Biomedical subjects

R J Dempsey

Publications and source records attributed to R J Dempsey.

At least 91 records · Page 5Linked to original sources

PubMed1993

Difluoromethylornithine decreases postischemic brain edema and blood-brain barrier breakdown.

Brain polyamines have been associated with posttraumatic vasogenic edema and blood-brain barrier (BBB) breakdown seen in some models of brain injury. We hypothesized that the inhibition of the enzyme responsible for polyamine production with the decarboxylase difluoromethylornithine (DFMO) may decrease BBB breakdown after a focal brain ischemic stroke. Thirty-two cats underwent 8 hours of middle cerebral artery occlusion and one of four treatments: sham operation (Sham), ischemia (Isc), ischemia/DFMO (Isc/DF), and ischemia/DFMO/putrescine (Isc/DF/PU). The regional brain specific gravity and the volume of Evans blue (EB) extravasation were measured at the time of death. The groups were monitored for temperature, heart rate, blood pressure, and arterial blood gases, and the values did not differ outside normal physiological ranges. EB results were expressed as the percentage of the hemisphere stained and showed the following: Sham, 2.23%; Isc, 32.8%; Isc/DF, 5.6%; Isc/DF/PU, 36.3%. As a measure of BBB, ischemia increased EB staining; DFMO pretreatment decreased the amount of EB staining to control levels; and the polyamine putrescine abolished the protective effect of DFMO (all significant at P = 0.05). DFMO pretreatment also resulted in a significant (P = 0.05) return to control values for specific gravity in the EB-stained regions (1.0328) of ischemic animals. This effect was present primarily in the white matter. Treatment with DFMO, an ornithine decarboxylase inhibitor, significantly decreased postischemic BBB breakdown and vasogenic edema in this model.

Animals↗

PubMed1992

Hyperglycemia suppresses c-fos mRNA expression following transient cerebral ischemia in gerbils.

The c-fos proto-oncogene is activated by transient cerebral ischemia. This activation may signify a specific genetic response to ischemia affecting tolerance to ischemia and ultimate cell survival. Hyperglycemia, which enhances brain injury from transient ischemia, was studied for its effects on this gene system in gerbils by measuring c-fos mRNA 2 h after 20 min of bilateral carotid artery occlusion. Brain c-fos mRNA was increased by ischemia (11.7 +/- 5.0, p less than or equal to 0.05, fold increase) compared to nonischemic controls (1.0 +/- 1.3). Pretreatment with 1 g/kg of glucose partially reduced postischemic c-fos mRNA (6.3 +/- 1.6, p less than or equal to 0.05) while 4 g/kg of glucose completely suppressed postischemic c-fos expression (0.7 +/- 0.3, p less than or equal to 0.05). These data indicate that hyperglycemia suppresses normal postischemic gene expression and suggest the possibility that such suppression is a predictor or even a contributor to hyperglycemia-enhanced ischemic brain damage.

Animals↗

PubMed1992

Amount of smoking independently predicts carotid artery atherosclerosis severity.

BACKGROUND AND PURPOSE: Cigarette smoking is correlated with extracranial carotid artery plaque thickness. Our aim in the present study was to determine whether the level of prior cigarette use is a significant predictor of carotid artery plaque thickness when age, history of hypertension, and history of diabetes are controlled. METHODS: We studied a continuous sample of 790 patients with a history of smoking referred for diagnostic ultrasound imaging of the carotid arteries. Subjects (mean age 61 years) had an average of 51 pack-years of cigarette use. History of hypertension was present in 44% and history of diabetes in 18%. RESULTS: Right and left maximum carotid artery plaque thicknesses were averaged for each patient; the average of this value for all 790 subjects was 1.9 mm. In bivariate analysis, age (p less than 0.0001), pack-years (p less than 0.0001), history of hypertension (p = 0.0003), and history of diabetes (p = 0.037) were each positively associated with carotid artery plaque thickness. In multiple regression analysis, age (p less than 0.0001), pack-years (p = 0.0005), and history of hypertension (p = 0.0044) were statistically significant independent predictors of carotid artery plaque thickness, but history of diabetes (p = 0.2451) was not. CONCLUSIONS: In smokers, the level of cigarette use is associated with an acceleration of carotid artery atherosclerosis development. This effect is independent of age, hypertension, and diabetes. These results support smoking abatement as an important element to stroke prevention in clinical practice.

