Unrecognised iron deficiency in critical illness.
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Biomedical subjects
Publications and source records attributed to U Frei.
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A case of panarteritis with purpura fulminans, mononeuritis multiplex, gastrointestinal manifestation and presumably cardiac involvement in a previously healthy 22-year-old man with a history of drug abuse including cocaine, cannabinoids and methamphetamines is described. Histopathological examination of the gut led to the diagnosis of panarteritis without immune deposits. Antineutrophil antibodies were negative. Besides the drugs, no other possible cause of vasculitis was found. The patient recovered completely after 1 year. Drug abuse is a thus possible cause of severe extracerebral disabling vasculitis.
OBJECTIVE: Inflammation and hypoxia are frequently associated, but their interaction is poorly understood. In vitro studies have shown that hypoxia stimulates the genes of acute phase proteins (APP) and cytokines known to induce APP. We decided to determine kinetics and potential determinants of an acute phase response after cardiac arrest and to assess whether isolated moderate hypoxia can induce APP in humans in vivo. DESIGN: Prospective, observational study in patients and human experiment. SETTING: Tertiary care university hospital. PATIENTS AND PARTICIPANTS: 22 patients after primarily successful cardiopulmonary resuscitation (CPR) and 7 healthy volunteers. INTERVENTIONS: None in patients; exposure of volunteers to simulated altitude (460 torr/6 h). RESULTS: Following CPR, type-1 APP (C-reactive protein, alpha 1-acidglycoprotein, serum amyloid A) and type-2 APP (haptoglobin, alpha 1-antitrypsin) increased consistently within 1-2 days and the 'negative' APP transferrin was downregulated. This APP response occurred irrespective of the cause of arrest, the estimated time of anoxia, clinical course or patient outcome and was not different in patients with and without infectious complications. Exposure of healthy volunteers to less severe but more prolonged hypoxia did not induce APP, although a time dependent increase of serum erythropoietin (EPO) was measurable under these conditions, indicating the activation of oxygen dependent gene expression. CONCLUSIONS: (i) A marked acute phase response occurs regularly after cardiac arrest, but within the complexity of this situation the severity of hypoxia is not a predominant determinant of this response. (ii) Despite in vitro evidence for similarities in the oxygen dependent regulation of APP and EPO production, the oxygen sensitivity of these proteins in vivo is different. (iii) Measurements of APP are not revealing regarding infectious complications in the early phase after CPR.
The aim of the present study was to differentiate acute rejection, chronic rejection, and tacrolimus nephrotoxicity with color and power Doppler imaging of renal transplants. One hundred examinations were obtained from 45 patients. Pulsatility and resistive indices were calculated from color Doppler images. The grade of renal vascularization was quantified using computer-assisted pixel analysis in a rectangular region-of-interest. The percentage of vessel-covered renal parenchyma (POV) was calculated using a histogram that discriminated renal vessels from renal parenchyma via power Doppler images. Furthermore, the distance from the most peripherally located vessels to the renal capsule (PVD) was measured. A reduced POV < or = 55% proved to be the best discriminator when chronic rejection was suspected (sensitivity 79%, specificity 87%). Tacrolimus nephrotoxicity showed not only a moderate elevation of the Doppler signal but also an increased PVD > or = 3.9 mm and a normal POV. We conclude that the evaluation of renal vessels by power Doppler images improves diagnostic accuracy for patients with renal allografts.
The microemulsion preparation of cyclosporine, Neoral, was introduced to improve the limited and sometimes unpredictable absorption of cyclosporine from the gut. Preclinical studies proved a superior bioavailability measured by the AUC and a definitively better predictability of the pharmacokinetic properties. Large-scale randomized and open-labeled studies have been carried out to prove and establish the safety, tolerability, and equal or superior efficacy of NEO if compared with SIM. There is broad evidence that NEO is safe and well tolerated in de novo and stable renal allografts. There are some arguments that NEO has favorable properties in poor absorbers, in patients in need for high dosage per kg body weight. Benefits for some populations such as children, African Americans, and diabetics have been detected. In combined kidney-pancreas transplantation a significant improvement of absorption has been proven. NEO has also been investigated in nonrenal transplants such as heart, lung, and liver transplantation. There are proven dose reduction in heart transplants; significant better absorption in lung transplants, in particular in patients with cystic fibrosis; and no further or even a diminished need for intravenously given CsA in liver transplantation. Studies are now reported for the use of NEO in differing indications of autoimmune disease. No characteristic profile of adverse events has been recognized, nor has an increase of nephrotoxicity if carefully monitoring in the first weeks after conversion was provided.
