Fibroblast Activation Protein Inhibitor-Positron Emission Tomography in Aortitis: Fibroblast pathology in active inflammation and remission.

OBJECTIVES: Epigenetically modified fibroblasts contribute to chronicity in inflammatory diseases. Reasons for the relapsing character of large vessel vasculitis (LVV) remain obscure, including the role of fibroblasts, in part due to limited access to biopsies of involved tissue.68Ga FAPI-46 (FAPI)-PET/CT detects activated fibroblasts in vivo. In this exploratory pilot study, we tested the detection of fibroblast activation in vessel walls using FAPI-PET/CT in LVV with aortitis. METHODS: 8 LVV patients with aortitis and 8 age- and gender-matched controls were included. Distribution of FAPI uptake was evaluated in the aorta and large vessels. FAPI-uptake was compared with MRI inflammatory activity scores. Imaging results were compared with clinical parameters such as serum inflammatory markers, time of remission and medication. RESULTS: Three aortitis patients were clinically active, five in remission. Irrespective of activity, FAPI uptake was significantly enhanced in aortitis compared with controls. Patients in remission had a mean duration of remission of 2.8 years (range 1-4 years), yet significant FAPI uptake in the vessel wall was found.In remitted aortitis, MRI inflammatory scores were close to be negative, while in 4/5 patients visually identifiable FAPI uptake was observed. CONCLUSIONS: This pilot feasibility study shows significant tracer uptake in the aortic walls in LVV. FAPI positivity indicates ongoing fibroblast pathology in clinically remitted LVV.

[The German snowball effect : An increasing aftercare problem in bariatric treatment]. / Der deutsche Schneeball-Effekt : Ein zunehmendes Nachsorgeproblem in der bariatrischen Therapie.

BACKGROUND: The surgical treatment of obesity in Germany is a rapidly developing field which is strictly controlled by national guidelines. OBJECTIVE: Depiction of the burden on obesity centers by the exponential increase in numbers of patients following bariatric treatment. METHODS: In a retrospective study the numbers of outpatients at this university obesity center (founded 2007) were descriptively analyzed. Outpatient visits were documented annually and divided into two groups: primary visit and follow-up visit. The frequency of bariatric operations as well as their acceptance/cost coverage by health insurances were evaluated. RESULTS: Overall 318 patients were seen in 2007: 156 primary and 162 follow-up visits. The health insurance rejection rate for cost coverage was 16.8%. There were 1691 outpatient visits in 2016 (2016 vs. 2007: +532%), of which 487 (+312%) were primary and 1204 (+743%) follow-up visits. The health insurance rejection rate dropped to 1.8%, while the frequency of operations increased nearly tenfold. CONCLUSION: With the increasing acceptance of bariatric surgery, a relatively low number of specialized centers have to deal with an exponentially rising follow-up frequency. In consideration of the extent of the obesity epidemic an adequate follow-up constitutes a socioeconomic problem, which can only be solved in an interdisciplinary setting under structural integration.

[Circulating tumor cells in pancreatic cancer : Results of morphological and molecular analyses and comparisons with the primary tumor]. / Zirkulierende Tumorzellen beim Pankreaskarzinom : Ergebnisse morphologischer und molekularer Analysen und Vergleiche mit dem Primärtumor.

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is a disease with a poor prognosis. PDAC shows characteristic mutations within codon 12/13. Circulating tumor cells (CTC) detected in blood samples of patients with cancer are hypothesized as the means of systemic tumor spread. But less is known about morphological/molecular characteristics or the pathophysiological meaning of PDAC CTC. OBJECTIVES: The aim of the study was a cytomorphological and genetic analysis of CTC from patients with PDAC followed by the correlation of the results with those of the corresponding tumor in the pancreas. MATERIAL AND METHODS: Blood samples of 58 patients with PDAC and 10 "normal" control donors were processed through a size-based CTC isolation. KRAS-mutation analyses were performed for CTC and the primary tumor and the results were compared. Furthermore, their potential as a prognostic marker was evaluated. RESULTS: In patients with different UICC stages CTC were detected, but not in normal control patients. There was a trend for a worse median overall survival (OS) for patients with >3 CTC/ml. Patients with a KRASG12V mutation showed a trend for a better median OS compared to those with other KRAS mutations (10 months) or even without KRAS mutation. Fifty-eight percent of the patients presented concordant KRAS mutations in the primary tumor and corresponding CTC, while 42% were discordant. The median OS for both groups was similar. CONCLUSIONS: Detection and characterization of CTC (for example by KRAS mutation analysis) may be useful for prognosis. Furthermore, it expands our knowledge of tumor biology and may detect possible tumor heterogeneity regarding the mutation profile of some cancer types.

