Biomedical subjects

C W Callaway

Publications and source records attributed to C W Callaway.

At least 19 recordsLinked to original sources

PubMed2007

Different mechanisms account for extracellular-signal regulated kinase activation in distinct brain regions following global ischemia and reperfusion.

Oxidative stress after cerebral ischemia and reperfusion activates extracellular signal-regulated kinases (ERK) in brain. However, the mechanism of this activation has not been elucidated. We have previously reported that in an in vitro model of oxidative stress in immature cortical neuronal cultures, the inhibition of ERK phosphatase activity contributes to ERK1/2 activation and subsequent neuronal toxicity. This study examined whether ERK activation was associated with altered activity of ERK phosphatases in a rat cardiac arrest model. Rats in experimental groups were subjected to asphyxial cardiac arrest for 8 min and then resuscitated for 30 min. Significant ERK activation was detected in both cortex and hippocampus following ischemia/reperfusion by immunoblotting. ERK phosphatase activity was reversibly inhibited in cerebral cortex but not affected in hippocampus following ischemia/reperfusion. MEK1/2 was activated in both cerebral cortex and hippocampus following ischemia/reperfusion. Using a specific inhibitor of protein phosphatase 2A (PP2A), okadaic acid (OA), we have identified PP2A to be the major ERK phosphatase that is responsible for regulating ERK activation in ischemic brain tissues. Orthovanadate inhibited ERK phosphatase activity in brain tissues, suggesting that tyrosine phosphatases and dual specificity phosphatases may also contribute to the ERK phosphatase activity in brain tissues. Together, these data implicate ERK phosphatase in the regulation of ERK activation in distinct brain regions following global ischemia.

Animals↗

PubMed2005

Uteroplacental insufficiency affects epigenetic determinants of chromatin structure in brains of neonatal and juvenile IUGR rats.

Intrauterine growth retardation (IUGR) increases the risk of neuroendocrine reprogramming. In the rat, IUGR leads to persistent changes in cerebral mRNA levels. This suggests lasting alterations in IUGR cerebral transcriptional regulation, which may result from changes in chromatin structure. Candidate nutritional triggers for these changes include altered cerebral zinc and one-carbon metabolite levels. We hypothesized that IUGR affects cerebral chromatin structure in neonatal and postnatal rat brains. Rats were rendered IUGR by bilateral uterine artery ligation; controls (Con) underwent sham surgery. At day of life 0 (d0), we measured cerebral DNA methylation, histone acetylation, expression of chromatin-affecting enzymes, and cerebral levels of one-carbon metabolites and zinc. At day of life 21 (d21), we measured cerebral DNA methylation and histone acetylation, as well as the caloric content of Con and IUGR rat breast milk. At d0, IUGR significantly decreased genome-wide and CpG island methylation, as well as increased histone 3 lysine 9 (H3/K9) and histone 3 lysine 14 (H3/K14) acetylation in the hippocampus and periventricular white matter, respectively. IUGR also decreased expression of the chromatin-affecting enzymes DNA methyltransferase 1 (DNMT1), methyl-CpG binding protein 2 (MeCP2), and histone deacetylase (HDAC)1 in association with increased cerebral levels of zinc. In d21 female IUGR rats, cerebral CpG DNA methylation remained lower, whereas H3/K9 and H3/K14 hyperacetylation persisted in hippocampus and white matter, respectively. In d21 male rats, IUGR decreased acetylation of H3/K9 and H3/K14 in these respective regions compared with controls. Despite these differences, caloric, fat, and protein content were similar in breast milk from Con and IUGR dams. We conclude that IUGR results in postnatal changes in cerebral chromatin structure and that these changes are sex specific.

Acetylation↗

PubMed2001

Scaling exponent predicts defibrillation success for out-of-hospital ventricular fibrillation cardiac arrest.

