Prospective evaluation of CT-guided HDR brachytherapy as a local ablative treatment for renal masses: a single-arm pilot trial.

PURPOSE: In this pilot trial, we investigate the safety of CT-guided high-dose-rate brachytherapy (HDR-BT) as a local ablative treatment for renal masses not eligible for resection or nephrectomy. METHODS: We investigated renal function after irradiation by HDR-BT in 16 patients (11 male, 5 female, mean age 76 years) with 20 renal lesions (renal cell carcinoma n = 18; renal metastases n = 2). Two patients had previous contralateral nephrectomy and two had ipsilateral partial nephrectomy. Six lesions had a hilar localization with proximity to the renal pelvis and would have not been favorable for thermal ablation. Renal function loss was determined within 1 year after HDR-BT by renal scintigraphy and laboratory parameters. Further investigations included CT and MRI every 3 months to observe procedural safety and local tumor control. Renal function tests were analyzed by Wilcoxon's signed rank test with Bonferroni-Holm correction of p-values. Survival and local tumor control underwent a Kaplan-Meier estimation. RESULTS: Median follow-up was 22.5 months. One patient required permanent hemodialysis 32 months after repeated HDR-BT and contralateral radiofrequency ablation of multifocal renal cell carcinoma. No other patient developed a significant worsening in global renal function and no gastrointestinal or urogenital side effects were observed. Only one patient died of renal tumor progression. Local control rate was 95% including repeated HDR-BT of two recurrences. CONCLUSION: HDR-BT is a feasible and safe technique for the local ablation of renal masses. A phase II study is recruiting to evaluate the efficacy of this novel local ablative treatment in a larger study population.

Towards instantaneous cellular level bio diagnosis: laser extraction and imaging of biological entities with conserved integrity and activity.

The prospect for spatial imaging with mass spectroscopy at the level of the cell requires new means of cell extraction to conserve molecular structure. To this aim, we demonstrate a new laser extraction process capable of extracting intact biological entities with conserved biological function. The method is based on the recently developed picosecond infrared laser (PIRL), designed specifically to provide matrix-free extraction by selectively exciting the water vibrational modes under the condition of ultrafast desorption by impulsive vibrational excitation (DIVE). The basic concept is to extract the constituent protein structures on the fastest impulsive limit for ablation to avoid excessive thermal heating of the proteins and to use strongly resonant 1-photon conditions to avoid multiphoton ionization and degradation of the sample integrity. With various microscope imaging and biochemical analysis methods, nanoscale single protein molecules, viruses, and cells in the ablation plume are found to be morphologically and functionally identical with their corresponding controls. This method provides a new means to resolve chemical activity within cells and is amenable to subcellular imaging with near-field approaches. The most important finding is the conserved nature of the extracted biological material within the laser ablation plume, which is fully consistent with in vivo structures and characteristics.

[Gait disorders in geriatric patients. Classification and therapy]. / Gangstörungen beim geriatrischen Patienten. Klassifikation und Therapie.

BACKGROUND: Slow walking with reduced body dynamics is a characteristic feature of locomotion in the elderly. Impaired mobility and falls associated with gait disorders significantly contribute to a reduced quality of life in the elderly. OBJECTIVES: A gait disorder is not an inevitable consequence of aging. This article shows that it is worth recognizing specific deficits and differentiating specific aspects in multifactorial disorders because many causes can be well treated. Also provided are the bases for clinical classification and therapeutic principles. METHODS: Review of recent literature and clinical review based on own experience and own scientific results. RESULTS: Common causes of disturbed gait in the elderly are neurological deficits, including sensory deficits (e.g. peripheral neuropathy and vestibulopathy), neurodegeneration (e.g. cerebellar ataxia and parkinsonian syndromes, cognitive impairment (e.g. degenerative dementia), degeneration of joints (e.g. coxarthrosis) and general loss of muscle mass (sarcopenia). Furthermore, a fear of falling also contributes to the gait disorder. Multimodal therapies are often necessary and the principles are presented. CONCLUSION: Identification of deficits is a prerequisite for specific therapy. As physical activity protects against cognitive impairment, reduces the risk of falling and improves overall quality of life, a structured assessment of causes for gait impairment is crucial.

