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Biomedical subjects

C Morgan

Publications and source records attributed to C Morgan.

At least 73 records · Page 4Linked to original sources

In vitro and in vivo analysis of murine lipoprotein lipase gene promoter: tissue-specific expression.

Lipoprotein lipase, an enzyme of central importance to lipid metabolism, is most abundant in adipose tissues, cardiac and skeletal muscle, and portions of the brain. The current work examined the murine lipoprotein lipase promoter using transient transfection, gel-retention analyses, and transgenic mice. Maximum expression of the luciferase reporter gene in transfected cells was observed with -101 bp of the promoter. Nuclear extracts from tissues expressing lipoprotein lipase contained DNA binding proteins that recognize the CCAAT box (-64 bp) and an octamer motif (-46 bp); this combination of factors was absent in nonexpressing tissues. Transgenic mice from three of five founders prepared with -1,824-bp promoter constructs expressed the luciferase reporter gene at highest levels in brown adipose tissue and brain. These findings suggest that the -1,824-bp promoter region contains sequence elements responsible for the tissue-specific transcription of lipoprotein lipase in vivo.

Animals↗

Saturable binding sites for the coenzyme A ester of nafenopin, a peroxisome proliferator, in rat liver cytosol.

1. At least three different molecular weight binding sites exist in rat liver cytosol for nafenopin-CoA, the coenzyme A ester and metabolic product of the carcinogenic peroxisome proliferator nafenopin. No binding sites for the free drug were observed. 2. Polypeptides of 35-40 kDa molecular weight range where no acyl-CoA binding proteins have been previously described bind the highest proportion of nafenopin-CoA (60-70%). Binding is displaceable by the CoA esters of other peroxisome proliferators (ciprofibrate and tibric acid) and also by oleoyl-CoA but by palmitoyl-CoA. Direct binding studies show that 35-40-kDa polypeptides bind oleoyl-CoA but not oleic or palmitic acid, or palmitoyl-CoA. 3. Polypeptides of 10-14 and 65-70 kDa also bind nafenopin-CoA. However, in contrast with 35-40-kDa polypeptides they also bind oleic and palmitic acid as well as their correspondent acyl-CoA thioesters.

Acetyl Coenzyme A↗

Psychosocial variables associated with teenage pregnancy.

This study investigated whether psychosocial factors differentiate sexually active teenagers who become pregnant from those who do not. Data were collected from 64 unmarried adolescents who attended a suburban health clinic for a pregnancy test or for contraceptive care. Thirty-nine percent of the sample had been or were now pregnant, and 61% had never been pregnant. Each teenager completed a questionnaire and three self-report measures (Life Events Checklist, Self-Worth, Health Locus of Control) prior to her medical visit. Information about family, medical, and psychosocial history was obtained from chart review. When girls who had positive pregnancy tests, and sexually active girls who had never been pregnant were compared, no significant differences emerged on socioeconomic status, race, religion, age or psychological variables. However, when adolescents with a previous or current history of pregnancy (N = 25) were compared with girls who had never been pregnant (N = 39), using the Mann Whitney test, two significant differences were found: adolescents with a history of pregnancy had first intercourse at the mean age of 15 rather than 16 (p < .02) and scored higher than never-pregnant teenagers on the "Powerful Other" Health Locus of Control subscale, a measure of strong belief in external control by others (p < .01). No significant differences were detected between the groups for self-worth or life events perceived as stressful during the past year. These data indicate that in a middle-class suburban population of sexually active teenagers, earlier age at first intercourse and the influence of powerful others are important variables associated with pregnancy.

Adolescent↗

Tropical spastic paraparesis occurring in HTLV-1 associated infective dermatitis. Report of two cases.

An association between HTLV-1 infection and infective dermatitis (ID) a relapsing eczematous condition of Jamaican children, was reported in 1990. These patients are at risk of developing other known HTLV-1 related diseases. We have observed the development of HTLV-1 associated myelopathy/tropical spastic paraparesis in two patients, ages 14 and 35 years, who were diagnosed with ID at ages 2 and 10 years, respectively. Infective dermatitis of children serves as an early marker of HTLV-I infection and may predict later development of either the malignant outcome, adult T-cell leukaemia/lymphoma or the neurologic manifestation HAM/TSP among adult carriers of HTLV-1 infection.

