. CONCLUSIONS: The border zone between the anterior and middle cerebral arteries is vulnerable to ischemia from carotid pathology, systemic hypotension, or both. We hypothesize that although these hypertensive patients were "well controlled" and had normal neuropsychological tests, they may have experienced ischemia severe enough to cause border zone reduction of functional neuronal connectivity as a result of carotid pathology, antihypertensive medications, hypotensive episodes with a right-shifted autoregulation curve, or other factors in isolation or combination.

Aged↗
PubMed1994

Neural-network classification of normal and Alzheimer's disease subjects using high-resolution and low-resolution PET cameras.

UNLABELLED: Neural-network classification methods were applied to studies of FDG-PET images of the brain acquired from a total of 77 "probable" Alzheimer's disease and 124 normal subjects at two different centers. METHODS: Classification performances, as determined by relative-operating-characteristic (ROC) analyses of cross-validation experiments, were measured for FDG PET images obtained with either a 15-mm FWHM PETT V or a 6-mm FWHM Scanditronix PC-1024-7B camera for various methods of data representation. Neural networks were trained to distinguish between normal and abnormal subjects on the basis of regional metabolic patterns. For both databases, classification performance could be improved by increasing the "resolution" of the representation (decreasing the region size) and by normalizing the regional metabolic values to the value of a reference region (occipital region). RESULTS: The optimal classification performance for Scanditronix data (ROC area = 0.95) was higher than that for PETT V data (ROC area = 0.87). Under Bayesian theory, the classification performance with Scanditronix data corresponded to an ability to change a pre-test probability of disease of 50% to a post-test probability of either 90% for a positive classification or 10% for a negative classification. CONCLUSION: This classification can be used to either strongly confirm or rule out the presence of abnormalities.

Aged↗
PubMed1993

Differential effect of metabolic fuels on the energy state and Na(+)-K(+)-ATPase in isolated cerebral microvessels.

Isolated bovine cerebral microvessels (ICMV) were incubated with different metabolic fuels to determine their ability to support microvessel Na(+)-K(+)-ATPase (quantitated as ouabain-sensitive 86Rb+ uptake) and the ATP/ADP ratio. In comparison with ICMV incubated with glucose, Na(+)-K(+)-ATPase activity was reduced by 55% after a 3-h incubation in fuel-free medium and by 30-40% after incubation with beta-hydroxybutyrate, acetoacetate, or glutamate. However, Na(+)-K(+)-ATPase activity was not significantly decreased in ICMV incubated with pyruvate or oleate plus carnitine. In contrast, only glucose was able to maintain the ATP/ADP ratio. To evaluate the effect of endogenous fatty acid metabolism on these parameters, ICMV were incubated with bromostearate, an inhibitor of fatty acid oxidation. Bromostearate decreased both Na(+)-K(+)-ATPase activity and the ATP/ADP ratio, even in the presence of glucose. These results indicate that the varying effects of different fuels on Na(+)-K(+)-ATPase in ICMV cannot be explained solely by their effects on the ATP/ADP ratio or on glycolytic ATP generation. They suggest that other fuel-modulated factors play a key role in regulating this enzyme.

3-Hydroxybutyric Acid↗
PubMed1992

Cerebral glucose metabolic rates after 30 and 45 minute acquisitions: a comparative study.

This study was undertaken to determine if measurements of absolute regional cerebral metabolic rate for glucose (rCMRglc) and variance of rCMRglc are independent of time between 30 and 45 min following injection of the radiotracer. Sixteen subjects received two sets of 18FDG PET scans commencing 30 and 45 min following intravenous injection of 18FDG. No statistically significant differences were detected in either absolute rCMRglc or rCMRglc variance between the two sets of scans. These data demonstrate that for most FDG PET studies, scanning can commence 30 min after injection of the radiotracer without compromising the metabolic data.

Adult↗
PubMed1991

Ethical issues in clinical trials.

