U Schiemann's research while affiliated with Inselspital, Universitätsspital Bern and other places

Intoxications are frequent and relevant medical problems in emergency units. We report of a mixed intoxication with monkshood and large yellow foxglove. A 39-year-old mentally ill drug addict, intent on committing suicide, swallowed an undefined amount of chaffed monkshood and large yellow foxglove. The typical symptoms of an intoxication occurred, including high-grade ventricular and supraventricular tachyarrhythmias, colic abdominal pain, and peripheral paralysis. After activated charcoal was repeatedly administered as well as FAB digitalis-antibodies, a lasting normalisation of the heart rhythm set in and a release of the clinical symptoms could be observed. FAB antibodies are a safe antidote for herbal digitalis intoxication. Therapy of choice for an aconitum poisoning is activated charcoal and intensive monitoring.

Current knowledge about risk factors promoting hypertensive crisis originates from retrospective data. Therefore, potential risk factors of hypertensive crisis were assessed in a prospective longitudinal study. Eighty-nine patients of the medical outpatient unit at the University Hospital of Bern (Bern, Switzerland) with previously diagnosed hypertension participated in this study. At baseline, 33 potential risk factors were assessed. All patients were followed-up for the outcome of hypertensive crisis. Cox regression models were used to detect relationships between risk factors and hypertensive crisis (defined as acute rise of systolic blood pressure (BP) > or =200 mm Hg and/or diastolic BP > or =120 mm Hg). The mean duration of follow-up was 1.6 +/- 0.3 years (range 1.0-2.4 years). Four patients (4.5%) were lost to follow-up. Thirteen patients (15.3%) experienced hypertensive crisis during follow-up. Several potential risk factors were significantly associated with hypertensive crisis: female sex, higher grades of obesity, the presence of a hypertensive or coronary heart disease, the presence of a somatoform disorder, a higher number of antihypertensive drugs, and nonadherence to medication. As measured by the hazard ratio, nonadherence was the most important factor associated with hypertensive crisis (hazard ratio 5.88, 95% confidence interval 1.59-21.77, P < 0.01). This study identified several potential risk factors of hypertensive crisis. Results of this study are consistent with the hypothesis that improvement of medical adherence in antihypertensive therapy would help to prevent hypertensive crises. However, larger studies are needed to assess potential confounding, other risk factors and the possibility of interaction between predictors.

Renal impairment is a common complication of multiple myeloma occurring in up to 50 % of patients at some stage in their disease. Due to occurrence of cast nephropathies we hypothesized circulatory dysregulation (vasoconstriction) in the kidneys with measurable elevation of the resistance index among these patients which would have a diagnostic impact. 36 patients with treated multiple myeloma (21 females, 15 males, mean age 61.6 +/- 8.5 years) were prospectively examined by conventional abdominal ultrasound with focussed investigation of the kidneys. First, length of the organs, parenchymal width and characterization of parenchymal echogenicity were determined. Then, intrarenal RI values were measured in segmental and arcuate arteries, respectively, in both kidneys. Additionally, serum creatinine, BUN and GFR of each patient were evaluated. RI values were compared to values of 78 healthy control subjects. Mean renal RI was 0.68 +/- 0.07 which was slightly higher than in controls with 0.62 +/- 0.05, but without statistical significance. Due to the laboratory analyses patients were subdivided in those with normal ( group 1, n = 21) and those with impaired (group 2, n = 15) renal function. In both groups kidney size and parenchymal width were normal. Significant more group 2 patients (60%) revealed hyperechogenic parenchyma than group 1 patients (24%) (p<0.01). Mean renal RI indices were 0.67 +/- 0.06 (right) and 0.69 +/- 0.06 (left) in group 1 patients and 0.71 +/- 0.08 (right) and 0.71 +/- 0.07 (left) in group 2 patients and showed no significant difference (p = 0.06 and 0.15). Renal RI values are not significantly elevated in patients with multiple myeloma even in those with renal impairment so that no hints to a relevant vasoconstriction could be evaluated. RI seems not to be a relevant parameter for the diagnosis of cast nephropathy of multiple myeloma patients. Routinely performed ultrasound examination should be more focussed on the qualification of parenchymal echogenicity.

