Complex chromosomal rearrangements in a secondary acute myeloblastic leukemia after chemotherapy in TRAPS

We report on the cytogenetic findings from a patient with a de novo TNF-receptor-associated periodic syndrome (TRAPS), who showed first symptoms at the age of four months. Thus, he obtained a long-term therapy with cortisone, chlorambucile, methotrexate and cyclophosphamide. At the age of 14 he developed a secondary acute myeloblastic leukemia. Highly complex chromosomal rearrangements were detected after banding analysis. The exact definition of karyotype and the involved breakpoints could only be resolved after application of sophisticated multicolor-FISH techniques: 44,XY,-5,der(6)t(6;7)(6pter right curved arrow 6q12::7p22.2 right curved arrow 7pter or 7pter right curved arrow 7p22.2), dic(7;19)t(6;19;6;7;19;7;19)(19qter right curved arrow 19q12::7p13 right curved arrow 7p11.1::19q12 right curved arrow 19p12 or 19p12 right curved arrow 19q12::7p11.1 right curved arrow 7q21.3::6q12 right curved arrow 6q26::19p13.3 right curved arrow 19p12::6q26-6qter),dic(12;13)(13qter right curved arrow 13p11.2::12p13.1 right curved arrow 12qter),ace(12;13)(13pter right curved arrow 13p11.2::12p13.1 right curved arrow 12pter), -19. The simultaneous presence of two dicentric chromosomes has not been reported previously and is striking, as such chromosomes are suggested to be instable. However, such chromosomes are observed frequently after chemo- or radiotherapy and in secondary, i.e. therapy related AML (tAML). Thus, AML in this case may result from a long-term therapy of TRAPS with methotrexate, cyclophosphamide, chlorambucile and cortisone.     

Gingko biloba (Rökan) therapy in tinnitus patients and measurable interactions between tinnitus and vestibular disturbances

Tinnitus is one of the most important symptoms in neurootology after vertigo, nausea, and hearing loss. In most cases, the origin of the tinnitus remains inexplicable. Well-known, however, is that tinnitus may arise in any part of the hearing pathway (i.e., both within the cochlea receptor and in the temporal lobe and projections). Tinnitus also is associated frequently with vertigo, nausea and hearing loss. An age predominance exists, with tinnitus more common among those older than 40 years. From this starting point, a great demand exists today for new ideas and developments in the diagnosis and treatment of tinnitus.     

Comparison of 18FDG-PET with CT scans in the evaluation of patients with residual and recurrent Hodgkin's lymphoma

The reliable assessment of residual masses after treatment as well as of new lesions suspected for relapse remains a diagnostic problem in patients with Hodgkin's disease (HD). The current study compares the results obtained by CT scan to FDG-PET imaging in a blind analysis with respect to the viability of residual masses and in case of suspected relapse. Between 1/94 and 10/99, 47 comparisons of PET and corresponding CT scans - 26 comparisons in 24 patients with residual tumors and 21 comparisons in 20 patients with suspected relapse of HD - were evaluated by independent reviewers blinded to he results of each other. Patients with primary diagnosis had been treated within trials of the German HD Trial study group. Relapsed patients received intensified salvage chemotherapy regimens. PET was assessed visually and by quantifying glucose uptake (SUV). Changes in size of tumor lesions as well as contrast medium enhancement served as criteria for assessment by CT scans. Results were validated either by histologic examination of a resected mass or biopsy (n=17) or by a clinical follow-up over 6 months following treatment (n=30). In 26 cases with residual lesions FDG-PET showed an increased tracer uptake in 8, 7 of which were true positive (TP) and 1 false positive (FP). Eighteen cases were classified as being negative (no viable HD), 17 true negative (TN) and 1 FN. In the blinded reading of the corresponding CT scans, 10 cases with residual lesions were considered to contain vital lymphoma (2 TP, 8 FP). Sixteen CT scans were classified as negative (10 TP, 6 FN). The resulting sensitivity and specificity of PET were 87.5% and 94.4% in contrast to only 25% and 56% for CT scans. The positive and negative predictive values of PET and CT scans were 87.5% and 94.4% and 20% and 62.5%, respectively. In patients with suspected relapse, sensitivity and positive predictive value for the diagnosis of the relapse were 100% and 86%, respectively, yielding the same results for both methods. FDG-PET performed in HD patients with residual masses appears to offer important additional information regarding the presence of viable HD in these residual lesions. In patients with suspected relapse of HD, FDG-PET seems not to offer any information over CT scans. Using SUVs is not superior to visual assessment of PET alone.     

