Impaired increase of retinal capillary blood flow to flicker light exposure in arterial hypertension

We hypothesized that the increase of retinal capillary blood flow (RCF) to flicker light exposure is impaired in subjects with arterial hypertension. In 146 nondiabetic untreated male subjects with (n=50) or without (n=96) arterial hypertension, RCF was measured before and after flicker light exposure noninvasively and in vivo using scanning laser Doppler flowmetry. In addition, in a subgroup of 28 subjects, the change of RCF to flicker light exposure was again assessed during parallel infusion of nitric oxide synthase inhibitor N-monomethyl-l-arginine (L-NMMA). The increase of RCF to flicker light exposure was lower in patients with untreated hypertension compared with normotensive subjects when expressed in absolute terms (7.69±54 versus 27.2±44 AU; P adjusted=0.013) or percent changes (2.95±14 versus 8.33±12%; P adjusted=0.023). Systolic (β=-0.216; P=0.023) but not diastolic blood pressure (β=-0.117; P=0.243) or mean arterial pressure (β=-0.178; P=0.073) was negatively related to the percent change of RCF to flicker light exposure, independently of other cardiovascular risk factors. In the subgroup of 28 subjects, the increase of RCF to flicker light exposure was similar at baseline and during parallel infusion of L-NMMA when expressed in absolute terms (20.0±51 versus 22.6±56 AU; P=0.731) or percent changes (7.12±16 versus 8.29±18%; P=0.607). The increase of RCF to flicker light exposure is impaired in arterial hypertension. In the subgroup of the total study cohort, nitric oxide was not a major determinant of the increase of RCF to flicker light exposure.     

Oxytocin Reduces Reward-Driven Food Intake in Humans

Experiments in animals suggest that the neuropeptide oxytocin acts as an anorexigenic signal in the central nervous control of food intake. In humans, however, research has almost exclusively focused on the involvement of oxytocin in the regulation of social behavior. We investigated the effect of intranasal oxytocin on ingestion and metabolic function in healthy men. Food intake in the fasted state was examined 45 min after neuropeptide administration, followed by the assessment of olfaction and reward-driven snack intake in the absence of hunger. Energy expenditure was registered by indirect calorimetry, and blood was repeatedly sampled to determine concentrations of blood glucose and hormones. Oxytocin markedly reduced snack consumption, restraining, in particular, the intake of chocolate cookies by 25%. Oxytocin, moreover, attenuated basal and postprandial levels of adrenocorticotropic hormone and cortisol and curbed the meal-related rise in plasma glucose. Energy expenditure and hunger-driven food intake as well as olfactory function were not affected. Our results indicate that oxytocin, beyond its role in social bonding, regulates nonhomeostatic, reward-related energy intake, hypothalamic-pituitary-adrenal axis activity, and the glucoregulatory response to food intake in humans. These effects can be assumed to converge with the psychosocial function of oxytocin and imply possible applications in the treatment of metabolic disorders.The hypothalamic nonapeptide oxytocin is released into the circulation by axonal terminals in the posterior pituitary and, moreover, acts directly on central nervous receptors. Oxytocin, which has been highly preserved during mammalian evolution, regulates physiological functions related to reproduction and mother-infant interaction, such as lactation, and in recent years, has been shown to modulate affiliative behavior (1). Research in humans has almost exclusively focused on the role of oxytocin in the regulation of prosocial behavior, including trust, attachment, and sexual behavior (2–5), largely ignoring potential effects of the neuropeptide on ingestive behavior and metabolism. In fact, evidence from rodent studies indicates that the neuropeptide acts as a strong inhibitor of food intake and affects energy expenditure and glucose homeostasis (6–9). Oxytocinergic neurons in the hypothalamic paraventricular nucleus are assumed to mediate the food intake–limiting effect of leptin, an adipokine that provides the brain with negative feedback on body fat stores and sensitizes caudal brainstem nuclei to satiety factors such as cholecystokinin (10). Hypothalamic oxytocin signaling, moreover, mediates anorexigenic effects of the satiety factor nesfatin-1 in a leptin-independent manner (11). Importantly, oxytocin reduces food intake not only in normal-weight rodents but also in animals with diet-induced obesity (8,12,13), so oxytocinergic pathways might be a promising target of clinical interventions in obese patients.The direct manipulation of neuropeptidergic central nervous signaling pathways can be achieved via the intranasal administration of peptides, which is known to bypass the blood–brain barrier and result in significant cerebrospinal fluid elevations in substance levels within 40 min, without the need for systemic infusion (14,15). This approach has been validated, among others, for vasopressin, a close homolog of oxytocin (14), and intranasal oxytocin administration has been shown to reliably modulate neuropsychological functions in a series of studies (2–5) in the absence of relevant side effects (16). Surprisingly, however, the effect of intranasal oxytocin on energy metabolism, including ingestive behavior, has not been investigated in humans so far. The assessment of respective effects of intravenous oxytocin (17) is hampered because peripheral oxytocin is not readily transported across the blood–brain barrier (18).In the present experiments, we studied the contribution of oxytocin signaling to the control of ingestive behavior and energy expenditure in normal-weight, healthy men, with a particular view to endocrine regulators of metabolism, such as ghrelin and insulin, as well as hypothalamic-pituitary-adrenal (HPA) axis secretory activity. Ingestive behavior is not only regulated homeostatically (i.e., by central nervous pathways that respond to energy depletion) but also by nonhomeostatic brain circuits that process the reward-related, “hedonic” qualities of food intake (19). Therefore, we applied a twofold assessment of food intake that relied, on the one hand, on a large breakfast buffet after an overnight fast to investigate homeostatic, primarily hunger-driven energy intake (20–22), and on the other hand, on a collection of snacks of varying palatability offered after breakfast intake for the measurement of reward-driven food intake (22–24).     

