Crush syndrome in polytrauma - octreotide in a novel therapeutic concept.
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Biomedical subjects
Publications and source records attributed to E Werle.
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We report here for the first time a patient with mu heavy-chain disease (HCD), hyperimmunoglobulinemia, and a positive direct antiglobulin test (DAT, Coombs test). The heavy-chain diseases involve the proliferation of lymphoplasma cells of B cell origin and are characterized by the production of incomplete heavy chains devoid of light chains. The association of mu heavy-chain disease with either hyperglobulinemia or a positive DAT has not been reported in the literature to date. In this patient, immunofixation of serum proteins with monospecific antisera to alpha-, gamma-, mu,- or delta-chains and to kappa- and lambda-chains revealed a precipitation band with antibody to IgM, but not with kappa and lambda light-chain antibodies, indicating mu heavy-chain disease. Hyperglobulinemia was present, which is very uncommon for HCD. A DAT of the patient's red blood cells (RBC) was found to be strongly positive for anti-IgG but negative for anti-IgM, -IgA, -C3c, and -C3d. However, when the eluate from the patient's red blood cells was investigated with nephelometry, it was found to contain antigens reactive with anti-y as well with anti-mu-antiserum. When a DAT was performed with a randomly chosen test cell incubated with the eluate, the antibody-containing eluate was shown to react with anti-IgG as well as with anti-IgM-antiserum. In summary, the eluate from the patient's RBCs contained IgG and an immunoglobulin structure reactive with anti-IgM in an RBC agglutination assay as well as with anti-mu antiserum in a nephelometric investigation. Whether this IgM on the patient's erythrocytes is penta- or oligomeric, complete IgM, or the heavy chain cannot be concluded from these observations.
The glycoprotein laminin, a cross-shaped complex of three genetically different polypeptide chains, is a structural component of the capillary basement membrane. Serum laminin concentrations of healthy controls (n = 60) and adult type I diabetic patients (n = 170) were not age-dependent. Laminin was correlated with hemoglobin A1 (HbA1) values in normoalbuminuric patients (rs = .33, P < .0005, n = 116). Type I diabetic patients without nephropathy or retinopathy in good metabolic control had normal laminin levels. However, increasing stages of microangiopathy were associated with higher laminin levels. The molecular size distribution of serum laminin of control subjects (n = 4) and type I diabetic patients (n = 15) was analyzed by molecular-sieve chromatography. Laminin was eluted in two peaks with a molecular mass of 900 and 300 kd, most likely representing intact laminin and its P1 fragment, respectively. The areas of the two peaks were determined by two-gaussian function fitting. In patients without microangiopathy in poor metabolic control, an increase in the high-molecular weight (HMW) fraction could be detected as compared with healthy subjects and patients with acceptable metabolic control. Furthermore, the HMW laminin fraction and the ratio between the areas of the first and second peak increased with the stage of nephropathy (P < .001, Jonckheere-Terpstra test). These results provide evidence that (1) laminin concentration is increased in chronic hyperglycemia, (2) laminin may be a marker of microangiopathic lesions, and (3) elevated laminin levels may reflect an increased synthesis and/or a defective incorporation of laminin into the capillary basement membrane.
We performed a case-control study to investigate the role of recent infection as stroke risk factor and to identify pathogenetic pathways linking infection and stroke. We examined 166 consecutive patients with acute cerebrovascular ischemia and 166 patients hospitalized for nonvascular and noninflammatory neurologic diseases. Control subjects were individually matched to patients for sex, age, and season of admission. We assessed special biochemical parameters in subgroups of stroke patients with and without recent infection (n = 21) who were similar with respect to demographic and clinical parameters. Infection within the preceding week was a risk factor for cerebrovascular ischemia in univariate (odds ratio [OR] 3.1; 95% confidence interval (CI), 1.57 to 6.1) and age-adjusted multiple logistic regression analysis (OR 2.9; 95% CI, 1.31 to 6.4). The OR of recent infection and age were inversely related. Both bacterial and viral infection contributed to increased risk. Infection elevated the risk for cardioembolism and tended to increase the risk for arterioarterial embolism. Stroke patients with and without preceding infection were not different with respect to factor VII and factor VIII activity, fibrin monomer, fibrin D-dimer, von Willebrand factor, C4b-binding protein, protein S, anticardiolipin antibodies, interleukin-1 receptor antagonist, soluble tumor necrosis factor-alpha receptor, interleukin-6, interleukin-8, and neopterin. In conclusion, recent infection is an independent risk factor for acute cerebrovascular ischemia. Its role appears to be more important in younger age groups. The pathogenetic linkage between infection and stroke is still insufficiently understood.
