The comorbidity and co-medication profile of patients with progressive supranuclear palsy

BackgroundProgressive supranuclear palsy (PSP) is usually diagnosed in elderly. Currently, little is known about comorbidities and the co-medication in these patients.ObjectivesTo explore the pattern of comorbidities and co-medication in PSP patients according to the known different phenotypes and in comparison with patients without neurodegenerative disease.MethodsCross-sectional data of PSP and patients without neurodegenerative diseases (non-ND) were collected from three German multicenter observational studies (DescribePSP, ProPSP and DANCER). The prevalence of comorbidities according to WHO ICD-10 classification and the prevalence of drugs administered according to WHO ATC system were analyzed. Potential drug-drug interactions were evaluated using AiDKlinik (R).ResultsIn total, 335 PSP and 275 non-ND patients were included in this analysis. The prevalence of diseases of the circulatory and the nervous system was higher in PSP at first level of ICD-10. Dorsopathies, diabetes mellitus, other nutritional deficiencies and polyneuropathies were more frequent in PSP at second level of ICD-10. In particular, the summed prevalence of cardiovascular and cerebrovascular diseases was higher in PSP patients. More drugs were administered in the PSP group leading to a greater percentage of patients with polypharmacy. Accordingly, the prevalence of potential drug-drug interactions was higher in PSP patients, especially severe and moderate interactions.ConclusionsPSP patients possess a characteristic profile of comorbidities, particularly diabetes and cardiovascular diseases. The eminent burden of comorbidities and resulting polypharmacy should be carefully considered when treating PSP patients

Objectifying Acupuncture Effects by Lung Function and Numeric Rating Scale in Patients Undergoing Heart Surgery

Rationale. Poststernotomy pain and impaired breathing are common clinical problems in early postoperative care following heart surgery. Insufficiently treated pain increases the risk of pulmonary complications. High-dose opioids are used for pain management, but they may cause side effects such as respiratory depression. Study Design. We performed a prospective, randomized, controlled, observer-blinded, three-armed clinical trial with 100 patients. Group 1 (n=33) and Group 2 (n=34) received one 20 min session of standardized acupuncture treatment with two different sets of acupoints. Group 3 (n=33) served as standard analgesia control without additional intervention. Results. Primary endpoint analysis revealed a statistically significant analgesic effect for both acupuncture treatments. Group 1 showed a mean percentile pain reduction (PPR) of 18% (SD 19, P<0.001). Group 2 yielded a mean PPR of 71% (SD 13, P<0.001). In Group 1, acupuncture resulted in a mean forced vital capacity (FVC) increase of 30 cm3 (SD 73) without statistical significance (P=0.303). In Group 2, posttreatment FVC showed a significant increase of 306 cm3 (SD 215, P<0.001). Conclusion. Acupuncture revealed specific analgesic effects after sternotomy. Objective measurement of poststernotomy pain via lung function test was possible

Altered expression of the Ca2+-binding protein S100A1 in human cardiomyopathy

AbstractThe Ca2+-binding protein S100A1 displays a tissue-specific expression pattern with highest levels in myocardium and has been shown to interact with SR-proteins regulating the Ca2+-induced Ca2+-release. We, therefore, hypothesized that changes in S100A1 gene expression might correlate with the pathognomonic finding of altered SR Ca2+-transients in human end stage heart failure. To test this hypothesis, we established a specific and sensitive method to analyse S100A1 expression in cardiac tissues by employing hydrophobic interaction-chromatography and reversed-phase high performance liquid chromatography (RP-HPLC) coupled with Electron-Ionisation-Mass-Spectrometry (ESI-MS). Porcine myocardium showed a differential expression of S100A1 with relative protein concentrations of 62 ± 8% in the right ventricle (RV), 57 ± 9% in the right atrium (RA), and 25 ± 15% in the left atrium (LA) as compared to the left ventricle (LV) (100 ± 10%; P < 0.001). Northern blot analyses confirmed a likewise distribution of porcine S100A1 mRNA implying a regulation on the transcriptional level. Analyses of left ventricular specimen of patients with end stage heart failure (CHF, n = 6; CHD, n = 6) revealed significantly reduced S100A1 protein levels, while integration of S100A1 peaks after RP-HPLC yielded two groups of patients with < 76% (69 ± 7%, n = 6) and < 35% (23 ± 12%, n = 6) respectively as compared to controls (100 ± 8%, n = 3). These data demonstrate for the first time that S100A1 is differentially expressed in myocardium and that in human cardiomyopathy a reduced expression of S100A1 may contribute to a compromised contractility

Tumor Induced Hepatic Myeloid Derived Suppressor Cells Can Cause Moderate Liver Damage

