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A 39-year-old woman presented with back pain at an orthopaedic clinic. Magnet resonance tomography revealed a spinal tumour. Further imaging also showed a pulmonary tumour, massive mediastinal lymphadenopathy as well as unilateral pleural effusion. Histology from biopsies from the spinal tumour and from a mediastinal lymph node revealed NUT carcinoma. The NUT carcinoma that earlier has been named NUT midline carcinoma is a very rare, aggressive tumour with a poor prognosis. Initially, the NUT carcinoma was thought to develop from organs in the midline such as upper airways or mediastinal cavity. However, the NUT carcinoma is not limited to structures in the midline. NUT carcinoma often affects young patients. Due to its low incidence, a standardized therapy could not be established until now.Eine 39-jährige Patientin hat sich initial wegen Rückenschmerzen orthopädisch vorgestellt. Nachdem sich in der Magnetresonanztomografie der Lendenwirbelsäule der Verdacht auf eine tumoröse Erkrankung gestellt hatte, war in den weiterführenden Untersuchungen eine pulmonale Raumforderung, eine ausgedehnte mediastinale Lymphadenopathie und ein großer einseitiger Pleuraerguss nachweisbar. Histologisch zeigte sich sowohl in den Proben des Tumors im Wirbelkörper als auch in den Proben der transbronchialen Nadelaspiration eines mediastinalen Lymphknotens ein NUT-Karzinom. Das NUT-Karzinom, das früher als NUT-Mittellinienkarzinom bezeichnet wurde, ist eine sehr seltene, aggressive Tumorentität mit ungünstiger Prognose. Der Tumor wurde zunächst gehäuft in der Mittellinie der oberen Atemwege und des Mediastinums beschrieben, ist aber nicht darauf beschränkt. Das NUT-Karzinom trifft häufig junge Patienten. Aufgrund der Seltenheit existiert bisher keine etablierte Therapie.

A 65 year old female presented to the emergency department with dyspnea and progressive cough with very viscous elongated secretion plugs. She suffered from multiple cardiac comorbidities and chronic heart failure. The CT scan of the thorax demonstrated extensive pulmonary infiltrates, unspecific mediastinal lymphadenopathy and enlargement of pulmonary lymph vessels. Bronchoscopy was performed and showed extensive occlusive bronchial casts. We diagnosed a case of bronchitis plastica. Therapy with inhalative heparin led to clinical improvement.bronchitis plastica is a rare disease with formation of occlusive bronchial casts. They are often found in cardiac disease or lymphatic disease.Eine 65-jährige Patientin stellte sich mit Dyspnoe, zunehmendem Husten und Abhusten von sehr zähen, länglichen Sekretpropfen vor. Sie war multipel schwer kardial vorerkrankt und litt an einer chronischen Herzinsuffizienz. Im CT-Thorax zeigten sich ausgedehnte pulmonale Infiltrate beidseits, eine unspezifische mediastinale Lymphadenopathie und eine Erweiterung der pulmonalen Lymphgefäße. Bronchoskopisch fanden sich gallertige zähe Ausgusspräparate der Atemwege. Es wurde die Diagnose einer Bronchitis plastica gestellt. Unter einer Therapie mit inhalativem unfraktioniertem Heparin kam es zu einer Besserung. Fazit: Die Bronchitis plastica ist eine seltene Erkrankung, die durch die Bildung von Bronchialausgüssen charakterisiert ist. Man findet sie gehäuft bei kardialen Erkrankungen oder Lymphgefäßerkrankungen.

BACKGROUND AND PURPOSE Hereditary spastic paraplegias (HSPs) are clinically and genetically heterogeneous monogenic disorders. To date, nearly 70 genes are known to be causative. The aim of this project was to identify the genetic cause of autosomal dominantly inherited pure HSP in two large, unrelated non-consanguineous families. METHODS The two families were characterized clinically and selected members underwent whole exome sequencing. Potentially disease-causing variants were confirmed by Sanger sequencing and their functional consequences on protein function were predicted by bioinformatic prediction tools. RESULTS The patients presented with pure spastic paraplegia with age of onset between 9 and 46 years. In both families, a novel heterozygous missense variant in ERLIN2, c.386G>C; p.Ser129Thr, was the only potentially pathogenic variant identified that segregated with the disease. CONCLUSIONS Biallelic variants in ERLIN2 are known to cause recessive HSP type SPG18. Here, the first two families with an autosomal dominant, pure form of HSP caused by a novel ERLIN2 heterozygous missense variant are described. These findings expand the mutational and inheritance spectrum of SPG18. ERLIN2 variants should also be considered in the diagnostic evaluation of patients with autosomal dominant HSP.

Postoperative delirium in elderly patients is a frequent complication and associated with poor outcome. The aim of this parallel group study was to determine whether monitoring depth of anaesthesia influences the incidence of postoperative delirium.Patients who were planned for surgery in general anaesthesia expected to last at least 60 min and who were older than 60 yr were included between March 2009 and May 2010. A total of 1277 patients of a consecutive sample were randomized (n=638 open, n=639 blinded) and the data of 1155 patients were analysed (n=575 open, n=580 blinded). In one group, the anaesthesiologists were allowed to use the bispectral index (BIS) data to guide anaesthesia, while in the other group, BIS monitoring was blinded. Cognitive function was evaluated at baseline, 1 week, and 3 months after operation.Delirium incidence was lower in patients guided with BIS. Postoperative delirium was detected in 95 patients (16.7%) in the intervention group compared with 124 patients (21.4%) in the control group (P=0.036). In a multivariate analysis, the percentage of episodes of deep anaesthesia (BIS values20) were independently predictive for postoperative delirium (P=0.006; odds ratio 1.027). BIS monitoring did not alter the incidence of postoperative cognitive dysfunction (7th day P=0.062; 90th day P=0.372).Intraoperative neuromonitoring is associated with a lower incidence of delirium, possibly by reducing extreme low BIS values. Therefore, in high-risk surgical patients, this may give the anaesthesiologist a possibility to influence one precipitating factor in the complex genesis of delirium. Clinical trial registration ISRCTN Register: 36437985. http://www.controlled-trials.com/ISRCTN36437985/.

The present guideline provides a new and updated concept of treatment and prevention of adult patients with community-acquired pneumonia. It replaces the previous guideline dating from 2009.The guideline was worked out and agreed on following the standards of methodology of a S3-guideline. This includes a systematic literature search and grading, a structured discussion of recommendations supported by the literature as well as the declaration and assessment of potential conflicts of interests.The guideline has a focus on specific clinical circumstances, an update on severity assessment, and includes recommendations for an individualized selection of antimicrobial treatment as well as primary and secondary prevention.

