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Biomedical subjects

C G Brown

Publications and source records attributed to C G Brown.

At least 127 records · Page 7Linked to original sources

Studies on the effect of chronic L-triiodothyronine (T3) treatment on brain Na+,K+-ATPase activity in the mature rat.

Mature rats were dosed with T3 by different routes and dose-levels at either 0.1 mg/kg for 14 days s.c. (Group A), 1 mg/kg for 3 alternative days i.p. (Group B), 5 mg/kg for 14 days p.o. (Group C), or with propylthiouracil (PTU 50 mg/day for 14 days p.o.-Group D). Measurement of cerebellar and striatal NA+,K+-ATPase activities showed that whereas Groups A, B and D were unaffected when compared with controls, there were 35-70% increases respectively in the activities of both molecular forms of the enzyme, alpha(+), high ouabain affinity, and alpha, low ouabain affinity, in Group C rat brains at the highest dose of T3 tested. Kidney Na+,K+-ATPase activity was also elevated (67% increase) in this group of animals showing significant changes in renal medullary tissue only. Acute elevation of brain dopamine levels by administration of an MAOI plus L-DOPA (50 mg/kg, 60 min) significantly elevated (20% increase) the activities of both molecular forms of Na+,K+-ATPase in corpus striatum. Treatment with L-tryptophan (50 mg/kg, 60 min) failed to produce any changes in the striatal activities. The possible relationship of increases in enzyme activities with T3 and increased brain monoamine function is discussed. Both plasma free T4(FT4) and total T4(TT4) were markedly depressed in all T3-treated rats. Although hypothalamic thyrotropin releasing hormone (TRH) concentrations were unaltered by any of the T3 treatments, pituitary thyroid stimulating hormone (TSH) concentrations were greatly diminished and it is thought that this may reflect a direct effect of T3 on TSH synthesis.

Animals↗

The effect of epinephrine versus methoxamine on regional myocardial blood flow and defibrillation rates following a prolonged cardiorespiratory arrest in a swine model.

Recent studies in swine have shown that larger doses of epinephrine than those currently employed for cardiopulmonary resuscitation (CPR) significantly improve regional myocardial blood flow following prolonged cardiac arrest. The dose-response effect of a pure alpha-adrenergic agonist, methoxamine, on regional myocardial blood flow has not been investigated in this setting. This study compared the effect of high-dose epinephrine with graded doses of methoxamine on regional myocardial blood flow, oxygen delivery/utilization, and defibrillation rates during CPR. Twenty swine were instrumented for regional myocardial blood flow measurements using radiolabeled tracer microspheres. Measurements of regional myocardial blood flow, oxygen delivery, and oxygen consumption were made during normal sinus rhythm. Ventricular fibrillation was then induced. Following 10 minutes of ventricular fibrillation, CPR was initiated with a pneumatic compressor. Regional myocardial blood flow, oxygen delivery, and oxygen consumption were then measured during CPR. Following 3 minutes of CPR, the swine were allocated to one of four treatment groups (five per group): group I, epinephrine 0.2 mg/kg; group II, methoxamine 0.1 mg/kg; group III, methoxamine 1.0 mg/kg; and group IV, methoxamine 10.0 mg/kg. One minute after drug administration, regional myocardial blood flow, oxygen delivery, and oxygen consumption measurements again were made. Three and one half minutes after drug administration, defibrillation was attempted. Regional myocardial blood flow following drug administration was compared using an analysis of covariance. Epinephrine (0.2 mg/kg) significantly improved myocardial blood flow (P less than .002) for all tissues examined compared with all doses of methoxamine.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

The beta error and sample size determination in clinical trials in emergency medicine.

