High cardiorespiratory fitness is an independent predictor of the reduction in liver fat during a lifestyle intervention in non-alcoholic fatty liver disease.

OBJECTIVE: Lifestyle intervention with diet modification and increase in physical activity is effective for reducing hepatic steatosis in patients with non-alcoholic fatty liver disease (NAFLD). However, for a similar weight loss, there is a large variability in the change in liver fat. We hypothesised that cardiorespiratory fitness may predict the response to the intervention. DESIGN: Longitudinal study with increase in physical activity and diet modification. SETTING: University teaching hospital. PATIENTS: 50 adults with NAFLD and 120 controls at risk for metabolic diseases. MAIN OUTCOME MEASURES: Total-, subcutaneous abdominal- and visceral adipose tissue by magnetic resonance tomography, liver fat by 1HMR spectroscopy and cardiorespiratory fitness (VO(2,max)) by a maximal cycle exercise test at baseline and after 9 months of follow-up. RESULTS: In all subjects total-, subcutaneous abdominal- and visceral adipose tissue decreased and fitness increased (all p<0.0001) during the intervention. The most pronounced changes were found for liver fat (-31%, p<0.0001). Among the parameters predicting the change in liver fat, fitness at baseline emerged as the strongest factor, independently of total- and visceral adipose tissue as well as exercise intensity (p = 0.005). In the group of subjects with NAFLD at baseline, a resolution of NAFLD was found in 20 individuals. For 1 standard deviation increase in VO(2,max) at baseline the odds ratio for resolution of NAFLD was 2.79 (95% confidence interval, 1.43-6.33). CONCLUSIONS: Cardiorespiratory fitness, independently of total adiposity, body fat distribution and exercise intensity, determines liver fat content in humans, suggesting that fitness and liver fat are causally related to each other. Moreover, measurement of fitness at baseline predicts the effectiveness of a lifestyle intervention in reducing hepatic steatosis in patients with NAFLD.

Cadaver dogs--a study on detection of contaminated carpet squares.

INTRODUCTION: Cadaver dogs are known as valuable forensic tools in crime scene investigations. Scientific research attempting to verify their value is largely lacking, specifically for scents associated with the early postmortem interval. The aim of our investigation was the comparative evaluation of the reliability, accuracy, and specificity of three cadaver dogs belonging to the Hamburg State Police in the detection of scents during the early postmortem interval. MATERIAL AND METHODS: Carpet squares were used as an odor transporting media after they had been contaminated with the scent of two recently deceased bodies (PMI<3h). The contamination occurred for 2 min as well as 10 min without any direct contact between the carpet and the corpse. Comparative searches by the dogs were performed over a time period of 65 days (10 min contamination) and 35 days (2 min contamination). RESULTS: The results of this study indicate that the well-trained cadaver dog is an outstanding tool for crime scene investigation displaying excellent sensitivity (75-100), specificity (91-100), and having a positive predictive value (90-100), negative predictive value (90-100) as well as accuracy (92-100).

[Acute thrombo-embolic elevated ST infarct in a patient with essential thrombocytosis]. / Akuter thrombembolischer ST-Hebungs-Infarkt bei einem Patienten mit essenzieller Thrombozytose.

A 48-year-old man presented with acute chest pain and a greatly increased platelet count. Emergency coronary angiographic revealed thrombotic occlusion of the right coronary artery. Coronary angioplasty and stenting were successfully combined with intracoronary abciximab administration. Due to inadequate postinterventional platelet inhibition an intensified dual antiplatelet therapy with acetylsalicylic acid (ASS) and clopidogrel was applied to prevent stent thrombosis. Due to the thrombo-embolic complication and a platelet count over 1 million/microl a cytoreductive treatment with hydroxyurea was initiated.

[Internally cooled bipolar radiofrequency ablation: is a lower power output more effective?]. / Intern gekühlte bipolare Radiofrequenzablation: Ist eine niedrige Leistung effektiver?

