Quantum Critical Point in the Itinerant Ferromagnet Ni_{1-x}Rh_{x}.

We report a chemical substitution-induced ferromagnetic quantum critical point in polycrystalline Ni_{1-x}Rh_{x} alloys. Through magnetization and muon spin relaxation measurements, we show that the ferromagnetic ordering temperature is suppressed continuously to zero at x_{crit}=0.375 while the magnetic volume fraction remains 100% up to x_{crit}, pointing to a second order transition. Non-Fermi liquid behavior is observed close to x_{crit}, where the electronic specific heat C_{el}/T diverges logarithmically, while immediately above x_{crit} the volume thermal expansion coefficient α_{V}/T and the Grüneisen ratio Γ=α_{V}/C_{el} both diverge logarithmically in the low temperature limit, further indication of a ferromagnetic quantum critical point in Ni_{1-x}Rh_{x}.

Magnetic and Structural Quantum Phase Transitions in CeCu_{6-x}Au_{x} are Independent.

The heavy-fermion compound CeCu_{6-x}Au_{x} has become a model system for unconventional magnetic quantum criticality. For small Au concentrations 0≤x<0.16, the compound undergoes a structural transition from orthorhombic to monoclinic crystal symmetry at a temperature T_{s} with T_{s}→0 for x≈0.15. Antiferromagnetic order sets in close to x≈0.1. To shed light on the interplay between quantum-critical magnetic and structural fluctuations we performed neutron-scattering and thermodynamic measurements on samples with 0≤x≤0.3. The resulting phase diagram shows that the antiferromagnetic and monoclinic phase coexist in a tiny Au concentration range between x≈0.1 and 0.15. The application of hydrostatic and chemical pressure allows us to clearly separate the transitions from each other and to explore a possible effect of the structural transition on the magnetic quantum-critical behavior. Our measurements demonstrate that at low temperatures the unconventional quantum criticality exclusively arises from magnetic fluctuations and is not affected by the monoclinic distortion.

Vascular complication after percutaneous femoral cerclage wire.

Cerclage wire is an effective fracture fixation method. However, its mechanical benefits are countered by local ischemia. Its efficacy for treating femoral periprosthetic fractures has been demonstrated since femoral fixation is possible even there is a stem in the diaphysis. It securely holds the proximal femur typically with an additional plate. The development of minimally-invasive surgery with plate fixation has led to the cerclage wire being inserted percutaneously. Here, we report on a case of secondary femoral ischemia following percutaneous cerclage wire of a periprosthetic femoral fracture. This was a Vancouver type B1 fracture. On the 3rd day after admission, minimally-invasive fixation with a femoral locking plate was performed with five cerclage wires added percutaneously. During the immediate postoperative course, the patient developed ischemia of the operated leg that required vascular surgery after confirmation by CT angiography. An arterial stop was visible with deviation of the superior femoral artery, which was not properly surrounded by the cerclage wire. The latter pulled perivascular tissues towards the femur. When combined with reduced arterial elasticity due to severe atherosclerosis, it resulted in arterial plication. The postoperative course was marked by multiple organ failure and death of the patient. Percutaneous surgery is an attractive option but has risks. The presence of severe atherosclerosis is a warning sign for loss of tissue elasticity. This complication can be prevented by preparing the bone surfaces and carefully positioning the patient on the traction table to avoid forced adduction. The surgeon must also be familiar with alternative techniques to cerclage wire such as polyaxial screws and additional plates.

Sexual development of the urodele amphibian Pleurodeles waltl.