Objectives: We aimed to identify clinical characteristics and to assess effectiveness of different initial antibiotic regimens in adult patients with community-acquired pneumonia (CAP) caused by Haemophilus influenzae. Methods: Characteristics were compared between patients with H. influenzae monoinfection versus CAP of other and unknown aetiology enrolled by the German prospective cohort study CAPNETZ. Impact of initial antibiotic treatment on "early clinical response" according to FDA criteria and overall clinical cure were analysed. Results: H. influenzae was found in 176 out of 2790 patients with pathogen detection (6.3%). Characteristics significantly associated with a H. influenzae CAP (p

Background Respiratory infection and failure is a commonly encountered problem in intensive care unit (ICU) patients. However, despite the accumulating body of evidence to suggest that herpes simplex virus type 1 (HSV-1) is associated with pneumonia, the exact role played by this virus in this process is still not fully understood. Therefore, to identify patients at risk, we have conducted a case–control study to characterize patients with HSV-1-positive pneumonia. Patients and methods Between 2007 and 2009, all patients with suspected viral pneumonia were tested for the presence of herpes viruses using a PCR assay approach with respiratory specimens. To identify possible associations, risk factors, and impact of HSV, HSV-1-positive ICU patients (n = 51) were compared to age-, gender-, and department- and season-matched HSV-negative patients (n = 52). Results HSV-positive patients differed significantly from the HSV-negative ones only in terms of time of mechanical ventilation (13 vs. 6 days, respectively; p = 0.002). Subgroup analysis in the patients aged >60 years and in those without bacterial detection revealed a similar trend (p = 0.01 and p = 0.004, respectively). Mortality did not differ between the groups or between the HSV-1-positive patients treated with aciclovir and those who were not. A viral load >10E+05 geq/ml was associated with mechanical ventilation (20/21 vs. 17/29; p = 0.004), acute respiratory distress syndrome (ARDS; 19/21 vs. 18/29; p = 0.005), sepsis (18/21 vs. 14/29; p = 0.008), detection of a bacterial pathogen in the same specimen (10/21 vs. 4/29; p = 0.01) and longer ICU stay (25 vs. 30 days; p = 0.04). Conclusion Despite several associations with high viral load, the clinical outcome of HSV-1-positive ICU patients did not differ significantly from the clinical outcome of HSV-negative patients. This finding indicates that HSV-1 viral loads in respiratory specimens are a symptom of a clinically poor condition rather than a cause of it. Longitudinal and therapy studies are therefore needed to distinguish between HSV-1 as a causative pathogen and HSV-1 as a bystander of pneumonia/ARDS.

The aim of the present study was to investigate the prognostic value, in patients with community-acquired pneumonia (CAP), of procalcitonin (PCT) compared with the established inflammatory markers C-reactive protein (CRP) and leukocyte (WBC) count alone or in combination with the CRB-65 (confusion, respiratory rateor=30 breaths x min(-1), low blood pressure (systolic value90 mmHg or diastolic valueor=60 mmHg) and ageor=65 yrs) score. In total, 1,671 patients with proven CAP were enrolled in the study. PCT, CRP, WBC and CRB-65 score were all determined on admission and patients were followed-up for 28 days for survival. In contrast to CRP and WBC, PCT levels markedly increased with the severity of CAP, as measured by the CRB-65 score. In 70 patients who died during follow-up, PCT levels on admission were significantly higher compared with levels in survivors. In receiver operating characteristic analysis for survival, the area under the curve (95% confidence interval) for PCT and CRB-65 was comparable (0.80 (0.75-0.84) versus 0.79 (0.74-0.84)), but each significantly higher compared with CRP (0.62 (0.54-0.68)) and WBC (0.61 (0.54-0.68)). PCT identified low-risk patients across CRB classes 0-4. In conclusion, procalcitonin levels on admission predict the severity and outcome of community-acquired pneumonia with a similar prognostic accuracy as the CRB-65 score and a higher prognostic accuracy compared with C-reactive protein and leukocyte count. Procalcitonin levels can provide independent identification of patients at low risk of death within CRB-65 (confusion, respiratory rateor=30 breaths x min(-1), low blood pressure (systolic value90 mmHg or diastolic valueor=60 mmHg) and ageor=65 yrs) risk classes.

Freehand positioning of the femoral drill guide is difficult during hip resurfacing and the surgeon is often unsure of the implant position achieved peroperatively. The purpose of this study was to find out whether, by using a navigation system, acetabular and femoral component positioning could be made easier and more precise. Eighteen patients operated on by the same surgeon were matched by sex, age, BMI, diagnosis and ASA score (nine patients with computer assistance, nine with the regular ancillary). Pre-operative planning was done on standard AP and axial radiographs with CT scan views for the computer-assisted operations. The final position of implants was evaluated by the same radiographs for all patients. The follow-up was at least 1 year. No difference between both groups in terms of femoral component position was observed (p > 0.05). There was also no difference in femoral notching. A trend for a better cup position was observed for the navigated hips, especially for cup anteversion. There was no additional operating time for the navigated hips. Hip navigation for resurfacing surgery may allow improved visualisation and hip implant positioning, but its advantage probably will be more obvious with mini-incisions than with regular incision surgery.

Chlamydia pneumoniae, a major cause of community-acquired pneumonia, primarily infects the respiratory tract. Chronic infection of nonrespiratory sites, such as the vascular wall, the brain or blood monocytes, requires evasion from the lungs and spreading via the bloodstream. The cell types involved in dissemination are insufficiently characterised. In this study, New Zealand White rabbits were infected intratracheally with C. pneumoniae, and lung manifestation and systemic dissemination were monitored by polymerase chain reaction and immunohistochemistry. Infection of the lungs was characterised by an early phase dominated by granulocytes and a late phase dominated by alveolar macrophages (AM). Granulocytes, AM and alveolar epithelial cells acted as host cells for chlamydiae, which remained detectable for up to 8 weeks. AM transported the pathogen to the peribronchiolar lymphatic tissue, and subsequently C. pneumoniae entered the spleen and the aorta via dissemination by peripheral blood monocytes. In conclusion, Chlamydia pneumoniae-infected alveolar macrophages transmigrate through the mucosal barrier, and give the pathogen access to the lymphatic system and the systemic circulation. Infected peripheral blood monocytes are the vector system within the bloodstream and transmit the infection to the vascular wall. This is the first description of granulocytes acting as a reservoir for Chlamydia pneumoniae early in infection.

Lactose intolerance with adult-onset is due to the inadequate enzymatic activity of lactasephlorizin hydrolase (LPH). It is frequently seen in patients with Crohn disease, but the mechanism remains to be elucidated. Two DNA genotypes, C/C(-13910) and G/G(-22018), located upstream from the LCT locus, the gene encoding for LPH, were recently identified as representing genetic markers for lactose intolerance. We utilized these two DNA genotypes to study their role in inflammatory bowel disease.We investigated the prevalence of these two DNA variants using specific restriction enzyme digest assays in 166 patients with Crohn disease, in 120 healthy first-degree relatives of Crohn disease patients, in 63 patients with ulcerative colitis and in 187 healthy individuals.The analysis revealed a frequency of 21.4% of the 2 genotypes for adult-type hypolactasia in our studied German cohort of healthy individuals, which is higher than previously reported (15%) based on the hydrogen (H2) breath test. This might indicate a higher sensitivity of genotyping, but it has to be confirmed in larger cohorts. No significant difference was detectable in the frequency of the C/C(-13910) and G/G(-22018) genotypes in patients with Crohn disease (C/C(-13910): 21.7%; G/G(-22018): 22.3%) compared to first-degree relatives (C/C(-13910): 21.7%; G/G(-22018): 20.8%), patients with ulcerative colitis (C/C(-13910): 20.3%; G/G(-22018): 20.3%) and healthy individuals (C/C(-13910): 21.4%; G/G(-22018): 21.4%).The C/C(-13910) and G/G(-22018) genotype of adult-type hypolactasia is not associated with susceptibility to the pathogenesis of Crohn disease and ulcerative colitis.

