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Biomedical subjects

D O'Donnell

Publications and source records attributed to D O'Donnell.

At least 19 recordsLinked to original sources
PubMed1992

Educational computer simulation of malignant hyperthermia.

An educational graphic simulator was developed to provide an interactive learning environment to practice the diagnosis and treatment of malignant hyperthermia. The program incorporates a set of dynamically interacting models to present the physiologic changes associated with malignant hyperthermia and the simulated patient's response to management. Cardiovascular, respiratory, and temperature changes are presented through a graphic display of the operating room monitors. Mouse-driven input is used to manage the airway, control ventilation, manage cardiovascular and rhythm disturbances, and control fluids, electrolytes, and temperature. Medications, including dantrolene, antidysrhythmics, diuretics, and sodium bicarbonate, can be administered. Four simulated patients with different presentations of malignant hyperthermia are included to illustrate variations in the syndrome. Two of these patients are described in detail.

Adult↗
PubMed1992

Anomalous lateral sulcus asymmetry and cognitive function in first-episode schizophrenia.

This study examines the cognitive functioning of first-episode schizophreniform patients within several weeks of hospitalization and at 2 years into the illness. Differences between patients and controls are also reported for measurements of the length of the lateral sulcus, which borders the planum temporal, an area of the brain integral to language function. Neuropsychological test results are also correlated to magnetic resonance imaging structural variables at the time of first hospitalization. Findings on neuropsychological summary scales reveal a diffuse pattern of cognitive impairment in schizophreniform patients compared to controls, which appears to improve over time. An atypical pattern of anatomic lateral symmetry is found in female schizophreniform patients, with female appearing to have a reduction in the normally occurring left greater than right length of the lateral sulcus. Such atypical asymmetry of the lateral sulcus is also associated with better cognitive function, particularly in schizophreniform patients. These findings suggest that atypical lateralization in an area critical to language function may be related to cognitive function in schizophreniform illness.

Adult↗
PubMed1992

Anesthesiologists' management of simulated critical incidents.

Human error is believed to contribute to the majority of negative anesthesia outcomes. Because retrospective analysis of critical incidents has several shortcomings and prospective studies are limited by the low frequency of critical incidents, an anesthesia simulator was used to evaluate the management of simulated emergency situations by ten anesthesia residents, ten faculty anesthesiologists, and ten anesthesiologists in private practice in order to identify specific patterns of errors in diagnosis and treatment. The simulator is a computer program that presents the patient, monitors, and management choices in a graphical display on an IBM or compatible personal computer. Many errors were observed in the management of these emergency situations, and even anesthesiologists with years of experience made serious errors. Although all experienced anesthesiologists correctly diagnosed simulated esophageal intubation, two residents misinterpreted the lack of end-tidal carbon dioxide. Only 40% of subjects correctly diagnosed simulated anaphylactic reaction; 27% adequately treated simulated myocardial ischemia; and 30% managed a simulated cardiac arrest according to Advanced Cardiac Life Support (ACLS) guidelines. Problems with continuous infusions of vasoactive agents were common. Fixation errors or failure to revise a plan in the presence of inconsistent cues were made by 63% of subjects. The subjects that gathered more information during simulated anaphylaxis made the correct diagnosis more often and made fewer treatment errors. The time since the last ACLS training was found to be an important predictor of correct management of simulated cardiac arrest.(ABSTRACT TRUNCATED AT 250 WORDS)

Anaphylaxis↗
PubMed1992

The prevalence of nonrepaired fractured incisors in visually impaired Chinese children and young adults in Hong Kong.

The purpose of this study was to determine the prevalence of nonrepaired fractured incisors in visually impaired Chinese children and young adults in Hong Kong. Eighty-eight children were examined, and it was found that there were significantly more fractures of anterior teeth in the totally blind than in the partially blind. The totally blind seem to be at greater risk of sustaining a fractured anterior tooth than were the sighted.

Adolescent↗
PubMed1991

Cellular mechanisms underlying the development and expression of individual differences in the hypothalamic-pituitary-adrenal stress response.

