The interplay of autophagy and ß-Catenin signaling regulates differentiation in acute myeloid leukemia.

The major feature of leukemic cells is an arrest of differentiation accompanied by highly active proliferation. In many subtypes of acute myeloid leukemia, these features are mediated by the aberrant Wnt/ß-Catenin pathway. In our study, we established the lectin LecB as inducer of the differentiation of the acute myeloid leukemia cell line THP-1 and used it for the investigation of the involved processes. During differentiation, functional autophagy and low ß-Catenin levels were essential. Corresponding to this, a high ß-Catenin level stabilized proliferation and inhibited autophagy, resulting in low differentiation ability. Initiated by LecB, ß-Catenin was degraded, autophagy became active and differentiation took place within hours. Remarkably, the reduction of ß-Catenin sensitized THP-1 cells to the autophagy-stimulating mTOR inhibitors. As downmodulation of E-Cadherin was sufficient to significantly reduce LecB-mediated differentiation, we propose E-Cadherin as a crucial interaction partner in this signaling pathway. Upon LecB treatment, E-Cadherin colocalized with ß-Catenin and thereby prevented the induction of ß-Catenin target protein expression and proliferation. That way, our study provides for the first time a link between E-Cadherin, the aberrant Wnt/ß-Catenin signaling, autophagy and differentiation in acute myeloid leukemia. Importantly, LecB was a valuable tool to elucidate the underlying molecular mechanisms of acute myeloid leukemia pathogenesis and may help to identify novel therapy approaches.

[Fever, atrial fibrillation, and angina pectoris in a 58-year-old man]. / Fieber, Vorhofflimmern und Angina pectoris bei einem 58-jährigen Patienten.

Primary cardiac lymphoma (PCL) respresents a very rare type of cardiac tumour. This report illustrates a case of PCL in an immunocompetent 58-year-old man presenting with atrial fibrillation and febrile syndrome. Comprehensive imaging [computer tomography (CT), cardiac magnetic resonance imaging (cMRI), 3-dimensional transesophageal echocardiography (3D-TEE)] identified a large right atrial tumour, leading to pericardial effusion. Isolated cardiac involvement was confirmed by positron emission tomography (PET)-CT. A diffuse large B-cell lymphoma (DLBCL) was diagnosed based on the results of a TEE-guided biopsy. A normalized PET scan (PETAL study) indicated complete remission following R-CHOP 14 immunochemotherapy. Thus, an interdisciplinary and multimodal approach avoided unnecessary cardiac surgery.

Human GII.4 norovirus VLP induces membrane invaginations on giant unilamellar vesicles containing secretor gene dependent α1,2-fucosylated glycosphingolipids.

Norovirus is a non-enveloped virus causing acute gastroenteritis. For human norovirus, no simple cell culture system is available and consequently knowledge on cellular entry of the virus is limited. The virus binds to ABH histo-blood group glycans on glycoproteins and glycosphingolipids. Non-secretors, characterized by the lack of ABH histo-blood group glycans in the gastrointestinal tract, are resistant to most norovirus infections, suggesting that these glycans may be part of the viral receptor. Recent studies have shown that polyomavirus enters the cell via membrane invaginations induced by the multivalent binding of the virus to receptor glycosphingolipids. In this study, we have investigated whether norovirus has the ability to induce membrane invaginations on giant unilamellar vesicles (GUVs) containing purified glycosphingolipids. First, we characterized the glycosphingolipid binding pattern of VLPs from the Dijon strain (genogroup II.4), using thin-layer chromatography. The VLP recognized the ABH active glycosphingolipids H type 1, Lewis b, B type 1, A type 1 and A Lewis b, but not lactotetraosylceramide or Lewis a, typically found in non-secretors. The binding pattern to glycosphingolipids incorporated into GUVs was in full agreement with the thin-layer chromatography experiments. Upon binding to the vesicles, the VLPs formed highly mobile clusters on the surface of the GUVs. VLP containing tubular invaginations were seen on the GUVs containing glycosphingolipids recognized by the VLP. In conclusion, this study suggests that human norovirus has the ability to induce membrane curvature by binding to and clustering glycosphingolipids, which may reflect the first step in cellular entry of the virus.

[Current clinical practice among German Internists regarding the prophylaxis of gastroduodenal ulcers associated with NSAIDs, aspirin and Helicobacter pylori]. / Klinische Praxis der Prophylaxe gastroduodenaler Ulzera.

