Influenza outbreaks in Ontario hospitals, 2012-2016.

BACKGROUND: Influenza outbreaks in hospital settings affect vulnerable patient populations and pose considerable risk of morbidity and mortality; however, key information regarding these outbreaks is limited. OBJECTIVE: To describe surveillance data on influenza outbreaks in Ontario hospitals between 2012-13 and 2015-16 and compare H3N2- and H1N1-dominant influenza seasons. METHODS: Hospital laboratory-confirmed influenza outbreaks occurring between September 1, 2012 and August 31, 2016 were analysed for indicators of outbreak duration and severity (case attack rate, pneumonia rate and fatality rate). Frequency, duration and severity of influenza A outbreaks were compared between H3N2- (2012-13, 2014-15) and H1N1-dominant seasons (2013-14, 2015-16). RESULTS: Over the four years, there were 256 hospital outbreaks involving 1,586 patients that included 91 cases of pneumonia and 40 deaths. The total number of outbreaks was lowest in the 2015-16 (n=36) and highest in the 2014-15 (n=117) influenza seasons. The 2014-15 season also had the highest number of influenza cases (n=753), pneumonia cases (n=46), fatalities (n=18) and hospital sites reporting ≥1 outbreak (n=72). Median outbreak duration ranged from 4.5 days in 2013-14 to 6.0 days in 2015-16. Comparisons of H3N2 and H1N1 seasons did not identify statistically significant differences in outbreak duration or severity; however, significantly more influenza A outbreaks than influenza B outbreaks were reported in H3N2 seasons compared with H1N1 seasons (p<0.05). CONCLUSION: While H3N2-dominant years contribute to influenza morbidity and mortality through an increased number of hospital outbreaks, the duration and severity of influenza A outbreaks are not significantly different in H3N2 and H1N1 seasons.

Interaction with gravitropism, reversibility and lateral movements of phototropically stimulated potato shoots.

Phototropic (PT) and gravitropic (GT) bending are the two major tropic movements that determine the spatial position of potato shoots. We studied PT bending of potato plantlets grown under long-day photoperiods in several prearranged position setups providing different interactions with the GT response. Starting with the standard PT stimulation setup composed of unilateral irradiation of vertically positioned shoots, experiments were also done in antagonistic and synergistic setups and in treatments with horizontal displacement of the light source. In the standard setup, PT bending suppressed the GT bending, which could occur only if the PT stimulation was cancelled. The antagonistic position, with phototropism and gravitropism attempting to bend shoots in opposite directions, showed phototropism and gravitropism as independent bending events with the outcome varying throughout the day reflecting diurnal changes in the competence of individual tropic components. Whilst gravitropism was constant, phototropism had a marked daily fluctuation of its magnitude with a prominent morning maximum starting an hour after the dawn in the growth room and lasting for the next 6 h. When phototropism and gravitropism were aligned in a synergistic position, stimulating shoot bending in the same direction, there was little quantitative addition of their individual effects. The long period of morning PT bending maximum enabled multiple PT bending events to be conducted in succession, each one preceded by a separate lag phase. Studies of secondary PT events showed that potato plantlets can follow and adjust their shoot position in response to both vertical and horizontal movements of a light source. PT bending was reversible, since the 180° horizontal change of a blue light (BL) source position resulted in reversal of bending direction after a 20-min-long lag phase.

Cognitive deficits following blast injury-induced neurotrauma: possible involvement of nitric oxide.

Blast injuries, that is injuries caused by the complex pressure wave generated by some explosions, show increasing frequency throughout the world. However, whether blast injury is capable of inducing memory dysfunction has not been previously investigated. The present study examines the effects of blast injury-induced neurotrauma on memory deficit in rats. Furthermore, it is hypothesized that blast injury, stimulating nitric oxide production in the medial mesodiencephalic reticular formation and the dorsal hippocampus, both structures being involved in memory processing, may induce memory deficits. Prior to blast injury, Wistar rats were trained for an active avoidance task for 6 days. On day 6, rats that had acquired the avoidance response were subjected to whole-body blast injury, using a BT-I shock tube. Neurotrauma was confirmed by electron microscopical examination. At the completion of cognitive testing, rats were sacrificed at 3, 24 hours and 5 days after injury. The nitric oxide production in the brain structures was determined by the total nitrite/nitrate concentration, and by the expression of inducible nitric oxide synthase mRNA. The rats with blast injury revealed significant deficits in performance of the active avoidance task that persisted up to 5 days post-injury. Electron microscopical findings in both brain structures showed swellings of neurons, glial reaction, myelin debris, and increased pinocytotic activity on the fifth day following trauma. In blast injured rats, there was a significant elevation in total nitrite/nitrate levels 3 and 24 hours following injury which was comparable with the changes in the expression of inducible nitric oxide synthase mRNA. The results indicate that blast injury-induced neurotrauma is able to cause cognitive deficits.