Several years ago Levine, Denenberg, Ader, and others described the effects of postnatal "handling" on the development of behavioral and endocrine responses to stress. As adults, handled rats exhibited attenuated fearfulness in novel environments and a less pronounced increase in the secretion of the adrenal glucocorticoids in response to a variety of stressors. These findings clearly demonstrated that the development of rudimentary, adaptive responses to stress could be modified by environmental events. We have followed these earlier studies, convinced that this paradigm provides a marvellous opportunity to examine how subtle variations in the early environment alter the development of specific neurochemical systems, leading to stable individual differences in biological responses to stimuli that threaten homeostasis. In this work we have shown how early handling influences the development of certain brain regions that regulate glucocorticoid negative-feedback inhibition over hypothalamic-pituitary-adrenal (HPA) activity. Specifically, handling increases glucocorticoid (type II corticosteroid) receptor density in the hippocampus and frontal cortex, enhancing the sensitivity of these structures to the negative-feedback effects of elevated circulating glucocorticoids, and increasing the efficacy of neural inhibition over ACTH secretion. These effects are reflected in the differential secretory pattern of ACTH and corticosterone in handled and nonhandled animals under conditions of stress. In more recent years, using a hippocampal cell culture system, we have provided evidence for the importance of serotonin-induced changes in cAMP levels in mediating the effect of postnatal handling on hippocampal glucocorticoid receptor density. The results of these studies are consistent with the idea that environmental events in early life can permanently alter glucocorticoid receptor gene expression in the hippocampus, providing evidence for a neural mechanism for the development of individual differences in HPA function.

Animals↗
PubMed1991

Hypoprothrombinaemia associated with use of cephamandole.

We report 4 cases in which the use of cephamandole was associated with coagulopathy. All 4 patients had renal impairment, but no other known predisposing factors. It is recommended that the coagulation profile be monitored during administration of cephamandole, especially when there is a background of renal impairment.

Adult↗
PubMed1990

Immunocytochemical localization of the glucocorticoid receptor in steroid-sensitive and -resistant human leukemic cells.

Because of their lympholytic action, glucocorticoids are included in most therapeutic regimens for the treatment of lymphomas and leukemias. The presence of functional glucocorticoid receptor may be predictive of the response to hormonal therapy in these diseases. We have developed an immunocytochemical procedure for human glucocorticoid receptor (GR) in order to assess its level and subcellular distribution in a well-studied system of childhood lymphoblastic leukemia cells (CEM), where sensitive and resistant subclones have been established. Several fixation and cell permeabilization protocols were compared. The most sensitive and reproducible one for light microscopy was prefixation in Bouin's solution followed by cytocentrifugation. Using various polyclonal and monoclonal antibodies, the GR was consistently localized predominantly in the cell cytoplasm in the absence of steroid. We compared localization of GR following glucocorticoid treatment in the glucocorticoid-sensitive clone CEM C7 with resistant subclones (4R4, 3R43, ICR27). Upon incubation with glucocorticoid, an increase in nuclear staining was clearly observed in the steroid-sensitive C7 cells. Although the resistant cell lines contain immunoreactive GR, they failed to show nuclear translocation following glucocorticoid treatment. This outlines the importance of the immunocytochemical procedure to distinguish between sensitive and resistant leukemic cells. Whether this test could be used prospectively to help select glucocorticoid therapy in human leukemias and lymphomas can now be examined.

Antibodies, Monoclonal↗
PubMed1990

'Leopard' syndrome.

'Leopard' syndrome is a rare inherited disorder associated with a high prevalence of cardiac abnormalities. General anaesthesia for dental treatment in a patient who had cardiomyopathy and bizarre electrocardiographic abnormalities associated with this syndrome is described. A thorough cardiac assessment is advised in a patient with multiple lentigines, although no clinical symptoms or signs may be found. Even if no cardiac abnormality is found before it is better to re-assess the patient, since abnormalities may develop later. The assessment should be repeated if any abnormality was detected before but without clinical significance, since the disease is progressive and may progress more rapidly in some patients than in others.

Adolescent↗
PubMed1990

Intestinal lymphangiectasia with protein losing enteropathy, toxic copper accumulation and hypoparathyroidism.

A 13-year-old girl presented with malabsorption which was ascribed to intestinal lymphangiectasia. Three years later a generalised seizure resulted from hypocalcaemia that was shown to be due to hypoparathyroidism during investigation of which toxic copper accumulation was recognised. The chance occurrence of three rare conditions is extremely remote making intestinal lymphangiectasia likely as the primary pathology. It is suggested that chronic intestinal loss of the copper-carrying caeruloplasmin resulted in toxic parathyroid deposition of copper leading to hypoparathyroidism with consequent hypocalcaemic seizure.

Adolescent↗
PubMed1990

Regulation of glucocorticoid receptor expression: I. Use of a specific radioimmunoassay and antiserum to a synthetic peptide of the N-terminal domain.

