Should an increase in cerebral neurochemicals following head kicks in full contact karate influence return to play?

BACKGROUND: Cerebral neurochemicals are markers of traumatic brain injury (TBI). OBJECTIVES: The aim of the study was to determine whether kicks to the head (KTH) in full contact karate significantly increased serum concentrations of protein S-100B, and neurone specific enolase (NSE). Kicks to the body (KTB) were also quantified to asses muscle tissue injury. Muscle damage was assessed by analysis of serum total creatine kinase (CK). METHODS: Twenty-four full contact karate practitioners were observed and filmed during actual competition and divided into two main groups post event: (1) Kicks to the head and body group (KTH): n = 12; mean ± SD; age, 30.4 ± 6.7 years; height, 1.74 ± 0.1 m; weight, 79.1 ± 2.1 kg; and (2): Kicks to the body group (KTB): n = 12; mean ± SD; age, 28.2 ± 6.5 years; height, 1.75 ± 0.1 m; weight, 79.2 ± 1.7 kg. The KTH group received direct kicks to the head, while group KTB received kicks and punches to the body. Blood samples were taken before and immediately post-combat for analysis of serum S-100B, NSE, CK and cardiac troponin. RESULTS: Significant increases in serum concentrations of S-100B (0.12 ± 0.17 vs. 0.37 ± 0.26, µg.L(-1)) and NSE (11.8 ± 4.1 vs. 20.2 ± 9.1 ng.mL(-1)) were encountered after combat in the KTH group and CK (123 ± 53 vs. 184 ± 103 U.L(-1)) in the KTB group (all P <0.05). CONCLUSIONS: Head kicks in full contact karate cause elevation of neurochemical markers associated with damaged brain tissue. The severity of injury is related to the early post-traumatic release of protein S-100B and NSE. The early kinetics and appearance post injury can reflect intracranial pathology, and suggest S-100B and NSE are extremely sensitive prognostic markers of TBI.

Direct hits to the head during amateur boxing is associated with a rise in serum biomarkers for brain injury.

Boxing exposes participants to the physiological response to high intensity exercise and also to direct body and brain trauma. Amateur boxing is increasing and females have also been included in the Olympics. The aim of this study is to assess the stress response and possible brain injury incurred during a match by measuring serum biomarkers associated with stress and cellular brain injury before and after combat. Sixteen male amateur boxers were studied retrospectively. The study population was divided into two groups: (a) a group that received predominantly punches to the head (PTH) and (b) a group that received predominantly punches to the body (PTB). Blood samples were taken before and five minutes after each contest. They were analysed for S-100B, neuron-specific enolase (NSE), creatine kinase (CK) and cortisol. The PTH group received direct contacts to the head (not blocked, parried or avoided) and to the body (n=8, age: 17.6 ± 5.3, years; height: 1.68 ± 0.13, meters; mass: 65.4 ± 20.3, kg). The PTB group received punches to the body including blocked and parried punches, but received no direct punches to the head, (n=8, mean ± SD, age: 19.1 ± 3.2 years; height: 1.70 ± 0.75, meters; mass: 68.5 ± 15 kg). Significant increases (P<0.05) were observed between pre- and post-combat serum concentrations in serum concentrations in PTH of S-100B (0.35 ± 0.61 vs. 0.54 ± 0.73, µg.L-1) NSE (19.7 ± 14 vs.31.1 ± 26.6, ng.ml-1) and cortisol (373 ± 202 vs. 756 ± 93, nmol.L-1). Significant increases (P<0.05) of creatine kinase were recorded in both groups. This study demonstrates significant elevations in neurochemical biomarkers in boxers who received direct blows to the head. However, further work is required to quantify this volumetric brain damage and long term clinical sequelae.

Evasion of human innate and acquired immunity by a bacterial homolog of CD11b that inhibits opsonophagocytosis.