Adolescent↗

Beliefs, knowledge, and behavior about cancer among urban Hispanic women.

As part of a cancer prevention program aimed at minority and disadvantaged urban women, cancer beliefs, knowledge, and behaviors were assessed among home-health attendants in the Bronx, N.Y. Information, was gathered from 876 Hispanic women who comprised 62% of the female home-attendant study population from whom data were collected (n = 1413). Of these women, 82% (n = 718) were Spanish speaking and 18% (n = 158) were English speaking as defined by their choice to complete the survey questionnaire in Spanish or English. As a whole, the population reported high levels of obtaining screening tests and engaging in preventive behaviors. However, nearly 60% did not know what cervical cancer was. The most important predictor of inadequate cancer screening was lack of knowledge. Large numbers of women subscribed to cancer misconceptions, such as the belief that bumps or bruises cause cancer. Fifty-eight percent believed that surgery causes cancer to spread, a belief that may prevent a woman with breast cancer from undergoing early intervention procedures, such as lumpectomy. This survey indicated that Hispanic women in our population engaged in relatively high levels of cancer preventive behaviors, even though their knowledge base was limited. Many of them hold misperceptions about cancer that can have an impact on preventive behaviors. We conclude that cancer prevention programs targeting the Hispanic populations should emphasize the provision of factual information about cancer and cancer-screening behaviors in the context of an exploration of inaccurate beliefs about cancer that may inhibit preventive health behaviors.

Adult↗

Importance of ST-segment depression as a determinant of ventricular premature complex frequency after thrombolysis for acute myocardial infarction. Tissue Plasminogen Activator: Toronto (TPAT) Study Group.

Ventricular premature complexes (VPCs) after acute myocardial infarction (AMI) remain important determinants of survival in the post-thrombolytic era. The role of thrombolysis, left ventricular function, and Holter ST-segment depression in modulating VPC frequency is unclear. In a placebo-controlled, randomized study of tissue-type plasminogen activator (t-PA) in 103 patients with AMI (Tissue Plasminogen Activator: Toronto study), VPC frequency and ST depression on Holter monitoring (day 7), ejection fraction by radionuclide scan (day 9), and infarct artery patency and cross-sectional area on day 1 (n = 42) were assessed. After administering t-PA, VPC frequency was 10 +/- 58/hour (mean +/- SD), similar to that after placebo (23.5 +/- 91.7, p = NS). However, patients with ST depression had greater VPC frequency (56 +/- 140/hour) than those without it (1.3 +/- 2.6/hour, p = 0.05). Ejection fraction was negatively correlated with VPC frequency (r = -0.33, p < 0.001). By multivariate analysis, ejection fraction (F = 7.0, p < 0.01) and ST depression (F = 5.8, p < 0.02) were the only independent predictors of VPC frequency. In this placebo-controlled study, VPC frequency after AMI was not related to thrombolytic administration but was associated with ST depression and ejection fraction. This suggests that the underlying extent of both infarcted and ischemic myocardium is important in modulating ventricular arrhythmias after AMI.

Aged↗

Cloning and expression of the A2a adenosine receptor from guinea pig brain.

A full-length complementary DNA (cDNA) clone encoding the guinea pig brain A2 adenosine receptor has been isolated by polymerase chain reaction (PCR) and low-stringency-hybridization screening of a guinea pig brain cDNA library. This cDNA contains a long open reading frame encoding a 409-amino acid-residue protein which is highly homologous to the A2 adenosine receptors previously cloned from other species. Hydrophobicity analysis of the deduced protein sequence reveals seven hydrophobic regions, characteristic of a member of the G-protein-coupled receptor superfamily. Radioligand binding assay and functional (GTPase and cAMP) assays of the receptor, transiently expressed in mammalian cells, demonstrate typical characteristics of the A2 type adenosine receptor. The messenger RNA (mRNA) of this A2 receptor is found in the brain, heart, kidney and spleen. Receptor autoradiography with [3H]CGS21680, a specific A2 agonist, and in situ hybridization with A2 cRNA probe in guinea pig brain indicate that the receptor is expressed exclusively in the caudate nucleus. The pharmacological profile and anatomical distribution of this receptor indicate that it is of the A2a subtype. This work represents the first cloning of an A2a receptor in a rodent species, offers a complete pharmacological characterization of the receptor and provides an anatomical comparison between binding profile and gene expression of the receptor.

