Hypertension and mild chronic kidney disease persist following severe haemolytic uraemic syndrome caused by Shiga toxin-producing Escherichia coli O104:H4 in adults.

BACKGROUND: Shiga toxin-producing, enteroaggregative Escherichia coli was responsible for the 2011 outbreak of haemolytic uraemic syndrome (HUS). The present single-centre, observational study describes the 1-year course of the disease with an emphasis on kidney function. Outcome data after 1 year are associated with treatment and patient characteristics at onset of HUS. METHODS: Patients were treated according to a standardized approach of supportive care, including a limited number of plasmapheresis. On top of this treatment, patients with severe HUS (n = 35) received eculizumab, a humanized anti-C5 monoclonal antibody inhibiting terminal complement activation. The per-protocol decision--to start or omit an extended therapy with eculizumab accompanied by azithromycin--separated the patients into two groups and marked Day 0 of the prospective study. Standardized visits assessed the patients' well-being, kidney function, neurological symptoms, haematological changes and blood pressure. RESULTS: Fifty-six patients were regularly seen during the follow-up. All patients had survived without end-stage renal disease. Young(er) age alleviated restoring kidney function after acute kidney injury even in severe HUS. After 1 year, kidney function was affected with proteinuria [26.7%; 95% confidence interval (CI) 13.8-39.6], increased serum creatinine (4.4%, CI 0.0-10.4), increased cystatin C (46.7%, CI 32.1-61.3) and reduced (<90 mL/min) estimated glomerular filtration rate (46.7%, CI 32.1-61.3). Nine of the 36 patients without previous hypertension developed de novo hypertension (25%, CI 10.9-39.1). All these patients had severe HUS. CONCLUSIONS: 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.

Prolonged blood pressure elevation following continuous infusion of angiotensin II-a baroreflex study in healthy humans.

ANG II interacts with the sympathetic nervous system at central nervous blood pressure-regulating structures, including the baroreflex. It is unknown whether prolonged BP elevation mediated by high ANG II plasma levels could induce a persistent shift of the central nervous baroreflex setpoint, lasting beyond the short ANG II plasmatic half time of a few seconds, thereby consolidating elevated BP and/or increased SNA in healthy humans. In a blinded crossover design, ANG II or placebo (saline) was infused for a 6-h period in 12 resting normotensive students (6 males, 6 females) raising BP to borderline hypertensive levels. Between 60 and 120 min after the infusion period, muscle sympathetic nerve activity (MSNA) was assessed microneurographically and correlated with oscillometric BP measurements and heart rate at supine rest (baseline) and during pharmacologic baroreceptor challenge. Infusion of ANG II increased BP to borderline-hypertensive levels, as intended, whereas heart rate remained unaltered. At baroreflex assessment (i.e., 60-120 min after end of infusion period), systolic BP was significantly higher compared with placebo (Δ8.4 ± 3.1 mmHg; P < 0.05), whereas diastolic values were nearly equal between conditions. Baseline MSNA was neither decreased nor increased, and baroreflex sensitivity to vasoactive drug challenge was not altered. Our results show that elevation of ANG II plasma levels over 6 h was able to increase systolic, but not diastolic, BP far beyond blood-mediated ANG II effects. MSNA or heart rate did not counter-regulate this BP elevation, indicating that ANG II had sustainably reset the central nervous BP threshold of sympathetic baroreflex function to accept elevated BP input signals without counter-regulatory response.

Does etiology of acute pancreatitis matter? A review of 391 consecutive episodes.

CONTEXT: Acute pancreatitis can be triggered by a variety of factors ranging from short lasting to sustained disruptions. It is plausible that the characteristics and course of disease differ among etiologies. Data distinguishing characteristics of patients with pancreatitis of biliary, alcoholic, idiopathic or other origin are scarce and conflicting. OBJECTIVE: To compare patients' characteristics, baseline parameters on admission, and outcome in patients with an episode of acute pancreatitis in whom the etiology was thoroughly determined. DESIGN: Retrospective study. SETTING: Single center. PATIENTS: Three-hundreds and 91 consecutive episodes of acute pancreatitis through the years 2008 to 2011. MAIN OUTCOME MEASURES: Gender, age, body mass index, Charlson comorbidity index, history of pancreatitis, heart rate, blood pressure, plasma lipase, hematocrit, plasma creatinine, white blood cell count, rate of persistent organ failure and necrosis, maximum C-reactive protein, duration of hospitalization, mortality. RESULTS: There were marked differences between the groups. Biliary etiology was associated with higher age and body weight, female predominance, higher plasma lipase, and a favourable outcome. Alcoholic etiology had male predominance, a tendency for initial hemoconcentration, a lower plasma lipase, and the highest rate of necrosis. Idiopathic etiology had the highest rate of persistent organ failure and the highest mortality. CONCLUSIONS: Biliary, alcoholic and idiopathic acute pancreatitis should be treated as distinct entities. While alcoholic episodes have the highest risk of necrosis, the worst outcome was observed in the idiopathic group. Hence, finding no causality for an episode of acute pancreatitis after thorough investigation might be a predictor for poor outcome. Larger studies are warranted to confirm this.