BACKGROUND: -Defibrillator shocks often fail to terminate ventricular fibrillation (VF) in out-of-hospital cardiac arrest (OOHCA), and repeated failed shocks can worsen the subsequent response to therapy. Because the VF waveform changes with increasing duration of VF, it is possible that ECG analyses could estimate the preshock likelihood of defibrillation success. This study examined whether an amplitude-independent measure of preshock VF waveform morphology predicts outcome after defibrillation. Methods and Results-Clinical data and ECG recordings from an automated external defibrillator were obtained for 75 subjects with OOHCA in a suburban community with police first responders and a paramedic-based emergency medical system. An estimate of the fractal self-similarity dimension, the scaling exponent, was calculated off-line for the VF waveform preceding shocks. Success of the first shock was determined from the recordings. Return of pulses and survival were determined by chart review. The first shock resulted in an organized rhythm in 43% of cases, and 17% of cases survived to hospital discharge. A lower mean value of the scaling exponent was observed for cases in which the first defibrillation resulted in an organized rhythm (P:=0.004), for cases with return of pulses (P:=0.049), and for cases surviving to hospital discharge (P:<0.001). Receiver operator curves revealed the utility of the scaling exponent for predicting the probability of restoring an organized rhythm (area under the curve=0.70) and of survival (area under the curve=0.84). CONCLUSIONS: -The VF waveform in OOHCA can be quantified with the scaling exponent, which predicts the probability of first-shock defibrillation and survival to hospital discharge.

Aged↗

PubMed2001

Effects of biphasic vs monophasic defibrillation on the scaling exponent in a swine model of prolonged ventricular fibrillation.

OBJECTIVE: Mathematical analyses of ventricular fibrillation (VF) have resulted in the derivation of a measure termed the scaling exponent (ScE) that characterizes the duration of VF and probability of defibrillation success. The purpose of this study was to compare the effects of biphasic defibrillation waveform (BDW) and monophasic defibrillation waveform (MDW) rescue shocks on ScE in a swine model of prolonged VF. METHODS: Utstein guidelines for the laboratory study of cardiopulmonary resuscitation were followed. Twenty mixed-breed domestic swine (mass range 20.5-26.8 kg) were instrumented and randomized to receive either MDW or BDW rescue shocks. Ventricular fibrillation was induced and untreated for a nonintervention interval of 8 minutes. Rescue shocks were delivered at 8, 10, and 12 minutes of elapsed VF time. The energy sequence for the three MDW shocks was 70, 100, and 150 J (approximately 3, 4, and 6 J/kg). All BDW shocks were delivered at 50 J (approximately 2.5 J/kg). Only VF was shocked. Chest compressions and drugs were not provided. Rhythm analysis and ScE calculation were performed offline. Continuous and discontinuous linear regression models were fit to plots of ScE vs time. Defibrillation success and progression of ScE slope were analyzed using Fisher's exact test, paired t-tests, and repeated-measures analysis of variance (ANOVA). RESULTS: Baseline characteristics were similar for both groups. Successful termination of VF occurred on the first rescue shock in 1 of 10 (10%) in the MDW group and 3 of 10 (30%) in the BDW group; this difference was not statistically significant (p = 0.58). No other defibrillation successes were observed. No animals achieved return of spontaneous circulation. The ScE values during the protocol progressed from 1.330 (95% CI = 1.287 to 1.373) to 1.724 (95% CI = 1.603 to 1.845) for MDW and 1.338 (95% CI = 1.261 to 1.415) to 1.639 (95% CI = 1.530 to 1.745) for BDW. Both groups showed a trend toward increasing ScE values with successive rescue shocks. Repeated-measures ANOVA using both continuous and discontinuous models demonstrated no difference in overall ScE slope progression between study groups. CONCLUSIONS: Mode of defibrillation waveform (BDW vs MDW) does not appear to impact ScE trends. Additional studies must be performed to better evaluate the clinical implications of this finding.