[Falls in German hospitals and nursing homes 2006-2013. Frequencies, injuries, risk assessment, and preventive measures]. / Stürze in deutschen Krankenhäusern und Pflegeheimen 2006-2013. Häufigkeiten, Verletzungen, Risikoeinschätzung und durchgeführte Prävention.

BACKGROUND: In Germany, a nationwide systematic collection of data regarding fall incidents within health-care facilities is lacking. The objective of the study was to provide valid and robust data on fall rates, the severity of the fall and its resulting injuries, fall risk assessment, and preventive measures offered by professional caregivers in German hospitals and nursing homes. MATERIALS AND METHODS: Each spring from 2006 to 2013, cross-sectional studies were conducted in 124 hospitals (n = 22,493 patients) and 332 nursing homes (25,384 residents) throughout Germany. Fully trained nurses obtained information on the recent history (< 14 days) of the fall and its consequences. Further, they assessed the individual fall risk by clinical judgment and recorded ongoing preventive measures. RESULTS: The total fall rate was 3.9 % (95 % CI 3.6-4.2) in the hospitals and 4.6 % (95 % CI 4.3-4.9) in the nursing homes. Of the fall victims, 6.4 % of the nursing home residents and 8.8 % of the hospital patients were badly injured (i.e., fracture). The fall risk was considered high for residents, with two thirds of all residents being affected, while it was lower for the patients, at one third. The following factors were associated with fall risk: limited mobility, cognitive impairment, recent history of falls for nursing home residents, and additionally urinary incontinence and higher age in hospital patients. The most common preventive measure was counseling of the individual in both settings. CONCLUSION: Although most falls have no severe consequences, the study shows that every 20-25th individual has a falling event in hospitals and nursing homes within 14 days. Despite the slight variance, the trend of the rates remains largely stable. Because specific fall risks were determined, preventive measures can be applied in a more personalized manner and care can be improved. Finally, the study provides valid and durable figures for national and international comparisons.

[Funnel plots for comparing pressure ulcer and fall rates in 76 nursing homes]. / Funnel-Plots zum Vergleich von Dekubitus- und Sturzkennzahlen in 76 Pflegeheimen.

AIM OF THE STUDY: The aim of this study was to display the values of the quality indicators "falls in the institution" and "institutionally acquired pressure ulcers" of 76 German nursing homes in bar graphs and funnel plots and to discuss the advantages and disadvantages of both methods. METHODS: In 2009 a nationwide prevalence study has been conducted in 76 nursing homes (n= 5 521). Among others two trained data collectors assessed the fall and pressure ulcer risks, the presence of pressure ulcers and whether nursing home residents fell. Risk adjusted fall and pressure ulcer prevalence rates were calculated per institution and displayed in bar graphs and funnel plots. RESULTS: The proportions of residents with pressure ulcers grade 2, 3 or 4 varied between 0 and 11%. The average pressure ulcer prevalence was 2.5%. On average, 6% of residents at risk for falling fell during the last 2 weeks. The proportions of fallen residents varied between 0% and 100%. In bar graphs differences between institutions and rankings can be displayed. However, the precision of the point estimates is not taken into account. Furthermore, criteria for determining conspicuous institutions are arbitrary. In funnel plots values are plotted against their precision. Although there were differences between the investigated nursing homes, most of them could be explained by chance. CONCLUSION: Funnel plots should be used when comparing medical or nursing performance between health care institutions. They take the precision of estimates into account that is usually the size of the institution. Despite differences, there was no nursing home with a prevalence of institutionally acquired pressure ulcers that was significantly higher than those in all the other institutions. In 2 out of 75 nursing homes the proportions of fallers were higher than expected by chance. In terms of performance improvement the reasons for this should be further investigated. However, in spite of the advantages of funnel plots they do not provide guidance as to whether the measured results can be tolerated and are acceptable.