Adolescent↗

PubMed1991

Modulation of ornithine decarboxylase mRNA following transient ischemia in the gerbil brain.

Ornithine decarboxylase (ODC) is the rate-limiting enzyme that catalyzes the synthesis of polyamines from ornithine and is thought to be involved in the cellular response to growth, differentiation, and stress. Previous studies have demonstrated that transient cerebral ischemia results in an increase in ODC activity and polyamine synthesis. We have used the Mongolian gerbil as a model system to test the hypothesis that the cellular response to ischemia induces a distinct pattern of ODC gene expression. Our results indicate that transient ischemia, induced by bilateral carotid occlusion, elevates ODC mRNA within 1-4 h after reperfusion, which correlates with increased ODC activity and polyamine synthesis. Increased ODC mRNA can be detected in the forebrain, striatum, hippocampus, and midbrain but not the cerebellum, which is not subject to ischemic injury. In contrast, c-fos mRNA increased by 15 min after reperfusion and actin mRNA did not demonstrate alterations in level after ischemia. Pentobarbital prevented the increase in ODC mRNA, whereas the glutamate antagonist MK-801 had no effect on the elevation of ODC gene expression after ischemia. We conclude that the ischemia-induced increase in ODC enzyme activity may be attributed in part to transcriptional activation of the ODC gene.

Animals↗

PubMed1991

Ischemic induction of protooncogene expression in gerbil brain.

Cerebral ischemia and reperfusion results in an active series of metabolic events, eventually leading to cell death. The expression of specific genes during cerebral ischemia and reperfusion may play an important, determinant role in the mechanisms controlling cellular processes. Ten minutes of bilateral carotid occlusion in the Mongolian gerbil was found to increase the messenger RNA for both the c-fos and c-jun protooncogenes. The changes in gene expression were detected in the regions of ischemia, specifically the cortex and striatum, and no increases were seen in either the brain stem or the cerebellum, which possess a separate circulation. Induction of protooncogene mRNA is correlated to the duration of ischemia, i.e., the longer the time of ischemia, the greater the increase in c-fos expression. Pretreatment of animals with pentobarbital reduced the effect of the ischemic insult and prevented the increase in c-fos mRNA. Analysis of the c-fos and c-jun proteins after ischemia demonstrated an increase in the formation of a functional transcriptional complex and association with the AP-1 binding region. These findings suggest that ischemic cell death and recovery in neurodegenerative disorders such as stroke may involve the regulated expression of these protooncogenes early in the pathway of ischemia.

Animals↗

PubMed1991

Intravenous ciprofloxacin versus ceftazidime for treatment of nosocomial pneumonia and urinary tract infection.

Intravenous ciprofloxacin and ceftazidime were compared for efficacy in the treatment of nosocomial pneumonia and urinary tract infection (UTI). Patients with nosocomial pneumonia were randomized to receive ciprofloxacin (as the lactate salt) 300 mg i.v. every 12 hours or ceftazidime (with sodium carbonate) 2 g i.v. every eight hours. Patients with UTI were randomized to receive ciprofloxacin 200 mg i.v. every 12 hours or ceftazidime 1 g i.v. every eight hours. Sputum and urine specimens were collected before, during, and after therapy. For patients with pneumonia, the organisms most frequently isolated before treatment began were Escherichia coli, Haemophilus influenzae, Klebsiella pneumoniae, and Proteus mirabilis. Of the 17 pneumonia patients who completed ciprofloxacin treatment, 15 (88%) had resolution of signs and symptoms or improvement. Of the 15 ceftazidime-treated pneumonia patients, 13 (87%) had resolution or improvement. Staphylococcus aureus, Streptococcus species, Acinetobacter species, and K. pneumoniae infections persisted for the ciprofloxacin treatment failures. Infections by Enterobacter cloacae and Acinetobacter species persisted for the ceftazidime treatment failures. For UTI patients, E. coli was the organism most frequently isolated before treatment. All 14 UTI patients who completed treatment showed resolution or improvement. In the ciprofloxacin group two patients were superinfected by Enterococcus species, and in the ceftazidime group there were two superinfections by Enterococcus species and one by Enterobacter cloacae. Intravenous ciprofloxacin was as effective as ceftazidime in the treatment of nosocomial pneumonia and urinary tract infection. Caution should be exercised when treating serious infections by streptococci or staphylococci.