A cross-sectional study was performed to examine the internal exposure of polychlorinated dibenzo-p-dioxins and polychlorinated dibenzofurans (PCDF) in former workers in a nonferrous metal recycling facility. Liver enzymes, lipid parameters, and thyroid hormones were measured to check possible biologic effects. Compared to background levels, the international toxicity equivalent levels of exposed workers were slightly elevated (median 42 ppt, range 13-281 ppt). The workers also had higher total PCDF concentrations (median 128 ppt, range 30-1138 ppt). Correlation analyses demonstrate significant associations with only one liver enzyme, alanine aminotransferase. There were no such associations with serum cholesterol levels or with serum thyroid hormones. Because of the cross-sectional design of the study, firm conclusions cannot be drawn. For further evaluation, a follow-up examination appears necessary.
Uremia raises lipoprotein(a) (Lp(a)) serum concentration and the risk of arteriosclerosis in dialysis patients. The treatment of high Lp(a) levels is not satisfactory today. The decrease of Lp(a) in hypothyroid patients on L-T4 therapy raised the question of whether dextro-thyroxine (D-thyroxine) reduces not only serum cholesterol, but also Lp(a) serum concentration. In a single-blind placebo-controlled study, the influence of D-thyroxine therapy on Lp(a) serum concentration was evaluated in 30 hemodialysis patients with elevated Lp(a) serum levels. Lp(a) was quantified in parallel by two methods, i.e., rocket immunoelectrophoresis and nephelometry, and apo(a) isoforms were determined by a sensitive immunoblotting technique. Regardless of the apo(a) isoforms, 6 mg/d D-thyroxine reduced elevated Lp(a) levels significantly by 27 +/- 13% in 20 dialysis patients (P < 0.001) compared with 10 control subjects (-9.9 +/- 8.4%). In parallel, D-thyroxine therapy significantly lowered total cholesterol (P < 0.001), LDL cholesterol (P < 0.001), and LDL cholesterol/HDL cholesterol ratio (P < 0.01); raised T4 and T3 serum levels; and suppressed thyroid-stimulating hormone secretion without causing clinical symptoms of hyperthyroidism in any of the patients. D-Thyroxine reduces elevated serum Lp(a) concentration in dialysis patients. The effect in nondialysis patients can be expected but remains to be proven.
OBJECTIVE: To examine the association of renal function in diabetic patients with apolipoprotein (apo) E polymorphism. RESEARCH DESIGN AND METHODS: Apo E genotypes, lipid and lipoprotein serum levels, creatinine clearance (CCr), and excretion of marker proteins were determined in German type 1 (IDDM; n = 162) and type 2 (NIDDM; n = 124) diabetic patients. Albumin and immunoglobulin (Ig) G are considered to reflect charge-size permselectivity of the glomerular capillary basement membrane, and increased alpha 1-microglobulin (MG) excretion indicates compromised reabsorptive capacity of the renal tubules. RESULTS: Patients with NIDDM had higher lipid levels and lower CCrs than patients with IDDM. In patients with IDDM, age- and sex-adjusted analysis of variance showed an association between apo E genotypes and CCr, and the Jonckheere-Terpstra test demonstrated a decreasing glomerular filtration rate in the following order of genotypes: epsilon 4 epsilon 4/epsilon 4 epsilon 3 > epsilon 3 epsilon 3 > epsilon 2 epsilon 2/epsilon 2 epsilon 3. Multiple linear regression analyses revealed that in patients with IDDM, the epsilon 2 allele was a negative predictor of CCr and a positive predictor of urinary excretion of albumin, IgG and alpha 1-MG independent from HDL and LDL cholesterol, TG concentration, age, and sex. CONCLUSIONS: Apo E polymorphism influences serum lipoprotein levels in patients with IDDM and NIDDM. Apo E polymorphism may be a renal risk factor of clinical relevance in normolipidemic patients with IDDM.
Collagen IV matrix of glomerular basement membrane may be involved in the development of various renal diseases, e.g. diabetic nephropathy. An immunoblotting method for the detection of the carboxy-terminal non-collagenous (NC1) domain of type IV collagen in plasma was developed. The high sensitivity down to the picogram range enabled characterization of NC1(IV) fragments in human blood for the first time. Both Western blotting and gel filtration chromatography coupled with an enzyme-linked immunoassay surprisingly revealed that the NC1(IV)-related components are bound to the fibrin clot forming during blood coagulation. About 40% of the NC1(IV) fragments in plasma had an apparent molecular mass higher than 340,000. Abnormal NC1(IV) immunoblot patterns were observed in about 50% of patients with insulin-dependent (n = 20) and non-insulin-dependent (n = 20) diabetes mellitus compared with less than 7% in healthy control subjects (n = 30). There were no obvious associations between abnormal immunoblots and stage of nephropathy or glycaemic control in diabetic subjects.