Amino Acid Sequence↗

Cloning and characterization of a pharmacologically distinct A1 adenosine receptor from guinea pig brain.

Three full-length cDNA clones encoding the guinea pig A1 adenosine receptor have been isolated by polymerase chain reaction (PCR) and low-stringency hybridization screening of a guinea pig brain cDNA library. These three cDNAs, though differing in their 5' untranslated regions, contain the same open reading frame encoding a 326 amino acid residue protein with seven hydrophobic alpha-helices long enough to form the transmembrane domains, suggesting that it belongs to the G protein-coupled receptor superfamily. This protein is highly homologous to the A1 adenosine receptors previously cloned from other species. Pharmacological characterization of this receptor transiently expressed in mammalian cells demonstrates that, despite its high homology to A1 adenosine receptors of other species, the guinea pig A1 adenosine receptor displays a unique pharmacological profile: high affinity for the A1-selective antagonist CPX, yet very low affinity for some A1-selective agonists such as CCPA, CHA and R-PIA. Northern blotting for different guinea pig tissues and in situ hybridization for guinea pig brain sections reveal an abundant and broad distribution of mRNA of this A1 subtype receptor in the brain.

Adenosine↗

Measurement of total urethral compliance in females with stress incontinence.

Urodynamic evaluation of stress incontinence has failed to result in consistent diagnostic parameters. Using retrospective female bladder pressure and urine flow data, we evaluated two parameters based on a conductance formula. This formula was derived from fitting a classical fluid dynamic equation to published data of voiding cystourethography. The Area Equivalent Factor-female at maximal flow represents maximal urethral opening and this value further divided by the pressure is the total urethral compliance. A stress incontinent group had a strong trend toward greater maximal urethral opening and total urethral compliance than a continent group. These parameters may, therefore, have potential in the evaluation and understanding of stress urinary incontinence.

Adult↗

Treatment with anti-vascular cell adhesion molecule 1 monoclonal antibody induces long-term murine cardiac allograft acceptance.

Daily in vivo treatment of murine H-2d --> H-2b cardiac allograft recipients with 400 micrograms/day i.p. of M/K-2, a mAb to the endothelial adhesion molecule VCAM-1, resulted in prolongation of graft survival. The surviving allografts showed little of the histologic changes observed in acutely rejecting control allografts. When antibody treatment was discontinued after 20 days, grafts continued to function for at least 40 more days. This was approximately 30 days after mAb was no longer detectable by ELISA in the circulation, or by immunoperoxidase staining at the graft site. The most notable feature of grafts that survived 60 days was the presence of mild interstitial fibrosis. Endothelial reactivity was minimal with the mAbs MECA-32 and M/K-2, which have been used in previous studies to visualize the extensive endothelial inflammation that develops during untreated acute rejection. There was a mild cellular infiltrate containing T cells, but few macrophages. However, infiltrating T cells appeared to be inactive in that IL-2R+ cells were immunohistologically undetectable and mRNA for IL-2, IL-4, or IFN-gamma was undetectable by polymerase chain reaction. In general, the immunologic conditions in these long-term grafts differed from those seen in normal cardiac tissue, cardiac isografts, or cardiac allografts. These data demonstrate that M/K-2 mAb can suppress cardiac allograft rejection and induce long-term graft acceptance. This graft survival appears to be associated with the development of a unique state of immunity at the graft site.

Animals↗

Influence of external defibrillator electrode polarity on cardiac resuscitation.

