Liver Injury after Selective Androgen Receptor Modulator Intake: A Case Report and Review of the Literature.

Liver injury associated with selective androgen receptor modulators (SARMs) is an issue that has not been reported often. We report a case of a previously healthy 24-year-old male, who was referred to our hospital for severe jaundice with intense pruritus. He had previously taken the SARM Enobosarm (also known as Ostarine) for muscle-building purposes. Blood serum levels of total bilirubin exceeded 30 mg/dL with only a slight elevation of liver enzymes. Liver biopsy revealed isolated hepatocellular cholestasis (bland cholestasis) with limited inflammation or necrosis. Supportive treatment was begun in our hospital with molecular adsorbent recirculation system (MARS) albumin dialysis, as well as cholestyramine for pruritus relief. During therapy, bilirubin levels and symptoms regressed, and after five sessions of dialysis, the patient could be released from our clinic in a markedly improved clinical and laboratory condition. However, bilirubin parameters regressed slowly after this, reaching normal levels as late as six months after first intake of the compound. Exome-based genetic testing brought about no pathogenic variants for cholestatic liver disease in our patient. Nevertheless, three common heterozygous polymorphisms associated with an increased risk for intrahepatic cholestasis could be identified. Our case demonstrates that SARMs can cause severe liver injuries not prominently mentioned in safety data sheets. Therefore, these compounds constitute a potential danger to the user's health. This holds especially true when taking SARMs without supervision by a medical professional, which should consist of a thorough monitoring of liver enzyme and bilirubin levels.

MRI-Based Liver Iron Content Determination at 3T in Regularly Transfused Patients by Signal Intensity Ratio Using an Alternative Analysis Approach Based on R2* Theory.

OBJECTIVES: To evaluate the feasibility of addressing liver iron content (LIC) in regularly transfused patients by MR imaging at 3 T based on the signal intensity ratio (SIR). An innovative data analysis approach was developed for this purpose. METHODS: 47 consecutive examinations of regularly transfused patients were included. In all cases, we expected high LIC levels. Patients were scanned with MRI at 3 T with multi-echo gradient echo sequences (GRE) at four different flip angles between 20° and 90° with echo times (TE) ranging from 0.9 to 9.8 ms. Spin-echo protocols were acquired to determine the LIC with a reference MRI method working at 1.5 T. 3 T GRE data were analyzed using the liver-to-muscle SIR. Since the method known for 1.5 T was not expected to be applicable for analyzing 3 T data, theoretic dependence of the SIR on the LIC was derived from the equation describing R2* signal decay. Obtained SIR values were correlated to reference LIC to get a relation for calculating LIC from SIR quantities. LIC values and their uncertainties were determined from GRE data and correlated to LIC reference values. For two LIC thresholds, the diagnostic accuracy was determined. RESULTS: LIC was reliably determined from SIR in our patient cohort even for large LIC values. Median of LIC uncertainties was 10 %, and the diagnostic accuracy was 0.92 and 0.91, respectively. CONCLUSION: Determination of even high LIC, resulting in small SIR values, is feasible at 3 T using appropriate SIR analysis. KEY POINTS: • Determination of Liver Iron Concentration (LIC) based on GRE MRI at 3T is feasible even for high LIC levels using Signal Intensiy Ratios. • Relative uncertainty of LIC determined with 3T GRE MRI was below 13 % in most cases. • The patient-management relevant threshold (LIC = 80 µmol/g (4.5 mg/g)) yielded an accuracy of .92 in our cohort. • The proposed method is quick and simple, both in terms of data acquisition and analysis. Citation Format: • Wunderlich AP, Cario H, Bommer M et al. MRI-Based Liver Iron Content Determination at 3T in Regularly Transfused Patients by Signal Intensity Ratio Using an Alternative Analysis Approach Based on R2* Theory. Fortschr Röntgenstr 2016; 188: 846 - 852.

[Value of fine needle aspiration cytology and core needle biopsy in the head and neck region]. / Stellenwert der Feinnadelaspirationszytologie und Stanzbiopsie im Kopf-Hals-Bereich.

