Inflammatory markers in primary aldosteronism.

Primary aldosteronism (PA) is the most common cause of endocrine hypertension with a high frequency of cardiovascular complications. The unfavorable cardiometabolic profile may be due to aldosterone-mediated activation of inflammatory cells, circulatory cytokines and activation of collagen synthesis in the vessel wall. Aim of our study was to evaluate differences in the levels of hsCRP, IL-6, TNF-alpha and N-terminal propeptide of collagen I (PINP) in patients with PA and essential hypertension (EH) as a control group, and between the subtypes of PA (aldosterone producing adenoma - APA, idiopathic hyperaldosteronism - IHA). We studied 28 patients with PA (IHA - 10 patients, APA - 12 patients, 6 unclassified) and 28 matched patients with EH. There were no differences in the levels of inflammatory markers between the followed groups [EH vs. PA: TNF-alpha (5.09 [3.68-6.32] vs. 4.84 [3.62-6.50] pg/ml), IL-6 (0.94 [0.70-1.13] vs. 0.97 [0.71-1.28] pg/ml), hsCRP (0.53 [0.25-1.54] vs. 0.37 [0.31-0.61] mg/l), leukocytes (6.35+/-1.42 vs. 5.97+/-1.29 10(9) l); APA vs. IHA: TNF-alpha (4.54 [3.62-7.03] vs. 5.19 [4.23-5.27] pg/ml), IL-6 (0.96 [0.63-1.21] vs. 0.90 [0.65-1.06] pg/ml), hsCRP (0.34 [0.29-0.47] vs. 0.75 [0.36-1.11] mg/l), leukocytes (6.37+/-1.41 vs. 5.71+/-1.21 10(9) l)]. Significant differences in the levels of PINP between PA and EH group were observed (35.18 [28.46-41.16] vs. 45.21 [36.95-62.81] microg/l, p

Combination antihypertensive therapy in clinical practice. The analysis of 1254 consecutive patients with uncontrolled hypertension.

The aim of the study was to analyze the clinical use of different types of combination therapy in a large sample of consecutive patients with uncontrolled hypertension referred to Hypertension Centre. We performed a retrospective analysis of combination antihypertensive therapy in 1254 consecutive patients with uncontrolled hypertension receiving at least triple-combination antihypertensive therapy. Among the most prescribed antihypertensive classes were renin-angiotensin blockers (96.8%), calcium channel blockers (82.5%), diuretics (82.0%), beta-blockers (73.0%), centrally acting drugs (56.0%) and urapidil (24.1%). Least prescribed were spironolactone (22.2%) and alpha-1-blockers (17.1%). Thiazide/thiazide-like diuretics were underdosed in more than two-thirds of patients. Furosemide was prescribed in 14.3% of patients treated with diuretics, while only indicated in 3.9%. Inappropriate combination therapy was found in 40.4% of patients. Controversial dual and higher blockade of renin-angiotensin system occurred in 25.2%. Incorrect use of a combination of two antihypertensive drugs with the similar mechanism of action was found in 28.1%, most commonly a combination of two drugs with central mechanism (13.5%). In conclusion, use of controversial or incorrect combinations of drugs in uncontrolled hypertension is common. Diuretics are frequently underdosed and spironolactone remains neglected in general practice. The improper combination of antihypertensive drugs may contribute to uncontrolled hypertension.

Biochemical Testing After Pheochromocytoma Removal: How Early?

Pheochromocytomas are catecholamine-producing tumors with typical clinical presentation. Tumor resection is considered as an appropriate treatment strategy. Due to its unpredictable clinical behavior, biochemical testing is mandatory to confirm the success of tumor removal after surgery. The aim of the study was to investigate the feasibility of a shorter interval of postoperative testing (earlier than the recommended 2-4 weeks according to recently published Guidelines). We investigated 81 patients with pheochromocytoma before and after surgery. Postoperative examination was performed of stable subjects after their transport from the surgical to the internal ward (7.1±2.2 days after surgery). Plasma metanephrines were used for the diagnosis of pheochromocytoma and confirmation of successful tumor removal. All subjects with pheochromocytoma had markedly elevated plasma metanephrines before surgery. No correlation between postoperative interval (the shortest being 3 days) and plasma metanephrine levels was found. Postoperative plasma metanephrine levels did not differ significantly from those taken at the one-year follow-up. In conclusion, we have shown that early postoperative diagnostic workup of subjects with pheochromocytoma is possible and may thus simplify early postoperative management of this clinical condition.

