General metabolism in head injury.

Seventy-six patients with closed head injuries alone were studied to define the relation between the severity of the head injury and secondary alterations of general metabolism. The effect of metabolic changes on neurological outcome and the importance of nutritional support on nutritional status and neurological outcome were also evaluated. Using a powerful statistical tool, convergence analysis, it was possible to take into consideration the effects of a number of confounding factors that obviously affected general metabolism. Most of the patients were hypermetabolic for prolonged periods. In addition, many did not receive even basal requirements of calories or protein for many days. Despite this, their outcomes were determined by their initial neurological status and the amounts that they were fed, admittedly relatively modest, did not influence their courses. Despite such feedings, their visceral protein levels, which often dropped initially, rose toward normal levels, indicating effective adaptation. Indeed, it could not be shown that these patients developed complications of malnutrition such as infections. However, it will require a sophisticated randomized clinical trial of vigorous intravenous hyperalimentation to determine whether this complex, dangerous, and expensive therapy is helpful for severely head-injured patients.

Neurobehavioral outcome after gunshot wounds to the head in adult civilians and children.

To assess the quality of long term outcome of civilian gunshot wounds to the head after intensive neurosurgical management, particularly with regard to the possibility of subtle problems due to diffuse injury, we administered neuropsychological tests to six survivors (four adults and two children) at about 1 year after injury. Five patients were moderately disabled, and one patient achieved a good recovery. Residual neurobehavioral sequelae were present in all cases. Defects in long term memory for new information were the most common sequelae, whereas the persistence of linguistic and visuospatial deficits was related to the hemispheric lateralization of injury. In comparison with the outcome reported for patients with closed head injuries who had similar Glasgow coma scale scores, our patients exhibited more severe impairment due to significant focal brain injuries and less evidence of diffuse damage.

Clinicopathological correlations of disseminated intravascular coagulation in patients with head injury.

To try to define the significance of disseminated intravascular coagulation (DIC) in head-injured patients, we correlated clinical, laboratory, and pathological findings in 16 patients with head injury as their main problem who had DIC, who died within 4 days of injury, and who were examined postmortem. Patients were ranked according to the number of abnormal laboratory screening tests for DIC and the severity of these abnormalities. The most frequently abnormal laboratory tests were the fibrinogen degradation products and fibrinogen, followed in order by the activated partial thromboplastin time, prothrombin time, and thrombin time. The platelet count was the least abnormal value. The patients with the fewest abnormalities had the least abnormal computed tomographic scans. Autopsy reports revealed necrosis and bleeding in the brain and in a number of other organs, particularly the lungs. Microthrombi were not reported in the original autopsy reports. However, when these cases were reevaluated and their slides were stained with an immunoperoxidase technique using rabbit anti-human fibrinogen antiserum, microthrombi were seen frequently. Large microthrombi were more common in patients who had died within less than 24 hours, suggesting a relationship to death or to less time for lysis. In order of frequency, the brain/spinal cord, liver, lungs, kidneys, and pancreas were most commonly affected, and the liver, pituitary gland, pancreas, thymus, brain/spinal cord, large intestine, kidneys, and lungs had the greatest density of microthrombi. Pulmonary dysfunction had been a frequent problem in these patients, which may have been related to the high incidence of microthrombi and bleeding found in the lungs.(ABSTRACT TRUNCATED AT 250 WORDS)

Adipose tissue, longissimus muscle and anterior pituitary growth and function in clenbuterol-fed heifers.

The present study was conducted to determine the effects of feeding clenbuterol on adipose tissue and longissimus muscle growth in heifers. For 50 d, 14 heifers were fed either a sucrose-based, clenbuterol supplement or a placebo in which the clenbuterol had been omitted. The heifers were slaughtered in two groups, based on initial weight. Adipose tissue from several anatomical sites and longissimus muscle (depending on slaughter group) were obtained fresh at slaughter. Changes in carcass characteristics elicited by clenbuterol were similar to those reported by others for steers and sheep. Subcutaneous (sc) and intramuscular (im), but not perirenal, adipocytes were smaller and there were more cells per g tissue in the adipose tissue depots of the clenbuterol-fed heifers. Clenbuterol decreased lipogenic enzyme activities, fatty acid-binding protein activity, basal lipolysis and acetate incorporation into glyceride-fatty acids (P less than .05) in sc adipose tissue, but had no effect (P greater than .05) on lipogenesis or lipolysis in im adipose tissue. Clenbuterol elicited a 20% increase in type II myofiber diameters (P less than .05) but had no effect on type I myofiber diameters. In vitro growth hormone release by perifused anterior pituitaries was not affected significantly by long-term in vivo exposure to clenbuterol. These data indicate that a depression in lipogenesis is the mechanism by which clenbuterol decreases subcutaneous fat accretion in cattle.