PURPOSE: Evaluation of bipolar radiofrequency (RF) ablation using internally cooled electrodes in an ex-vivo experiment. MATERIALS AND METHODS: Bipolar RF ablations (n = 154) were performed in ex-vivo bovine liver. Both electrodes with a total length of the active tip of 4 cm were located on the same shaft of an internally cooled applicator. The power output was systematically varied between 20 and 100 watts (W). The energy application was continuous or modulated depending on the tissue resistance. In relationship to the maximum power output, the volume of coagulation was assessed. RESULTS: In continuous energy application the induced volume of coagulation was increased at lower power outputs up to 33.7 cm (3) (20 watts). Parallel to an increased volume of coagulation, the required duration of energy application was increased up to a maximum of 51.6 minutes. Modulation of the power output as a function of the tissue resistance enabled application of a wide range of power outputs (40 - 75 watts) leading to a comparable extent of coagulation with a maximum of 14.9 cm (3) (10 min.), 16.8 cm (3) (15 min.), and 19.1 cm (3) (20 min.). CONCLUSION: Continuous application of RF energy leads to an inverse relationship between volume of coagulation and power output. Modulation of the power output as a function of the tissue resistance enables application of a wider range of power outputs compared to continuous application of RF energy.

[Intravascular lymphoma causing acute abdomen]. / Intravaskuäres Lymphom als Ursache für akutes Abdomen.

A 65-year old man presented with acute abdominal pain and fever. The initial diagnosis was small bowel gangrene. Pathology revealed small to large abdominal vessels obliterated by cells of intravascular B-cell-lymphoma (IVL). Visceral IVL involvement is common at autopsy but rarely reported in patients with acute abdomen. The subtype of diffuse large B-cell lymphoma is a rare and aggressive malignancy, which in typical cases is characterized by cephalic or cutaneous manifestation. Few cases showed involvement of large vessels which in combination to fibrin thrombi may lead to infarction of the organ involved. Thus IVL should be considered in cases of ischemic diseases with fever of unknown origin.

[Recurrent transient ischaemic attacks in a patient with pansinusitis]. / Rezidivierende transitorische ischämische Attacken bei einer Patientin mit Pansinusitis.

A 31-year-old woman presented with neurological deficits after an operation for sinusitis. The cranial MRI revealed multiple ischaemic lesions. Laboratory results showed a hypereosinophilia as well as elevated creatine kinase and troponin levels. The ECG implied ST elevations, the left ventricular ejection fraction was highly reduced and the cardiac MRI was suspicious for endomyocarditis. The cardiac biopsy demonstrated the findings of Loeffler's endocarditis. In conclusion the diagnosis of hypereosinophilic syndrome was made and identified as the cause of the neurological deficits.

[Mental neuropathy and pathologic fracture of the mandible as initial symptoms of metastatic prostate carcinoma]. / Sensibilitätsstörung und pathologische Unterkieferfraktur als Erstsymptome bei metastasiertem Prostatakarzinom.

BACKGROUND: Distant metastases of solid tumors account for about 1% of all malign neoplasms. In about 30% of all patients who present with an oral metastasis, the distant primary tumour has not been diagnosed yet. CASE REPORT: We report the case of a 71-year-old man who clinically demonstrated unilateral mental neuropathy as well as pathologic fracture of the mandible. Prostate carcinoma was identified as a primary tumor. Clinically, there was significant hypesthesia of the skin area innervated by the left inferior alveolar nerve. X-ray examination revealed an osteolytic lesion of the ascending ramus of the mandible as well as a pathologic fracture of the mandible. Further imaging showed an extensive neoplasm of the mandible and adjacent soft tissues and significant supraclavicular lymph node enlargement. The diagnosis of metastatic carcinoma of the prostate was histopathologically confirmed. CONCLUSION: Mental neuropathy without a dental focus indicates screening for an osseous metastasis. In cases of left-sided supraclavicular lymph node enlargement in men over 45 years, metastatic prostate carcinoma must be excluded.

[Patients with ornithine transcarbamylase deficiency. Anaesthesiological and intensive care management]. / Der Patient mit Ornithintranscarbamylasemangel. Anästhesiologisches und intensivmedizinisches Management.

