T2 mapping cardiovascular magnetic resonance identifies the presence of myocardial inflammation in patients with dilated cardiomyopathy as compared to endomyocardial biopsy.

Aims: The aim of this study was to determine the value of T2 mapping for the non-invasive assessment of myocardial inflammation in different stages of systolic left ventricular dysfunction in dilated cardiomyopathy (DCM) in comparison with endomyocardial biopsy (EMB). Methods and results: A total of 132 subjects were enrolled between 2013 and 2016 (62 controls and 70 patients with DCM). All patients underwent CMR at 1.5 T and received coronary angiogram and EMB. CMR applied standard protocols including T2 mapping with Gradient And SpinEcho sequence (GRASE). Global T2 relaxation time was significantly increased in patients with DCM compared to the healthy controls (T2 time DCM vs. controls: 65.9 ± 6.2 vs. 60.0 ± 4.2 ms; P < 0.001). Of note, patients with the presence of inflammatory cells in EMB exhibited further elevation of T2 values (T2 time in patients with the presence of inflammatory cells vs. T2 time in patients without: 68.8 ± 5.8 vs. 64.7 ± 5.9 ms; P = 0.02). Receiver operating characteristic analysis of our data deciphered a global myocardial T2 time >65.3 ms as the best cut-off for distinction between the healthy controls and patients with myocardial inflammation [sensitivity 93%, specificity 90%, P < 0.01, area under the curve (AUC) 0.95]. In patients with DCM, this threshold identified patients with biopsy-proven inflammation with a sensitivity of 79% and specificity 58% (AUC 0.72). Conclusion: In patients with DCM and presence of inflammatory cells in the myocardium, myocardial T2 relaxation times may help to non-invasively detect myocardial inflammation. Although there is an overlap of T2 values between patients and healthy controls, T2 mapping may facilitate the identification of patients who may benefit from EMB for therapeutic decision-making.

Prognostic impact of blast cell counts in dysplastic bone marrow disorders (MDS and CMML I) with concomitant fibrosis.

In a retrospective study, 43 patients with dysplastic neoplasms of the bone marrow (myelodysplastic syndromes and myelodysplastic/myeloproliferative-overlap neoplasms) associated with marked (grades 2-3) fibrosis were examined. Histopathologic and morphologic findings as well as cytogenetic and molecular results were correlated with clinical endpoints. Multilineage dysplasia (34 of 43 patients, 79 %) and hypercellular bone marrow (64 %) were found in most patients. In ten of 35 patients, poor risk karyotypes according to the International Prognostic Scoring System (IPSS) were recorded. The JAK2 V617F mutation was detected in four of 30 patients (13 %), and the KIT D816V mutation was found in two of 30 patients (6 %). Patients were mainly treated with palliative drugs and best supportive care. After an observation time of 1-41 (median 21) months, ten of 43 patients (23 %) had developed a secondary acute leukemia. The median survival of all 43 patients was 21.4 months (range 1.8-88.2 months). Of all prognostic parameters examined, the blast cell count at diagnosis was found to be a most reliable and most predictive marker concerning survival and leukemia progression. This confirms previous studies in dysplastic bone marrow neoplasms without fibrosis.

[Development of neointimal matrix after incorporation of modern alloplastic prostheses: comparison between ePTFE and Dacron]. / Entwicklung neointimaler Matrix nach Einheilen moderner Prothesen: Vergleich zwischen ePTFE und Dacron.

BACKGROUND: In the therapy for peripheral arterial occlusive disease there remain inadequacies in the use of alloplastic material concerning thrombogenicity and biological compliance. In the 1960s, Sparks tried to combine the advantages of alloplastic prostheses with those of autologous reconstructions by using incorporated prostheses. No extensive myointimal hyperplasia was noted, but besides infections aneurysmatic dilatation were limiting factors in clinical practice. MATERIAL AND METHODS: The incorporation of modern alloplastic prostheses without connection to circulation concerning the thickness of neointima as well as the percentage of smooth muscle cells was examined in a dog model. RESULTS: The thickness of the neointima increased significantly in Dacron grafts with a peak on day 70 (p = 0.022), additionally a significantly greater percentage of smooth muscle cells was noted in Dacron grafts after 44 and 58 days (p = 0.008, p = 0.036). CONCLUSION: Due to the decreased thickness of the incorporating matrix as well as the lower percentage of smooth muscle cells, PTFE grafts should be preferred for peripheral arterial revascularisation.