Pleurodeles waltl is a urodele amphibian that displays a ZZ/ZW genetic mode of sex determination involving a putative W-borne dominant determinant. This determining pathway can be environmentally inhibited since heat treated ZW larvae undergo a functional female to male sex reversal. Moreover, both genetic sexes can be reversed by treatment of larvae with steroid hormones suggesting they are the major players in the differentiation process. Indeed we demonstrated that i) aromatase expression and activity increase just before ovarian differentiation, ii) aromatase inhibitors induce a female to male sex reversal, iii) estrogens induce male to female sex reversal whereas the opposite is obtained with non-aromatizable androgens, iv) steroidogenic factor 1 and estrogen receptor alpha both display a female-enriched expression following the increase in aromatase activity. The role of endogenous hormones was investigated in a parabiosis model. Surprisingly, in ZW/ZZ associations, the ZW gonad could not differentiate suggesting that the ZZ parabiont produces an inhibiting factor, prior to ovarian differentiation. The role of AMH in this process is discussed, keeping in mind that Mullerian ducts are maintained in males. The development of antibodies and new molecular tools in the near future should help us to better understand the sexual development of this vertebrate.

Female-enriched and thermosensitive expression of steroidogenic factor-1 during gonadal differentiation in Pleurodeles waltl.

In the urodele amphibian Pleurodeles waltl, sex differentiation is genetically controlled, that is, ZZ male vs ZW female, but may be influenced by temperature, which induces a female-to-male sex reversal. We investigated whether steroidogenic factor 1 (SF-1) could be involved in Pleurodeles sex differentiation or in temperature-dependent sex reversal by cloning a Pleurodeles SF-1 cDNA and examining its developmental expression. The 468-amino-acid deduced protein is highly conserved in comparison with other species. In ZZ and ZW control larvae, SF-1 mRNA is detected at the first stage of the thermosensitive period (TSP) in the gonad-mesonephros-interrenal complex (GMI). By the end of TSP at stage 55, SF-1 is expressed in the gonad (Gd) and in the mesonephros-interrenal (MI) both in ZZ and ZW larvae. During this stage, a transient, ZW-specific increase of SF-1 transcription occurs not only in Gd but also in MI, this increase starting earlier in Gd than in MI. Therefore, in P. waltl, an SF-1 upregulation occurs after the onset of the ovarian-specific increase of aromatase mRNA expression. At the end of metamorphosis, the SF-1 transcription level in Gd and MI is nearly the same in both ZZ and ZW larvae. Besides, after long-term heat treatment leading to sex reversal, SF-1 mRNA upregulation is not observed in ZW larvae, in either Gd or MI. However, SF-1 expression is not decreased after a 48-h heat shock applied at the end of the TSP, suggesting that temperature has no inhibitory effect by itself in long-term heat treatment. Estradiol benzoate treatments show that, at the end of the TSP, SF-1 gene transcription could be controlled by the estrogen level. This is in accordance with the female-enriched SF-1 expression and the decreased SF-1 expression following long-term, sex-reversing heat treatment, which is known to decrease aromatase expression and activity. Thus, it is unlikely that SF-1 is directly involved in Pleurodeles temperature-dependent sex reversal.

[Are there predictors for proliferative retinopathy of prematurity and is supplemental oxygen a useful conservative treatment option?]. / Gibt es Prädiktoren für proliferierende Stadien der Retinopathia praematurorum und ist eine Sauerstoffsupplementation als konservative Therapiemöglichkeit sinnvoll? Eine Analyse anhand des eigenen Patientenguts.

BACKGROUND: Especially very immature preterm babies develop retinopathy of prematurity (ROP). This study aims at analysing risk factors for proliferative ROP and realizing the efficiency of supplemental oxygen therapy. PATIENTS: 180 preterm babies with birth weight < or = 1 500 grams were included retrospectively. METHODS: To determine potential predictors all preterm babies with ROP grade > or = 3 were matched to pairs with similar immature babies with ROP 1 or 2. Additionally we examined the influence of supplemental oxygen therapy on the coagulation rate of high grade retinopathy. RESULTS: 44 % of the preterm babies showed ROP. A longer duration of ventilation (21 vs. 33 days), a longer duration of oxygen supplementation (59 vs. 78 days), relapsing sepsis (10 vs. 19 babies with sepsis > 2 times), a large total volume of transfusions (median: 150 mL vs. 105 mL), chronic lung disease (CLD) (6 vs. 15 babies with oxygen requirements at 36 weeks post-menstrual age), a duration of intubation for more than 28 days (13 vs. 6 babies) and the lack of phototherapy (21 vs. 9 babies) were risk factors associated with ROP > or = 3 using univariate analysis [p < 0.05]. Only the both last criteria correlated with high grade ROP after logistic regression. The supplemental oxygen therapy showed no influence on the coagulation rate of high grade ROP. Possibly this therapy influences the frequency of surgical treatment of amotio- and of putting on a cerclage, but this remains still speculative because of the low case number. We saw no negative effect on the frequency of CLD and on the survival of the babies. CONCLUSIONS: Especially measures against long duration of intubation could help to prevent high grade ROP. The supplemental oxygen therapy may have a positive effect on course.

