Fulminant gastrointestinal bleeding caused by EBV-triggered hemophagocytic lymphohistiocytosis: report of a case.

Hemophagocytic lymphohistiocytosis (HLH) is a rare and often fatal hyperinflammatory syndrome characterized by fever, cytopenia, dramatically increased ferritin and hepatosplenomegaly. Here, we describe a previously healthy 39 year old pregnant woman in 30th week of her pregnancy with diarrhoea, intermittent gastrointestinal bleeding and fever of unknown focus. After cesarean section of twins in the 31st week she deteriorated with fulminant upper and lower gastrointestinal bleeding and disseminated intravascular coagulation. Gastro-, ileocolonoscopy and capsule endoscopy identified multiple bleeding punched ulcerations in the stomach, the entire small bowel and in parts of the colon. Emergency surgery with intraoperative endoscopy for uncontrolled hemorrhagic shock resulted in the resection of actively bleeding ulcers in the jejunum which temporally stabilized the critically ill patient. Jejunal histology and in situ hybridisation showed extensive ulcerations, focal lymphohistiocytic infiltration and EBV-positive immunoblasts. The diagnosis fulminant EBV-related HLH was confirmed based on the HLH-2004 diagnostic criteria and through detection of a reactivated EBV infection (up to 3 × 10(7) DNA copies/mL serum). Despite immunosuppressive therapy with steroids, cyclosporine A and etoposide in combination with Rituximab, the patient died from this sepsis-like, hyper-inflammatory syndrome in multiorgan failure with uncontrolled bleeding.

[54-year-old male with hepatic cirrhosis and therapy-associated torsade de pointes tachycardia]. / 54-jähriger Patient mit Leberzirrhose und therapiebedingten Torsade-de-pointes-Tachykardien.

We present a case of a patient with newly diagnosed cirrhosis and kidney failure who underwent cardiopulmonary resuscitation twice after treatment with terlipressin. After the second application a QT interval prolongation and torsade de pointes were documented. Since other causes were excluded, we interpret both events as terlipressin-induced ventricular arrhythmia. Therefore, it seems important to consider this rare but potentially lethal side effect when administering this drug to patients.

Extra cellular matrix remodelling after heterotopic rat heart transplantation: gene expression profiling and involvement of ED-A+ fibronectin, alpha-smooth muscle actin and B+ tenascin-C in chronic cardiac allograft rejection.

Chronic cardiac rejection is represented by cardiac allograft vasculopathy (CAV) and cardiac interstitial fibrosis (CIF) known to cause severe complications. These processes are accompanied by remarkable changes in the cardiac extra cellular matrix (cECM). The aim of our study was to analyse the cECM remodelling in chronic rejection and to elucidate a potential role of ED-A domain containing fibronectin (ED-A(+) Fn), alpha smooth muscle actin (ASMA) and B domain containing tenascin-C (B(+) Tn-C). A model of chronic rejection after heterotopic rat heart transplantation was used. Allografts, recipient and control hearts were subjected to histological assessment of rejection grade, to real-time PCR based analysis of 84 genes of ECM and adhesion molecules and to immunofluorescence labelling procedures, including ED-A(+) Fn, ASMA and B(+) Tn-C antibodies. Histological analysis revealed different grades of chronic rejection. By gene expression analysis, a relevant up-regulation of the majority of ECM genes in association with chronic rejection could be shown. For 8 genes, there was a relevant up-regulation in allografts as well as in the corresponding recipient hearts. Association of ASMA positive cells with the grade of chronic rejection could be proven. In CAV and also in CIF there were extensive co-depositions of ED-A(+) Fn, ASMA and B(+) Tn-C. In conclusion, chronic cardiac allograft rejection is associated with a cECM remodelling. ASMA protein deposition in CAV, and CIF is a valuable marker to detect chronic rejection. Interactions of VSMCs and Fibro-/Myofibroblasts with ED-A(+) Fn and B(+) Tn-C might functionally contribute to the development of chronic cardiac rejection.

Social and behavioural aspects and their consequences in obese teenagers: importance of family's history.

OBJECTIVES: Overweight, the metabolic syndrome and accompanying diseases are dramatically increasing problems. We investigated social and behavioral variables that influence overweight in adolescents and tested their influence on plasma markers related to diabetes and endothelial dysfunction. METHODS: 79 male adolescents were enrolled (age 13-17 years). Endothelial progenitor cells were counted by flow cytometry. Adiponectin and soluble E-selectin (sEselectin) were determined by ELISA. RESULTS: Body weight differs significantly if the family's history was positive for arterial hypertension (p < 0.001), diabetes (p < 0.001), hypercholesterolemia (p<0.001), and coronary artery disease (CAD, p < 0.01). The hours of physical activity represent a predictor of BMI in linear regression analysis (p < 0.001; R(2) = 0.195). Markers for endothelial damage are altered in adolescents with positive family history for hyperlipidemia and CAD. CONCLUSION: The family's history is an important variable influencing the body weight of teenagers. Via obesity and independently, it influences the early development of endothelial damage. It might serve to detect teenagers at risk for appropriate intervention.