Adult↗

PubMed1990

A randomized trial of surgery in the treatment of single metastases to the brain.

To assess the efficacy of surgical resection of brain metastases from extracranial primary cancer, we randomly assigned patients with a single brain metastasis to either surgical removal of the brain tumor followed by radiotherapy (surgical group) or needle biopsy and radiotherapy (radiation group). Forty-eight patients (25 in the surgical group and 23 in the radiation group) formed the study group; 6 other patients (11 percent) were excluded from the study because on biopsy their lesions proved to be either second primary tumors or inflammatory or infectious processes. Recurrence at the site of the original metastasis was less frequent in the surgical group than in the radiation group (5 of 25 [20 percent] vs. 12 of 23 [52 percent]; P less than 0.02). The overall length of survival was significantly longer in the surgical group (median, 40 weeks vs. 15 weeks in the radiation group; P less than 0.01), and the patients treated with surgery remained functionally independent longer (median, 38 weeks vs. 8 weeks in the radiation group; P less than 0.005). We conclude that patients with cancer and a single metastasis to the brain who receive treatment with surgical resection plus radiotherapy live longer, have fewer recurrences of cancer in the brain, and have a better quality of life than similar patients treated with radiotherapy alone.

Adult↗

PubMed1990

Inducible ornithine decarboxylase expression in brain subject to vasogenic oedema after transient ischaemia: relationship to C-fos gene expression.

Ornithine Decarboxylase (ODC) is the rat controlling enzyme of polyamine biosynthesis and has been shown to be produced in a delayed fashion in response to cerebral ischaemia. Its appearance has been linked to the development of vasogenic brain oedema. To understand the genetic control of this protein, Mongolian gerbils were studied for the possible expression of the ODC gene as compared to that of the inducible proto oncogenes c-fos and c-jun after transient bilateral carotid artery occlusion. Total cellular RNA was isolated from gerbil brains by guanidine-thiocyanate extraction and characterized by northern blot analysis for c-fos, c-jun, and ODC mRNA over reperfusion times. c-fos and c-jun expression rose rapidly with peak level reached at 60 min of reperfusion (70 x control, p less than or equal to 0.01). Peak levels of ODC mRNA induction were seen at 4 hrs reperfusion (2.83 x control, p less than or equal to 0.01) consistent with the period of maximum of brain oedema as measured by specific gravity (1.0386 +/- 0.0009, p less than or equal to 0.05). These data indicate the differential timing of genetic expression during the reperfusion period after transient ischaemia. Such studies suggest that potential therapies may be possible by addressing the delayed ODC component of ischaemic oedema formation and allow a greater understanding of the role of gene induction in the multifaceted cerebral response to ischaemia.

Animals↗

PubMed1990

Focal cerebral infarction in cats in the presence of hyperglycemia and increased insulin.

