Mixed intoxication with Aconitum nappellans (monkshood) and Digitalis grandiflora (large yellow foxglove).

BACKGROUND: Intoxications are frequent and relevant medical problems in emergency units. CASE REPORT: 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. CONCLUSIONS: FAB antibodies are a safe antidote for herbal digitalis intoxication. Therapy of choice for an aconitum poisoning is activated charcoal and intensive monitoring.

Novel genetic risk markers for ulcerative colitis in the IL2/IL21 region are in epistasis with IL23R and suggest a common genetic background for ulcerative colitis and celiac disease.

OBJECTIVES: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.

rs224136 on chromosome 10q21.1 and variants in PHOX2B, NCF4, and FAM92B are not major genetic risk factors for susceptibility to Crohn's disease in the German population.

OBJECTIVES: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Biliary diseases in heart transplanted patients: a comparison between cyclosporine A versus tacrolimus-based immunosuppression.

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.

Prevalence of cholecystolithiasis and its management among kidney/pancreas-transplanted type 1 (insulin-dependent) diabetic patients.

BACKGROUND: Simultaneous pancreas/kidney transplantation (SPK) should be the procedure of choice for (pre)uremic patients with type 1 diabetes. All standard immunosuppressive protocols for SPK include a calcineurin-inhibitor. Both calcineurin inhibitors, cyclosporine (CyA) and probably tacrolimus (FK506) too, are associated with the occurrence of cholelithiasis due to their metabolic side effects. PATIENTS AND METHODS: We evaluated the prevalence of cholelithiasis in 83 kidney/pancreas transplanted type I-diabetic patients (46 males, 37 females, mean age 42.8 +/- 7.5 years) by conventional B-mode ultrasound 5 years after transplantation. 56 patients received CyA (group 1) and 27 received tacrolimus (group 2) as first-line-immunosuppressive drug. Additional immunosuppression consisted of steroids, azathioprine or mycophenolate mofetil. Additionally, laboratory analyses of cholestasis parameters (gamma-GT and alcalic phosphatasis) were performed. RESULTS: In total, 23 patients (28%) revealed gallstones and 52 patients (62%) revealed a completely normal gallbladder. In eight patients (10%) a cholecystectomy was performed before or during transplantation because of already known gallstones. No concrements in the biliary ducts (choledocholithiasis) could be detected. In group 2 the number of patients with gallstones was slightly lower (22%) compared with group 1 patients (30%), but without statistical significance. - Cholestasis parameters were not increased and HbA1c values were normal in both groups of patients. CONCLUSION: The prevalence of biliary disease in kidney/pancreas transplanted type I-diabetic patients with 28% is increased in comparison to the general population (10-15%). Lithogenicity under tacrolimus seems to be lower as under cyclosporine based immunosuppressive drug treatment. We recommend regular sonographical examinations to detect an acute or chronic cholecystis as early as possible, which may develop occultly in these patients.

[Malignant lymphoma of the prostate--diagnosis on the second biopsy]. / Lymphom der Prostata--Diagnose auf den "zweiten Stich".

BACKGROUND: Malignant lymphoma of the prostate is rare. In the literature, about 165 cases with either a primary lymphoma of the prostate or secondary infiltration of the prostate by a lymphoma are described. CASE REPORT: The case of a 59-year-old patient with an irregular tumor in the prostatic region, but normal prostate-specific antigen (PSA), a fracture in the vertebral column and a bilateral enlargement of the suprarenal glands is presented. Repetitive prostate biopsy revealed the diagnosis of a diffuse large B cell lymphoma. Further staging examinations gave hints to an epidural infiltration. A polychemotherapy including intrathecal drug applications was initiated. Staging after four therapeutic cycles already showed good partial remission of all lymphoma manifestations. After two further therapeutic cycles, a CT scan showed a small rest of prostatic bulk, but PET-CT did not detect vital lymphatic tissue (complete remission). CONCLUSION: In cases of irregular prostatic enlargements, carcinoma has to be considered as the most frequent diagnosis. Nevertheless, also a solitary lymphoma or infiltration of the prostate by a systemic lymphoma has to be taken into account, especially if the PSA value is in the normal range.