BACKGROUND: Fine-needle aspiration cytology (FNAC) and core-needle biopsy (CNB) represent 2 minimal invasive methods for further assessment of suspect lesions of the head and neck area. However, only limited data on the direct comparison of both methods has been published. The aim of this retrospective study was to evaluate the diagnostic value of FNAC and CNB and to compare their sensitivity and specificity. MATERIAL AND METHODS: Between 2005 and 2012, CNB was performed in 86 patients and FNAC in 408 patients. 52 of 86 CNB-patients and 224 of 408 FNAC-patients underwent surgery afterwards and were included into the study (n=276). In order to compare the results of both methods the corresponding final histopathological finding from surgery was considered. RESULTS: The sensitivity of the FNAC-group was higher (85%) compared to the CNB-group (80%), the specificity (87 vs. 94%) as well as the positive predictive value (64 vs. 97%) was lower. The negative predictive value (92 vs. 71%) and also the false negative value of the FNAC (5 vs. 13%) were superior to the results of the CNB-group. Concerning the false positive value the CNB-group showed better results (2 vs. 15%). CONCLUSION: Both methods are well suited to clarify the dignity of lesions in the head and neck region. In the current case series, FNAC seemed particularly suitable for diagnosis of hematologic diseases and the exclusion of malignancy in suspicious lymph nodes. The GNP has proven to be valid in the detection of tumor recurrences in irradiated or previously operated tissue, furthermore the definitive oncological treatment can be planed, based on the histopathological results obtained by GNP.

[Pronounced pancytopenia with concomitant jaundice in a 66-year-old woman]. / Ausgeprägte Trizytopenie mit Ikterus bei einer 66-jährigen Patientin.

HISTORY AND ADMISSION FINDINGS: A previously healthy 66-year-old women presented with onset of general weakness, shortness of breath and significant weight loss. Due to appearance of jaundice, biliary obstruction had been ruled out by a CAT scan previous to the patients presentation in our practice. INVESTIGATIONS: The laboratory tests already arranged by the patients general practitioner showed a pronounced pancytopenia with megaloblastic anemia and hyperbilirubinemia. The bone marrow aspiration revealed a hypercellular bone marrow with megaloblastic erythropoiesis. The diagnosis of pernicious anemia was confirmed by the low cobalamin (vitamin B12) serum level and the presence of atrophic gastritis. TREATMENT: Pernicious anemia was treated with intramuscular injection of Cyanocobalamin (1000 µg) which resulted in an immediate reticulocytosis and a widely normalized blood cell count and bilirubin level four weeks after initiation of treatment. CONCLUSION: The differential diagnosis of megaloblastic anemia covers a wide spectrum of diseases with different etiology. This case report demonstrates an example of a pernicious anemia with atypical and foudroyant clinical course.

Is domestic tap water a risk for infections in neutropenic patients?

BACKGROUND: Home care has become popular in the management of hemato-oncologic patients. Therefore, we conducted a prospective study to assess whether tap water from the domestic environment of neutropenic patients poses a risk for infections from the waterborne pathogens nontuberculous mycobacteria (NTM), Legionella spp., and Pseudomonas aeruginosa. MATERIALS AND METHODS: Tap water samples were taken in the homes of 65 hemato-oncologic patients who were discharged from the hospital whilst neutropenic and had a suspected period of neutropenia of a minimum of 10 days. Selective culture for Legionella, P. aeruginosa, and NTM was performed. Patients who required hospital readmission were monitored for infection with the aforementioned pathogens over the following 3 months. RESULTS: NTM were cultured in 62 (95.4%) households in concentrations from 1 to 1,000 CFU/500 ml. The facultative pathogenic species Mycobacterium chelonae (58.5% of taps) and M. mucogenicum (38.5% of taps) were most frequently detected. Legionella spp. was cultured from six households (9.2%), including five households with L. pneumophila in concentrations from 25 to 2,500 CFU/500 ml. P. aeruginosa was found in seven households (10.8%) in concentrations from 5 to 2,500 CFU/500 ml. While clinical infection with Legionella spp. was not detected in any patients, infection with M. chelonae and P. aeruginosa occurred in one and seven patients, respectively. However, transmission from household water could not be confirmed. CONCLUSION: Although the risk of infection from household water-borne pathogens appears low, preventive measures may be considered on an individual basis in patients with long-term immunosuppression as well as in patients with long-term central-vascular catheterization.