Microbial pathogens must evade the human immune system to survive, disseminate and cause disease. By proteome analysis of the bacterium Group A Streptococcus (GAS), we identified a secreted protein with homology to the alpha-subunit of Mac-1, a leukocyte beta2 integrin required for innate immunity to invading microbes. The GAS Mac-1-like protein (Mac) was secreted by most pathogenic strains, produced in log-phase and controlled by the covR-covS two-component gene regulatory system, which also regulates transcription of other GAS virulence factors. Patients with GAS infection had titers of antibody specific to Mac that correlated with the course of disease, demonstrating that Mac was produced in vivo. Mac bound to CD16 (FcgammaRIIIB) on the surface of human polymorphonuclear leukocytes and inhibited opsonophagocytosis and production of reactive oxygen species, which resulted in significantly decreased pathogen killing. Thus, by mimicking a host-cell receptor required for an innate immune response, the GAS Mac protein inhibits professional phagocyte function by a novel strategy that enhances pathogen survival, establishment of infection and dissemination.

Concentrations of salivary testosterone, cortisol, and immunoglobulin A after supra-maximal exercise in female adolescents.

The aim of this study was to examine the effect of supra-maximal exercise on circulating concentrations of salivary testosterone, salivary cortisol, and salivary immunoglobulin A in female adolescents. Nineteen apparently healthy females aged 15-16 years participated in this study. All participants completed 668 s sprints, interspersed with 30 s recovery intervals on a cycle ergometer. Salivary testosterone, cortisol, and immunoglobulin A samples were taken before and 5 min after exercise. Experimental procedures continued over two mornings, at least 3 h after a light breakfast. Participants refrained from performing any strenuous physical activity for at least 24 h prior to the exercise test. None of the participants were engaged in a structured training programme. The group mean (± s) for peak power output was 562 ± 113.0 W. Female adolescents recruited for this study showed no changes in salivary testosterone, cortisol or immunoglobulin A following repeated bouts of supra-maximal cycling (P > 0.05). To date, there has been a paucity of information concerning adolescents' hormonal and mucosal immune function responses to supra-maximal exercise. Our data provide further guidance with regard to physical activities and sports prescription for female adolescents. Further research, on a larger sample of females, is required to elucidate the physiological significance of these findings.

C-reactive protein in schoolchildren and its relation to adiposity, physical activity, aerobic fitness and habitual diet.

OBJECTIVE: To investigate the relation between C-reactive protein (CRP), adiposity, physical activity, aerobic fitness and habitual diet in a cohort of schoolchildren. METHODS: A cross-sectional study of 164 schoolchildren aged 12-13 years was conducted in two schools. Adiposity was estimated using body mass index and waist circumference. Blood samples were taken after an overnight fast and measured for CRP. Aerobic fitness and habitual physical activity were assessed using the 20 metres multistage fitness test, and a seven-day recall, respectively. A seven-day food diary provided measures of dietary intake. RESULTS: To improve the distribution of this variable, CRP levels were logarithmically transformed in all analyses. There was no significant difference in mean CRP concentration between boys (1.07 (1.33) mg/l) and girls (1.24 (1.87) mg/l) (p> or =0.05). Compared to girls, boys reported significantly higher (i) aerobic fitness 59.2 (20.3) shuttles vs 42.9 (15.3) shuttles, (ii) vigorous activity levels per week 92 (123) minutes vs 11.2 (34.6) minutes and (iii) waist circumference 69.8 (1.1) cm vs 65.2 (0.9) cm (p< or =0.05). Among boys and girls, adiposity was significantly associated with log transformed CRP (p< or =0.05). CRP was not significantly related to any other variable. CONCLUSION: Elevated CRP was evident in this cohort; however, whether high CRP levels during childhood and adolescence leads to an increased risk of CVD in later life has not been determined. Adiposity was related to CRP concentration, suggesting that reducing adiposity may be effective in lowering CRP and preventing future cardiovascular events.

Homocyst(e)ine, folate, and vitamin B12 status in a cohort of Welsh young people aged 12-13 years old.

The aim of this unique study was to consider the relationship between folate and vitamin B(12) on homocyst(e)ine (Hcy) concentration in an apparently healthy cohort of Welsh young people. A cohort of 179, 12-13 year olds (88 boys and 91 girls) were measured for Hcy, folate, vitamin B(12), adiposity, and dietary habits. Boys had significantly higher waist circumference and folate concentration than girls. Folate was negatively associated with Hcy in both sexes, whereas vitamin B(12) was negatively associated with Hcy in boys only. Adiposity was not associated with Hcy. Folate was an independent predictor of Hcy in both sexes, whilst vitamin B(12) was an independent determinant of Hcy in boys only. Familial history of cardiovascular disease (CVD) risk factors was identified in 69% of the children with elevated Hcy (> or = 8.5 mumol.L(-1)). Young people might be encouraged to increase their folate intake through diet, particularly by increasing their consumption of leafy vegetables and fruit. Further research is necessary to determine the exact contribution of genetics and diet on Hcy levels in young people, and whether Hcy levels during childhood and adolescence might influence future CVD risk.