The precuneus and visuospatial attention in near and far space: a transcranial magnetic stimulation study.

BACKGROUND: There is a large body of evidence for the involvement of the parietal cortex in orientation and navigation in space. This has been supplemented by investigation of the contribution of a number of subregions using transcranial magnetic stimulation. OBJECTIVE: The role of the precuneus area, located in the medial plane of posterior parietal cortex (PPC), in visuospatial functions is not well understood. We investigated the contribution of this area using the landmark task. METHODS: Participants were asked to make forced-choice judgments of which side of prebisected line was longer for near and far viewing conditions (70 and 180 cm, respectively). Online 10 Hz, repetitive transcranial magnetic stimulation (rTMS) was delivered for 500 ms over the right precuneus, rPPC and vertex (control), in separate blocks of trials. The rPPC stimulation was used as a positive control, having previously resulted in "neglect like" spatial bias effects in a number of studies. RESULTS: A no-TMS condition showed a leftward spatial bias (pseudoneglect) for near space judgments but not for far space and was used as the baseline. Precuneus stimulation resulted in rightward spatial bias from the midpoint in near space similar to the rPPC neglect-like effect. No significant effects were seen with vertex stimulation. CONCLUSION: This study shows that precuneus, like other parietal areas, is involved in visuospatial functions. Further work is required to clarify how the contribution of this area differs from other parietal regions.

Importance of thorough investigation of resistant hypertension before renal denervation: should compliance to treatment be evaluated systematically?

Catheter-based renal denervation (RD) has been introduced recently as a potentially effective invasive treatment of refractory hypertension. The proportion of patients with severe hypertension suitable for RD is not clear. The aim of this study was to identify what percentage of patients has truly resistant essential hypertension and are thus potentially eligible for RD. We investigated 205 consecutive patients referred to a university hypertension center for severe hypertension within 12 months. Ambulatory 24-h blood pressure (BP) monitoring (24 h ABPM), secondary hypertension screening and compliance to treatment testing (by use of plasma drug level measurements) were performed in all patients. Fifty-seven patients (27.8%) did not have truly resistant hypertension (RH) based on clinical BP. Among the remaining 122 patients (59.5%) with RH confirmed by 24 h ABPM, 50 patients (24.4% of the original cohort) had a secondary cause of hypertension and in 27 (13.2%) non-compliance to treatment was confirmed. Thus, only 45 patients (22%) had truly resistant essential hypertension and were considered for RD. Only one-third (n=15, 7.3% of the original cohort) was, however, finally referred for RD (14 were excluded due to contraindications for RD and 16 refused the invasive treatment). In conclusion, thorough examination of severe hypertension including 24 h ABPM, secondary hypertension exclusion and drug compliance testing before considering RD reveals that majority of these patients are not suitable for RD. Specifically, compliance to treatment testing should be mandatory in order to identify eligible candidates for RD.

Motor empathy is a consequence of misattribution of sensory information in observers.

Human behavior depends crucially on the ability to interact with others and empathy has a critical role in enabling this to occur effectively. This can be an unconscious process and based on natural instinct and inner imitation (Montag et al., 2008) responding to observed and executed actions (Newman-Norlund et al., 2007). Motor empathy relating to painful stimuli is argued to occur via the mirror system in motor areas (Rizzolatti and Luppino, 2001). Here we investigated the effects of the location of emotional information on the responses of this system. Motor evoked potential (MEP) amplitudes from the right first dorsal interosseus (FDI) muscle in the hand elicited by single pulses of transcranial magnetic stimulation (TMS) delivered over the left motor cortex were measured while participants observed a video of a needle entering a hand over the FDI muscle, representing a painful experience for others. To maintain subjects' internal representation across different viewing distances, we used the same size of hand stimuli both in peripersonal and extrapersonal space. We found a reduced MEP response, indicative of inhibition of the corticospinal system, only for stimuli presented in peripersonal space and not in extrapersonal space. This empathy response only occurring for near space stimuli suggests that it may be a consequence of misidentification of sensory information as being directly related to the observer. A follow up experiment confirmed that the effect was not a consequence of the size of the stimuli presented, in agreement with the importance of the near space/far space boundary for misattribution of body related information. This is consistent with the idea that empathy is, at least partially, a consequence of misattribution of perceptual information relating to another to the observer and that pain perception is modulated by the nature of perception of the pain.

The potential of transcranial magnetic stimulation for population-based application: a region-based illustrated brief overview.