Recently, a genome-wide association study showed that single-nucleotide polymorphisms (SNPs) in the chromosome 4q27 region containing IL2 and IL21 are associated with celiac disease. Given the increased prevalence of inflammatory bowel disease (IBD) among celiac disease patients, we investigated the possible involvement of these SNPs in IBD. Five SNPs strongly associated with celiac disease within the KIAA1109/TENR/IL2/IL21 linkage disequilibrium block on chromosome 4q27 and one coding SNP within the IL21 gene were analyzed in a large German IBD cohort. The study population comprised a total of 2,948 Caucasian individuals, including 1,461 IBD patients (ulcerative colitis (UC): n=514, Crohn's disease (CD): n=947) and 1,487 healthy unrelated controls. Three of the five celiac disease risk markers had a protective effect on UC susceptibility, and this effect remained significant after correcting for multiple testing: rs6840978: P=0.0082, P(corr)=0.049, odds ratio (OR) 0.77, 95% confidence interval (CI) 0.63-0.93; rs6822844: P=0.0028, P(corr)=0.017, OR 0.73, 95% CI 0.59-0.90; rs13119723: P=0.0058, P(corr)=0.035, OR 0.75, 95% CI 0.61-0.92. A haplotype consisting of the six SNPs tested was markedly associated with UC susceptibility (P=0.0025, P(corr)=0.015, OR 0.72, 95% CI 0.58-0.89). Moreover, in UC, epistasis was observed between the IL23R SNP rs1004819 and three SNPs in the KIAA1109/TENR/IL2/IL21 block (rs13151961, rs13119723, and rs6822844). Similar to other autoimmune diseases such as celiac disease, rheumatoid arthritis, type 1 diabetes, Graves' disease, and psoriatic arthritis, genetic variation in the chromosome 4q27 region predisposes to UC, suggesting a common genetic background for these diseases.

A cyclosporine (CsA)-based immunosuppression is associated with an increased incidence of cholelithiasis after heart transplantation. It is not known if tacrolimus (Tac) has comparable biliary side effects in humans. We evaluated the incidence of gallbladder sludge and cholelithiasis under Tac-based immunosuppression by ultrasound examinations in 31 cardiac transplants (25 male, 6 female, mean age: 59 ± 11 years). Data were compared to 57 patients (47 male, 10 female, mean age: 58 ± 11 years) who received CsA-based immunosuppression. 6 patients receiving Tac and 6 patients receiving CsA had already gallstones prior to transplantation so that finally 25 patients of the Tac group and 51 patients of the CsA group could be evaluated. In the Tac group the incidence of biliary sludge was 4% (1 of 25), of gallstones 28% (7 of 25). In comparison, patients receiving CsA developed biliary sludge in also 4% (2 of 51) and gallstones in 25% (13 of 51). Nine of 42 males in the CsA group (21%) and eight of 20 males in the Tac group (40%) developed either gallstones or sludge (n.s). Six of nine females in the CsA group (67%), but none of five females in the Tac group (0%) developed either gallstones or sludge (p = 0.01). In summary, the incidence of biliary disease in patients with Tac is comparable with CsA-based immunosuppression. We recommend regular sonographical examinations to detect biliary diseases as early as possible. In cases of clinically, laboratory and sonographical signs of cholecystitis cholecystectomy is indicated. It seems that towards lithogenicity female patients benefit more from a Tac-based treatment because the occurrence of gallstones is rare.

Recently, a North American genome-wide association study identified three novel gene variants in PHOX2B, NCF4, and FAM92B as well as one single nucleotide polymorphisms (SNP; rs224136) in the intergenic region on chromosome 10q21.1 as being associated with Crohn's disease (CD). However, their influence on European CD patients as well as ulcerative colitis (UC) is unknown. Therefore we aimed to replicate these novel CD susceptibility variants in a large European cohort with inflammatory bowel disease and analyzed potential gene-gene interactions with variants in the NOD2/CARD15, IL23R, and ATG16L1 genes. Genomic DNA from 2,833 Caucasian individuals including 854 patients with CD, 476 patients with UC, and 1,503 healthy unrelated controls was analyzed for SNPs in PHOX2B (rs16853571), NCF4 (rs4821544), and FAM92B (rs8050910), including rs224136 on chromosome 10q21.1. In our study population, no association of PHOX2B (P=0.563), NCF4 (P=0.506), FAM92B (P=0.401), and rs224136 (P=0.363) with CD was found. Similarly, none of these SNPs was associated with UC. In contrast, all analyzed SNPs in NOD2/CARD15, IL23R, and ATG16L1 were strongly associated with CD with P values ranging from 5.0x10(-3) to 1.6x10(-22), but there was no epistasis with polymorphisms in PHOX2B, NCF4, FAM92B, and rs224136. In contrast to the North American population, PHOX2B, NCF4, FAM92B, and rs224136 are not associated with CD in the European population, whereas NOD2/CARD15, IL23R, and ATG16L1 are strongly associated with CD in both the North American and European populations, confirming these three genes as major CD susceptibility genes in Caucasian populations.