Toward a genome-scale understanding of group A Streptococcus pathogenesis.

Recent significant contributions have been made to the understanding of Group A Streptococcus (GAS) pathogenesis. New regulatory pathways have been discovered, insight into the molecular basis of epidemics of serotype M1 disease has been obtained, the crystal structures of four toxins have been reported and a genome sequence of one GAS strain has been determined. Genome-scale approaches to the study of GAS pathogenesis are now rapidly emerging and will advance our fundamental understanding of the molecular basis of host-pathogen interactions.

Homocysteine induced cardiovascular events: a consequence of long term anabolic-androgenic steroid (AAS) abuse.

OBJECTIVES: The long term effects (>20 years) of anabolic-androgenic steroid (AAS) use on plasma concentrations of homocysteine (HCY), folate, testosterone, sex hormone binding globulin (SHBG), free androgen index, urea, creatinine, haematocrit (HCT), vitamin B12, and urinary testosterone/epitestosterone (T/E) ratio, were examined in a cohort of self-prescribing bodybuilders. METHODS: Subjects (n = 40) were divided into four distinct groups: (1) AAS users still using AAS (SU; n = 10); (2) AAS users abstinent from AAS administration for 3 months (SA; n = 10); (3) non-drug using bodybuilding controls (BC; n = 10); and (4) sedentary male controls (SC; n = 10). RESULTS: HCY levels were significantly higher in SU compared with BC and SC (p<0.01), and with SA (p<0.05). Fat free mass was significantly higher in both groups of AAS users (p<0.01). Daily energy intake (kJ) and daily protein intake (g/day) were significantly higher in SU and SA (p<0.05) compared with BC and SC, but were unlikely to be responsible for the observed HCY increases. HCT concentrations were significantly higher in the SU group (p<0.01). A significant linear inverse relationship was observed in the SU group between SHBG and HCY (r = -0.828, p<0.01), indicating a possible influence of the sex hormones in determining HCY levels. CONCLUSIONS: With mounting evidence linking AAS to adverse effects on some clotting factors, the significantly higher levels of HCY and HCT observed in the SU group suggest long term AAS users have increased risk of future thromboembolic events.

Steroid and prescription medicine abuse in the health and fitness community: A regional study.

BACKGROUND: The purpose of this study was to identify the prevalence of abuse of certain prescription medicines (POM) amongst health club attendees. The non-therapeutic use of such medicines has previously been considered to be restricted to the professional athlete. METHODS: In the summer of 2005, health club users in the South Wales area were given questionnaires and asked to return them in a stamped, addressed envelope. Anonymity of the respondents was assured. RESULTS: From the distribution of 210 questionnaires, the response rate was 69.5% (146 questionnaires). The mean age of the sample was 33.6+/-6.7 years (range 15-72 years). Anabolic-androgenic steroid (AAS) use is prominent amongst recreational gym users in this regional sample, with 70% (102 individuals) reporting AAS use, 65.8% (96 individuals) of whom were currently still using. Some 7% of respondents (10 individuals) were female and they also reported taking medication. This research demonstrated an enormous increase in the use of growth hormone (24%), insulin (14%), and tamoxifen (22%), with smaller increases in other drugs. CONCLUSION: Drug users were from all levels of society and reported various physiological and psychological side effects from their use. The present study indicated that the most used medicine/drug from less than reputable sources was still AAS but that, as a consequence of the internet revolution, they were being caught up by the more expensive designer drugs, particularly growth hormone. Physicians and medical personnel must become aware that the use of AAS and other prescription medicines is on the increase and appears to be predominantly used for cosmetic reasons.

Cloning and characterization of the exbB-exbD-tonB locus of Pasteurella haemolytica A1.