Although it has been well established that hyperglycemia increases cerebral damage following transient cerebral ischemia, its effect on permanent focal ischemia is controversial. We hypothesized that other factors associated with hyperglycemia, such as plasma insulin, may alter the brain's response to hyperglycemia. The objective of this study was to determine if hyperglycemia changes infarction size following 8 hr of middle cerebral artery occlusion in the anesthetized cat and to examine if changes in plasma insulin levels alter hyperglycemia's effects. Infarct size in hyperglycemic cats with increased plasma insulin (38.3 +/- 8.4, mean +/- SE) or in hyperglycemic cats without increased plasma insulin (30.5 +/- 7.6%) was not significantly different from that of ischemic controls (33.8 +/- 2.8%). However, the variability in infarct size tended to be greater (P = 0.0647) among all hyperglycemic cats compared to control animals. The source of the variability is unknown, but this observation is dependent on the exact nature of the focal ischemic insult (i.e., degree of collateral blood supply) and that this effect may vary greatly from individual to individual within a population.

Analysis of Variance↗

PubMed1990

In vivo 31phosphorus spectroscopy during transient cerebral ischaemia in the gerbil.

The depletion of the high energy phosphates; phosphocreatine and ATP, during cerebral ischaemia disrupts normal cellular function and can lead to cerebral infarction. Using in vivo nuclear magnetic resonance spectroscopy, the metabolic effects of the gerbil model of transient bilateral carotid artery occlusion were quantified. By examining the changes in the inorganic phosphate (Pi), phosphocreatine (PCr) and beta-ATP peaks, the PCr/Pi ratio, the PCr/beta-ATP ratio and intracellular pH (pHi) before, during and after an ischaemic insult were calculated. Preischaemic values for these parameters were: PCr/Pi = 2.466 +/- 0.130, PCr/beta-ATP = 1.691 +/- 0.053, pHi = 7.112 +/- 0.021. By the end of 20 min of global ischaemia, the PCr and beta-ATP peaks fell to levels similar to background in most animals. Calculated values were: PCr/Pi = 0.488 +/- 0.126, PCr/beta-ATP = 1.833 +/- 0.179, pHi = 6.551 +/- 0.258. With reperfusion, PCr/Pi increased rapidly back towards preischaemic levels but pHi improvement was delayed 10 min after that of PCr/Pi. By 1 h of reperfusion, both PCr/Pi and pHi were statistically equivalent to preischaemic values. During ischaemia, ATP was lost more rapidly than the storage form, PCr, but recovery of both was parallel. This suggested an intact ability to store such energy. These data indicate that the gerbil brain recovers normal high energy phosphate levels within an hour following a 20 min ischaemic insult, but that initial reperfusion does not immediately correct intracellular acidosis. Such a delay may prove a useful marker of those animals with more severe ischaemic injury.

Adenosine Triphosphate↗

PubMed1990

Unilateral carotid artery ligation in the Mongolian gerbil as a model for testing infarction-reducing therapies.

This study evaluates infarct size measurement as an indicator of cerebral ischaemia outcome in a placebo-controlled trial of potential cerebral protection in the unilateral carotid artery ligation in the Mongolian gerbil. Ibuprofen was used in an effort to manipulate infarct size as this agent has been shown to reduce ischaemia in myocardial infarction. Using measurements obtained through an infarct-sizing technique and a statistical power analysis of the method, the sample sizes needed to obtain significant results were projected for this model. In this case, it was not possible to demonstrate an effect of ibuprofen on infarct size although a tendency towards larger infarct size in ibuprofen-treated compared with placebo-treated gerbils was observed (36.1 +/- 10.1% versus 30.0 +/- 17.5%). The sample sizes needed to find significant changes in infarct size indicate that this model finds a practical use in studying therapies which will alter infarct size by at least 50%. For example, to detect a 30% change in infarct size, 33 successfully infarcted gerbils per group would be needed, but a 50% change would require a more tenable 13 infarcted gerbils per group. However, given the 40% infarction rate of occluded gerbils seen in this study, almost 33 gerbils per group would be required to detect a 50% change. In addition, somatosensory evoked potential was compared with neurological examination as a predictor of infarction. It would be helpful to be able to pre-screen for infarcted gerbils immediately after occlusion in order to direct infarcted gerbils into control and treated groups. Somatosensory evoked potential successfully predicted infarction with a 90% accuracy in 21 gerbils compared with neurological evaluation which was 100% accurate. But the somatosensory evoked potential prediction was made within 15 min of occlusion as opposed to the 6 h of observation during which the neurological evaluation was made.