Steroids, aromatase and sex differentiation of the newt Pleurodeles waltl.

In the newt Pleurodeles waltl, genetic sex determination obeys female heterogamety (female ZW, male ZZ). In this species as in most of non-mammalian vertebrates, steroid hormones play a key role in sexual differentiation of gonads. In that context, male to female sex reversal can be obtained by treatment of ZZ larvae with estradiol. Male to female sex reversal has also been observed following treatment of ZZ larvae with testosterone, a phenomenon that was called the "paradoxical effect". Female to male sex reversal occurs when ZW larvae are reared at 32 degrees C during a thermosensitive period (TSP) that takes place from stage 42 to stage 54 of development. Since steroids play an important part in sex differentiation, we focussed our studies on the estrogen-producing enzyme aromatase during normal sex differentiation as well as in experimentally induced sex reversal situations. Our results based on treatment with non-aromatizable androgens, aromatase activity measurements and aromatase expression studies demonstrate that aromatase (i) is differentially active in ZZ and ZW larvae, (ii) is involved in the paradoxical effect and (iii) might be a target of temperature. Thus, the gene encoding aromatase might be one of the master genes in the process leading to the differentiation of the gonad in Pleurodeles waltl.

Effect of cadmium on gonadogenesis and metamorphosis in Pleurodeles waltl (urodele amphibian).

In the amphibian Pleurodeles waltl, steroid hormones play a key role in sex differentiation. Since cadmium has been reported to block receptors of sex steroid hormones, we analyzed the effects of this heavy metal on Pleurodeles larvae gonadogenesis. At stage 42, larvae die in the presence of 10.9 microM Cd in the rearing tap water, with TL(50) of 46.3 h, but the concentration of 5.5 microM is tolerated for more than 60 days. When used at 5.5 microM cadmium accumulation measured by atomic absorption spectrophotometry (AAS) in total homogenates of larvae at stage 54 (after 77 days of exposure to the heavy metal) reached 58.1 microg/g of dry weight. At stage 54, we did not detect inhibitory effects on gonadogenesis in larvae reared in the presence of 5.5 microM Cd since stage 42. When the exposure to 5.5 microM Cd was lengthened after stage 54, metamorphosis was delayed and could not be completed. When larvae were exposed to 10.9 microM Cd from stage 54, metamorphosis did not occur and gonad development was stopped. Our study demonstrates a lack of a direct effect of cadmium on sex determination-differentiation but a strong inhibitory effect on metamorphosis, which impairs further gonadal development.

Differential expression of P450 aromatase during gonadal sex differentiation and sex reversal of the newt Pleurodeles waltl.

A better understanding of vertebrate sexual differentiation could be provided by a study of models in which genetic sex determination (GSD) of gonads can be reversed by temperature. In the newt Pleurodeles waltl, a P450 aromatase cDNA was isolated from adult gonads, and the nucleotide or deduced amino acid sequences showed a high level of identity with various vertebrate species. In adults, aromatase expression was found in gonads and brain. In developing gonads, the expression was found to fit with the thermo-sensitive period (TSP) and was detected in both ZZ and ZW larvae, as well as in ZW submitted during the whole TSP to a masculinizing temperature. In the latter individuals, in situ hybridization and semi quantitative RT-PCR showed that, at the end of TSP, aromatase expression was at the same level than in normal ZZ larvae and was significantly lower than in normal ZW ones. Furthermore, temperature-induced down regulation did not occur when heating was performed at the end of TSP. Our results confirm the importance of aromatase regulation in female versus male differentiation and demonstrate that a down regulation of aromatase expression is involved in the process of sex reversal.