Animals↗

PubMed2001

Surrogate consent by family members for out-of-hospital cardiac arrest research.

OBJECTIVES: To evaluate the availability of family members of potential subjects to provide consent for participation in out-of-hospital cardiac arrest (OOHCA) research and to estimate the time required to contact a family member. METHODS: This study was a prospective observational study of adult patients (>18 years old) with nontraumatic OOHCA treated by an urban emergency medical service. Emergency medicine resident physicians responded to each scene and noted the presence of family members. A subsequent convenience sample of family members answered standardized questions about their ability to provide consent for research participation on behalf of the patient. RESULTS: Physicians were present at 100 of the 112 adult medical cardiac arrests during the study period. A family member was present at 57% of the scenes (95% CI = 47% to 67%). Patients with family present were older and were less likely to have bystander cardiopulmonary resuscitation (CPR) or live in a nursing home. The mean time (+/-SE) from emergency dispatch to family contact was 24.40 (+/-2.60) minutes and from physician arrival to family contact was 2.45 (+/-0.87) minutes (n = 20). Eight of 13 family members were willing to enroll the patient into a resuscitation study, but five family members were unable to understand the explanation of informed consent. CONCLUSIONS: Family members were present for an unrepresentative subset of OOHCA cases, and were contacted after the therapeutic window for many interventions. The emotional nature of the emergency situation also limited the reliability of surrogate consent for OOHCA research.

Adult↗

PubMed2001

Bench to bedside: resuscitation from prolonged ventricular fibrillation.

Ventricular fibrillation (VF) remains the most common cardiac arrest heart rhythm. Defibrillation is the primary treatment and is very effective if delivered early within a few minutes of onset of VF. However, successful treatment of VF becomes increasingly more difficult when the duration of VF exceeds 4 minutes. Classically, successful cardiac arrest resuscitation has been thought of as simply achieving restoration of spontaneous circulation (ROSC). However, this traditional approach fails to consider the high early post-cardiac arrest mortality and morbidity and ignores the reperfusion injuries, which are manifest in the heart and brain. More recently, resuscitation from cardiac arrest has been divided into two phases; phase I, achieving ROSC, and phase II, treatment of reperfusion injury. The focus in both phases of resuscitation remains the heart and brain, as prolonged VF remains primarily a two-organ disease. These two organs are most sensitive to oxygen and substrate deprivation and account for the vast majority of early post-resuscitation mortality and morbidity. This review focuses first on the initial resuscitation (achieving ROSC) and then on the reperfusion issues affecting the heart and brain.

Animals↗

PubMed2000

Ventricular fibrillation exhibits dynamical properties and self-similarity.

Electrocardiographic recordings of ventricular fibrillation (VF) appear chaotic. Previous attempts to characterize the chaotic nature of VF have relied on peak-to-peak intervals [Witkowski et al., Phys. Rev. Lett. 1995;75(6):1230-3; Garfinkel et al., J. Clin. Investig. 1997;99(2):305-314; Hastings et al., Proc. Natl. Acad. Sci. USA 1996;93:10495-9], the frequency spectrum [Goldberger et al., 1986;19:282-289] or other derived measures [Kaplan and Cohen, Circ. Res. 1990;67:886-92], with results that demonstrate some characteristics of chaos. We have sought to determine whether VF is chaotic rather than random and whether the waveform can be described quantitatively using the tools of fractal geometry. We have constructed an attractor, measured the correlation dimensions, estimated the embedding dimension and measured Lyapunov exponents. When the digitized waveform is analyzed directly, VF exhibits nonrandom, chaotic behavior over a decade of sampling frequency. Within the scaling range we have estimated the Hurst exponent, and the self-similarity dimension of the VF waveform, supporting the presence of chaotic dynamics. Furthermore, these characteristics are measurable in a porcine model of VF under different recording conditions, and in VF recordings taken from human subjects immediately prior to defibrillation. Analyses of the Hurst exponents and self-similarity dimensions are correlated with the duration of VF, which may have clinical applications.

