Antonia Zapf

Onset and spreading patterns of upper and lower motor neuron symptoms in amyotrophic lateral sclerosis.

The potential linkage between upper (UMN) and lower motor neuron (LMN) involvement in amyotrophic lateral sclerosis (ALS) has not yet been fully elucidated. There is ongoing discussion as to whether ALS is primarily a disease of UMNs or LMNs.

Weight loss, dysphagia and supplement intake in patients with amyotrophic lateral sclerosis (ALS): impact on quality of life and therapeutic options

BackgroundWeight loss is a frequent feature in the motor neuron disease Amyotrophic lateral sclerosis (ALS). In this study we investigated possible causes of weight loss in ALS, its impact on mood/quality of life (QOL) and the benefit of high calorie nutritional/other dietary supplements and percutaneous endoscopic gastrostomy (PEG).Methods121 ALS patients were interviewed and answered standardized questionnaires (Beck depression inventory - II, SF36 Health Survey questionnaire, revised ALS functional rating scale). Two years after the initial survey we performed a follow-up interview.ResultsIn our ALS-cohort, 56.3% of the patients suffered from weight loss. Weight loss had a negative impact on QOL and was associated with a shorter survival. Patients who took high calorie nutritional supplements respectively had a PEG stated a great benefit regarding weight stabilization and/or QOL.38.2% of our patients had significant weight loss without suffering from dysphagia. To clarify the reasons for weight loss in these patients, we compared them with patients without weight loss. The two groups did not differ regarding severity of disease, depression, frontotemporal dementia or fasciculations, but patients with weight loss declared more often increased respiratory work.ConclusionsWeight loss is a serious issue in ALS and cannot always be attributed to dysphagia. Symptomatic treatment of weight loss (high calorie nutritional supplements and/ or PEG) should be offered more frequently.

Comparison of ultrasonic irrigation and RinsEndo for the removal of calcium hydroxide and Ledermix paste from root canals

AIMnTo compare the efficacy of ultrasonic irrigation and RinsEndo in removing calcium hydroxide and Ledermix paste from simulated root canal irregularities.nnnMETHODOLOGYnThe root canals of sixty extracted single-rooted teeth were prepared using FlexMaster rotary instruments to size 60, 0.02 taper. The roots were split longitudinally, and a standardized groove was prepared in the apical part of one segment. The teeth were randomly allocated into two groups (n = 30), according to the intracanal dressing. In the first group, grooves were filled with calcium hydroxide paste (Calxyl), whereas the grooves in the second group were filled with Ledermix paste. After reassembly, the root canals were completely filled with the respective medicament using a lentulo. The removal of medicament dressing was performed after 7 days with either passive ultrasonic irrigation or RinsEndo and 1% sodium hypochlorite for 3 min. The amount of remaining medicament was evaluated under a microscope with 30 × magnification using a four-grade scoring system. A regression analysis with P ≤ 0.05 was performed.nnnRESULTSnLedermix paste removal was significantly more effective than the removal of calcium hydroxide (P < 0.0001), whereas irrigation technique was not a significant factor (P = 0.3712). The percentages of complete removal of calcium hydroxide and Ledermix paste were 11.7% and 51.7%, respectively.nnnCONCLUSIONSnNone of the irrigation techniques was able to completely remove the intracanal medicaments from the apical part of the root canal. Irrespective of the irrigation technique, significantly less Ledermix paste was detected compared with calcium hydroxide.

Speech therapy and communication device: Impact on quality of life and mood in patients with amyotrophic lateral sclerosis

Dysarthria has a drastic impact on the quality of life of ALS patients. Most patients suffering from dysarthria are offered speech therapy. Communication devices are prescribed less frequently. In the present study we investigated the impact of these therapeutic arrangements on quality of life in ALS patients. Thirty-eight ALS patients with dysarthria or anarthria, who underwent speech therapy and/or used communication devices answered three standardized questionnaires (Beck Depression Inventory - II (BDI), SF-36 Health Survey questionnaire (SF-36) and ALS Functional Rating Scale-revised (ALSFRS-R)) and were further interviewed about their experience with and benefit of speech therapy and communication devices. Most of the patients described a high impact of the communication device on their quality of life while the influence of speech therapy was rated less. By multiple regression analysis we confirmed an independent positive effect of communication device use on depression and psychological distress. In conclusion, communication systems improve or at least stabilize quality of life and mood in dysarthric ALS patients, and should be provided early in the disease course.

