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Biomedical subjects

C G Brown

Publications and source records attributed to C G Brown.

At least 55 records · Page 3Linked to original sources
PubMed1996

Theileria annulata: altered gene expression and clonal selection during continuous in vitro culture.

Kept in continuous in vitro culture, the protozoan parasite Theileria annulata gradually loses virulence when inoculated into cattle. These attenuated cell lines form the basis of the in vitro live vaccines which have been used successfully to control tropical theileriosis in several endemic regions. In the study reported here, events occurring during in vitro culture of an Indian (Hisar) cell line, which may be associated with the reduction in virulence, have been investigated. Hybridization with two polymorphic DNA probes following Southern blotting showed that selection of particular parasite genotypes occurs very rapidly with culture; a novel hybridization pattern is observed with both probes after 50-100 passages in vitro. In addition to this selection process, immunofluorescence studies using a monoclonal antibody which specifically recognizes virulent T. annulata revealed alterations in antibody reactivity following in vitro culture. This loss of reactivity was observed in three cloned cell lines derived from the early, virulent Hisar line and implies that phenotypic changes resulting from alterations to parasite gene expression are taking place during the attenuation process. When considered with the results from in vivo infections with serial passages of this cell line, it can be proposed that both altered gene expression and selection may be involved in the loss of pathogenicity of T. annulata during continuous in vitro culture.

Animals↗
PubMed1996

A preliminary study on the attenuation of Tunisian schizont-infected cell lines of Theileria annulata.

Four Theileria annulata cell lines were characterised at low passage levels using two polymorphic markers and then used to infect calves. Their virulence seemed to be related to the number of genotypes present within the cell line. In all, 3 of the 4 cell lines were cultured up to passage 100 or 200 and inoculated into calves. Their characterisation using the same markers indicated that the attenuation was related to a reduction in the parasite polymorphism down to a single genotype. The immunogenicity of the three attenuated cell lines was assessed in calves using two types of challenge. Optimal protection was observed against homologous challenges. The level of immunity to heterologous challenges appeared to decrease with attenuation and seemed to depend on the cell line used.

Animals↗
PubMed1996

Signal analysis of the human electrocardiogram during ventricular fibrillation: frequency and amplitude parameters as predictors of successful countershock.

STUDY OBJECTIVE: To determine whether there is information in the human ventricular fibrillation (VF) ECG signal that is predictive of successful countershock. METHODS: We carried out a retrospective analysis of ECG signals recorded during out-of-hospital treatment of adult patients in VF. Four parameters--centroid frequency (FC), peak power frequency (FP), average segment amplitude (SA), and average wave amplitude (WA)--were extracted from the recorded ECG signal immediately before each countershock and compared with countershock outcome. RESULTS: The outcome of each countershock (total, 128 countershocks) administered to 55 patients in VF was determined from available emergency medical services data sheets and time-domain ECG signal and voice recordings. The original 4-second time-domain ECG segment immediately before the countershock was used to extract SA and WA. The 4-second ECG segment immediately before each countershock was transformed into the frequency domain by means of Fourier analysis, and the parameters FC and FP were extracted from the result. These parameters were compared with countershock outcome by means of Kolmogrov-Smirnov analysis. Sensitivity and specificity of these parameters, as well as receiver operating characteristic curves, were constructed. FC was statistically higher for successful countershocks (FC, 5.48 +/- .67 Hz) than for successful countershocks (FC, 4.85 +/- 1.16 Hz; P=.012). We found no statistical difference for FP (P=.066), SA (P=.549), and WA (P =.337). FP and FC, when used in combination and in certain ranges (3.5 Hz < or = FP < or = 7.75 Hz and 3.86 Hz < or = FC < or = 6.12 Hz) had a sensitivity of 100% and a specificity of 47.1% in predicting successful countershock. The probabilities of predicting countershock outcome for FC, FP, SA, and WA were .72, .70, .52, and .53, respectively. CONCLUSION: FC and FP are predictive of countershock outcome for patients in VF and hold the potential to guide therapy during cardiac arrest.

Adult↗
PubMed1996

Research directions in emergency medicine.