[Extraordinary manifestation of a gastric carcinoma by leptomeningeal carcinomatosis and spinal metastasis]. / Aussergewöhnliche Manifestation eines Magenkarzinoms mit Meningeosis carcinomatosa und spinaler Metastase.

BACKGROUND: Leptomeningeal carcinomatosis is a rare complication of solid tumors, e. g., breast, lung and gastrointestinal carcinomas. Clinical manifestations are variable with radicular pains with or without neurologic deficiencies as well as headache and hallucinations. CASE REPORT: The rare case of a 57-year-old patient with neurologic symptoms caused by a leptomeningeal carcinomatosis and a spinal metastasis of an asymptomatic signet-ring cell gastric carcinoma is reported. In spite of combined radiochemotherapy the patient died already 4 weeks after discharge from hospital due to an intracerebral hemorrhage. CONCLUSION: Until today, prognosis of leptomeningeal carcinomatosis is poor with a median survival between 3-4 months independently of the primary tumor.

Role of the NFKB1 -94ins/delATTG promoter polymorphism in IBD and potential interactions with polymorphisms in the CARD15/NOD2, IKBL, and IL-1RN genes.

BACKGROUND: Recently, an association of the NFKB1 polymorphism -94ins/delATTG with ulcerative colitis (UC) has been reported. This 4-bp insertion/deletion polymorphism is localized in the promoter region of the NFKB1 gene and appears to be functionally relevant. The aim of the present study was to confirm the association of the -94ins/delATTG (W/D) NFKB1 promoter polymorphism with UC in a population of German origin and to test for a potential association with Crohn's disease (CD). Furthermore, potential interactions of the -94ins/delATTG polymorphism with the IKBL and the IL-1RN genes should be determined. MATERIALS AND METHODS: The study population comprised 630 patients with CD, 365 patients with UC, and 974 healthy controls. Genotyping was performed using polymerase chain reaction and restriction fragment length polymorphism analysis. For statistical evaluation, the chi-square test and the Fisher exact test were used. RESULTS: No significant association of the W/D NFKB1 polymorphism with CD or UC was detected. In addition, no significant interactions between the -94ins/delATTG NFKB1 polymorphism and polymorphisms within the IKBL and the IL-1RN genes, respectively, were found in CD or UC. Also, no significant interactions of the NFKB1 polymorphism with mutations of the CARD15/NOD2 gene and with clinical phenotypes were detected in CD. Moreover, no associations of the NFKB1 polymorphism were found in UC depending on disease localization. CONCLUSIONS: The present study could not confirm the reported association of the -94ins/delATTG NFKB1 polymorphism with UC and also found no evidence for a role of this polymorphism in CD. The results do not give evidence for a role of this NFKB1 polymorphism in the pathogenesis of UC and CD.

Rapid measurement of S-100B serum protein levels by Elecsys S100 immunoassay in patients undergoing carotid artery stenting or endarterectomy.

OBJECTIVES: This study was designed to apply the rapid Elecsys S100 immunoassay for real-time measurement of S100 protein serum levels indicating acute brain damage in patients undergoing carotid artery stenting (CAS) or endarterectomy (CEA). DESIGN AND METHODS: Data of 14 CAS patients were compared to those of 43 CEA and 14 control patients undergoing coronary angiography (CA). S100 serum levels were measured by the full-automatic Elecsys S100 immunoassay and compared to those obtained by the well-established LIA-mat S100 system. RESULTS: In contrast to CAS and CA patients, median S100 serum levels of CEA patients significantly increased to 0.24 ng/mL before declamping, but subsequently returned to baseline. Three CEA patients with neurological deficits showed sustained elevated S100 levels 6 h after extubation. Absolute S100 values were not significantly different between the two methods. Bland-Altman plot analyses displayed a good agreement, mostly indicating slightly smaller values applying the Elecsys S100 system. CONCLUSIONS: The Elecsys S100 system appears to be suitable for rapid real-time detection of neurological deficits in patients undergoing CAS and CEA. Persistent elevations of Elecsys S100 levels during CEA were associated with prolonged neurological disorders, whereas transient increases seem to represent impaired blood-brain barrier integrity without neurological deficits.