[A curricular training of fourth year medical students in writing discharge summaries: the graduate view after two years]. / Curriculare Übung zum Verfassen von Arztbriefen im vierten Jahr des Medizinstudiums - Einschätzungen der Teilnehmer nach zwei Jahren.

BACKGROUND: Preparing high quality discharge summaries is difficult for first year residents. For 5 years we have been training fourth year students how to write discharge summaries. Our goal is to facilitate the students' start into clinical work. Moreover, we intend to provide the students with a scheme to better memorize patients' histories. Two years after the tutorial the graduates were asked to evaluate the tutorial and to comment on its learning effects. METHODS: A total of 1228 fourth year students wrote a discharge summary on a patient in whose care the specific student was involved during his or her training in internal medicine. All summaries were read, commented on and graded by a consultant. Two years after the tutorial 310 graduates were invited to complete an online survey on this tutorial. RESULTS: 106 (34%) of all invited graduates completed the survey. The opinions on the tutorial greatly differed. In principal the students agreed that the tutorial was an important part of medical training and helped to better structure patients' medical data. The majority of the surveyed graduates, however, were not convinced of its practical usefulness for daily work. The students with the poorer grading found their grade less appropriate than the students with the better grading. CONCLUSIONS: Though our main goal could not be achieved in the view of the graduates, the overall opinion was rather positive. Problems with this kind of tutorial lay in the enormous effort of correction and in the discouraging effect of grading on the students with difficulties in the task.

Detrimental effect of high volume fluid administration in acute pancreatitis - a retrospective analysis of 391 patients.

BACKGROUND: Early fluid resuscitation is recommended for the therapy of acute pancreatitis in order to prevent complications. There are, however, no convincing data supporting this approach. METHODS: We reviewed 391 consecutive cases of confirmed acute pancreatitis. Admitting physicians had been advised to administer an aggressive fluid resuscitation in the early phase of disease, if possible. We tested whether disease severity according to the revised Atlanta Classification, local complications, and maximum C-reactive protein levels were predictable by the initial volume therapy in logistic and linear regression models, respectively. We also determined which parameters on admission encouraged a more aggressive fluid resuscitation. RESULTS: The recorded fluid administered within the first 24 h was 5300 [3760; 7100] ml (median [1st; 3rd quartile]). More aggressive volume therapy was associated with disease severity and a higher rate of local complications. There was a linear relationship between administered volume and the maximum C-reactive protein. The amount of administered fluid was significantly attributed to age, hematocrit, and white blood cell count on admission. When adjusted for these parameters the impact of administered volume on outcome was still present but attenuated. CONCLUSIONS: We found detrimental effects of fluid therapy on major outcome parameters throughout the whole range of administered volume. More volume was administered in younger patients and in patients with evidence of hemoconcentration and inflammation. The adverse effects of volume therapy persisted after elimination of these parameters. Caution should therefore be advised with regards to volume therapy in patients with acute pancreatitis.

Association between azithromycin therapy and duration of bacterial shedding among patients with Shiga toxin-producing enteroaggregative Escherichia coli O104:H4.

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 Lübeck, 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 (>28 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 (P < .001). All 22 patients receiving azithromycin treatment had at least 3 STEC-negative 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. CONCLUSION: Treatment with azithromycin was associated with a lower frequency of long-term STEC O104:H4 carriage.

Effects of selective slow-wave sleep deprivation on nocturnal blood pressure dipping and daytime blood pressure regulation.

Nocturnal 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 < 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.

Effect of facial cooling and cold air inhalation on sympathetic nerve activity in men.

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 degrees 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 < or = 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.

Heart rate variability and metabolic rate in healthy young adults with low birth weight.

