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PubMed2000

Mammalian acyl-CoA:cholesterol acyltransferases.

Cholesterol, the chief sterol found in vertebrates, exists both as a free sterol and as a component of cholesterol esters, which are synthesized by acyl-CoA:cholesterol acyltransferase (ACAT) enzymes. Considerable knowledge concerning cholesterol ester metabolism has accumulated during the past century. However, rapid advances have occurred in the past 7 years since the cloning of an ACAT gene, including the discovery that two ACATs function in mammalian biology. A clearer picture of the functions of ACAT enzymes in cellular cholesterol metabolism and physiologic processes is now emerging. These insights may have relevance for the development of ACAT inhibitors for treating hypercholesterolemia or atherosclerosis in humans.

Amino Acid Sequence↗
PubMed1987

Disorders of neuronal migration.

Neuronal migration constitutes one of the major processes by which the central nervous system takes shape. Detailed knowledge about this important process now exists for different brain regions in rodent and monkey models as well as in the human. In the human, distinct genetic, chromosomal and environmental causes are known that affect neuronal migration, often in a morphologically distinct pattern, but the underlying pathological mechanisms are largely unknown. This review is intended to integrate our basic knowledge of the field with the accumulated intelligence on a large number of disorders and syndromes that represent the human part of the story.

Abnormalities, Multiple↗
PubMed1999

First-trimester nuchal translucency screening for fetal aneuploidy.

The objective was to review current literature pertaining to first-trimester nuchal translucency screening for fetal aneuploidy. To this goal, all manuscripts published in the English language regarding this topic obtained from a MEDLINE search for 1966 through November 1998 were selected and reviewed. Additional sources were identified through cross-referencing. Current widespread application of first-trimester ultrasonography has enabled accumulation of an increasing body of knowledge pertaining to early screening for fetal aneuploidy. Following initial reports, recent studies of large populations of patients (> 500 participants) at either high- or low-risk for fetal chromosomal abnormalities, demonstrate that nuchal thickness of > 3 mm between 10 and 14 weeks' gestation by either transabdominal or transvaginal ultrasonography may serve as screening tool for fetal aneuploidy. Sensitivity and specificity rates improve when first-trimester maternal serum free beta-human chorionic gonadotropin (hCG) and pregnancy associated plasma protein A (PAPP-A) levels are added to this ultrasonographic tool. Current data regarding nuchal translucency including: nomograms, repeatability, optimal timing of measurement, accuracy and effect of confounding factors upon this ultrasonographic measurement, pathophysiology, increased associated incidence of fetal cardiac anomalies, and arrhythmias as well as other structural anomalies, Doppler velocimetry, spontaneous subsequent miscarriage, implications of nuchal translucency in twin gestations, and effect upon performance of subsequent midtrimester maternal serum screening are presented.

Aneuploidy↗
PubMed2000

Prostate cancer: how much do we know and how do we know it?

We use data from the Massachusetts Male Aging Study to approximate the total current knowledge about prostate cancer and to evaluate the relative contributions of various risk factors. The sum total of current knowledge is assessed using the area under the receiver operating characteristic curve (AUROC) and by the Hosmer-Lemeshow statistic in a logistic regression model that includes 30 risk factors identified in the literature that are available in the data set. Relative contributions are measured using the adjusted generalized R2 (AR2). To measure relative contributions, we group risk factors with similar etiology and then remove groups and compare the AR2 attained without each group to the AR2 with all variables included. The overall model fits adequately. The A UROC is 0.788, relatively far from its default value of 0.5, and the Hosmer-Lemeshow statistic has a p value of 0.926. We conclude that, while some knowledge about prostate cancer has been accumulated, there are still more risk factors yet unsuspected. The relative importance analysis shows that immutable factors (i.e. age, genotype) contribute 42%, dietary factors 30%, other lifestyle factors 15%, and endocrinological factors 11%. We recommend that age and other unchanging factors should be the primary focus of screening and risk evaluation and that future interventions should center on nutritional behavior.

Journal Article↗
PubMedDate not supplied

Epidural lipomatosis secondary to indinavir in an HIV-positive patient.