Interaction of physical function, quality of life and depression in Amyotrophic lateral sclerosis: characterization of a large patient cohort

BackgroundDue to lack of any curative therapy for ALS, symptomatic treatment and maintenance of quality of life (QoL) is very important. We aimed to characterize the affected domains of QoL in ALS patients and to identify factors which are associated with reduced QoL and increased depression.Methods159 ALS patients answered standardized questionnaires (Beck Depression Inventory-II, SF-36 Health Survey questionnaire, revised ALS functional rating scale). Multiple regression analysis was used to identify correlations between clinical features of ALS patients and depression/QoL scores. In addition, QoL data from ALS patients were compared to age-matched reference values representing the German normal population.ResultsQoL of ALS patients was reduced in nearly all SF-36-categories. Progression of physical impairment was positively correlated with depression but reduced QoL scores only in items directly related to physical function. However, QoL was considerably influenced by depression, independently from physical impairment. Regarding distinct patient characteristics one of the most interesting findings was that increasing age was correlated with significantly worse QoL results regarding social functioning.ConclusionsDepressive symptoms had a strong influence on QoL, hence their detection and treatment is of particular importance. Different domains of QoL are differently affected in subgroups of ALS patients. Being aware of these differences can be valuable for both ALS professional and family caregivers and physicians.

Efficacy and Safety of an Everolimus- vs. a Mycophenolate Mofetil-Based Regimen in Pediatric Renal Transplant Recipients.

Introduction Data on the efficacy and safety of everolimus in pediatric renal transplantation compared to other immunosuppressive regimens are scarce. Patients/Methods We therefore performed a multicenter, observational, matched cohort study over 4 years post-transplant in 35 patients on everolimus plus low-dose cyclosporine, who were matched (1:2) with a control group of 70 children receiving a standard-dose calcineurin-inhibitor- and mycophenolate mofetil-based regimen. Results Corticosteroids were withdrawn in 83% in the everolimus vs. 39% in the control group (p<0.001). Patient and graft survival were comparable. The rate of biopsy-proven acute rejection episodes Banff score ≥ IA during the first year post-transplant was 6% in the everolimus vs. 13% in the control group (p = 0.23). The rate of de novo donor-specific HLA antibodies (11% in everolimus, 18% in controls) was comparable (p = 0.55). At 4 years post-transplant, mean eGFR in the everolimus group was 56±33 ml/min per 1.73 m² vs. 63±22 ml/min per 1.73 m² in the control group (p = 0.14). Everolimus therapy was associated with less BK polyomavirus replication (3% vs. 17% in controls; p = 0.04), but with a higher percentage of arterial hypertension and more hyperlipidemia (p<0.001). Conclusion In pediatric renal transplantation, an everolimus-based regimen with low-dose cyclosporine yields comparable four year results as a standard regimen, but with a different side effect profile.

In hypertrophic cardiomyopathy reduction of relative resting myocardial blood flow is related to late enhancement, T2-signal and LV wall thickness

Objectives To quantify resting myocardial blood flow (MBF) in the left ventricular (LV) wall of HCM patients and to determine the relationship to important parameters of disease: LV wall thickness, late gadolinium enhancement (LGE), T2-signal abnormalities (dark and bright signal), LV outflow tract obstruction and age. Materials and Methods Seventy patients with proven HCM underwent cardiac MRI. Absolute and relative resting MBF were calculated from cardiac perfusion MRI by using the Fermi function model. The relationship between relative MBF and LV wall thickness, T2-signal abnormalities (T2 dark and T2 bright signal), LGE, age and LV outflow gradient as determined by echocardiography was determined using simple and multiple linear regression analysis. Categories of reduced and elevated perfusion in relation to non- or mildly affected reference segments were defined, and T2-signal characteristics and extent as well as pattern of LGE were examined. Statistical testing included linear and logistic regression analysis, unpaired t-test, odds ratios, and Fisher’s exact test. Results 804 segments in 70 patients were included in the analysis. In a simple linear regression model LV wall thickness (p<0.001), extent of LGE (p<0.001), presence of edema, defined as focal T2 bright signal (p<0.001), T2 dark signal (p<0.001) and age (pu200a=u200a0.032) correlated inversely with relative resting MBF. The LV outflow gradient did not show any effect on resting perfusion (pu200a=u200a0.901). Multiple linear regression analysis revealed that LGE (p<0.001), edema (pu200a=u200a0.026) and T2 dark signal (pu200a=u200a0.019) were independent predictors of relative resting MBF. Segments with reduced resting perfusion demonstrated different LGE patterns compared to segments with elevated resting perfusion. Conclusion In HCM resting MBF is significantly reduced depending on LV wall thickness, extent of LGE, focal T2 signal abnormalities and age. Furthermore, different patterns of perfusion in HCM patients have been defined, which may represent different stages of disease.