Ultrastructural and functional characteristics of blast injury-induced neurotrauma.

OBJECTIVE: The present study investigates whether whole-body or local (chest) exposure to blast overpressure can induce ultrastructural, biochemical, and cognitive impairments in the brain. METHODS: Male Wistar rats were trained for an active avoidance task for 6 days. On day 6, rats that had acquired the avoidance response were subjected to whole-body blast injury (WBBI), generated by large-scale shock tube (n = 40); or local (chest) blast injury (LBI), induced by blast overpressure focused on the right middle thoracic region and generated by small-scale shock tube (n = 40) while the heads of animals were protected. At the completion of cognitive testing, rats were killed at 3 hours, 24 hours, and 5 days after injury. Ultrastructural changes in the hippocampus were analyzed electron microscopically. Parameters of oxidative stress (malondialdehyde and superoxide anion generation) and antioxidant enzyme defense (superoxide dismutase and glutathione peroxidase activity) were measured in the hippocampus to assess biochemical changes in the brain after blast. RESULTS: Ultrastructural findings in animals subjected to WBBI or LBI demonstrated swellings of neurons, glial reaction, and myelin debris in the hippocampus. All rats revealed significant deficits in performance of the active avoidance task 3 hours after injury, but deficits persisted up to day 5 after injury only in rats subjected to WBBI. Oxidative stress development and altered antioxidant enzyme defense was observed in animals in both groups. Cognitive impairment and biochemical changes in the hippocampus were significantly correlated with blast injury severity in both WBBI and LBI groups. CONCLUSION: These results confirm that exposure to blast overpressure induces ultrastructural and biochemical impairments in the brain hippocampus, with associated development of cognitive deficits.

Therapeutic equivalence of inhaled beclomethasone dipropionate with CFC and non-CFC (HFA 134a) propellants both delivered via the Easibreathe inhaler for the treatment of paediatric asthma.

Chlorofluorocarbon (CFC)-containing inhalers for use in the treatment of asthma are to be phased out under the terms of the Montreal Protocol (1). In this multi-centre, randomized, double-blind study, the therapeutic equivalence of two formulations of beclomethasone dipropionate (BDP) containing CFC or non-CFC (HFA134a) propellant, both delivered via the Easibreathe (Norton Healthcare Ltd, London, U.K.) inhaler, was determined in 229 asthmatic children. Each child received 100 microg doses of BDP (containing either CFC or HFA propellant) twice daily for 12 weeks. Both CFC and HFA formulations produced statistically and clinically significant improvements in patient's lung function and symptom scores when administered via the Easibreathe inhaler. The improvements in mean morning peak expiratory flow (PEF) were 41 l min(-1) and 34 l min(-1) for the BDP-HFA and BDP-CFC products respectively (P<0.001) and for mean evening PEF the improvements were 38 l min(-1) and 38 l min(-1), respectively (P<0.001). Similar findings were demonstrated for the other efficacy parameters. The two formulations were statistically equivalent with respect to efficacy. For mean morning PEF the estimated treatment difference (BDP-CFC/BDP-HFA ratio) was 102.6% (95% CI 99.1, 106.2). Similar equivalence was shown for the other efficacy parameters. Both products were well tolerated, with no difference in the adverse event profiles, effects on 24 h urinary cortisol or Candida colonisation. This study demonstrates that the new formulation of BDP with HFA-134a propellant is equivalent to and directly substitutable for BDP with the older CFC propellant in a dose for dose manner. This should enable a seamless transition from one product to the other when CFC containing products are eventually phased out. In addition this study has also shown that the Easibreathe inhaler is an effective delivery system for use with inhaled products for the treatment of asthma in children.

[Experimental study of the pathogenesis of frostbite. Part III. Significance of energy status of muscle tissue in the pathogenesis of frostbite]. / Eksperimentalno istrazivanje patogeneze smrzotina--III deo. Znacaj energetskog statusa misicnog tkiva u patogenezi smrzotina.