A human immunodeficiency virus-positive patient receiving indinavir therapy developed a slowly progressive paraparesis. Magnetic resonance imaging findings were consistent with epidural lipomatosis. On discontinuing indinavir, symptoms gradually remitted. Although indinavir, a protease inhibitor, is known to cause abnormal fat accumulation, to the best of our knowledge this is the first report of epidural lipomatosis.

Adult↗
PubMedDate not supplied

Pericardial "sleeve" recess of right inferior pulmonary vein mimicking adenopathy: computed tomography findings.

OBJECTIVE: The purpose of this study was to assess the computed tomography (CT) features of the pericardial "sleeve" recess of the right inferior pulmonary vein misinterpreted as adenopathy. METHOD: Six patients with fluid in the pericardial sleeve recess mistaken for adenopathy were retrospectively identified. The following CT features were assessed: location of fluid in relation to the vein, size, shape, attenuation, and mass effect on the inferior pulmonary vein. RESULTS: The most common presentation was fluid inferior and posterior to the vein. The anterior and posterior components are typically spindle shaped, whereas the superior and inferior components are ovoid. The attenuation values of the fluid ranged from 2-32 H (mean = 13 H). None of the fluid collections exerted mass effect on the right inferior pulmonary vein. CONCLUSION: Although fluid in the right pulmonary venous sleeve pericardial recess can mimic adenopathy, this accumulation has a characteristic appearance, and knowledge of this normal variant is useful in preventing misinterpretation.

Aged↗
PubMed1997

Helicobacter pylori: challenges for the paediatrician.

During the last 15 years, a great body of knowledge about Helicobacter pylori has been accumulated. Much, however, remains to be studied, particularly in relation to children. The vast majority of infections occur in childhood. It is towards children that any widespread screening, prevention or treatment strategies would need to be aimed. In this annotation, we discuss the epidemiology, symptomatology, diagnosis and treatment of H. pylori in children.

Anti-Bacterial Agents↗
PubMed1995

Hepatic purine and pyrimidine metabolism: implications for antiviral chemotherapy of viral hepatitis.

The use of nucleoside analogues as antiviral agents is expanding. For most nucleoside analogues, intracellular phosphorylation is the major prerequisite for activity. Antiviral activity may be limited by poor uptake, absence of appropriate activating enzymes, catabolism, and competition from endogenous nucleotides. Appreciation of these factors, which are species-, tissue- and cell-specific is important in the understanding of the pharmacology and toxicology of nucleoside analogues. The use of nucleoside analogues against the agents of viral hepatitis is inherently problematic for many reasons including active hepatic nucleoside catabolism, probable absence of virus-specific activating enzymes, competition from endogenous nucleotides synthesised de novo or derived from RNA turnover, and factors related to mitochondrial toxicity. Despite these drawbacks, some nucleoside analogues have been found efficacious against hepatitis B virus and it is likely that as knowledge of their mechanism of action accumulates, their efficacy can be improved both by rational drug design and by use in combination with other drugs, including interferon.

Animals↗
PubMed2001

Judging a protein by more than its name: GSK-3.

As knowledge of cellular signal transduction has accumulated, general truisms have emerged, including the notion that signaling proteins are usually activated by stimuli and that they, in turn, mediate the actions of specific agonists. Glycogen synthase kinase-3 (GSK-3) is an unusual protein-serine kinase that bucks these conventions. This evolutionarily conserved protein kinase is active in resting cells and is inhibited in response to activation of several distinct pathways, including those acting by elevation of 3' phosphorylated phosphatidylinositol lipids and adenosine 3'-5'-monophosphate (cAMP). In addition, GSK-3 is distinctly regulated by, and is a core component of, the Wnt pathway. This review describes the unique characteristics of this decidedly oddball protein kinase in terms of its diverse biological functions, plethora of targets, role in several human diseases, and consequential potential as a therapeutic target.

Alzheimer Disease↗
PubMed1991

On the efficacy of psychoanalysis.