Effects of androgens on sex differentiation of the urodele Pleurodeles waltl.

In nonmammalian vertebrates, steroids have been hypothesized to induce somatic sex differentiation, since manipulations of the steroidal environment of gonads have led to various degrees of sex reversal. Whereas the critical role of estrogens in ovarian differentiation is well documented, studies on androgens have produced a perplexing variety of results depending upon species variations and nature of androgens used. In this way, testosterone induces masculinization of females in some species but provokes paradoxical feminization of males in many other species such as the urodelan Pleurodeles waltl. In reptiles this phenomenon could be interpreted by conversion of exogenous testosterone to estradiol by aromatase. Treatments of Pleurodeles larvae with nonaromatizable androgens bring support to this hypothesis and suggest a role of androgens in sex differentiation. Dihydrotestosterone (DHT) could not induce the paradoxical feminization of ZZ larvae. In addition, DHT as well as 11beta-hydroxy-androstenedione could drive a functional male differentiation of ZW larvae. Moreover, other 5alpha reduced androgens also induced sex reversal of female larvae. Yet, the 5alpha reductase inhibitor CGP 53133 and antiandrogens such as flutamide or cyproterone acetate did not exert any effect on male sex differentiation of ZZ larvae. Though the precise role of androgens is still unknown, especially for 11-oxygenated androgens, our results suggest an implication in male sex differentiation. In this way, testosterone could play a pivotal role in being metabolized either into other androgens during testis differentiation or into estradiol during ovarian differentiation.

Flavonoids with epidermal growth factor-receptor tyrosine kinase inhibitory activity stimulate PEPT1-mediated cefixime uptake into human intestinal epithelial cells.

We have tested 33 flavonoids, occurring ubiquitously in foods of plant origin, for their ability to alter the transport of the beta-lactam antibiotic cefixime via the H+-coupled intestinal peptide transporter PEPT1 in the human intestinal epithelial cell line Caco-2. Of the flavonoids tested, quercetin, genistein, naringin, diosmin, acacetin, and chrysin increased uptake of [14C]cefixime dose dependently by up to 60%. All other flavonoids were either without effect or decreased the absorption of cefixime. Quercetin was shown to increase the Vmax of cefixime influx without changing the apparent Km for transport. However, the expected concomitant increase in intracellular acidification due to PEPT1-mediated cefixime/H+-cotransport was less pronounced in the presence of quercetin. This suggested that pH regulatory systems such as apical Na+/H+-exchange could be activated by quercetin and maintain the proton-motive driving force for cefixime uptake. Since quercetin and genistein have been shown to inhibit epidermal growth factor (EGF)-receptor tyrosine kinases, we applied tyrphostin 25 to prove whether such an inhibition could explain the stimulatory effects seen on cefixime uptake. It was found that tyrphostin 25 simulated the effects of quercetin by increasing cefixime absorption due to maintenance of the transmembrane pH gradient. In conclusion, our studies show that flavonoids with EGF-receptor tyrosine kinase inhibitory activities enhance the intestinal absorption of the beta-lactam antibiotic cefixime in Caco-2 cells by activation of apical Na+/H+-exchange and a concomitant increase of the driving force for PEPT1.

Challenges in research with incarcerated parents and importance in violence prevention.

Incarcerated parents present several risk factors for later violence by their children. This study uses comparison groups and repeated measures to evaluate an inmate parenting program. Subjects are inmates at a county detention center, their children, and primary caregivers. Challenges to program implementation and longitudinal research with inmates were identified, along with recommendations to assist future research and programming. Training material should use illustrated, basic language format. Acceptance and participation by inmates and staff require ongoing outreach and communication. Severed relationships are common and future research on inmates with stable family relationships is recommended. Because of inmate transience, integrating parent training into post-release programming is suggested.