Animals↗

PubMed1990

Thickness of carotid artery atherosclerotic plaque and ischemic risk.

Noninvasive duplex scanning of carotid artery atherosclerotic plaque was performed in 286 consecutive patients referred to a cerebrovascular diagnostic laboratory. The presence and thickness of such plaque in the region of the carotid bifurcation were examined for association with the degree of vessel stenosis, age, sex, smoking history, history of prior transient ischemic attack or stroke, and systemic manifestations of atherosclerotic disease. Atherosclerotic plaque thickness was positively correlated with degree of vessel stenosis (P less than 0.0001). Both parameters were independent predictors of cerebrovascular events but plaque thickness was a better predictor of prior transient ischemic attacks (P less than 0.05), and vessel stenosis was a better predictor of prior stroke (P less than 0.005). Patient age (P less than 0.001) and pack-years of cigarette use (P less than 0.001) were independent positive predictors of carotid atherosclerotic plaque thickness. The greatest effect of smoking and atherosclerotic plaque thickness was seen in heavy smokers younger than age 55. Both carotid artery plaque thickness and pack-years of smoking were significant independent predictors of other systemic manifestations of atherosclerotic disease (P less than 0.05). Such noninvasive scanning of carotid artery atherosclerotic plaque demonstrates the significant role of age and smoking in the progression of disease. It also suggests a significant role for carotid atherosclerotic artery plaque in the pathophysiology of cerebrovascular events, especially transient ischemic attacks, even prior to the production of a flow-limiting stenosis. Finally, noninvasive screening of carotid artery plaque may provide a useful marker for the patient at risk for systemic atherosclerotic disease and identify the patient for whom maximal atherosclerotic risk factor modification is needed.

Adult↗

PubMed1990

Relationship between plasma glucose, brain lactate, and intracellular pH during cerebral ischemia in gerbils.

The dose-response relation between plasma glucose and brain lactate and the relation of these parameters to intracellular pH during severe cerebral ischemia have not been well characterized over a wide range of plasma glucose levels. Experiments to delineate these relations in the gerbil model of global ischemia were performed by using phosphorus-31 nuclear magnetic resonance spectroscopy to measure intracellular pH and a new method to measure brain lactate. Ischemia increased final brain lactate linearly 4 mumol/g for every 100 mg/dl increase in plasma glucose up to 650 mg/dl (p = 0.0001, r2 = 0.9); beyond 650 mg/dl, saturation of the glucose transport-glycolysis system occurred. Plasma glucose correlated better with ischemic intracellular pH than did brain lactate. However, when brain lactate levels are compared with intracellular pH during ischemia, the relation may be threshold rather than linear. A narrow transition zone, during which ischemic intracellular pH decreased precipitously with increasing brain lactate, was observed between 17 and 22 mumol/g; below 17 mumol/g, intracellular pH remained stable at 6.8-6.9, whereas above 22 mumol/g, intracellular pH decreased maximally to about 6.2. The marked decrease in intracellular pH that occurs when brain lactate surpasses 17 mumol/g suggests that this sudden drop in intracellular pH may account for the "lactate threshold" for increased cerebral ischemic damage.

Analysis of Variance↗

PubMed1989

The effect of total parenteral nutrition on vasogenic edema development following cold injury in rats.