The authors have investigated energy status of muscle tissue of the lower legs of Wistar rats subjected to freezing, as well as the dependence of ultrastructure changes in muscle tissue mitochondria on the intensity of freezing. The animals were divided into three experimental groups: two groups were exposed to cryoinjury of different intensity, while the third was the control one. Cryoinjury was applied over an experimental after thawing were taken samples of muscle tissue for the analysis of content of energy phosphates and carbohydrates' metabolites, respectively, as well as for morphometric analysis of mitochondria volume out of frozen right and unfrozen left lower legs. Results obtained from different experimental groups were compared mutually and with control group that was not exposed to cryoinjury, respectively. It was found that the freezing in muscle tissue caused hydrops degeneration of mitochondria, depletion of energy reserves, reduction of energy status and the activation of mechanism of anaerobic metabolism. All these alterations were proportional to the intensity of freezing and considerably influenced contractility function of muscle cells, causing prolonged spasm of arterioles in thawed tissue, i.e., rigor congelationis that was primarily defined as an important factor in the pathogenesis of ischemic impairment of thawed tissues.

Inhibition of leukotriene formation by diethylcarbamazine modifies the acid-base balance in the rabbits with blast injuries of the lungs.

Our previous investigations have shown that leukotrienes are important mediators/modulators in local response of the lungs to the blast injury. The aim of the present study was to investigate the effects of diethylcarbamazine (DEC), an 5-lipoxygenase inhibitor, on the acid-base balance following pulmonary blast injury. The experiments were performed on rabbits (n = 16) subjected to focused blast over-pressure on the middle thoracic region. Immediately prior to blast injury one group was treated with DEC (50 mg/kg, i.v.), and the other with the same volume of saline. Parameters of acid-base balance were measured in arterial and venous blood before and 30 minutes after injury. Obtained results indicated that DEC treatment reduced some disturbances induced by blast injury (prevents edema formation in the lungs, permits respiratory compensation of metabolic acidosis in general circulation, normalization of respirations and slightly improves the oxygen saturation of hemoglobin), in spite of intensified hemodynamic insufficiencies associated with increased hypotension and acidosis in the peripheral circulation.

[Experimental study of the pathogenesis of frostbite. Part II. Role of the sympathetic-adrenergic system in tissue reperfusion immediately after thawing]. / Eksperimentalno istrazivanje patogeneze smrzotina--II deo. Uloga simpaticko-adrenergickog sistema u reperfusiji tkiva neposredno po odmrzavanju.

The authors have investigated the role of sympathetic-adrenergic system in reperfusion of muscular tissue of the feet of Wistar rats immediately after thawing using alpha adrenergic blocker phentolamine methanesulfonate (Regitin). Cryoinjury was applied over an experimental model of local, controlled freezing of different intensity for certain experimental groups. Blood flow through microcirculation was measured by scintigraphy, following Tc-99m-pertechnetate clearance that was given in muscular mass of frozen right, as well as unfrozen left feet of rats. Results obtained in some experimental groups were compared mutually, as well as with the control group that was not exposed to cryoinjury. The investigations have revealed that immediately after thawing existed significant reduction, non-dependent of the intensity of freezing, in blood flow in microcirculation of both frozen and unfrozen feet of rats compared to the control group. Significant increase of microcirculatory blood flow in unfrozen feet was caused by blockade of sympathetic-adrenergic system, while the blood flow remained unchanged in the frozen ones. The reduction of blood flow in microcirculation of frozen tissues immediately after thawing was not associated with sympathetic-adrenergic factor.

Blast injury from explosive munitions.

OBJECTIVE: To evaluate the effect of blast in common war injuries. METHODS: One thousand three hundred and three patients injured by explosive munitions and demonstrating extremity wounds without other penetrating injuries were admitted to the Military Medical Academy in Belgrade between 1991 and 1994. Of these, 665 patients (51%) had symptoms and physical signs that were compatible with the clinical diagnosis of primary blast injury, whereas the remaining 658 patients did not. RESULTS: Random sampling of 65 patients in the blast group during the early posttraumatic period showed statistically significant elevations in blood thromboxane A2 (TxA2), prostacyclin (PGI2), and sulfidopeptide leukotrienes compared with the random sample of 62 patients in the nonblast group. This difference could not be accounted for by differing injury severity between the groups, because the severity of wounds as measured by both the Injury Severity Score and the Red Cross Wound Classification was similar in both groups. Amongst blast patients, 200 patients (30%) had long-term (1 year) symptoms and signs reflecting central nervous system disorders. These symptoms and signs were only sporadically found in 4% of the nonblast patients. These findings indicate that primary blast injury is more common in war injuries than previously thought and that of those affected by blast, a surprisingly high proportion retain long-term neurologic disability. The elevation in eicosanoids could be used to confirm and monitor blast injury. CONCLUSION: In relation to the immediate management of patients injured by explosive weapons, it follows that particular attention should be paid to the presence and/or development of blast injury. Our findings indicate that blast is more common in war injuries than previously thought. Eicosanoid changes after blast injury suggest that blast injury causes a major physiologic stress. A variety of effects on the central nervous system suggest that blast injury could be responsible for some aspects of what is now considered to be the posttraumatic stress disorder.