Prevalence and risk factors of focal sparing in hepatic steatosis.

PURPOSE: The prevalence, localization and potential risk factors for focal sparing were prospectively assessed in subjects with sonographically detectable hepatic steatosis as part of a population-based cross-sectional study. MATERIALS AND METHODS: A total of 1,624 persons (n = 906 women; n = 718 men) were evaluated using ultrasonography, laboratory testing and a standardized questionnaire. The following were excluded from the analysis: subjects with reported alcohol consumption > 40 g/day (males) or > 20 g/day (females), those with known chronic hepatitis B or C infection, elevated serum transaminases (AST: m > 44 U/l, f > 33 U/l; ALT: m > 45 U/l, f > 35 U/l) and prior right nephrectomy. RESULTS: The prevalence of focal sparing in patients with hepatic steatosis (grade I) was 25.6 % for men and 13.0 % for women. In patients with grade II/III disease, the prevalence was 70.9 % for men and 77.6 % for women. The most common site of focal sparing was in segment IV. The average diameter was 22.3 mm (range 7 - 84 mm). No correlation was found for postulated risk "age" (p = 0.09) or "status post cholecystectomy" (p = 0.09). Male sex (p = 0.02) and metabolic syndrome (odds ratio, 2.1; 95 % confidence interval, 1.1 - 4.1; p = 0.02) were confirmed as risk factors. CONCLUSION: Sonographic evidence of focal sparing in subjects with hepatic steatosis is associated with an increased risk for metabolic syndrome and may be an easily obtained diagnostic criterion in routine clinical settings.

[Supportive therapy of urogenital tumors: diagnostic and therapy of common complications]. / Supportivtherapie bei Urogenitaltumoren : Diagnostik und Therapie häufiger Komplikationen.

Within the framework of systemic therapy with cytostatic agents and advanced stages of tumor diseases, therapy-induced and disease-related complications can severely impair the quality of life. This article gives a brief synopsis of the current literature on the diagnosis and therapy concerning anemia thrombotic events and tumor-related hypercalcemia as well as recommendations on treating therapy-associated neutropenia.

CMV monitoring using blood cells and plasma: a comparison of apples with oranges?

Quantitative cytomegalovirus (CMV) monitoring is still far from being standardized between transplant centers. In the present study, we compared assays for quantitative CMV monitoring using blood cells and plasma. Four hundred and thirty-five consecutive samples from 29 patients with active CMV infection after allogeneic T-cell-depleted hemopoietic stem cell transplantation were tested in parallel using pp65 antigenemia and quantitative CMV polymerase chain reaction (PCR) in blood cells and plasma (COBAS AMPLICOR CMV MONITOR). Although only 142 (53.1%) of 253 positive samples were concordantly identified by all three assays, the number of positive samples detected by each assay was not different and the quantitative values were correlated, provided that nucleic acid (NA) in plasma was isolated by COBAS AmpliPrep and not by the manual protocol. Six (18%) of 34 episodes with active CMV infection were not detected using CMV PCR in plasma; whereas in times of white blood cell aplasia or blast crisis of leukemia, samples with active CMV infection in plasma could not be detected using blood cells. We conclude that CMV monitoring in whole blood could be favorable compared with assays using plasma or blood cells alone. Automated NA isolation could become an attractive tool for a more sensitive and better standardized molecular diagnostics.

Moxifloxacin prophylaxis in neutropenic patients.

OBJECTIVES: Recent studies have shown a beneficial impact of fluoroquinolones on infection-related morbidity and mortality for patients with haematological malignancies during neutropenia. Among the fluoroquinolones moxifloxacin currently provides one of the broadest spectra of antibacterial activity and may be suitable for prophylaxis during neutropenia. PATIENTS AND METHODS: In this controlled before and after observational study, moxifloxacin chemoprophylaxis was used during prolonged neutropenia in haemato-oncological patients (period 2; 282 episodes). Data were compared with two periods with levofloxacin prophylaxis, one preceding period (period 1; 399 episodes) and a post-observational period (period 3; 53 episodes). Endpoints for evaluation were the rates of Gram-negative and Gram-positive bacteraemia and infection-related mortality. RESULTS: We found similar survival rates as compared with levofloxacin. The rate of Gram-negative bacteraemia was higher during prophylaxis with moxifloxacin (11%) when compared with levofloxacin (6% for period 1 and 6% for period 3). In addition we observed a marked increase in diarrhoea associated with Clostridium difficile toxin A (CDAD) after a formula change from levofloxacin to moxifloxacin (attack rate 6% versus 33%). A decrease was attained after changing back to levofloxacin and reinforcing hygienic measures (13%). CONCLUSIONS: During moxifloxacin prophylaxis, we observed a significantly increased incidence of Gram-negative bacteraemia and CDAD. Careful attention must be paid not to trade the particularly beneficial effects of fluoroquinolones in the neutropenic setting for such disadvantageous effects. Until further data are obtained, caution is warranted when applying fluoroquinolones with high anaerobic activity in the neutropenic setting.