Total parenteral nutrition (TPN) has been shown to decrease mortality and to increase the rate of recovery in head-injured patients. However, a recent short-term animal experiment has raised concern over the potential enhancement of vasogenic edema by TPN. The experiment described here was undertaken to examine longer-term effects of TPN infusion on vasogenic edema development. Twenty-four rats received an infusion of a TPN solution (35% glucose) or 0.9% saline at 4 ml/kg/hr for 4 or 26 hours following cold injury. In the 4-hour experiment, TPN increased the serum glucose level to 772 +/- 57 mg/dl compared to 160 +/- 14 mg/dl in the saline-treated animals (p = 0.0001) and increased serum osmolality to 312 +/- 3 mOsm/kg compared to 291 +/- 3 mOsm/kg in the saline-treated group (p = 0.0006). In the 26-hour experiment, TPN-infused rats were also hyperglycemic and hyperosmotic by 4 hours postinjury and remained hyperglycemic at 26 hours postinjury (serum glucose level 374 +/- 97 mg/dl compared to 141 +/- 3 mg/dl in saline-treated animals; p = 0.0371). Although by 26 hours the TPN-infused rats appeared hyperosmotic compared to the saline-treated rats, high variability in the TPN group prevented statistical confirmation of this observation (serum osmolality 337 +/- 35 mOsm/kg in the TPN group compared to 287 +/- 6 mOsm/kg in the saline group). A three-way analysis of variance with repeated measures was used to analyze the effect of infusion (saline vs. TPN), time (4 vs. 26 hours), and cold injury on the specific gravity of the five brain regions studied. Cold injury significantly increased edema development in the injured versus uninjured hemisphere for every region studied (p less than or equal to 0.0034, all five regions), and edema development increased significantly between 4 and 26 hours in three of the five regions (p less than or equal to 0.0207, all three regions). The infusion fluid was not a significant factor in any of the analyses. In conclusion, TPN infusion produced hyperglycemia and hyperosmolality in cold-injured rats but did not enhance vasogenic edema development in any brain region studied.

Analysis of Variance↗

PubMed1988

Ornithine decarboxylase activity and immunohistochemical location in postischemic brain.

Ornithine decarboxylase, rate-limiting in polyamine formation, has been found to be necessary for the development of vasogenic edema after cryogenic cerebral injury and is postulated to be of importance in late ischemic brain edema formation. Ornithine decarboxylase activity and accompanying edema was studied after transient cerebral ischemia in Mongolian gerbils. Bilateral carotid artery occlusion was utilized to produce dense forebrain ischemia. After 4 h of reperfusion a significant elevation in ornithine decarboxylase activity was present (72.5 +/- 24.7 vs 8.5 +/- 2 pmoles/mg protein/h, p less than 0.05). Immunohistochemical localization of ornithine decarboxylase indicated its presence in cortical neurons of ischemic gerbils. This was typically located in the perinuclear cytoplasm and extended into proximal dendrites. Nonischemic animals did not contain ornithine decarboxylase immunoreactivity. These studies show the presence and location of ornithine decarboxylase in cerebral tissue subjected to transient ischemia. The increase in this marker of polyamine activity paralleled previous studies in this model of cerebral edema formation and reperfusion deficit in blood flow and evoked potential, suggesting that ornithine decarboxylase is a marker for and may be associated with those late metabolic events leading to progressive functional deterioration after incomplete cerebral ischemia.

Animals↗

PubMed1988

Polyamine inhibition preserves somatosensory evoked potential activity after transient cerebral ischaemia.

We tested the hypothesis that the increase in polyamines observed after cerebral ischaemia is related to deficits in electrocortical function as measured by somatosensory evoked potential (SEP). Adult Mongolian gerbils were anaesthetized with ketamine and prepared for monitoring SEP, cerebral blood flow (CBF) in parietal and frontal regions by H2 clearance, and for bilateral carotid artery occlusion (BCO). Seven animals served as controls and received saline. Another 7 animals were treated with the ornithine decarboxylase inhibitor, difluoromethylornithine (DFMO) (100 mg/kg I.P.) just prior to 40 min BCO followed by 4 h reperfusion. With BCO, both CBF and SEP declined significantly. In control animals, CBF fell from basal 37.8 +/- 4.7 cc/100 g/min to 2.9 +/- 1.2 cc/100 g/min and recovered to 22.7 +/- 3.5 cc/100 g/h over the 4 h reperfusion period. DFMO treatment did not alter this CBF pattern. SEP amplitude declined to 11.3 +/- 3.2% basal during occlusion. DFMO preserved SEP during ischaemia (35.5 +/- 16.8% basal) and remained significantly more preserved during reperfusion (p less than 0.05). These results suggest that polyamines are involved in the progressive decline in neuroelectrical function which occurs during occlusion/reperfusion in the Mongolian gerbil. The observation that polyamine inhibition preserves electrical function despite not altering blood flow indicates that the effects of polyamines are not manifested at the level of the vasculature but perhaps at the neuronal membrane.