Comparison of two noninvasive devices for measurement of central systolic blood pressure with invasive measurement during cardiac catheterization

J Clin Hypertens (Greenwich). 2012; 14:575–579. © 2012 Wiley Periodicals, Inc. Recently, a new device for noninvasive assessment of central systolic blood pressure (cSBP) (BPro device with A‐Pulse) was approved by the US Food and Drug Administration, but available data are limited. In 52 patients undergoing invasive elective cardiac evaluation, central hemodynamics were measured invasively. Immediately thereafter, radial artery waveforms were sampled by two noninvasive techniques, the BPro and, as a comparator, the SphygmoCor System. Then, central hemodynamics were measured invasively for a second time. The invasively recorded cSBP (137±27 mm Hg) did not differ with both noninvasively assessed cSBP by BPro (136±21 mm Hg, P=.627 vs invasive cSBP) and by SphygmoCor (136 ± 23 mm Hg, P=.694 vs invasive cSBP) and correlated highly between invasively recorded and both noninvasively assessed cSBP. However, using Bland‐Altman plots, spreading of compared data of both devices can be found (BPro: 0.87±13 mm Hg vs invasive cSBP; SphygmoCor: 0.77±14 mm Hg vs invasive cSBP). There was an excellent correlation of both noninvasive devices for the calculation of cSBP (r=0.961, P<.001). cSBP differed by only 0.1±6 mm Hg (P=.913) between the two noninvasive devices. Therefore, both noninvasive devices showed an accurate agreement in cSBP compared with invasively measured cSBP.     

Accuracy of ICD-9 codes to identify nonunion and malunion and developing algorithms to improve case-finding of nonunion and malunion

ObjectiveTo evaluate the accuracy of using ICD-9 codes to identify nonunions (NU) and malunions (MU) among adults with a prior fracture code and to explore case-finding algorithms.Study designMedical chart review of potential NU (N = 300) and MU (N = 288) cases. True NU cases had evidence of NU and no evidence of MU in the chart (and vice versa for MUs) or were confirmed by the study clinician. Positive predictive values (PPV) were calculated for ICD-9 codes. Case-finding algorithms were developed by a classification and regression tree analysis using additional automated data, and these algorithms were compared to true case status.SettingGroup Health Cooperative.ResultsCompared to true cases as determined from chart review, the PPV of ICD-9 codes for NU and MU were 89% (95% CI, 85–92%) and 47% (95% CI, 41–53%), respectively. A higher proportion of true cases (NU: 95%; 95% CI, 90–98%; MU: 56%; 95% CI, 47–66%) were found among subjects with 1 + additional codes occurring in the 12 months following the initial code. There was no case-finding algorithm for NU developed given the high PPV of ICD-9 codes. For MU, the best case-finding algorithm classified people as an MU case if they had a fracture in the forearm, hand, or skull and had no visit with an NU diagnosis code in the 12-month post MU diagnosis. PPV for this MU case-finding algorithm increased to 84%.ConclusionsIdentifying NUs with its ICD-9 code is reasonable. Identifying MUs with automated data can be improved by using a case-finding algorithm that uses additional information. Further validation of the MU algorithms in different populations is needed, as well as exploration of its performance in a larger sample.     

Penumbra around chronic cerebral infarction?

In a series of 13 patients with cerebrovascular occlusive disease regional cerebral blood flow (rCBF) measurements (two-dimensional intravenous ¹³³Xe clearance method) and quantitative EEG analysis (sensorimotor rhythms) as well as electronic measurement of handforce were performed before and during intravenous infusion of 1 μg kg/min of one of the lipophilic dihydropyridine calcium channel blocker nimodipine (Nimotop®). The aim of the study was to test the hypothesis of the existence of hypoperfusion (ischaemic penumbra) in the surroundings of chronic cerebral infarcts. All 3 parameters improved in one patient. Sensorimotor rhythms increased in 5 patients, rCBF in 3. EEG and rCBF improved in 2 patients. In 3 instances, a redistribution of rCBF in favour of the peri-infarct zone was noted (significant increase of rCBF from 35 ± 2 sem to 53 ± 4 ml/100 g/min (p > 0.01), whereas rCBF fell from 61 ± 5 to 46 ±2 ml/100 g/min on a collimator remote from the infarct but in the infarcted hemisphere. The parallel improvement of rCBF and EEG in brain regions surrounding chronic infarcts in 3 patients was interpreted as functional improvement as a consequence of nimodipine-induced normalization of peri-infarct hypoperfusion, i.e. reversal of flow-dependent neuronal silence and/or dysfunction.