Nonparasitic Cysts of the Liver: Results and Options of Surgical Treatment

n = 9) should be regarded as a palliative measure. Within a short period, CT-guided aspiration led to recurrence of symptoms in seven of our patients. Standard treatment of NPHC is fenestration with widest possible excision of the cystic wall, which can be performed laparoscopically ( n = 10) or by the conventional surgical mode ( n = 54). One patient was initially operated by the laparoscopic technique but developed bleeding, which necessitated conversion to the open mode. Three patients underwent synchronous laparoscopic cholecystectomy. Recurrence rates were similar: 11% in the laparoscopically treated group and 13% in the group that underwent conventional open surgery. Conventional surgical treatment was always successful in cases of solitary cysts. However, in cases of multiple cysts measuring more than 5 cm, conventional surgery was followed by recurrence of symptoms in 26% of patients (7/27), who then had to undergo a second operation. Partial resection of the liver ( n = 9) was successfully performed in cases of polycystic disease ( n = 5) with concomitant enlargement of the organ as well as in cases of large solitary cysts of the left lobe of the liver ( n = 4). In patients in whom we found that the cysts communicated with the ductal system ( n = 3), we performed a cystojejunostomy to drain the bile. The complication rate was low. In addition to frequent postoperative ascites, which necessitated no further intervention, we observed infectious complications in four patients. Twenty patients (22%) expired during a mean follow-up period of 6.2 years. Interestingly, deaths were frequently associated with malignancy (11/20). After fenestration of multiple cysts measuring > 5 cm, the patients are at high risk for recurrence. Hence partial resection of the liver is an excellent therapeutic alternative in selected patients with polycystic disease and massive enlargement of the organ in whom the disease could not be controlled by simple fenestration. The results of this study show that laparoscopic fenestration should replace the conventional surgical technique as the gold standard in cases of NPHC because the laparoscopic technique is less stressful for the patient and is associated with a rate of success similar to that of the conventional technique.     

To beat the heat – engineering of the most thermostable pyruvate decarboxylase to date

Pyruvate decarboxylase (PDC) is a key enzyme for the production of ethanol at high temperatures and for cell-free butanol synthesis. Thermostable, organic solvent stable PDC was evolved from bacterial PDCs. The new variant shows >1500-fold-improved half-life at 75 °C and >5000-fold-increased half-life in the presence of 9 vol% butanol at 50 °C.

Pyruvate decarboxylase (PDC) is a key enzyme for the production of ethanol at high temperatures and for cell-free butanol synthesis.