Animals↗

PubMed1988

Brain ornithine decarboxylase activity following transient cerebral ischaemia: relationship to cerebral oedema development.

Ornithine decarboxylase (ODC) activity, the first and generally rate-limiting enzyme for polyamine synthesis, is stimulated in permanent focal cerebral ischaemia in areas of incomplete ischaemia which are developing ischaemic brain oedema. As polyamines are ubiquitous ornithine-derived molecules which are obligatory in cold-induced vasogenic oedema, we studied the effect of transient dense cerebral ischaemia with reperfusion on ischaemic oedema development and ODC activity. Fifty-nine Mongolian gerbils were anaesthetized with ketamine hydrochloride (160 mg/kg i.p. plus supplementation as needed). Both common carotid arteries were isolated and a tracheotomy placed in position. EEG was monitored with needle electrodes and temperature maintained at 37-38 degrees C. Twenty-nine gerbils underwent 40 min of bilateral carotid artery occlusion followed by reperfusion times of 10 min, 1, 2, 4, 6 or 8 h. Non-ischaemic control groups were monitored for equal intervals. At sacrifice, the brain was rapidly removed and forebrain samples analysed for ODC activity (enzymatic assay) and cerebral oedema (gravimetric determination). Marked loss of EEG amplitude was noted in all gerbils subjected to bilateral carotid artery occlusion. Ischaemia produced significant levels of cortical oedema throughout the reperfusion period (maximal decrease in specific gravity at 4 h postischaemia; control: 1.0456 +/- 0.0013; ischaemia: 1.0355 +/- 0.0021, mean +/- SD; p less than 0.0001). Significant subcortical oedema was produced at 10 min, 2 and 4 h postischaemia. A biphasic response was observed in brain ODC activity.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1988

Comparison of administration of two standard intravenous amino acid formulas to severely brain-injured patients.

Twenty severely brain-injured patients with Glasgow Coma Scale scores of 4-9 were prospectively randomized to receive one of two standard amino acid formulas, starting with the first day of hospital admission up to day 14 postinjury. Formula 2 (patient group 2) had 54 percent more leucine, 53 percent more isoleucine, 74 percent more valine, 28 percent less phenylalanine, 31 percent less methionine, 111 percent more proline, 38 percent less alanine, and 38 percent less glycine than formula 1 (patient group 1). Groups 1 and 2 received statistically equal overall mean parenteral nutrition calories and protein (2173 +/- 147 vs. 2059 +/- 143 kcal, and 77 +/- 12 vs. 83.1 +/- 6 g, respectively). There was a significant difference in overall mean urinary urea nitrogen excretion (group 1 = 24.6 +/- 1.3 vs. group 2 = 18.3 +/- 1.1, p = 0.02) and nitrogen balance (group 1 = -8.0 +/- 2.1 vs. group 2 = +1.8 +/- 1.2, p = 0.01). Mean overall isoleucine values were significantly higher in group 2 (overall mean 77 mumol/L vs. 62 mumol/L, p = 0.04). Phenylalanine levels were significantly higher in group 1 (107 mumol/L) versus group 2 (82 mumol/L) patients (p = 0.01). Arginine levels were significantly higher in group 1 (78 mumol/L) versus group 2 (49 mumol/L) patients (p = 0.0002). This observation suggests that some standard intravenous amino acid formulas may be more apt to promote positive nitrogen balance than others.

Adolescent↗