A recombinant plasmid (pMG1) carrying Pasteurella haemolytica A1 DNA which complements a tonB mutation of Escherichia coli has been isolated. E. coli tonB metE which carries pMG1 exhibits growth kinetics in the presence of vitamin B12 similar to that of the wild-type host. In addition, the complemented E. coli is susceptible to killing by bacteriophage phi 80 and colicin B. Analysis of the nucleotide sequence in the complementing DNA showed that it codes for three genes in the order of exbB-exbD-tonB. This genetic organization has been reported in Haemophilus influenzae, H. ducreyi, Pseudomonas putida and Vibrio cholerae, and may represent a separate lineage of evolution from that of the Enterobacteriaceae in which tonB is unlinked with the accessory genes exbB and exbD. A comparison of the DNA flanking the exbB-exbD-tonB locus in P. haemolytica A1 and H. influenzae showed that the flanking regions are completely different between the two organisms.

Fractal or biologically variable delivery of cardioplegic solution prevents diastolic dysfunction after cardiopulmonary bypass.

OBJECTIVE: To determine whether myocardial protection is improved by restoring physiologic variability to the cardioplegia pressure signal during cardiopulmonary bypass, we compared cardiac function in pigs in the first hour after either conventional cold-blood cardioplegia (group CC) or computer-controlled biologically variable pulsatile cardioplegia (group BVC). METHODS: Invasive monitors and sonomicrometry crystals were placed, and cardiopulmonary bypass was initiated. The aorta was crossclamped, and cold blood cardioplegic solution was infused intermittently through the aortic root with either conventional cardioplegia (n = 8) or biologically variable pulsatile cardioplegia (n = 8; mean pressure, 75 mm Hg for 85 minutes). The crossclamp was released, cardiac function was restored, and separation from cardiopulmonary bypass was completed. With stable temperature and arterial blood gases, hemodynamics and systolic and diastolic indices were compared at 15, 30, and 60 minutes after cardiopulmonary bypass. RESULTS: Diastolic stiffness doubled from 0.027 +/- 0.016 mm Hg/mm (mean +/- SD) at baseline to 0.055 +/- 0.036 mm Hg/mm (P =.003) at 1 hour after bypass in group CC, associated with increased left ventricular end-diastolic pressure from 9 +/- 2 to 11 +/- 2 mm Hg (P =.001), mean pulmonary artery pressure from 14 +/- 2 to 20 +/- 3 mm Hg (P =.003), and serum lactate levels from 2.0 +/- 0.5 to 5.6 +/- 2.3 mmol/L (P =.008). Systolic function was not affected. In group BVC diastolic stiffness, left ventricular end-diastolic pressure, and pulmonary artery pressure values were not different from control values at any time after bypass, and serum lactate levels were significantly less than with conventional cold blood cardioplegia. Peak pressure variability with biologically variable pulsatile cardioplegia fit a power-law equation (exponent = -3.0; R(2) = 0.97), indicating fractal behavior. CONCLUSION: Diastolic cardiac function is better preserved after cardiopulmonary bypass with biologically variable pulsatile cardioplegia and fractal perfusion. This may be attributed to enhanced microcirculatory perfusion with improved myocardial protection. A model supporting these results is presented.

A nuclear magnetic resonance study of the metal binding sites in bacitracin.

Carbon-13 nuclear magnetic resonance spectroscopy has been used to identify sites in bacitracin which bind Cu2+ and Mn2+. Results are presented which implicate the free carboxyl groups of the aspartic and glutamic acid residues and the imidazole ring of the histidine residue as metal complexation sites between pH 6 and 8. Evidence is presented which also indicates that the thiazoline ring of bacitracin binds Mn2+. Bacitracin does not bind Cu2+ or Mn2+ at pH values of 2.5 or less.

Left ventricular systolic and diastolic function is unaltered during propofol infusion in newborn swine.