[Dignity of carotid body tumors. Review of the literature and clinical experiences]. / Dignität von Glomus-caroticum-Tumoren. Literaturübersicht und klinische Erfahrungen.

INTRODUCTION: Tumors of the carotid body are rare paragangliomas (incidence 0.012%) originating from sympathetic fibres of the carotid bifurcation. Growth is slow and they frequently become symptomatic through local mechanical compression of neighboring vascular and neural structures. The aim of this study is to present the diagnosis, therapy and course in patients with a carotid body tumor treated at our department of the Düsseldorf University Hospital and to discuss rates of recurrence and also dignity during the long-term follow-up. PATIENTS AND METHODS: Included in this retrospective study were all patients treated for a carotid body tumor between January 1988 and June 2008. At follow-up examination the current history was recorded and a physical examination, sonography and duplex sonography were carried out. Furthermore each patient completed the questionnaires QLQ-C30 of the European Organisation for Research and Treatment of Cancer (EORTC) and the module for head and neck QLQ-H&N35 to assess quality of life. RESULTS: In our collective of 36 patients consisting of 13 men (36%) and 23 women (64%) with an average age of 48.33 years (range 17-78 years), 16 patients presented with a local neck swelling and 5 patients each had difficulties swallowing or hoarseness, respectively. Preoperatively Horner's syndrome was found in one patient. A total of 22 tumors were found on the right side of the neck (52.38%), 20 were found on the left side (47.62%) and 6 patients showed a bilateral carotid body tumor (16.67%), 3 of which were bilaterally excised. The other 3 patients are still under surveillance without surgery. Altogether surgery of 39 carotid body tumors was performed in 36 patients. In all 39 cases (primary surgery n=34, recurrence surgery n=5) the tumors were macroscopically excised in toto. Parts of the vagus nerve had to be resected in 3 patients (7.69% Shamblin type II n=1, Shamblin type III n=1) and resection of blood vessels was necessary during 10 operations. The survival rate after 1 year was 100%, after 2 years 96.3% and after 5 years 92.6%. A local recurrence was diagnosed in 2 patients (5.13%). In one patient a second operation was necessary and in the other patient there was a non-progressive swelling in the carotid bifurcation which had existed for 14 years and which was conservatively left untreated. Peripheral neural lesions could be found in 12% (3/25) at long-term follow-up. None of the patients showed evidence of local or remote metastasization of a carotid body tumor. CONCLUSIONS: Surgical extirpation of carotid body tumors can be regarded as the only curative option with an overall mortality of 0%. Morbidity is low when applying vascular surgical techniques (2.56% for central lesions). The incidence of peripheral nervous lesions is high reflecting the radicality of the resection (64.10%) but is outweighed by the benefits. In the long-term follow-up the rate of permanent peripheral neural lesions decreased to 12%. Due to a potentially infiltrating and disseminating growth, carotid body tumors should be regarded as semi-malignant and should therefore be indicated for surgery at the time of diagnosis. Whether the incidence of carotid body tumors will rise due to increased routine diagnostic examination of the head and neck region using sonography and tomography remains to be seen.

Sorafenib (Nexavar) induces molecular remission and regression of extramedullary disease in a patient with FLT3-ITD+ acute myeloid leukemia.