Eight hundred forty-seven consecutive patients discovered in cardiac arrest by first responding firefighters received initial defibrillation attempts using automatic external defibrillators. The effect of electrode polarity on defibrillation and resuscitation was determined in the subset of 289 (34%) with ventricular fibrillation in a prospective, randomized trial. The ECG was recorded in 205 consecutive patients whose initial rhythm was ventricular fibrillation. Eighty-seven of 114 patients (76%) in whom the apex chest electrode was positive were defibrillated with the first 200-joule shock, compared to 70 of 91 patients (77%) in whom the apex electrode was negative. There was no difference in the type of rhythm established, e.g., organized versus brady-asystole following defibrillation with either electrode polarity. Resuscitation was possible in 56% of patients in whom the apex electrode was positive and 60% of those in whom the apex electrode was of negative polarity. Hospital survival rates (26% vs 27%) were also similar for both treatment groups. Unlike results during experimental external defibrillation of animals or those obtained using implantable defibrillators, this randomized trial of external defibrillation conducted during attempted out-of-hospital resuscitation showed no difference in outcomes related to electrode polarity.

Aged↗

The Australian Incident Monitoring Study. Errors, incidents and accidents in anaesthetic practice.

Human error is a pervasive and normal part of everyday life and is of interest to the anaesthetist because errors may lead to accidents. Definitions of, and the relationships between, errors, incidents and accidents are provided as the basis to this introduction to the psychology of human error in the context of the work of the anaesthetist. Examples are drawn from the Australian Incident Monitoring Study (AIMS). An argument is put forward for the use of contemporaneous incident reporting (eliciting relevant contextual information as well as details of use to cognitive psychologists), rather than the use of accident investigation after the event (with the inherent problems of scant information, altered perception and outcome bias). A classification of errors is provided. "Active" errors may be classified into knowledge-based, rule-based, skill-based and technical errors. Different strategies are required for the prevention of each type and it may now be useful to place more emphasis in anaesthetic practice on categories to which little attention has been directed in the past. "Latent" errors make an enormous contribution to problems in anaesthesia and several categories are discussed (e.g. environment, physiological state, equipment, work practices, personnel training, social and cultural factors). An approach is provided for the prevention and management of errors, incidents and accidents which allows clinical problems to be categorized, the relative importance of various contributing factors to be established, and appropriate preventative strategies to be devised and implemented on the basis of priorities determined from the AIMS data. Accidents cannot be abolished; however, an understanding of the factors underlying them can lead to the rational direction of resources and effort to prevent them and minimise their effects.

Accident Prevention↗

The Australian Incident Monitoring Study. The capnograph: applications and limitations--an analysis of 2000 incident reports.

The first 2000 incidents reported to the Australian Incident Monitoring Study were analysed with respect to the role of the capnograph. One hundred and fifty-seven (8%) were first detected by a capnograph and there were a further 18 (1%) in which capnography was contributory. Of the 1256 incidents which occurred in association with general anaesthesia 48% were "human detected" and 52% "monitor detected". The capnograph was ranked second and detected 24% of these monitor detected incidents; this figure would have been nearly 30% if a correctly checked, calibrated capnograph had always been used. The capnograph is a "front-line" monitor for oesophageal intubation, failure of ventilation, anaesthetic circuit faults, gas embolism, sudden circulatory collapse and malignant hyperthermia. It is a valuable "back-up" monitor when other monitors (e.g. low pressure alarm, pulse oximeter) are not in use, are being used incorrectly or fail. Such situations, in order of frequency of detection were: circuit-leak, overpressure of the breathing circuit, bronchospasm, leak of ventilator-driving-gas into the patient circuit, aspiration and/or regurgitation and hypoventilation. There were 20 reports of "failure", over two-thirds of which would not have occurred with appropriate checking and calibration. Seven were due to gas sampling problems and 6 to apnoea alarm failure. Two circuit leaks and 2 faulty unidirectional valves were not detected; on 3 occasions problems occurred due to power failure, calibration problems, or misinterpretation of an alarm.(ABSTRACT TRUNCATED AT 250 WORDS)

Accidents↗

The Australian Incident Monitoring Study. Blood pressure monitoring--applications and limitations: an analysis of 2000 incident reports.