[Internal Hernia Following Laparoscopic Roux-Y Gastric Bypass - a Challenge not only for the General Surgeon]. / Innere Hernien nach laparoskopischem Roux-Y-Magenbypass ­ eine Herausforderung nicht nur für den Allgemeinchirurgen.

The frequency of bariatric operations has increased in Germany. Primary operations are usually performed at specialised centres. However, late complications may develop months or even years after the operation, and every general and visceral surgeon may be confronted with them, regardless of the size and specialisation of their clinics. The laparoscopic Roux-Y gastric bypass is the most frequently performed bariatric operation worldwide. During this procedure, the alimentary loop is lifted up in front of the colon to form a pouch, which creates a mesenteric space, also called the Petersen space, dorsal to the alimentary loop and below the transverse colon. Both here and around the mesenteric space of the Roux anastomosis, an internal hernia may develop, i.e. the small intestine can twist on its own axis. Abdominal discomfort due to intestinal obstruction is unspecific, but very pronounced. Clinically, patients either present with an acute abdomen or with intermittent unspecific abdominal pain with nausea, and rarely also with vomiting. Clinical examinations and lab chemistry tests usually do not reveal any indicative findings. In cases of doubt, therefore, contrast-enhanced computed tomography of the abdomen is the diagnostic imaging procedure of choice. A diagnostic laparoscopy should be performed in every patient with a clinical suspicion of an internal hernia, even if the CT scan is unremarkable. This should be done by a surgeon who is well-versed in laparoscopy and experienced in bariatric surgery, since classification of the intestinal loops is very difficult without knowledge of the hernial orifices. First, an inframesocolic view is obtained with the transverse colon being lifted. From here, the open Petersen space offers a direct view of the ligament of Treitz from the right side. If small intestine is found to the right of the ligament, there is a Petersen hernia. After the inframesocolic view, the gastroenterostomy should be located and the alimentary loop should be followed in distal direction towards the jejunojejunostomy, where the second possible space may be found. Once both spaces have been located and a hernia has been reduced as appropriate, the spaces should be closed with non-absorbable suture.

[Repetitive Transcranial Magnetic Stimulation (rTMS) as a Therapeutic Tool in Psychiatry - Current State of Application in Germany]. / Die repetitive transkranielle Magnetstimulation (rTMS) als therapeutische Option in der Psychiatrie ­ Stand der Anwendung in Deutschland.

The repetitive transcranial magnetic stimulation (TMS) opens new therapeutic options in neuropsychiatric disorders. The use of rTMS in depressive disorders has been most preferably investigated in clinical trials. In Germany, the application of rTMS outside of clinical trials is already increasingly common, not only for depression. Our nationwide survey in psychiatric hospitals was used to detect the current state of the application of rTMS in clinical practice, and should serve as a basis for the development of quality standards.

Pilot study of the application of magnetic bead protein profiling to the study of biomarkers in addiction research.

OBJECTIVES: Proteomic technologies based on mass spectrometry are increasingly used as a valuable tool in clinical research allowing high-throughput protein and peptide profiling to be undertaken. Whilst previous research has focussed the application of this novel technology on the study of patients with disorders compared to comparable individuals from the healthy population, this current study seeks to determine the effect of successful treatment for alcoholism on the serum protein profile obtained. METHODS: Serum samples were collected from patients after initial treatment for alcohol abuse and also 6 months after treatment. The serum samples were prepared for analysis using reverse phase magnetic bead fractionation and the resulting peptides analysed by matrix assisted laser desorption ionisation time-of-flight (MALDI-ToF) mass spectrometry. RESULTS: Whilst the majority of the peptides detected by this approach exhibited constant levels between the two time points, three peptides were elevated at the 6-month time point compared to the initial sampling. CONCLUSIONS: Whilst disorders with very clear biological causes (such as cancer) exhibit significantly different peptide profiles, psychiatric disorders such as alcohol addiction which are multifactorial show less obvious changes. Despite this the two groups of samples could statistically be distinguished by certain peptides expression levels.