The goal of emergency medicine is to improve health while preventing and treating disease and illness in patients seeking emergency medical care. Improvements in emergency medical care and the delivery of this care can be achieved through credible and meaningful research efforts. Improved delivery of emergency medical care through research requires careful planning and the wise use of limited resources. To achieve this goal, emergency medicine must provide appropriate training of young investigators and attract support for their work. Promotion of multidisciplinary research teams will help the specialty fulfill its goals. The result will be the improvement of emergency medical care which will benefit not only the patients emergency physicians serve but also, ultimately, the nation's health.

Emergency Medicine↗
PubMed1995

Theileria annulata sporozoite antigen fused to hepatitis B core antigen used in a vaccination trial.

A C terminal fragment (SR1) of SPAG-1, a sporozoite surface antigen of Theileria annulata, has been expressed as a fusion protein in the e1 loop of hepatitis B core antigen (HBcAg). This recombinant antigen (HBcAg-SR1) is produced in the form of self-assembling polyhedral particles which have been visualised under the electron microscope. Cattle immunised with HBcAg-SR1 produced high titres of neutralising antibodies. A significant T cell response to both the HBcAg and SR1 determinants was observed but evidence of a T suppressor determinant in SR1 was also revealed. Immunised cattle showed some evidence of protection to sporozoite challenge as assessed by severity of the disease. The significance of these findings for the development of a sub-unit vaccine against T. annulata is discussed.

Animals↗
PubMed1995

Nitric oxide inhibits establishment of macroschizont-infected cell lines and is produced by macrophages of calves undergoing bovine tropical theileriosis or East Coast fever.

Nitric oxide (NO) was produced when bovine peripheral blood mononuclear cells (PBMC) or purified, adherent PBMC (macrophages) were incubated in vitro with bovine recombinant interferon gamma (Bo rIFN-gamma). NO was produced by cells from naive, uninfected calves as well as by cells from cattle either infected with or recovered from infection with Theileria annulata or Theileria parva. PBMC of cattle undergoing tropical theileriosis (T. annulata infection) or East Coast fever (T. parva infection) synthesized NO spontaneously in vitro. NO was also induced when PBMC of immune, but not of naive, cattle were cultured with T. annulata macroschizont-infected cell lines. Macrophages alone were not stimulated to produce NO by such infected cells. In vitro establishment of macroschizont-infected cell lines was suppressed either by incubating sporozoites with S-nitroso-N-acetyl-DL-penicillamine (SNAP), a NO releasing molecule, prior to invasion of PBMC or by pulsing developing cultures of trophozoite-infected cells with SNAP. Proliferation of established macroschizont-infected cell lines was not affected by SNAP. Taken together with the well documented roles of NO in neutrotransmission, vasodilatation, cell and tissue damage and immunosuppression, the results presented here indicate that NO may not only protect cattle against T. annulata and T. parva but, if produced in excess, play a prominent role in the pathogenesis of tropical theileriosis and East Coast fever.

Animals↗
PubMed1994

Outcome of insulin-treated diabetics receiving epinephrine during cardiac arrest.

The purpose of this study was to determine the effects of epinephrine in insulin-treated diabetics (DM) compared with nondiabetic (ND) controls during cardiopulmonary resuscitation (CPR). A retrospective analysis from a multicenter study of out-of-hospital cardiac arrest included 62 DM and 1,151 ND. Outcome parameters included return of spontaneous circulation (ROSC), blood pressure (BP), emergency department admissions (EDA), hospital admissions (HA), and hospital discharge (DC). In DM treated with standard-dose epinephrine (SDE), there were trends toward improved ROSC, BP, EDA, and HA compared with ND. DC was not different. With high-dose epinephrine (HDE) these outcomes were not different. Comparison of the outcomes of DM given SDE versus those given HDE were not different. However, none of the DM given HDE (n = 24) were discharged from the hospital. These results suggest that DM may have improved resuscitation rates with SDE and may be adversely affected with HDE. Larger prospective studies are needed to confirm these findings.

Aged↗
PubMed1994

Genomic and phenotypic diversity of Tunisian Theileria annulata isolates.