Background and purpose Multiple structural white matter abnormalities have been described in patients with juvenile myoclonic epilepsy (JME). In the present study, the question of whether microstructural variations exist between the two subgroups of JME, with and without photoparoxysmal responses (PPR positive and negative), was addressed using diffusion tensor imaging. Methods A selection of 18 patients (eight PPR positive) from a tertiary epilepsy center diagnosed with JME and 27 healthy controls was studied. The following regions of interest were investigated: the ascending reticular activating system, lateral geniculate nucleus, genu of the internal capsule, ventromedial thalamus and inferior cerebellar peduncle. Results Widespread white matter microstructural abnormalities in JME and in particular in PPR positive cases were identified. PPR positive patients demonstrated increased fractional anisotropy in the ascending reticular activating system and ventromedial thalamus compared to PPR negative patients and healthy controls. Reduced fractional anisotropy of the lateral geniculate nucleus was observed in the entire JME group compared to healthy controls. Conclusions Several microstructural variations between PPR positive and negative JME patients have been identified. Our findings highlight the pivotal role of the thalamus in the pathophysiology of primary generalized seizures and suggest that thalamo-premotor connections are both an essential part of epileptic networks and important in the pathogenesis of photosensitivity.

Background Betulinic acid and other triterpenes have shown strong antitumour activity in vitro and in vivo. A triterpene extract of birch bark formed the base of Oleogel-S10 and allowed topical application. Two previous trials have shown efficacy and tolerability in the treatment of actinic keratoses (AKs) with betulin-based Oleogel-S10. Objectives To confirm the efficacy and tolerability/safety of Oleogel-S10 in the treatment of AKs in a multicentre placebo-controlled study. Methods Patients (n = 165) were treated topically for 3 months in a four-arm parallel study design, randomly allocated to A (n = 53) Oleogel-S10 once daily, B (n = 51) Oleogel-S10 twice daily, or C (n = 25) or D (n = 28) placebo (petroleum jelly) once or twice daily, respectively. Clinical efficacy in this double-blind study was assessed by the investigators. Final and baseline biopsies were evaluated by central histopathology. Results Complete clearance of the target lesions was seen in 4% of patients in group A and 7% in group B, but not in the placebo groups. A clearance rate of > 75% was seen for 15% and 18% of patients in groups A and B, respectively, and for 13% in the placebo groups. These differences were not statistically significant. Histopathologically, 43·9% of patients showed a downgrading or clearance of the marker AK with no significant differences between the groups. Treatment with Oleogel-S10 was well tolerated. The tolerability as assessed by the investigator was mostly 'very good' (78·8%), followed by 'good' (18·2%) and only 1·2% assessed it as 'intolerable'. Patient-assessed tolerability was graded mostly 'very good' (56·4%) or 'good' (34·5%). Conclusions Treatment with Oleogel-S10 was well tolerated during a treatment period of 3 months, yet was no better than placebo in terms of efficacy in the treatment of AKs. What's already known about this topic? Previous single open-label trials have shown activity for Oleogel-S10 in actinic keratoses, with a clearance of > 75% of the lesions in 79% and 86% of patients. What does this study add? In this multicentre randomized double-blind trial Oleogel-S10 was highly tolerable but could not demonstrate superiority over placebo treatment.

Ultrasonography of a six-year-old Simmental cow revealed an abscess like structure, approximately 15 cm in diameter, in place of the right kidney. The cow had a history of colic for 4 days and was referred to our clinic with a tentative diagnosis of caecal dilatation. The cow voided dark opaque urine with white floccules. Laboratory examination yielded increased haematocrit, leukocytosis with left shift, hyperbilirubinaemia and azotaemia. The diagnosis was confirmed, the caecum emptied surgically and the pus-filled structure at the site of the right kidney removed. A diagnosis of pyonephrosis was made after pathological examination of the pus-filled structure.Bei einer 6 Jahre alten Fleckviehkuh wurde mittels Ultraschalluntersuchung anstelle der rechten Niere ein ca. 15 cm grosses abszessartiges Gebilde gefunden. Die Kuh hatte seit 4 Tagen Anzeichen von Kolik gezeigt und war mit der Verdachtsdiagnose Blinddarmdilatation in die Klinik eingewiesen worden. Die Blinddarmdilatation konnte bestätigt werden. Der Spontanharn war dunkelgelb und trüb mit weisslichen Flocken. Im Blut wurden ein erhöhter Hämatokrit, eine Leukozytose mit Linksverschiebung, eine Hyperbilirubinämie und eine Azotämie festgestellt. Die Kuh wurde operiert. Dabei wurden der Blinddarm entleert und das mit Eiter gefüllte Gebilde entfernt. Bei der pathologisch-anatomischen Untersuchung stellte sich heraus, dass es sich dabei um eine Pyonephrose handelte.

Thehaemophilicarthropathyaffects thefunction of theknee joint muscles. The aim of thisstudywas to investigatethe myoelectrical signal ofknee jointmusclesin different agestages during upright standing. Surface EMG (SEMG) amplitudes of quadriceps, hamstrings and gastrocnemii were measured in 191 patients with severe haemophilia A (n=164) and B (n=27) while standing on an even surface. After an age-based classification of patients into the subgroups H(A): 17-29 (n = 37), H(B): 30-39 (n = 50), HC: 40-49 (n = 61), H(D): 50-70 in years (n = 43) the clinical WFH score for the ankle and knee joint was determined. To normalize the SEMG values amplitude ratios (percentage of cumulated activity) were calculated with respect to the specific limb. With increasing age, the patient showed descriptively a deterioration of the joint situation. The extensors of the knee joint reached significantly higher absolute and percentage levels in the muscle activity with increasing age (p0.05). The absolute amplitude values of the Mm. gastrocnemii showed no differences in the age groups while the relative levels were decreased. The present study shows that patients with increasing age and degree of haemophilic arthropathy develop a modified control strategy during upright standing, in the form of a shift from the plantar flexors to the extensors of the knee joint.

Inherited susceptibility to breast cancer is associated with an early onset and bilateral disease. The extent of familial risks has not, however, been fully assessed in population-based incidence studies. The purpose of the study was to quantify the risks for cancers of the breast, ovary and other sites of close relatives of women in whom breast cancer was diagnosed at an early age. Records collected between 1943 and 1990 at the Danish Cancer Registry were searched, and 2860 women were found in whom breast cancer was diagnosed before age 40. Population registers and parish records were used to identify 14 973 parents, siblings and offspring of these women. Cancer occurrence through to 31 December 1993 was determined within the Cancer Registry's files and compared with national incidence rates. Women with early-onset breast cancer were at a nearly fourfold increased risk of developing a new cancer later in life (268 observed vs 68.9 expected). The excess risk was most evident for second cancer of the breast (181 vs 24.5) and for ovarian cancer (20 vs 3.3). For mothers and sisters, risks for cancers of the breast and ovary were significantly increased by two- to threefold. Bilateral breast cancer and breast–ovarian cancer were very strong predictors of familial risks, with one in four female relatives predicted to develop breast and/or ovarian cancer by age 75. Mothers had a slightly increased risk of colon cancer, but not endometrial cancer. The risk for breast cancer was also increased among fathers (standardized incidence ratio 2.5; 95% CI 0.5–7.4) and especially brothers (29; 7.7–74), although based on small numbers. The risk for prostatic cancer was unremarkable. In this large population-based survey, the first-degree relatives of women who developed breast cancer before age 40 were prone to ovarian cancer as well as male and female breast cancer, but not other tumours that may share susceptibility genes with breast cancer. © 1999 Cancer Research Campaign