For many years, bioethanol has been used widely as an additive in gasoline or as a fuel by itself.¹ To avoid competition with food, production of ethanol from plant-derived starch or sugar (first generation) has shifted to lignocellulosic biomass (second generation). To date, most of the bioethanol produced industrially still utilises yeasts as the main fermentation organism.^1–3 However, in recent years, several efforts have been made to use thermophilic microorganisms as the new framework.^1,3 The main motivating forces behind this are the volatility of ethanol at higher temperatures, which facilitates easy product removal, reduced risk of contamination and feasibility of consolidated bioprocessing (CBP). In this process, cellulolytic ethanologenic thermophilic microorganisms are applied, thus reducing the energy consumption required for heat exchange between biomass pre-treatment, fermentation and product separation and to avoid cellulase inhibition by accumulating glucose.^3,4There are two major pathways for producing ethanol from pyruvate, the central metabolite in glycolysis: non-oxidative decarboxylation via pyruvate decarboxylase (PDC) and oxidative decarboxylation via pyruvate dehydrogenase (PDH) or pyruvate ferredoxin oxidoreductase (PFOR). Non-oxidative ethanol productions are commonly found in yeasts and other ethanologenic bacteria, while PDH and PFOR routes are described in thermophilic microorganisms.^3,4 PDC mode may offer advantages compared with PDH and PFOR, as it is thermodynamically more favourable and will not lead to any other organic acid by-products.^3–5 In fact, all industrially relevant ethanol producing organisms use PDC. Thermostable PDCs are, therefore, suggested to play an important role in creating homo-ethanologenic, thermophilic microorganisms.^5,6Until recently, there were only limited efforts described in literature for improving the thermostability of PDC. Ancestral sequence reconstruction, supposedly a powerful method of resurrecting ancient thermostable enzymes, did not yield more thermostable PDC.⁷ A computational Rosetta-based design resulted in several variants with improved stability, determined by differential interference contrast (DIC) microscopy; unfortunately, the work was not corroborated by kinetic activity and stability data.⁸ Another effort to redirect the specificity of a thermostable, acetolactate synthase to perform a PDC-like reaction by conventional directed evolution did not yield variants either, with activity similar to that of bacterial PDC.⁹ Thus, creating thermostable PDC variants remains as the main challenge towards second generation ethanol production by thermophilic microorganisms.Besides acting as an important enzyme for ethanol production, PDC has also been applied in the in vitro production of n-butanol (Scheme 1).^10,11 Butanol together with other longer-chain alcohols, such as 1-propanol, isobutanol and isopentanol, is regarded as the next-generation biofuel, due to its closer resemblance to traditional gasoline.¹² Thus, there is an increasing demand to produce longer-chain alcohols sustainably.¹² Industrially, butanol is still produced from petroleum-derived propene utilizing Co-catalyst, H₂, and CO via oxo synthesis and Reppe process.¹³ Albeit its efficiency, production of butanol from petroleum is not sustainable.Open in a separate windowScheme 1Simplified pathway to produce ethanol and 1-butanol from lignocellulosic biomass via pyruvate decarboxylase (PDC). There are two major pathways for producing 1-butanol via pyruvate: CoA-dependent or proline-dependent condensation. ADH is an alcohol dehydrogenase.In a more sustainable way, butanol can be produced via an acetone–butanol–ethanol (ABE) process, utilising Clostridium acetobutylicum.^12,14 Recent work on metabolic engineering has demonstrated the possibility of producing butanol in other microorganisms.^15,16 However, one of the major challenges in butanol fermentation is still the toxicity of butanol to many microorganisms at relatively low concentrations (<2 vol%).^17,18 This effect, however, is less pronounced for the enzymes catalysing butanol production in vitro.^10,19 Many enzymes can already tolerate higher organic solvent concentrations than the corresponding microorganisms.²⁰ Furthermore, engineering enzyme stability towards organic solvents is less challenging than evolving microorganisms to withstand the same concentration of organic solvents.^17,21 Therefore, in vitro butanol production emerges as a very promising alternative to traditional butanol fermentation. Thus, in this work, we focused on the engineering of PDC towards higher thermal stability for prospective ethanol production in thermophilic microorganisms and improved stability in butanol for applications in in vitro, artificial butanol synthesis.Prior to engineering a PDC, we characterised two new yeast PDCs from Candida glabrata (CgPDC) and Zygosaccharomyces rouxii (ZrPDC), as well as other PDCs reported in the literature, to determine the most suitable template. As presented in 22 Characterisation of bacterial PDCs showed similar findings to the previous report, with PDC from Acetobacter pasteurianus (ApPDC) demonstrating the highest kinetic stability (T₅₀^{1 h}) and melting temperature (T_m).²²T₅₀^{1 h} is defined as the temperature at which 50% of the enzymes remained active after 1 h incubation, while T_m is defined as the temperature at which 50% of the enzymes are in an unfolded state.²³ In general, bacterial PDCs showed higher activity at 25 °C and overall stability (T₅₀^{1 h} and T_m) than newly characterised CgPDC and ZrPDC.Summary of kinetic characterisations and thermostability of WT PDCs and variants

Disease management programmes in Germany: first reactions by patients suffering from diabetes

The performance of health delivery for chronic diseases in Germany has been considered deficient for a long time and in need of improvement. The launch of Disease Management Programmes (DMP) for type 2 diabetes in the summer of 2002 can be seen as an attempt to optimise health care for the chronically ill. The aim of our study was to find out at an early stage of DMP development which factors, personal or otherwise, would have an influence on whether diabetic patients know of, and are willing to participate in, such a programme. The data of 679 diabetic patients, collected between late 2002 and the end of 2003, presented here have been extracted from a written follow-up study to the three baseline surveys S1 (1984/85), S2 (1989/90) und S3 (1994/95) in Augsburg as part of the WHO-MONICA project with more than 13,000 participants. The study population is characterised by a rather high age (mean: 67.4 years), a long duration of the disease (mean: 9.8 years) as well as a high intensity of contacts with physicians. Only 28 % of the diabetic patients had heard of the DMP, but a majority of the participants (54 %) stated their readiness to participate in DMP once offered. Higher age, low education as well as no participation in diabetes education have been identified in logistic regression models as impeding factors both for the knowing of and the participation in DMP. As a consequence, promotion of the DMP should be directed to those sections of the diabetic population outside the effective reach of the traditional diabetes care organisations.     