This study describes polymorphism in Theileria annulata, an intracellular protozoan parasite of bovine leucocytes and red blood cells. Fifty-three different stocks of T. annulata, isolated from 17 sites (districts) in Tunisia, have been characterized by anti-parasite monoclonal antibody (MAb) reactivity, glucose phosphate isomerase (GPI) isoenzyme electrophoresis, and Southern blotting with two genomic DNA probes. These appears to be considerable diversity amongst T. annulata stocks from Tunisia, no two isolates being identical, even those from animals on the same farm. Two distinct antigenic populations were detected by MAb 7E7. They were defined by negative and positive cells in the indirect fluorescent antibody test. The percentage of positive cells in different isolates ranged between 0 and 100%. The population variation seen by GPI analysis and DNA probes was greater; 7 different GPI phenotypes were identified amongst the stocks studied, while DNA probes T. annulata Tunis (TaT) 17 and 21 detected up to 5 different variants. The majority of isolates were shown to contain more than one parasite population, the number of variants per isolate ranging from 1 to 4. No correlation between particular parasite phenotypes or genotypes and their geographical site of isolation was observed. Selection of parasite populations in vivo and in vitro is also discussed.

Animals↗
PubMed1994

Angiotensin II administration improves cerebral blood flow in cardiopulmonary arrest in swine.

BACKGROUND AND PURPOSE: Cerebral blood flow during cardiopulmonary resuscitation is inadequate to meet cerebral metabolic demand. Adrenergic agonists improve cerebral blood flow, but clinical trials of increased doses in adults have not shown improved outcome from cardiac arrest. This may be due to adverse beta-agonist-mediated effects. The purpose of this study was to determine the effect of angiotensin II, a potent nonadrenergic vasopressor, on cerebral blood flow in cardiac arrest. METHODS: Eleven immature swine were anesthetized and instrumented for regional blood flow measurements with radiolabeled microspheres. A sagittal sinus catheter was placed for blood gas determination. A blood flow measurement was performed in normal sinus rhythm and ventricular fibrillation induced. After 10 minutes of ventricular fibrillation, cardiopulmonary resuscitation was begun and a blood flow measurement performed. Angiotensin II at a dose of 50 micrograms/kg was administered intravenously at 13 minutes of ventricular fibrillation. A blood flow measurement was performed and defibrillation attempted. A fourth blood flow measurement was obtained if return of spontaneous circulation occurred. RESULTS: Total cerebral blood flow was 46.4 mL/min per 100 g in normal sinus rhythm. This fell to 6.9 mL/min per 100 g with cardiopulmonary resuscitation alone and rose to 30.8 mL/min per 100 g after the administration of angiotensin II. The improvement following angiotensin II was statistically different (P = .002). Cerebral blood flow further rose in the animals that had return of spontaneous circulation to 73.9 mL/min per 100 g. CONCLUSIONS: Angiotensin II in a dose of 50 micrograms/kg significantly improves cerebral blood flow in this model of cardiac arrest.

Angiotensin II↗
PubMed1993

Phenotypic analysis of bovine leukocyte cell lines infected with Theileria annulata.

Six cell lines that were infected with Theileria annulata were compared for expression of a range of surface molecules. Immunofluorescence staining with the panel of monoclonal antibodies formulated for the Second Workshop was analysed by flow cytometry. Four lines generated from bovine peripheral blood mononuclear cells by exposure to sporozoites in vitro and one line generated in vivo from an infected calf were phenotypically similar. Phenotypic analysis of those lines did not demonstrate a monocyte or B cell origin, but indicated they were not derived from T cells. An uncloned line generated in vivo from an infected calf was CD3+ and gamma/delta TCR+. The results indicate that a wider range of host cell types may be infected in vivo than suspected hitherto and that some of the cells may express an abnormal pattern of surface molecules. Both could have profound consequences for the pathogenesis of T. annulata infection.

Animals↗
PubMed1993

The effect of intravenous magnesium administration on aortic, right atrial and coronary perfusion pressures during CPR in swine.