UNLABELLED: Propofol is a cardiac depressant with minimal diastolic effects in the adult myocardium. Cardiac effects of propofol in the newborn are unknown. We examined hemodynamic variables and systolic and diastolic left ventricular function in 12 newborn pigs exposed to propofol at three different infusion rates (7.5, 15, and 30 mg x kg(-1) x h(-1)) in random order with a background of fentanyl (100 microg x kg(-1) x h(-1)). Left ventricular (LV) pressure (Plv) and LV anterior-posterior dimension, determined by sonomicrometry, were continuously monitored. Mean arterial pressure (MAP), heart rate (HR), and LV end-diastolic pressure (LVEDP) were determined at every infusion. Systolic function was assessed by the maximal pressure-time derivative (dP/dt(max)), the slope of the end-systolic pressure-dimension relationship (ESP-D), and by the preload recruitable stroke work index (PRSWI). Diastolic function was assessed by relaxation indices, the minimal pressure-time derivative (dP/dt(min)) and the relaxation time constant (tau), and by a stiffness index, the slope of the EDP-D relationship. MAP decreased approximately 25%, from 75.9 +/- 15.6 to 56.3 +/- 14.8 mm Hg (P < 0.05) with propofol, with no dose effect. HR and LVEDP were unchanged from control. Both dP/dt(max) and dP/dt(min) decreased with propofol infusion, but load-independent indices of systolic function (ESP-D slope and PRSWI) and tau were unchanged. Diastolic stiffness was not affected with either 7.5- or 30-mg x kg(-1) x h(-1) infusions but decreased significantly from 0.27 +/- 0.18 mm Hg/mm at control to 0.18 +/- 0.18 mm Hg/mm (P < 0.05) with propofol 15 mg x kg(-1) x h(-1). With this profile, propofol may be useful for the newborn requiring anesthesia. IMPLICATIONS: Most anesthetics depress heart function in the newborn. We examined both heart contraction and relaxation during anesthesia with propofol in newborn pigs. Propofol had minimal influence on heart function in this model at the doses studied. This may therefore be a useful anesthetic to test in the newborn human.

Isoflurane and halothane impair both systolic and diastolic function in the newborn pig.

PURPOSE: Volatile anaesthetics have considerable effects on diastolic relaxation in the adult myocardium. We hypothesized that isoflurane (1) and halothane (H) may have even greater effects on diastolic function in the newborn, as the newborn heart has increased passive stiffness and altered calcium handling relative to the adult. Using a newborn pig model, we compared I and H at three clinically relevant concentrations with respect to both systolic and diastolic function. METHODS: Sixteen newborn pigs were randomized for study at control (background fentanyl 100 micrograms.kg-1.hr-1 and 0.5, 1.0 and 1.5 MAC of I (n = 8) or H (n = 8). Temperature, arterial blood gases, and LVEDP were controlled. Left ventricular pressure (LVP) was monitored continuously and LV anterior-posterior dimension was determined by using sonomicrometry crystals. Systolic function was assessed by peak positive dP/dT (dP/dTmax) and the slope of the end-systolic pressure-dimension (ESP-D) relationship. Diastolic relaxation was given by peak negative dP/dT (-dP/dTmax) and the time constant for ventricular relaxation (tau). Left ventricular stiffness was calculated from the slope of the end-diastolic pressure-dimension (EDP-D) relationship. RESULTS: At equal MAC concentrations, I and H were identical in effect for every variable studied. Systolic function was depressed at all anaesthetic concentrations. Control dP/dTmax (I:1815 +/- 561 (SD) mmHg.sec-1, H:1841 +/- 509) decreased to 832 +/- 341 with 1.5 MAC I and 691 +/- 127 with 1.5 MAC H (P < 0.05 vs control). ESP-D slope decreased from 62 +/- 31 mmHg.mm-1 at control to 15 +/- 11 with 1.5 MAC I and from 79 +/- 16 to 37 +/- 15 with 1.5 MAC H (P < 0.05 vs control). Diastolic function was affected only at higher MAC anaesthesia. Control tau increased from 18.0 +/- 6 msec to 29.1 +/- 7.5 with 1.5 MAC I and from 20.8 +/- 5.9 to 30.0 +/- 11.3 with 1.5 MAC H (P < 0.05). EDP-D slope was increased at both 1 and 1.5 MAC anaesthesia. EDP-D slope increased from 0.16 +/- 0.24 mmHg.mm-1 at control to 0.58 +/- 0.46 with I MAC I and from 0.16 +/- 11 to 0.50 +/- 0.35 with 1 MAC H. The -dP/dTmax decreased at every MAC level of anaesthesia. CONCLUSION: These combined systolic and diastolic effects help to explain the increased sensitivity of the newborn myocardium to volatile anaesthetics.