In the analysis of a clinical trial an investigator may fail to discern a statistically significant difference in outcome between control and experimental groups, when in fact one exists. Failure to demonstrate such a difference when it actually exists is known as "type II" error, and its probability of occurring is termed "beta." The purpose of our study was to determine the distribution of beta errors in negative trials in the Journal of the American College of Emergency Physicians (JACEP) (1972-1979) and Annals of Emergency Medicine (1980-1984). All negative comparative clinical trials appearing in JACEP and Annals from volume 1 (1972) to volume 13 (1984) were surveyed and were eligible for inclusion in the study. A trial was defined as negative if the investigator specifically stated that there was no significant difference in outcome between the experimental and control groups. For each negative trial the following parameters were calculated: beta error, based on the sample size used and the difference determined to be important to detect clinically; sample size required to detect a clinically meaningful difference as determined by the authors of this study; and minimum true difference that had to be detected in the trial at a beta equal to 0.20, to discern a statistically significant result. For the 13 years surveyed, we found 21 endpoints in 14 negative trials that were analyzable. Only one of the trials (7.1%) addressed the issues of beta errors and sample size determination. In the remaining 13 negative trials, the calculated beta error ranged from .60 to .97. For the endpoints analyzed, a sample size of up to 450 times larger than that used would have been required to detect a clinically important difference.(ABSTRACT TRUNCATED AT 250 WORDS)

Clinical Trials as Topic↗

The effect of high-dose phenylephrine versus epinephrine on regional cerebral blood flow during CPR.

Prior studies have not found the alpha agonist phenylephrine, in a dose of 0.1 mg/kg, to be as effective as 0.20 mg/kg of epinephrine in improving regional cerebral blood flow (CBF) during CPR in swine. We undertook this study to assess whether higher doses of phenylephrine might improve regional CBF. Fifteen swine were allocated to receive either epinephrine 0.2 mg/kg, phenylephrine 1.0 mg/kg, or phenylephrine 10 mg/kg. Regional CBF measurements were made during normal sinus rhythm, during CPR, and during CPR following drug administration. Epinephrine 0.2 mg/kg was significantly better in improving regional CBF to the left and right cerebral cortices, cerebellum, midbrain, and cervical cord than was phenylephrine 1.0 mg/kg. There was no significant difference in regional CBF between the animals receiving epinephrine 0.2 mg/kg and phenylephrine 10 mg/kg. The study shows that large doses of epinephrine and phenylephrine may be required during CPR to improve regional cerebral blood flow following a prolonged arrest.

Animals↗

Methoxamine versus epinephrine on regional cerebral blood flow during cardiopulmonary resuscitation.

The improvement in cerebral blood flow (CBF) during CPR after epinephrine administration has been attributed to epinephrine's alpha-adrenergic properties. Methoxamine, a pure alpha-1 agonist, has only been shown to be comparable to epinephrine in restoring circulation after cardiac arrest in a canine model. This study compares the effectiveness of equipotent doses of epinephrine and methoxamine in improving CBF during CPR after a prolonged cardiac arrest in a swine model. Twenty-five swine, weighing 15.9 to 28.2 kg, underwent instrumentation for regional CBF using tracer microspheres. CBF was determined during normal sinus rhythm. After 10 min of ventricular fibrillation, CPR was begun with a pneumatic compressor. CBF measurements were again made during CPR. After 3 min of CPR, the swine were randomized to receive 0.02 or 0.2 mg/kg epinephrine, 0.1, 1.0, or 10.0 mg/kg methoxamine. Five swine were allocated to each group. CBF measurements were determined after drug administration and compared using a Bonferroni multiple comparison procedure. A p-value less than .05 was considered statistically significant. This study demonstrated that, after a 10-min cardiac arrest, CBF was extremely low, averaging less than 7 ml/min X 100 g during external CPR. There were no clinically significant improvements in regional CBF after 0.02 mg/kg of epinephrine, or the two lowest doses of methoxamine. The addition of 10 mg/kg of methoxamine clinically improved blood flow only to the most caudal CNS structures, including the pons, medulla, and cervical spinal cord.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

The effects of graded doses of epinephrine on regional myocardial blood flow during cardiopulmonary resuscitation in swine.