OBJECTIVE: Rapidly growing information on adverse gastrointestinal effects of non-steroidal anti-inflammatory drugs (NSAIDs) and Helicobacter pylori (Hp) causes continuous changes in clinical patient management. Decisions on the prevention of gastroduodenal ulcers in individual patients often do not follow guidelines. We aimed to assess the current management of gastroduodenal ulcers by internists in southern Germany. METHODS: All 965 members of the Association of Bavarian Internists, a German province with about 8000 internists, were invited to participate in answering a 12-item questionnaire. The questions addressed different clinical scenarios regarding ulcer disease associated with traditional NSAIDs (tNSAIDs), aspirin and Hp. Particularly, we asked for the clinical approach to patients with NSAID-/aspirin-associated ulcers and prophylactic measures before the beginning of a potentially ulcerogenic medication. RESULTS: N = 225 (23.3 %) physicians returned completed questionnaires. In patients with Hp-negative, NSAID-/aspirin-associated ulcers, > 80 % of respondents would initiate long-term proton pump inhibitor (PPI) therapy, whereas 20 % and 17.8 % would prescribe COX-2 selective inhibitors or opiates instead of non-selective NSAIDs and clopidogrel instead of aspirin. The management of Hp-positive ulcers, especially in cases with additional use of aspirin or NSAIDs, was very heterogenous, including Hp-eradication only, eradication +  long-term PPI, eradication +  clopidogrel or COX-2-inhibitors/opiates. CONCLUSION: This survey depicts individual discrepancies in the clinical management of patients receiving NSAIDs and/or aspirin, regarding the prophylaxis of gastroduodenal ulcer disease.

[SPECT/CT - Technical aspects and optimization possibilities]. / SPECT/CT - Technische Aspekte und Optimierungsmöglichkeiten.

In contrast to positron emission tomography/computed tomography (PET/CT), the currently available single photon emission computed tomography/computed tomography (SPECT/CT) systems are very heterogeneous. On the side of the gamma cameras, dual-head systems are established, which are not very different from one manufacturer to the other. For the CT component, there are low dose tubes on the one side and flat detector-based cone beam CT and multislice-CT on the other. The CT image data can be used for anatomic correlation of suspicious findings as well as for attenuation correction of SPECT data. Attenuation correction enables on the one hand enhancement of SPECT image quality and on the other hand quantification of the radioactivity concentration becomes possible. Modern iterative reconstruction algorithms allow scatter correction and attenuation correction of SPECT data using the density values from CT. It still has to be shown to what extent attenuation-corrected whole body SPECT/CT studies will be able to improve the sensitivity of scintigraphy studies. As SPECT/CT primarily aims at morphologic correlation and not detection of additional lesions, an attempt should be made to balance the necessary anatomic information and the additional radiation exposure. Besides SPECT-guided CT all technical possibilities for dose reduction should be exhausted.

Effect of CT-based attenuation correction on uptake ratios in skeletal SPECT.

UNLABELLED: The AIM of this study was to determine the clinical relevance of compensating SPECT data for patient specific attenuation by the use of CT data simultaneously acquired with SPECT/CT when analyzing the skeletal uptake of polyphosphonates (DPD). Furthermore, the influence of misregistration between SPECT and CT data on uptake ratios was investigated. METHODS: Thirty-six data sets from bone SPECTs performed on a hybrid SPECT/CT system were retrospectively analyzed. Using regions of interest (ROIs), raw counts were determined in the fifth lumbar vertebral body, its facet joints, both anterior iliacal spinae, and of the whole transversal slice. ROI measurements were performed in uncorrected (NAC) and attenuation-corrected (AC) images. Furthermore, the ROI measurements were also performed in AC scans in which SPECT and CT images had been misaligned by 1 cm in one dimension beforehand (ACX, ACY, ACZ). RESULTS: After AC, DPD uptake ratios differed significantly from the NAC values in all regions studied ranging from 32% for the left facet joint to 39% for the vertebral body. AC using misaligned pairs of patient data sets led to a significant change of whole-slice uptake ratios whose differences ranged from 3,5 to 25%. For ACX, the average left-to-right ratio of the facet joints was by 8% and for the superior iliacal spines by 31% lower than the values determined for the matched images (p < 0.05). CONCLUSIONS: AC significantly affects DPD uptake ratios. Furthermore, misalignment between SPECT and CT may introduce significant errors in quantification, potentially also affecting left-to-right ratios. Therefore, at clinical evaluation of attenuation-corrected scans special attention should be given to possible misalignments between SPECT and CT.