A large number of benign melanocytic nevi is the major risk factor for malignant melanoma (MM). In a multicenter case-control study, the number of common (CN) and clinically atypical (AN) nevi were counted separately at individual sites in 278 melanoma patients and 278 age- and gender-matched non-melanoma controls. Relative risk (RR) adjusted for age and sex was calculated. In men as well as women, the number of CN on the legs was the best predictor of overall melanoma risk. In men, RR for developing MM when > or = 1 AN were present on the trunk was 4-fold (vs. none). In women, presence of AN on the arms increased RR 9.5-fold. For men and women combined, after adjusting for age and gender, the RR for developing MM on the trunk and on the legs was best predicted by counts of CN at the respective body region. However, high counts of CN on the arms were associated with high melanoma risk on the legs (somewhat lower on the trunk). For AN, no site-specificity of melanoma risk was found. Our data suggest that nevus counts of the legs are the best predictor of overall melanoma risk if total body nevus counts are not feasible. Although high counts of CN on the trunk and legs are associated with a higher risk of developing MM at the respective site than at another site, our data do not unequivocally support a direct site-specific melanoma risk.

Background Recent reports indicate that the prevalence of bipolar disorder (BD) in patients with an acute major depressive episode might be higher than previously thought. We aimed to study systematically all patients who sought therapy for major depressive episode (MDE) within the BRIDGE study in Germany, reporting on an increased number (increased from 2 in the international BRIDGE report to 5) of different diagnostic algorithms. Methods A total of 252 patients with acute MDE (DSM-IV confirmed) were examined for the existence of BD (a) according to DSM-IV criteria, (b) according to modified DSM-IV criteria (without the exclusion criterion of ‘mania not induced by substances/antidepressants’), (c) according to a Bipolarity Specifier Algorithm which expands the DSM-IV criteria, (d) according to HCL-32R (Hypomania-Checklist-32R), and (e) according to a criteria-free physician's diagnosis. Results The five different diagnostic approaches yielded immensely variable prevalences for BD: (a) 11.6; (b) 24.8%; (c) 40.6%; (d) 58.7; e) 18.4% with only partial overlap between diagnoses according to the physician's diagnosis or HCL-32R with diagnoses according to the three DSM-based algorithms. Conclusions The diagnosis of BD in patients with MDE depends strongly on the method and criteria employed. The considerable difference between criteria-free physician's diagnosis and the remaining algorithms indicate the usefulness of criteria lists within the everyday clinical setting. Limitations Diagnoses based on DSM were only made with checklists. The diagnoses of (hypo-) manic episodes in the patient history were not systematically verifiable by indirect anamnesis.

A 10-year-old Swiss Braunvieh cow near term was referred to our clinic because of severe abdominal distension, which caused loss of demarcation between the udder and ventral abdominal wall. Ultrasonographic examination revealed marked ascites and multiple echogenic nodules in the greater omentum. Based on the findings, non-inflammatory ascites attributable to neoplasia was diagnosed. Rupture of the prepubic tendon from the pubic symphysis was also suspected. Because of a grave prognosis, parturition was induced and a live calf was delivered. The cow was euthanized and a postmortem examination was carried out. The abdominal cavity contained 248.5 litres of clear fluid. The greater omentum was thickened and oedematous and regionally contained fluid-filled cystic structures, which varied in size with a maximum diameter of 10 centimetres. Based on the histological, immunohistochemical and electron microscopical findings, biphasic mesothelioma with cyst formation affecting the entire abdominal cavity was diagnosed.

Background Malignant catarrhal fever (MCF) is a fatal herpesvirus infection, affecting various wild and domestic ruminants all over the world. Water buffaloes were reported to be particularly susceptible for the ovine herpesvirus-2 (OvHV-2) causing the sheep-associated form of MCF (SA-MCF). This report describes the first case of possibly caprine-associated malignant catarrhal fever symptoms in a domestic water buffalo in Switzerland. Case presentation The buffalo cow presented with persistent fever, dyspnoea, nasal bleeding and haematuria. Despite symptomatic therapy, the buffalo died and was submitted to post mortem examination. Major findings were an abomasal ulceration, a mild haemorrhagic cystitis and multifocal haemorrhages on the epicardium and on serosal and mucosal surfaces. Eyes and oral cavity were not affected. Histopathology revealed a mild to moderate lymphohistiocytic vasculitis limited to the brain and the urinary bladder. Although these findings are typical for MCF, OvHV-2 DNA was not detected in peripheral blood lymphocytes or in paraffin-embedded brain, using an OvHV-2 specific real time PCR. With the aid of a panherpesvirus PCR, a caprine herpesvirus-2 (CpHV-2) sequence could be amplified from both samples. Conclusions To our knowledge, this is the first report of malignant catarrhal fever in the subfamily Bovinae, where the presence of CpHV-2 could be demonstrated. The etiological context has yet to be evaluated.

Interventional radiological procedures for the treatment of primary and secondary pulmonary malignancies have become increasingly important. In addition to thermally ablative treatment, selective chemoembolisation by a vascular access allows localised therapy. These treatments are considered to be palliative for patients in a reduced general condition which does not allow systemic chemotherapy. In functionally inoperable patients especially the ablative procedures are potentially curative alternatives to surgery. This article provides an overview of the currently used interventional radiological procedures in lung oncology and assesses their importance. Further studies are needed to show whether interventional radiological procedures, which are promising due to their favourable risk-benefit ratio, may represent an alternative to radiotherapy or be effective in multimodal approaches.

Biomarkers have been intensively studied in community-acquired pneumonia (CAP) in recent years. In the context of the CAPNETZ study we had the unique opportunity to evaluate old and new biomarkers in a multicentre study with a high number of patients.In several substudies we found the following results: procalcitonin, CRP and leukocytes show highest values in patients with typical bacterial etiology of CAP, but do not allow individual prediction of etiology. Patients without antibiotic pre-treatment show higher values of biomarkers compared to patients with antibiotic pre-treatment. New cardiovascular biomarkers are good predictors for short- and long-term mortality in CAP, superior to the inflammatory markers procalcitonin, CRP and leukocytes and at least comparable to the clinical CRB-65 score. Pro-Adrenomedullin is among the new biomarkers the one with the best prognostic value.Biomarkers correlate with the severity of CAP but do not allow individual prediction of etiology. New cardiovascular biomarkers are suitable for the evaluation of short- and long-term prognosis in CAP. The combination of several biomarkers reflecting different pathophysiological pathways has the potential to improve management of CAP in the future.

A 53-year-old woman presented with recurrent episodes of cough and non-specific pulmonary symptoms. For many years she had been known to have primary biliary cirrhosis.The chest X-ray showed multiple pulmonary nodules. Microbiological examination did not detect any pathogen and transbronchial biopsy of the pulmonary nodules failed to provide a diagnosis. Histology of a surgical lung biopsy showed interstitial inflammation, vasculitis and non-caseating granulomas.The findings indicated necrotizing sarcoid granulomatosis. During oral corticoid therapy the pulmonary nodules regressed within a few weeks. The patient has remained free of pulmonary symptoms.Pulmonary necrotizing sarcoid granulomatosis is a rare condition to consider in the differential diagnosis of pulmonary nodules. Because of the histological findings and its benign course it resembles sarcoidosis.