OBJECTIVE: To determine the effect of magnesium administration on aortic, right atrial and coronary perfusion pressure (CPP) during cardiopulmonary resuscitation (CPR). DESIGN: Twelve swine weighing 23.2 +/- 3.1 kg were instrumented for CPP, aortic systolic (AOSP) and aortic diastolic (AODP) pressures. INTERVENTION: Ventricular fibrillation was induced and after 20 min of CPR the animals were allocated to receive epinephrine 0.2 mg/kg, or epinephrine 0.2 mg/kg plus magnesium 0.14 g/kg. Epinephrine was repeated every 5 min. Arterial blood gases were determined during normal sinus rhythm and prior to drug administration. RESULTS: Pressures were recorded and averaged over four consecutive 5-min intervals following initial drug administration. AOSP, AODP and CPP were compared using an analysis of covariance. AOSP was statistically lower in the group receiving magnesium. There was a trend toward lower AODP and CPP in the group receiving magnesium as well. These statistical differences and trends were absent after adjusting for pressures during normal sinus rhythm and serum bicarbonate prior to drug administration. CONCLUSIONS: In this model of prolonged cardiac arrest, the administration of magnesium with epinephrine appeared to have a negative effect on aortic pressures during CPR. Further study is needed to determine the confounding effect of serum bicarbonate on the response to epinephrine and magnesium during CPR.

Animals↗
PubMed1993

Initial countershock in the treatment of asystole.

BACKGROUND: Routine provision of defibrillatory countershock (CS) in the initial management of asystolic cardiac arrest has been advocated because certain cases of ventricular fibrillation (VF) may present as asystole (AS). OBJECTIVE: To determine the value of initial CS versus endotracheal intubation and pharmacologic therapy alone in the treatment of asystolic cardiac arrest. DESIGN/PARTICIPANTS: A retrospective analysis of data collected prospectively during a multicenter study of out-of-hospital cardiac arrest. The study subjects were all patients whose initial cardiac arrest rhythm was AS and were treated with standard advanced cardiac life support (ACLS). SETTING: Six urban emergency medical services (EMS) systems. INTERVENTION: Patients in AS were treated initially with CS followed by ACLS therapy (CS Group), and were compared to those patients receiving endotracheal intubation and pharmacologic therapy alone (No CS Group). OUTCOME MEASURES: Those receiving initial CS were compared to those not receiving CS using both Chi-square and logistic regression analysis. Outcome parameters included: rates of return of spontaneous circulation (ROSC), emergency department admission, hospital admission and hospital discharge. RESULTS: Of the 194 patients presenting with AS, 77 received CS as their initial therapy. Of these, 13 (16.9%) had ROSC compared to 27 of the 117 (23.1%) from the No CS Group (P = 0.30). Emergency department and hospital admission rates were not significantly different; 13.0% versus 18.0% (P = 0.36), and 13.0% versus 11.1% (P = 0.69) for CS versus No CS, respectively. None of the patients in the CS Group were discharged alive versus two (1.7%) from No CS (P = 0.52). Of 42 patients with bystander-witnessed cardiac arrests, 13.3% in the CS Group had ROSC compared to 40.7% in the No CS Group (P = 0.07). Emergency department admission rates were 6.7% for the CS Group and 33.3% for the No CS Group (P = 0.07); while hospital admission rates were 6.7% and 22.2%, respectively (P = 0.39). When these comparisons were adjusted for bystander-initiated CPR, CPR interval, and paramedic response interval, the P-values became 0.10, 0.05 and 0.17, respectively. CONCLUSIONS: Although, statistically, the results for both groups were not distinguishable, outcomes for asystolic patients had a tendency to be better when the initial therapy did not involve CS. Larger study populations are recommended to confirm these preliminary observations.

Aged↗
PubMed1993

Angiotensin II improves myocardial blood flow in cardiac arrest.

Epinephrine is used to increase coronary perfusion pressure and improve myocardial blood flow during cardiac arrest. Alternative vasopressors may have hemodynamic advantages over epinephrine. The purpose of this investigation was to test the effect of the vasopressor angiotensin II on myocardial blood flow in a swine model of cardiac arrest. Eleven swine were anesthetized and instrumented for regional blood flows by radiolabeled microsphere technique. A baseline blood flow measurement (BFM), coronary sinus and aortic blood gases were obtained in normal sinus rhythm (NSR). Ventricular fibrillation (VF) was induced and mechanical CPR begun after 10 min of VF. A BFM and blood gases were obtained during CPR. Angiotensin II, 50 micrograms/kg, was administered at 13 min of VF. A repeat BFM and blood gases were obtained following angiotensin II. Defibrillation was attempted at 16.5 min of VF. If return of spontaneous circulation (ROSC) occurred a fourth BFM and blood gases were obtained. Myocardial blood flow was 134.2 +/- 40.1 ml/100 g per min during NSR. This fell to 15.1 +/- 19.9 with CPR alone, and rose to 66.9 +/- 69.8 following angiotensin II administration (P = 0.04; by two tailed T-test). Myocardial blood flow following ROSC further increased to 212.6 +/- 58.0. Angiotensin II in a dose of 50 micrograms/kg significantly increases myocardial blood flow in this model of cardiac arrest.

