Severity of intervertebral disc herniation regulates cytokine and chemokine levels in patients with chronic radicular back pain.

OBJECTIVE: The contributions of intervertebral disc disease and subject-specific covariates to systemic inflammation in low back pain are unknown. We examined the effects of symptomatic disc herniation (DH) and MRI herniation severity on serum cytokine levels in clinical subjects. DESIGN: Cytokine levels from lumbar DH subjects (N = 78) were compared to control subjects (N = 57) accounting for effects of DH, age, body mass index (BMI) and gender. Effect of DH severity on cytokine levels was analyzed on subsets of subjects with acute or chronic pain. Serum cytokines were also analyzed in a subset of patients between pre- and 3 months post-surgery. RESULTS: Cytokine levels were elevated in the serum of patients with symptomatic DH, and the covariates age, BMI and gender significantly contributed to levels of some cytokines. Severity of herniation was a significant contributor to pain intensity (VAS), serum levels of HMGB1, PDGFbb, and IL-9. The relationship between DH severity and cytokine levels was confirmed in subjects with chronic, but not acute symptoms. Serum levels of macrophage migration inhibitory factor (MIF) decreased, whereas levels of CCL3, CCL11, CXCL1, and CXCL10 were significantly elevated post surgery. CONCLUSIONS: This study is the first to show that DH severity is coordinately associated with changes in serum levels of inflammatory cytokines in chronic pain subjects. HMGB1, PDGFbb and IL-9 are novel mediators of increasing DH severity, indicative of cellular damage, neuro-inflammation and angiogenesis. Resolution of inflammation was observed with decrease in MIF post surgery. However, elevated chemokine levels indicate ongoing remodeling and wound healing at 3-month time point.

Childhood and later life stressors and increased inflammatory gene expression at older ages.

Adverse experiences in early life have the ability to "get under the skin" and affect future health. This study examined the relative influence of adversities during childhood and adulthood in accounting for individual differences in pro-inflammatory gene expression in late life. Using a pilot-sample from the Health and Retirement Study (N = 114) aged from 51 to 95, OLS regression models were run to determine the association between a composite score from three proinflammatory gene expression levels (PTGS2, ILIB, and IL8) and 1) childhood trauma, 2) childhood SES, 3) childhood health, 4) adult traumas, and 5) low SES in adulthood. Our results showed that only childhood trauma was found to be associated with increased inflammatory transcription in late life. Furthermore, examination of interaction effects showed that childhood trauma exacerbated the influence of low SES in adulthood on elevated levels of inflammatory gene expression-signifying that having low SES in adulthood was most damaging for persons who had experienced traumatic events during their childhood. Overall our study suggests that traumas experienced during childhood may alter the stress response, leading to more sensitive reactivity throughout the lifespan. As a result, individuals who experienced greater adversity in early life may be at higher risk of late life health outcomes, particularly if adulthood adversity related to SES persists.

Evidence of accelerated aging among African Americans and its implications for mortality.

Blacks experience morbidity and mortality earlier in the life course compared to whites. Such premature declines in health may be indicative of an acceleration of the aging process. The current study uses data on 7644 black and white participants, ages 30 and above, from the third National Health and Nutrition Examination Survey, to compare the biological ages of blacks and whites as indicated from a combination of ten biomarkers and to determine if such differences in biological age relative to chronological age account for racial disparities in mortality. At a specified chronological age, blacks are approximately 3 years older biologically than whites. Differences in biological age between blacks and whites appear to increase up until ages 60-65 and then decline, presumably due to mortality selection. Finally, differences in biological age were found to completely account for higher levels of all-cause, cardiovascular and cancer mortality among blacks. Overall, these results suggest that being black is associated with significantly higher biological age at a given chronological age and that this is a pathway to early death both overall and from the major age-related diseases.

The role of physiological markers of health in the association between demographic factors and periodontal disease.

