Objective To evaluate the effect of different treatment strategies on enterohaemorrhagic Escherichia coli O104:H4 induced haemolytic uraemic syndrome.Design Multicentre retrospective case-control study.Setting 23 hospitals in northern Germany.Participants 298 adults with enterohaemorrhagic E coli induced haemolytic uraemic syndrome.Main outcome measures Dialysis, seizures, mechanical ventilation, abdominal surgery owing to perforation of the bowel or bowel necrosis, and death.Results 160 of the 298 patients (54%) temporarily required dialysis, with only three needing treatment long term. 37 patients (12%) had seizures, 54 (18%) required mechanical ventilation, and 12 (4%) died. No clear benefit was found from use of plasmapheresis or plasmapheresis with glucocorticoids. 67 of the patients were treated with eculizumab, a monoclonal antibody directed against the complement cascade. No short term benefit was detected that could be attributed to this treatment. 52 patients in one centre that used a strategy of aggressive treatment with combined antibiotics had fewer seizures (2% v 15%, P=0.03), fewer deaths (0% v 5%, p=0.029), required no abdominal surgery, and excreted E coli for a shorter duration.Conclusions Enterohaemorrhagic E coli induced haemolytic uraemic syndrome is a severe self limiting acute condition. Our findings question the benefit of eculizumab and of plasmapheresis with or without glucocorticoids. Patients with established haemolytic uraemic syndrome seemed to benefit from antibiotic treatment and this should be investigated in a controlled trial.

In nine healthy subjects, cold stimuli were administered to the forehead and hand, to the oral and nasal cavities via ice cubes and to the bronchial system via inhalation of cold air (−25 • C). Blood pressure, heart rate and muscle sympathetic nerve activity (MSNA) from the peroneal nerve were recorded. MSNA expressed as total activity increased during cold air inhalation, cooling of the forehead (P < 0.001, ANOVA), hand and mouth (P ≤ 0.05), paralleled by a rise in blood pressure during cold air inhalation and cooling of the forehead and hand (P < 0.01). Cooling of the forehead provoked a faster increase of MSNA expressed as total activity (P < 0.05) and higher levels of diastolic blood pressure (P = 0.05) compared with cooling of the hand. Bradycardia was observed only during cooling of the nasal cavity (P < 0.001) and the forehead (P < 0.05). It is concluded that cooling of the skin and mucous membranes of the tracheobronchial tract elicits sympathetically mediated hemodynamic adaptations, probably via stimulation of cold-sensitive afferents.

turnal blood pressure (BP) decline or "dipping" is an active, central, nervously governed process, which is important for BP regulation during daytime. It is, however, not known whether the sleep process itself or, more specifically, slow-wave sleep (SWS) is important for normal dipping. Therefore, in the present study, healthy subjects (6 females, 5 males) were selectively deprived of SWS by EEG-guided acoustic arousals. BP and heart rate (HR) were monitored during experimental nights and the following day. Additionally, nocturnal catecholamine excretion was determined, and morning baroreflex function was assessed by microneurographic measurements of muscle sympathetic nerve activity (MSNA) and heart rate variability (HRV). Data were compared with a crossover condition of undisturbed sleep. SWS was successfully deprived leading to significantly attenuated mean arterial BP dipping during the first half (P Ͻ 0.05), but not during the rapid-eye-movement-dominated second half of total sleep; however, dipping still evolved even in the absence of SWS. No differences were found for nighttime catecholamine excretion. Moreover, daytime resting and ambulatory BP and HR were not altered, and morning MSNA and HRV did not differ significantly, indicating that baroreflex-mediated sympathoneural BP regulation was not affected by the preceding SWS deprivation. We conclude that in healthy humans the magnitude of nocturnal BP dipping is significantly affected by sleep depth. Deprivation of SWS during one night does not modulate the morning threshold and sensitivity of the vascular and cardiac baroreflex and does not alter ambulatory BP during daytime.nondipping; baroreflex; muscle sympathetic nerve activity UNDISTURBED NOCTURNAL SLEEP is a prerequisite for health and well being. Particularly a proper nocturnal blood pressure decline commonly termed "dipping" is important for cardiovascular health. This process is not merely the consequence of physical inactivity but is actively governed by the central nervous system and mediated by an interplay between the autonomic nervous system and (neuro-)endocrine pathways, some of which are rather sleep dependent, while others are subject to circadian rhythms (1, 13, 34). Importantly, this sleep-associated blood pressure decline does not induce any sympathetic counterregulation, which is in contrast to the vigorous baroreflex activation to a blood pressure decrease of the same degree in awake subjects.The sleep-dependent modulation of blood pressure seems to result from the sleep stage-specific integration between cardiovascular reflexes and decreased central autonomic commands (7,25). In fact, sympathetic nervous traffic to the vasculature continuously decreases with the progressive deepening of nonrapid-eye-movement (NREM) sleep (11,27). Such decrease of vasoconstrictive sympathetic activity to the muscle vascular bed combined with the decline of blood pressure indicates a downward resetting of sympathovagal baroreflex setpoints being most relevant during slow-wave sleep (SWS) (7,25). Ba...

