Mortality in human sepsis is associated with downregulation of Toll-like receptor 2 and CD14 expression on blood monocytes

Pattern recognition receptors are a key component of the first line host defense against infection, recognizing specific microbial products. We hypothesize that monocyte hyporesponsiveness in human sepsis is associated with a downregulation of the pattern recognition receptors Toll-like receptor (TLR)-2 and TLR4

Do asymptomatic STEC-long-term carriers need to be isolated or decolonized? New evidence from a community case study and concepts in favor of an individualized strategy

Asymptomatic long-term carriers of Shigatoxin producing Escherichia coli (STEC) are regarded as potential source of STEC-transmission. The prevention of outbreaks via onward spread of STEC is a public health priority. Accordingly, health authorities are imposing far-reaching restrictions on asymptomatic STEC carriers in many countries. Various STEC strains may cause severe hemorrhagic colitis complicated by life-threatening hemolytic uremic syndrome (HUS), while many endemic strains have never been associated with HUS. Even though antibiotics are generally discouraged in acute diarrheal STEC infection, decolonization with short-course azithromycin appears effective and safe in long-term shedders of various pathogenic strains. However, most endemic STEC-strains have a low pathogenicity and would most likely neither warrant antibiotic decolonization therapy nor justify social exclusion policies. A risk-adapted individualized strategy might strongly attenuate the socio-economic burden and has recently been proposed by national health authorities in some European countries. This, however, mandates clarification of strain-specific pathogenicity, of the risk of human-to-human infection as well as scientific evidence of social restrictions. Moreover, placebo-controlled prospective interventions on efficacy and safety of, e.g., azithromycin for decolonization in asymptomatic long-term STEC-carriers are reasonable. In the present community case study, we report new observations in long-term shedding of various STEC strains and review the current evidence in favor of risk-adjusted concepts

No Elevated Plasma Catecholamine Levels during Sleep in Newly Diagnosed, Untreated Hypertensives

The sympatho-adrenergic system is highly involved in regulating sleep, wake and arousal states, and abnormalities in this system are regarded as a key factor in the development and progression of arterial hypertension. While hypertension is associated with a hyperadrenergic state during wakefulness, the effect of hypertension on plasma-catecholamine levels during sleep is not yet known. Twelve young participants with newly diagnosed, untreated hypertension and twelve healthy controls slept for 7 hours in the sleep laboratory. Before and after sleep, subjects rested in a supine position for 3-h periods of wakefulness. We sampled blood at a fast rate (1/10 min) and monitored blood pressure and heart rate continuously. We show that plasma NE and E levels did not differ between hypertensives and normotensive during sleep as well as before and after sleep. Blood pressure was higher in hypertensives, reaching the largest group difference in the morning after sleep. Unlike in the normotensives, in the hypertensive participants the morning rise in blood pressure did not correlate with the rise in catecholamine levels at awakening. Our results suggest that hypertension in its early stages is not associated with a strong hyperadrenergic state during sleep. In showing a diminished control of blood pressure through sympatho-adrenergic signals in hypertensive participants, our data point towards a possible involvement of dysfunctional sleep-related blood pressure regulation in the development of hypertension

Differential Effects of Angiotensin-II Compared to Phenylephrine on Arterial Stiffness and Hemodynamics: A Placebo-Controlled Study in Healthy Humans

The α1-adrenoceptor agonist phenylephrine (PE) and Angiotensin II (Ang II) are both potent vasoconstrictors at peripheral resistance arteries. PE has pure vasoconstrictive properties. Ang II, additionally, modulates central nervous blood pressure (BP) control via sympathetic baroreflex resetting. However, it is unknown whether Ang II vs. PE mediated vasoconstriction at equipressor dose uniformly or specifically modifies arterial stiffness. We conducted a three-arm randomized placebo-controlled cross-over trial in 30 healthy volunteers (15 female) investigating the effects of Ang II compared to PE at equal systolic pressor dose on pulse wave velocity (PWV), pulse wave reflection (augmentation index normalized to heart rate 75/min, AIx) and non-invasive hemodynamics by Mobil-O-Graph™ and circulating core markers of endothelial (dys-)function. PE but not Ang II-mediated hypertension induced a strong reflex-decrease in cardiac output. Increases in PWV, AIx, total peripheral resistance and pulse pressure, in contrast, were stronger during PE compared to Ang II at equal mean aortic BP. This was accompanied by minute changes in circulating markers of endothelial function. Moreover, we observed differential hemodynamic changes after stopping either vasoactive infusion. Ang II- and PE-mediated BP increase specifically modifies arterial stiffness and hemodynamics with aftereffects lasting beyond mere vasoconstriction. This appears attributable in part to different interactions with central nervous BP control including modified baroreflex function

Data_Sheet_1_Do asymptomatic STEC-long-term carriers need to be isolated or decolonized? New evidence from a community case study and concepts in favor of an individualized strategy.PDF

Asymptomatic long-term carriers of Shigatoxin producing Escherichia coli (STEC) are regarded as potential source of STEC-transmission. The prevention of outbreaks via onward spread of STEC is a public health priority. Accordingly, health authorities are imposing far-reaching restrictions on asymptomatic STEC carriers in many countries. Various STEC strains may cause severe hemorrhagic colitis complicated by life-threatening hemolytic uremic syndrome (HUS), while many endemic strains have never been associated with HUS. Even though antibiotics are generally discouraged in acute diarrheal STEC infection, decolonization with short-course azithromycin appears effective and safe in long-term shedders of various pathogenic strains. However, most endemic STEC-strains have a low pathogenicity and would most likely neither warrant antibiotic decolonization therapy nor justify social exclusion policies. A risk-adapted individualized strategy might strongly attenuate the socio-economic burden and has recently been proposed by national health authorities in some European countries. This, however, mandates clarification of strain-specific pathogenicity, of the risk of human-to-human infection as well as scientific evidence of social restrictions. Moreover, placebo-controlled prospective interventions on efficacy and safety of, e.g., azithromycin for decolonization in asymptomatic long-term STEC-carriers are reasonable. In the present community case study, we report new observations in long-term shedding of various STEC strains and review the current evidence in favor of risk-adjusted concepts.</p

Sleep characteristics in normotensive or hypertensive subjects (mean±s.d.).^*

<p>*There were no significant differences in sleep parameters between normotensive and hypertensive subjects.</p

Means ± S.E.M. Norepinephrine and Epinephrine plasma concentrations, blood pressure (BP) and heart rate during 3-h periods of wakefulness prior to (pre-wake) and after sleep (post-wake), and during the 7-h sleep period for hypertensives (white) and healthy normotensive controls.

<p>*<i>P</i><0.05; **<i>P</i><0.01, for pairwise comparisons between hyper- and normotensives.</p

Subjects' characteristics.

<p>Age, body mass index, diastolic and systolic blood pressure of the 12 normotensive and 12 hypertensive subjects (means ± standard deviation). Blood pressure values are means of three consecutive oscillometric measurements in sitting subjects after a rest of 10 min. *p<0.05 compared to the respective blood pressure values of normotensives.</p