[Tumor profiling of renal cell tumors: relevance for diagnostics and therapy]. / Molekulares Tumorprofiling von Nierenzelltumoren: Relevanz für Diagnostik und Therapie.

Molecular biological tumor markers and prognostic parameters are necessary for differential diagnosis, individual prognosis, and therapy in patients with renal cell tumors. By using high throughput technologies, it is possible to characterize tumor samples comprehensively. Based on specific genetic alterations, histopathological subtypes were defined as independent tumor entities. Genetic characteristics can be used for diagnosis of primary tumor samples and also of biopsies. Furthermore, specific molecular patterns of metastatic tumors are known, allowing the determination of the primary tumor's metastatic potential. The specific protein patterns of serum samples of tumor patients were analyzed, and several candidate proteins have been identified. One of these is SAA-1, which is elevated in patients with clear cell renal cell carcinomas (RCC). New therapeutic options are now available for patients with metastatic RCC. Therefore, it is necessary to select the best therapy for each patient and to detect therapy resistance very early. Biomarkers in tumor tissue and serum were found to correlate with therapy response.

[Molecular characterization of metastatic renal cell carcinomas. Differentiation of prognosis and therapy]. / Molekulare Charakterisierung der metastasierten Nierenzellkarzinome. Individuelle Prognosebewertung und Therapiewahl.

Molecular biological tumor markers and prognostic parameters are necessary for differential diagnosis, individual prognosis, and therapy in patients with renal cell tumors. By using high throughput technologies for DNA, RNA, and protein analysis, it is possible to comprehensively characterize tumor samples. We identified specific molecular patterns of metastatic tumors, allowing the determination of metastatic potential of the primary tumor. Different therapeutic options are now available for patients with metastatic renal cell carcinoma. Therefore, it is necessary to select the best therapy for each patient and to detect therapy resistance very early. Biomarkers in tumor tissue and serum were found correlating with therapy response.

Preliminary investigation of blood concentrations of insulin-like growth factor, insulin, lactate and ß-hydroxybutyrate in dogs with lymphoma as compared with matched controls.

It is well established that tumour cells have metabolic differences when compared with normal cells. This is particularly true for energy metabolism in which dogs with cancer have been reported to have higher blood insulin and lactate concentrations than control dogs. Moreover, some human and animal studies suggest that the insulin-like growth factor 1 (IGF-1) signalling pathway may play a role in tumorigenesis and tumour progression. At present, IGF-1 has not been evaluated in dogs with multicentric lymphoma. In this prospective, cross-sectional study, blood levels of IGF-1, as well as other markers of energy metabolism-insulin, glucose, lactate, and ß-hydroxybutyrate-were measured in 16 dogs with histologically or cytologically confirmed treatment-naïve lymphoma. These results were compared with 16 age-, sex- and weight-matched healthy controls. Dietary histories were collected, and protein, fat and carbohydrate intake were compared between groups. Results demonstrated that IGF-1, insulin, glucose and insulin:glucose ratio were not different between groups. However, lactate and ß-hydroxybutyrate were higher in the dogs with lymphoma than that in the control dogs (1.74 ± 0.83 mmoL/L vs 1.08 ± 0.27 and 2.59 ± 0.59 mmol/L vs 0.77 ± 0.38 mmol/L, respectively). Median dietary protein, fat and carbohydrates did not differ between the groups. This preliminary study suggests that higher insulin and IGF-1 levels relative to controls may not be a consistent finding in dogs with lymphoma. The significance of increased ß-hydroxybutyrate in dogs with lymphoma warrants further investigation in a larger prospective study.

[Fall prevention in people with dementia - do experiences from long-term-care offer new methods of resolution?]. / Sturzprävention bei Menschen mit Demenzerkrankungen - Bieten die Erfahrungen der Altenpflegepraxis neue Lösungsansätze?

