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Biomedical subjects

K Parker

Publications and source records attributed to K Parker.

At least 37 records · Page 2Linked to original sources

Clomipramine versus haloperidol in the treatment of autistic disorder: a double-blind, placebo-controlled, crossover study.

Clomipramine, haloperidol, and placebo were compared with baseline in the treatment of autism, and overall outcome, specific symptoms, and side effects were examined. It was hypothesized that clomipramine would be better tolerated than haloperidol and prove superior on a measure of stereotypy. Individuals with a DSM-IV diagnosis of autistic disorder (mean age, 16.3 years; range, 10-36 years) were randomly assigned, by using a Latin square design, to the following 7-week trials: placebo, clomipramine (mean daily dose, 128.4 mg; range, 100-150 mg), or haloperidol (mean daily dose, 1.3 mg; range, 1-1.5 mg). Data on 36 subjects were analyzed and taken together; the results favored haloperidol. In those patients who were able to complete a full therapeutic trial, clomipramine proved comparable to haloperidol in terms of improvement compared with baseline. However, significantly fewer individuals receiving clomipramine versus haloperidol were able to complete the trial (37.5% vs. 69.7%, respectively) for reasons related to both side effects and efficacy or behavior problems. In the intent-to-treat sample, which is perhaps more clinically relevant, only haloperidol proved superior to baseline on a global measure of autistic symptom severity, as well as specific measures for irritability and hyperactivity. Clomipramine did not seem more effective on a measure of stereotypy, nor was it better tolerated.

Adolescent↗

A thin film phantom for blood flow simulation and Doppler test.

The thin film phantom is a new type of ultrasound resolution test object. It consists of a thin planar substrate that is acoustically matched to the surrounding media. Precisely located scatterers on the surface of the substrate generate echo signals. The patterning of scatterers on the substrate allows echogenicity to be controlled as a function of position, which enables the production of a test object with highly reproducible and controllable scattering characteristics. We show that by vibrating the substrate in a suitable manner, an echo signal may be generated that simulates bi-directional flow. We demonstrate that a vibration of low amplitude at frequency f0 produces a Doppler spectral signal at f0 and -f0, within the limits of aliasing. Furthermore, by driving the film with a bandlimited noise signal, we illustrate how a velocity distribution may be simulated. A time-varying flow velocity may be simulated by varying the noise bandwidth with time. Finally, using this technique, we demonstrate a system that simulates an arterial flow pattern, including its characteristic velocity distribution in forward and reverse directions simultaneously.

Blood Flow Velocity↗

Disruption of the gene encoding SF-1 alters the distribution of hypothalamic neuronal phenotypes.

The ventromedial nucleus of the hypothalamus (VMH) in mice first emerges as a histologically distinct cell cluster around embryonic day 17 (E17). The earliest known marker for cells destined to form the VMH is the orphan nuclear receptor, steroidogenic factor 1 (SF-1), which can be detected in the hypothalamic primordium by E11. Strikingly, the VMH is absent in newborn SF-1 knockout mice, suggesting that SF-1 is essential for the development of VMH neurons. We reported previously that the VMH can be identified before it emerges as a histologically distinct nucleus (i.e., at E13) by the exclusion of cells that are immunoreactive for both gamma-aminobutyric acid (GABA) and the synthetic enzyme, glutamic acid decarboxylase (GAD67). Subsequently, by E15, the developing VMH is demarcated further by cells that are immunoreactive for neuropeptide Y, estrogen receptor alpha (ERalpha), and galanin. It is noteworthy that the normal exclusion of GABA from the developing VMH is not seen in SF-1 knockout mice, and cells that are immunoreactive for neuropeptide Y, ERalpha, and galanin also are distributed aberrantly in this region. Thus, the absence of SF-1 profoundly affects the cellular architecture of the VMH from early stages in its formation. These data suggest that, directly or indirectly, SF-1 plays important roles in determining the distribution of cells in the mediobasal hypothalamus.

Animals↗

Developmental expression of aquaporin 2 in the mouse inner ear.