BACKGROUND AND OBJECTIVE: Age is highly related to oral health status. The higher prevalence of oral disease within subgroups of the population may reflect a tendency towards "early aging" and dysregulation of multiple physiological systems. This study examines whether the association between periodontal disease and demographic factors is mediated by physiological measures of health. MATERIAL AND METHODS: Logistic regression was used to examine whether biomarkers and demographic factors, such as socio-economic status (SES) and race/ethnicity, were associated with periodontal disease, and then whether the strength of these relationships could be attributed to associations between demographic variables and physiological measures of systemic health. RESULTS: Periodontal disease was associated with measures of SES and race/ethnicity. Furthermore, 1-unit increases in cytomegalovirus (CMV), optical density, C-reactive protein (CRP) and glycated hemoglobin (HbA1c) were associated with a 25% [odds ratio (OR) = 1.25; 95% confidence interval (CI): 1.14-1.36], 13% (OR = 1.13; 95% CI = 1.03-1.24) and 19% (OR = 1.19; 95% CI = 1.12-1.27) increased likelihood of periodontal disease, respectively. However, when biomarkers and socio-demographic variables were both included in the model, their associations with periodontal disease were significantly reduced or eliminated. CONCLUSIONS: The risk of periodontal disease is higher among black and/or low-income individuals; however, these associations appear to be partly due to the greater probability of elevated levels of CRP, CMV or HbA1c among these groups.

Sarcopenic obesity and cognitive functioning: the mediating roles of insulin resistance and inflammation?

This study examined the influence of insulin resistance and inflammation on the association between body composition and cognitive performance in older adults, aged 60-69 and aged 70 and older. Subjects included 1127 adults from NHANES 1999-2002. Body composition was categorized based on measurements of muscle mass and waist circumference as sarcopenic nonobese, nonsarcopenic obese, sarcopenic obese, and normal. Using OLS regression models, our findings suggest body composition is not associated with cognitive functioning in adults ages 60-69; however, for adults aged 70 and over, sarcopenia and obesity, either independently or concurrently, were associated with worse cognitive functioning relative to non-sarcopenic non-obese older adults. Furthermore, insulin resistance accounted for a significant proportion of the relationship between cognitive performance and obesity, with or without sarcopenia. Additionally, although high CRP was significantly associated with poorer cognitive functioning in adults ages 60-69, it did not influence the association between body composition and cognitive performance. This study provides evidence that age-related physiological maladaptations, such as metabolic deregulation, which are associated with abdominal fat, may simultaneously contribute to lower cognition and muscle mass, reflecting a degradation of multiple physiological systems.

The effect of meals of varying nutritional composition on subjective and physiological markers of nausea in response to optokinetic motion.

BACKGROUND: Protein ingestion has been shown to decrease subjective and physiological markers of nausea. AIM: To elucidate the importance of drink palatability and nutritional composition in preventing subjective symptoms of nausea, decreased normal gastric electrogastrographic activity, and withdrawal of vagal tone in response to optokinetic motion. METHODS: Participants received a liquid high protein/low carbohydrate, moderate protein/high carbohydrate, low protein/high carbohydrate or water meal 30 min prior to exposure to an optokinetic drum. Subjective symptoms of nausea, electrogastrograms and cardiac vagal tone were measured during the 30-min post-drink rest period, a 10-min baseline period in the stationary drum, and during a 16-min drum rotation period. RESULTS: Regardless of nutritional composition, a pleasant taste predicted a reduction of the subjective experience of nausea. Subjective symptoms were significantly more severe in the moderate protein/high carbohydrate and water groups compared to the high protein/low carbohydrate and low protein/high carbohydrate groups. Electrogastrographic indicators of nausea were reduced in the high protein/low carbohydrate and low protein/high carbohydrate groups versus water, while cardiac vagal tone was reduced in the high protein/low carbohydrate and moderate protein/high carbohydrate groups versus the low protein/high carbohydrate and water groups. CONCLUSIONS: Palatability and high protein meals appear to be important factors in attenuating the nausea associated with exposure to optokinetic motion.

Protein-predominant meals inhibit the development of gastric tachyarrhythmia, nausea and the symptoms of motion sickness.

BACKGROUND: Meal ingestion has been suggested to reduce susceptibility to the development of gastric tachyarrhythmia, the abnormal activity of the stomach that frequently accompanies nausea. AIM: To determine the types of meal that are most effective in preventing the development of gastric tachyarrhythmia, nausea and the symptoms of motion sickness provoked by a rotating optokinetic drum. METHOD: Participants received a carbohydrate beverage, a protein-predominant beverage or nothing immediately before exposure to the rotating drum. Subjective symptoms of motion sickness and electrogastrograms were collected during a 6-min baseline period and a subsequent 16-min drum rotation period. RESULTS: Subjective symptoms of motion sickness scores were significantly more severe during the no-meal condition than during either the protein or carbohydrate condition. Central, peripheral and, to some extent, gastrointestinal symptoms were more severe during the carbohydrate condition than during the protein condition. Gastric tachyarrhythmia increased significantly less from baseline to drum rotation during both the protein and carbohydrate conditions than during the no-meal condition. CONCLUSIONS: Liquid protein-predominant meals were most effective in suppressing both the development of gastric tachyarrhythmia and the entire spectrum of motion sickness symptoms, including nausea.