Collection and preparation of sidestream cigarette smoke for trace elemental determinations by graphite furnace atomic absorption spectrometry and inductively coupled plasma mass spectrometry.

A novel method for the collection and preparation of sidestream cigarette smoke condensate is described for trace elemental analysis by inductively coupled plasma mass spectrometry and graphite furnace atomic absorption spectrometry. The smoke collection method utilizes a specially designed chimney that collects and directs the sidestream smoke (SS) to a 2-stage trapping system consisting of an impaction trap followed by a 0.8 microm mixed cellulose ester filter. The samples are digested with nitric acid in a commercial heating block before analysis. The method limits of detection (LODs) are 1, 0.2, 2, 9, 6, and 7 ng/cigt for As, Cd, Pb, Ni, Se, and Cr, respectively. The SS collected from an industry reference cigarette, 1R4F, produced by the University of Kentucky was analyzed. The concentrations of As, Cd, and Pb in 1R4F were determined to be 27.3+/-2.1, 412+/-14, and 43.8+/-2.0 ng/cigt, respectively, while the concentrations of Ni, Cr, and Se are below the method LOD. Consequently, this novel method successfully addresses contamination, instrumentation, and collection issues for performing trace elemental analysis of sidestream cigarette smoke condensate.

Effects of nonsteroidal antiinflammatory drugs on ulcerogenesis and gastric secretion in pylorus-ligated rat.

The effects of nonsteroidal antiinflammatory drugs on ulcerogenesis and gastric secretion were evaluated in a pylorus-ligated rat model. Oral administration of salicylate (50 mg/kg), aspirin (50 mg/kg), and indomethacin (3.5 mg/kg) significantly increased ulcerogenesis over the basal value by six- to sevenfold, but ibuprofen's (10 mg/kg) fourfold increase was not significant. Aspirin in conjunction with histamine (0.5 mg/kg subcutaneously) significantly increased ulcerogenesis by 2.7-fold compared to histamine alone. Basal acid secretion was increased significantly by 156% after indomethacin, but not by other nonsteroidal antiinflammatory drugs. In contrast, all nonsteroidal antiinflammatory drugs, except indomethacin, significantly decreased histamine-stimulated acid secretion. Non-steroidal antiinflammatory drugs had no effect on pepsinogen secretion. Ranitidine pretreatment (25 mg/kg intraperitoneally) significantly decreased basal acid and pepsinogen secretion in all treatment groups by > 85% and > 40%, respectively, and ulcerations induced by salicylate, aspirin, and indomethacin were also inhibited by 90%, 60%, and 60%, respectively. The observed inhibition of prostaglandin E2 generation by nonsteroidal antiinflammatory drugs under basal secretory conditions appeared to correlate with the extent of ulcerogenesis. Our data support the concept that acid, in addition to inhibition of prostaglandin E2 synthesis, plays an important role in the pathogenesis of nonsteroidal antiinflammatory drug-induced gastropathy.

Relationships between amplitudes and kinetics of rapid cytosolic free calcium fluctuations in GH4C1 rat pituitary cells: roles for diffusion and calcium-induced calcium release.

We have examined statistical relationships between the amplitudes and the kinetics (rise times, fall times, and decay constants) of cytosolic free calcium fluctuations (spikes) in a population of 353 individual GH4C1 rat pituitary cells. The fast falling phase was approximated by a single exponential decay, and the decay time constant, tau, increased linearly with spike amplitude in 80% of the cells studied. The slope of the tau versus amplitude plot for each cell was inversely related to the cell's mean spike amplitude. Thus, some process responsible for prolonging the decay phase of spikes appeared to operate strongly in cells with spikes of low amplitude, but to become less prominent in cells with high amplitude spikes. Mean tau correlated more strongly with mean rise and fall times than with mean spike amplitude, indicating that the kinetic properties of spikes were not tightly coupled to spike amplitude. These findings are consistent with a model wherein the rise phase corresponds to entry of extracellular calcium via L-type calcium channels into localized sub-plasmalemmal domains, followed by diffusion of subplasmalemmal calcium into the cell interior; and the falling phase corresponds to further calcium diffusion combined with activation of cytoplasmic calcium-induced calcium release, which prolongs the falling phase.