Although epinephrine has been shown to improve myocardial blood flow during cardiopulmonary resuscitation (CPR), the effects of standard as well as larger doses of epinephrine on regional myocardial blood flow have not been examined. In this study we compared the effects of various doses of epinephrine on regional myocardial blood flow after a 10 min arrest in a swine preparation. Fifteen swine weighing greater than 15 kg each were instrumented for regional myocardial blood flow measurements with tracer microspheres. Regional blood flow was measured during normal sinus rhythm. After 10 min of ventricular fibrillation, CPR was begun and regional myocardial blood flow was determined. Animals were then randomly assigned to receive 0.02, 0.2, or 2.0 mg/kg epinephrine by peripheral injection. One minute after drug administration, regional myocardial blood flow measurements were repeated. The adjusted regional myocardial blood flows (ml/min/100 g) for animals given 0.02, 0.2, and 2.0 mg/kg epinephrine, respectively, were as follows: left atrium, 0.9, 67.4, and 58.8; right atrium, 0.3, 46.2, and 38.5; right ventricle, 0.7, 82.3, and 66.9; right interventricular septum, 1.7, 125.5, and 99.1; left interventricular septum, 2.8, 182.8, 109.5; mesointerventricular septum, 16.8, 142.2, and 79.2; left ventricular epicardium, 19.2, 98.5 and 108.7; left ventricular mesocardium, 22.8, 135.0, and 115.8; and left ventricular endocardium, 2.5, 176.1, and 132.9). All comparisons between the groups receiving 0.02 and 0.2 mg/kg epinephrine were statistically significant (p less than .05).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Approach to decreased hearing.

This article is designed to review proper procedure by an emergency or primary care physician when evaluating a patient with decreased hearing. It will cover the anatomy and physiology of hearing, as well as the evaluation and initial management of conductive and sensorineural hearing loss.

Adolescent↗

Emergency evaluation and management of epistaxis.

Epistaxis is a problem that is commonly seen by emergency physicians. Its complete evaluation requires an understanding of the anatomy in addition to the various etiologies, including mechanical, traumatic, hematologic, cardiovascular, inflammatory, and congenital causes. Although the management of epistaxis will vary according to the cause, the basic principles of hemostasis and packing are emphasized. In cases in which the bleeding cannot be controlled.

Emergencies↗

Cryopreservation of Theileria-infected lymphoblastoid cells with functional assessment of viability.

Bovine lymphoblastoid cell cultures infected with Theileria annulata were frozen to -60 degrees C in a programmable cooling apparatus using continuous cooling rates of 1 degree C/min, 10 degrees C/min and 120 degrees C/min and a two-step cooling rate with an equilibration period of 20 min at -30 degrees C. The cryopreservative was DMSO at concentrations of 5, 10 and 15%. Aliquots of cryopreserved material were stored in the vapour phase of a liquid nitrogen refrigerator and resuscitated by rapid thawing in a 40 degrees C water bath. The efficiency of the freezing methods was compared by assessing the viability and plating efficiency of cells after resuscitation, dilution and equilibration in cell culture medium. A significant correlation was recorded between the results obtained by these two methods which showed that the two-step method yielded cells with viability of 95 to 97% and a plating efficiency equal to that of unfrozen cells. It was concluded that such a freezing method would be ideal for the cryopreservation and storage of banks of Theileria annulata-infected cells for vaccine purposes.

Animals↗

The comparative effects of epinephrine versus phenylephrine on regional cerebral blood flow during cardiopulmonary resuscitation.