The stomach's response to unappetizing food: cephalic-vagal effects on gastric myoelectric activity.

The aim of this investigation was to determine the effects of sham feeding food that was perceived as unappetizing on the cephalic-vagal reflex as measured by changes in gastric myoelectric activity. Thirty-eight healthy human participants experienced one of two conditions: (i) an appetizing sham feeding condition in which participants chewed and expectorated two cooked frankfurters, and (ii) an unappetizing sham-feeding condition in which participants chewed and expectorated two cold tofu frankfurters. All participants were asked to chew each mouth-full of food 6-7 times and to be very careful not to swallow any of the food. Electrogastrograms (EGGs) were recorded for 10 min prior to, during, and for 15 min after sham feeding. A questionnaire was given to each participant after the procedure as a manipulation check and to assess food palatability. Results from the questionnaire showed, as expected, that the cooked frankfurters were significantly more appetizing than the cold tofu frankfurters (P < 0.01). In the group sham fed appetizing food, 3 cycles per minute (cpm) power increased during sham feeding, but the change was not significant; however, 3 cpm power decreased in the group sham fed unappetizing food. This difference was significant (P < 0.05). In conclusion, we have demonstrated that the cephalic-vagal reflex, as measured by power in the 3 cpm frequency region of the EGG, is sensitive to the subjective palatability of the food.

A questionnaire for the assessment of the multiple dimensions of motion sickness.

BACKGROUND: A limited number of attempts have been made to develop a questionnaire that assesses the experience of motion sickness. Further, many available questionnaires quantify motion sickness as a unidimensional construct. METHOD: Exploratory and confirmatory factor analyses of motion sickness descriptors were used to derive and verify four dimensions of motion sickness, which were defined as gastrointestinal, central, peripheral, and sopite-related. These dimensions of motion sickness were then used to construct a motion sickness assessment questionnaire (MSAQ) that was administered to individuals who were exposed to a rotating optokinetic drum. RESULTS: Total scores from the MSAQ correlated strongly with overall scores from the Pensacola Diagnostic Index (r = 0.81, p < 0.001) and the Nausea Profile (r = 0.92, p < 0.001). CONCLUSIONS: The MSAQ is a valid instrument for the assessment of motion sickness. In addition, the MSAQ may be used to assess motion sickness as a multidimensional rather than unidimensional construct.

The effects of serotonin (5-HT3) receptor antagonists on gastric tachyarrhythmia and the symptoms of motion sickness.

BACKGROUND: The purpose of this study was to determine the effects of the serotonin (5-HT3) receptor-antagonist antiemetics ondansetron and granisetron on the development of gastric tachyarrhythmia, nausea, and other symptoms of motion sickness. METHODS: In a double-blind, counterbalanced, repeated measures design, 12 motion sickness susceptible college students participated in 3 sessions with an intersession interval of 1 wk. Participants received either 8 mg of ondansetron, 2 mg of granisetron, or placebo 1 h before exposure to a rotating optokinetic drum. Electrogastrograms (EGGs) were recorded during a 6-min baseline period and a subsequent 16-min drum rotation period. Subjective symptoms of motion sickness (SSMS) were obtained every 3 min during drum rotation. RESULTS: During drum rotation, gastric tachyarrhythmia increased significantly more during the placebo condition than during either of the serotonin (5-HT3) receptor antagonist conditions. However, maximum SSMS scores were not different among conditions. CONCLUSIONS: The serotonin (5-HT3) receptor antagonists inhibited the development of tachyarrhythmia, but did not prevent the development of nausea and other symptoms of motion sickness. The antiemetics ondansetron and granisetron may act as gastric anti-dysrhythmics, but their ability to arrest the development of gastric tachyarrhythmia was not sufficient for the prevention of nausea.

Alcoholic typology and season of birth.

OBJECTIVE: This study analyzed the half years of birth of a large (n = 113,276) population of alcoholic patients in the U.S. Army Alcohol and Drug Abuse Prevention and Control Program from 1986 through 1990. METHOD: Subjects were enrolled for treatment of alcoholism or alcohol-related problems, and were analyzed for half year of birth. Groupings by age and gender, consistent with current theories of alcoholic typology, were compared, by means of chi-square tests, and by comparisons of two rates or proportions. RESULTS: The 17-21 year old and the 22-39 year old age groups differed by 5.1% in regard to half year of birth (chi-square = 260.317, p < 0.001, 95% CI:4.481 to 5.725, odds ratio: 1.23). Both groups differed significantly from the normal circannual birth pattern, but in opposite directions. CONCLUSIONS: The findings support the differentiation of types of alcoholics by age, which is a characteristic of Cloninger's classification, suggesting a biological, pre-natal factor.