Myeloid growth factors in acute myeloid leukemia: systematic review of randomized controlled trials

Randomized controlled trials (RCT) investigating administration of colony-stimulating factors (CSF) during or after chemotherapy in acute myeloid leukemia (AML) patients have not been systematically reviewed. We performed a meta-analysis of all reported RCTs comparing prophylactic or concurrent use of CSFs in adult AML patients. Two reviewers extracted data independently. Summary estimates with 95% confidence intervals (CIs) were calculated using a fixed effects model. Fourteen RCTs (nu2009=u20094,069 patients) were identified investigating prophylactic CSF administration. Time to neutrophil recovery (>500/μl) was significantly reduced in the CSF group (−4.13xa0days; 95% CI, −4.23 to −4.04) as was the length of hospitalization (−2.06 days; 95% CI, −2.36 to −1.76). However, no significant reduction in infection-related mortality was observed in CSF-treated compared with control patients (odds ratio (OR) 0.94; 95% CI, 0.8 to 1.1). Prophylactic CSF administration did not impact complete remission (CR) rate or survival. Fourteen RCTs (nu2009=u20094,518 patients) were identified investigating administration of CSFs during chemotherapy. Summary estimates of CR, disease/event-free, or overall survival were not significantly different for CSF versus control patients. Prophylactic CSF administration reduces the time to neutrophil recovery and length of hospitalization, but has no impact on documented infections or outcome. Economic analyses of prophylactic CSF administration in AML patients are warranted.

Difference of two dependent sensitivities and specificities: Comparison of various approaches.

In diagnostic studies, a new diagnostic test is often compared with a standard test and both tests are applied on the same patients, called paired design. The true disease state is in general given by the so-called gold standard (most reliable method for classification), which has to be known for all patients. The benefit of the new diagnostic test can be evaluated by sensitivity and specificity, which are in fact proportions. This means, for the comparison of two diagnostic tests, confidence intervals for the difference of the dependent estimated sensitivities and specificities are calculated. In the literature, many comparisons of different approaches can be found, but none explicitly for diagnostic studies. For this reason we compare 13 approaches for a set of scenarios that represent data of diagnostic studies (e.g., with sensitivity and specificity ≥0.8). With simulation studies, we show that the nonparametric interval with normal approximation can be recommended for the difference of two dependent sensitivities or specificities without restriction, the Wald interval with the limitation of slightly anti-conservative results for small sample sizes, and the nonparametric intervals with t-approximation, and the Tango interval with the limitation of conservative results for high correlations.

The Axon Guidance Protein Semaphorin 3A Is Increased in the Motor Cortex of Patients With Amyotrophic Lateral Sclerosis

Amyotrophic lateral sclerosis (ALS) is a degenerative motor neuron disorder that leads to progressive paralysis of skeletal muscles and death by respiratory failure. There is increasing evidence that ALS is at least in part an axonopathy and that mechanisms regulating axonal degeneration and regeneration might be pathogenetically relevant. Semaphorin 3A (Sema3A) is an axon guidance protein; it acts as an axon repellent and prevents axonal regeneration. Increased Sema3A expression has been described in a mouse model of ALS in which it may contribute to motor neuron degeneration. This study aimed to investigate Sema3A mRNA and protein expression in human CNS tissues. We assessed Sema3A expression using quantitative real-time PCR, in situ hybridization, and immunohistochemistry in motor cortex and spinal cord tissue of 8 ALS patients and 6 controls. We found a consistent increase of Sema3A expression in the motor cortex of ALS patients by all 3 methods. In situ hybridization further confirmed that Sema3A expression was present in motor neurons. These findings indicate that upregulation of Sema3A may contribute to axonal degeneration and failure of regeneration in ALS patients. The inhibition of Sema3A therefore might be a promising future therapeutic option for patients with this disease.