Elderly persons suffering dementia are at increased risk for falls. Because of this, an investigation of the state of the science and the state of the art in fall prevention in patients suffering dementia has been made. A systematic literature review showed lack of documentation of effective interventions in preventing falls in persons with cognitive impairment. This was the reason for studying which measures nurses undertake in the field of long-term-care. Focus-group interviews with experienced geriatric nurses were undertaken. Nurses assume that there are specific risk factors in this patient group which have to be taken into account. Cognitive deficits are causing an increased fall risk in a specific manner. Geriatric nurses have ideas about how to adapt interventions for persons with dementia. They also assume that interventions primarily addressing cognitive disorders may also reduce the risk of falling. The interventions mentioned by the interviewed experts have not yet been examined concerning their effectiveness, therefore, fall prevention for people with dementia has to be further differentiated and systemized on a scientific basis.

Normal pressure hydrocephalus: Increase of utricular input in responders to spinal tap test.

OBJECTIVE: To investigate whether there is a change in ocular (oVEMP) and cervical (cVEMP) vestibular evoked myogenic potentials in patients with normal pressure hydrocephalus (NPH) before and after spinal tap test (STT). METHODS: In 25 patients (6 females, age 62-83years) c/oVEMP were measured before and after STT. Patients with an increase of >20% of walking velocity were classified as responders (n=10). VEMP were also measured in a control group of 13 non-NPH patients. RESULTS: All patients had reproducible oVEMP; 68% had cVEMP. There was a significant increase of the peak-to-peak (pp) oVEMP amplitude after STT in responders (8.5±2.7 to 18.9±7.5µV (p=0.010)). No significant changes were found in non-responders (13.4±7.6 to 15.3±8.6µV) or controls (12.4±7.6 to 12.5±6.8µV). There were no significant differences in cVEMP before and after spinal tap test (STT). CONCLUSION: One third of patients with suspected NPH had impaired otolith function. Responders to STT only had a significant increase of oVEMP and thereby utricular input, probably due to a decrease of pressure. SIGNIFICANCE: Both findings indicate that otolith dysfunction may contribute to imbalance in NPH and that increased utricular function after STT may be relevant for gait improvement.

Association between Body Condition Score and Cancer Prognosis in Dogs with Lymphoma and Osteosarcoma.

BACKGROUND: In humans and rodents obesity appears to promote some cancers by increasing incidence, tumor aggressiveness, recurrence, and fatality. However, the relationship between obesity and cancer in dogs has not been thoroughly evaluated. HYPOTHESIS/OBJECTIVES: Whether body condition score (BCS) at the time of lymphoma (LSA) or osteosarcoma (OSA) diagnosis in dogs is predictive of survival time (ST) or progression-free interval (PFI). We hypothesized that an overweight body state at the time of cancer diagnosis would be associated with negative outcomes. ANIMALS: Dogs with LSA (n = 270) and OSA (n = 54) diagnosed and treated between 2000 and 2010. METHODS: Retrospective case review. Signalment, body weight, BCS, cancer diagnosis and treatment, relevant clinicopathologic values, and survival data were collected. Dogs were grouped by BCS (underweight, ideal, and overweight) and ST and PFI were compared. RESULTS: Overall, 5.5% of dogs were underweight, 54.0% were ideal weight, and 40.4% were overweight at diagnosis. Underweight dogs with LSA had shorter ST (P = .017) than ideal or overweight dogs. BCS was not associated with ST for OSA (P = .474). Progression-free interval did not differ among BCS categories for either cancer. CONCLUSIONS AND CLINICAL IMPORTANCE: Obesity was not associated with adverse outcomes among dogs with LSA or OSA in this retrospective study; however, being underweight at the time of diagnosis of LSA was associated with shorter survival. More research is needed to elucidate the relationship between excessive body weight and cancer development and progression in dogs.

Evaluation of owner experiences and adherence to home-cooked diet recipes for dogs.