Epinephrine in larger doses than currently recommended during cardiopulmonary resuscitation (CPR) has been shown to improve cerebral blood flow (CBF) following a 10-min arrest in a swine model. The purpose of this pilot study was to measure CBF during CPR, comparing high-dose epinephrine to a pure alpha-1 agonist, phenylephrine. Ten swine each weighing greater than 15 kg, were instrumented for regional CBF measurements using tracer microspheres. CBF was measured during normal sinus rhythm (NSR). Following 10 min of ventricular fibrillation, CPR was begun and regional CBF was again measured. Following 3 min of CPR, the swine were randomized to receive either epinephrine (0.2 mg/kg), or phenylephrine (0.1 mg/kg), through a peripheral intravenous line. Regional CBF was again measured 1 min after drug administration. Regional CBF following drug administration was compared using an analysis of covariance. Adjusted CBFs are expressed in ml/min per 100 g for epinephrine and phenylephrine, respectively: left cerebral cortex (12.5 vs. 2.3, P = 0.002); right cerebral cortex (13.0 vs. 2.8, P = 0.003); cerebellum (32.9 vs. 4.1, P = 0.004); midbrain (35.7 vs. 2.6, P = 0.0004), pons (30.3 vs. 2.9, P = O.006); medulla (49.5 vs. 13.6, P = 0.02) and cervical spinal cord (49.6 vs. 14.1, P = 0.003).

Animals↗

Antigenic diversity of Theileria annulata macroschizonts.

A series of monoclonal antibodies has been produced which reacts with the intracellular macroschizont of Theileria annulata, and this series has been used to examine the level of antigenic diversity between and within stocks of the parasite in addition to species specificity within the genus. The majority of the monoclonal antibodies (six of eight) reacted with all stocks tested and four were species-specific. Two monoclonal antibodies detected variation between stocks and within stocks. The variation within a stock was manifest as only a proportion of the macroschizonts reacting with the monoclonal antibody. This was demonstrated as being due to the strain containing more than one antigenic type of parasite by cloning the infected lymphocyte cell line and showing that the resulting cloned cell lines were antigenically homogeneous. The variation between stocks allowed them to be divided into three groups on the basis of antigenic profile.

Animals↗

Utility of urine cultures in the emergency department.

Urinary tract infection (UTI) is a common problem treated by emergency physicians. A midstream urine sample remains the most frequent method of culture collection. Although midstream urine culture growing more than 10(5) colony-forming units per milliliter (cfu/mL) has been considered diagnostic of UTI, high false-positive and false-negative rates as well as a lack of precision have been associated with this method of collection. Alternative methods of establishing the diagnosis of UTI have excellent sensitivity and may be utilized at the time of patient presentation. These include the detection of leukocyte esterase activity in urine and the presence of one or more bacteria on microscopic examination of an unspun urine sample. Women of child-bearing age represent the vast majority of patients seen with UTI. Uncomplicated infection of the urinary tract has a generally benign course in these patients, and is rarely associated with long-term complications. In addition, these patients are infected with a predictable spectrum of uropathogens that respond to the commonly used antibiotics. It appears that urine cultures provide little additional information in this patient population. Urine cultures should be obtained in patients at high risk for pyelonephritis or bacteremia/urosepsis, as well as in those expected to have uncommon or resistant organisms.

Adolescent↗

Comparative effect of graded doses of epinephrine on regional brain blood flow during CPR in a swine model.

Cerebral blood flow (CBF) with conventional closed-chest cardiopulmonary resuscitation (CCPR) has been measured at only 2% to 11% of prearrest values. The purpose of our study was to determine whether the peripheral administration of higher doses of epinephrine than currently recommended during CCPR following a prolonged cardiac arrest improves CBF compared to CCPR using a standard dose of epinephrine. Fifteen swine were randomized to receive CCPR plus 0.02 mg/kg, 0.2 mg/kg, or 2.0 mg/kg epinephrine through a peripheral IV line following a ten-minute cardiopulmonary arrest and three minutes of CCPR. Regional CBF measurements were made by radionuclide microsphere technique during normal sinus rhythm (NSR), CCPR, and following epinephrine administration. The adjusted regional blood flows (in mL/min/100 g) following epinephrine administration for the 0.02-, 0.2-, and 2.0-mg/kg groups were, respectively, left cerebral cortex (3.3, 13.1, 11.8); right cerebral cortex (3.9, 13.8, 12.2); cerebellum (9.2, 32.0, 33.1); midbrain/pons (9.9, 32.1, 32.3); medulla (10.6, 61.5, 54.2); and cervical spinal cord (12.2, 53.8, 35.8). In this swine model, 0.2 mg/kg and 2.0 mg/kg epinephrine significantly increased regional CBF over that seen with standard doses. Because neuronal survival is dependent on flow rates of 10 to 15 mL/min/100 g, this preliminary evidence suggests that these higher doses of epinephrine may help improve neurological outcome in CCPR.

