Autoantibodies to double-stranded DNA--intermethod comparison between four commercial immunoassays and a research biosensor-based device.

Patients with systemic lupus erythematosus (SLE) often develop a wide variety of serological manifestations including the presence of antibodies to double-stranded DNA (anti-dsDNA). Positivity for anti-dsDNA constitutes one of the laboratory criteria for the diagnosis of SLE and is therefore clinically relevant. We analyzed the diagnostic accuracies of four commercial anti-dsDNA immunoassays and compared the results with a recently established surface plasmon resonance (SPR) biosensor chip with covalently chip-immobilized dsDNA. The anti-dsDNA measurements were performed retrospectively in 50 patients with clinically proven SLE, 39 patients with other autoimmunopathies and 20 healthy controls. Data were evaluated by Receiver-Operator Characteristic (ROC) analysis, with special regard to SLE patients suffering from lupus nephritis. The ROC analyses for the four immunoassays and the SPR biosensor resulted in the following area-under-the-curve (AUC) and diagnostic efficiency (DE) values in descending order: Bindazyme AUC, 0.89; DE, 0.88; ELiA AUC, 0.89; DE, 0.86; SPR biosensor AUC, 0.82; DE, 0.80; Farrzyme AUC, 0.77; DE, 0.77; Farr AUC, 0.77; DE, 0.70. When considering the 22 nephritis SLE patients the following AUC were observed: Bindazyme 0.98; EliA 0.95; SPR biosensor 0.93; Farr 0.89; Farrzyme 0.88. Although various methodologies for the determination of anti-dsDNA were compared, the overall diagnostic accuracy was found satisfactory in all immunoassays. Best data were found for the Bindazyme assay. We referenced the measurements to our in-house SPR biosensor device which showed good AUC and DE values. When optimized, this technique, allowing to monitor antigen/ antibody interactions in real-time, may add a new analytical quality to the existing methods, potentially beneficial in diagnosis and clinical monitoring of SLE.

L-2-hydroxyglutaric aciduria: identification of ten novel mutations in the L2HGDH gene.

L-2-hydroxyglutaric aciduria (L-2-HGA) is a metabolic disease with an autosomal recessive mode of inheritance. It was first reported in 1980. Patients with this disease have mutations in both alleles of the L2HDGH gene. The clinical presentation of individuals with L-2-HGA is somewhat variable, but affected individuals typically suffer from progressive neurodegeneration. Analysis of urinary organic acids reveals an increased signal of 2-hydroxyglutaric acid, mainly as the L-enantiomer. L-2-HGA is known to occur in individuals of various ethnic backgrounds, but up to now mutation analysis has been mainly focused on patients of Turkish and Portuguese origin. This led us to confirm the diagnosis on the DNA level and undertake the corresponding mutation analysis in individuals of diverse ethnicity previously diagnosed with L-2-HGA on the basis of urinary metabolites and clinical/neuroimaging data. In 24 individuals from 17 families with diverse ethnic and geographic origins, 13 different mutations were found, 10 of which have not been reported previously. At least eight of the patients were compound heterozygotes. The identification of two mutations (c.751C > T and c.905C > T in exon 7) in patients with different origins supports the view that they occurred independently in different families. In contrast, the mutation c.788C > T was detected in all six Venezuelan patients originating from the same Caribbean island of Margarita, but not in other patients, thus rendering a founder effect likely. None of the mutations was found in the control population, indicating that they are most probably causative. Mutation analysis may improve the quality of diagnosis and prenatal diagnosis of L-2-HGA.

Anti-dsDNA antibody subtypes and anti-C1q antibodies: toward a more reliable diagnosis and monitoring of systemic lupus erythematosus and lupus nephritis.