OBJECTIVES: The maintenance of endolymph homeostasis is critical for the inner ear to perform its functions of hearing and maintaining balance. The identification and cloning of aquaporins (a family of water channel proteins) has allowed the study of a novel cellular mechanism potentially involved in endolymph homeostasis. The objective of the present study was to define the developmental temporal and spatial expression pattern of aquaporin 2 (Aqp2) in the developing mouse inner ear. STUDY DESIGN: A systematic immunohistochemical study of Aqp2 protein expression was performed on embryonic mouse inner ears ranging from embryonic day 10 (otocyst stage) to embryonic day 18 (just before birth). METHODS: Serial cryosections of embryonic mouse inner ears were used for immunohistochemical experiments. A rabbit polyclonal antisera raised against a synthetic Aqp2 peptide was used with a standard nickel intensified 3,3-diaminobenzidine reaction protocol for immunolocalization of Aqp2 in tissue sections. RESULTS: Aquaporin 2 is expressed diffusely in the early otocyst, then becomes progressively restricted as the inner ear matures. During early cochlear duct formation (embryonic days 12 and 13), expression of Aqp2 is homogeneous; later, it becomes restricted to specific regions of the endolymphatic compartment (embryonic days 15 and 18). Similar restriction of expression patterns could be noted for the vestibular structures. Endolymphatic duct and sac and stria vascularis expression of Aqp2 was noted to occur fairly late during development but demonstrated a distinct pattern of immunolabeling. CONCLUSIONS: Aquaporin 2 shows an early and specific pattern of expression in the developing mouse inner ear, suggesting a significant role for this water channel protein in the development of endolymph homeostasis and meriting further functional studies of Aqp2 in the inner ear.

Animals↗

Human herpesvirus 8 open reading frame 26 and open reading frame 65 sequences from multiple myeloma patients: a shared pattern not found in Kaposi's sarcoma or primary effusion lymphoma.

Human herpesvirus 8 (HHV-8), also known as Kaposi's sarcoma-associated herpesvirus, has been implicated in the pathogenesis of Kaposi's sarcoma (KS), primary effusion lymphoma (PEL), multicentric Castleman's disease, and recently multiple myeloma (MM). DNA sequence analyses of HHV-8 suggest that multiple HHV-8 strains exist. We extracted DNA from 24 patients with MM and 3 patients with monoclonal gammopathy of undetermined significance and compared HHV-8 open reading frames (ORFs) 26 and 65 sequences with those derived from patients with KS, PEL, and two HHV-8-positive PEL cell lines KS-1 and BC-1. ORF26 sequence data suggest that MM patients are consistently carriers of HHV-8 strain subtype C3. All MM patients also consistently revealed either a single bp deletion or substitution at position 112197 in ORF65. This unique alteration is not present in patients with KS or PEL or in PEL cell lines. It occurs in the portion of ORF65 that is known to be responsible for a serological response to HHV-8.

Amino Acid Sequence↗

Otoliths developed in microgravity.

Little is known about mechanisms that regulate the development of the otoliths in the gravity-sensing organs. Several reported experiments suggest that the growth of the otoliths is adjusted to produce a test mass of the appropriate weight. If this is the case, larger than normal otoliths would be expected in animals reared in reduced gravity and a reduced mass, relative to 1-g controls, would be expected in animals reared at elevated g. In gastropod mollusks, the gravity-sensing organ is the statocyst, a spherical organ whose wall is made largely of sensory receptor cells with motile cilia facing the lumen. Dense statoconia in the cyst lumen interact with cilia of receptor cells at the bottom of the cyst and action potentials in their axons carry information on direction and magnitude of gravity and linear acceleration. In the marine mollusk, Aplysia californica, larvae reared at 2 to 5-g, the volume of statoconia was reduced in a graded manner, compared to 1-g control animals. In the statocyst of the fresh-water pond snail, Biomphalaria glabrata, reared in space in the Closed Equilibrated Biological Aquatic System (CEBAS), the number and total volume of statoconia was increased approximately 50%, relative to ground-reared controls. Lychakov found the utricular otolith to be 30% larger in space-reared Xenopus, whereas we found the saccular otolith to be significantly larger in newt larvae reared in space. In cichlid fish reared on a centrifuge, the saccular otolith was smaller than in 1-g controls. Here, we demonstrate that the otoliths of late-stage embryos of the swordtail fish, Xiphophorus helleri, reared in space on STS-89 and STS-90 (Neurolab) were significantly larger than those of ground-controls reared in functionally identical hardware.

Animals↗

Evaluation and treatment of weight loss in adults with HIV disease.