Angiotensin II↗
PubMed1993

Effect of first-responder automated defibrillation on time to therapeutic interventions during out-of-hospital cardiac arrest. The Multicenter High Dose Epinephrine Study Group.

STUDY OBJECTIVES: The effect of automated defibrillation provided by basic emergency medical technician (EMT) first-responder units on the time intervals to other critical interventions in the management of out-of-hospital cardiac arrests is unknown. The purpose of this study was to define and compare elapsed time intervals to basic CPR, paramedic arrival, initial countershock, endotracheal intubation, IV access, and initial adrenergic drug therapy in first-responder automated defibrillation/paramedic versus basic EMT/paramedic emergency medical services systems. DESIGN: Prospectively collected data from a 15-month multicenter study of out-of-hospital, nontraumatic cardiac arrests were analyzed. The mean time intervals to critical therapeutic interventions between first-responder automated defibrillation/paramedic and basic EMT/paramedic groups were compared using the Student's t-test with Bonferroni correction. SETTING: Three first-responder automated defibrillation/paramedic and three basic EMT/paramedic urban emergency medical services systems. PARTICIPANTS: 1,578 patients with out-of-hospital cardiac arrest. INTERVENTIONS: The first-responder automated defibrillation/paramedic group received initial ECG analysis and/or automated countershock by first-responder/EMTs; the basic EMT/paramedic group received initial ECG analysis and/or manual countershock by paramedics. RESULTS: Elapsed time intervals in minutes +/- SD for first-responder automated defibrillation/paramedic versus basic EMT/paramedic groups, respectively, were as follows: Collapse to CPR, 4.3 +/- 3.9 versus 5.4 +/- 5.2 (P = .017); collapse to countershock, 10.7 +/- 5.9 versus 13.0 +/- 6.0 (P = .017); collapse to paramedic arrival, 13.0 +/- 5.4 versus 10.3 +/- 6.1 (P = .0001); paramedic arrival to IV access, 5.1 +/- 3.9 versus 7.0 +/- 5.0 (P = .0001); paramedic arrival to endotracheal intubation, 4.8 +/- 4.0 versus 6.8 +/- 5.8 (P = .0001); paramedic arrival to initial adrenergic drug therapy, 7.4 +/- 4.5 versus 8.2 +/- 4.7 (P = .015); collapse to IV access, 17.7 +/- 6.1 versus 16.6 +/- 7.4 (P = .10); collapse to endotracheal intubation, 17.3 +/- 6.4 versus 16.6 +/- 7.8 (P = .32); collapse to initial adrenergic drug therapy, 20.4 +/- 6.7 versus 18.1 +/- 7.2 (P = .010). The time intervals from paramedic arrival to IV access, endotracheal intubation, and initial adrenergic drug therapy remained shorter in the first-responder automated defibrillation/paramedic systems despite stratification by presenting cardiac rhythm. CONCLUSION: First-responder automated defibrillation/paramedic systems provide not only shorter times to initial countershock, as compared with basic EMT/paramedic systems, but by having delegated initial countershock to first-responders, they also allow for significantly shorter times from paramedic arrival to IV access, endotracheal intubation, and initial adrenergic drug therapy interventions.

Electric Countershock↗
PubMed1993

Angiotensin II effects in a swine model of cardiac arrest.