The authors report on a profound increase in creatine kinase isoenzyme MB (CK-MB) activity in three patients following uneventful cryoablation of the prostate under general anaesthesia: Just after the arrival at the recovery room CK-MB levels were 321 U/l, 245 U/l and 433 U/l, respectively. Other clinical investigations as well as additional laboratory tests ruled out myocardial infarction in all three patients. Electrophoresis of the CK-isoenzymes revealed an increase in CK-BB activity and an increase in atypical CK-BB as a cause of these findings. The presence of these isoenzymes leading to interferences with the antibody commonly used in CK-MB assays could explain the determination of a false positive CK-MB elevation in the three patients. Moreover, it is shown that this method of CK-MB activity determination may result in CK-MB levels higher than 100% of the whole CK activity. In addition, it is discussed that in patients suffering from prostatic carcinoma or other malignoma, "non-CK-M elevations" may occur. Therefore, the authors conclude that after cryoablation of the prostate additional tests like troponin T test and 12 channel ECG are required to rule out suspected myocardial infarction.
In 154 subjects (age 63 +/- 11 years; 63 women and 91 men) randomly selected from the population, we tested the hypothesis that inflammatory parameters are associated with vascular risk factors and particularly with a history of ischemic vascular diseases. The subjects were part of the control group (n = 197) in a case-control study investigating recent infection as a risk factor for acute cerebrovascular ischemia and had been matched for sex and age with patients suffering from acute ischemic stroke or transient ischemic attack. Subjects with malignant or inflammatory diseases, with recent trauma, surgery or vascular diseases (n = 43) were excluded from the present analysis. In multivariate analysis, current smoking, diabetes mellitus, age > or = 65 years, and a history of stroke independently increased the leukocyte count. Hypertriglyceridemia, peripheral arterial disease, and diabetes mellitus were positively associated with C -reactive protein (CRP). Age > or = 65 years and diabetes mellitus independently increased fibrinogen. (p < 0.05, respectively) Subjects with a history of cerebrovascular, cardiovascular or peripheral arterial disease had higher leukocyte counts, fibrinogen and CRP than subjects without vascular risk factors and higher leukocytes and fibrinogen than subjects with one or more risk factors. Subjects under the age of 65 with vascular risk factors but without ischemic diseases had higher leukocyte count, fibrinogen and CRP and subjects older than 65 with risk factors had higher CRP than subjects without risk factors or ischemic diseases in the same age group. (p < 0.05, respectively) These results support the hypotheses that low-grade inflammation is associated with vascular risk factors and that inflammatory mechanisms may contribute to the risk of organ ischemia.
To test the value of carbohydrate-deficient transferrin (CDT) as a marker for chronic alcohol consumption, its concentration was measured in the serum of 74 patients (48 men, 26 women; mean age 48 [18-71] years) with various alcohol-related liver diseases, ten patients (six men, four women; mean age 61 [24-90] years) with non-alcohol related liver diseases and 30 healthy controls (12 men, 18 women; mean age 37 [19-84] years). In the healthy women the mean CDT concentration was 19.7 +/- 6.1 U/L, in healthy men 15.4 +/- 4.1 U/l (P < 0.05). The upper limit of normal (mean + 2 standard deviations) was 31.9 U/l in women and 23.6 U/l in men. Serum CDT levels were significantly raised in chronic alcohol abuse, depending on the degree of liver damage. The CDT level in alcohol-dependent women without liver disease was 31.1 +/- 4.3 U/l (P < 0.05), while in those with liver damage it was 42.3 +/- 14.2 U/l (not significant). The mean CDT concentration in male alcoholics without liver damage was 35.5 +/- 5.0 U/l (P < 0.01 compared with controls). In male alcoholics with liver damage the mean CDT level was 53.4 +/- 9.0 U/l (P < 0.001). In none of the ten patients with non-alcohol related liver disease was the CDT level above the upper limit of normal. The sensitivity of CDT as a marker for chronic alcohol consumption was 57% (42% for women, 65% for men) with a 100% specificity. For serum-gamma-glutamyl transferase the sensitivity was 87%, but its specificity only 73%. Because of its high specificity the serum CDT level is an added useful marker for demonstrating chronic alcohol consumption.