Adequate dietary phosphorus intake and the use of phosphorus binders are the main tools for treating hyperphosphatemia. Thus, its success depends essentially on the patient's ability to understand and adhere to the dietary plan and the use of phosphate binders.To evaluate hyperphosphatemic patients adherence and knowledge about phosphate control treatment.This is a cross-sectional study. One hundred and twelve patients on hemodialysis (60 males; age = 49.3 ± 13.3 years), from five dialysis centers with mean serum phosphorus5.5 mg/dL between July and December of 2008 (mean = 6.57 ± 0.73 mg/dL) were included. A questionnaire with questions about the consequences of hyperphosphataemia, foods high in phosphorus, appropriate use of phosphate binders and patient's opinion about reasons for treatment failure was administered. Laboratory parameters assessed were serum urea, calcium, phosphorus and parathormony (PTH), and dialysis adequacy by means of urea Kt/V.The average score of questionnaire was 78.5%. Regarding the reasons for the failure of the treatment of hyperphosphataemia, 87% indicated the response "because I eat more phosphorus than I should" and / or "because I do not take the phosphate binder as I should". Among those who said they did not use phosphate binder correctly, most (62%) justified to forget as the reason. The serum phosphorus correlated directly with serum urea (R = 0.33, p0.01) and inversely with Kt/V (R = -0.20, p0.05). There was no correlation between the phosphorus, the education level and the scores on questionnaire.Patients showed a good level of knowledge about the hyperphosphatemia treatment, but the vast majority were noncompliant to that. Strategies to improve compliance are necessary to decrease the incidence of hyperphosphatemia in hemodialysis patients.

At least half of all patients with psychiatric disorders are female. Depressive disorders occur twice as often in women than in men. Despite the need for a gender-specific approach in treating psychiatric disorders, little is known about gender issues in psychopharmacology. It has been recognized that women respond better than men to serotonin-modulating substances but that this effect is reversed after menopause. Furthermore, women develop gynecological complications under medication with certain psychopharmacological agents which calls the use of these drugs into question. Side effects such as weight gain, hyperglycemia, cardiac arrhythmias, and sexual dysfunction also occur more frequently in women than in men. Pregnancy is a particularly sensitive aspect. The risk that a mother with a psychiatric disorder could relapse if the drug is discontinued has to be weighed against the risk of the child being born with an anomaly or developing prenatal complications.

Women and men differ in drug needs and drug metabolism. Usually women are smaller and lighter and have a higher body fat percentage and lower kidney function. Primary drug-metabolizing enzymes in the intestinal wall and liver, which are part of the cytochrome P450 family, have different activities in men and women. Their substrates (beta-blockers, blockers of calcium channels such as nifedipine and verapamil, cyclosporine, and many others) are metabolized differently. Sex differences were observed after administration of digitalis, which is often overdosed in women. Furthermore, beta-blockers are found at higher plasma levels in women and ACE inhibitors cause more side effects in women than in men. In women, acetylsalicylic acid provides effective primary prophylaxis against stroke but not myocardial infarction. In men, these drugs have opposite effects. Anticoagulants and thrombolytics often lead to bleeding complications in women, QT prolonging drugs produce more frequently arrhythmia. It is therefore very important to control drugs following approval and to look out for these differences between men and women.

In this prospective study, reliability of integrated (18)F-FDG PET/CT for staging of NSCLC was evaluated and compared to MDCT or PET alone.240 patients (pts) with suspected NSCLC were examined using PET/CT. Of those patients 112 underwent surgery comprising 80 patients with NSCLC (T1 n = 26, T2 n = 37, T3 n = 11, T4 n = 6). Imaging modalities were evaluated independently.MDCT, PET and PET/CT diagnosed the correct T-stage in 40/80 pts (50%; CI: 0.39-0.61), 40/80 pts (50%; CI: 0.39-0.61) and 51/80 pts (64%; CI: 0.52-0.74), respectively, whereas equivocal T-stage was found in 15/80 pts (19%; CI: 0.11-0.19), 12/80 pts (15%; CI: 0.08-0.25) and 4/80 pts (5%; CI: 0.01-0.12), respectively. With PET/CT, T-stage was more frequently correct compared to MDCT (p = 0.003) or PET (p = 0.019). Pooling stages T1/T2, T-stage was correctly diagnosed with MDCT, PET and PET/CT in 54/80 pts (68%; CI: 0.56-0.78), 56/80 pts (70%; CI: 0.59-0.80) and 65/80 pts (81%; CI: 0.71-0.89). T3 stage was most difficult to diagnose. T3 tumors were correctly diagnosed with MDCT in 2/11 pts (18%; CI: 0.02-0.52) versus 0/11 pts (0%; CI: 0.00-0.28) with PET and 5/11 pts (45%; CI: 0.17-0.77) with PET/CT. In all imaging modalities, there were no equivocal findings for T4 tumors. Of these, MDCT found the correct tumor stage in 4/6 pts (67%; CI: 0.22-0.95), PET in 3/6 pts (50%; CI: 0.12-0.88) and PET/CT in 5/6 pts (83%; CI: 0.36-0.99).Integrated PET/CT was significantly more accurate for T-staging of NSCLC compared to MDCT or PET alone. The advantages of PET/CT are especially pronounced combining T1- and T2-stage as well as in advanced tumors.

Clusterin (CLU) is involved in a variety of biological processes and has been found to be expressed even in many human malignancies, including breast cancer. Currently, there are only few data on the prognostic value of CLU in breast cancer. We therefore evaluated the relationship between CLU expression and clinicopathological parameters as well as relapse-free survival (RFS) and metastasis-free survival (MFS) of 141 breast cancer patients using the monoclonal antibody 7D1. CLU expression was found in 26% of cases and correlated significantly with high histological tumor grade and high Ki-67 labeling index (p=0.026 and p=0.010, respectively). Univariate Cox regression analysis revealed that CLU expression was tendentiously associated with RFS (p=0.068; relative risk [RR]: 1.77) and MFS (p=0.122; RR: 1.57). In a multivariate analysis, tumor grade, stage, estrogen receptor status and patients age (concerning RFS) as well as grade and lymph node status (concerning MFS) were identified as significant independent prognosticators. CLU expression showed an independent prognostic relevance concerning prediction of RFS by trend (p=0.110; RR: 1.81). We conclude from our data that estimation of CLU immunoreactivity may be helpful as a supplementary criterion to better assess the tumors propensity to relapse in selected cases of breast carcinoma.