Association of polymorphisms in the interleukin-18 gene in patients with Crohn's disease depending on the CARD15/NOD2 genotype.

UNLABELLED: An increased expression of interleukin-18 (IL-18), a proinflammatory cytokine inducing interferon-gamma, has been found in Crohn's disease (CD). In the IL-18 gene, several partly functional relevant polymorphisms are known. This study sought to investigate associations of IL-18 polymorphisms in inflammatory bowel disease and CD according to CARD15/NOD2 mutation status and clinical phenotypes. METHODS: The IL-18 polymorphisms -607, -137, and the third position of codon 35 (c35/3) were genotyped in 210 patients with CD, 140 patients with ulcerative colitis, and 265 healthy controls using polymerase chain reaction and restriction fragment length polymorphism analysis. RESULTS: Frequencies of alleles and genotypes of the 3 polymorphisms and of the respective haplotypes and diplotypes displayed no significant differences between the whole groups of patients with CD and ulcerative colitis, respectively, compared with the controls. After stratification of patients with CD for CARD15/NOD2 status, significant associations of genotypes -137 CC (P = 0.018) and c35/3 CC (P = 0.010) and of the diplotype 2-2 (P = 0.018) were found in cases carrying CARD15/NOD2 mutations. Associations of genotypes -137 GG (P = 0.015) and c35/3 AA (P = 0.030) with colonic disease only in cases positive for CARD15/NOD2 mutations and of the genotype -607 AA (P = 0.007) with fistulas in cases negative for CARD15/NOD2 mutations were observed. CONCLUSIONS: In this study, significant differences of several genotypes and diplotypes within the IL-18 gene in CD depending on CARD15/NOD2 status have been found. In context with an increased expression of IL-18 in CD, it remains to be shown whether the expression of IL-18 is influenced by CARD15/NOD2 mutation status.

Thyroid echogenicity in manic-depressive patients receiving lithium therapy.

BACKGROUND: Lithium is known to induce subclinical or overt hypothyroidism and changes of thyroid volume in manic-depressive patients. Little is known about alterations of thyroid echogenicity due to drug-induced dysfunction. METHODS: Twenty manic-depressive patients receiving lithium therapy for at least 6 months and 20 euthyroid volunteers without any antidepressive medication as control group, matched in age and gender, were investigated by laboratory measurements and thyroid ultrasonography including standardized grey scale analyses in representative regions of interest (ROI). RESULTS: Thyroid function was normal in all patients (mean FT4 1.1+/-0.2 ng/dl, mean TSH 1.6+/-0.9 micro U/ml) and controls (mean FT4 1.5+/-0.4 ng/dl, TSH 1.1+/-0.3 micro U/ml). Except for two patients, no thyroid autoantibody levels could been detected. Thyroid volumetry revealed significant higher mean values for the lithium treated patients (16.9+/-11.9 ml) compared with the controls (11.4+/-4.5 ml, P<0.05) with a considerable number of goiters (six patients vs. one control). Thyroid echogenicities in both groups were similar (patients 23.9+/-3.7 grey scales, Grauwerteinheiten = GWE, controls 24.2+/-1.3 GWE) and did not depend on the size of the organs. CONCLUSION: Lithium treatment contributes to increased thyroid volumes, probably due to inhibition of thyroid function and TSH upregulation, but not to changes of thyroid echo levels in patients with still euthyroid function. Further echogenicity studies on patients with lithium-induced overt hypothyroidism and autoimmune activity will be of special interest.

Extraluminal gastrointestinal stromal tumour in the second portion of the duodenum.