In this study we critically review the formal research literature pertinent to the outcomes of psychoanalysis and the factors influencing these outcomes. Our inquiry was conducted from a psychoanalytic perspective. We found the research yield consistent with the accumulated body of clinically derived psychoanalytic knowledge, e.g., patients suitable for psychoanalysis derive substantial therapeutic benefit; analyzability and therapeutic benefit are relatively separate dimensions and their extent is relatively unpredictable from the perspective of initial evaluation among seemingly suitable cases. The studies all contain clinical and methodological limitations which are no more substantial than in other forms of psychotherapy research, but they have not substantially advanced psychoanalytic knowledge. This raises challenges for the further development of formal research strategies native to psychoanalysis.

Adult↗
PubMed1979

Substitution of outpatient care for inpatient care:problems and experience.

This paper provides a logical framework for considering possible alternatives to inpatient care. First it presents the concept of a substitute-complement relationship among factors of production (or goods and services in consumption) and examines several problems often encountered when applying this concept. Second, it presents four general sources of substitution: (1) technological innovation; (2) changes in organization; (3) capital accumulation; and (4) the dissemination of knowledge. Third, it examines nine activities which are frequently mentioned as providing alternatives to inpatient care. Fourth, it examines some problems and consequences of governmental efforts to plan substitution. The general thrust of the paper is that the substitution process is complex and often depends upon amorphous variables whose influences are subtle, generally nonquantifiable, and often of overriding importance. These variables introduce a downward bias in estimates of program costs and an upward bias in the estimates of program accomplishments. The result is that government attempts to plan substitution are not well conceived and will generally fall short of announced goals and/or cost significantly more than original estimates.

Ambulatory Care↗
PubMedDate not supplied

Putting CATS/APEL accreditation into practice.

Expanding opportunities mean that many nurses wish to update and extend their knowledge. A comprehensive framework for credit accumulation is needed. All practitioners must record their professional development in a personal profile or portfolio.

Accreditation↗
PubMed1994

Contrast nephrotoxicity.

Iodinated contrast media have some nephrotoxic potential but rarely cause significant renal failure in patients with normally functioning kidneys. Patients with existing renal impairment, with or without diabetes, those with current congestive heart failure of Class III or IV, those with reduced effective arterial volume (e.g., nephrotic, cirrhotic), or those receiving drugs that may impair renal function or increase contrast nephrotoxicity are at higher risk. Contrast nephrotoxicity may be clinically important in patients with other factors simultaneously affecting the renal response to contrast or in whom acute renal failure would seriously affect prognosis. The pathogenesis of contrast nephrotoxicity probably involves a combination of direct tubular toxicity and renal ischemic injury. Knowledge of the pathogenetic pathways is accumulating and is leading to the discovery of rational specific prophylactic measures to reduce the burden of nephrotoxicity. After the efficacy of these measures has been established, they should be considered for use in patients at high risk. Existing data indicate a limited role for the newer low-osmolality media for the prevention of nephrotoxicity.

Acute Kidney Injury↗
PubMed2003

Classic histamine H1 receptor antagonists: a critical review of their metabolic and pharmacokinetic fate from a bird's eye view.

The so-called "classic" histamine H(1) receptor antagonists are highly lipophilic compounds associated with significant biotransformation and tissue distribution. They are categorized according to their chemical structure into ethanolamines, alkylamines, ethylenediamines, piperazines, phenothiazines and piperidines, all of which have characteristic metabolic fates. The former four categories undergo primarily cytochrome P450-mediated oxidative N-desalkylations and deamination whereas the aromatic rings of the latter two undergo P450-mediated oxidative hydroxylation and/or epoxide formation. The common tertiary amino group is susceptible to oxidative metabolism by flavin containing monooxygenases forming N-oxides, and the alicyclic tertiary amines produce small amounts (up to 7%) of N-glucuronides in humans. Species, sex and racial differences in the metabolism and pharmacokinetics of antihistamines are known. Specific P450-isozymes implicated in the metabolism were identified in a few cases, such as CYP2D6 that contributes to the metabolism of promethazine, diphenhydramine and chlorpheniramine. Low circulating plasma concentrations of antihistamines are in part explained by significant first-pass effect and tissue distribution. Antihistaminic effects last up to 6 hours though some compounds exhibit a longer duration of action due to circulating active metabolites. Importantly, diphenhydramine inhibited CYP2D6 leading to a clinically significant drug-drug interaction with metoprolol. Other classic antihistamines were shown to be potent in vitro inhibitors of CYP2D6 and CYP3A4. The prescription-free access to most classic antihistamines can easily lead to their co-administration with other drugs metabolized by the same enzyme system thereby leading to drug accumulation and adverse effects. In depth knowledge of the metabolic pathways of classic antihistamines and the enzymes involved is crucial to prevent the high incidence of drug interactions in humans, which are predictable based on pre-clinical data but unexpected when such data is unavailable.