The oncology nurse may assume many different roles in clinical trials, including direct care provider, educator, advocate, data collector, primary investigator, and member of the IRB. Regardless of the role, the nurse is in a key position to promote the interests of the individual subject as well as helping to assure that the clinical trial is conducted with scientific and ethical integrity. The nurse can help to assure that the subject is adequately informed and facilitate rational decision making. The nurse can also assure that the requirements of the protocol are consistently attended to and that subjects are well monitored and data precisely collected. "In oncology, perhaps more than in any other medical specialty, there is a blurring of the distinction between research, therapeutic innovation, and medical practice. The frontiers of knowledge in cancer are continuously advancing. The final step in the process of procuring usable knowledge is the clinical trial, a meeting place of the practice of medicine and clinical research. Because of this there are many ethical considerations which must be attended to in the justification of and conduct of a clinical trial.

Beneficence↗
PubMed1991

Confidentiality: a survey in a research hospital.

Despite the many justifications for protecting patient confidentiality, we recognize that confidentiality cannot be absolute. Our world of automated information and easy access and storage poses many threats to confidentiality. This paper has described a survey conducted at the NIH Clinical Center to assess the knowledge, attitudes, and behaviors of clinical physicians and nurses about confidentiality of patient information. The survey findings demonstrate the need for reminders and increased awareness about confidentiality in our setting. Most of the survey respondents had a good knowledge of what was expected of them, and they believed that confidentiality was important and maintaining it was their responsibility. Of interest was that in several simulated clinical situations, there was a discrepancy between what respondents indicated they should do and what they thought they would do. The biggest discrepancies appeared in situations that involved overhearing a patient conversation on the elevator, approaching an unfamiliar person who is reading a medical record in the nurses' station, and answering a patient's inquiry about the status of another patient. The findings support the speculation that this difference may be attributed to discomfort or decreased awareness, and not necessarily to lack of knowledge. Results indicate that policies and administrative expectations should be frequently communicated and enforced, and that educational programs that address issues of confidentiality should be provided. The results of this survey have been influential in guiding educational strategies and administrative activities at the clinical center. The clinical center initiated a confidentiality awareness campaign, displaying a new poster every three months in strategic locations and distributing other tangible reminders (such as pens, magnets, and buttons) containing the same confidentiality message.(ABSTRACT TRUNCATED AT 250 WORDS)

Attitude of Health Personnel↗
PubMed1991

High-resolution PET studies in Alzheimer's disease.

Forty-seven patients with probable dementia of the Alzheimer type (DAT) and 30 healthy age-matched controls were scanned using [18F]-2-fluoro-2-deoxy-D-glucose on a Scanditronix PC 1024-7B tomograph (inplane resolution = 6 mm, axial resolution = 10 mm). Patients and controls were scanned in the resting state with their eyes patched and ears occluded. The regional cerebral metabolic rates for glucose (rCMRglc) in most major neocortical and subcortical gray matter regions, and certain metabolic ratios (rCMRglc/ calcarine rCMRglc), quantitatively discriminated even the mildly demented patients from healthy controls. The association neocortices showed metabolic abnormalities that were more severe than those in the sensorimotor and calcarine regions. All demented groups showed significant neuropsychological disturbances when compared to healthy controls. These data demonstrated widespread metabolic disturbances, particularly in the association areas, relatively early in Alzheimer's disease, and more profound involvement with disease progression.

Alzheimer Disease↗
PubMed1990

Self-assessed learning needs of oncology nurses caring for individuals with HIV-related disorders. A national survey.

A national survey of 10% of the members of the Oncology Nursing Society (ONS) was conducted to determine the knowledge and experience of oncology nurses caring for individuals with HIV-related disorders. This information was to serve as the framework for developing subsequent education and preparation of oncology nurses. A questionnaire containing 109 questions was mailed to 1,006 members of the ONS. Response rate was 70% (N = 693). Fifty-five of the 109 questions assessed clinical knowledge, experience, and care planning for adults. Additional questions elicited information about staff attitudes, problems in care delivery, priorities in nursing administration and research, and nurses' preferred methods of instruction. Results showed that oncology nurses are experienced in certain areas of importance to patients with AIDS but have educational and experiential deficits in the disease specifics associated with HIV-related disorders and in the nursing care of adults with multisystem involvement and in their treatment. Validity and reliability of this questionnaire were established (alpha = 0.93-0.97). Readers are encouraged to adapt this questionnaire to assess the learning needs of nurses in all specialty groups, and to develop appropriate educational programs to prepare nurses to provide care for this patient population.