The putative distinct diagnostic and pathogenic potential of aDNA-Ab subtypes, differing in their affinity or epitope specificity, was subject of several studies with controversial results. Comparing five assays, characterized by different reaction conditions and nature/source of dsDNA, we investigated the abovementioned problem in a retrospective study on 100 systemic lupus erythematosus (SLE) patients and 100 controls (other CTD, autoimmune hepatopathies). As demonstrated, only assay 3 (Farrzyme, TBS, UK) and 5 (Farr-RIA, Trinity Biotech, Ireland) are really suitable to detect primarily high avidity aDNA-Ab. Both were significantly linked to lupus nephritis (specificity 84%) and highly specific for SLE (95 and 96%). Thereby, assay 3 was found to be the first solid phase ELISA probably suitable to replace the Farr-RIA. Classical ELISAs (assay 1, Orgentec, Germany, and 2, Bindazyme, TBS, UK), detecting aDNA-Ab more or less independent from their avidity, or tests with only intermediate specificity for high avidity Ab (assay 4, ELIAdn, Sweden Diagnostics, Germany), were less specific for SLE (83, 79, 91%, respectively) and not associated with renal involvement (specificity 54-57%). At least in the patients studied here, obvious antigen-related differences could not be observed. With slight differences, all assays were suitable to monitor disease activity and therapy in SLE, agreeing with the ECLAM score in about 70-80% of cases. For lupus nephritis, aC1q-Ab are as specific as high avidity aDNA-Ab and capable to close a diagnostic gap in some cases. Thus, to enhance the specificity (up to 98%) and to consider the distinct diagnostic/pathogenic potential of aDNA-Ab subtypes in SLE, under routine clinical laboratory conditions it should be recommended to combine a sensitive screening test with a more specific second assay.

[Two-tier screening process (TEOAE/AABR) reduces recall rates in newborn hearing screening]. / Sequenzielles Neugeborenen-Hörscreening (TEOAE/AABR) reduziert Recall-Rate. Erfahrungen in einem Berliner Perinatalzentrum.

BACKGROUND: 1-2/1,000 newborns are affected by connatal permanent hearing impairment. Clinical diagnosis is often delayed. This demands newborn hearing screening (NHS). Some questions regarding the optimal method remain unsolved. METHODS: The newborns in the obstetrical department (low-risk group) are tested by automated transitory evoked otoacustic emissions (TEOAE). TEOAE-fail is followed by automated auditory brainstem response (AABR) examination. All sick newborns admitted to the pediatric department (high-risk group) are primarily tested using AABR. Pathological AABR-testing leads to pedaudiological diagnostic work-up. RESULTS: In the low-risk group, 82 out of 1,584 newborns failed TEOAE-testing (recall 5.18%). Only 5 of these patients failed consecutive AABR examination (recall 0.32%). Permanent hearing loss was finally confirmed in 3 children (0.13%). 10 out of 755 newborns in the high-risk group failed AABR-testing (1.32%). In 6 of these children, hearing loss was confirmed (0.79%). CONCLUSION: A two-tier screening process as described is able to reduce recall rate, overall expenses and parental anxiety.

Autoantibodies to prothrombin and phosphatidylserine/prothrombin-complexes: do they contribute to the serodiagnosis of primary and secondary anti-phospholipid syndrome?

The diagnostic and clinical relevance of Ab to pure and phosphatidylserine-complexed prothrombin for primary and secondary APS was investigated in a total of 357 patients with (n = 169) and without (n = 188) connective tissue diseases. The overall frequency of anti-prothrombin Ab in sAPS, pAPS and patients without APS-related symptoms were found to be 50.0, 37.5 and 22.0%, respectively. From a total of 72 anti-prothrombin-positive samples, 12.5% were specific for pure prothrombin, 31.9% for phosphatidylserine/prothrombin-complexes and 55.6% recognized both antigenic forms. The simultaneous occurrence of other anti-phospholipid Ab was observed in 84% of all sera. Both types of anti-prothrombin Ab are significantly associated with lupus anticoagulant activity, but only Ab to pure prothrombin display such a relationship to clinical manifestations of APS. Based on these results, it cannot be recommended at present to include anti-prothrombin assays in the routine procedure for the serodiagnosis of APS. However, patients negative for lupus anticoagulant and typical APS-related anti-phospholipid Ab should be tested for anti-prothrombin reactivity, favoring, mainly due to its higher specificity, the ELISA containing pure prothrombin as antigen.

Reactivity profiles of autoantibodies to different phospholipids and the phospholipid-binding protein beta2-glycoprotein I in patients with clinical symptoms related to thromboembolic and/or vasculopathic events with or without connective tissue diseases.