[Prolonged neuroleptic malignant syndrome after Haloperidol injection]. / Protrahiertes malignes neuroleptisches Syndrom nach Haloperidolgabe.

Neuroleptic malignant syndrome (NMS) is a rare disorder caused by drug-induced dopamine-receptor-blockage or low dopamine concentration in the brain. It is a severe reaction to neuroleptic drugs in antipsychotic therapy. Symptoms in NMS typically consist of fever, muscle rigidity and cognitive changes; laboratory findings include elevated infectious disease markers and creatine kinase as well as signs of rhabdomyolysis. To differentiate NMS from other malignant hyperthermia syndromes identifying the offending drug and clinical history are essential. Therapy in NMS includes withdrawal of the causative medication and intensive care treatment possibly with administration of dantrolene.In this case report, we describe the clinical course of a 48 year old man who developed typical clinical symptoms and laboratory parameters of malignant hyperthermia syndrome after injection of haloperidol.

Treatment with granulocyte-colony stimulating factor in patients with acute myocardial infarction. Evidence for a stimulation of neovascularization and improvement of myocardial perfusion.

BACKGROUND: Stem cell therapy has been suggested to be beneficial in patients after acute myocardial infarction (AMI). Strategies of treatment are either a local application of mononuclear bone marrow cells (BMCs) into the infarct-related artery or a systemic therapy with the granulocyte-stimulating factor (G-CSF) to mobilize BMCs. Nevertheless, the mechanisms responsible for improvement of cardiac function and perfusion are speculative at present. This study has been performed to investigate the effect of G-CSF on systemic levels of vascular growth factors and chemokines responsible for neovascularization, that might help to understand the positive effects of a G-CSF therapy after AMI. METHODS AND RESULTS: Five patients in the treatment group and 5 patients in the control group were enrolled in this study. The patients in the treatment group received 10 microg/kg bodyweight/day of G-CSF subcutaneously for a mean treatment duration of 6.6 +/- 1.1 days. In both groups, levels of vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF) and monocyte chemotactic protein-1 (MCP-1) were measured on day 2 to 3 and day 5 after AMI. The regional wall perfusion and the ejection fraction (EF) were evaluated before discharge and after 3 months with ECG-gated MIBI-SPECT and radionuclide ventriculography, respectively. Significant higher levels of VEGF (p < 0.01), bFGF (p < 0.05) and MCP-1 (p < 0.05) were found in the treatment group compared to the control group. Levels of VEGF and bFGF remained on a plateau during the G-CSF treatment and decreased significantly in the control group. The wall perfusion improved significantly within the treatment group and between the groups (p < 0.05), respectively. The EF improved significantly within the treatment group (p < 0.05), but the change of the EF between the groups was not significant. CONCLUSION: In patients with AMI, the treatment with G-CSF modulates the formation of vascular growth factors that might improve neovascularization and result in an improved myocardial perfusion and function.

Laminar shear stress upregulates the complement-inhibitory protein clusterin : a novel potent defense mechanism against complement-induced endothelial cell activation.

BACKGROUND: The complement system is implicated in the pathogenesis of atherosclerosis. Complement has been shown to activate endothelial cells (ECs) by inducing a proinflammatory response. Physiological levels of shear stress exert potent antiatherosclerotic effects. Therefore, we investigated whether shear stress antagonizes the effects of complement on ECs. METHODS AND RESULTS: Incubation of ECs with nonlytic concentrations of complement serum (CS: 0.2 U/mL for 6 hours) resulted in an upregulation of interleukin-8 (IL-8) (165+/-12%) and monocyte chemoattractant protein-1 (MCP-1) mRNA expression (267+/-34%). Preexposure of ECs for 18 hours with laminar shear stress (15 dyne/cm(2)) abrogated CS-induced IL-8 release to 106+/-10% (P<0.001) and reduced CS-induced MCP-1 expression (170+/-31%; P<0.05). To examine the mechanism of the protective effect of shear stress, expression of the complement-inhibitory protein clusterin was analyzed under shear exposure. Shear stress increased clusterin mRNA (225+/-76%, 6 hours) and protein expression (164+/-22%, 18 hours). Specific inhibition of clusterin by transfection with antisense oligonucleotides reversed the protective effect of shear stress on CS-induced MCP-1 and IL-8 upregulation (P<0.05 versus sense-transfected cells). Moreover, clusterin overexpression inhibited CS-induced EC activation. CONCLUSIONS: Shear stress abrogates the complement-induced proinflammatory response of ECs by upregulation of the complement-inhibitory protein clusterin. Upregulation of clusterin may contribute to the potent antiatherosclerotic effects of shear stress by preventing endothelial activation through the complement cascade.