Recognizing, scoring, and predicting blast injuries.

The aim of this study was to find relevant signs and readily available parameters for the recognition of blast injuries and estimation of their severity. The injury severity, estimated by the Injury Severity Score (ISS), Red Cross Wound Classification (RCWC), and experimentally defined Pathology Scoring System for Blast Injuries (PSS/IS) according to Yelverton and modified for use in humans, was compared with a great number of subjective sensations, clinical signs, parameters of hemodynamic, metabolic, neuroendocrine and immune conditions. On the basis of these data, the confidence of the above-mentioned methods was analyzed in the evaluation of blast injuries. This study included 1303 casualties, wounded by explosive devices and with suspected blast injuries, treated at the Military Medical Academy in Belgrade (MMA) from 1991 to 1994. The patients were examined on admission at the MMA (<18 hours) and during hospitalization (1, 2, 5, and 7 days after wounding). The casualties with confirmed blast injury (n = 665, 51%) had an ISS ranging from 0 to 34 (mean 13) had wounds ranging from G1ST (soft tissue wounds caused by low energy transfer) to G3VF (massive wounds with fractures and injury of vital structures) according to the RCWC, with PSS/IS scores from 2 to 105 (mean 60). Statistically significant correlation was found between ISS and PSS/IS as well as RCWC and PSS/IS. Cytokines (IL-1, TNF|ga) and amino acids responded to a blast injury in similar manner as to gunshot wounds with a greater ISS or more severe RCWC injury type. The subjective sensations in blasted patients (deafness, thoracic pain, vertigo) and mediators, confirmed in previous experimental investigations as important factors in the pathogenesis of blast injuries (TxA2, sulfidopeptide leukotrienes) were relationed only to the PSS/IS.

The cardiovascular effects of the administration of L-NAME during the early posthemorrhagic period.

1. The effects of the various doses of NG-nitro-L-arginine methyl ester (L-NAME, 10 and 30 mg/kg) on some cardiovascular and biochemical parameters during the early posthemorrhagic period were studied in anesthetized rabbits subjected to hemorrhagic hypovolemia. 2. Hemorrhagic shock was produced by intermittent bleeding of 40% of the estimated blood volume for 15 min. Blood samples were taken before and after bleeding (0, 15 and 60 min). Simultaneously, the mean arterial pressure (MAP) and the heart rate (HR) were measured. Hemorrhaged rabbits were treated by L-NAME10 or L-NAME30 (10 or 30 mg/kg, i.v. bolus injection, respectively) or the corresponding volumes of saline (0.6 ml, i.v. bolus) immediately after the end of bleeding. 3. The observed cardiovascular parameters (MAP, HR) were significantly reduced after the end of bleeding in all rabbits. 4. The rise of the MAP was significantly more pronounced 30 min after the injection of L-NAME30 in comparison with the corresponding values in the saline (S) group. In contrast, L-NAME10 produced only a small, insignificant increase in the MAP in hemorrhaged rabbits. 5. The L-NAME30-induced rise of the MAP was accompanied by a severe bradycardia, hyperkalemia and an aggravated metabolic acidosis, more severe than the corresponding disturbance of the acid-base status in the S group. The changes in the acid-base parameters were observed both in arterial (pH, excess base) and in venous blood (pH) of hemorrhaged rabbits. 6. In conclusion, the i.v. bolus injection of L-NAME30 (immediately after the end of bleeding) produced a significant increase in the MAP during the first hour after the injury, but the presumable inhibition of the endothelial constitutive nitric oxide synthase during the early posthemorrhagic period resulted in severe cardiovascular and metabolic disturbances.

Relations among plasma prolactin, testosterone, and injury severity in war casualties.