To study the antigenic and epitope specificities of anti-phospholipid Ab in detail, we investigated 177 patients without (62 with APS-related systemic clinical symptoms, 115 with microangiopathies) and 164 patients with connective tissue diseases (CTD). Ab associated with primary APS (pAPS) seem to show a restricted specificity (phospholipid/beta2-GPI-complexes), whereas those in secondary APS (sAPS) react additionaly with pure beta2-GPI. Simultaneously, beta2-GPI-independent Ab were also frequently present in both conditions (50% of all Ab-positive sera). In CTD patients, the reactivity profile "pure beta2-GPI + phospholipid/beta2-GPI-complexes" is significantly associated with clinically manifest sAPS. Comparing cardiolipin and phosphatidylserine as antigenic target, the overall concordance (crossreactivity?) between both assays was lower than expected (52%), being highest in pAPS (87%) and sAPS (65%). Based on these results, a two-step procedure for reliable serological diagnosis of APS could be recommended: Ab-screening using a mix of phospholipids complexed with beta2-GPI (sensitivity > 90% for Ab concentrations above 20 U/ml) followed by an assay allowing the simultaneous detection of all relevant antigenic and epitope specificities.

Monocyte function and plasma levels of interleukin-8 in acute ischemic stroke.

Activated monocytes may contribute to the pathogenesis of ischemic stroke. We tested the hypothesis that release products and procoagulant activity of monocytes are increased in acute ischemic stroke. In patients on days 1, 3 and 7 after ischemic stroke and in age- and sex-matched healthy control subjects, we assessed plasma levels of interleukin 8 (IL-8) and neopterin (enzyme linked immunosorbent assay, ELISA) and investigated superoxidanion release (ferricytochrome C reduction), procoagulant activity (one-stage clotting assay) and tissue factor (TF) gene transcription (reverse transcriptase polymerase chain reaction) by monocytes. As compared to control subjects (n=23), IL-8 levels were increased on day 1 after stroke (n=22; p=0.005) and remained elevated on days 3 and 7. Neopterin levels were elevated on days 3 and 7 (p<0.05, respectively) but not on day 1. Neopterin and IL-8 were not correlated with monocyte counts. Superoxid anion production by stimulated and unstimulated monocytes was not different between groups. TF mRNA could neither be detected in monocytes from patients investigated within 12 h after ischemia (n=12) nor in control subjects (n=10) and procoagulant activity of cells was similar in both groups. Our results indicate increased monocyte activation after ischemic stroke although not all activation parameters were elevated. We found no support for the hypothesis that circulating monocytes express TF and possess increased procoagulant activity. Elevated IL-8 may contribute to stroke pathophysiology by activating polymorphonuclear leukocyte (PMNL) activation early after ischemia.

Metabolites of the L-arginine-NO pathway in patients with left-to-right shunt.

OBJECTIVES: The endogenous production of metabolites of the L-arginine-NO pathway has been found to be altered in patients with left-to-right shunt and pulmonary hypertension. The objective of this study was to analyze the influence of age and of the magnitude of the left-to-right shunt on plasma levels of L-arginine, cyclic guanosine monophosphate (cGMP), nitrite and nitrate in children and young adults presenting with left-to-right shunt. METHODS: Twenty-nine patients with ventricular septal defect (n=18), atrial septal defect (n=6) and atrioventricular canal (n=5) were assigned to group I when the ratio of pulmonary to systemic blood flow (Qp/Qs) was less than 1.5 (n=10) and to group II when Qp/Qs > or = 1.5 (n=19). At cardiac catheterization blood samples were taken from the pulmonary vein or left ventricle. In 33 controls peripheral venous blood was obtained. cGMP levels were determined by radioimmunoassay, L-arginine, nitrite and nitrate by high performance liquid chromatography (HPLC). RESULTS: L-arginine plasma levels were lower in group II than in controls (51.7 [23.3-82.2] versus 60.5 [32.4-85.9] pmol/l; p < 0.05 by KRUSKAL-WALLIS). Age did not influence the L-arginine plasma levels (p = 0.30). cGMP levels depended on age (p<0.01) and mean pulmonary artery pressure (p <0.01) but not on high pulmonary blood flow (p=0.85; ANOVA). Plasma nitrite and nitrate were not different in both groups and when compared with controls (nitrite: 26.0 [23.5-31.0] micromol/l; nitrate: 26.8 [24.0-32.0] micromol/l). CONCLUSIONS: Age and pulmonary artery pressure exert important effects on plasma cGMP. Measurement of nitrite and nitrate in plasma alone may not reflect the endogenous NO production. Future studies should evaluate the role of plasma levels of L-arginine in patients with high pulmonary blood flow undergoing repair of their defect.