Weight loss late in the course of human immunodeficiency virus (HIV) disease is common and often multifactorial. Increased energy expenditure in response to opportunistic disease, as well as to HIV infection itself, can lead to protein-calorie malnutrition similar to that observed in starvation. Weight loss of as little as 5 percent in patients with HIV infection is associated with an increased risk of disease progression. Loss of body cell mass carries a particularly poor prognosis, and aggressive measures should be taken to stop such depletion. Patients exhibiting unexpected weight loss should be carefully examined to exclude decreased food intake, malabsorption, occult infection or neoplasm as the etiology of the weight loss. Early aggressive treatment of HIV disease and underlying opportunistic pathology, along with adequate pharmacologic, hormonal, nutritional and physical therapy, can often restore normal weight and body composition.

AIDS-Related Opportunistic Infections↗

Promoting evidence-based practice: managing change in the assessment of pressure damage risk.

AIMS: This study set out to facilitate the development of evidence-based practice in the assessment of pressure damage risk to patients within a large acute hospital. BACKGROUND: The importance of nursing practice being based on the best available evidence is emphasized in recent health policy. Meeting this objective is not easy as both individual and organizational factors create barriers to the implementation of research findings and the achievement of change. METHODS: The study was based on an action research model. It comprised three stages: a review of the research evidence; a survey of qualified nurses' knowledge of risk assessment of pressure damage and an audit of record keeping, and a multifaceted approach to achieving change in which researchers, managers, practitioners and clinical nurse specialists worked together collaboratively. FINDINGS: The findings from the survey and audit indicated a shortfall in nurses' knowledge of risk assessment of pressure damage and in their record keeping. The researchers, with the help of the clinical nurse specialist, built upon these findings by assisting practitioners and managers to take ownership of the need to base practice on the appropriate evidence. CONCLUSIONS: Achieving evidence-based practice is a complex undertaking that requires the development of an evaluative culture and a commitment by practitioners and managers to change practice. Researchers can play a valuable role in facilitating this process.

Evidence-Based Medicine↗

Health status and access to care among rural minorities.

This paper provides a review of the scholarly and applied literature published between 1970 and 1993 on health and health care access problems among racial and ethnic minority group members living in rural U.S. areas. Results on the distribution of specific illnesses and diseases, and utilization of medical services are summarized for two major minority groups--African Americans and Hispanic Americans. Findings generally document the expected pattern of rural and minority disadvantage. A review of the conceptual and methodological limitations of existing research suggests that research does not yet permit any clear understanding of the underlying structures and processes that give rise to racial health disparities. Very little is known about the health of rural minorities living in some areas of the country, for example, the west north central United States (Kansas, Missouri, Nebraska, Iowa, North Dakota, South Dakota and Minnesota).

Black or African American↗

Investigation of distal aortic compliance and vasodilator responsiveness in heart failure due to proximal aortic stenosis in the guinea pig.

Hypotension and syncope are recognized features of chronic aortic stenosis. This study examined vasomotor responses and dynamic compliance in isolated abdominal aortae after chronic constriction of the ascending aorta. Guinea pigs underwent constriction of the ascending aorta or sham operation. Sections of descending aorta were removed for studies of contractile performance and compliance. Dynamic compliance was measured using a feedback-controlled pulsatile pressure system at frequencies of 0.5, 1.5 and 2.5 Hz and mean pressures from 40 to 100 mmHg. Chronic (149+/-6 days) aortic constriction resulted in significant increases in organ weight/body weight ratios for left ventricle (58%), right ventricle (100%) and lung (61%). The presence of heart failure was indicated by increased lung weights, left ventricular end-diastolic pressure and systemic vascular resistance, reduced cardiac output and increased levels of plasma atrial natriuretic peptide (166%), adrenaline (x20), noradrenaline (106%) and dopamine (x3). Aortic rings showed similar constrictor responses to phenylephrine and angiotensin II, but maximal vasodilator responses to acetylcholine and isoprenaline were significantly increased (144% and 48% respectively). Dilator responses to sodium nitroprusside, forskolin and cromokalim were unchanged. Compliance of all vessels decreased with increasing pulsatile frequency and to a lesser extent with increased mean pressure, but were similar in aortic-constricted and control groups. Chronic constriction of the ascending aorta resulted in heart failure and increased vasodilator responses to acetylcholine and isoprenaline in the distal aorta while dynamic compliance was unchanged. We hypothesize that increased endothelium-mediated vasodilatation may contribute to hypotension and syncope in patients with left ventricular outflow obstruction.