Emphysematous pyelonephritis is a rare, often severe infection of one or both kidneys that is most often caused by bacterial infection. Surgical intervention is often necessary. We describe a case of a diabetic patient with bilateral emphysematous pyelonephritis caused by Candida infection that was treated conservatively. Renal function recovered almost completely in spite of giving a potential nephrotoxic drug for 6 weeks.
During the past 3 years, the basis of a German Renal Registry has been established. An agreement between end-stage renal disease (ESRD) therapy providers, insurance companies and the government has been reached to fund and support the registry office and its electronic data base. An overall acceptable compliance has been achieved to provide data voluntarily, although in the future the data submission will have to be mandatory to achieve complete data sampling within an acceptable time frame. In Germany, 713 patients per million population (p.m.p.) are on renal replacement therapy (RRT). The incidence of new patients commencing RRT is 156 p.m.p. These numbers are comparable with those reported from other European countries such as France, Italy and Spain, but significantly lower than those reported from the US or Japan. More than 92% of all dialysis patients are treated by haemodialysis and only a limited number with peritoneal dialysis. Approximately 25% of the patients have a functioning kidney graft. The transplantation rate of 25 p.m.p. is far from sufficient if compared with Spain, Austria or the US. Although an increasing number of diabetic patients commenced RRT, the percentage, i.e. approximately 30%, is less than in the US or Japan. The annual growth of the population on renal replacement cannot currently be given precisely because the database is still limited, but it seems to be approximately 3-4%.
BACKGROUND: Moderate elevations of cardiac troponin (Tn) T, up to levels presumably diagnostic for minor myocardial damage, are suspected to be false positive in nearly 0.3 of end-stage renal disease (ESRD) patients undergoing haemodialysis (HD). It is not clear whether cardiac TnI is superior to TnT in those patients, if differences between ESRD and pre-ESRD occur, and what the prognostic meaning of these troponin elevations might be. SUBJECTS AND METHODS: We examined 40 chronic renaldisease patients [56.4 SD 13.9 years; 22 male, 18 female) without evidence of an acute coronary syndrome (ACS) for at least 28 days prior to the investigation. Cardiac status was determined by history, physical examination, ECG and echocardiography. Patients were divided into subgroups with HD (n = 20) and without HD (n = 20). Patients without HD had a mean creatinine clearance (CC) of 13.45 ml/min. Tn were measured by immunoassay techniques. TnT was compared to two different TnI tests (TnID, TnIB), CK/CKMB activity and myoglobin (MYO) concentrations. In all patients, a 9-month follow-up for acute myocardial infarction, re-hospitalization, and death was completed. RESULTS: None of the troponins significantly predicted patient outcome. Tn did not correlate with CC (r<0.6). Applying the lowest reported threshold values for all tests in the HD group, 0.3 patients were positive for TnT, 0.55 patients were positive for TnID, and 0.15 for TnIB. In the group without HD, 0.2 patients were positive for TnT and TnID and 0.1 for TnIB. CONCLUSIONS: Moderate elevations of cardiac troponins are common in clinically stable patients with renal disease and are neither diagnostic for an acute coronary syndrome nor predictive of outcome. It is concluded that increased troponins in asymptomatic renal patients are of questionable value for risk stratification, most probably due to unspecific elevations.
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OBJECTIVE: To determine incidence, severity, characteristics, and causes of anemia and transfusion requirements in medical intensive care patients. DESIGN AND SETTING: Open prospective clinical study in a 24-bed medical intensive care unit in a tertiary-care university hospital. PATIENTS: Patients (N = 96) treated in the intensive care unit for >3 days. INTERVENTIONS: None. MEASUREMENTS: Parameters of erythropoiesis and red blood cell metabolism, including hemoglobin, reticulocyte counts, serum iron, transferrin, ferritin, haptoglobin, vitamin B12, folic acid, and erythropoietin concentrations were determined serially. Diagnostic blood loss and red blood cell transfusions were recorded, and the total blood loss was estimated from changes in hemoglobin concentrations and the amount of hemoglobin transfused. MAIN RESULTS: The median hemoglobin concentration was 12.1 g/dL at admission and 11.2 g/dL at the end of the intensive care unit stay. A total of 74 patients (77%) suffered from anemia and received 257 red blood cell units, approximately half of which were given within the first 5 days. Three patients who received 19 red blood cell units were admitted with acute gastrointestinal bleeding, but in the remainder, a median total blood loss of 128 mL/d was not (n = 60) or not solely (n = 11) a result of overt bleeding. Diagnostic blood loss declined from a median of 41 mL on day 1 to <20 mL after 3 wks and contributed 17% (median) to total blood loss. Acute renal failure, fatal outcome, and simplified acute physiology score >38 on admission were associated with a 5.8-, 7.0-, and 2.8-fold increase in total blood loss. Reticulocyte counts and erythropoietin concentrations were inappropriately low for the degree of anemia, and plasma transferrin saturation was mostly <20%. CONCLUSIONS: Anemia is frequent and results in a high requirement for red blood cell transfusions in the medical intensive care setting. A major proportion of blood loss is not caused by overt bleeding or diagnostic blood sampling but, rather, may result from various other reasons, e.g., occult gastrointestinal bleeding and renal replacement therapy. The erythropoietic response to anemia is blunted, probably as a consequence of an inappropriate increase in erythropoietin production and diminished iron availability. (Crit Care Med 1999; 27:2630-2639)
