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Articles by S Muller
Total Records ( 5 ) for S Muller
  F Bloos , S Muller , A Harz , M Gugel , D Geil , K Egerland , K Reinhart and G. Marx

Adherence to guidelines to avoid complications associated with mechanical ventilation is often incomplete. The goal of this study was to assess whether staff training in pre-defined interventions (bundle) improves the quality of care in mechanically ventilated patients.


This study was performed on a 50-bed intensive care unit of a tertiary care university hospital. Application of a ventilator bundle consisting of semirecumbent positioning, lung protective ventilation in patients with acute lung injury (ALI), ulcer prophylaxis, and deep vein thrombosis prophylaxis (DVTP) was assessed before and after staff training in post-surgical patients requiring mechanical ventilation for at least 24 h.


A total of 133 patients before and 141 patients after staff training were included. Overall bundle adherence increased from 15 to 33.8% (P<0.001). Semirecumbent position was achieved in 24.9% of patient days before and 46.9% of patient days after staff training (P<0.001). Administration of DVTP increased from 89.5 to 91.5% (P=0.048). Ulcer prophylaxis of >90% was achieved in both groups. Median tidal volume in patients with ALI remained unaltered. Days on mechanical ventilation were reduced from 6 (interquartile range 2.0–15.0) to 4 (2.0–9.0) (P=0.017). Rate of ventilator-associated pneumonia (VAP), ICU length of stay, and ICU mortality remained unaffected. In patients with VAP, the median ICU length of stay was reduced by 9 days (P=0.04).


Staff training by an ICU change team improved compliance to a pre-defined ventilator bundle. This led to a reduction in the days spent on mechanical ventilation, despite incomplete bundle implementation.

  C. S Clemen , K Tangavelou , K. H Strucksberg , S Just , L Gaertner , H Regus Leidig , M Stumpf , J Reimann , R Coras , R. O Morgan , M. P Fernandez , A Hofmann , S Muller , B Schoser , F. G Hanisch , W Rottbauer , I Blumcke , S von Horsten , L Eichinger and R. Schroder

Mutations of the human valosin-containing protein gene cause autosomal-dominant inclusion body myopathy associated with Paget disease of bone and frontotemporal dementia. We identified strumpellin as a novel valosin-containing protein binding partner. Strumpellin mutations have been shown to cause hereditary spastic paraplegia. We demonstrate that strumpellin is a ubiquitously expressed protein present in cytosolic and endoplasmic reticulum cell fractions. Overexpression or ablation of wild-type strumpellin caused significantly reduced wound closure velocities in wound healing assays, whereas overexpression of the disease-causing strumpellin N471D mutant showed no functional effect. Strumpellin knockdown experiments in human neuroblastoma cells resulted in a dramatic reduction of axonal outgrowth. Knockdown studies in zebrafish revealed severe cardiac contractile dysfunction, tail curvature and impaired motility. The latter phenotype is due to a loss of central and peripheral motoneuron formation. These data imply a strumpellin loss-of-function pathogenesis in hereditary spastic paraplegia. In the human central nervous system strumpellin shows a presynaptic localization. We further identified strumpellin in pathological protein aggregates in inclusion body myopathy associated with Paget disease of bone and frontotemporal dementia, various myofibrillar myopathies and in cortical neurons of a Huntington’s disease mouse model. Beyond hereditary spastic paraplegia, our findings imply that mutant forms of strumpellin and valosin-containing protein may have a concerted pathogenic role in various protein aggregate diseases.