Ornithine transcarbamylase deficiency (OTCD) is the most common inborn urea cycle disorder. Patients with OTCD are at risk of acute metabolic decompensation with hyperammonemia and subsequent encephalopathy, coma and death. Symptoms may be triggered by infections, drugs and stress, evoked by trauma, pain, fear, surgery and anaesthesia or by episodes of protein catabolism, i.e. fasting-induced, post partum or during gastrointestinal bleeding. Several specific considerations must be made for anaesthetic and intensive care management in patients with this disease in order to avoid metabolic decompensation. We report the intensive care management of the first manifestation of late-onset OTCD in a 16-year-old girl and a course of inconspicuous general anaesthesia with midazolam, s-ketamine, fentanyl and isoflurane in a 22-year-old girl with known OTCD.

Dual-phase multidetector thin-section CT in detecting duodenal gastrinoma.

Preoperative localization of gastrinomas, especially of extrapancreatic origin, remains a challenge to the radiologist. Most patients with extrapancreatic gastrinomas undergo surgery without preoperative identification of the primary tumor. The appropriate imaging modality to localize gastrinomas is under continuing debate. We report a case of a duodenal gastrinoma with regional lymph node metastases that presented with Zollinger-Ellison syndrome. The small primary tumor was detected noninvasively by dual-phase multidetector thin-section computed tomography with adequate bowel distention and confirmed by endoscopy and histopathologic examination. The case illustrates that appropriate computed tomographic technique and scanning protocol are crucial for success in localizing extrapancreatic gastrinoma.

Complete remission of third recurrence of acute myeloid leukemia after treatment with imatinib (STI-571).

We report the case of a 76-year old patient with third relapse of AML who was successfully treated with Imatinib. The decision to try Imatinib was guided by bright expression of c-kit on the patient's blasts. Treatment was well tolerated but the dose was reduced for pancytopenia and later stopped completely because of pneumonia. The patient recovered with i.v. antibiotics, antimycotics and s.c. G-CSF. Reevaluation of the bone marrow after the end of treatment demonstrated the absence of malignant blasts. Treatment with Imatinib was started again with the intention to prolong remission duration. During the following months peripheral blood counts stabilized in the normal range indicating that a fourth complete remission has been achieved in this patient. This is the first report demonstrating that Imatinib can induce complete remission in relapsed c-kit positive AML in an elderly patient. Prolonged cytopenia remains a considerable problem indicating that normal haematopoiesis is not completely independent of the signalling cascades inhibited by Imatinib. Nevertheless our report supports further study of this drug in c-kit positive AML.

Lymphatic vessels in the colonic mucosa in ulcerative colitis.

In the normal colonic mucosa, lymphatics are found only in a narrow band associated with the muscularis mucosae and are absent from the rest of the mucosa. This study examined whether this arrangement of lymphatics is also valid in ulcerative colitis. Histological sections of colon from 15 long-standing cases were investigated with antibodies against CD 34 (negative for lymphatics; positive for blood vessel endothelium) and, in selected cases, podoplanin (positive for lymphatic endothelium; negative for blood vessel endothelium). Whereas inflammation of the mucosa was not associated with changes in lymphatics, an increase in intramucosal lymphatics was seen when the pathological changes included widening of the muscularis mucosae or penetration of the mucosa by muscle fibers, filiform changes in the mucosa, and hyperplasia of the mucosa-associated lymphoid tissue (MALT). In specimens with epithelial dysplasia, an association between the dysplastic epithelium and ectatic and quantitatively increased lymphatics was observed. With superimposed carcinoma, no relationship between the malignant tumor and lymphatics was identifiable. Nevertheless, pre-existing lymphatics in the muscularis mucosae were involved in lymphatic tumor spread. The immunohistochemical findings demonstrated that lymphatics occurred in all areas of the mucosa in ulcerative colitis (or, in effect, at sites which were not normally found under physiological conditions) and in regions that favored lymphatic tumor dissemination. Whether these lymphatics were actually involved in metastasis remains to be defined.

Extranodal marginal zone B cell lymphoma of MALT type involving the mucosa of both the urinary bladder and stomach.