Neuroanesthesia adjunct therapy (mannitol and hyperventilation) is as effective as cerebrospinal fluid drainage for prevention of paraplegia after descending thoracic aortic cross-clamping in the dog.

We compared cerebrospinal fluid (CSF) drainage (Group D; n = 8) to neuroanesthesia adjunct therapy (hyperventilation and mannitol administration; Group N; n = 8) for the prevention of paraplegia using a canine model of descending thoracic aortic cross-clamping (AXC; 2.5 mm distal to the left subclavian artery for 30 min). We expected no difference in neurologic outcome between groups. After surgical preparation and a 30-min stabilization period, dogs in Group D had CSF drained prior to application of the AXC. During the period of AXC, CSF was allowed to drain freely in an attempt to have cerebrospinal fluid pressure (CSFP) no greater than central venous pressure (CVP). Dogs in Group N were hyperventilated (PaCO2 28-32 mm Hg) and received 2 g/kg of mannitol prior to AXC and then 1 g.kg-1.hr-1 during clamping. Systemic hemodynamics, CSFP, and arterial blood gases were measured at 1) baseline, 2) 2 min after AXC, 3) 20 min after AXC, 4) 5 min after AXC release, and 5) 30 min after resuscitation. With release of the AXC, PaCO2 was not controlled in Group D; in Group N the minute ventilation was further increased to maintain PaCO2 constant. At precisely 24 h after AXC, the animals were assessed for incidence and severity of paraplegia, using the Tarlov score, by an observer unaware of the experimental protocol. The animals were then killed, and the entire spinal cord was removed for histologic assessment. Multiple sections of the lumbar spinal cord were processed and stained with hematoxylin and eosin, then examined by light microscopy for nonviable neurons in the anterior spinal cord.(ABSTRACT TRUNCATED AT 250 WORDS)

Paraplegia following thoracic aortic cross-clamping in dogs. No difference in neurological outcome with a barbiturate versus isoflurane.

BACKGROUND AND PURPOSE: We compared the incidence and severity of paraplegia following thoracic aortic cross-clamping in dogs for two anesthetic regimens. Animals were randomly assigned to receive methohexital (group M; n = 9) or isoflurane (group I; n = 9). We expected a better neurological outcome in animals administered methohexital because of superior neuronal protection and greater spinal cord perfusion pressure (mean arterial pressure below the cross-clamp site minus mean cerebrospinal fluid pressure). METHODS: After surgical preparation and a 30-minute stabilization period, dogs in group M received 14 +/- 6 mg.kg-1 i.v. methohexital to induce an isoelectric electroencephalogram followed by a continuous infusion of methohexital at 20 mg.kg-1 x h-1. Dogs in group I received 1.4 +/- 0.2% end-tidal isoflurane (1 minimum alveolar concentration). The thoracic aorta was then occluded 2.5 cm distal to the left subclavian artery for 30 minutes and then released. Hemodynamics and cerebrospinal fluid pressure were measured at (1) baseline, (2) 2 minutes after aortic cross-clamping, (3) 20 minutes after aortic cross-clamping, (4) 5 minutes after aortic unclamping, and (5) 30 minutes after resuscitation. At 24 hours a neurological assessment was performed. After the clinical assessment the dogs were killed and the spinal cord removed immediately for histopathologic study. RESULTS: There were no differences in nasopharyngeal temperature, PaCO2, pH, or hemoglobin at any time between groups. With cross-clamping, the spinal cord perfusion pressure decreased precipitously. However, there was no difference in spinal cord perfusion pressure between groups at any time (P = .5555). The neurological outcome, assessed at 24 hours after thoracic aortic cross-clamping by a veterinarian unaware of the anesthetic protocol, was not different between groups (P > .5, two-tailed Mann-Whitney rank-sums test). When anesthetized with methohexital 5 of 9 dogs were paraplegic; with isoflurane 7 of 9 dogs were paraplegic. By Spearman's rank test, a strong inverse correlation between the Tarlov score and the ratio of dead to total lumbar anterior spinal cord neurons was seen (Spearman's correlation coefficient = -.8358; P = .0001). CONCLUSIONS: We conclude that no advantage was offered by the choice of anesthesia to neurological outcome after 30 minutes of thoracic aortic cross-clamping in this canine model.