Antibodies against serotonin have no diagnostic relevance in patients with fibromyalgia syndrome.

OBJECTIVE: To determine the prevalence and potential diagnostic relevance of autoantibodies against serotonin, thromboplastin, and ganglioside Gm1 in patients with fibromyalgia syndrome (FM). METHODS: Sera from 203 patients with FM and 64 pain-free control subjects were analyzed with enzyme immunoassays. Clinical and psychometric data of the patients were analyzed for the presence or absence of autoantibodies. RESULTS: Compared with control subjects patients with FM had a significantly higher prevalence of autoantibodies against serotonin (20% vs 5%; p = 0.003) and thromboplastin (43% vs 9%; p < 0.001), but not against ganglioside Gm1 (15% vs 9%; p = 0.301). Differences in autoantibody prevalence between controls and FM patients were not related to age or sex. No association was found between autoantibody pattern and clinical or psychometric data, e.g., pain, depression, pain related anxiety, and activities of daily living. CONCLUSION: There is an elevated prevalence of antibodies against serotonin and thromboplastin in patients with FM. The pathophysiological significance of this finding is unknown. Calculation of positive predictive values of antiserotonin antibodies shows that measurement of these antibodies has no diagnostic relevance.

Plasma levels of asymmetrical dimethyl-L-arginine in patients with congenital heart disease and pulmonary hypertension.

Asymmetrical dimethyl-L-arginine (ADMA) is an endogenous inhibitor of nitric oxide synthase. We hypothesized that plasma levels of ADMA could be increased in patients with congenital heart disease and pulmonary hypertension. Cardiac catheterization was performed in 20 children and young adults with congenital heart disease with a median age of 10 years (range, 4 months to 33 years). The patients were assigned to group I (high flow, low pressure; n = 14) when Qp/Qs was 1.5 or greater and the mean PAP was less than 25 mm Hg or to group II (high pressure, high resistance; n = 6) when the mean PAP was greater than 25 mm Hg and Rp/Rs was greater than 0.3. Blood samples were taken from pulmonary vein or left ventricle. ADMA was measured by high-performance liquid chromatography. In addition, levels of ADMA were measured in peripheral venous blood obtained from eight control patients. Levels of ADMA in control patients (median, 0.21 microM/l; range, 0.08-0.27 microM/l) did not differ from levels obtained in group I (median, 0.30 microM/l; range, 0.06-0.49) microM/l). Patients in group II showed increased plasma levels of ADMA (median, 0.55; range, 0.25-0.79) (p < 0.01). Inhibition of nitric oxide synthase by increased levels of ADMA might contribute to pulmonary hypertension in patients with congenital heart disease.

Assessment of plasma lactoferrin in Parkinson's disease.

Iron may play an important role in the pathogenesis of Parkinson's disease (PD). Recent studies have shown that the iron-transporting glycoprotein lactoferrin (LF) and its receptor are increased in the substantia nigra (SN) in PD. We investigated whether plasma levels of LF are altered in dopa-responsive PD. Plasma LF was not different between patients with PD (n = 23; 306 +/- 116 [mean +/- standard deviation] ng/ml) and age- and sex-matched healthy control subjects (n = 15; 359 +/- 126 ng/ml ). However, LF was inversely correlated with PD severity (r = -0.68, P = 0.002), an association that remained significant after adjustment for treatment with levodopa, monoaminooxidase inhibitors, and dopa agonists (r = -0.53, P = 0.017). Plasma transferrin and ferritin levels were not different between groups and neither correlated with disease severity nor with LF levels. Together with the result of increased nigral lactoferrin, this finding is compatible with the hypothesis of an imbalance between LF levels in blood and SN in progressing PD. Larger and particularly longitudinal studies and measurements of LF in cerebrospinal fluid are warranted to further examine the role of LF in PD.