Impaired resensitization and recycling of the cholecystokinin receptor by co-expression of its second intracellular loop.

Intermolecular interaction represents an important theme in regulation of intracellular trafficking of organelles that can be interrupted by competitive overexpression of a relevant molecular domain. We attempted to identify the functional importance of intracellular domains of the cholecystokinin (CCK) receptor by their over-expression in receptor-bearing Chinese hamster ovary (CHO-CCKR) cell lines. Although clathrin-dependent endocytosis and recycling of this receptor are well-established (J Cell Biol 128:1029-1042, 1995), any influence of distinct receptor domains is not understood. In this work, constructs representing each of the intracellular domains of the CCK receptor were coexpressed with wild-type receptor, and stable clonal cell lines were selected. Each was characterized for ligand binding and agonist-stimulated biological activity (inositol 1,4,5-trisphosphate generation), desensitization, resensitization, receptor internalization, and recycling. Each cell line expressed normal CCK radioligand binding, signaling, internalization, and desensitization. Three independent cell lines that coexpressed the 25-residue second intracellular loop domain exhibited deficient resensitization. In morphological assessment of receptor trafficking, this construct was also shown to interfere with receptor recycling to the plasma membrane. As a control, recycling of an unrelated G protein-coupled receptor was demonstrated to occur normally in this cell line. These observations suggest that rather than representing passive cargo within an endosome, a receptor can influence its own trafficking within the cell.

CCK receptor phosphorylation exposes regulatory domains affecting phosphorylation and receptor trafficking.

Agonist-stimulated phosphorylation of guanine nucleotide-binding protein (G protein)-coupled receptors has been recognized as an important mechanism for desensitization by interfering with coupling of the activated receptor with its G protein. We recently described a mutant of the CCK receptor that modified two of five key sites of phosphorylation (S260,264A) and eliminated agonist-stimulated receptor phosphorylation, despite normal ligand binding and signaling (20). As expected, this nonphosphorylated mutant had impaired rapid desensitization but was ultimately able to be desensitized by normal receptor internalization. Here we demonstrate that this mutant receptor is also defective in resensitization, with abnormal recycling to the cell surface. To explore this, another receptor mutant was prepared, replacing the same serines with aspartates to mimic the charge of serine-phosphate (S260,264D). This mutant was expressed in a Chinese hamster ovary cell line and shown to bind CCK normally. It had accelerated kinetics of signaling and desensitization and was phosphorylated in response to agonist occupation, with all other normal sites of phosphorylation modified. It was internalized like wild-type receptors and was resensitized and trafficked normally. This provides evidence for an additional important function for phosphorylation of G protein-coupled receptors. Phosphorylation may induce a conformational change in the receptor to expose other potential sites of phosphorylation and to expose domains involved in the targeting and trafficking of endosomes. The hierarchical phosphorylation of these sites may play a key role in receptor regulation.

Stimulated acoustic emission: pseudo-Doppler shifts seen during the destruction of nonmoving microbubbles.

The purpose of this study was to evaluate the appearance and the characteristics of stimulated acoustic emission (SAE) as an echo contrast-specific color Doppler phenomenon with impact on myocardial contrast echocardiography (MCE). Stationary microbubbles of the new contrast agent SH-U 563A (Schering AG) were embedded within a tissue-mimicking gel material. Harmonic power Doppler imaging (H-PDI), color Doppler and pulse-wave Doppler data were acquired using an HDI-5000 equipped with a phased-array transducer (1.67/3.3 MHz). In color Doppler mode, bubble destruction resulted in random noise like Doppler signals. PW-Doppler revealed short "pseudo-Doppler" shifts with a broadband frequency spectrum. Quantification of SAE events by H-PDI demonstrated an exponential decay of signal intensities over successive frames. A strong linear relationship was found between bubble concentration and the square root of the linearized H-PDI signal for a range of concentrations of more than two orders of magnitude (R = 0.993, p < 0.0001). Intensity of the H-PDI signals correlated well with emission power (R = 0.96, p = 0.0014). SAE results from disintegration of microbubbles and can be demonstrated by all Doppler imaging modalities, including H-PDI. Intensity of SAE signals is influenced by the applied acoustic power and correlates highly with the concentration of microbubbles. Because intensity of SAE signals correlates highly with echo contrast concentrations, analysis of SAE signals might be used for quantitative MCE.