Use of neuroanesthesia adjuncts (hyperventilation and mannitol administration) improves neurological outcome after thoracic aortic cross-clamping in dogs.

BACKGROUND AND PURPOSE: Using a canine model of thoracic aortic cross-clamping, we compared the incidence and severity of paraplegia with and without standard neuroanesthesia adjuncts (mannitol administration and deliberate hyperventilation). Better outcome was predicted for animals treated with mannitol and hyperventilation. METHODS: Nineteen dogs (mean +/- SD weight, 21 +/- 3 kg) were anesthetized with methohexital to an isoelectric electroencephalogram. Animals were randomized to group C (control; n = 9) or group M (mannitol administration and deliberate hyperventilation; n = 10). In group C, animals were maintained normocapnic (PaCO2, 38 to 42 mm Hg). In group M, animals were hyperventilated to a PaCO2 of 28 to 32 mm Hg and received mannitol 2 g.kg-1 during surgical preparation, then 1 g.kg-1.h-1 by continuous infusion. The thoracic aorta was cross-clamped for 30 minutes. Systemic hemodynamics, cerebrospinal fluid pressure, and arterial blood gases were measured at (1) baseline, (2) 2 minutes after cross-clamp, (3) 20 minutes after cross-clamp, (4) 5 minutes after cross-clamp release, and (5) 30 minutes after resuscitation. No attempt was made to control the hemodynamic consequences of cross-clamping in either group. With release of the cross-clamp, PaCO2 was not controlled in group C; in group M the minute ventilation was further increased to maintain PaCO2 constant. At precisely 24 hours after cross-clamp the animals were assessed for incidence and severity of paraplegia, using the Tarlov score, by an observer unaware of the experimental protocol. The animals were killed, and the entire spinal cord was removed for histological assessment. Multiple sections of the lumbar spinal cord were processed and stained with hematoxylin and eosin. RESULTS: With application of the cross-clamp, cerebrospinal fluid pressure and central venous pressure increased significantly in both groups. However, in group M the maximal mean cerebrospinal fluid pressure never exceeded baseline values in group C. With cross-clamp release, spinal cord perfusion pressure (distal mean aortic pressure minus mean cerebrospinal fluid pressure) was significantly greater in group M (86 +/- 23 vs 65 +/- 17 mm Hg; P = .0017 between groups). Acid-base balance was better maintained in group M. The incidence and severity of paraplegia were significantly lower in group M (P = .043; Mann-Whitney rank-sums test, two-tailed). In this group 10 of 10 animals could walk and 4 of 10 had complete recovery. In group C 4 of 9 animals were paraplegic. There was a strong negative correlation between the Tarlov score and the ratio of dead to total anterior spinal cord neurons in the lumbar region as assessed by light microscopy (P = .0004; Spearman's rank test). CONCLUSIONS: We conclude that a protocol using standard neuroanesthesia adjuncts (mannitol administration and deliberate hyperventilation) is associated with improved neurological outcome after thoracic aortic cross-clamping of 30 minutes' duration in dogs anesthetized with methohexital.

Biologically variable ventilation prevents deterioration of gas exchange during prolonged anaesthesia.

We have studied the time course of changes in gas exchange and respiratory mechanics using two different modes of ventilation during 7 h of isoflurane anaesthesia in pigs. One group received conventional control mode ventilation (CV). The other group received biologically variable ventilation (BVV) which simulates the breath-to-breath variation in ventilatory frequency (f) that characterizes normal spontaneous ventilation. After baseline measurements with CV, animals were allocated randomly to either CV or BVV (FIO2 1.0 with 1.5% end-tidal isoflurane). With BVV, there were 376 changes in f and tidal volume (VT) over 25.1 min. Ventilation was continued over the next 7 h and blood gases and respiratory mechanics were measured every 60 min. The modulation file used to control the ventilator for BVV used an inverse power law frequency distribution (I/fa with a = 2.3 +/- 0.3). After 7 h, at a similar delivered minute ventilation, significantly greater PaO2 (mean 72.3 (SD 4.0) vs 63.5 (6.5) kPa) and respiratory system compliance (1.08 (0.08) vs 0.92 (0.16) ml cm H2O-1 kg-1) and lower PaCO2 (6.5 (0.7) vs 8.7 (1.5) kPa) and shunt fraction (7.2 (2.7)% vs 12.3 (6.2)%) were seen with BVV, with no significant difference in peak airway pressure (16.3 (1.2) vs 15.3 (3.7) cm H2O). A deterioration in gas exchange and respiratory mechanics was seen with conventional control mode ventilation but not with BVV in this experimental model of prolonged anaesthesia.