Reactivities to the Sm autoantigenic complex and the synthetic SmD1-aa83-119 peptide in systemic lupus erythematosus and other autoimmune diseases.

The Sm antigenic complex is, besides dsDNA, the most important and specific autoimmune target in systemic lupus erythematosus (SLE). The population of anti-Sm Ab elicited is very heterogeneous in terms of epitope specificity resulting in a strong assay dependent detectability. Based on the description of a new autoantigenic target, the SmD1-aa83-119 peptide, we analysed 50 healthy persons and 205 patients with different autoimmune and other disorders with regard to their anti-Sm reactivities using different assays. The prevalence of anti-SmD1 peptide Ab and anti-Sm Ab in SLE was 36.0 (40/111) and 9.9% (11/111), respectively. The respective values obtained for non-SLE patients were 2.8 (4/144) and 5.3% (5/94). In SLE, anti-SmD1 peptide Ab are positively correlated to disease activity, nephritis and anti-dsDNA Ab. The association between reactivities of SLE samples in the traditional anti-Sm and the anti-SmD1 peptide ELISA was found to be 63.6%, contrasting markedly with the situation in non-SLE patients (no double-positive sera). SLE samples with an anti-Sm response restricted to the SmD1 peptide are completely negative in immunoblot, supporting the conformational nature of this epitope. Positive immunoblot reactions with the SmD1 polypeptide are not inhabitable by the synthetic SmD1-aa83-119 peptide. Comparing anti-Sm reactivities detected by ELISAs with those in immunoblot, different patterns were observed, reflecting the heterogeneous autoimmune response to this antigen. In conclusion, the anti-SmD1-aa83-119 peptide ELISA substantially completes the panel of methods for autoantibody testing. As none of the assays presently available covers the whole spectrum of epitope specificities of anti-Sm Abs elicited in SLE, it does not replace traditional anti-Sm ELISAs.

[Cerebrospinal fluid protein tau levels in the differential diagnosis of Alzheimer's disease]. / Tau-Protein-Spiegel in der Diagnostik der Alzheimer-Demenz.

Tau protein concentration in cerebrospinal fluid was determined in 55 patients with Alzheimer's disease (AD), 18 patients with vascular dementia (VD), 19 patients with dementia caused by other disorders and 14 patients with major depression. Significantly (p < 0.05) elevated protein tau concentrations were found in AD patients (564.5 +/- 275.5 pg/ml) compared to all other patient groups (VD: 406.5 +/- 263.9 pg/ml; other dementia: 275.0 +/- 135.4 pg/ml; depression: 212.9 +/- 115.6 pg/ml). However, tau levels in AD patients covered a broad range (163.2 pg/ml-1200 pg/ml). AD patients with tau levels below the 25%-percentile of the distribution (among them a high percentage of patients with presenile onset) showed tau levels similar to those of the patients with late life depression. No significant correlations between tau levels and clinical variables such as severity of dementia, age, age of onset, duration of illness, and cerebral changes as assessed by volumetric magnetic resonance imaging could be demonstrated. Similarly, we could not find an influence of either APO-E genotype or psychotropic medication on the tau levels in AD patients. In accordance with other studies our results confirm elevated tau levels in AD compared to elderly not demented control subjects. Comparing groups, this finding applies as well with respect to VD and other dementing disorders. However, elevated tau levels cannot be detected in a subgroup of AD patients. This finding needs to be further investigated in future studies.

G-CSF plasma levels in clozapine-induced neutropenia.