Adult↗
PubMed1989

Ethical issues in providing nursing care to human immunodeficiency virus-infected populations.

During the past few years, an incredible body of knowledge about HIV infection and all of its ramifications has been accumulated. As we consider whether or not our conduct toward persons who are HIV infected is right, however, many unanswered questions still exist. All health care professionals must be involved in reflection, re-examination of values, and ethical analysis of our behaviors. Nurses have an obligation to be informed about HIV infection, its clinical manifestations, treatments, and the care of affected persons. We must help our patients to know their needs and their options. We must listen to them. We must advocate for them. It has been said that nurses caring for patients with AIDS require two dominant characteristics: courage and impartiality. They need courage to face risks and impartiality to temper prejudice. In addition to these characteristics, nurses need a strong sense of caring, compassion for fellow human beings, and a conviction that they can make a difference in promoting a person's welfare and preserving his or her dignity.

Acquired Immunodeficiency Syndrome↗
PubMed1989

Acquired immunodeficiency syndrome. The impact on professional nursing practice.

The epidemic of human immunodeficiency virus (HIV) infection and all of its consequences has had a significant impact on our society and on the delivery of health care. This article explores the impact that HIV infection and AIDS has had on professional nursing practice. The risk of occupational exposure, the question of obligation to care, the need for reexamination of values, philosophy of nursing, and some of the ethical issues, the need for learning and relearning, and the need for supporting each other as individuals, co-workers, and co-professionals are discussed.

Acquired Immunodeficiency Syndrome↗
PubMed1988

HIV: epidemiology, immunopathogenesis, and clinical consequences.

HIV infection is a global problem, with the largest number of cases occurring in the United States. HIV affects men, women, and children with varying frequency in different parts of the world. The spectrum of HIV infection and its consequences is broad. HIV, a retrovirus, is responsible for gradual and progressive damage to the human immune system. Over the course of years (more than 7 in many), the resultant deficiency in cell-mediated immunity leaves the host susceptible to infections, malignancies, and possible neuropsychiatric abnormalities. Current efforts to better understand this virus, its interaction with the human immune system, its clinical consequences, and its detection will continue to bring us closer to finding effective means of preventing and treating HIV infection. In addition, an understanding of the epidemiology, immunopathogenesis, and clinical consequences of HIV infection will contribute to a more knowledgeable approach to caring for HIV-infected individuals and anticipating their many needs.

Acquired Immunodeficiency Syndrome↗
PubMed1987

Cerebral metabolism, anatomy, and cognition in monozygotic twins discordant for dementia of the Alzheimer type.

One pair of monozygotic twins discordant for dementia of the Alzheimer type (DAT) was studied using neuropsychological testing, quantitative x-ray computed tomography (QCT) and magnetic resonance imaging (MRI) of the brain. Cerebral glucose metabolism was measured using positron emission tomography (PET) and 2-[18-F]fluoro-2-deoxy-D-glucose (FDG). The affected twin had a seven year history of progressive cognitive impairment and was severely demented. Neuropsychological testing of the affected twin demonstrated marked deficits in all areas of cognitive function. The asymptomatic twin showed some impairment on tests of perceptual organisation and delayed recall. The affected twin had loss of gray matter and ventricular enlargement on QCT and MRI compared with healthy controls (p less than 0.05). He also had frontal and parietal lobe hypometabolism and increased asymmetry of metabolism on PET compared to both his twin and healthy age-matched controls (p less than 0.05). PET, QCT, and MRI distinguished changes in the twin with DAT compared with his brother and healthy controls. Although the subtle neuropsychological abnormalities of the asymptomatic twin may be signs of early DAT, they were not accompanied by any changes in regional cerebral metabolism or brain structure.

Alzheimer Disease↗