[The neuroleptic treatment of delusional parasitosis: first experiences with aripiprazole]. / Neuroleptische Behandlung des Dermatozoenwahns: Erste Erfahrungen mit Aripiprazol.

Delusional parasitosis can occur as an isolated delusional syndrome, or it may be associated with an underlying psychiatric disorder or physical illness. The benefit of treatment with antipsychotics in the treatment of delusional parasitosis is well known. Because of their efficacy and side effects profile, atypical neuroleptics have been suggested as potential alternatives to classical neuroleptics. In the case presented, the positive experiences with the novel neuroleptic aripiprazole are described.

Antidepressant effects of augmentative transcranial magnetic stimulation: randomised multicentre trial.

BACKGROUND: Repetitive transcranial magnetic stimulation (rTMS) has been proposed as a new treatment option for depression. Previous studies were performed with low sample sizes in single centres and reported heterogeneous results. AIMS: To investigate the efficacy of rTMS as augmentative treatment in depression. METHOD: In a randomised, double-blind, sham-controlled multicentre trial 127 patients with moderate to severe depressive episodes were randomly assigned to real or sham stimulation for 3 weeks in addition to simultaneously initiated antidepressant medication. RESULTS: We found no difference in the responder rates of the real and the sham treatment groups (31% in each) or in the decrease of the scores on the depression rating scales. CONCLUSIONS: The data do not support previous reports from smaller samples indicating an augmenting or accelerating antidepressant effect of rTMS. Further exploration of the possible efficacy of other stimulation protocols or within selected sub-populations of patients is necessary.

Crystallization of the major cytosolic glutathione S-transferase from Onchocerca volvulus.

Glutathione S-transferases (GSTs) are a family of detoxification enzymes that catalyse the conjugation of glutathione to xenobiotic and endogenous electrophilic compounds, thus facilitating their elimination from cells. The recombinant Onchocerca volvulus GST2 has been expressed in Escherichia coli, purified and crystallized by the hanging-drop vapour-diffusion technique. Two different crystal forms were grown under identical conditions. They belong to space groups P2(1)2(1)2 and P2(1), respectively. The unit-cell parameters obtained are a = 112.6, b = 84.3, c = 45.1 A for the P2(1)2(1)2 crystal form and a = 51.6, b = 82.3, c = 56.7 A, beta = 95.89 degrees for the P2(1) form. Complete data sets to 2.6 and 1.5 A, respectively, have been collected at 100 K with synchrotron radiation.

Segmental chromosomal aberrations and centrosome amplifications: pathogenetic mechanisms in Hodgkin and Reed-Sternberg cells of classical Hodgkin's lymphoma?

Tumor cell metaphases of classical Hodgkin's lymphoma (cHL) characteristically display highly rearranged karyotypes with chromosome numbers in the hyperploid range and marked intraclonal variability. The causes of this cytogenetic pattern remain largely unknown. An unusual type of chromosomal abnormality coined as segmental chromosomal aberration (SCA) has been recurrently observed in HL cell lines and was suggested to be associated with ribosomal DNA (rDNA) rearrangements. Moreover, centrosome abnormalities provoking deficient chromosome segregation have been reported in many solid tumors and also in cHL cell lines. Whether SCA, rDNA rearrangements or centrosome abnormalities also occur in primary cHL is not yet known. Thus, we performed extensive molecular cytogenetic and immunohistological studies in two cHL cases. Both cases presented SCA associated with genomic gains of the REL and JAK2 loci, respectively. The SCA involving JAK2 was associated with rDNA rearrangements. The absolute centrosome size of HRS cells in both cases was significantly larger than in non-HRS cells, but the relative centrosome size of HRS cells corrected for nuclear size was in the same range as that of the non-neoplastic cells. These findings demonstrate that the various mechanisms associated with chromosomal instability warrant a more detailed characterization in cHL.