OBJECTIVES: To evaluate owner experiences and adherence to home-cooked diet recipes for dogs. METHODS: Clients of a veterinary teaching hospital clinical nutrition service who had a home-cooked diet recipe formulated for their dogs between March 2011 and December 2013 were given a survey by email, postal mail and telephone. Survey questions addressed motivations, positive and negative aspects of feeding home-cooked diets and current feeding practices. Responses were compared to animals' medical records to determine adherence. RESULTS: Of the 93 owners who were contacted, 53 (57%) completed the survey. Of the 53 respondents, 43 owners (81%) reported that they were still feeding an home-cooked diet or had fed an home-cooked diet until the time of their dogs' deaths. The most common motivation for feeding a home-cooked diet was suitability for specific medical needs. Of the 30 surveys that included a complete diet history, only four (13%) demonstrated exact adherence to home-cooked diet recipes. CLINICAL SIGNIFICANCE: Most respondents liked and continued to feed a home-cooked diet, but few owners adhered to prescribed recipes and many dogs required recipe modifications. It is important to counsel dog owners about benefits and drawbacks of feeding home-cooked diets, importance of recipe adherence and necessity for follow-up after diet formulation with a board-certified veterinary nutritionist.

Peptide-derived broad-reacting antisera against tospovirus NSs-protein.

Sequence alignments of tospovirus species of serogroup I to IV revealed a stretch of 24 amino acids at the C terminus of the non-structural protein NSs with a highly conserved sequence. Based on this sequence the 24 amino acids peptide YFLSKTLEVLPKNLQTMSYLDSIQC was synthesized and used to raise antisera in two rabbits. The specificity of the antisera against NSs from infected plants was confirmed with Western blots and by immunogold labelling and electron microscopy. These antisera detected tospovirus isolates of serogroup I to III in antigen-coated plate ELISA and Western blots but failed to detect isolates of serogroup IV. Epitope scanning using overlapping octopeptides composing the peptide suggested that the antisera contained antibodies against two different epitopes. Strongly reacting peptides were found at the C-terminus of the original peptide sequence when probing with one of the antisera. In this part the sequence was homologous to serogroup I, II and III, with all deviations from serogroup IV located here. Additional octopeptides, based on this region, synthesized with sequence modifications back to the serogroup IV sequence in all possible combinations, had low reactivity. However two of the modified peptides with partly restored serogroup IV sequences revealed promising reactivity and could be suitable to raise an antiserum with broader reactivity, including serogroup IV.

Early events of tomato spotted wilt transcription and replication in protoplasts.

A protoplast transfection system for tomato spotted wilt tospovirus (TSWV) was established by PEG-mediated infection of tobacco protoplasts. Analysis of viral RNA synthesis revealed an asymmetric production of viral (v) and viral-complementary (vc) strands of all three genomic RNA segments and a separation in time of subgenomic transcription during the first 72 hr post infection (p.i.). Synthesis of vc-RNA was detectable 8-10 hrs prior to v-RNA production. During the first 72 h of infection the accumulation of S-RNAs exceeded M- and L-RNAs and the amount of vc-RNAs was larger than that of genomic v-RNAs. The subgenomic N-mRNA was first detected 5 hr p.i., followed by vc-S RNA and the mRNA for the nonstructural protein (NSs) 15 hr later. The two subgenomic mRNA species of the S RNA appeared to be regulated independently from each other and from other viral mRNA species. Defective interfering (DI) elements from L RNA associated with the virus inoculum, were not preferentially replicated at the expense of full-sized L-RNA.

Variability of the N-protein and the intergenic region of the S RNA of tomato spotted wilt tospovirus (TSWV).