Context An outbreak of Shiga toxin-producing enteroaggregative Escherichia coli (STEC O104:H4) infection with a high incidence of hemolytic uremic syndrome (HUS) occurred in Germany in May 2011. Antibiotic treatment of STEC infection is discouraged because it might increase the risk of HUS development. However, antibiotic therapy is widely used to treat enteroaggregative E coli infection. In the German outbreak, a substantial number of patients received prophylactic azithromycin treatment as part of a therapeutic regimen with the C5 antibody eculizumab.Objective To analyze the duration of bacterial shedding in patients with STEC infection who did and did not receive oral azithromycin therapy.Design, Setting, and Patients At a single center in Lü beck, Germany, 65 patients with STEC infection, including patients with HUS as well as STEC-infected outpatients without manifestation of HUS, were investigated between May 15 and July 26, 2011, and were monitored for a mean of 39.3 days after onset of clinical symptoms. Main Outcome Measure Carriage of STEC after azithromycin therapy.Results Twenty-two patients received oral azithromycin and 43 patients did not receive antibiotic treatment. Among antibiotic-treated patients, long-term STEC carriage (Ͼ28 days) was observed in 1 of 22 patients (4.5%; 95% CI, 0%-13.3%) compared with 35 of 43 patients (81.4%; 95% CI, 69.8%-93.0%) who were not treated with antibiotics (PϽ.001). All 22 patients receiving azithromycin treatment had at least 3 STECnegative stool specimens after the completion of treatment, and no recurrence of STEC was observed in these patients. As proof of principle, 15 patients who initially were not treated with antibiotics and were long-term STEC carriers were treated with oral azithromycin given for 3 days and subsequently had negative stool specimens. ConclusionTreatment with azithromycin was associated with a lower frequency of long-term STEC O104:H4 carriage.

1 Bradykinin (BK) has been shown to exert cardioprotective e ects which are potentiated by inhibitors of angiotensin I-converting enzyme (ACE). In order to clarify the signi®cance of ACE within the whole spectrum of myocardial kininases we investigated BK degradation in the isolated rat heart. 2 Tritiated BK ( 3 H-BK) or unlabelled BK was either repeatedly perfused through the heart, or applied as an intracoronary bolus allowing determination of its elution kinetics. BK metabolites were analysed by HPLC. Kininases were identi®ed by ramiprilat, phosphoramidon, diprotin A and 2-mercaptoethanol or apstatin as speci®c inhibitors of ACE, neutral endopeptidase 24.11 (NEP), dipeptidylaminopeptidase IV and aminopeptidase P (APP), respectively. 3 In sequential perfusion passages, 3 H-BK concentrations in the perfusate decreased by 39% during each passage. Ramiprilat reduced the rate of 3 H-BK breakdown by 54% and nearly abolished [1-5]-BK generation. The ramiprilat-resistant kininase activity was for the most part inhibited by the selective APP inhibitor apstatin (IC 50 0.9 mM). BK cleavage by APP yielded the intermediate product [2-9]-BK, which was rapidly metabolized to [4-9]-BK by dipeptidylaminopeptidase IV. 4 After bolus injection of 3 H-BK, 10% of the applied radioactivity were protractedly eluted, indicating the distribution of this fraction into the myocardial interstitium. In samples of such interstitial perfusate fractions, 3 H-BK was extensively (by 92%) degraded, essentially by ACE and APP. The ramiprilat-and mercaptoethanol-resistant fraction of interstitial kininase activity amounted to 14%, about half of which could be attributed to NEP. Only the product of NEP, [1-7]-BK, was continuously generated during the presence of 3 H-BK in the interstitium. 5 ACE and APP are located at the endothelium and represent the predominant kininases of rat myocardium. Both enzymes form a metabolic barrier for the extravasated fraction of BK. Thus, only interstitial, but not intravascular concentrations of BK are increased by kininase inhibitors to the extent that a signi®cant potentiation of BK e ects could be explained. NEP contributes less than 5% to the total kininase activity, but is the only enzyme which is exclusively present in the interstitial space.

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Although shiga toxin-producing Escherichia coli (STEC)-HUS induced by O104:H4 was a life-threatening acute disease, follow-up showed a good recovery of organ function in all patients. Whereas kidney function recovered even after longer duration of dialysis, chronic hypertension developed after severe HUS with neurological symptoms and could not be prevented by the extended therapy.