Of the first 2000 incidents reported to the Australian Incident Monitoring Study, 1256 occurred in relation to general anaesthesia and 81 of the latter were first detected by blood pressure (BP) monitoring. A further 25 incidents not associated with general anaesthesia were first detected by blood pressure monitoring, giving a total of 106. In the monitor detection of incidents in relation to general anaesthesia, BP monitoring ranked fourth after oximetry, capnography and low pressure alarms. On the other hand, 38 incidents in which the problem was primarily one of significant change in BP were first detected by means other than the BP monitor (20 clinically, 12 by pulse oximetry and 6 by ECG). Early detection rates of hypotension were 60% for invasive methods, 40% for automated non-invasive (NIBP) devices and 30% for manual sphygmomanometry. There were 21 reports of BP monitor "failure"; the 11 of these which occurred with NIBPs involved unexplained false "low" or "high" readings and failure to detect profound hypotension, and led to considerable morbidity and at least one death. The 10 cases of invasive monitoring failure were predominantly due to mains power loss, hardware breakage or operator error. In a theoretical analysis of the 1256 GA incidents, it was considered that on its own, BP monitoring would have detected 919 (73%), but in the vast majority, by the time this detection has occurred, potential organ damage could not be excluded. It is recommended that BP be measured at regular intervals dictated by clinical requirements (usually at least every five minutes).(ABSTRACT TRUNCATED AT 250 WORDS)

Accidents↗

The Australian Incident Monitoring Study. The "wrong drug" problem in anaesthesia: an analysis of 2000 incident reports.

Amongst the first 2000 incidents reported to the Australian Incident Monitoring Study, there were 144 incidents in which the "wrong drug" was nearly or actually administered to a patient. Thirty-three percent of the incidents involved ampoules and just over 40% syringes; in over half of the latter the syringes were of the same size, and also, in over half, they were correctly labelled. In 81% of the 144 incidents the "wrong drug" was actually given. This was more common with syringes (93%) than ampoules (58%). Thus the most common error was actually giving the wrong drug from a correctly labelled syringe. The most common drug involved was a muscle relaxant in both ampoule and syringe incidents. In 74% of all reports, there was the potential for serious harm to the patient; however no deaths were reported. Factors which contributed significantly to the incidents were similar appearance, inattention and haste. "Failure of communication" was a significant factor in syringe incidents when two or more staff were involved. The only significant factor which minimised the outcome was rechecking of the syringe or drug ampoule before giving the drug. Strategies suggested to address the "wrong drug" problem include education of staff about the nature of the problem and the mechanisms involved; colour coding of selected drug classes for both ampoules and syringes; the use of standardised drug storage, layout and selection protocols; having a drawing up and labelling convention; and the use of checking protocols.

Anesthesia↗

The Australian Incident Monitoring Study. Recovery room incidents in the first 2000 incident reports.

Of the first 2000 incidents reported to the Australian Incident Monitoring Study 120 (6%) occurred in the recovery room after general, regional or local anaesthesia. Over two thirds (69%) of these involved the respiratory system, 19% were cardiovascular, 3% involved the central nervous system and 9% were miscellaneous in nature. These recovery room incidents were associated with significantly more adverse outcomes (56%) than incidents in the operating theatre (24%). The types and relative frequencies of these recovery room incidents were similar to those of serious recovery complications in a recent analysis of closed malpractice claims; this suggests that incident monitoring may be useful in the study and prevention of recovery room complications. Over three quarters (77%) of all recovery incidents (and 88% of respiratory incidents) were detected clinically; the remainder were first detected by a monitor. A theoretical analysis showed that over 95% of respiratory events, had they been allowed to evolve, would have been detected by pulse oximetry before organ damage occurred, emphasising the potential importance of pulse oximetry in reducing adverse outcome from any complication in the recovery ward which might be "missed" by clinical observation. The findings of this study underline the importance of having an adequate number of trained recovery nursing staff supported by the availability of a pulse oximeter for each patient at least until the return of protective reflexes and the ability to maintain adequate arterial saturation has been established.

Accidents↗