Are microbubbles free flowing tracers through the Myocardium? Comparison of indicator-dilution curves obtained from dye dilution and echo contrast using harmonic power Doppler imaging.

BACKGROUND: Harmonic power Doppler imaging (H-PDI) has been introduced into the field of contrast echocardiography as a contrast-specific imaging modality. However, there has been considerable skepticism as to whether H-PDI would be quantifiable, because it depends on the destruction of microbubbles and has more complex signal processing than gray scale imaging. The aim of the present study was to evaluate the relationship between the concentration of microbubbles and the resulting H-PDI signals even under conditions where bubble destruction is most likely. Furthermore, we evaluated whether microbubbles of Levovist freely pass the microcirculation, which is a prerequisite for the assessment of myocardial blood flow. METHODS AND RESULTS: A strong positive correlation was found between the H-PDI signals and the amount of microbubbles up to the onset of acoustic shadowing (r = 0. 968, P<0.001). Time-intensity curves for H-PDI of air-filled microbubbles were compared with time-concentration curves of indocyanine green (ICG) in both a flow phantom and a working heart setup. The mean transit times (MTTs) through the myocardium of both agents were compared after a bolus injection into the left coronary artery. A close correlation was observed between 1/MTT and flow in both setups (r>0.98, P<0.0001). However, at high flow rates, the MTTs of the microbubbles were slightly, albeit not significantly, faster than those of indocyanine green. CONCLUSIONS: We conclude that microbubbles fulfill the prerequisites of free flowing tracers through the myocardium. Furthermore, H-PDI technology allows a reliable assessment of time-concentration curves of air-filled microbubbles up to the onset of acoustic shadowing.

Dietary flavone is a potent apoptosis inducer in human colon carcinoma cells.

Flavonoids are polyphenolic compounds that occur ubiquitously in plants. They are discussed to represent cancer preventive food components in a human diet that is rich in fruits and vegetables. To understand the molecular basis of the putative anticancer activity of flavonoids, we investigated whether and how the core structure of the flavones, 2-phenyl-4H-1-benzopyran-4-one (flavone) affects proliferation, differentiation, and apoptosis in HT-29 human colon cancer cells. Moreover, the effects of flavone in transformed epithelial cells were compared with those obtained in nontransformed primary mouse colonocytes. Proliferation, differentiation, and apoptosis in transformed as well as nontransformed colon cells were measured by fluorescence-based techniques. Apoptosis was also determined by changes in membrane permeability, FACScan analysis, and detection of DNA fragmentation. Semiquantitative reverse transcription PCR was performed to assess the effects of flavone on transcript levels. Flavone was found to reduce cell proliferation in HT-29 cells with an EC(50) value of 54.8 +/- 1.3 microM and to potently induce differentiation as well as apoptosis. The flavonoid proved to be a stronger apoptosis inducer than the clinically established antitumor agent camptothecin. The effects of flavone in HT-29 cells were associated with changed mRNA levels of cell-cycle- and apoptosis-related genes including cyclooxygenase-2 (COX-2), nuclear transcription factor kappaB (NF-kappaB), and bcl-X(L). Moreover, flavone, but not camptothecin, displayed a high selectivity for the induction of apoptosis and of growth inhibition only in the transformed colonocytes. In conclusion, the plant polyphenol flavone induces effectively programmed cell death, differentiation, and growth inhibition in transformed colonocytes by acting at the mRNA levels of genes involved in these processes. Because these genes play a crucial role in colon carcinogenesis, flavone may prove to be a potent new cytostatic compound with improved selectivity toward transformed cells.