Tissue trauma leads to a complex hormonal response of pituitary end-organ axis. This response can be recorded by determining parameters that represent the functional integrity of these systems. The concentrations of serum prolactin (PRL), serum testosterone, and plasma adrenocorticotropin (ACTH) were measured in 62 adult male casualties from the recent war in former Yugoslavia. Patients with brain injury were not included. Venous blood samples were taken as soon as possible (2-18 hours) after admission and at 1, 2, 5, and 14 days after injury. The severity of gunshot/missile wounds was assessed by the Injury Severity Score (ISS). The control group consisted of healthy blood donors. Uninjured subjects who had undergone great stress on the battlefield (explosion in the vicinity without injury) served as the sham-control group. Tissue trauma leads to a severity-dependent decrease in serum testosterone concentrations during the first 5 days following injury. Significant correlations were observed between ACTH, prolactin, and ISS during the first 18 hours after injury. A strong negative correlation between testosterone and prolactin serum concentrations was found during the first 18 hours. In patients with additional complications or unsatisfactory outcome, the prolactin concentrations remained elevated, whereas testosterone concentrations were reduced. Our results support the usefulness of recording hormonal changes for determining trauma severity and monitoring the clinical course. Such monitoring also helps assess the efficacy of therapeutic strategies. The relation between testosterone and prolactin might be helpful for predicting the clinical course and trauma outcome.

Involvement of the central nervous system in the general response to pulmonary blast injury.

The local, general, and cerebral responses of rabbits exposed to pulmonary blasts were examined to define the role of vagal afferentation in cardiorespiratory as well as metabolic control after a blast injury. Two series of experiments were conducted on rabbits to analyze the general, local, and cerebral responses to pulmonary injury caused by blast overpressure, and to evaluate the effects of bilateral vagotomy on the general, local, and cerebral responses to local (pulmonary) blast injury. The blast wave was generated in laboratory conditions using an air-driven shock tube that was able to cause moderate pulmonary blast injury, i.e., four pulmonary contusions characterized as confluent ecchymoses involving 30 to 60% of the lungs. One group of animals was subjected to pulmonary deafferentation, performed by bilateral transections of the vagus, glossopharyngeal, and hypoglossal nerves. Numerous hemodynamic as well as biochemical parameters were observed in systemic circulation and in lung and brain (medulla oblongata) tissues. After observation during the early posttraumatic period, rabbits were sacrificed by decapitation 30 minutes after the blast injury. On the basis of obtained results, it was concluded that vagal afferents have an important role in the modification of general and local responses to a pulmonary blast injury. Furthermore, it was suggested that functional changes in medulla oblongata may be the consequences of afferent neural impulses from the injured region (lungs) rather than consequences of ischemia, energy transfer to the brain, or both.

Glucose as an adjunct triage tool to the Red Cross Wound Classification.

The plasma concentrations of glucose, adrenaline, noradrenaline, insulin, and cortisol were measured in 59 patients within 18 hours of military gunshot/missile (MG/M) wound. The wounds were categorized by the Red Cross Wound Classification (RCWC) and assessed by the Injury Severity Score (ISS) method. The majority of the measured biochemical parameters, except insulin, were significantly increased after MG/M wounds, compared with control values. Plasma glucose concentration in wounded patients was positively related to ISS over the whole severity range. Plasma insulin concentration increased with glucose. Noradrenaline and cortisol were positively related to glucose. Because hemorrhage is the most common cause of general response to MG/M wound, we concluded that glucose measurement could be a useful adjunct tool to the RCWC in rapid and accurate assessment of severely wounded patients, especially those with occult thoraco-abdominal wounds.

Leukotrienes in the pathogenesis of pulmonary blast injury.

Our previous studies demonstrate a significant increase of sulfidopeptide leukotriene concentrations in animals exposed to a free air blast. The aim of this study was to analyze the role of leukotrienes in the local response of lung tissue as well as in the general response of organisms to blast overpressure. The study was conducted on adult rabbits exposed to moderate blast overpressure (four pulmonary contusions characterized as confluent ecchymoses involving 30 to 60% of the lungs), generated in laboratory conditions. One group of experimental animals was treated with 5-lipoxygenase (5-LO) inhibitor, diethylcarbamazine (DEC, Sigma, St. Louis, Missouri) (50 mg/kg, i.v.), immediately before blast. The early posttraumatic period was observed (30 minutes after blast). Hemodynamic parameters (mean arterial pressure, heart rate, blood gases) as well as arterial plasma levels of conjugated dienes were observed. The myeloperoxidase activity, lipid peroxidation products levels, and water contents were measured in the lung tissue of injured rabbits. We observed that 5-LO inhibition reduced edema formation, accumulation of neutrophils, and generation of lipid peroxidation products in injured lungs. In this study, we demonstrated that treatment with DEC inhibits the increased systemic generation of conjugated dienes after blast injury. Although DEC exerts local antioxidant activity with beneficial effects on lung tissue, this 5-LO inhibitor intensifies the blast overpressure caused hemodynamic insufficiency.