Animals↗

PubMed2000

Hypothermia differentially increases extracellular signal-regulated kinase and stress-activated protein kinase/c-Jun terminal kinase activation in the hippocampus during reperfusion after asphyxial cardiac arrest.

Mitogen-activated protein kinases are signal transduction mediators that have been implicated in cell survival and cell death. This study characterized the activation of pathways in the hippocampus during reperfusion after global cerebral ischemia, as well as the influence of a regimen of hypothermia that reduces ischemic cell death in the hippocampus. Circulatory arrest was induced in rats by 8 min of asphyxia. Relative levels of phosphorylated and total extracellular signal-regulated kinase, stress-activated protein kinase/c-Jun N-terminal kinase and p38 mitogen-activated protein kinase were measured in the hippocampus after 6, 12 or 24h of reperfusion using immunoblotting. Asphyxia induced a progressive increase in phosphorylated extracellular signal-regulated kinase and stress-activated protein kinase/c-Jun N-terminal kinase, but no change in phosphorylated p38 mitogen-activated protein kinase. Induction of mild hypothermia (33 degrees C) during reperfusion increased extracellular signal-regulated kinase phosphorylation and produced a smaller increase in stress-activated protein kinase/c-Jun N-terminal kinase phosphorylation at 24h. Hypothermia did not alter extracellular signal-regulated kinase activation in rats not subjected to ischemia. Extracellular signal-regulated kinase activation was associated with an increase in phosphorylation of the mitogen-activated protein kinase kinase 1/2, and was inhibited by administration of the specific mitogen-activated protein kinase kinase 1/2 inhibitor SL327. Immunohistochemical staining showed an increase in active extracellular signal-regulated kinase in the CA1, CA2, CA3 and dentate gyrus regions of the hippocampus after ischemia and reperfusion. In contrast, active stress-activated protein kinase/c-Jun N-terminal kinase immunoreactivity was most intense in the CA3 and dentate gyrus regions. These data demonstrate that both extracellular signal-regulated kinase and stress-activated protein kinase/c-Jun N-terminal kinase pathways are activated during the first 24h of reperfusion after global cerebral ischemia, and that hypothermia increases the activation of extracellular signal-regulated kinase relative to stress-activated protein kinase/c-Jun N-terminal kinase. Thus, an increase in extracellular signal-regulated kinase activation may be associated with improved neuronal survival after ischemic injury.

Animals↗

PubMed2000

Delayed, spontaneous hypothermia reduces neuronal damage after asphyxial cardiac arrest in rats.