Rhenium-188 for inhibition of human aortic smooth muscle cell proliferation

PURPOSE: To evaluate dose-dependent growth-modulating effects of the beta-gamma emitter Rhenium-188 on cultured human aortic smooth muscle cells (haSMC). METHODS AND MATERIALS: HaSMC were plated in 25 cm(2) flasks. Two days after plating, cells were incubated with the Re-188 (beta E(max) 2.12 MeV, tissue range(max) < 10 mm, T(1/2) 17 h) for five days. The doses administered were 0.2 Gy, 1, 4, 6, 8, 16, and 32 Gy. After five days, the radionuclide was removed. Cell growth, cell cycle distribution, and clonogenic activity were analyzed for the following 25 days. RESULTS: The 0.2 and 1 Gy groups did not show relevant growth-inhibiting effects compared to the control groups. The 4 to 32 Gy groups presented dose-dependent growth inhibition, with a complete growth arrest of the 16 and 32 Gy groups. Clonogenic activity of the smooth muscle cell was strongly inhibited from doses > or =8 Gy. Flow cytometry showed a lasting dose-dependent G2/M phase block. CONCLUSION: Smooth muscle cell (SMC) growth can be controlled effectively with Re-188 for at least 25 days after radiation in vitro. As the first four weeks after arterial angioplasty are crucial concerning neointimal formation, Re-188 may be a valuable radionuclide to inhibit restenosis after arterial angioplasty.     

Adenosine stress cardiac magnetic resonance imaging for the assessment of ischemic heart disease

Aims  This prospective study was designed to determine the diagnostic value of adenosine stress cardiac magnetic resonance imaging (CMRI) in patients referred to elective coronary angiography. Methods and results  Myocardial perfusion measurements at rest and adenosine stress were performed in 141 patients (105 men, 36 women, mean age 63.4 years) at 1.5 T with a Turbo Flash sequence. Stress-induced perfusion deficits were correlated to angiographic stenoses ≥75%. The overall sensitivity for CMRI depicting coronary artery disease (CAD) with relevant stenoses was 90.4%, the specificity was 77.4%, the positive predictive value was 85.9%, the negative predictive value was 84.2% and the accuracy 85.2%. Subgroup analysis was performed for 3-vessel disease (n = 44, sensitivity 92.3%, specificity 75.0%), 2-vessel disease (n = 43, sensitivity 92.6%, specificity 92.9%), 1-vessel disease (n = 27, sensitivity 93.1%, specificity 71.4%) and patients without CAD (n = 27, specificity 70.4%) as well as for patients with prior myocardial infarction (n = 44, sensitivity 92.9%, specificity 86.7%), prior coronary artery bypass surgery (n = 21, sensitivity 88.2%, specificity 66.7%), prior coronary interventions (n = 88, sensitivity 91.9%, specificity 75.0%), or diabetics (n = 27, sensitivity 90.5%, specificity 83.3%). Conclusion  Our study shows that stress perfusion CMRI can accurately predict relevant CAD and contributes to the identification of hemodynamic relevant stenoses in patients scheduled for coronary angiography. C. Doesch and A. Seeger have equally contributed to this publication.     

Cumulative deprivation and cause specific mortality. A census based study of life course influences over three decades

OBJECTIVE: To examine whether increasing cumulative deprivation has an incremental effect on total as well as cause specific mortality. DESIGN: Census data on housing conditions as indicators of deprivation from 1960, 1970, and 1980 were linked to 1990-98 death registrations. Relative indices of inequalities were computed for housing conditions to measure the cumulative impact of differences in social conditions. PARTICIPANTS: 97 381 (71.1%) 30-49 year old and 70701 (80.0%) 50-69 year old inhabitants of Oslo, Norway, in 1990 with census information on housing conditions and recorded length of education. MAIN RESULTS: Mortality risk was increased when all censuses' housing conditions were summed in both age groups and sex. The cause specific analysis indicated such an effect particularly for coronary heart disease, chronic obstructive lung disease, and smoking related cancers. Violent deaths were essentially associated with housing conditions closer to the time of death in men in both age groups and in young women. CONCLUSIONS: To fully account for socially mediated risk of death, a full life course approach should be adopted. The relative importance of each stage seems to vary by cause of death.     

Solitary pulmonary nodules: dynamic contrast-enhanced MR imaging--perfusion differences in malignant and benign lesions

PURPOSE: To determine whether dynamic contrast material-enhanced magnetic resonance (MR) imaging with use of kinetic and morphologic parameters reveals statistically significant differences between malignant and benign solitary pulmonary nodules. MATERIALS AND METHODS: Fifty-eight patients met the inclusion criteria of a solitary 5-40-mm pulmonary nodule without calcification or fat at computed tomography. Fifty-one patients were examined successfully; 46 received a histologic diagnosis, and five received a diagnosis by means of observation over 2 years. Dynamic MR images were acquired every 10 seconds for a total of 4 minutes. Diagnostic characteristics for differentiation were examined by using threshold values for maximum peak enhancement, slope of enhancement, and washout. Receiver operating characteristic curves were calculated to test the usefulness of these parameters. The diagnostic performance of a combination of curve profiles and morphologic contrast material distribution were tested by using a decision tree. RESULTS: Frequency of malignancy was 53% (27 of 51 nodules). Malignant nodules showed stronger enhancement with a higher maximum peak and a faster slope (P <.001). Significant washout (>0.1% increase in signal intensity per second) was found only in malignant lesions (14 of 27 lesions). Sensitivity, specificity, and accuracy were 96%, 88%, and 92%, respectively, for maximum peak; 96%, 75%, and 86% for slope; and 52%, 100%, and 75% for washout. When curve profiles and morphologic enhancement patterns were combined, sensitivity increased to 100%. CONCLUSION: Dynamic MR imaging delineates significant kinetic and morphologic differences in vascularity and perfusion between malignant and benign solitary pulmonary nodules. Washout seems to be highly specific for malignancy.