Leukocyte infiltration plays a major role in ischemia-associated organ dysfunction and damage. A crucial step for extravasation of white blood cells is binding of leukocyte beta-integrins to endothelial adhesion molecules intercellular adhesion molecule-1 (ICAM-1) and vascular adhesion molecule-1 (VCAM-1). To test for direct effects of oxygen on this process we studied ICAM-1 and VCAM-1 expression in human dermal microvascular and umbilical vein endothelial cells (EC) exposed to different oxygen tensions in the absence or presence of tumor necrosis factor-alpha (TNF-alpha). Hypoxia (95% N2-5% CO2) resulted in a downregulation of basal but not TNF-alpha-induced expression of ICAM-1 and VCAM-1. Subsequent rises in oxygen (21, 40, or 95% O2) led to marked increase of ICAM-1 and VCAM-1 cell surface and mRNA expression in both EC types, which after 16 h amounted to about one-third to one-half of maximal TNF-alpha-induced expression. This increase was greatest after 0.5-h hypoxia and was blunted with prolonged hypoxic preincubation. Exposure of cells preincubated under "normoxic" (21% O2) conditions to hyperoxia (40 or 95% O2) also enhanced expression of both adhesion molecules, but the increase was lower than in cells preexposed to hypoxia. The nitric oxide synthesis inhibitor NG-nitro-L-arginine methyl ester (L-NAME) enhanced ICAM-1 and VCAM-1 expression under basal and hypoxic conditions, but in the presence of L-NAME, levels in reoxygenated cells were not higher than basal levels. Moreover, the oxygen-induced rise could be mimicked by addition of H2O2 to normoxic cells, and the oxygen-induced expression of VCAM-1 but not of ICAM-1 was inhibited by addition of the free radical scavengers superoxide dismutase, N-acetyl-L-cysteine, and pyrrolidinedithiocarbamate. These data indicate that an increase in oxygen availability stimulates ICAM-1 and VCAM-1 expression on micro- and macrovascular EC, which may contribute to adhesion and transmigration of different leukocyte populations in ischemia-reperfusion injuries.
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Anemia is a common complication of chronic renal failure (CRF). With the availability of recombinant human erythropoietin (rhEPO) over the last decade, much progress has been made in the management of anemia in patients with end-stage renal disease (ESRD) [Eschbach 1995, Gimenez and Scheel 1994, Muirhead et al. 1995, Winearls 1995]. The clearest benefit of rhEPO in ESRD is a substantial reduction in transfusion dependency, which reduces the need for hospital admission and the risk of viral transmission. Improvements in hemostasis and a decrease in human leucocyte antigen (HLA) antibodies have also been reported. Beneficial effects of rhEPO on the cardiovascular system in ESRD include regression of left ventricular hypertrophy (LVH), improvement of angina, and a modest increase in aerobic work capacity. Treatment of anemia with rhEPO has also been shown to improve cognitive function, socialization and quality of life in dialysis patients, although this has not led to better vocational rehabilitation or employment status. It has also been reported that a lower hemoglobin (Hb) content is an independent risk factor for increased mortality in hemodialysis patients [Harnett et al. 1995]. Clearly, therefore, treatment of anemia associated with ESRD is required and beneficial. The optimum treatment of anemia prior to dialysis, however, is still a matter for debate.
Since August 1992, 18 patients underwent combined liver and kidney transplantation. Eight patients had lymphocytotoxic antibodies pretransplant and 5 of these patients (27.7%) had a positive crossmatch. Fifteen patients received cyclosporine-based immunosuppression and 3 patients were treated with a tacrolimus-based immunosuppressive protocol. One patient died in the postoperative course due to intractable bleeding episodes after 96 days and one kidney graft was lost due to technical complications. The 1 year survival rate of patients with combined transplantation was 95% vs 87% in patients with liver transplantation alone. None of the patients with a positive crossmatch experienced a hyperacute rejection of the kidney. The long-term patient and graft survival was not impaired in patients with a positive crossmatch. These results suggest that combined liver-kidney transplantation is a safe treatment for end-stage liver and renal disease. A positive crossmatch or positive lymphocytotoxic antibodies are not contraindications for a combined transplantation.
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