S-Ketamine Anesthesia Increases Cerebral Blood Flow in Excess of the Metabolic Needs in Humans

Background: Animal studies have demonstrated neuroprotective properties of S-ketamine, but its effects on cerebral blood flow (CBF), metabolic rate of oxygen (CMRO2), and glucose metabolic rate (GMR) have not been comprehensively studied in humans.

Methods: Positron emission tomography was used to quantify CBF and CMRO2 in eight healthy male volunteers awake and during S-ketamine infusion targeted to subanesthetic (150 ng/ml) and anesthetic (1,500-2,000 ng/ml) concentrations. In addition, subjects' GMRs were assessed awake and during anesthesia. Whole brain estimates for cerebral blood volume were obtained using kinetic modeling.

Results: The mean +/- SD serum S-ketamine concentration was 159 +/- 21 ng/ml at the subanesthetic and 1,959 +/- 442 ng/ml at the anesthetic levels. The total S-ketamine dose was 10.4 mg/kg. S-ketamine increased heart rate (maximally by 43.5%) and mean blood pressure (maximally by 27.0%) in a concentration-dependent manner (P = 0.001 for both). Subanesthetic S-ketamine increased whole brain CBF by 13.7% (P = 0.035). The greatest regional CBF increase was detected in the anterior cingulate (31.6%; P = 0.010). No changes were detected in CMRO2. Anesthetic S-ketamine increased whole brain CBF by 36.4% (P = 0.006) but had no effect on whole brain CMRO2 or GMR. Regionally, CBF was increased in nearly all brain structures studied (greatest increase in the insula 86.5%; P < 0.001), whereas CMRO2 increased only in the frontal cortex (by 15.7%; P = 0.007) and GMR increased only in the thalamus (by 11.7%; P = 0.010). Cerebral blood volume was increased by 51.9% (P = 0.011) during anesthesia.     

Knowledge expectations of patients on dialysis treatment

In order to be empowered in different situations related to dialysis care, patients need knowledge. This study describes the knowledge expectations of patients on dialysis treatment (n = 47) and selected background variables. The results indicated that patients expressed moderate knowledge expectations. Most important were the biophysiological, functional, and ethical dimensions of knowledge. The least important were the social and experiential dimensions of knowledge. Patients' age, employment status, dialysis modality, and length of dialysis were positively correlated with knowledge expectations.     

Heritability of low back pain and the role of disc degeneration

Twin studies suggest that both disc degeneration and back pain have a genetic component. We were interested in estimating the heritability of low back pain in men and examining whether genetic influences on back pain are mediated through genetic influences on disc degeneration. Thus, we conducted a classic twin study with multivariate quantitative genetic models to estimate the degree to which genetic (or environmental) effects on back pain were correlated with genetic (or environmental) effects on disc degeneration. Subjects included 147 monozygotic and 153 dizygotic male twin pairs (N=600 subjects) from the population-based Finnish Twin Cohort. All subjects underwent lumbar magnetic resonance imaging and completed an extensive interview, including back pain history and exposure to suspected risk factors. Disc height narrowing was the degenerative finding most associated with pain history, and was used to index disc degeneration in the models. Statistically significant genetic correlations were found for disc height narrowing and different definitions of back pain, such as duration of the worst back pain episode (r(g)=0.46) and hospitalization for back problems (r(g)=0.49), as well as disability in the previous year from back pain (r(g)=0.33). The heritability estimates for these back pain variables ranged from 30% to 46%. There also were statistically significant, but weaker, environmental correlations for disc height narrowing with back symptoms over the prior year. A substantial minority of the genetic influences on pain was due to the same genetic influences affecting disc degeneration. This suggests that disc degeneration is one pathway through which genes influence back pain.     

The role of genetics and environment in lifting force and isometric trunk extensor endurance

BACKGROUND AND PURPOSE: Our understanding of what different back performance tests are measuring is limited. The purpose of this study was to investigate the relative contributions of genetics and unique and common environmental factors for 3 tests of back muscle performance in a classic twin analysis. SUBJECTS: The subjects were a population-based sample of 122 monozygotic and 131 dizygotic male twin pairs aged 35 to 69 years (mean=49.9, SD=7.7). METHODS: Variance component analysis was applied to estimate genetic and environmental influences on isokinetic and psychophysical lifting and isometric trunk extensor endurance test performance. The Cholesky decomposition genetic factor model was used to estimate genetic and environmental correlations of these variables. Path analysis was applied to study determinants of isokinetic and psychophysical lifting and isometric trunk extensor endurance test performance. RESULTS: Genetic effects accounted for 60%, 33%, and 5% of the total variance of isokinetic and psychophysical lifting forces and isometric trunk extensor endurance, respectively, and unique environmental factors accounted for 35%, 49%, and 61% of the variance. DISCUSSION AND CONCLUSION: Genetics had a dominant role in isokinetic lifting and unique environmental factors in isometric trunk extensor endurance. The relatively high role of genetics in lifting force suggests the potential to increase and sustain changes in back muscle force in the general population may be particularly challenging.     