Animals↗

Research priorities for nephrology nursing: American Nephrology Nurses' Association's Delphi Study.

The purpose of this study was to identify and prioritize research topics of importance for nephrology nursing and the American Nephrology Nurses' Association (ANNA). This was an explorative survey design using the Delphi technique. Nephrology nurses who are members of ANNA participated in the study. In Round 1 participants included 90 members of the Advanced Practice Special Interest Group. Round 2 participants were 537 nephrology nurses who attended the 28th ANNA National Symposium. Participants in Round 3 were 491 ANNA members who had at least a master's degree in nursing or another field. A three-round Delphi technique was used to solicit, identify, and prioritize problems for nephrology nursing research. In Round 1, 90 nurses identified problems in response to an open-ended question. These responses were analyzed and categorized into a 21-item research survey that was used for subsequent rounds. Round 2 participants rated each research question/topic on the survey on a 1 to 5 scale for level of importance. In addition, they were asked to identify the top-ranked research priorities from the 21 questions. In Round 3, the participants were asked to do the same as in Round 2. In addition, they indicated whether the research priority was primarily a nursing responsibility or a collaborative effort with other health care personnel. Based on 3 rounds of the Delphi study and analysis of both level of importance and rated-research priority, the five areas that were identified as research priorities are (a) nursing interventions to prevent vascular access infections, (b) nursing interventions to maintain vascular access patency, (c) educational needs of patients and families, (d) levels of nursing competence and the effect on patient outcomes, and (e) validation of nursing interventions to achieve patient outcomes. These research priorities provide direction for nephrology nursing research and the ANNA. This Delphi study represents a significant step for ANNA in its commitment to research.

Adult↗

Botanical medicines with gynecological anticancer activity: a literature review.

This article reviews the existing scientific literature reporting effects of botanical substances on the prevention and treatment of gynecological cancers. Anticancer effects were reported for 14 of 27 herbal substances searched for, 8 of which had reported effects specifically in gynecological cancer models. Research reviewed included in vitro studies in gynecological cancer cell lines, animal studies, an ex vivo study, and an epidemiological study. No clinical trials on gynecological cancer prevention or treatment were found for any of the 8 identified agents. Despite the increasing use of botanical medicines in the prevention and treatment of cancer in general, there is a paucity of studies describing their efficacy or safety in gynecological cancer. Given the prevalent use of botanical medicine in complementary and alternative cancer therapy, the need for research to evaluate safety and efficacy using both in vitro and in vivo methods is pressing.

Animals↗

Determinants of mortality in elderly patients with heart failure: the role of angiotensin-converting enzyme inhibitors.

BACKGROUND: Despite randomized controlled trials demonstrating mortality reduction, many studies have documented persistent low rates of prescription of angiotensin-converting enzyme inhibitors (ACE-I) in patients with heart failures; the reasons for this pattern remain poorly defined. In addition, some authors have argued that the results of carefully controlled clinical trials do not translate well into the uncontrolled world of clinical practice, and the mortality benefits of ACE-I may not extend into special populations such as the elderly. OBJECTIVES: To understand the reasons for failure to prescribe ACE-I to Medicare patients with heart failure and to assess the impact of this failure on mortality. METHODS: We obtained data by reviewing charts of Medicare patients discharged from 7 Colorado hospitals with a diagnosis of heart failure during 1994. RESULTS: We identified a diagnosis of heart failure in 1016 patients without a contraindication to ACE-I. Three hundred seventy-eight of these patients were receiving ACE-I at the time of admission. Of the 638 remaining, 257 had their left ventricular systolic function assessed and 92 had diminished function. Of these 92, 50 (54.3%) were discharged on a regimen of ACE-I. The only significant difference in baseline comorbidity or demographic variables between those given and those not given ACE-I was that patients not prescribed ACE-I were older. Using multivariate analysis, younger age and cardiology consultation predicted ACE-I prescription (P = .02). By life-table analysis, mortality at 1 year following discharge from the index hospitalization was lower in those treated with ACE-I than in those not so treated (P = .03). The Deyo index of comorbidity, prescription of an ACE-I, site of treatment, and presence or absence of cardiology consultation were significantly associated with 1-year mortality by multivariate analysis (P<.001). CONCLUSIONS: Underinvestigation and undertreatment of chronic heart failure persists. Failure to treat elderly patients with ACE-I is associated with a mortality that appears to be greater than that seen in the placebo arms of large clinical trials of ACE-I therapy. Within the population studied, older patients are less likely to be treated. Failure of age to significantly add to prediction of mortality implies that the apparent bias against treating older patients with chronic heart failure with ACE-I is not justified. Because mortality is dependent on provider and site of treatment, further reductions in mortality from chronic heart failure may require intensive and selective local efforts, or development of regional heart failure centers.