Dysfunction of transcallosally mediated motor inhibition and callosal morphology in patients with schizophrenia.

OBJECTIVE: In order to assess the functional integrity of motor pathways through the corpus callosum (CC) in patients with schizophrenia transcallosally mediated inhibition (TI) of voluntary tonic EMG activity of first dorsal interosseus muscle following ipsilateral focal transcranial magnetic stimulation (fTMS) was investigated. In addition thickness and length of CC were calculated. METHOD: Twelve patients suffering from schizophrenia and 12 healthy controls were investigated. CC morphology was measured in mid-sagittal MRI-slices. Latency and duration of TI were calculated. RESULTS: In schizophrenics the duration of TI was significantly prolonged, whereas latencies were not. In addition, a lack of TI was found unilaterally in three patients. Measurements of CC revealed a significantly reduction of the length and thickness in the anterior part of CC in patients. CONCLUSION: These findings indicate that measurement of TI could be used to detect clinical silent affection of transcallosal motor pathways in schizophrenics. The effect of neuroleptic drugs has to be explored.

[Diagnosis and management of an intraoperative vertebral artery injury]. / Diagnose und Notfallmanagement einer intraoperativen Verletzung der Arteria vertebralis.

A patient with cervical myelopathy caused by marked degenerative alterations of the cervical spinal column at the level of cervical vertebrae 3/4 and relative spinal canal stenosis in the area of cervical vertebrae 5-7 was treated in the department of neurosurgery because of progressive myatrophy and paresis of muscles innervated from cervical nerves 5-7. The operation was performed with vertebrectomy of cervical vertebra 6, implantation of a Harms titanium cage with autograft and a plate and spongy bone screw fixation system. There exists an unusual--and not often publicized--complication during this surgical procedure in the area of the cervical spine, namely penetrating injury of the vertebral artery caused by the treatment with a plate and spongy bone screw fixation system. We describe such an injury of the left vertebral artery. The vertebral artery was intraoperatively embolized using mechanical embolization coils.

[Marchiafava-Bignami syndrome. Extrapontine myelinolysis in chronic alcoholism]. / Marchiafava-Bignami-Syndrom. Extrapontine Myelinolyse bei chronischem Alkoholmissbrauch.

Until now, the pathogenesis of Marchiafava-Bignami disease, an extrapontine myelinolysis, is unknown. Accept an abuse of alcohol for many years additional metabolic and vascular disturbances are supposed. The early performance of magnetic resonance imaging in patients with a sudden encephalopathy and history of alcoholism is essential for an assessment of the diagnosis. The bilateral lack of transcallosal inhibition--a parameter for the integrity of the transcallosal connections between motor cortices--is the consequence of the axonal degeneration of transcallosal fibers. Clinical and neuroradiological features of three patients with extrapontine myelinolysis are reported and possible etiologies of the complex disease are discussed. In two cases a severe alcohol abuse was present with the typical picture of the Marchiafava-Bignami disease. In a third patient an intoxication with methanol was present with a similar clinical picture. Although severe neurological disturbances were initially apparent in the patients, during the follow-up there was a significant amelioration of the clinical course under a high-dose vitamin B supplementation.

Demyelination and axonal degeneration in corpus callosum assessed by analysis of transcallosally mediated inhibition in multiple sclerosis.