OBJECTIVE: Core temperature is reduced spontaneously after asphyxial cardiac arrest in rats. To determine whether spontaneous hypothermia influences neurologic damage after asphyxial arrest, we compared neurologic outcome in rats permitted to develop spontaneous hypothermia vs. rats managed with controlled normothermia. INTERVENTIONS: Male Sprague-Dawley rats were asphyxiated for 8 mins and resuscitated. After extubation, a cohort of rats was managed with controlled normothermia (CN) by placement in a servo-controlled incubator set to maintain rectal temperature at 37.4 degrees C for 48 hrs. CN rats were compared with permissive hypothermia (PH) rats that were returned to an ambient temperature environment after extubation. Rats were killed at either 72 hrs (PH72hr, n = 14; CN72hr, n = 9) or 6 wks (PH6wk, n = 6, CN6wk, n = 6) after resuscitation. PH72 rats were historic controls for the CN72 rats, whereas PH6 and CN6 rats were randomized and studied contemporaneously. MEASUREMENTS: A clinical neurodeficit score (NDS) was determined daily. A pathologist blinded to group scored 40 hematoxylin and eosin -stained brain regions for damage by using a 5-point scale (0 = none, 5 = severe). Quantitative analysis of CA1 hippocampus injury was performed by counting normal-appearing neurons in a defined subsection of CA1. MAIN RESULTS: Mean rectal temperatures measured in the PH6wk rats (n = 6) were 36.9, 34.8, 35.5, 36.7, and 37.4 degrees C at 2, 8, 12, 24, and 36 hrs, respectively. Mortality rate (before termination) was lower in PH compared with CN (0/20 vs. 7/15; p < .005). PH demonstrated a more favorable progression of NDS (p = .04) and less weight loss (p < .005) compared with CN. Median histopathology scores were lower (less damage) in PH72hr vs. CN72hr for temporal cortex (0 vs. 2.5), parietal cortex (0 vs. 2), thalamus (0 vs. 3), CA1 hippocampus (1.5 vs. 4.5), CA2 hippocampus (0 vs. 3.5), subiculum (0 vs. 4), and cerebellar Purkinje cell layer (2 vs. 4) (all p < .05). There was almost complete loss of normal-appearing CA1 neurons in CN72hr rats (6 +/- 2 [mean +/- SD] normal neurons compared with 109 +/- 12 in naïve controls). In contrast, PH72hr rats demonstrated marked protection (97 +/- 23 normal-appearing neurons) that was still evident, although attenuated, at 6 wks (42 +/- 24 normal-appearing neurons, PH6wk). CONCLUSION: Rats resuscitated from asphyxial cardiac arrest develop delayed, mild to moderate, prolonged hypothermia that is neuroprotective.

Animals↗

PubMed2000

Hypothermia during reperfusion after asphyxial cardiac arrest improves functional recovery and selectively alters stress-induced protein expression.

This study examined whether prolonged hypothermia induced 1 hour after resuscitation from asphyxial cardiac arrest would improve neurologic outcome and alter levels of stress-related proteins in rats. Rats were resuscitated from 8 minutes of asphyxia resulting in cardiac arrest. Brain temperature was regulated after resuscitation in three groups: normothermia (36.8 degrees C x 24 hours), immediate hypothermia (33 degrees C x 24 hours, beginning immediately after resuscitation), and delayed hypothermia (33 degrees C x 24 hours, beginning 60 minutes after resuscitation). Mortality and neurobehavioral deficits were improved in immediate and delayed hypothermia rats relative to normothermia rats. Furthermore, both immediate and delayed hypothermia improved neuronal survival in the CA1 region of the hippocampus assessed at 14 days. In normothermia rats, the 70-kDa heat shock protein (Hsp70) and 40-kDa heat shock protein (Hsp40) were increased within 12 hours after resuscitation in the hippocampus. Delayed hypothermia attenuated the increase in Hsp70 levels in the hippocampus but did not affect Hsp70 induction in the cerebellum. Hippocampal expression of Hsp40 was not affected by hypothermia. These data indicate that prolonged hypothermia during later reperfusion improves neurologic outcome after experimental global ischemia and is associated with selective changes in the pattern of stress-induced protein expression.

Animals↗

PubMed2000

Scaling structure of electrocardiographic waveform during prolonged ventricular fibrillation in swine.

Ventricular fibrillation (VF) is the most common arrhythmia causing sudden cardiac death. However, the likelihood of successful defibrillation declines with increasing duration of VF. Because the morphology of the electrocardiogram (ECG) waveform during VF also changes with time, this study examined a new measure that describes the VF waveform and distinguishes between early and late VF. Surface ECG recordings were digitized at 200 samples/s from nine swine with induced VF. A new measure called the scaling exponent was calculated by examining the power-law relationship between the summation of amplitudes of a 1,024-point (5.12 second) waveform segment and the time scale of measurement. The scaling exponent is a local estimate of the fractal dimension of the ECG waveform. A consistent power-law relationship was observed for measurement time scales of 0.005-0.040 seconds. Calculation of the scaling exponent produced similar results between subjects, and distinguished early VF (< 4-minute duration) from late VF (> or = 4-minute duration). The scaling exponent was dependent on the order of the data, supporting the hypothesis that the surface ECG during VF is a deterministic rather than a random signal. The waveform of VF results from the interaction of multiple fronts of depolarization within the heart, and may be described using the tools of nonlinear dynamics. As a quantitative descriptor of waveform structure, the scaling exponent characterizes the time dependent organization of VF.