The genetic heterogeneity of the N protein gene and the intergenic region (IGR) of the S RNA from tomato spotted wilt virus (TSWV) isolates, collected in Bulgaria, were compared with isolates from other parts of the world. The results substantiated the highly conserved nature of the N protein. Twenty six independent sequences revealed only seven variable amino acid positions, common to all isolates. The type of amino acids present in these positions seems to be independent of the geographical origin. In contrast to the structural N protein, comparisons of the related IGR-sequences led to clusters correlated with the geographical origin of the isolates. Although the overall sequence homology in the IGRs was much lower than for the N proteins, three conserved parts within this region were identified. The outstanding part was a central area of 31 nucleotides with a significantly increased GC-content. This was located in both viral- and viral-complement RNA at structures with similar foldings, which led to the assumption that this stabilised structure, rather than a sequence motive, might serve as a transcription terminator during the synthesis of the two mRNAs from the ambisense segments.

[Knowledge of professional rules of ethics among professional nurses]. / Der Bekanntheitsgrad berufsethischer Grundregeln innerhalb der Berufsgruppe der Pflegenden.

During recent years numerous publications on ethical issues appeared in German nursing literature. Nursing theorists repeatedly refer to the Code of Ethics of the International Council of Nursing (ICN). The implementation of codes of ethics is discussed as an indispensable stage within the development of independent nursing ethics. However, it is not clear whether nurses in Germany know about the ICN Code of Ethics or other codes of ethics. The authors' objective is to learn more about how much is known about codes of ethics by practical nurses in four selected hospitals. In addition, it is of interest to know, which advantages nurses might associate with codes of ethics and secondly from which sources nurses prefer to receive ethical education. The study shows that only 25% of the participants know about codes of ethics. It also reveals that further education offered by hospitals or the basic nursing education are seen as the most important source of information related to ethics. The major advantage of codes of ethics seen by the participants is to provide guidance in the decision-making process of ethical dilemma situations in nursing. Secondly the Code of Ethics is regarded as a useful framework to define obligations and rights of nurses in the relationship with patients and relatives. The results of the study indicate that the ICN Code of Ethics is practically unknown among nurses and should be discussed more extensively by practical nurses and nursing theorists.

Effect of dietary omega-3 fatty acids on red blood cell lipid composition and plasma metabolites in the cockatiel, Nymphicus hollandicus.

Although dietary n-3 fatty acids have been extensively studied in poultry, they have not yet been prospectively investigated in psittacines, despite potential benefits for preventing and treating atherosclerosis, osteoarthritis, and other chronic disease processes. The objectives of this study were to investigate the incorporation of dietary n-3 fatty acids into red blood cells (RBC) and to determine the effects of supplementation of psittacine diets with fish or flax oil on plasma lipids and lipoproteins in the cockatiel. Adult cockatiels were fed a custom-formulated diet containing either 4% (wt/wt, as-fed) beef tallow (CON), 3% fish oil + 1% tallow (FSH), or 3.5% flax oil + 0.5% tallow (FLX; n = 20 per diet group). Baseline measurements were obtained for RBC fatty acid composition, triacylglycerides (TAG), and cholesterol. After 8 to 13 wk on the study diets, plasma chemistry profiles, lipoprotein density profiles, and RBC fatty acid composition were determined. At 8 wk, total plasma cholesterol was least in FSH birds (P < 0.05) and TAG concentrations were less in FSH birds than FLX birds (P < 0.05). Total n-3 fatty acids, docosahexaenoic acid, docosapentaenoic acid, and eicosapentaenoic acid were markedly greater in the RBC of FSH birds than FLX or CON birds (P < 0.05). Alpha linolenic acid was greatest in FLX (P < 0.05). Initial and final BW, and nonlipid plasma chemistry values did not differ among diet groups. No adverse effects of dietary supplementation of cockatiels with 3.5% flax oil or 3% fish oil were observed during the 13-wk feeding period. Although fish and flax oils provided similar total n-3 PUFA to the diets, fish oil caused greater reductions in cholesterol and TAG, and greater total RBC n-3 incorporation. Thus, dietary modification of psittacine diets with long chain n-3 PUFA from fish oil appears safe and may be beneficial to these long-lived companion birds.