Alterations in the frequency and shape of Ca2+ fluctuations in GH4C1 cells induced by thyrotropin-releasing hormone and Bay K 8644.

We have examined statistically the actions of thyrotropin-releasing hormone (TRH) and Bay K 8644, an L-type Ca(2+)-channel agonist, on the frequency and shape of cytosolic Ca2+ spikes in individual GH4C1 rat pituitary cells. TRH induced a brief (0-40 s) suppression of Ca2+ spikes followed by a period (40-200 s) of increased spike frequency. TRH treatment reduced the rate of rise and amplitude of Ca2+ spikes, and increased the rate of fall, relative to spontaneous spikes before treatment. TRH had no significant effect on the correlation between spike amplitude and the spike decay time constant tau, suggesting that the increased rate of fall was due to enhanced Ca2+ extrusion and not to decreased Ca(2+)-induced Ca2+ release. Bay K rapidly (t1/2 = 9-13 s) induced a 2-fold increase in the rate of rise of spikes with no change in the total rise time, leading to an increase in spike amplitude. It increased by 2-fold the fall time of spikes, as predicted solely by the previously observed relationship between spike amplitude and fall time. Bay K therefore appeared to increase the number of Ca2+ channels participating in each spike event without altering the kinetics of channel activation or deactivation, and without influencing Ca2+ extrusion. After addition of Bay K, the interval between spikes gradually (t1/2 approximately 100 s) increased, whereas the rate of rise remained constant and maximal. To explain these actions of TRH and Bay K, we postulate that a fraction of L-type Ca2+ channels are inactivated during each spike and must be re-activated in order to participate in a subsequent spike. We conclude further that the changes in spike frequency and profiles induced by these secretagogues are most consistent with a model in which TRH induces increases in both Ca2+ influx and efflux while Bay K induces a large increase in Ca2+ influx but has little effect on efflux.

Mechanism of spontaneous intracellular calcium fluctuations in single GH4C1 rat pituitary cells.

Individual unstimulated GH4C1 cells exhibited spontaneous dynamic fluctuations in cytosolic free Ca2+ concentration ([Ca2+]i). Either chelation of extracellular Ca2+ with EGTA or treatment with nifedipine inhibited spontaneous [Ca2+]i fluctuations, indicating that the [Ca2+]i profile was dependent on the entry of extracellular Ca2+ via voltage-operated Ca2+ channels (VOCC). Spontaneous [Ca2+]i fluctuations did not resume immediately after exposure of EGTA-pretreated cells to extracellular Ca2+, supporting the hypothesis that the complex [Ca2+]i profiles observed in unstimulated cells required filling of an intracellular Ca2+ pool. BAY K 8644 elicited large rapid oscillations in [Ca2+]i. After chelation of extracellular Ca2+, however, re-addition of Ca2+ plus BAY K 8644 did not result in [Ca2+]i oscillations. The intracellular Ca2+ pool necessary for BAY K-induced oscillations was not the same Ins(1,4,5)P3-sensitive pool stimulated by thyrotropin-releasing hormone (TRH), because the TRH-stimulated Ins(1,4,5)P3-induced [Ca2+]i spike and the BAY K 8644-induced oscillations were differentially sensitive to chelation of extracellular Ca2+ and thapsigargin. Caffeine caused an increase in [Ca2+]i fluctuations in quiescent cells, supporting a role for Ca(2+)-induced Ca2+ release (CICR) in the generation of spontaneous [Ca2+]i fluctuations. In conclusion, the complex spontaneous changes in [Ca2+]i observed in single GH4C1 cells depend on both the influx of extracellular Ca2+ through VOCC and the action of an intracellular Ca2+ pool that increases [Ca2+]i through a CICR-like mechanism.

Temporal organization of atrial activity and irregular ventricular rhythm during spontaneous atrial fibrillation: an in vivo study in the horse.