The fms-related tyrosine kinase 3 internal tandem duplication (FLT3-ITD) can be found in about one quarter of patients with acute myeloid leukemia (AML) [Small D. FLT3 mutations: biology and treatment. Hematology Am Soc Hematology. Educ. Program 2006;178-84 [Review]]. Patients who carry this mutation have a high risk of relapse even after allogeneic stem cell transplantation [Sheikhha MH, Awan A, Tobal K, Liu Yin JA. Prognostic significance of FLT3 ITD and D835 mutations in AML patients. Hematol J 2003;4:41-6; Meshinchi S, Arceci RJ, Sanders JE, Smith FO, Woods WB, Radich JP, et al. Role of allogeneic stem cell transplantation in FLT3/ITD-positive AML. Blood 2006;108(1):400-1]. Recent reports show that Sorafenib, a multikinase inhibitor has significant activity against FLT3-ITD(+) blasts in vitro [Auclair D, Miller D, Yatsula V, Pickett W, Carter C, Chang Y, et al. Antitumor activity of sorafenib in FLT3-driven leukemic cells. Leukemia 2007;21(3):439-45]. We here report the first clinical case of molecular remission induced by Sorafenib in a patient with FLT3-ITD(+) AML and extramedullary disease after allogenic stem cell transplantation.

Polymorphism of the bovine POU1F1 gene: allele frequencies and effects on milk production in three Iranian native breeds and Holstein cattle of Iran.

The aim of this study was to estimate the allele frequencies in polymorphic site of exon six of POU1F1 gene in three Iranian native and Holstein cattle. Genomic DNA was extracted from 3 Iranian native cattle breeds, including 97 Mazandarani, 87 Sarabi, 112 Golpaygani and also 110 Holstein cattle. A 451 bp fragment of intron 5 and exon 6 were amplified and digested with HinfI restriction enzyme. Frequencies of allele A were 0.37, 0.27, 0.34 and 0.21 for Mazandarani, Sarabi, Golpaygani and Holstein cattle, respectively. Significant differences in genotype frequencies were found between Mazandarani or Golpaygani and Holstein cattle. No significant differences in genotype frequencies were found between Sarabi and Holstein cattle. Transition A to G in nucleotide 1256 is responsible for HinfI(-) allele. No significant association was observed between POU1F1 polymorphism and milk production. Differences in allelic frequency between native Bos indicus breeds (Mazandarani, Golpaygani) and Holstein at the present study might be due to differences in origin breeds, low number of samples and/or as the effect of natural selection in native breeds.

Multifocal epithelioid hemangioendothelioma: case report of a clinical chamaeleon.

Epithelioid hemangioendothelioma is an extremely rare vascular bone tumor with a slow growth and poor prognosis. The term was designed to describe neoplasms that had an appearance in between hemangiomas and sarcomas. Various synonyms for epithelioid hemangioendothelioma are used clinically: low grade anaplastic angiosarcoma, cellular hemangioma, histiocytoid hemangioma and angioendothelioma. However, it represents 1% of all vascular neoplasms and is locally aggressive. We report the course of disease of a 47-year-old man who presented to our clinic with unspecific abdominal and back pain. Radiological findings revealed multiple lesions in the spine as well as liver and spleen involvement. Tumor histology of the bone and liver biopsies confirmed the diagnosis of epithelioid hemangioendothelioma. Although treatment was initiated with thalidomide, the patient developed multiple organ dysfunction syndrome (MODS) and succumbed to his disease. This case report may contribute to the data on clinical findings and natural history of this rare tumor.

[Bilateral large conjunctival tumours as primary manifestation of sarcoidosis--successful treatment with steroid-depot-injections]. / Beidseitige ausgeprägte konjunktivale Tumoren als Primärmanifestation einer Sarkoidose -- erfolgreiche Therapie mit Steroid-Depot-Injektionen.