<div><p>Subcutaneous tumors induce the accumulation of myeloid derived suppressor cells (MDSC) not only in blood and spleens, but also in livers of these animals. Unexpectedly, we observed a moderate increase in serum transaminases in mice with EL4 subcutaneous tumors, which prompted us to study the relationship of hepatic MDSC accumulation and liver injury. MDSC were the predominant immune cell population expanding in livers of all subcutaneous tumor models investigated (RIL175, B16, EL4, CT26 and BNL), while liver injury was only observed in EL4 and B16 tumor-bearing mice. Elimination of hepatic MDSC in EL4 tumor-bearing mice using low dose 5-fluorouracil (5-FU) treatment reversed transaminase elevation and adoptive transfer of hepatic MDSC from B16 tumor-bearing mice caused transaminase elevation indicating a direct MDSC mediated effect. Surprisingly, hepatic MDSC from B16 tumor-bearing mice partially lost their damage-inducing potency when transferred into mice bearing non damage-inducing RIL175 tumors. Furthermore, MDSC expansion and MDSC-mediated liver injury further increased with growing tumor burden and was associated with different cytokines including GM-CSF, VEGF, interleukin-6, CCL2 and KC, depending on the tumor model used. In contrast to previous findings, which have implicated MDSC only in protection from T cell-mediated hepatitis, we show that tumor-induced hepatic MDSC themselves can cause moderate liver damage.</p></div

Cytokine secretion profiles of different tumor models.

<p>Duplicates of tumor-conditioned media (A, N = 4–6 media samples per tumor cell line culture) or serum samples from tumor-bearing mice (B, N = 4–6 serum samples per group) were analyzed for interleukin-6, CCL-2, GM-CSF, M-CSF, KC and VEGF (A) or interleukin-6, CCL-2, KC, VEGF, IFN-γ and interleukin 10 (B). Serum samples from tumor-bearing mice were normalized to serum from naïve wild-type mice. ND  =  not detected. Data are expressed as mean ±SEM. *<i>p</i><0.05, **<i>p</i><0.01, ***<i>p</i><0.001 (by One-way ANOVA).</p

Increased expansion of liver damage-inducing MDSC exacerbates liver damage.

<p>Mice with different size subcutaneous tumors were analyzed for absolute numbers of hepatic MDSC (A and B), M-MDSC or (C), PMN-MDSC (D) and serum ALT levels (B–D). B–D, graphs correlate ALT levels with absolute numbers of MDSC and MDSC subsets. (N = 6–9 mice per tumor, 3 independent experiments). Data are expressed as mean ±SEM. *<i>p</i><0.05, **<i>p</i><0.01 (by two-tailed Student's <i>t</i> test).</p

Melanoma and lymphoma subcutaneous tumor-bearing mice suffer from mild liver damage.

<p>C57BL/6 and BALB/c mice bearing indicated subcutaneous tumors were sacrificed, when tumor diameter reached 15 mm. ALT (A) and AST (B) levels were analyzed in mouse serum (N≥8 mice per tumor, N≥6 naïve mice, 3 independent experiments). Naïve C57BL/6 mice (C, left image) or mice bearing B16 subcutaneous tumors (C, right image) were sacrificed, when tumor diameter reached 20 mm. TUNEL assays were performed on liver specimen (C; scale bar  = 100 µm; N = 2 mice per group, total of 5 TUNEL assays per group) and TUNEL positive cells were counted in 20 non-overlapping visual fields. Means of TUNEL positive cells per liver section were plotted (D). C, Representative examples of visual fields are shown. Data are expressed as mean ±SEM. *<i>p</i><0.05, ***<i>p</i><0.001, ****<i>p</i><0.0001 (by One-way ANOVA).</p

Liver injury depends on the presence of hepatic MDSC with damage-inducing potency.

<p>EL4 tumor-bearing mice were treated with 5-FU or saline. Liver immune cells were analyzed for MDSC and MDSC subsets and mouse serum was analyzed for ALT and AST levels (A) (N = 6 mice per treatment group, 2 independent experiments). B, 5×10⁷ CD11b⁺ cells isolated from livers of indicated untreated subcutaneous tumor-bearing mice were injected intravenously into naïve or RIL175 tumor-bearing recipient mice and ALT and AST serum levels were analyzed 16 h after transfer (N≥6 recipient mice, 2 independent experiments). Data are expressed as mean ±SEM. **<i>p</i><0.01, ***<i>p</i><0.001, ****<i>p</i><0.0001 (A was analyzed by two-tailed Student's <i>t</i> test. B was analyzed by One-way ANOVA).</p

Analysis of hepatic immune cells in mice with subcutaneous tumors.

<p>C57BL/6 naïve mice or mice bearing EL4 or B16 tumors were sacrificed, when tumor diameter reached 15 mm. Hepatic immune cells were analyzed by flow cytometry and frequency and absolute cell number per gram liver were calculated for the myeloid compartment (A) and the lymphoid compartment (B) (N = 5 mice per tumor). C, Frequencies of CD11b⁺Gr-1⁺CD244⁺ cells in livers of naïve mice or mice bearing indicated tumors (N = 3 mice per group). D, Change of frequency of myeloid (including MDSC) and lymphoid cells in naïve vs. EL4 or B16 tumor-bearing mice. E, fold increase of absolute numbers of MDSC (CD11b⁺Gr-1⁺ cells) or non-MDSC (total number of liver leukocytes minus number of CD11b⁺Gr-1⁺ cells) in tumor bearing vs. naïve mice (N = 8 mice per tumor). Data are expressed as mean ±SEM. *<i>p</i><0.05, **<i>p</i><0.01 (C was analyzed by One-way ANOVA. E was analyzed by two-tailed Student's <i>t</i> test).</p