Aged↗

The P2X1 receptor, an adenosine triphosphate-gated cation channel, is expressed in human platelets but not in human blood leukocytes.

Extracellular adenosine triphosphate (ATP) and adenosine diphosphate (ADP) activate multiple types of P2-nucleotide receptors expressed in platelets or leukocytes. Electrophysiological and biochemical studies have indicated expression of the P2X1 receptor, an ATP-gated cation channel, in human and rat platelets, rat basophilic leukemia (RBL) cells, and phorbol myristate acetate (PMA)-differentiated HL-60 myeloid cells. Although these findings suggest that P2X1 receptors are present in both blood leukocytes and blood platelets, the relative levels of P2X1 receptor expression and function in human blood leukocytes and platelets have not been directly characterized. On the basis of both immunoblot analysis and functional assays of P2X1 receptor-mediated ionic fluxes, we report that there is significant expression of P2X1 receptors in human platelets, but not in neutrophils, monocytes, or blood lymphocytes. Thus, unlike platelets and myeloid progenitor cell lines, fully differentiated human blood leukocytes do not express functionally significant numbers of P2X1 receptors, suggesting the downregulation of P2X1 receptor gene expression during the differentiation of phagocytic leukocytes. By contrast, P2X1 receptor expression is strongly maintained during megakaryocytic differentiation and platelet release. Immunoblot analysis indicated that the platelet P2X1 receptor migrates as an approximately 60-kD protein during SDS-electrophoresis under reducing or nonreducing conditions. Treatment of platelet membranes with endoglycosidase-F causes the P2X1 receptor band to migrate as a 46-kD protein, verifying the highly glycosylated nature of the mature receptor protein. Additional studies of nucleotide-induced changes in Ca2+ influx/mobilization demonstrated that the platelet P2X1 receptors are pharmacologically distinct from the well-characterized ADP receptors of these cells. This finding suggests a unique role for these ATP-gated ion channels during hemostasis or thrombosis.

Adenosine Triphosphate↗

3D visual presentation of shoulder joint motion.

The 3D visual presentation of biodynamic events of human joints is a challenging task. Although the 3D reconstruction of high contrast structures from CT data has been widely explored, then there is much less experience in reconstructing the small low contrast soft tissue structures from inhomogeneous and sometimes noisy MR data. Further, there are no algorithms for tracking the motion of moving anatomic structures through MR data. We represent a comprehensive approach to 3D musculoskeletal imagery that addresses these challenges. Specific imaging protocols, segmentation algorithms and rendering techniques are developed and applied to render complex 3D musculoskeletal systems for their 4D visual presentation. Applications of our approach include analysis of rotational motion of the shoulder, the knee flexion, and other complex musculoskeletal motions, and the development of interactive virtual human joints.

Adult↗

Comparison of three solid phase supports for promoting three-dimensional growth and function of human liver cell lines.

An extracorporeal liver support system will require that liver cells maintain their normal differentiated function. This is more likely to be achieved utilizing a three-dimensional culture configuration rather than a simple monolayer culture. We present data on a human liver cell line attached and maintained on different three-dimensional supports, porous glass (Siran), silicon (Immobasil), and calcium-alginate beads. Albumin, fibrinogen, prothrombin, alpha1-acid glycoprotein and alpha1-antitrypsin secretions were measured. Proliferation was slower on each of the three-dimensional supports than on the monolayer culture. The protein secretion of all 5 proteins was highest in cells encapsulated in alginate; silicon beads supported greater protein secretion than glass. Cells on silicon or within alginate were rounded; those on glass grew in 2 configurations as flattened monolayers and as rounded colonies. Cells in alginate secreted as much protein as the whole liver (e.g., albumin, 14.88 g/10(12) cells/day compared to the whole liver, approximately 12 g/day). Three-dimensional culture of a human liver cell line leads to both proliferation and a high synthetic capacity, an important feature of cells suitable for an extracorporeal liver support system.

Albumins↗