  N. F Saba , M Choi , S Muller , H. J. C Shin , M Tighiouart , V. A Papadimitrakopoulou , A. K El Naggar , F. R Khuri , Z. G Chen and D. M. Shin

Inhibition of cyclooxygenase-2 (COX-2) pathways may have significant implications for the prevention and treatment of head and neck squamous cell carcinoma (HNSCC). COX-2 is overexpressed in both premalignant lesions and invasive HNSCC. We examined COX-2 expression by immunohistochemistry in normal tissues, different stages of premalignant lesions, and carcinoma in situ (CIS). We also evaluated the correlation between COX-2 expression and clinical characteristics of HNSCC patients. Tissue specimens were obtained from the following: premalignant lesions from 25 subjects enrolled in a biochemoprevention trial, tumor samples collected at diagnosis from 38 HNSCC patients enrolled in an induction chemotherapy trial, and normal control tissues from 10 noncancer, nonsmoking subjects. COX-2 was expressed in early and intermediate stages of premalignant lesions, increasing first in the basal and parabasal layers, then lower spinous, and upper spinous layers. This correlation was noted in normal epithelium (P < 0.0001), histologically normal in-field samples (P < 0.0001), low-grade dysplasia (P = 0.024), and moderate-grade dysplasia (P = 0.009), but was lost in the majority of high-grade dysplasia/CIS (P = 0.896). COX-2 expression was also noted to increase progressively through the early stages of premalignancy, and to decrease in severe/CIS stage and invasive carcinoma. COX-2 expression in tumors from patients treated with induction chemotherapy was correlated with overall survival after controlling for clinical variables. These findings elucidate the differential expression pattern of COX-2 in stages of head and neck premalignant lesions and invasive carcinoma, supporting the rationale for COX-2 inhibition as an important strategy for cancer chemoprevention. Further validation of COX-2 expression is needed in prospective ongoing chemoprevention trials.

  S Muller , O. J How , O Jakobsen , S. E Hermansen , A Rosner , T. A Stenberg and T. Myrmel

Background— We addressed the hypothesis that the inotropic drugs dobutamine and levosimendan both induce surplus oxygen consumption (oxygen wasting) relative to their contractile effect in equipotent therapeutic doses, with levosimendan being energetically more efficient.

Methods and Results— Postischemically reduced left ventricular function (stunning) was created by repetitive left coronary occlusions in 22 pigs. This contractile dysfunction was reversed by infusion of either levosimendan (24 µg/kg loading and 0.04 µg · kg–1 · min–1 infusion) or an equipotent dose of dobutamine (1.25 µg · kg–1 · min–1). Contractility and cardiac output were normalized by both drug regimens. The energy cost of drug-induced contractility enhancement was assessed by myocardial oxygen consumption related to the mechanical indexes tension-time index, pressure-volume area, and total mechanical energy. ANCOVA did not reveal any increased oxygen cost of contractility for either drug in these doses. However, both dobutamine and levosimendan at supratherapeutic levels (10 µg · kg–1 · min–1 and 48 µg/kg loading with 0.2 µg · kg–1 · min–1 infusion, respectively) induced a highly significant increase in oxygen consumption related to mechanical work, compatible with the established oxygen-wasting effect of inotropy (P<0.001 for all mechanical indexes with dobutamine; P=0.007 for levosimendan as assessed by pressure-volume area).

Conclusion— Therapeutic levels of neither dobutamine nor levosimendan showed inotropic oxygen wasting in this in vivo pig model. Thus, relevant hemodynamic responses can be achieved with an adrenergic inotrope without surplus oxygen consumption.

  J Barber , S Muller , T Whitehurst and E. Hay

Background. Epidemiological surveys often rely on self-report as a measure of morbidity in a population. However, these data can also be extracted from primary care records.

Objective. To compare morbidity estimates based on self-report with those obtained from primary care records.

Methods. A cross-sectional survey and accompanying medical record review were carried out in all consenting adults aged ≥50 years in three general practices in North Staffordshire, UK. Self-reported morbidity was compared with computerized general practice consultation records for the 2 years prior to the survey.

Results. Of the 7878 survey responders, 5889 consented to medical record review. Agreement between self-reported and consultation data was excellent for diabetes. Agreement between the two sources of data was lower for hypertension, heart problems, chest problems and eyesight problems. It was poor for deafness and falls.

Conclusions. Self-report and consultation data provide comparable estimates of the prevalence of specific diagnoses such as diabetes. For other conditions, self-report and consultation records provide different measures of prevalence, and the choice of measure will depend on the morbidity being studied.

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