Animals↗
PubMed1998

Integration of bioInformatics tools at the National University of Singapore (NUS).

In the past decade "Big Science" such as the Genome Project has generated an enormous amount of data in the life sciences. Concurrently, the synergy of this project with existing research has quickened the pace of biological discovery. But the major drawback that is beginning to be felt worldwide is the primitive level of organisation in the data accumulated. Without a proper framework or knowledge scaffold to hang and interconnect the various bits of data and information, the national knowledge-to-data ratio is declining rapidly. We are trying to serve a solution to this enigma by providing a World Wide Web (WWW) interface to Biosoftware and at the same time have come up with a database integration tool that can query heterogeneous, geographically scattered and disparate databases simultaneously. In this report we will talk about BioInformatics in general with specific reference to BioInformatics Centre (BIC) at the National University of Singapore.

Computational Biology↗
PubMed1994

[Fragmentary materials of history of Yi-nationality medicine].

Early in the matriarchal society 4000 years ago, medical activities of the Yi-nationality had already begun. Through long process of struggle against diseases, the ancestor of Yi-nationality accumulated a huge wealth of medical knowledge, including acupuncture, medicinal wine and herbs, from which the theory of "Ba Fang" (eight-direction) "Ba Jiao" (eight-corner) and Yin-Yang system were formed, and became the core of rationale of Yi-medicine. Due to geographical reasons, Yi-medicine was isolated and scarcely communicated with the outside world. Hence, so far it preserves much of its own features and thus, it offers excellent materials for the studies on the provenance and development of the medicine of Chinese minorities.

China↗
PubMed2004

Reasoning process characteristics in the diagnostic skills of beginner, competent, and expert dentists.

The purpose of this study was to evaluate qualitative differences in the diagnostic reasoning process at different developmental stages of expertise. A qualitative design was used to study cognitive processes that characterize the diagnosis of oral disease at the stages of beginner (five junior students who had passed the NBDE I), competent (five GPR first-year residents), and expert dentists (five general dentists with ten or more years of experience). Individually, each participant was asked to determine the diagnosis of an oral condition based on a written clinical case, using the think aloud technique and retrospective reports. A subsequent interview was conducted to obtain the participants' diagnostic process model and pathophysiology of the case. The analysis of the verbal protocols indicated that experts referred to the patient's sociomedical context more frequently, demonstrated better organization of ideas, could determine key clinical findings, and had an ability to plan for the search of pertinent information. Fewer diagnostic hypotheses were formulated by participants who used forward reasoning, independent of the stage of development. Beginners requested additional diagnostic aids (radiographs, laboratory tests) more frequently than the competent/expert dentists. Experts recalled typical experiences with patients, while competent/beginner dentists recalled information from didactic courses. Experts evidenced cognitive diagnostic schemas that integrate pathophysiology of disease, while competent and beginner participants had not achieved this integration. We conclude that expert performance is a combination of a knowledge base, reasoning skills, and an accumulation of experiences with patients that is qualitatively different from that of competent and beginner dentists. It is important for dental education to emphasize the teaching of cognitive processes and to incorporate a wide variety of clinical experiences in addition to the teaching of disciplinary content.

Clinical Competence↗
PubMedDate not supplied

[Paracetamol. Present status of knowledge in 1989].

Today paracetamol (acetaminophen), the oldest known synthetic analgesic-antipyretic drug, is one of the most frequently used around the world. The present general review presents the essential knowledge about this drug which has accumulated during the last decade, 1978 from to 1988. It includes recent data concerning toxicity, pharmacokinetics, mechanisms of analgesic and antipyretic action, and therapeutic efficacy. Readers interested in the original papers are referred to 264 bibliographical references.

Acetaminophen↗