Animals↗

PubMed2000

Cardiac arrest and the role of thrombolytic agents.

Thrombolytic agents may have clinically significant beneficial effects in cardiac arrest. The application of thrombolytic drugs in the setting of current and antecedent cardiopulmonary resuscitation is well documented; however, it has not been systematically studied nor has it been widely considered. We provide a literature review of thrombolytic agents and cardiopulmonary resuscitation to discuss the need for randomized controlled trials and the possibility of benefits in acute resuscitation.

Cardiopulmonary Resuscitation↗

PubMed1999

Normoxic ventilation during resuscitation and outcome from asphyxial cardiac arrest in rats.

The formation of reactive oxygen species during reperfusion is one trigger for neuronal injury after global cerebral ischemia. Because formation of reactive oxygen species requires delivery of molecular oxygen to ischemic tissue, restricting inspired oxygen during reperfusion may decrease neurological damage. This study examined whether ventilation with room air rather than pure oxygen during resuscitation would improve neurological recovery after cardiac arrest in rats. Adult, male rats were subjected to 8 min of asphyxia resulting in cardiac arrest. During resuscitation, rats were ventilated either with hyperoxia (FiO2 = 1.0) or normoxia (FiO2 = 0.21, room air). Neurobehavioral deficits were scored daily for 72 h after resuscitation, after which brains were collected for histology. Normoxia decreased arterial oxygen content. Other physiological parameters and mortality did not differ between groups. All surviving rats exhibited behavioral and histological signs of brain damage. Neurological deficit scores did not differ between normoxia and hyperoxia conditions at any time point. The number of ischemic neurons in the hippocampus also did not differ between groups. These data indicate neither benefit nor detriment of reducing inspired oxygen concentration during resuscitation from asphyxial cardiac arrest in rats.

Air↗

PubMed1999

Geldanamycin provides posttreatment protection against glutamate-induced oxidative toxicity in a mouse hippocampal cell line.

The benzoquinoid ansamycin geldanamycin interferes with many cell signaling pathways and is currently being evaluated as an anticancer agent. The main intracellular target of geldanamycin is the 90-kDa heat shock protein, hsp90. In this report we demonstrate that geldanamycin is effective at preventing glutamate-induced oxidative toxicity in the HT22 mouse hippocampal cell line, even if given 4 h after glutamate treatment. Geldanamycin prevents glutamate-induced internucleosomal DNA cleavage in the HT22 cells but does not reverse the depletion of glutathione levels brought about by glutamate treatment. Both anabolic and catabolic effects are generated by geldanamycin treatment of HT22 cells, as evidenced by the induction of hsp70 expression and degradation of c-Raf-1 protein, respectively. Thus, geldanamycin may provide an effective strategy for manipulating signaling pathways in neuronal cells that use hsp90 as they proceed through a programmed cell death pathway in response to oxidative stress.

Animals↗

PubMed1999

Elements of a paracrine tubular renin-angiotensin system along the entire nephron.

The renin-angiotensin system is a major regulator of body sodium, predominantly through the actions of intrarenal angiotensin II of unclear origin. We show that polarized epithelium of the proximal tubule synthesizes and secretes angiotensinogen at its apical side and that the protein can be detected in urine as a function of dietary sodium. Furthermore, we demonstrate that renin is expressed and secreted in a restricted nephron segment, the connecting tubule, also in a sodium-dependent fashion. A paracrine renin-angiotensin system operating along the entire nephron may contribute to long-term arterial pressure regulation by integrating distant tubular sodium-reabsorbing functions.