Anatomical accuracy of interactive and automated rigid registration between X-ray CT and FDG-PET.

AIM: Comparison of anatomical accuracy of software-based interactive (IRR) and automated rigid registration (ARR) of separately acquired CT and FDG-PET data sets. PATIENTS, METHODS: Independently acquired PET and helical CT data from 22 tumour patients were registered manually using the Syngo advanced Fusion VC20H tool. IRR was performed separately for the thorax and the abdomen using physiological FDG uptake in several organs as a reference. In addition, ARR was performed with the commercially available software tool Mirada 7D on all of the patients. For both methods, the distances between the representation of 53 malignant lesions on PET and CT were measured in X-, Y-, and Z-direction with reference to a common coordinate system (X-, Y-, Z-distances). RESULTS: The percentage of lesions misregistered by less than 1.5 cm was in X-direction 91% for IRR and 89% for ARR; in Y-direction 85% and 68%; in Z-direction 72% and 51%, respectively. The average X-, Y- and Z-distances for IRR ranged from 0.58 +/- 0.55 cm (X-direction) to 1.17 +/- 1.66 cm (Z-direction). For ARR, the average X-, Y- and Z-distances varied between 0.66 +/- 0.61 cm (X-direction) and 1.81 +/- 1.37 cm (Z-direction). Mixed effects analysis of the absolute X-, Y- and Z-distances revealed a significantly better alignment for IRR compared to ARR in Z-direction (p < 0.01). Lesion size and localization either in thorax or abdomen had no significant influence on the accuracy of registration. CONCLUSION: For the majority of malignant lesions, manual image registration with the possibility to separately align different body segments was more accurate than the automated approach. Current software for ARR does not reach the anatomical accuracy reported for PET/CT hybrid scanners.

Antithrombin deficiency and its relationship to severe burns.

Antithrombin (AT) is an important endogenous anticoagulant and exhibits marked anti-inflammatory properties. To evaluate the incidence of AT deficiency in severe burn and its correlation to the variables of the abbreviated burn severity index (ABSI), length of hospital stay (LOS) and mortality we collected data on the substitution of human plasma-derived AT concentrate in 201 consecutive patients suffering from severe burn. One hundred and eight patients (54%) developed AT deficiency during their hospitalisation and, according to our institutional practice, received substitution therapy by continuous infusion to maintain physiological plasma activity (70-120%). The mean administered dose served as a measure of AT deficiency. The percentage of patients in an AT deficient state was highest within the first 5 days after injury. It was 26% on day 1 and between 38% and 41% on days 2-5 and thereafter decreased constantly over time. A multiple regression analysis between the dependent variable mean administered dose of AT concentrate and the independent variables age, total body surface area burned (TBSA), gender, inhalation injury (INHAL), full thickness burn (FTB), LOS and mortality was performed. Age, gender and FTB showed no significant influence on the development of AT deficiency. Increasing TBSA and INHAL clearly increase the risk of developing AT deficiency (p-values 0.0001 and 0.037). The analysis also identified AT deficiency as an independent predictor of LOS and mortality (p-values 0.036 and 0.003). Development of AT deficiency is a frequent event after burn with significant correlation to TBSA and INHAL, increased mortality rates and longer hospital stays.

Trafficking of Shiga toxin/Shiga-like toxin-1 in human glomerular microvascular endothelial cells and human mesangial cells.

This study has determined the intracellular transport route of Shiga-like toxin (Stx) and the highly related Shiga toxin in human glomerular microvascular endothelial cells (GMVECs) and mesangial cells. In addition, the effect of tumor necrosis factor-alpha (TNF-alpha), which contributes to the pathogenesis of hemolytic-uremic syndrome, was evaluated more profound. Establishing the transport route will provide better understanding of the cytotoxic effect of Stx on renal cells. For our studies, we used receptor-binding B-subunit (StxB), which is identical between Shiga toxin and Stx-1. The transport route of StxB was studied by immunofluorescence microscopy and biochemical assays that allow quantitative analysis of retrograde transport from plasma membrane to Golgi apparatus and endoplasmic reticulum (ER). In both cell types, StxB was detergent-resistant membrane associated and followed the retrograde route. TNF-alpha upregulated Gb3 expression in mesangial cells and GMVECs, without affecting the efficiency of StxB transport to the ER. In conclusion, our study shows that in human GMVECs and mesangial cells, StxB follows the retrograde route to the Golgi apparatus and the ER. TNF-alpha treatment increases the amount of cell-associated StxB, but not retrograde transport as such, making it likely that the strong TNF-alpha-induced sensitization of mesangial cells and GMVECs for the toxic action of Stx is not due to a direct effect on the intracellular trafficking of the toxin.