OBJECTIVE: Low birth weight (LBW) is associated with obesity and a higher cardiovascular risk in adult life. Since autonomic dysfunction could be a pathophysiological factor for this association, we assessed the impact of LBW on cardiac autonomic activity and metabolic rate in young adulthood. We hypothesized that the autonomic tone could be coupled with the metabolic rate in subjects with LBW. METHODS: Heart rate variability (HRV) from 24-hour Holter-electrocardiograms was measured in 15 healthy adults aged 20 to 30 years with LBW (<2500g at term) and 15 paired subjects with normal birth weight (NBW). The pairs were closely matched by gender, age, and body mass index. Resting energy expenditure was measured by indirect calorimetry and body composition by bioimpedance. RESULTS: Global HRV parameters were significantly higher in the LBW group and a marked difference was observed in the long wave fluctuations of the frequency domain (very low frequency). These fluctuations were positively correlated with the resting energy expenditure per body weight in the LBW and negatively in the NBW group. Only in the LBW group HRV was closely related to body fat. INTERPRETATION: This case-control study indicates that autonomous nervous function is not generally deteriorated in young adults with LBW and has a significant association with metabolic rate. Thus, it may be a determinant of the body weight regulation in this group. The higher cardiovascular risk in ageing individuals with LBW would therefore rather be a consequence of weight gain than of a primary autonomous nervous dysfunction.

Lethal hemorrhage caused by aortoesophageal fistula secondary to stent-graft repair of the thoracic aorta.

Aortoesophageal fistula (AEF) is a rare but life-threatening complication after endovascular or surgical aortic repair. Here we report a patient with AEF secondary to aortic stent-placement 2 years earlier who presented with hematemesis and died from hemorrhagic shock. By means of this case and the literature, we highlight potential bleeding sources in such a scenario because this is of crucial importance for the management strategy.

Cold-induced alteration of adipokine profile in humans.

Adipose tissue function and sympathetic nervous system (SNS) activity are tightly interconnected. Adipose tissue is densely innervated by the SNS. Adipokines secreted by adipose tissue are implicated in maintaining energy homeostasis, the control of blood pressure, immune system function, hemostasis, and atherosclerosis. Little is known about a direct effect of SNS activation on influencing adipose tissue endocrine function in humans. In 10 lean, healthy male volunteers, SNS was activated by whole-body exposure to cold for 2 hours; a group of 10 subjects served as controls. Vital parameters were evaluated, plasma adipokine levels were measured, and adipokine gene expression in subcutaneous abdominal adipose tissue was determined. Cold exposure caused an increase in cold sensation and a drop in body temperature and heart rate. Norepinephrine, but not epinephrine, plasma levels were elevated. Adiponectin plasma concentrations were acutely and significantly decreased. There was a trend of increased monocyte chemoattractant protein-1 plasma concentrations. Interleukin-6 and leptin levels increased and decreased, respectively, in both groups. Vascular endothelial growth factor plasma levels were unaffected. Subcutaneous adipokine gene expression was unchanged. Cold exposure caused SNS activation and differentially influenced adipokine secretion. Adiponectin levels were acutely reduced, whereas monocyte chemoattractant protein-1 concentrations tended to increase. No specific changes in leptin and IL-6 concentrations were detectable. The observed alterations appeared to be posttranscriptional because adipokine gene expression was found to be unaltered.

Premedication with orally administered lorazepam in adults undergoing ERCP: a randomized double-blind study.

BACKGROUND: Restlessness often complicates ERCP and may be a reason for premature termination of the procedure. OBJECTIVE: Our purpose was to evaluate whether a premedication with orally administered lorazepam could reduce the need for sedatives and improve sedation quality. DESIGN: Randomized double-blind trial. SETTING: Therapeutic ERCP with an intravenous sedation containing midazolam, propofol, and S(+)-ketamine. PATIENTS: 95 inpatients (aged 20-91 years). INTERVENTIONS: 1 mg of lorazepam (n=47) or placebo (n=48) given orally before ERCP. MAIN OUTCOME MEASUREMENT: Total amount of administered propofol. RESULTS: Heart rate, blood pressure, number of oxygen desaturations, and states of restlessness did not differ between the groups. The same amount of midazolam was administered in both groups. There was no significant difference in the total amount of propofol to achieve adequate sedation (lorazepam vs placebo: 71+/-5 vs 63+/-4 microg/kg/min, mean+/-SE). Paradoxically, patients pretreated with lorazepam even needed more propofol in the early phase of sedation (275+/-39 vs 159+/-37 microg/kg in minutes 5-10, P<.05) and the total amount of ketamine administered was higher in this group as well (15.8+/-1.4 vs 11.3+/-1.2 microg/kg/min, P<.05). In both groups there were high rates of satisfaction with the course of the procedure evaluated both by the endoscopists and the patients. CONCLUSION: The trial failed to show an advantage of an oral premedication with lorazepam. The amount of sedatives administered in the lorazepam group even tended to be higher. A premedication with lorazepam may be counterproductive when followed by sedation containing another benzodiazepine.