Primary lymphoma of the urinary bladder is a very rare tumour. A bladder tumour was found in a 57 year old man with obstructive dysuria. It was found by histological and immunohistohistochemical investigation to be an extranodal marginal zone B cell lymphoma. Lymphoepithelial lesions were absent, but were found in a clinically silent gastric lymphoma discovered four weeks later during staging investigations; this gastric lymphoma was negative for Helicobacter pylori by breath test and molecular biological analysis. Sequencing of the clonal immunoglobulin heavy chain gene in both tumours indicated the same precursor cell, of follicular or post follicular origin. In synopsis, the data suggested that this was a case of primary lymphoma of the bladder with involvement of the stomach. The application of a chromosome 3 specific alpha satellite probe revealed trisomy 3. A tumour with these characteristics arising as a lymphoma of the bladder with a metachronous involvement of the gastric mucosa has not been described previously.

[Cystic neck lymph node metastases as an indication of occult tonsillar carcinoma]. / Zystische Halslymphknotenmetastasen als Hinweis auf ein okkultes Tonsillenkarzinom.

BACKGROUND: Cystic carcinomas of the neck without evidence of a primary tumor are diagnostically challenging lesions. Differentiation between a cystic lymph node metastasis of an occult primary tumor and a carcinoma arising in a branchiogenic cyst is frequently not possible even with histological examination. In order to clarify the diagnosis, an intensive search for a primary lesion in the upper aerodigestive tract must be carried out. DIAGNOSIS: An occult carcinoma might be situated in Waldeyer's ring, especially in the tonsillar crypts. These tumors tend to produce cystic metastases in the jugulodigastric region. Therefore, multiple biopsies have to be taken from the tissue of Waldeyer's ring. In the case of a positive histological result, adequate therapy of both the primary and the metastasis can be carried out. The diagnosis of a malignant branchiogenic cyst is only permissible after a primary lesion has been thoroughly excluded.

Intralesional rituximab for cutaneous B-cell lymphoma.

Rituximab, a chimeric anti-CD20 monoclonal antibody, has been approved for systemic treatment of relapsed or refractory CD20-positive B-cell non-Hodgkin's lymphoma. As cutaneous B-cell lymphoma (CBCL) also expresses the CD20 molecule, three patients with histologically and immunohistochemically confirmed CBCL without systemic involvement were treated with low-dose intralesional rituximab in a pilot study. Single doses applied ranged from 10 to 30 mg per lesion, according to lesion extent, with a cumulative dose of up to 350 mg. Injections were given two or three times weekly for 3-5 weeks, with a second cycle after 6 weeks in one patient with incomplete remission. Complete and lasting remission was achieved in each patient; this has persisted for up to more than 1 year. The observed adverse events were of grade 1 severity. Results suggest that intralesional rituximab may be a safe and effective new therapy modality for CBCL.

Acute lymphoblastic leukaemia: correlation between morphological/immunohistochemical and molecular biological findings in bone marrow biopsy specimens.

BACKGROUND: Although numerous antibodies suitable for use on paraffin wax embedded sections are available for the subtyping of acute leukaemia (acute myelogenous leukaemia (AML) and acute lymphoblastic leukaemia (ALL)) in bone marrow biopsy sections, unequivocal identification of the cell line involved is sometimes impossible. METHODS: Forty eight formalin fixed, paraffin wax embedded bone marrow biopsy specimens that had been decalcified in EDTA were investigated, including 42 thought to exhibit ALL on the basis of bone marrow smears. Five specimens exhibited AML and one biphenotypic leukaemia, as diagnosed immunohistochemically in bone marrow biopsies. Immunostaining was performed with antibodies against relatively specific B and T cell antigens. The blasts were investigated for rearrangements of the immunoglobulin heavy chain (IgH) and the T cell antigen receptor (TCR) genes. RESULTS: Amplifiable DNA was obtained from all 48 specimens. An IgH gene rearrangement was detected in 20 of 23 c-ALL specimens. Four of seven T cell ALL (T-ALL) specimens had a TCR-gamma gene rearrangement, and the one B cell ALL (B-ALL) specimen exhibited a clonal IgH gene. Three of four cases of unclassifiable ALL could be assigned to the B cell lineage on the basis of gene rearrangement analysis. Seven cases originally diagnosed in smears as ALL were rediagnosed as AML (n = 5) or biphenotypic leukaemia (n = 2) because of immunohistochemical reactivity for myeloperoxidase or lysozyme. Two of these AML cases and two of three cases of biphenotypic leukaemia exhibited a monoclonal IgH gene rearrangement. CONCLUSIONS: Acute leukaemia can be subtyped in bone marrow sections with a limited panel of antibodies suitable for use on paraffin wax embedded sections (against CD3, CD10, CD20, CD79a, myeloperoxidase, and lysozyme). In patients with ALL and a diagnostically equivocal immunophenotype, gene rearrangement analysis might indicate whether the B or T cell lineage is involved.