Retrospective interactive rigid fusion of (18)F-FDG-PET and CT. Additional diagnostic information in melanoma patients.

AIM: This study investigates whether interactive rigid fusion of routine PET and CT data improves localization, detection and characterization of lesions compared to separate reading. For this purpose, routine PET and CT scans of patients with metastases from malignant melanoma were used. PATIENTS, METHODS: In 34 patients with histologically confirmed malignant melanoma, FDG-PET and spiral CT were performed using clinical standard protocols. For all of these patients, gold standard was available. Clinical and radiological follow-up identified 82 lesions as definitely pathological. Two board-certified nuclear medicine physicians and two board-certified radiologists analyzed PET and CT images independently from each other. For each patient up to 32 anatomical regions (24 lymph node regions, 8 extranodular regions) were systematically classified. Discordant areas were interactively analyzed in manually and rigidly registered images using a commercially available fusion tool. No side-by-side reading was performed. RESULTS: Image fusion disclosed that the evaluation of the PET images alone led to a mislocalization in 26 of 91 focally FDG enhancing lesions. The overall sensitivities of PET, CT, and image fusion were 85, 88, and 94%, respectively; the overall specificities of PET, CT and image fusion were 98, 95 and 100%, respectively. Image fusion exhibited statistically significant higher specificity values as compared with CT. Ten definitely malignant sites were false-negative in CT, but could be detected by PET. On the other hand, twelve metastases were false-negative in PET, but could be detected by CT. These included two lesions, which had a clear correlate on the PET image when the fused images were evaluated. On the whole, registration of the PET and CT images yielded additional diagnostic information in 44% of the definitely malignant lesions. CONCLUSION: Retrospective image fusion of independently obtained PET and CT data is particularly valuable in exactly localizing foci of abnormal FDG uptake and improves the detection of metastases of malignant melanoma.

[Anatomical accuracy of lesion localization. Retrospective interactive rigid image registration between 18F-FDG-PET and X-ray CT]. / Genauigkeit der Lokalisierung maligner Herde mittels retrospektiver, interaktiver starrer Bildfusion von FDG-PET und CT.

UNLABELLED: The aim of this study was to evaluate the anatomical accuracy and reproducibility of retrospective interactive rigid image registration (RIR) between routinely archived X-ray computer tomography (CT) and positron emission tomography performed with 18F-deoxyglucose (FDG-PET) in oncological patients. METHODS: Two observers registered PET and CT data obtained in 37 patients using a commercially available image fusion tool. RIR was performed separately for the thorax and the abdomen using physiological FDG uptake in several organs as a reference. One observer performed the procedure twice (O1a and O1b), another person once (O2). For 94 malignant lesions, clearly visible in CT and PET, the signed and absolute distances between their representation on PET and CT were measured in X-, Y-, and Z-direction with reference to a coordinate system centered in the CT representation of each lesion (X-, Y-, Z-distances). RESULTS: The mean differences of the signed and absolute distances between O1a, O1b, and O2 did not exceed 3 mm in any dimension. The absolute X-, Y-, and Z-distances ranged between 0.57 +/- 0.58 cm for O1a (X-direction) and 1.12 +/- 1.28 cm for O2 (Z-direction). When averaging the absolute distances measured by O1a, O1b, and O2, the percentage of lesions misregistered by less than 1.5 cm was 91% for the X-, 88% for the Y-, and 77% for the Z-direction. The larger error of fusion determined for the remaining lesions was caused by non-rigid body transformations due to differences in breathing, arm position, or bowel movements between the two examinations. Mixed effects analysis of the signed and absolute X-, Y-, and Z-distances disclosed a significantly greater misalignment in the thorax than in the abdomen as well as axially than transaxially. CONCLUSION: The anatomical inaccuracy of RIR can be expected to be <1.5 cm for the majority of neoplastic foci. Errors of alignment are bigger in the thorax and in Z-direction, due to non-rigid body transformations caused, e.g., by breathing.