BACKGROUND: Clinical reports emphasize the therapeutic usefulness of granulocyte colony-stimulating factor (G-CSF) in clozapine-induced granulocytopenia. Only sparse information exists, however, on the natural course of endogenous G-CSF plasma levels in this condition. METHODS: We monitored G-CSF and white blood cell (WBC) counts in a 73-year-old patient who developed granulocytopenia while being treated with clozapine for schizoaffective disorder. Clozapine treatment was discontinued immediately, and G-CSF serum levels were determined repeatedly during the clinical course. RESULTS: Whereas WBC counts increased again within 6 days after discontinuation of clozapine, G-CSF level decreased significantly within the same period. The rapid decrease of endogenous G-CSF levels paralleled by a normalization of neutrophil count was interpreted as the result of an intact regulatory mechanism of granulocytopoesis. Therefore G-CSF therapy was not initiated. Owing to lack of therapeutic alternatives, it was decided to reintroduce clozapine. G-CSF levels decreased further, accompanied by an increase of WBCs, indicating stable bone marrow functioning. CONCLUSIONS: Based on this observation, we assume that the course of G-CSF and WBC counts indicated an abortive form of toxic bone marrow damage with subsequent recovery. We conclude that monitoring of G-CSF levels may serve as a useful tool in the follow-up of patients in whom clozapine-induced bone marrow damage is suspected.

Elevated plasma concentrations of lipoprotein(a) in medicated epileptic patients.

Lipoprotein(a) [Lp(a)] has been identified as an independent risk factor for vascular diseases. There are no data on Lp(a) levels in patients on long-term medication with carbamazepine, phenytoin, phenobarbital, or valproate. To investigate the effects of such treatment on Lp(a) levels and common carotid artery intima media thickness we studied 51 epileptic outpatients on long-term antiepileptic medication and 51 age-and sex-matched controls. Lp(a) levels above 45 mg/dl were found in 11 of 50 patients, but in only 4 of 51 controls (P < 0.05). The mean serum concentration of Lp(a) was 33.0+/-7.0 mg/dl in patients and 16.9+/-2.7 mg/dl in controls (P < 0.05). Epileptic patients also had a thicker intima media of the common carotid artery (0.79+/-0.04 mm) than controls (0.69+/-0.02 mm, P < 0.05) as measured by B-mode ultrasonography. Our results suggest an untoward effect of long-term antiepileptic medication on Lp(a) serum concentrations. Elevated Lp(a) levels might be a risk factor for arteriosclerosis in epileptic patients.

The influence of the ACE inhibitor lisinopril on the glomerular metabolism of proteolytic enzymes in diabetic rats.

Clinical studies indicate a nephro-protective effect in conjunction with the use of ACE inhibitors. This study's aim was to determine whether ACE inhibitors influence the metabolism of glomerular cells in addition to their known hemodynamic effects. Streptozotocin diabetic rats were treated with lisinopril (DLis 1.5 mg/l water), or hydralazine (Dhyd, 50 mg/l water) over 4 weeks. Untreated diabetic rats (DC) and non-diabetic rats (C) served as controls. After four weeks of treatment, urinary excretion of albumin, blood pressure and metabolic control (Glyc-Hb) were measured. After treatment glomeruli were isolated and homogenized, and beta-NAG and total proteolytic activity against azocasein were measured. Glycated hemoglobin levels were similar in all diabetic groups (DC, 12%, Dhyd, 10%; DLis 11%). Blood pressure of DLis rats (79 +/- 3 mmHg) and DHyd rats (46 +/- 2 mmHg) was lower than that of DC rats (111 +/- 3 mmHg). Urinary albumin excretion of diabetic groups was lowest in DLis. Diabetic rats showed a decrease in glomerular beta-NAG (10 vs. 60.5 U/g protein) and total proteolytic activity against azocasein (148 vs. 170 U/mg protein hour) compared to non-diabetic rats. Lisinopril increased beta-NAG (30 vs. 14 U/g protein) and total proteolytic activity (160.5 vs. 141.5 U/mg protein hour) compared with hydralazine. Our study confirms that the nephro-protective effect of ACE inhibitors is partially due to modulatory effects on the metabolism of basement membrane proteins.

Effects of restorative proctocolectomy on renal and adrenal function.