Early plasma amino acid pool alterations in patients with military gunshot/missile wounds.

Plasma amino acid profiles in patients during the early period (first 18 hours) following military gunshot/missile wounds were investigated. Patients (n = 29) were casualties from the war in the former Yugoslavia with injury severity scores ranging from 4 to 18. They were divided into three groups: soft tissue (muscle) damage, wounds with fractures, and vital structures injured. Controls were normal blood donors (n = 17). Free amino acids were analyzed in venous plasma. Increased concentrations of phenylalanine and glutamine associated with increased molar phenylalanine/tyrosine ratio in plasma indicated increased net protein catabolism in the peripheral tissues, regardless of the type of injured tissues. Decreased plasma arginine, ornithine and citrulline levels, accompanied with increased molar glutamine/valine ratio, suggested disturbance in urea cycle activity, although urea level was not altered. We concluded that early changes in plasma amino acid pool characteristics after wounds were of systemic origin, not related to the type of injured tissues.

Experimental magnesium depletion in adult rabbits caused by blast overpressure.

The complex pressure wave (blast) generated by some explosions causes pulmonary pathological changes which resemble the histological findings of the adult respiratory distress syndrome (ARDS). The development of indirect neurotrauma following experimental pulmonary blast injury has been shown previously. The purpose of this study was to evaluate lung and brainstem total tissue magnesium concentrations in adult rabbits following pulmonary blast injury. In order to assess the interrelationship between magnesium and other secondary injury factors, total calcium and high energy phosphate (phosphocreatine, PCr; adenosine triphosphate, ATP) contents were simultaneously measured. Twenty adult male rabbits were divided into two groups. Group C (n = 10) served as control, while group B (n = 10) was subjected to a focused blast wave, generated in laboratory conditions using an air-driven shock tube. Moderate pulmonary blast injury was verified by histological examination in group B. Total tissue magnesium and calcium contents were measured by atomic absorption spectrophotometry in the lungs and brainstem of adult rabbits 30 min following blast overpressure and in their uninjured controls. Simultaneously, PCr and ATP contents were measured by fluorimetric enzymatic analyses in same structures. Lung and brainstem water contents were determined by wet weight to dry weight ratio. Blast overpressure to the lungs induced significant magnesium depletion, increased calcium and decreased the Mg/Ca ratio in lung tissue of injured animals. Increases in water content and PCr/ATP ratio were also observed. Significant correlations between these Mg/Ca and PCr/ATP and between Mg and ATP parameters confirmed the functional relationship between magnesium depletion and impaired bioenergetic state in indirect neurotrauma in adult rabbits through blast overpressure.

Ionizing radiation-induced expression of the genes associated with the acute response to injury in the rat.

Total-body irradiation of rats with doses ranging from an LD10/30 to an LD100/30 induced a dose-dependent increase in the concentration of serum protein associated with the acute response to the irradiation. However, this increase was reached at a later time and was not as pronounced as described previously during the typical acute phase of the response found experimentally (A. Koj, in Structure and Function of Plasma Proteins, Vol. 1, pp. 73-131, Plenum Press, London, 1974). The greatest increase in the serum concentrations of acute-phase proteins was found from the third to the seventh days postirradiation. At these times, the serum concentrations of alpha 2-macroglobulin, haptoglobin, fibrinogen and cysteine protease inhibitor were raised from two- to fivefold, whereas alpha 1-acid glycoprotein was increased sixfold. Incorporation of [35S]methionine into total serum and acute-phase proteins indicated that the increase in the concentration of the acute-phase proteins was preceded by their de novo synthesis in the liver. The results that were obtained by dot-blot analysis showed that the basic course of change in the relative mRNA concentrations in the liver for the acute-phase proteins examined correlated with the changes in their protein concentrations in the serum; only the relative increase in the concentration of alpha 1-acid glycoprotein mRNA was significantly lower than the increase in proteins in the serum, suggesting that a fraction of the serum alpha 1-acid glycoprotein had an extrahepatic origin. On the basis of these results we concluded that total-body irradiation increased the expression of acute-phase protein genes.