INTRODUCTION: Ocular manifestations of sarcoidosis vary enormously. They include the conjunctiva, lacrimal gland, orbita, intraocular structures and eye-lid, either isolated or combined. We describe a female patient who presented with unusually large, bilateral conjunctival tumours as a primary manifestation of sarcoidosis. PATIENT: A 79-year-old white woman was referred to us for further management of a persisting "conjunctivitis", which had been refractory to treatment with multiple medications. Initial examination disclosed swollen eye-lids and bilateral large hard tumours of the inferior fornix. The obtained brush smear, which was cytopathologically evaluated, revealed epitheloid cells and multinucleate giant cells. After 4 weeks she developed three reddish-brown maculopapular lesions on her face. The subsequent biopsy from the left inferior fornix and the skin showed histopathologically a granulomatous epitheloid cell inflammation without central necrosis and without acid-proof bacilli. Therefore a sarcoidosis was included into the differential diagnosis. The systemic evaluation revealed no other manifestation. At first we tried to reduce the chronically inflammatory tumours with different immunomodulating local treatment forms. Only the repeated intralesional injection of a steroid depot showed a complete disappearance of all conjunctival and skin tumours. CONCLUSION: An isolated bilateral primary manifestation of sarcoidosis with large massive conjunctival tumours is very rare and clinically not typical. The non-invasive, cytopathological examination by means of brush smears offers a new perspective in the fast diagnosis of conjunctival manifestation of sarcoidosis. The tumours respond excellently to the intralesional injection of steroid depots.

Analysis of properdin (BF) genotypes associated with litter size in a commercial pig cross population.

Properdin (BF) was investigated as a candidate gene influencing litter size in a commercial pig cross population. The BF gene was chosen because of its integral role in influencing uterine epithelium growth and because several quantitative trait loci (QTL) with impact on reproductive traits have been detected near the centromere of porcine chromosome 7. A total of 123 F2 (Large White x Landrace) x Leicoma sows were genotyped using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. The sows were divided into two extreme performance groups, one with a high litter size (n = 61, > or = 14.3 piglets per litter) and the other with a low litter size (n = 62, < or = 11.3 piglets per litter). Although genotype and allele frequencies were uneven with 2.4% (AA), 16.3% (AB), 81.3% (BB) and 0.11 (A): 0.89 (B), the allele A was the unfavourable one, leading to less offspring. With regard to the level of significance at p < 0.05, the total number of born (TNB) and number of born alive (NBA) piglets were associated with BF genotypes. The genotype AA led to 10.55 TNB and 10.00 NBA, whereas the genotype BB led to 13.19 TNB and 12.11 NBA. The genotype AB was intermediate. In future, a systematic mating test is necessary in order to obtain more balanced genotype frequencies. Furthermore, it should be taken into consideration that the investigated polymorphism is located in an intronic region and the causative mutation is not clear yet.

Disseminated microvascular pulmonary tumor cell embolism: a rare cause of fulminant pulmonary hypertension.

BACKGROUND: Disseminated pulmonary tumor embolization is a rare cause of pulmonary hypertension and is often diagnosed only after the patient has died. CASE REPORT: We report on a 41-year-old male who was admitted because of severe dyspnea and tachycardia. Contrast enhanced spiral computed tomography did neither establish pulmonary thromboembolism nor pulmonary metastasis. Right heart catheterization revealed severe pulmonary hypertension (pulmonary vascular resistance (PVR) 678 dyn x sec x cm(-5)). PVR did not respond to therapy with intravenous nitrate or inhaled iloprost in this critically ill patient. 2 days after admission, the patient died because of refractory right heart failure. Autopsy revealed microscopic pulmonary tumor embolism due to a metastasizing adenocarcinoma of the pancreas. CONCLUSION: Disseminated tumor cell embolism should be considered as a rare differential diagnosis in patients with refractory pulmonary hypertension.

[Mycotic visceral artery aneurysm: clinical picture, diagnosis, differential therapy, and discussion of the literature]. / Das mykotische Viszeralarterienaneurysma. Klinik, Diagnostik und Differenzialtherapie mit Darstellung der Literatur.

Bacterially infected arterial aneurysms were named mycotic aneurysms by William Osler in 1885 due to their morphology. This rare vascular disease is mainly localized in the femoral artery but also occurs in the aorta and visceral arteries. After the first surgically treated mycotic visceral aneurysm in 1949, we found 36 casuistics in the literature. We report on two patients treated in our department with mycotic visceral aneurysms and discuss the literature concerning topography, differential diagnosis, and surgical management.