The preoperative diagnosis of extraluminal gastrointestinal stromal tumours in the duodenum is difficult to establish due to their rare occurrence and the lack of pathognomonic signs. This report describes the case of a 61-year-old woman who suffered from an immunohistologically confirmed gastrointestinal stromal tumour in the second portion of the duodenum. Preoperative, abdominal, multislice computed tomography showed an extraluminal but intramural tumour located between the head of the pancreas and the duodenum. Rapid postprocessing analysis by three-dimensional, volume-rendered images revealed a strong arterial blood supply and an early draining vessel into the superior mesenteric vein during the portal-venous phase. The combination of endoscopic ultrasonography and non-invasive multislice computed tomography provided an early suggestion of gastrointestinal stromal tumour.

Improved procedure of colonoscopy under accompanying music therapy.

BACKGROUND: Administration of sedatives and analgetics during colonoscopy includes the risk for arterial hypotension and respiratory depression. The aim of this study was to assess whether music therapy increases patients tolerance and reduces the need of analgo-sedative premedication. METHODS: 146 consecutive patients were examined in a randomized, prospective study. Colonoscopy was performed under intravenous administration with titrated dosages of midazolam and pethidin. Oxygen was given in cases of blood desaturation below values of 90%. Patients younger than 18 and older than 80 years, patients with history of partial colectomy, gastrectomy or hysterectomy and patients with colonic tumorous or inflammatory stenosis were excluded. 60 patients underwent conventional procedure (Group A), whereas 59 patients received additional music therapy (Group B). Time required to reach the cecum (examination time) was measured and the rate of successful colonoscopies was determined. RESULTS: Most of the patients required sedation with midazolam in both groups (97 vs. 93%), whereas more group A patients required analgesia with pethidin than group B patients (43 vs. 31%, p<0.05). Under music therapy the rate of completed colonoscopies was higher (group A 93%, group B 98%) and examination time was significantly accelerated (group A 22.8 +/- 14.6 min, group B 16.8 +/- 11.8 min, p<0.03). CONCLUSIONS: Accompanying music therapy reduces requirement of analgesia during colonoscopy, favours completion of the procedure and shortens examination time. Music therapy seems to promote safer conditions for endoscopical practice and diminishs patients discomfort.

Risk factors promoting hypertensive crises: evidence from a longitudinal study.

BACKGROUND: 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. METHODS: 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). RESULTS: 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). CONCLUSIONS: 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.

Prehospital ultrasound in emergency medicine: incidence, feasibility, indications and diagnoses.

BACKGROUND: Sonography is an established diagnostic procedure in hospitals, but is not routinely used in prehospital emergency medicine. Several studies have addressed the use of ultrasound during helicopter flights and in emergency rooms, few in prehospital settings, but most focused on abdominal blunt trauma. Several case reports describe crucial decisions distinguished by ultrasound. METHODS: In this study, four different handheld ultrasound systems in 4 helicopters and one emergency vehicle were used over a cumulative period of 3 years. Incidence, feasibility, indication, diagnoses and exploration time (in subgroups) were investigated in an overall profile of emergency patients, encompassing the area of internal medicine. RESULTS: On 971 missions ultrasound systems were available. In 17% of the cases ultrasound was considered valuable, in 144 patients (14.8%) sonographic studies were performed. Additional information could be given in 130 cases (90%). Compared with the available clinical data (return rate of 76%) there were no false-positive findings during this study, resulting in a specificity and positive predictive value of 100%, showing this technique to be reliable. Sensitivity was 85%, accuracy was 96% and negative predictive value was 95%. CONCLUSION: Ultrasound is the only imaging modality and a useful diagnostic tool in prehospital emergency medicine. Helpful information can be provided in at least one of six cases (or even more) in a trauma-dominated collective. Examination time is short; it will not significantly delay medical care. Ultrasound examination could improve triage in cases of more than one patient in disaster medicine, but further studies are necessary.