Animals↗

Identification of infection-associated antigens in Theileria annulata transformed cells.

The protozoan parasite Theileria annulata causes a severe disease of cattle in tropical countries; one stage in the parasite life cycle involves the transformation of bovine lymphocytes leading to rapid lymphoproliferation. Immunity to this disease is largely cell mediated and directed against the infected lymphocyte. In this paper we report the identification of three classes of infection specific antigen (using monoclonal antibodies) one of which is found on the surface of the lymphocyte. Such antigens can be used in parasite strain typing, in providing an understanding of the molecules involved in immunity and in providing the basis for a vaccine.

Animals↗

Specific lysis of Theileria annulata-infected lymphoblastoid cells by a monoclonal antibody recognizing an infection-associated antigen.

A monoclonal antibody (4H5) recognizing a Theileria annulata infection-associated antigen was assayed to see if it could either suppress the proliferation of T. annulata-infected lymphoblastoid cells, as monitored by the incorporation of tritiated thymidine by proliferating host cells, or lyse T. annulata-infected lymphoblastoid cells, as assessed by counts of target cell numbers and examination of Giemsa stained smears. These assays showed that binding of the monoclonal antibody, in the presence of complement, both lysed and suppressed the proliferation of the T. annulata Hissar-infected cell line against which this monoclonal antibody was raised. This effect extended both to other (allogeneic) T. annulata Hissar-infected cell lines and to lymphoblastoid cell lines infected with other geographical stocks of T. annulata. An uninfected bovine lymphoid cell line was not affected by the antibody. The results obtained in these in vitro experiments are taken to mean that binding of the monoclonal antibody 4H5 to a T. annulata infection-associated antigen, in the presence of complement, will lyse and suppress specifically the proliferation of T. annulata-infected lymphoblastoid cells. These observations raise the possibility that immunization of cattle with the purified T. annulata infection-associated antigen recognized by this monoclonal antibody may provoke immune responses which are capable of suppressing the proliferation of T. annulata-infected lymphoblastoid cells in vivo and thus provide an effective method of immunoprophylaxis against tropical theileriosis.

Animals↗

White blood cell count and differential count.

Current methods for performing the white blood cell count and differential count along with recent technologic advances are discussed. Sources of error and variation in these tests are presented. The use of the white blood cell count and the differential count in a variety clinical situations is reviewed.

Adolescent↗

Studies on oestrogen-2/4-hydroxylase activity in mammalian brain, using a radioenzymatic assay method.

The activity of oestrogen-2/4-hydroxylase in brain tissue was studied using a radioenzymatic assay which controlled for non-specific formation of catechol oestrogen. The ontogeny of enzyme activity in male and female rat brain was examined between 1 and 70 days of age. Until 10 days of age, both sexes showed low enzyme activity. Between days 10 and 15 enzyme activity in the female significantly increased but was unchanged in the male. Male brain enzyme activity increased between days 15 and 20 whereas activity was unchanged in the female. Both males and females showed increases in enzyme activity between 20 and 25 days of age. Thereafter enzyme activity plateaued but at all ages between day 20 and day 70 male brain enzyme activity was significantly greater than in the female. A study of the distribution of the oestrogen-2/4-hydrolase in the sheep hypothalamus revealed that the stalk/median eminence had approx 10 times greater activity than either the anterior, medial or posterior hypothalamus. These findings are discussed in relation to sexual differentiation of the brain.

Aging↗