PURPOSE: Restorative proctocolectomy is a standard procedure in the surgical treatment of ulcerative colitis and familial adenomatous polyposis. The radical removal of the colorectum with construction of an ileostomy often results in high stoma losses. These may lead to changes in the electrolyte and acid-base balance and to alterations in renal and suprarenal gland function. METHODS: In this study 33 patients who received an ileoanal pouch before and after proctocolectomy were investigated at different time intervals for electrolyte changes, alteration of the acid-base balance, kidney function, and hormonal changes of the suprarenal glands. Measurements were performed before proctocolectomy, ten days after proctocolectomy with ileal pouch-anal anastomosis under protective loop ileostomy, before ileostomy closure, and 6 to 12 months after ileostomy closure. Neither acute renal failure nor other vital complications were observed. RESULTS: Statistical analysis showed a significant decrease of urine pH to 5.4 +/- 0.22 (before ileostomy closure) and metabolic acidosis (pH 7.32 +/- 0.04; base excess -1.3 +/- 5.6 (before ileostomy closure)). Likewise, we found a decrease in renal clearance to 86 ml/minute (before ileostomy closure) without signs of tubular damage. The most important change during the phase with ileostomy was a functional secondary hyperaldosteronism with aldosterone levels of 63.2 +/- 70.8 ng/dl (before ileostomy closure). In comparison with preoperative levels, there was a ten-fold increase in mineralocorticoid adrenal activity. Additionally, during the period with protective ileostomy, the hepatic synthesis of aldosterone-18-glucuronide was only slightly increased, and the cortisol/cortisone ratio was extremely decreased. CONCLUSIONS: These results show that restorative proctocolectomy with ileal pouch-anal anastomosis and protective loop ileostomy significantly influences fluid, electrolyte, and acid-base balance. Functional secondary hyperaldosteronism is of central importance for subsequent renal recompensation. Approximately one-half year after ileostomy closure, the endogenous hormones with mineralocorticoid effects returned to normal levels.

Association of cervical artery dissection with recent infection.

BACKGROUND: Cervical artery dissection (CAD) is an important cause of ischemic stroke in younger patients. However, its cause is insufficiently understood. OBJECTIVE: To test the hypothesis that CAD is frequently associated with recent infection. SUBJECTS AND METHODS: We compared the prevalence of infection during the preceding week in 43 consecutive patients with acute CAD and 58 consecutive patients younger than 50 years with acute cerebral ischemia from other causes (control patients). In subgroups of patients, we correlated infectious status with electron microscopic studies of skin biopsy specimens and investigated pathways potentially linking infection and CAD. RESULTS: Recent infection was more common in patients with CAD (25/43 [58.1%]) than in control patients (19/58 [32.8%]; P=.01). Respiratory tract infection was preponderant in both groups. Recent infection, but not the mechanical factors cough, sneezing, or vomiting, was independently associated with CAD in multivariate analysis. Investigation of serum antibodies against Chlamydia pneumoniae, smooth muscle cells, endothelial cells, collagen types I through IV, and heat shock protein 65 and assessment of serum alpha1-antitrypsin and HLA did not contribute to the understanding of the pathogenesis of CAD. More patients with pathologic findings in skin biopsy specimens tended to have had a recent infection (13/21 [62%]) than patients without pathologic findings (2/9 [22%]; P=.11). CONCLUSION: Our results suggest a significant association between recent infection and CAD that is not explained by mechanical factors occurring during infection.

Cerebrospinal fluid A beta42 is increased early in sporadic Alzheimer's disease and declines with disease progression.

All mutations known to cause familial Alzheimer's disease (AD) act by increasing the levels of soluble beta-amyloid peptide (A beta), especially the longer form, A beta42. However, in vivo elevation of soluble A beta in sporadic AD has so far not been shown. In the present study, we used enzyme-linked immunosorbent assays specific for A beta42 and A beta40 to investigate cerebrospinal fluid from sporadic AD at different stages of disease severity, to clarify the roles of A beta42 and A beta40 during disease progression. We also evaluated three other groups--one group of patients with mild cognitive impairment who were at risk of developing dementia, a cognitively intact, nondemented reference group diagnosed with depression, and a perfectly healthy control group. We found that A beta42 is strongly elevated in early and mid stages of AD, and thereafter it declines with disease progression. On the contrary, A beta40 levels were decreased in early and mid stages of AD. The group of cognitively impaired patients and the depression reference group had significantly higher levels of A beta42 than the healthy control group, implying that A beta42 is increased not only in AD, but in other central nervous system conditions as well. Our data also point out the importance of having thoroughly examined control material. The initial increase and subsequent decrease of A beta42 adds a new biochemical tool to follow the progression of AD and might be important in the monitoring of therapeutics.