Novel spectral indexes of heart rate variability as predictors of sudden and non-sudden cardiac death after an acute myocardial infarction

BACKGROUND: Various indexes of 24-hour heart rate variability (HRV) have been able to predict all-cause mortality after an acute myocardial infarction (AMI), but their value in predicting specific modes of cardiac death has been limited. AIM: The aim of this study was to assess the role of two novel spectral indexes of HRV as predictors of either sudden (SCD) or non-sudden cardiac death after an AMI. Method. We used two novel methods of spectral analysis of HRV: 1) the high-frequency (HF) spectral component, V(index), calculated as an average HF power from the most linear portion of HF power versus the R-R interval regression curve, and 2) the prevalent low-frequency oscillation of heart rate (PLF). V(index), conventional HRV measures, and PLF were analyzed from 24-hour Holter recordings of 590 patients with a recent AMI. RESULTS: During the mean follow-up of 39+/-14 months, SCD occurred in 3% (n = 17) and non-sudden cardiac death in 5% (n = 28) of the patients. In univariate analysis, V(index) was the most potent predictor of SCD (RR: 6.0, 95% CI: 1.7-20.7, P<0.01), also remaining the most powerful predictor of SCD after adjustment for clinical variables and ejection fraction (RR: 4.2, 95% CI: 1.2-15.2, P<0.05). PLF was a potent predictor of non-sudden cardiac death (RR: 13.9, 95% CI: 5.9-32.5, P<0.001), but it did not predict SCD. CONCLUSIONS: Novel spectral HRV analysis methods, V(index) and PLF, provide significant information of the risk of the specific mode of death after an AMI.     

The roles of adulthood behavioural factors and familial influences in bone density among men

BACKGROUND: A primary strategy in osteoporosis prevention is advice on exercise, smoking, and calcium intake, although its practical value is unclear. AIM: To investigate the roles of such factors on bone density (BMD) after considering the influences of familial aggregation (combined effects of genetics and familial influences) in Finnish men 35-69 years old. METHODS: We selected 105 male monozygotic twin pairs, with discordance in suspected determinants. RESULTS: Dietary calcium was associated with BMD of the femoral neck; and body weight and lifetime frequency of endurance and ball game sport activities were associated with both femoral neck and lumbar BMD. Occupational loading and smoking were associated with neither. However, age and familial aggregation explained 73% of the variance of BMD in both the femoral neck and lumbar spine; calcium intake explained 1% in femoral neck and lifetime exercise 1% in lumbar spine. CONCLUSIONS: The effects of dietary calcium and physical activity that are not 'embedded' in the familial influences had very modest effects on the variance of BMD. Thus our chances of influencing BMD in later adulthood by targeting behavioural habits are likely to be limited. Interventions focused on childhood and the family unit may achieve more beneficial long-term results.     

Aging is associated with quantitative and qualitative changes in circulating cell-free DNA: the Vitality 90+ study

As a marker of cellular death, cell-free DNA (cf-DNA) has a utility in diagnosis and prognosis of various disorders. Since aging accompanies increased cellular senescence and death, we aimed to characterize potential age-related alterations in cf-DNA. The study population consisted of 12 nonagenarian women (participants in the Vitality 90+ Study) and 11 healthy control women (aged 22-37 years). Some of the nonagenarians (n=8) were also recruited for follow-up after one year. cf-DNA was extracted using two different methods. Total cf-DNA was quantified directly in plasma and the amplifiable cf-DNA was assessed using quantitative PCR. Quality of cf-DNA was analysed with a DNA Chip assay. For all the quantification methods, the concentration of cf-DNA was significantly higher (p<0.05) in nonagenarians as compared to controls. The quality of the cf-DNA also displayed a marked difference between nonagenarians and controls; a fragmented pattern or appearance of low molecular weight cf-DNA was observed in the majority of the nonagenarians, whereas in controls, cf-DNA was intact and had a quasi-genomic, high molecular weight appearance. In nonagenarians, the quality of cf-DNA appeared similar in the original and follow-up samples. We propose that some, as yet uncharacterized, aspects of aging are reflected in the appearance of cf-DNA.