Attenuation correction of SPECT images based on separately performed CT: Effect on the measurement of regional uptake values.

AIM: A new software approach uses separately acquired CT images for attenuation correction after retrospective fusion with the SPECT data. This study evaluates the effect of this CT-based attenuation correction on indium-111-pentetreotide-SPECT images. METHODS: Indium-111-pentetreotide-SPECT imaging using a dual-head gamma camera e.cam (Siemens Medical Solutions, Erlangen, Germany) as well as separate spiral computed tomography (CT) was performed in 13 patients. After fusion of SPECT and CT data, the bilinear attenuation coefficients were calculated for each pixel in the CT image volume using their Hounsfield unit values and attenuation-corrected images were reconstructed iteratively (OSEM 2D). Regions of interest (ROIs) were drawn on 24 suspicious foci and background, and target to background ratios were calculated for corrected (TBAC) and uncorrected (TBNAC) images. The shortest distance from the centre of the lesion to the surface of the body (DS) was measured on the corresponding CT slice. Furthermore, ROIs were drawn over the rim and the centre of the liver. Ratios of hepatic count rates for corrected (LRAC) and uncorrected (LRNAC) images were also compared. RESULTS: In lesions located more centrally, TBAC was up to 52% higher, whereas in peripherally located lesions, TBAC was up to 63% lower than TBNAC. The TBAC/TBNAC quotient was linearly correlated with DS. In the liver, attenuation correction resulted in a 35% increase of LRAC compared with LRNAC. CONCLUSIONS: Attenuation correction of SPECT images performed by separately acquired CT data is quick and simple. It improves the contrast between target and background for lesions located more centrally in the body and improves homogeneity of the visualisation of tracer uptake in the liver.

[CT and MRI of the petrous bone]. / CT und MRT des Felsenbeins.

Diseases of the petrous bone should now be diagnosed by means of high-resolution multislice spiral computed tomography (MSCT) and/or magnetic resonance imaging (MRI). The first step in the process of diagnosis, however, must be conventional X-ray photographs (according to Schüller, Mayer, Stenvers) for screening purposes, because of the high cost of the other procedures mentioned. Because of the excellent imaging of bone structures with MSCT, this technique is especially suitable for the diagnosis both of acquired pathologies and of congenital abnormalities of the external auditory meatus, the middle ear and the mastoid, of trauma-induced pathologies of the entire petrous bone, and of osteogenic diseases. MRI is the method of choice for examination of the labyrinthine system, the interior auditory meatus and the cerebellopontine angle because it gives much the best depiction of soft tissue. Sometimes when questions remain unsolved after computed tomography (CT) examination of the middle ear MRI can be applied to complement CT, and it can yield additional information. Lesions affecting the apex of the petrous pyramid should be examined by MRI. High-resolution CT through the bone window and thin-layer MRI are both components of the presurgical diagnosis before cochlear implant (CI) surgery. For postoperative monitoring a conventional transorbital X-ray of the petrous bone is sufficient; CT is indicated only in complicated cases, and MRI is absolutely contraindicated after CI.

[Indications and diagnostic sensitivity of CT and MRI in the otorhinolaryngology field]. / Indikation und Aussagekraft von CT und MRT im Kopf-Hals-Bereich.

Of all malignant tumors, 4-5% affect the head and neck region. Computed tomography (CT) and magnetic resonance imaging (MRI) provide the means for us to determine the precise extent and depth of infiltration of space-occupying lesions, detect submucosal growth, stage lymph nodes preoperatively, and thus facilitate better preoperative planning. Thinner collimations of sections and shorter examination times are possible with modern multilayer spiral CT. Two-dimensional and three-dimensional images can be calculated from the volume specifications to assess the skull base (coronal and sagittal sections) and the midline crossover of tumors as well as staging of lymph nodes (coronal section). Examination of laryngeal and hypopharyngeal function as well as determination of tumor perfusion are also possible. Detection of tumors that do not absorb any contrast medium (approximately 15%) is more difficult with CT. In addition to providing a high degree of tissue contrast, MRI makes it possible to directly acquire images in any number of planes. In contrast to CT, metallic artefacts hardly come into play. Infiltration of the dura and the cerebrum can be depicted better with MRI than with CT. The long examination time with MRI carries the risk of movement artefacts. In the head and neck region, it is important to suppress fat in T2-weighted sequences and in T1-weighted sequences after administration of contrast media. Inflammations in the head and neck region are only exceptionally clarified with CT or MRI. It is imperative that CT be performed before functional endoscopic operations of the paranasal sinuses. Further indications for CT and MRI in cases of inflammation are the diagnosis of retrotonsillar and parapharyngeal abscesses and ensuing complications as well as the diagnosis of osteomyelitis. Since conventional sialography is contraindicated in acute inflammation in sialolithiasis, magnetic resonance sialography can be employed.