In order to study glucocorticoid receptor (GR) gene expression at the protein level, we have produced an anti-serum to the GR using a 14 amino acid peptide (14-mer) of amino terminus domain of the human GR, and established a simple and specific RIA to quantitate both the human and rat GR. The antibody was raised in rabbits to the 14-mer coupled to either BSA or keyhole limpet hemocyanin. This antibody immunoblots the Mr = 94,000 bona fide GR in tissue extracts and localizes the GR at the subcellular level by immunocytochemistry. In addition, cytosolic GR, previously labeled by the affinity ligand, [3H]dexamethasone mesylate, was immunoprecipitated by the peptide antibody. The 14-mer was iodinated at its tyrosine residue and used in a standard RIA. The binding of the antibody to the 125I-14-mer was displaced by increasing concentrations of either the 14-mer (standard curve) pure GR or tissue cytosol containing native GR. This RIA reliably detects glucocorticoid receptor level between 20 and 500 fmol/tube in human, rat, and mouse tissues. In two well established cell line systems and their subclones (human CEM and in rat hepatoma tissue culture cells transfected or not with GR cDNA) the GR level, as assessed by this RIA, was compared to GR values using the classical radioreceptor or previously published mRNA assays. The relative amount of GR in wild-type cells and in subclones, as assessed by the novel RIA, was identical to the above-mentioned assays. Using the RIA, we demonstrated the down-regulation of GR level in liver following glucocorticoid administration and its up-regulation following adrenalectomy. This study, which constitutes the first description of an RIA for a steroid receptor using a synthetic peptide, provides a powerful tool for a standardized, sensitive, and simple assay for the GR in human and animal tissues.

Adrenalectomy↗
PubMed1990

The Anesthesia Simulator-Recorder: a device to train and evaluate anesthesiologists' responses to critical incidents.

The Anesthesia Simulator-Recorder is a computer program that trains and evaluates anesthesiologists' management of critical incidents. The program executes on IBM compatible personal computers, combining a graphic display of the operating room with mouse-driven input and using an integrated set of physiological and pharmacological models to predict patient responses. The program records the simulated patient's vital signs and all management decisions, and produces a printed case summary. The Anesthesia Simulator-Recorder was evaluated by 44 resident and attending anesthesiologists at seven different anesthesia training centers. These anesthesiologists found the simulator easy to use with clear presentation of the case and management options. The physiological and pharmacological models produced clinically realistic predictions of patient behavior (mean score = 8.5, where 10 is highly realistic and 1 is unrealistic). The Anesthesia Simulator-Recorder was appraised as an excellent training device (mean score = 8.5, where 10 is outstanding and 1 is poor) because it provides the ability to repeatedly practice the management of critical incidents. The simulator was judged to be a good evaluation device (mean score = 6.6, where 10 is outstanding and 1 is poor). No significant differences were found in evaluations between the institution where the program was developed and other institutions, or between residents and attendings.

Anesthesiology↗
PubMed1989

Demonstration of the intracellular localization and up-regulation of glucocorticoid receptor by in situ hybridization and immunocytochemistry.

Glucocorticoid response in target cells closely correlates with glucocorticoid receptor (GR) level. We have compared the localization of GR (by immunocytochemistry) and GR mRNA levels (by in situ hybridization) in steroid-sensitive and steroid-resistant subclones derived from the human CEM lymphoid cell line. In addition, GR was localized in lymphoid cells from patients with various hematological malignancies. In the absence of preincubation with the steroid, GR was localized at the light and electron microscopic level predominantly in the cytoplasm and to a weaker extent in the nucleus. In the presence of steroid, the GR was shown to translocate to the nucleus in the steroid-sensitive but not in the steroid-resistant cell lines. Furthermore, GR and GR mRNA levels were increased following glucocorticoid treatment of the sensitive cell line but not the resistant one. These data support a role for receptor regulation and translocation in the overall mechanism of glucocorticoid hormone action.

Base Sequence↗
PubMed1989

Acute renal failure following surgery for abdominal aortic aneurysm.

Between January 1974 and April 1986, 440 patients underwent elective or emergency repair of abdominal aortic aneurysms at this hospital. Acute renal failure requiring dialysis following repair occurred in 32 patients (7.3%) and form the basis of this report. All were male patients of mean age 69 years; 21 (66%) gave a history of other major medical problems and 19 (59%) used medication for these medical conditions. Twelve patients (37.5%) survived to leave hospital. No differences were observed between survivors and non-survivors with regard to age, previous medical condition, drug therapy, or creatinine value on admission. Mode of presentation, duration of surgery, frequency of hypotension and number of blood transfusions were similar in both groups. Total hospital stay and duration of intensive care were distributed equally between the two groups. Those who survived seemed to require less inotropic support and a shorter duration of ventilation than the non-survivors; the continued need for these support and persistent leucocytosis greater than 15,000/mm3 were associated with little chance of survival.

Acute Kidney Injury↗