[Polytopic manifestations of paragangliomas. Diagnosis, differential diagnosis and indications for therapy]. / Polytopes Auftreten von Paragangliomen. Diagnostik, Differentialdiagnostik und Therapieindikationen.

Paragangliomas of the glomus caroticum are relatively rare, but highly vascularized neoplasmas, which develop from chemoreceptors. They can be develop at any age, but most often in the third or fourth decade of life. Paragangliomas grow very slowly and are most always of benign origin. There is a familial predisposition, and an autosomal-dominant transmission is presumed. They are commonly located in the jugular region; in rare cases a polytopic manifestation is found. We describe the case of a 47-year-old male patient who was referred to our department because of a progressive swelling of the neck on both sides. Contrast-enhanced computed tomography had displayed soft tissue tumors in the jugular regions. We performed an operative exploration, which showed a highly vascularized tumor. Histopathologic analysis revealed the diagnosis of a paraganglioma. An angiography of the neck and thoracic region, furthermore, revealed an additional paraganglioma in the anterior mediastinum. Using a surgical approach via lateral cervicotomies and thoracotomy the paragangliomas were extirpated. Our case report demonstrates the rare polytopic manifestation of paragangliomas. This perivascular neoplasms have to be removed before haemodynamic complications develop. The extent of this tumors is clearly illustrated by use of an angiography. Because of the familial predisposition, clinical and radiological examinations of relatives are mandatory.

Reactive and neoplastic lymphocytes in human bone marrow: morphological, immunohistological, and molecular biological investigations on biopsy specimens.

BACKGROUND: Slight, diffuse or focal lymphocyte proliferation is relatively common in bone marrow biopsy specimens. It may be impossible to determine whether this represents a reactive lymphocytosis or low grade non-Hodgkin lymphoma (NHL) on the basis of routine investigations alone. AIM: To investigate the supplementary use of molecular biological techniques in this situation. METHODS: 529 formalin fixed, paraffin embedded bone marrow biopsy specimens from the iliac crest were subjected to histological and immunohistochemical staining to determine the number and nature of the lymphocytes present. The cases were divided into three groups according to the lymphocyte count: normal (< 10% of nucleated bone marrow cells), slightly increased (10-30%), and markedly increased (> 30%). All of the last group could be diagnosed as NHL from the morphological findings alone. The clonality of rearrangements of the IgH and TCR gamma genes was investigated by polymerase chain reaction (PCR). RESULTS: Monoclonality was observed in 7.5% of the 372 cases with a normal lymphocyte count, in 50% of the cases with a modest increase in lymphocyte numbers (suggesting a diagnosis of low grade NHL not detected by immunostaining), and in 77% of the cases with markedly increased lymphocyte numbers. CONCLUSIONS: If PCR is used in addition to the immunohistochemical investigation of bone marrow biopsies, considerably more cases of NHL can be identified, making this of particular use in staging and detection of recurrences.

Intracranial inflammatory tumors: a survey of their various etiologies by presentation of 5 cases.

Due to similar clinical and neuroradiological features, intracranial inflammatory tumors (IITs) are frequently misdiagnosed as brain neoplasms, from which they notably differ in respect to therapy and prognosis. In this article, five cases of such tumors are presented. Three of the patients with brain tumors (cases 3, 4 and 5) presented a history of 'pararheumatic' syndromes but no diagnosis of defined immunopathies. On the basis of radiological findings, all processes were classified as genuine brain neoplasms, but histology showed reactive inflammatory features. The possible etiologies of these 'tumors' are discussed on the basis of all clinical and histological data of the patients. The spectrum of diseases potentially leading to the manifestation of an IIT is reviewed. Additionally, the presentation of case 5, who developed a highly malignant B-cell-lymphoma 6 months after the removal of an IIT without any histological signs of atypia, shows that this differential diagnosis always has to be kept in mind.