Increased expression of the lymphocyte early activation marker CD69 in peripheral blood correlates with histologic evidence of cardiac allograft rejection.

BACKGROUND: The human leukocyte membrane protein CD69 is an early activation marker induced in T lymphocytes, B cells, and natural killer cells in response to inflammatory stimuli. Cardiac catheterization and endomyocardial biopsy remain the "gold standard" for diagnosis of rejection after transplantation, and noninvasive methods of rejection surveillance have long been sought. We studied CD69 membrane protein expression in peripheral blood T lymphocytes obtained from pediatric cardiac transplant recipients at the time of biopsy and correlated the results with histologic rejection scores. METHODS: Heparinized whole blood samples were obtained from pediatric cardiac transplant recipients at the time of cardiac biopsy, as well as from control subjects. Lymphocytes were labeled with antibodies for CD3, CD4, CD8, and CD69 and analysis performed using flow cytometric methods. RESULTS: Resting CD69 expression (measured as a percentage of gated events) was significantly increased in patients with concurrent histologic evidence of rejection (International Society for Heart and Lung Transplantation grade > or =3A) when compared to those with minimal or no rejection and controls. Although statistically significant for both lymphocyte subsets, this relationship was more pronounced for CD8+ T cells (P<0.001) than for CD4+ T cells (P=0.001). When data were analyzed by rejection score, a percentage activation of the CD8+ subset (CD69+/CD8+ cells as a percentage of total gated events) exceeding 15% correlated with significant rejection. CONCLUSIONS: Measurement of the expression of the early activation marker CD69 in peripheral blood lymphocytes by flow cytometry may provide a noninvasive means of assessing immune activation and possible rejection in cardiac transplant recipients.

[Heart failure as a cardiac symptom of sarcoidosis. Successful treatment of heart failure with steroids, digitalis and an angiotensin-1-receptor antagonist in sarcoidosis]. / Herzinsuffizienz als kardiale Manifestation einer Sarkoidose. Erfolgreiche Therapie der Herzinsuffizienz mit Steroiden, Digitalis und einem Angiotensin-1-Rezeptor-Antagonisten bei Sarkoidose.

BACKGROUND: Sarcoidosis is a multisystemic disorder that may involve every organ. A symptomatic manifestation of the myocardium is possible, in these cases arrhythmias are the most common symptoms. CASE REPORT: This case report presents a 26-year-old female with the recurrence of Boeck's sarcoid. Fever, chill and a severe reduction in stress tolerance were the first symptoms. At the time of admission she complained of Grade III dyspnea according to the NYHA classification. The echocardiogram showed a severe impairment of the global and left ventricular function. The left ventricular ejection fraction was reduced to 30% and the Tei index was elevated to 1.0. A specimen taken from a mediastinal tumor confirmed the hypothesis of the recurrence of the sarcoidosis. Myocardial perfusion scintigraphy showed typical lesions for myocardial sarcoidosis. There were signs of an old anteroseptal infarction in the resting ECG without evidence of myocardial ischemia during a stress test. Repeated Holter-ECGs were without signs of severe arrhythmias whereas ventricular late potentials were positive. After the combined therapy with steroids, digitalis and an angiotensin-1 receptor antagonist, mediastinal mass and Tei index were reduced and the ejection fraction moved to 56%. Dyspnoea was classified with Grade II according to the NYHA classification. CONCLUSION: Treatment of asymptomatic sarcoidosis is still controversial, whereas the treatment of life-threatening sarcoidosis, eye involvement or severe hypercalcemia is accepted. This case report presents the successful treatment of severe heart failure with prednisone, glycosides and an angiotensin-1 receptor antagonist. With this combined therapy an improvement of subjective and objective parameters was possible.