Characteristics of sodium uptake across the basolateral membrane of oxyntic cells.

To characterize further serosal Na uptake into gastric oxyntic cells under resting conditions, cellular element concentrations were determined in isolated frog (Rana temporaria) gastric mucosae using electron microprobe analysis. The epithelia were kept short circuited in Ussing-type chambers, and element analysis was performed on freeze-dried cryosections. After ouabain (10(-4) M), the [Na] in oxyntic cells increased within 30 to 60 minutes from approximately 25 to 100 mmol/kg wet wt, and [K] decreased similarly (from 100 to 25 mmol/kg wet wt). These changes occurred regardless of whether the basolateral incubation medium contained HCO3 or N-2-hydroxyethylpiperazine-N'-2-ethanesulfonic acid (HEPES) as buffers. When, prior to the addition of ouabain, 10(-3) M amiloride was applied to the serosal side to inhibit the Na-H antiporter, the ouabain-induced increase in cellular [Na] was prevented completely in HEPES-, but not in HCO3-Ringer. The data are compatible with the notion that Na is taken up by a Na-H antiporter and a Na-HCO3 symporter. At least under these experimental conditions, these transporters seem to contribute substantially to basolateral Na uptake in oxyntic cells.

Altered red blood cell distribution width in overweight adolescents and its association with markers of inflammation.

BACKGROUND: Obesity and the metabolic syndrome are dramatically increasing problems. Red blood cell distribution width (RDW), the variability in size of circulating red blood cells, has been demonstrated to be altered in different clinical settings. This analysis aimed to investigate the relationship between RDW and obesity in adolescents and in an animal model of diet-induced obesity (DIO). METHODS: Seventy-nine male adolescents (aged 13-17 years) were studied. Thirty-seven of them were overweight (body mass index ≥ 90th percentile). RDW, markers of inflammation and stem cell factor (SCF) were determined. In an animal study, mice were fed with different diets for 15 weeks. RDW was determined using an animal blood count machine. RESULTS: RDW differed significantly between normal-weight adolescents (13.07 ± 0.09) and overweight adolescents (13.39 ± 0.10, P = 0.015), whereas erythrocyte counts and haematocrit did not differ. RDW correlated to markers of inflammation and inversely to SCF. In the mice animal model, nutritional changes increased RDW, whereas overweight per se did not change RDW. CONCLUSIONS: RDW is elevated in overweight and reflects the inflammatory state. RDW potentially represents an additional and cost-effective tool to indicate inflammation. Future studies are needed to understand the differential influences of nutrition and overweight on RDW.

[Evaluation of microcirculation in cardiogenic shock]. / Messung der Mikrozirkulation im kardiogenen Schock.

The prognosis of cardiogenic shock is still dismal despite advancements in diagnostic and therapeutic options. One of the major problems is the development of multi-organ failure caused by impaired organ perfusion with inadequate microcirculation. The diagnosis of cardiogenic shock is based on clinical signs of hypoperfusion, echocardiography, and hemodynamic parameters. Because of its high prognostic relevance microcirculation has become more interesting for clinicians recently. Signs of severe cardiogenic shock are reduced vascular density and impaired microflow, especially in the smallest vessels and the location of exchange of gas and nutrients. Recent studies revealed that intravital-microscopy is a valuable tool for on-line and in-vivo measuring of microcirculatory parameters. The assessment of microcirculation during modifications of the treatment of cardiogenic shock is valuable, e. g. during catecholamine therapy or when using of circulatory assist devices. This article summarizes new findings regarding microcirculation in cardiogenic shock, the use of assist devices, and novel pharmacological treatment. Evaluation of microcirculatory changes with its new insights in the complex pathophysiology of cardiogenic shock has the potential to become part of diagnostic algorithms.

In vivo evaluation of tissue microflow under combined therapy with extracorporeal life support and intra-aortic balloon counterpulsation.

Treatment with percutaneous extracorporeal mechanical assist devices provides the ultimate therapeutic option to improve the macrocirculation in patients suffering from refractory cardiac arrest, severe cardiogenic shock or during high-risk interventions. However, the flow in the smallest vessels in these critical periods is poorly understood but prognostically of high importance. Using sidestream darkfield intravitalmicroscopy, we visualised the sublingual microflow in a patient suffering from severe cardiogenic shock supported by extracorporeal membrane oxygenation and intra-aortic balloon pump. Our results show that intra-aortic balloon counterpulsation applied in addition to extracorporeal membrane oxygenation further improves the microflow. This in vivo finding supports pilot studies favouring the application of devices supporting cardiac output (extracorporeal membrane oxygenation) together with devices aimed at pulsatility (intra-aortic balloon pump).