KOC is a novel molecular indicator of malignancy.

The detection of malignant cells in fine-needle aspirates (FNA's) using marker genes is hampered by the fact that these markers are only expressed by certain malignancies or lack sensitivity and/or specificity. Here we report the results of a prospective pilot study examining the expression of KOC (KH-domain containing protein over expressed in cancer), a novel onco-foetal gene, in 76 patients who underwent fine-needle aspiration for further diagnosis of abdominal lesions, aszites, cysts or cerebrospinal fluid. Aspirates were examined by cytology and by a KOC RT-PCR assay. KOC expression was a highly sensitive and specific indicator of malignancy. The KOC assay could be useful to facilitate screening for malignant disease and to improve the diagnostic accuracy of FNAs.

Initial results in the assessment of multiple myeloma using 18F-FDG PET.

This prospective study was undertaken to investigate the appearance of multiple myeloma on fluorine-18 fluorodeoxyglucose positron emission tomography (FDG-PET). Furthermore, the accuracy of FDG-PET in detecting myeloma lesions and its influence on patient management were evaluated. Forty-three patients with known multiple myeloma (n=28) or solitary plasmacytoma (n=15) underwent FDG-PET. The results of routinely performed radiographs and of scans obtained using all available imaging modalities (MRI, CT), as well as the clinical course, were used for verification of detected lesions. Focally increased tracer uptake was observed in 38 of 41 known osteolytic bone lesions (sensitivity 92.7%) in 23 patients. In addition, 71 further bone lesions which were negative on radiographs were detected in 14 patients. Twenty-six (36.6%) of these lesions could be confirmed in ten patients. As a result of FDG-PET imaging, clinical management was influenced in five (14.0%) patients. The positive predictive value for active disease was 100% in patients with focal or mixed focal/diffuse skeletal FDG uptake and 75% in patients with diffuse bone marrow uptake. Depending on the interpretation of the PET scans in patients with diffuse bone marrow uptake, the sensitivity ranged from 83.8% to 91.9% and the specificity from 83.3% to 100%. FDG-PET thus proved highly accurate in detecting multiple myeloma, and revealed a greater extent of disease than routine radiographs in 14 of 23 (60.9%) patients who had osteolytic bone lesions. FDG-PET might contribute to the initial staging of solitary plasmacytoma.

Psychopathological and neuropsychological symptoms in patients with subclinical and remitted hyperthyroidism.

To investigate relationships between hyperthyroidism and behavior, 45 formerly hyperthyroid patients (now euthyroid) and 51 control subjects were investigated by (a) a semi-structured psychiatric examination, (b) self-rating scales to assess mood states and personality, and (c) neuropsychological tests. Patients with "subclinical" or "remitted" hyperthyroidism showed more abnormalities than the controls in all dimensions investigated. Forty-three percent of patients (10% of controls) complained of "seriously reduced" well-being with feelings of fear, hostility, and inability to concentrate. While a fearful-agitated syndrome dominated in the initial phase of the illness, a mainly depressive syndrome was characteristic after a longer period of remission. More than 25% of the patients (2% of controls) showed "markedly impaired" neuropsychological functioning. Patients with a relapse within 2.5 years exhibited the most abnormal results. Even after a longer period of hormonal remission, there was no complete psychopathological and neuropsychological normalization. A thorough follow-up of hyperthyroid patients is recommended.

In vivo modulation of rat hypothalamic opioid peptide content by intracerebroventricular injection of guanidinoethylmercaptosuccinic acid (GEMSA): possible physiological role of enkephalin convertase.