BACKGROUND AND PURPOSE: Currently, recent infection (primarily bacterial infection) is discussed as a risk factor for cerebrovascular ischemia. The aim of this study was to investigate whether the association of ischemic stroke with recent infection is restricted to stroke subtypes and whether recent infection influences the severity of the postischemic deficit; we also aimed to define biochemical pathways linking infection and ischemic stroke. METHODS: Analyzing the data of a prospective case-control study, we classified the etiology of cerebrovascular ischemia on the basis of clinical, neuroradiological, sonographical, cardiological, and biochemical data in 159 patients without and in 38 patients with infection within 1 week before ischemia. We assessed the severity of neurological deficits using the Scandinavian Stroke Scale. RESULTS: In patients with recent infection compared with patients without infection, the neurological deficit on admission was more severe (median of scores, 41 versus 30.5; P < .005), cortical infarcts in the middle cerebral artery territory were more frequent (60% versus 26%; P < .001), the prevalence of extracranial artery stenoses was lower (9% versus 26%; P < .05), and definite or presumed cardioembolic stroke was more frequent (34% versus 19%; P < .05), as was stroke from cervical artery dissection (8% versus 1.3%; P = .05). Serum levels of C-reactive protein were higher in patients with (20.7 +/- 26.8 mg/L) than in those without infection (9.2 +/- 23.7 mg/L; P < .01). CONCLUSIONS: Recent infection may be associated with a more severe postischemic deficit and with an increased risk of stroke from cardioembolic origin and from cervical arterial dissection.
The aim of the study was to investigate the frequency and clinical significance of anticardiolipin antibodies (aCL) in systemic lupus erythematosus (SLE). 32 of 100 patients with SLE had positive anticardiolipin antibodies. Increased aCL were associated with thrombosis, thrombocytopenia, miscarriage, vasculitic skin changes and neurological symptoms. The incidence of thrombosis, thrombocytopenia, and neurological symptoms was significantly increased in the aCL-positive group as compared to the aCL-negative group. These findings confirm the results of former investigations and underline the role of aCL in systemic lupus erythematosus.
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Severe Plasmodium falciparum malaria is characterized by multiple organ involvement due to sequestration of infected erythrocytes in small vessels. Endothelial cell adhesion molecules play an important role in this interaction. During the course of a severe cerebral P. falciparum malaria infection we found very markedly elevated levels of the soluble adhesion molecules intercellular adhesion molecule-1, E-selectin, and vascular cell adhesion molecule-1, with a maximum increase of nine, seven, and eight times, respectively. These very high levels of soluble adhesion molecules point to an endothelial cell injury as an additional cause to physiological release or shedding due to receptor interactions. Soluble thrombomodulin (sTM) levels showed an extremely marked elevation up to 332 ng/ml (up to 13 times the normal value) as well. Malaria patients without severe organ involvement/cerebral manifestation showed only a mild elevation of sTM levels. TM is a parameter independent of the immunological system. It is regarded as a marker of vasculitis and endothelial cell destruction. Therefore, markedly elevated sTM levels document a substantial endothelial cell injury in severe malarial infection and may be of diagnostic and prognostic importance.
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Anti-Candida antibodies were determined in 2053 sera with an indirect hemagglutination test (HAT; Labor Diagnostika, Heiden, Germany) and with an enzyme immunoassay (ELISA) which detects IgG antibodies (Institut Virion, Würzburg, Germany). Antigen diagnostics was performed with the Cand-Tec-test (Ramco, Houston, USA). Eighty-eight sera from sixteen patients which were positive for IgG antibodies were screened for IgA and IgM antibodies by ELISA. A humoral immune response during the hospital stay of the sixteen patients was detected first by the HAT. The HAT was also reactive when the IgG and/or IgA antibodies rose above the upper reference value and the IgM antibody level remained unchanged. Synchronous changes of IgG, IgM and IgA antibody concentrations even within the normal range are detected by the HAT several days before one or more of these antibodies rose above the upper reference value. In most patients the IgM immune response preceded an increase in IgG and/or IgA antibody concentration by several days. In patients in whom the serum HAT titer remains constant as a consequence of a decreasing IgM antibody level and an increasing IgG antibody concentration, the selective determination of IgM antibodies by ELISA may yield additional information, e.g. a drop in IgM antibodies may be due to a successful therapy. In several patients antigen detection and antibody screening by HAT should be complemented by an immunoglobulin specific measurement of anti-Candida antibodies.