Biologically variable ventilation increases arterial oxygenation over that seen with positive end-expiratory pressure alone in a porcine model of acute respiratory distress syndrome.

OBJECTIVES: We compared biologically variable ventilation (BVV) (as previously described) (1) with conventional control mode ventilation (CV) in a model of acute respiratory distress syndrome (ARDS) both at 10 cm H2O positive end-expiratory pressure. DESIGN: Randomized, controlled, prospective study. SETTING: University research laboratory. SUBJECTS: Farm-raised 3- to 4-month-old swine. INTERVENTIONS: Oleic acid (OA) was infused at 0.2 mL/kg/hr with FIO2 = 0.5 and 5 cm H2O positive end-expiratory pressure until PaO2 was < or =60 mm Hg; then all animals were placed on an additional 5 cm H2O positive end-expiratory pressure for the next 4 hrs. Animals were assigned randomly to continue CV (n = 9) or to have CV computer controlled to deliver BVV (variable respiratory rate and tidal volume; n = 8). Hemodynamic, expired gas, airway pressure, and volume data were obtained at baseline (before OA), immediately after OA, and then at 60-min intervals for 4 hrs. MEASUREMENTS AND MAIN RESULTS: At 4 hrs after OA injury, significantly higher PaO2 (213+/-17 vs. 123+/-47 mm Hg; mean+/-SD), lower shunt fraction (6%+/-1% vs. 18%+/-14%), and lower PaCO2 (50+/-8 vs. 65+/-11 mm Hg) were seen with BVV than with CV. Respiratory system compliance was greater by experiment completion with BVV (0.37+/-0.05 vs. 0.31+/-0.08 mL/cm H2O/kg). The improvements in oxygenation, CO2 elimination, and respiratory mechanics occurred without a significant increase in either mean airway pressure (14.3+/-0.9 vs. 14.9+/-1.1 cm H2O) or mean peak airway pressure (39.3+/-3.5 vs. 44.5+/-7.2 cm H2O) with BVV. The oxygen index increased five-fold with OA injury and decreased to significantly lower levels over time with BVV. CONCLUSIONS: In this model of ARDS, BVV with 10 cm H2O positive end-expiratory pressure improved arterial oxygenation over and above that seen with CV with positive end-expiratory pressure alone. Proposed mechanisms for BVV efficacy are discussed.

Global differential gene expression in response to growth temperature alteration in group A Streptococcus.

Pathogens are exposed to different temperatures during an infection cycle and must regulate gene expression accordingly. However, the extent to which virulent bacteria alter gene expression in response to temperatures encountered in the host is unknown. Group A Streptococcus (GAS) is a human-specific pathogen that is responsible for illnesses ranging from superficial skin infections and pharyngitis to severe invasive infections such as necrotizing fasciitis and streptococcal toxic shock syndrome. GAS survives and multiplies at different temperatures during human infection. DNA microarray analysis was used to investigate the influence of temperature on global gene expression in a serotype M1 strain grown to exponential phase at 29 degrees C and 37 degrees C. Approximately 9% of genes were differentially expressed by at least 1.5-fold at 29 degrees C relative to 37 degrees C, including genes encoding transporter proteins, proteins involved in iron homeostasis, transcriptional regulators, phage-associated proteins, and proteins with no known homologue. Relatively few known virulence genes were differentially expressed at this threshold. However, transcription of 28 genes encoding proteins with predicted secretion signal sequences was altered, indicating that growth temperature substantially influences the extracellular proteome. TaqMan real-time reverse transcription-PCR assays confirmed the microarray data. We also discovered that transcription of genes encoding hemolysins, and proteins with inferred roles in iron regulation, transport, and homeostasis, was influenced by growth at 40 degrees C. Thus, GAS profoundly alters gene expression in response to temperature. The data delineate the spectrum of temperature-regulated gene expression in an important human pathogen and provide many unforeseen lines of pathogenesis investigation.