Estradiol, testosterone, dehydroepiandrosterone and androstenedione: novel derivatives and enantiomers. Interactions with rat liver microsomal cytochrome P450 and antioxidant/radical scavenger activities in vitro.

Interactions of 27 steroids, among them 17 derivatives such as ethers, sulfates and amidosulfonates derived from 17 beta- and 17 alpha-estradiol, from testosterone and alpha- and beta-dihydrotesosterone and from dehydroepiandrosterone with rat liver microsomal cytochromes P450 (P450) were investigated in vitro by assessing binding to P450 and effects on P450 mediated monooxygenase functions as measured by different model reactions: ethoxyresorufin O-deethylation (EROD), ethoxycoumarin O-deethylation (ECOD) and ethylmorphine N-demethylation (EMND). With the exception of 17 alpha-estradiol-3-dimethylamidosulfonate, estrone, its -3-methylether and -3-amidosulfonate and testosterone, all other steroids displayed type I or reverse type I binding to P450. All steroids inhibited EROD activity in micromolar concentrations. An additional strong inhibition of ECOD and EMND activities was only demonstrated for the androgens and progestins. Estriol, estrone and mestranol displayed less inhibitory actions on the model reactions than estradiol. No major differences in comparison to the parent compounds were noted with the other derivatives. The only exceptions were 17 beta-(8,9-dehydro-14 alpha,15 alpha-methylene)estradiol, which displayed stronger effects than estradiol, and dehydroepiandrosterone-3-sulfate, which was less effective than dehydroepiandrosterone. Possible antioxidant properties of the steroids were examined by the stimulated lipid peroxidation (LPO), H2O2 production, and lucigenin (LC) and luminol (LM) amplified chemiluminescence (CL) using rat liver microsomes. Additionally, the influence on rat whole blood chemiluminescence (WB-CL) was assessed. All the estrogens, but not their methylethers and amidosulfonates inhibited LPO in micromolar concentrations. The effects on the other oxidase model reactions or on WB-CL were less distinct. Only ethinylestradiol and 17 beta-(8,9-dehydro-14 alpha,15 alpha-methylene)estradiol displayed a strong inhibitory action on all model reactions. With the exception of dehydroepiandrosterone-3-sulfate, which in general had only weak effects, the androgen and progestin derivatives, in contrast, strongly decreased H2O2 formation and LM- and LC-CL, but were mostly ineffective on LPO and WB-CL.

Antiatherogenic effects of 17 beta-estradiol and 17 alpha-estradiol and its derivative J811 in cholesterol-fed rabbits with thyroid inhibition.

OBJECTIVE: The aim of this study was to investigate the antiatherogenic effects of 17 beta-estradiol and 17 alpha-estradiol and its derivative J811 (estra-1,3,5(10),8-tetraene-3, 17 alpha-diol), having a non-feminizing effect and high antioxidant potential, in male rabbits. EXPERIMENTAL DESIGN: Male White-Russian rabbits weighing 2.1-2.6 kg were fed either a standard or a high-cholesterol (200 mg/kg) diet, with thyroid function-inhibiting thiouracil (20 mg/kg) combined with cholic acid (40 mg/kg) administered daily in sunflower oil for 3 months. During the last month of the study, estrogens were administered by gavage at a dose of 0.02 or 0.1 mg/kg. RESULTS AND CONCLUSIONS: All three estrogens exerted remarkable antiatherosclerotic effects. Decreases in serum and aortic-wall lipid parameters and the index of atherogenicity were dependent on estrogen dose. Morphological evaluation of the aortic wall (height of plaques, size of plaque relative to aortic half-circumference) showed only weak therapeutic effects with all three estrogens. It is an open question whether the treatment period was too short to reverse the above changes. On the other hand, the data clearly suggest that 17 alpha-estradiol and J811 offer new perspectives for the prevention of atherosclerosis in men, which is similar to that found with 17 beta-estradiol in women.