Angiotensinogen↗

PubMed1998

Electron spin resonance measure of brain antioxidant activity during ischemia/reperfusion.

An electron spin resonance technique was used to measure cerebral antioxidant activity during asphyxial cardiac arrest and reperfusion. There were significant decreases in ascorbate (48%), glutathione (44%), total thiols (42%), protein thiols (38%) and alpha-tocopherol (26%) in the hippocampus 10 min after reperfusion (p < 0.05 vs respective baselines) but not during asphyxial cardiac arrest. The levels of antioxidants returned to baseline values by 120 min after reperfusion. The results support the hypothesis that reperfusion from asphyxial cardiac arrest, but not arrest alone, produced a significant oxidative stress as reflected by a depletion of both water and lipid soluble antioxidants. Furthermore, antioxidant depletion was transient, with normal antioxidant levels observed 120 min, 24 h and 72 h after reperfusion.

Analysis of Variance↗

PubMed1998

Noninvasive cerebral cooling in a swine model of cardiac arrest.

OBJECTIVE: Mild cerebral hypothermia improves neurologic outcome in animals resuscitated from cardiac arrest. This study examined whether one practical external cooling method, i.e., local application of ice to the heads and necks of swine, during resuscitation induces cerebral cooling. METHODS: Local external cerebral cooling was examined in a prospective laboratory investigation using 24 female swine in a model of cardiac arrest. The swine were randomized into hypothermia and normothermia groups. Intracerebral temperature was measured in the parietal cortex. Eight minutes after induction of ventricular fibrillation, chest compressions and mechanical ventilation were initiated. The hypothermia group was treated with 1,500 mL of ice in plastic bags applied to the head and neck, while the normothermia group received no extra interventions. Data were analyzed using repeated-measures ANOVA. RESULTS: In the normothermia group, there was no significant change in nasopharyngeal (-0.8 +/- 0.6 degree C), intracerebral (-0.6 +/- 0.8 degree C), or esophageal (-0.2 +/- 0.6 degree C) temperatures during 20 minutes of resuscitation. However, in the hypothermia group, application of ice during resuscitation significantly reduced nasopharyngeal (-2.9 +/- 1.4 degrees C), intracerebral (-2.1 +/- 0.6 degrees C), and esophageal (-1.4 +/- 0.8 degrees C) temperatures. CONCLUSIONS: External application of ice packs during resuscitation effectively reduced intracerebral temperatures in swine by an amount that improved neurologic outcomes in previous large animal studies. These data suggest that clinically significant cerebral cooling could be accomplished with a noninvasive, inexpensive, and universally available intervention. Further studies are required to assess the clinical feasibility and therapeutic efficacy of this intervention.

Analysis of Variance↗

PubMed1997

Dietary guidelines for Americans: an historical perspective.

Since 1980, Dietary Guidelines for Americans have been published jointly, every 5 years, by the U.S. Department of Agriculture (USDA) and the Department of Health and Human Services (DHHS). They benefit from the recommendations of a formally appointed Dietary Guidelines Advisory Committee. The Guidelines are an example of public health recommendations that are based upon published original research and analysis of that data by expert panels. The Guidelines are intended for healthy adults, so they might reduce their risks for certain diet-related chronic conditions. They are suggestions; they do not serve-and should not be used-as regulations. Greater individualization of dietary recommendations, for both major subgroups of the population and for individual patients, can improve our effectiveness in preventing and treating specific diet-related chronic conditions. To accomplish this objective, we need to move beyond the use of "indicators" (e.g., body mass index or blood cholesterol levels) as if they were "diagnostic," and focus on dietary and pharmacologic interventions (or, in some cases, no intervention) based on more specific diagnostic criteria (e.g., lipid patterns, fat distribution patterns, evidence of insulin resistance, and family history). Better targeting of dietary recommendations should improve their effectiveness, while reducing costs.

Diet↗