Background. Integrated positron emission tomography (PET)/computed tomography (CT) scanners have been recently introduced in the diagnostic work-up of suspected pulmonary malignancy and demonstrate encouraging results in the staging of nonsmall-cell lung cancer. Objective. To evaluate the usefulness of integrated FDG PET/CT in pulmonary carcinoid tumours. Setting. University hospital. Methods. We studied 13 patients (mean age ± 1 SD, 57 ± 11 years) with pulmonary carcinoid tumours. All patients demonstrated a single pulmonary lesion. Integrated PET/CT scan and surgical resection were performed in all patients. Results. The pulmonary lesion size ranged from 1.1 to 5.0 cm. Final histological diagnosis confirmed 12 typical and one atypical pulmonary carcinoid. Mean proliferation rate of the typical carcinoids was 1.7 ± 1.4%. None of the patients had recurrent carcinoid disease or died during follow-up (864 ± 218 days). Mean standardized uptake value (SUV) of 18F-fluorodeoxyglucose (FDG) in typical carcinoids was 3.0 ± 1.5 (range 1.2 – 6.6); SUV in the atypical carcinoid was remarkably high with a value of 8.5. The SUV was lower than 2.5 in 6 of 12 patients (50%). Mediastinal lymph node metastases or extrathoracic metastases were not detected in any patient. Conclusions. 18F-fluorodeoxyglucose PET/CT imaging improves accurate localization of metabolic activity and thus the interpretation of pulmonary lesions on CT. FDG uptake in pulmonary carcinoid tumours is often lower than expected for malignant tumours. Therefore, surgical resection or biopsy of lesions suspected to be carcinoids should be mandatory, even if they show no hypermetabolism on FDG PET images.

We report on a 67-year-old female patient who was admitted to our intensive care unit with acute renal failure and severe hypoxemia. Transiently, the patient had to be treated with kidney replacement therapies and artificial ventilation. The actual illness started with general weakness, recurrent bloody diarrhea and intermittent dermatitis of the lower legs. Skin symptoms were initially observed 2 years before the actual clinical findings. The bloody diarrhea was attributed to an inflammatory stenosis of the sigma. The life-threatening clinical aggravation was due to diffuse alveolar hemorrhage and alveolitis. In the search for the cause of the systemic disease, both a monoclonal y-globulinemia, causing a cryoglobulinemia type II and an acute cytomegalovirus infection were diagnosed. Additionally, the course of the disease was complicated by a secondary antibody deficiency as well as an endocarditis of the aortic valve caused by Enterococcus faecium. A cryoglobulinemic vasculitis type II was histologically found in biopsy specimen of the kidney. Thus, the present case reports on a coincidence of a monoclonal gammopathy causing a cryoglobulinemia type II with extensive organ involvement and a florid CMV infection. We hypothesize that the CMV infection has triggered the cryoglobulinemia and its particular severe organ involvement.

Odontogenic tumors are a heterogenic group of neoplasias of the oral cavity, whose biological behaviour reaches from true hamartomas to highly malignant tumors.We describe the case of a 4 year old caucasian girl presenting with eruption disturbance of a primary tooth and corresponding maxillary tumor. After surgical removal of the mass, histological examination classified the tumor as ameloblastic fibroodontoma. This very rare neoplasm is of odontogenic origin.Following our case report, the variety of odontogenic tumors regarding tumor biology, clinical symptoms and therapeutic options in childhood are discussed.In case of complaints or clinical symptoms paediatricians should take the possibility of such neoplasias into consideration.

Comparative analysis of the incidence rates and epidemiological features of cutaneous malignant melanoma (CMM) between different ethnic groups exposed to varying environmental factors is critical for consideration of the causes of CMM but can also be utilized in a public health approach to control of the disease.To compare incidence rates and clinical features of CMM in a Greek and a central European population (central Baden-Württemberg, Germany).Incident cases of CMM were traced in all hospitals of the island of Crete for the period 1999-2002. Age-standardized incidence rates per 100 000 inhabitants per year for the European Standard Population were calculated based on the Cretan population statistics. A comparison was performed between the Cretan findings and those of southern Germany as registered by the hospital-based Central Malignant Melanoma Registry, which likewise documents more clinical features than normally recorded by population-based cancer registries.Mean incidence rates in Crete for 1999-2002 were 4.01 per 100 000 inhabitants per year for males and 4.05 for females as compared with 10.6 for males and 11.1 for females in southern Germany. There were striking differences in the clinical characteristics of CMMs, with significantly higher tumour thickness in Crete (median 1.4 mm vs. 0.7 mm in southern Germany). Correspondingly, significantly more nodular melanomas were observed in Crete (29%) as compared with southern Germany (11%).Incidence of CMM in Crete, with about four cases per 100 000 inhabitants per year, is clearly higher than previously estimated, and there is an urgent necessity for earlier recognition of CMM in Crete. However, the incidence of CMM in southern Germany is much higher.

This paper introduces a case of local pigmented villonodular synovits (PVNS) of the upper ankle joint in a 37-year old patient. PVNS is a neoplasia of the synovial membrane. Two different entities of PVNS are known: generalized diffuse and local nodular. They differ in their degree of destruction and growth configuration, which is crucial for prognosis and operative treatment. The most common location of the local nodular form is the knee joint, followed by the finger joints. Occurrence in the ankle joint is not common but should be considered if clinical findings are present. MRI is the method of choice for diagnosis and assessment of the bone situation. Treatment consists of radical excision of the neoplasia. Radiosynoviorthesis is recommended as a post-operative treatment to increase the probability of a total removal of persisting PVNS cells. The rate of recurrence seems to be between 8 and 46%.

Endobronchial lipoma is a very rare benign lung tumor. Therapeutic alternatives are the interventional bronchoscopic laser resection or surgical treatment.From 1996 to 2002 we diagnosed 16 patients with endobronchial lipoma in our institution. We examined the clinical data of the patients and their influence on the individual patient treatment.14 (88 %) out of the 16 patients (60 +/- 14 y.) were male. Clinical symptoms were cough (81 %), dyspnea (75 %), pulmonary infiltration (63 %) and fever (31 %). In the right lung 11 lipomas (69 %) were located, in the left lung 5 lipomas (31 %). The distribution to main bronchus, upper lobe, middle lobe and lower lobe bronchus were 2 (12.5 %), 6 (37.5 %), 2 (12.5 %) und 6 (37.5 %). 14 (88 %) lipomas were found in the central airways, 2 were located in the periphery of the lung. All lipomas in the central airways were successfully treated by bronchoscopic laser therapy with a mean of 1.1 +/- 0.3 laser sessions. One patient died of concomitant bronchial carcinoma before therapy. Surgical treatment was only necessary in a very peripherally located huge lipoma and a lipoma with extensive parenchym destruction.Bronchoscopic laser resection should be considered as first line therapy in cases of endobronchial lipoma. It is safe, successful, rapid and less expensive compared to surgical resection. Surgery should only be indicated in patients with lipomas with very peripherally localisation or parenchym destruction, extrabronchial growth, suspected malignancy or technical problems at bronchoscopic resection.

Mutations within the NOD2/CARD15 gene have recently been shown to be associated with Crohn's disease.To investigate the clinical impact of the three common NOD2/CARD15 mutations in patients with Crohn's disease.We investigated the prevalence of the three common NOD2/CARD15 mutations (Arg702Trp, Gly908Arg, 3020insC) in 180 patients with Crohn's disease, 70 patients with ulcerative colitis and 97 controls. In patients with Crohn's disease, prevalence of NOD2/CARD15 mutations were correlated to clinical and demographical parameters.In Crohn's disease patients, 35.6% carried at least one mutant allele of NOD2/CARD15 mutations compared with 14.3% of patients with ulcerative colitis (P = 0.006) and to 15.5% of controls (P = 0.0001). Genotype phenotype analyses revealed that NOD2/CARD15 mutations determined younger age at disease diagnosis (P = 0.03), ileal disease location (P = 0.01) and ileocecal resections (P = 0.0002). Interestingly, reoperation with resection of the anastomosis was significantly more frequent in patients with NOD2/CARD15 mutations (P = 0.01).Our investigations support the current hypothesis that NOD2/CARD15 mutations are associated with a phenotype of Crohn's disease with younger age at diagnosis, ileal involvement, ileocecal resections and a high risk of postoperative relapse and reoperation. NOD2/CARD15 mutations might therefore be used to identify high risk patients for relapse prevention strategies.