Seasonal variation of the amino acid, L-tryptophan, in interior Alaska.

The seasonal pattern of L-tryptophan was studied in a Fairbanks, Alaska, population that was unadapted to the extreme light variations of the North. Previously, this population was shown to exhibit seasonal behavior effects such as increases in fatigue and sleep duration, as well as endocrine effects such as increases in melatonin levels and phase shifting. Caloric and macronutrient intake have been reported to vary seasonally in humans, thereby potentially influencing the plasma levels of L-tryptophan, which is a precursor of serotonin and melatonin. Plasma levels of L-tryptophan from volunteers, whose average duration of stay in Alaska was eight months, were determined by automated amino acid analysis. Prominent results included finding increased levels in the winter at several different diurnal time points. These findings support hypotheses which relate underlying physiological adaptations to the North to the increased incidence of behavioral disorders such as depression and alcoholism.

Seasonal symptoms in the sub-Arctic.

To obtain information regarding the frequency and severity of seasonal symptoms in the sub-Arctic, 361 Seasonal Pattern Assessment Questionnaires (SPAQ) were collected from four separate populations, all either assigned to Fort Wainwright, in Interior Alaska, or receiving treatment there. The study included both civilian and military personnel, of both genders, over 16 years of age. The mean score on the SPAQ was in the low end of the range of sub-syndromal seasonal affective disorder. Females scored significantly higher than males, the mean score approaching that found in seasonal affective disorder. Active duty females scored higher than civilians, and were found to have symptoms severe enough to qualify as true seasonal affective disorder in 10.9% of cases. The highest scores and highest rates of true seasonal affective disorder were found in a group of 25 Medical Activity (MEDDAC) female non-commissioned officers who were not in patient status.

The rhetoric of nursing theory.

Skeptics who question the validity and relevance of nursing theory in the nursing curriculum demonstrate the failure to persuade nurses of the importance of theory. Attempts to justify theory by forcing its use in contexts where it barely fits have contributed to the increasing disenchantment. But however misused and misunderstood, theory is nevertheless a lasting and essential part of nursing knowledge. Theory is the intellectual life of nursing. To further research, experiment, and insight in nursing as a discipline, theorizing must be encouraged--subject as all intellectual efforts must be--to honest critique and a healthy willingness to acknowledge success or failure.

Diurnal and seasonal rhythms of melatonin, cortisol and testosterone in interior Alaska.

The diurnal variations in the secretory patterns of melatonin, cortisol and testosterone were studied in a Fairbanks, Alaska population who were unadapted to the extreme light variations of the North. Statistically significant variations in hormonal levels were found in both diurnal and seasonal rhythms. Prominent findings included unusually high levels of cortisol at 0200 and 0800 in the fall and elevated daytime levels (1030) of melatonin in the winter. These results indicate a delayed phase secretory pattern when compared to the normal pattern at lower latitudes. These findings imply possible underlying physiological causes for the high incidence of behavior disorders such as depression and alcoholism in Alaska and circumpolar environments in general.

Ration or rescue: the elderly patient in critical care.

1. Persons who require the intensive interventions of critical care units enter with a contract of trust. They place their well-being, and often their lives in the hand of caregivers. To respect that trust by the most vigorous effort is a moral responsibility. 2. It is not the task of the practitioner in critical care to evaluate the social worth of the patient. Judgments as to the quality of life of individual patients are inappropriate and unsupportable and should never be used as a rationale for withholding or withdrawing essential care. 3. The decisions for introducing treatments should be based (as they have been historically) on the physician's evaluation of the patient's condition and the consequent appropriate interventions. The interference of third party payers in this clinical relation in which therapeutic decisions are dictated by cost or any other extraneous factors is morally repugnant. 4. Life or death decisions are not properly those of caregivers and should never be left to those whose mission is to protect life and relieve suffering. Decisions to use extraordinary means of sustaining life processes should be made in advance of the actual events by the informed wisdom of the physician whenever possible. The caregivers--physicians and nurses-should bring all their skills to bear to alleviate suffering, but that does not include hastening the death of another human being.