Social and behavioural aspects and their consequences in obese teenagers -importance of family’s history / Aspectos sociales y conductuales y sus consecuencias en adolescentes obesos - importancia de los antecedentes familiares

Objectives: Overweight, the metabolic syndrome and accompanying diseases are dramatically increasing problems. We investigated social and behavioral variables that influence overweight in adolescents and tested their influence on plasma markers related to diabetes and endothelial dysfunction. Methods: 79 male adolescents were enrolled (age 13-17 years). Endothelial progenitor cells were counted by flow cytometry. Adiponectin and soluble E-selectin (sEselectin) were determined by ELISA. Results: Body weight differs significantly if the family's history was positive for arterial hypertension (p < 0.001), diabetes (p < 0.001), hypercholesterolemia (p<0.001), and coronary artery disease (CAD, p < 0.01). The hours of physical activity represent a predictor of BMI in linear regression analysis (p < 0.001; R2 = 0.195). Markers for endothelial damage are altered in adolescents with positive family history for hyperlipidemia and CAD. Conclusion: The family's history is an important variable influencing the body weight of teenagers. Via obesity and independently, it influences the early development of endothelial damage. It might serve to detect teenagers at risk for appropriate intervention (AU)

Objetivos: El sobrepeso, el síndrome metabólico y sus enfermedades asociadas son problemas que están aumentando de forma notable. Investigamos las variables sociales y conductuales que influyen en el sobrepeso en adolescentes y probamos su influencia sobre los marcadores plasmáticos relacionados con la diabetes y la disfunción endotelial. Métodos: Se reclutaron 79 adolescentes varones (edad 13-17 años). Se contaron las células progenitoras endoteliales con citometría de flujo. Se determinaron la adiponectina y la selectina-e soluble (selectina-s) mediante ELISA. Resultados: El peso corporal difiera significativamente si los antecedentes familiares son positivos para hipertensión arterial (p < 0,001), diabetes (p < 0,001), hipercolesterolemia (p < 0,001) y arteriopatía coronaria (APC, p < 0,01). Las horas de actividad física representan un predictor del IMC en el análisis de regresión linear (p < 0,001; r2 = 0,195). Los marcadores de lesión endotelial están alterados en los adolescentes con unos antecedentes familiares positivos para hiperlipidemia y APC. Conclusión: Los antecedentes familiares son una variable importante que influye en el peso corporal de los adolescentes. A través de la obesidad y de forma independiente, influye en el desarrollo precoz de lesión endotelial. Podría servir para detectar a los adolescentes con riesgo para realizar una intervención apropiada (AU)

[Mobilization of stem cells by granulocyte colony-stimulating factor for the regeneration of myocardial tissue after myocardial infarction]. / Mobilisation von Stammzellen durch den Granulozyten-Kolonie stimulierenden Faktor zur Regeneration myokardialen Gewebes nach Herzinfarkt.

BACKGROUND AND OBJECTIVE: Animal data suggest that mobilized bone marrow cells (BMC) may contribute to tissue regeneration after myocardial infarction (MI). However the safety, feasibility and efficacy of treatment with granulocyte colony-stimulating factor (G-CSF) to mobilize BMC after acute myocardial infarction in patients is unknown. We analysed cardiac function and perfusion in 5 patients who were treated with G-CSF in addition to standard therapeutical regimen. METHODS AND RESULTS: 48 h after successful recanalization and stent implantation in 5 patients with acute MI, the patients received 10 micro g/kg bodyweight/day G-CSF subcutaneously for a mean treatment duration of 7.6+/-0.5 days. Peak value of CD34 (+) cells, a multipotent subfraction of bone marrow cells, was reached after 5.0+/-0.7 days. After 3 months of follow-up global left ventricular ejection fraction (determined by radionuclid-ventriculography) increased significantly from 42.2+/-6.6 % to 51.6+/-8.3 % (P<0.05). The wall motion score and the wall perfusion score (determined by ECG gated SPECT) decreased from 13.5+/-3.6 to 9.9+/-3.5 (P<0.05) and from 9.6+/-2.9 to 7.0+/-4.5 (P<0.05), respectively, indicating a significant improvement of myocardial function and perfusion. No severe side effects of G-CSF treatment could be observed. Malignant arrhythmias were not observed either. CONCLUSION: In patients with acute MI, treatment with G-CSF to mobilize BMC appears to be well tolerable under clinical conditions. Improved cardiac function and perfusion may be attributed to BMC-associated promotion of myocardial regeneration and neovascularization.