To determine whether the combination of prolonged QRS duration and brain natriuretic peptide (BNP) levels predicts left ventricular systolic dysfunction (LVSD) with a higher accuracy compared with QRS duration or BNP alone.University hospital.We studied 128 consecutive patients with suspected cardiac disease. At rest the QRS duration on 12-lead ECG and BNP levels were determined. A left ventricular ejection fraction (LVEF)50% at echocardiography was defined as LVSD.QRS duration in the LVSD group (n = 66, LVEF 30 +/- 8%) was longer than in the group without LVSD (n = 62, LVEF 60 +/- 5%; QRS 129 +/- 34 vs. 96 +/- 20 ms, P0.001). BNP was higher in the LVSD group compared with controls (467 +/- 397 vs. 169 +/- 242 pg mL(-1), P0.001). A QRS duration of0.1,0.11 or0.12 s was highly specific (63, 90 and 98%) but less sensitive (84, 81 and 75%) for the prediction of LVSD. A QRS cut-off value of 106 ms was moderately sensitive (65%) but very specific (87%) for the prediction of LVSD, whereas a BNP cut-off value of84 pg mL(-1) was highly sensitive (89%) but only modestly specific (58%). The positive likelihood ratio for LVSD of abnormal BNP (2.0) and QRS prolongation0.1 s (2.3) was improved by the combination of both criteria (5.1). In multivariate analysis, BNP and QRS duration were independent predictors of LVSD.The combination of abnormal BNP and QRS prolongation yields a higher positive likelihood ratio for the detection of LVSD compared with the two criteria alone.

Cathepsins are involved in lysosomal protein degradation, proenzyme activation, antigen processing, and hormone maturation. They are secreted by tumor cells and macrophages and catalyze the remodeling of extracellular matrix proteins. To gain insight into the expression pattern of cathepsins during fetal lung development, the expression of cathepsins B, H, K, L, and S at protein and mRNA levels were evaluated by using immunohistochemistry and in situ hybridization. Early expression of cathepsins B, H, and K was found in epithelial cells of the branching presumptive bronchi (12th week of gestation). The most intense cathepsin K-specific immunoreactivity was found in developing airways with a lumen. Cathepsin K was found in epithelial cells only, whereas in contrast, cathepsins B and H were detected both in epithelial and interstitial cells. During fetal maturation, interstitial cells displayed cathepsin L immunoreactivity and, in the saccular phase (26th week of gestation), both cathepsin L and S immunoreactivities. A continuous decline in the proportion of cathepsin H-positive interstitial CD68-positive cells was observed. These discrete temporal and spatial variations in cathepsin expression during organogenesis of the human lung indicate different physiological roles for the individual enzymes in different cell types and developmental stages.

Chronic heart failure often coincides with secondary pulmonary hypertension. In this study the influence of pulmonary hypertension on exercise capacity and ventilatory parameters in patients with chronic heart failure was examined.21 patients with chronic heart failure (six women, 15 men, mean age 55 +/- 10 years) and a left ventricular ejection fraction of 25 % +/- 5 % were studied by right heart catheterization, bodyplethysmography including carbonmonoxide diffusion testing and spiroergometry. Seven patients suffered from ischemic and 14 patients from dilative cardiomyopathy. Pulmonary hypertension (defined as pulmonary artery mean pressure25 mmHg) was found in ten patients.Patients with pulmonary hypertension showed a reduced vital capacity (75 % +/- 20 % of normal values vs. 93 % +/- 14 % of normal values, p0.001), a lower forced expiratory volume in one second (FEV1 68 % +/- 21 % of normal values vs. 91 % +/- 15 % of normal values, p0.001), and a reduced carbonmonoxide-diffusing capacity (58 % +/- 21 % vs. 77 % +/- 21 %, p0.001) compared to patients without pulmonary hypertension. Mean expiratory flow at 25 % and 75 % of the exspiration time was lower in patients with pulmonary hypertension (30 % +/- 13 % vs. 50 % +/- 29 % and 62 % +/- 25 % vs. 81 % +/- 20 %, each p0.05). In patients with pulmonary hypertension, the flow-volume diagram characteristically showed signs of "small airway disease". Spiroergometry revealed a significantly lower maximum oxygen-uptake (12.5 +/- 2.1 vs. 15.2 +/- 4.1 ml/min/kg, p0.05), oxygen-uptake at the anaerobic threshold (9.7 +/- 1.6 vs. 12.0 +/- 3.0 ml/min/kg, p0.05), carbon dioxide ventilatory efficiency (EqCO2 38 +/- 9 vs. 31 +/- 3, p0.05) and ventilatory reserve (39 % +/- 22 % vs 51 % +/- 21 %, p0.05) in patients with pulmonary hypertension.In patients with chronic heart failure the presence of pulmonary hypertension leads to a reduction of exercise capacity and impaired ventilatory parameters. Lung functional testing reveals bronchial obstruction, "small airway disease" and a reduced ventilatory efficiency.

A 73-year-old previously healthy woman presented with recurrent weakness, vertigo and perioral paresthesia of 3 months' duration. Physical examination on admission was unremarkable and revealed a patient in good condition.Recurrent episodes of fasting hypoglycemia let us to proceed with a fasting test. The test was stopped after 24 hours when the patient became presyncopal and was found to have a blood sugar value of 2.2 mmol/l (accompanied by inadequately increased values for proinsulin, insulin and C-peptide). Ultrasound and computertomography of the abdomen showed a huge inhomogeneous mass in the tail of pancreas and multiple lesions in the liver, respectively. Core needle biopsies revealed typical histopathological findings of a neuroendocrine carcinoma.Eight cycles of chemotherapy were given using streptozotocin/doxorubicin for three cycles and streptozotocin/5-fluorouracil for the remaining therapy over a period of 16 months resulting in a reduction in size of liver metastases and improvement of symptoms. Following 6 months without any therapy new episodes of severe hypoglycemia and progression of the liver metastases occurred. Despite seven further cycles of chemotherapy and additional treatment with diazoxide/octreotide the patient remained hypoglycemic and continuous glucose infusions became necessary. Therefore, chemoembolization of the liver with streptozotocin/5-fluorouracil and lipiodol-emulsion was performed. This resulted in a significant improvement of symptoms and the patient could subsequently be discharged. The patient died 4 months later.Chemoembolization is an effective possibility in the palliative treatment of advanced malignant insulinoma.