Twice-daily intracerebroventricular (i.c.v.) injections for three days of increasing doses of guanidino-ethyl-mercapto-succinic acid (GEMSA) produced a dose-dependent decrease in methionine-enkephalin- and leucine-enkephalin levels in rat hypothalami. GEMSA is a specific and potent inhibitor of a carboxypeptidase B-like processing enzyme, referred to as enkephalin convertase (EC). The administration of GEMSA (0.1 microgram) resulted in more than 50% reduction in the levels of these two opioid peptides. However, no changes occurred in the hypothalamic content of beta-endorphin or dynorphin1-17. Moreover, in GEMSA-treated animals, hypothalamic luteinizing hormone-releasing hormone and serum luteinizing hormone levels were increased by 75%. Serum prolactin concentrations were decreased by 60% at the same time. Subcutaneous naloxone administration resulted in a 75% elevation of serum LH concentrations in control animals whereas GEMSA-treated animals showed a blunted response, most likely due to a decreased amount of opioid-active peptides. The present study is in agreement with the putative role of EC in the processing of the multivalent opioid precursor (proenkephalin A) in the rat hypothalamus. The enzyme inhibition by GEMSA may result in a reduced enkephalinergic tone, which is then accompanied by an altered endocrine status.

Neuropeptides and other secretagogues in bovine chromaffin cells: their effect on opioid peptide metabolism.

Bovine adrenal medullary cells released significant amounts of opioid pentapeptides (Methionine- and Leucine-enkephalin), when stimulated with neuropeptides like angiotensin II (AT), bradykinin (BK) or neurotensin (NT). Dose-response curves for angiotensin II and bradykinin were shown to be double-sigmoidal, with the first EC50 in the nM range; much lower than that for acetylcholine, nicotine or histamine. Secretory effects were dependent on extracellular CA++ and impaired by the Ca++ channel blockers D600. Moreover, these peptides produced an increase in opioid peptide cell content after 48 h of incubation, as did nicotine-, histamine- and K+ treated cells. The compound's capacity to induce long-term Met-enk secretion was similar to their efficacy in raising intracellular opioid peptide levels, suggesting compensatory increases. Besides affecting opioid peptide metabolism, AT, BK and NT produced a significant accumulation of inositol-1-phosphates (IP1), the role of which remains to be clarified. The physiological significance of vasoactive compounds in the adrenal medulla will be discussed.

H1-histaminergic activation of catecholamine release by chromaffin cells.

Bovine adrenal medullary chromaffin cells, prelabeled with [3H]norepinephrine, released a large proportion of cellular 3H-labeled catecholamines (CAs) when stimulated with nicotine, K+, histamine, gamma-aminobutyric acid (GABA) and several peptidic hormones [bradykinin, angiotensin II, thyrotropin releasing hormone (TRH) and neurotensin]. The histamine-induced response was dose dependent and occurred through H1 histaminergic receptors. Quantitatively and temporally the histamine- and nicotine-induced responses differed. Nicotine, during the first minutes, induced a large increase of [3H]CAs, but this response was desensitized rapidly. In contrast, histamine initially provoked a smaller release of [3H]CAs than nicotine but, with prolonged exposure (hours), a much greater response was found with histamine. Moreover, little desensitization was observed with histamine even during extended stimulation. External Ca2+ was obligatory for the histamine response, and both inorganic (Co2+ and Ni2+) and organic (verapamil, nifedipine and D-600) Ca2+ channel blockers significantly reduced release of [3H]CAs. These studies suggest that histamine as well as certain other neuroactive substances could play an important role in the physiology and biochemistry of adrenal medullary chromaffin cells.

Inhibition of nicotine-induced secretion from bovine chromaffin cells by the amidated C-terminal sequence of the opioid peptide amidorphin.

The nicotine-induced release of catecholamines and opioid peptides from bovine chromaffin cells is inhibited by the amidated opioid peptide amidorphin. The active site of this inhibitory activity is located at the peptide's C-Terminus, which is, in contrast to the N-terminal sequence TYR-GLY-GLY-PHE, not responsible for the opioidergic activity of opioid peptides. The noradrenaline-secretion induced by histamine, a non-cholinergic secretagogue, has not been inhibited by amidorphin.