[Homologous vein transplantation in cruropedal arterial reconstruction]. / Die homologe Venentransplantation zur kruropedalen arteriellen Rekonstruktion.

Allogenic venous transplantation represents an alternative procedure for preventing leg amputation. This study reviewed the question of whether immunologic monitoring and immunosuppressive therapy provide results close to those of autologous reconstructions. Twenty-eight patients received 31 homologous venous transplants. The average age in this group of 15 women and 13 men was 64.5 years. Limbs in danger of amputation could be kept longer in two thirds of them. These promising results show the superiority of this method over the use of alloplastic material in regions with cruropedal vessels. Therefore, it can be recommended in acute leg ischemia with lack of autologous vascularity. Improving guidelines for indication will be an interesting research field, and more contributions are needed.

Chemotherapeutic potential of plant alkaloids and multidrug resistance mechanisms in malignant fibrous histiocytoma of the heart.

Primary malignant fibrous histiocytoma (MFH) of the heart is a rare and highly malignant soft tissue tumor, which is largely resistant to conventional chemotherapy and radiotherapy. Therefore, we analyzed growth inhibitory effects of different chemotherapeutic agents and mechanisms of drug resistance in the recently established cell line MFH-H derived from a human primary cardiac MFH. The growth inhibitory effects of etoposide, vincristine, and paclitaxel were tested using the MTT assay. The expression and function of multidrug resistance-related proteins, i.e. the P-glycoprotein, the multidrug resistance-associated protein (MRP) and the lung resistance-related protein (LRP) were determined by FACScan and functional assays of cellular drug efflux. The concentration required for a 50% inhibition of growth (IC50) was 0.001 microM for etoposide and 0.035 microM for vincristine. Paclitaxel dissolved in Cremophor EL/ethanol inhibited the cell growth of MFH-H cells more intensively (IC50: 0.27 microM) than paclitaxel dissolved in DMSO (IC50: 11.09 microM) suggesting that Cremophor EL is contributing to the inhibitory effects of paclitaxel. The response of MFH-H to etoposide, vincristine and paclitaxel/Taxol could not be predicted by the expression and function of P-glycoprotein, MRP and LRP. This study demonstrates that etoposide and to a lesser extent vincristine can effectively inhibit the growth of MFH-H cells, irrespective of the multidrug resistance phenotype. MFH-H cells are relatively insensitive to paclitaxel dissolved in DMSO, in contrast to paclitaxel dissolved in Cremophor EL/ethanol indicating that the diluent Cremophor contributes to the antiproliferative effects of the taxane paclitaxel.

Postarthroplasty histiocytic lymphadenopathy in a patient with uterine carcinoma.

INTRODUCTION: Postarthroplasty histiocytic lymphadenopathy is a benign reactive sinus histiocytosis. CASE REPORT: We report on the case of a 68-year-old woman presenting with pelvic postarthroplasty histiocytic lymphadenopathy after hysterectomy because of uterine carcinoma. CONCLUSION: This unusual form of histiocytic lymphadenopathy should be included in the differential diagnosis of gynecologic oncology patients who have had joint replacements to avoid misdiagnosis of a neoplasm.

Fabry disease in patients with hypertrophic cardiomyopathy (HCM).