Zinc deficiency causes abnormalities of the immune response. In chronic hemodialysis therapy abnormalities in zinc metabolism as well as an impaired immune response to vaccination have been reported. Therefore we performed a vaccination study against diphtheria and hypothesized that the response to diphtheria vaccination is related to serum zinc deficiency in hemodialysis patients. Serum zinc concentrations were assayed in 16 chronic hemodialysis patients (10 male, 6 female; mean age 65 years) without a documented vaccination history against diphtheria. Nine of these patients were triple immunized against diphtheria while seven received a single vaccination. The response to diphtheria vaccination was measured by ELISA detecting specific antibodies to diphtheria-toxoid. Seroconversion 6 and 12 months after vaccination was defined as the doubling of antibody titers in patientsor = 0.1 IU/ml prior to vaccination or as titers0.1 IU/ml in all other patients. Only 6/16 hemodialysis patients responded to immunization against diphtheria by specific antibody production (0.1 IU/ml). Twelve months after the single injection 3/7 patients seroconverted while six months after the triple vaccination 3/9 patients responded to immunization. This was not age-dependent, whereas in non-responders we detected significantly decreased serum zinc levels. In contrast, responders showed similar serum zinc levels as age-matched controls. Furthermore, we measured a decreased alpha 2-macroglobulin concentration only in the responders amongst the hemodialysis patients. Protection against diphtheria and the immune response to diphtheria vaccination in hemodialysis patients is poor. The failure to respond to active diphtheria vaccination is related to a significantly decreased serum zinc concentration in hemodialysis patients.

Cathepsin K is a cysteine protease with high matrix-degrading activity. Initially, cathepsin K was described as being expressed exclusively by osteoclasts. It was suggested that cathepsin K expression is a specific feature of cells involved in bone remodelling. The aim of this study was to investigate the hypothesis that cathepsin K is expressed not only in bone-resorbing macrophages, but also more generally in specifically differentiated macrophages, such as epithelioid cells and multinucleated giant cells in soft tissues. Specimens obtained from different organs and anatomical locations of patients suffering from sarcoidosis, tuberculosis, granulomas caused by foreign materials, and sarcoid-like lesions were investigated for the expression of cathepsins B, K, and L. Immunohistochemistry and in situ hybridization showed cathepsin K in epithelioid cells and multinucleated giant cells irrespective of the pathological condition and anatomical location, but not in normal resident macrophages. By immunoelectron microscopy, cathepsin K was discovered in cytoplasmic granules of multinucleated giant cells. In contrast, cathepsin B and cathepsin L were expressed ubiquitously in CD68-positive tissue macrophages, epithelioid cells, and multinucleated giant cells. The results demonstrate that cathepsin K, but not cathepsin B or cathepsin L, differentiates specific phenotypes of macrophages independently of the anatomical site. Its enzymatic characteristics, particularly its high matrix-degrading activity, suggest that cathepsin K-positive epithelioid cells and multinucleated giant cells are characterized by an enhanced specific proteolytic capability.

To determine the frequency of obsessive-compulsive disorder (OCD) in inpatient subjects with bipolar disorder (BD) and to examine the clinical characteristics of BD subjects with OCD.The sample consisted of 143 inpatient subjects with DSM-III-R BD-I and BD-NOS (BD-II), recovered from a current episode of either depression or mania. Demographic and clinical variables were obtained on the day of admission. Current comorbid conditions including OCD were determined by the Structured Clinical Interview for DSM-III-R Ifollowing recovery from the acute affective episode.The frequency of current OCD was 7% (N = 10). All BD subjects with OCD were BD-II, were male, and had a diagnosis of current dysthymia. They had fewer episodes and a higher incidence of prior suicide attempts than bipolar subjects without OCD. None of the bipolar subjects with OCD fulfilled criteria for cyclothymia.Our findings suggest that BD-II, OCD, dysthymia, and suicidality cluster together in some subjects with BD. We discuss the clinical implications of our findings.

The onset of a malignant transformation in long-standing ulcerative colitis is difficult to predict. The value of the clinical and histomorphological parameters in current use is limited. It was thus aim of the present study to investigate the value of DNA-ploidy for the early detection of a malignant transformation in long-standing ulcerative colitis. This retrospective study comprised 20 patients with long-standing ulcerative colitis. The average observation time was 7.3 years (range: four to twelve years). All patients took part in a surveillance program and had between four and seven colonoscopies within a minimum period of time of five years. At these instances mucosal biopsies were taken in a standardized manner at eight different locations throughout the colon. These paraffin-embedded specimens (n = 542) were analyzed histomorphologically and DNA-cytometrically. During the observation time five patients developed an ulcerative colitis-associated colorectal carcinoma (UCA). In these patients epithelial dysplasias were not more common than in the remaining 15 cases. The vast majority of the specimen of the patients with UCA showed distinct DNA-cytometrical alterations, i.e. they were aneuploid. Such aneuploid mucosal cell populations were distributed over the whole colon, irrespectively of the later site of the carcinoma. These aneuploid lesions were found in one case eleven years, in an average seven years prior to the final diagnosis of a UCA. In contrast, the colon epithelium of the patients without UCA showed only proliferative-diploid DNA-distribution patterns during the observation time. In summary, affected patients had multiple highly aneuploid lesions of the colon mucosa at an average of seven years prior to the final diagnosis of UCA. These lesions came from macroscopically chronic inflamed tissue, and where histomorphologically without signs of dysplastic transformation. DNA-cytometrical investigations could thus be of additional predictive value for the individual risk assessment as regards an impending malignant transformation.

The sonographic measurement of the Doppler perfusion index (DPI)--the ratio of blood flow in the hepatic artery to total liver blood flow--has been suggested to represent a method of detecting even small liver metastases.To evaluate the DPI measurement in our patients with liver metastases of colorectal cancer, gastric and bronchial carcinoma.36 patients with liver metastases were compared to 21 control subjects. The hepatic arterial and portal venous blood flows were calculated from the product of the average velocity of flow and the cross-sectional lumen of the vessel. Each measurement was performed three times by two independent examiners.Patients with metastases had a significantly higher hepatic blood flow and a significantly higher DPI (p = 0.0004; M +/- SD 0.23 +/- 0.11; r 0.06-0.52) compared with controls (M +/- SD 0.14 +/- 0.06, r. 0.05-0.26). No significant difference was seen in the portal vein blood flow. The DPI-values measured by the two examiners differed by 25.98% +/- 23.20.DPI values in patients with liver metastases differ from those in control subjects due to an increased hepatic arterial blood flow. No clear separation of the two groups was possible because DPI values overlapped. The inter observer agreement in DPI seems clinically acceptable.

To investigate to what extent analysis of silver-stained nucleolar organizer regions (AgNORs) is cell cycle dependent in breast cancer and to assess the prognostic value of an AgNOR analysis that takes into consideration the cell cycle status of tumor cells.In 97 cases of invasive breast carcinoma, morphometric AgNOR analysis was performed in tumor cells with immunohistochemical MIB-1 reactivity (NORcyc analysis) and in MIB-1-negative tumor cells (NORnon analysis). Additionally, conventional (NORconv) analysis without preceding MIB-1 staining was done. Findings were compared with the Nottingham prognostic index (NPI).In comparison to noncycling tumor cells, cycling ones exhibited significantly higher AgNOR numbers (mean values, 3.84 +/- 1.09 vs. 2.40 +/- 0.78 per nucleus), higher total AgNOR areas (5.95 +/- 3.17 vs. 5.62 +/- 3.05 micron 2, NS) and significantly lower mean AgNOR areas (2.08 +/- 1.14 vs. 2.93 +/- 1.69 micron 2). When related to NPI, correlation coefficients of NORnon analysis were higher than those of NORcyc analysis but lower than those of NORconv analysis. Among the different AgNOR parameters, total AgNOR area correlated best with NPI.Cell cycle status has a high impact on AgNOR analysis. However, the best prognostic information in breast cancer is derived from an AgNOR analysis that considers both cycling and noncycling tumor cells.