STUDY OBJECTIVE: To evaluate the effect of different doses of the vasopressor angiotensin II on aortic diastolic and coronary perfusion pressures in a swine model of cardiac arrest. DESIGN: Immature swine were anesthetized and hemodynamically monitored. Ventricular fibrillation was induced; CPR was begun after ten minutes of ventricular fibrillation. Aortic and right atrial pressures were recorded continuously throughout the experiment. SETTING: Animal research laboratory. PARTICIPANTS: Immature swine weighing 21 to 32 kg. INTERVENTIONS: Angiotensin II was administered in doses of 25, 50, 75, and 100 micrograms/kg at 13 minutes of ventricular fibrillation. Each dose was tested in four swine. RESULTS: Except for animals receiving 25 micrograms/kg, aortic diastolic pressure increased significantly in all groups after administration of angiotensin II compared with groups receiving CPR alone. Coronary perfusion pressure increased significantly only with 50- and 75-micrograms/kg doses. There were no significant differences in hemodynamic parameters among the different dose groups. CONCLUSION: Angiotensin II in doses of 50, 75, and 100 micrograms/kg significantly increased aortic diastolic pressure, and doses of 50 and 75 micrograms/kg significantly increased coronary perfusion pressure in this model of cardiac arrest.

Angiotensin II↗
PubMed1993

Physiologic measurement of the ventricular fibrillation ECG signal: estimating the duration of ventricular fibrillation.

Estimating the duration of ventricular fibrillation may help determine the best initial therapy and provide estimates of the most appropriate dose of epinephrine to administer during cardiac arrest and resuscitation. In addition, estimating this time can provide a more sound methodologic approach to stratifying patients in the analysis of cardiac arrest studies. In an initial series of studies in swine, we attempted to determine whether changes in the frequency or amplitude (power) of the ventricular fibrillation ECG signal during cardiac arrest could be used to estimate this time. These studies characterized the dynamics of both the total power and the frequency distribution of the power in the ECG over time during ventricular fibrillation in swine. Our purpose was to determine whether sufficient information existed in either parameter to estimate the duration of ventricular fibrillation. The median frequency of the power spectrum was used to track power distribution. Both parameters followed a dynamic and repeatable pattern. A mathematical model of median frequency was developed and used with data obtained from additional swine to estimate the duration of ventricular fibrillation. The model estimated the duration of ventricular fibrillation to within +/- 1.3 minutes of the actual duration from one to ten minutes after the onset of ventricular fibrillation. We recently characterized the time course of the median frequency during ventricular fibrillation in human beings. The median frequency was extracted from each four-second segment of the ventricular fibrillation ECG recordings and plotted versus time from the onset of cardiac arrest. The median frequency in human beings followed a repeatable time course during ventricular fibrillation.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Effect of standard-dose versus high-dose epinephrine on myocardial high-energy phosphates during ventricular fibrillation and closed-chest CPR.

STUDY OBJECTIVE: To evaluate the effects of standard-dose versus high-dose epinephrine on myocardial high-energy phosphate metabolism during resuscitation from cardiac arrest. DESIGN: Prospective, nonrandomized, controlled study using a swine model of cardiac arrest and resuscitation. INTERVENTIONS: After anesthesia, intravascular pressure instrumentation, and ten minutes of ventricular fibrillation arrest, closed-chest CPR was begun. After three minutes of CPR, animals were allocated to receive either 0.02 mg/kg i.v. standard-dose epinephrine (eight) or 0.2 mg/kg i.v. high-dose epinephrine (nine). The animals underwent thoracotomy and rapid-freezing transmural myocardial core biopsy for high-energy phosphate analysis 3.5 minutes after epinephrine administration. High-energy phosphate values were blindly determined using high-pressure liquid chromatography. RESULTS: Intravascular pressure (mm Hg) and high-energy phosphate (nmol/mg protein) results for standard-dose epinephrine versus high-dose epinephrine are, respectively, coronary perfusion pressure, 15.3 +/- 7.8 versus 23.7 +/- 5.5 (P = .0009); phosphocreatine, 0.4 +/- 0.8 versus 6.2 +/- 4.4 (P = .0003); adenosine triphosphate, 9.8 +/- 4.8 versus 12.7 +/- 5.7 (P = .30); adenosine diphosphate, 5.4 +/- 2.1 versus 6.1 +/- 1.3 (P = .41); and adenylate charge, 0.68 +/- 0.12 versus 0.72 +/- 0.12 (P = .87). CONCLUSION: High-dose epinephrine does not deplete myocardial high-energy phosphate when given in this model of prolonged ventricular fibrillation. High-dose epinephrine increases coronary perfusion pressure compared with standard-dose epinephrine. High-dose epinephrine administration repletes phosphocreatine during closed-chest CPR, thereby increasing myocardial energy stores.

Adenosine↗