The awareness of the global trends in neuroscience study, especially in the cognitive neuroscience field, should be increased. One notable approach is the use of transcranial magnetic stimulation (TMS) not only as a research tool but also as a choice for treatment and rehabilitation in neurological disorders, such as post-stroke hemiplegia, visuospatial neglect syndrome, Alzheimer's disease (AD) and psychiatric conditions such as major depression and schizophrenia. All of these occur in significant numbers in highly populated regions. This paper briefly discusses the basic protocols and potential benefits of using TMS with the aim of providing insight that is useful in the design of future public health strategies in highly populated regions with a large neurocognitive burden of disease where this technique is currently underemployed.

Far-space neglect in conjunction but not feature search following transcranial magnetic stimulation over right posterior parietal cortex.

Near- and far-space coding in the human brain is a dynamic process. Areas in dorsal, as well as ventral visual association cortex, including right posterior parietal cortex (rPPC), right frontal eye field (rFEF), and right ventral occipital cortex (rVO), have been shown to be important in visuospatial processing, but the involvement of these areas when the information is in near or far space remains unclear. There is a need for investigations of these representations to help explain the pathophysiology of hemispatial neglect, and the role of near and far space is crucial to this. We used a conjunction visual search task using an elliptical array to investigate the effects of transcranial magnetic stimulation delivered over rFEF, rPPC, and rVO on the processing of targets in near and far space and at a range of horizontal eccentricities. As in previous studies, we found that rVO was involved in far-space search, and rFEF was involved regardless of the distance to the array. It was found that rPPC was involved in search only in far space, with a neglect-like effect when the target was located in the most eccentric locations. No effects were seen for any site for a feature search task. As the search arrays had higher predictability with respect to target location than is often the case, these data may form a basis for clarifying both the role of PPC in visual search and its contribution to neglect, as well as the importance of near and far space in these.

Peripheral arterial stiffness in primary aldosteronism.

Aldosterone overproduction increases arterial wall stiffness by accumulation of different types of collagen fibres and growth factors. Our previous studies showed that central (aortic) arterial stiffness is increased in primary aldosteronism (PA) independently of concomitant hypertension and that these changes might be reversible after successful adrenalectomy. There is limited data available on the potential impact of mineralocorticoid overproduction on the deterioration of peripheral arterial stiffness. The current study was thus aimed at investigating the effect of aldosterone overproduction on peripheral arterial stiffness assessed by peripheral (femoral-ankle) pulse wave velocity (PWV) in PA patients compared with essential hypertension (EH) patients. Forty-nine patients with confirmed PA and 49 patients with EH were matched for age, blood pressure, body mass index, lipid profile, and fasting glucose. PWV was obtained using the Sphygmocor applanation tonometer. Both peripheral and central PWV were significantly higher in PA patients compared to EH patients, while clinical blood pressures were similar. Plasma aldosterone level was the main predictor of peripheral PWV in PA. Our data indicate aldosterone overproduction in PA does not preferentially affect central arterial system. Fibroproliferative effect of higher aldosterone levels lead to alteration of central-elastic as well as peripheral-muscular arteries with subsequent increase in its stiffness.

Have main types of primary aldosteronism different phenotype?

Primary aldosteronism (PA) is the most common cause of endocrine hypertension with a high frequency of cardiovascular complications. We found in our previous study higher occurrence of metabolic disturbances in patients with idiopathic hyperaldosteronism (IHA) compared to subjects with aldosterone-producing adenoma (APA). The aim of our present study is to evaluate potential differences in the frequency of end-organ damage (arterial stiffness and microalbuminuria) between two main types of PA. The diagnosis of the particular form of PA was based on adrenal venous sampling and/or histopathological examination. We analyzed clinical and laboratory data from 72 patients with PA (36 with IHA, 36 with APA). The arterial stiffness was expressed as the carotid-femoral pulse wave velocity (PWV) and the renal damage as urinary albumin excretion levels (UAE). Patients with IHA had significantly (p<0.03) higher prevalence of metabolic syndrome (17 % in APA, 35 % in IHA), higher triglycerides (1.37+/-0.71 mmol/l in APA, 1.85+/-0.87 mmol/l in IHA), lower HDL cholesterol (1.25+/-0.28 mmol/l in APA, 1.06+/-0.25 mmol/l in IHA), higher PWV (7.91+/-1.61 m/s in APA, 8.99+/-1.77 m/s in IHA) and higher UAE (12.93+/-2.21 mg/l in APA, 28.09+/-6.66 mg/l in IHA). It seems that patients with IHA may have a slightly different phenotype compared to APA.