Fabry disease is an X-linked recessive lysosomal storage disorder with variable phenotype characterized by the accumulation of glycosphingolipid in various tissues. Unlike patients with the classical systemic Fabry disease entity, who present with multiple organ involvement, patients with a cardiac variant of Fabry disease are characterized mainly by myocardial hypertrophy. Therefore, the cardiac variant of Fabry disease may be defined as a cardiomyocytic storage disorder, thus, mimicking the clinical features of hypertrophic obstructive and especially non-obstructive cardiomyopathy. In patients with unexplained left ventricular hypertrophy the diagnosis of a cardiac variant of Fabry disease is performed by light- and electron microscopic evaluation of endomyocardial catheter biopsy specimens and/or serologic investigations (decreased activity of alpha-galactosidase A in plasma or leucocytes). Several studies show that between 4% and 8% of unselected patients with the clinical features of hypertrophic non-obstructive cardiomyopathy have a cardiac variant of Fabry disease. In each patient with unexplained myocardial hypertrophy concealed myocardial storage disease, especially cardiac Fabry disease has to be considered and should be ruled out or confirmed by endomyocardial catheter biopsy. This is important because of the recently reported alpha-galactosidase A enzyme replacement therapy in Fabry disease. Randomized, multicenter studies are mandatory to test the hypothesis that enzyme replacement therapy leads to a beneficial clinical effect in the cardiac variant form of Fabry disease and may prevent the progression of the disease in asymptomatic patients.

Secretion of GM-CSF and M-CSF by human renal cell carcinomas of different histologic types.

OBJECTIVES: To analyze the secretion of hematopoietic growth factors and the expression of their corresponding receptors in 40 newly established renal cell carcinoma (RCC) cell lines of different histologic types. Little is known about the secretion and function of hematopoietic growth factors by human RCCs. METHODS: The expression of the hematopoietic growth factors (ie, erythropoietin, interleukin [IL]-3, IL-5, granulocyte colony-stimulating factor [G-CSF], granulocyte-macrophage colony-stimulating factor [GM-CSF], and macrophage colony-stimulating factor [M-CSF]) was determined by enzyme-linked immunosorbent assay analysis under different culture conditions, including suspension culture and monolayer cultures (plastic and Matrigel-coated culture flasks). The expression of their corresponding receptors was defined by fluorescence activated cell scanner analysis and by reverse-transcriptase polymerase chain reaction. The response of the RCC cell lines to exogenous hematopoietic growth factors was analyzed by MTT assay. RESULTS: In almost all of the cell lines, significant amounts of GM-CSF and M-CSF were secreted, and in four cell lines, a secretion of G-CSF was detected. Fourteen RCC cell lines showed secretion of IL-3, and production of IL-5 and erythropoietin was not observed in any cell line. Secretion of GM-CSF and M-CSF was affected by the substratum offered for cell attachment in the adherent cultures. GM-CSF secretion was more pronounced under culture conditions with a reduced frequency of cell-to-cell contacts. Two cell lines were shown to express receptors for M-CSF, but receptors for G-CSF and GM-CSF could not be detected in any cell line. Exposure to exogenous G-CSF, GM-CSF, and M-CSF did not affect the proliferation of our RCC cell lines. CONCLUSIONS: The results of our study clearly demonstrate that human RCC cells can secrete significant amounts of G-CSF, GM-CSF, M-CSF, and IL-3, and are thereby theoretically able to modulate the host's tumor-directed immune response.

[Circular hemorrhagic subendocardial necrosis after heart arrest and resuscitation]. / Zirkuläre hämorrhagische Innenschichtnekrose nach Herzstillstand und Reanimation.

A 19 year old boy, previously healthy suffered a cardiac arrest by getting up. Ten minutes afterwards the general practitioner commenced cardiopulmonary resuscitation, 15 minutes later ventricular fibrillation developed and the emergency physician carried out intubation and repeated defibrillation. During the next few hours a stabilization of the circulatory system was achieved. Five days after the cardiac arrest brain death occurred. The postmortem findings on the heart (only a heart section was performed) showed extensive circular hemorrhagic subendocardial necrosis with initial organization of the left ventricular wall and the septum with a well-preserved subendocardial area. In the right ventricular wall only a few small areas of organization were observed. All lesions were consistent with the cardiac arrest suffered 5 days previously. The morphological changes differ from those of a usual hemorrhagic infarction and of the sequences of a cardiopulmonary resuscitation. The circular subendocardial necroses occur after a cardiac arrest which exceeds the resuscitation time of the heart. They do not respect the area of coronary distribution and their hemorrhagic component develops after successful reanimation within the necrotic myocardium.