INTRODUCTION: Atrial fibrillation (AF) is common in healthy horses. We studied the temporal organization of AF to test the hypothesis that the arrhythmia is governed by a high degree of periodicity and therefore is not random in the horse. Further, we surmised that concealed conduction of AF impulses in the AV node results in an inverse relationship between AF frequency and ventricular frequency. METHODS AND RESULTS: Fast Fourier transform (FFT) analysis of atrial activity was done on signal-averaged ECGs (n = 11) and atrial electrograms (n = 3) of horses with AF at control (C), after quinidine sulfate (22 mg/kg by mouth every 2 hours) at 50% time to conversion (T50), and immediately before conversion (T90) to sinus rhythm. FFT always revealed a single dominant frequency peak. The mean dominant frequency decreased until conversion (C = 6.84 +/- 0.85 Hz, T50 = 4.87 +/- 1.5 Hz, T90 = 3.41 +/- 1.18 Hz; P < 0.001). Mean AA intervals (n = 500) gradually increased after quinidine. Mean RR intervals (n = 500), standard deviation of the mean (SDM), Poincaré plots, and serial autocorrelograms (SACs) of 500 RR intervals were measured at C and T90 to determine the ventricular response to AF and quinidine-induced changes in the variability of the ventricular response. Mean RR interval and SDM were reduced after quinidine (C = 1431 +/- 266 msec and 695 +/- 23 msec; T90 = 974 +/- 116 msec and 273 +/- 158 msec, respectively; P < 0.01). Poincaré plots and SAC at C and at T90 revealed a significant correlation of consecutive RR intervals typical of a system with a deterministic behavior. At T90, the variability of RR intervals was reduced and the overall periodicity of RR intervals was increased after quinidine administration. CONCLUSION: In the horse, AF is a complex arrhythmia characterized by a high degree of underlying periodicity. The inverse AA-to-RR interval relationship and reduced variability of RR intervals after quinidine suggest that the ventricular response during AF results from rate-dependent concealment of AF wavelets bombarding the AV node, which nevertheless results in a significant degree of short-term predictability of beat-to-beat changes in RR intervals.

Taste preference synergy between glutamate receptor agonists and inosine monophosphate in rats.

Monosodium glutamate (MSG) elicits a taste called umami and interacts synergistically with nucleotide monophosphates such as 5'-inosine monophosphate (IMP) to potentiate this taste intensity. Indeed, the synergistic interaction of nucleotide monophosphates and MSG is a hallmark of umami. We examined interactions between MSG and other taste stimuli, including IMP, by measuring the lick rates of non-deprived rats during 30 s trials. To control for non-linear psychophysical functions, the concentration of one taste stimulus in a binary mixture was systematically increased while the concentration of the second taste stimulus was decreased (stimulus substitution method). Synergy between two stimuli was detected if the lick rate for a binary mixture exceeded that expected from the sum of the lick rates for each stimulus alone. In initial experiments, taste synergy was observed when rats were presented with mixtures of MSG and IMP but not with mixtures of MSG and sucrose. In subsequent experiments, glutamate receptor agonists other than MSG were presented with IMP to test for taste synergy. No evidence of synergy was seen when rats were presented with mixtures of IMP and kainic acid or IMP and N:-methyl-D-aspartate. However, taste synergy between IMP and L-AP4, a potent agonist at mGluR4 receptors, was observed. These results suggest that a metabotropic glutamate receptor similar to mGluR4 may be involved in the taste synergy that characterizes umami.

Civilian gunshot wounds: the limits of salvageability.

Patients who have suffered gunshot wounds in civilian settings, who present with posturing and in whom the bullet has passed through the geographical centre of the brain have generally not been felt to be salvageable. However, surprisingly favourable outcomes in two such patients have led us to believe that some such patients may deserve aggressive treatment.

Head injury. Variability of course and presence of confounding factors.

Review of a large data base on 76 patients who had suffered head injuries and whose metabolic changes were being studied demonstrated the variability of their neurological courses and the importance of considering confounding factors in the analysis of such a group. It was apparent that many such patients continue to change neurologically and functionally for long periods of time, and that their ultimate outcome cannot be determined for at least 1 year. The study demonstrates the inherent complexity of a group of patients with head injuries and the need to use sophisticated statistical tools and a computer to demonstrate whether apparent trends are statistically valid in light of confounding factors and variabilities. Failure to take this complexity into account seems to be a major factor in many of the ongoing controversies in research on head injuries. A possible solution to the problem of potential biases introduced by lost patients would be to develop a method to use government records to obtain current addresses for patients involved in federally funded research.

Post-traumatic subdural hygromas: observations concerning a surgical enigma.

Four per cent (38) of 881 head injured patients developed known subdural hygromas. Their times of onset and course were variable. However, only two large hygromas seemed clinically significant. Hygromas were more frequent when intracranial pressure monitors were placed, possibly due to opening of the arachnoid, particularly if intracranial pressure was low. But, of course, monitors were only inserted in more severely injured patients. The use of Richmond bolts to drain subdural hygromas in a controlled fashion while monitoring intracranial pressure is suggested.