OBJECTIVE: Following focal transcranial magnetic cortex stimulation (fTMS), inhibition of voluntary EMG activity in the ipsilateral first dorsal interosseus (FDI) muscle was studied, in order to assess the functional integrity of the corpus callosum in patients with multiple sclerosis (MS). METHODS AND RESULTS: Thirty-four patients suffering from definite MS and 12 healthy, age-matched normal subjects were examined. In mid-sagittal slices, 29 patients showed lesions within the truncus corporis callosi in T2-weighted MRI. In 20 patients, all areas (anterior, middle and posterior parts), in one both the anterior and posterior part, in 3 exclusively the anterior, in 4 the middle and in one the posterior area were affected. In 5 patients, lesions of corpus callosum were lacking. In normal subjects, fTMS elicited a transient inhibition (TI) of preactivated (50% of maximal force) isometric voluntary ipsilateral FDI muscle activity. Mean onset latencies of TI were 35.5+/-5.4 ms in right and 36.1+/-4.2 ms in left FDI. Mean duration of TI amounted to 23.0+/-8.4 ms for right and 24.6+/-8.4 ms for left FDI. In the MS group, TI latencies were significantly increased in 23 and TI durations in 16 cases, whereas a lack of TI was found in 5 patients bilaterally and in 6 unilaterally. In patients, mean onset latencies of TI were 40.4+/-13.8 ms in right and 43.3+/-14.4 ms in left FDI, TI duration amounted to 30.5+/-17.4 ms for right and 31.0+/-25.2 ms for left FDI. Increase of onset latencies and durations of TI were positively correlated with the summed area of lesions of corpus callosum in representative mid-sagittal MRI slices. Significant correlations between TI onset latencies and duration on the one hand, and central motor conduction latencies along corticospinal tracts (CML) on the other hand, were not found. CONCLUSION: The present investigation indicates that measurement of TI elicited by fTMS seems to be a sensitive method for an assessment of demyelination and axonal degeneration within corpus callosum in MS patients.

Two new missense mutations in a non-Jewish Caucasian family with type 3 Gaucher disease.

Gaucher disease is an autosomal recessive, lysosomal storage disease caused by a deficiency of the enzyme glucocerebrosidase. The prevalence of this disorder differs significantly among various populations and is highest in some Jewish populations. More than 35 disease-producing mutations of the gene have been reported. The change of the amino acid leucine at position 444 to proline (444Leu-->Pro) is the most common mutation in non-Jewish populations, and a second mutation at amino acid 370 (370Asn-->Ser) is the most common one in Jewish populations. However, most of the mutations have been reported in very few cases or even in only one pedigree. We performed a direct DNA sequencing analysis of the complete functional glucocerebrosidase gene in a 22-year-old neuronopathic non-Jewish patient with Gaucher disease type 3 with myoclonic epilepsy and slight mental disturbances and in most members of his family. After selective amplification of the complete coding region of the patient's functional glucocerebrosidase gene, we identified two hitherto unreported mutations in exon 9 (genomic nucleotide 5224G-->C; 417Val-->Leu) and in exon 11 (genomic nucleotide 6668C-->T; 510Thr-->Ile). Each parent showed one of these mutations. Once we sequenced the complete active gene, we could rule out the existence of further mutations. Data that show that in about 15 to 25% of non-Jewish patients with Gaucher disease no mutations within the glucocerebrosidase gene are found may be due to inappropriate screening methods, mostly used for the genotyping. Until we have precise information about the frequency and distribution of single-point mutations in patients with Gaucher disease, it is necessary to analyze the complete glucocerebrosidase gene.

Anterior sacrodural attachments - Trolard's ligaments revisited.

In contrast to the attention paid to the structures surrounding spinal nerve roots in the intervertebral foramina, the anterior dural attachments are largely ignored, although they have been described since the last decades of the 19th century. These anterior attachments were systematically studied in a series of 30 cadaver dissections and were found to be present in almost 94% of cases. Four types of anterior attachments were observed. The most frequent form (84%) being a system of filaments that present as a double cross vault between the dura mater and the posterior longitudinal ligament extending from L3 to S3 levels. Less frequent were sagittal filaments (30%), short strong ligaments (17%) and a median septum from L3 to the end of the dural sac (7%). No attachments were found in two cadavers. Further studies are needed to clarify the possible role of these structures in transmitting movement to the dural sac and periradicular sleeves when mobilising the last three lumbar vertebrae or the sacrum.

[An unusual intubation (author's transl)]. / Eine ungewöhnliche Intubation

Report of an unusual intubation in a patient who had had resection of maxilla and exenteration of the orbits. Because of a lock jaw the intubation had to be performed through the orbita.