Patientenorientierung durch Patientenbefragungen als ein Qualitätsmerkmal der Krankenversorgung

Contrary but simultaneous to the dominant economic and fiscal aspects of the health system, patient oriented care is also gaining increasing importance in Germany's health-political debate as a criterion of quality for the treatment of patients. It is becoming increasingly clear that patient oriented care must be a central procedural maxim for all institutions and professions within the health care system, and that it is important to implement at all levels of the health care system the most important elements of patient oriented care – transparency of the treatment offers and the participation of the effected persons in the shaping of these offers. Surveys of users, patients and insurance holders represent one method for the involvement of citizens in the shaping of the health care system, for the comparison of the available facilities' health services by the consumers that use them, and for the patient oriented determination of quality deficits within these facilities. Systematic patient surveys, however, are not equally possible in all forms of institutions. Even in locations where no difficultly surmountable situational and patient related hindrances are present, namely in hospitals and rehabilitation clinics, the surveys and their results are often devaluated by the fact that they lack a solid methodical foundation or that no practical consequences are drawn from them. There are, however, surveying techniques which aid in minimizing methodic difficulties or practical implementation deficits such that patient surveys can indeed offer a profound contribution to the promotion of patient orientation and the improvement of the treatment quality in health care institutions.     

Ratiometric calcium concentration estimation using LED excitation during mechanotransduction in single sensory neurons

In a previous study using Oregon Green BAPTA-1 fluorescence we found that intracellular calcium concentration in spider mechanoreceptor neurons rose during mechanical stimulation. We also showed that calcium elevation required the opening of voltage-dependent calcium channels by action potentials, and could not be produced by the receptor potential alone. While evidence for mechanisms of calcium elevation in these neurons was clear, our estimates of actual calcium concentration depended on properties of the fluorescent dye in the neuron cytoplasm that could not be verified. We have now developed a method for ratiometric estimation of calcium concentration in these neurons using Fura Red dye, excitation by two light emitting diodes (LEDs) of different wavelengths, and an avalanche photodiode fluorescence detector. The method is simple and economical to implement, allows concentration changes to be measured in the millisecond time range, and could easily be applied to a wide range of preparations. Resting calcium concentration in these neurons was about 70nM and rose to a maximum of about 400nM at firing rates above 20 action potentials per second.     

Intergenerational participatory discussion groups foster knowledge exchange to improve child nutrition and food security in northern Malawi

This article assesses the effectiveness of a participatory, intergenerational, dialogue approach in addressing gender and generational conflicts related to both child nutrition and agriculture. Analysis of 46 interviews and 3 focus groups with smallholder farmers in rural agrarian communities with high rates of child malnutrition in northern Malawi suggested that participatory discussion can lead to positive change, including increasing child feeding frequency and dietary diversity. An intergenerational, transformative, and holistic approach to nutrition education which integrates agricultural and gender issues can effectively address sensitive conflicts within households and communities that affect child nutrition, and come up with local solutions.     

Universities preparing health professionals for the 21st century: can something new come out of the traditional establishment?

To address clinical education in chronic disease management, the University of Alberta partnered with the local health authority to develop interprofessional team placements in diabetes chronic disease management. The objectives were to determine a meaningful and sustainable approach to interprofessional team placements. Pre-licensure students from medicine, nursing, nutrition and pharmacy participated in a project-based team experience designed to increase their discipline-specific knowledge of diabetes while enhancing their team process skills. Quantitative and qualitative research methods were used to evaluate project implementation and student outcomes. The majority of students reported learning "a great deal" about the roles of other health professionals and knowledge regarding the management of diabetes from the perspective of other health disciplines. However, several key learning outcomes were not fully accomplished; to enhance student's interprofessional team skills, increase their knowledge of interprofessional team functions and learn how to modify team function in a clinical setting. Creativity concerning relevant projects, varying settings, and differing models of service delivery should be encouraged, and flexibility within the project and process is essential for self-directed learning of student teams. New models of interprofessional clinical education, such as the chronic disease management model used in this study, have potential, if supported by the shift in health science programs culture.     

Chirurgische Therapie des Magenkarzinoms

Background

Gastric cancer is one of the few tumor entities with a decreasing incidence but still constitutes a main cause of cancer-related deaths worldwide. The gold standard in therapy regimes with curative intent is surgery; however, palliative regimes should also include surgery in selected cases. Minimally invasive techniques are becoming established leading to improved perioperative outcomes.

Objective

Review of current oncological standards with a focus on the surgical approach in gastric cancer patients, discussion of current controversies regarding surgery with curative and palliative intent and outcomes of minimally invasive techniques.

Material and methods

Review of the literature on surgery of gastric cancer including conventional and minimally invasive tecnhniques.

Results

Surgery is the gold standard in regimes with curative intent for gastric cancer patients. The histological subtype is the basis for decision-making with respect to the extent of gastric resection. Radical D2 lymphadenectomy is the current standard in western countries. Multivisceral resection for locally advanced cancer is worthwhile in selected patients in terms of improved long-term survival despite potentially higher morbidity rates.. In palliative settings surgery can be a tool to improve the quality of life and to control tumor-related complications

Conclusion

Minimally invasive techniques are one of the main technical options to improve the perioperative outcome in gastric cancer patients. Multimodal therapy regimes may improve the quality of life and survival in curative and palliative settings.

     

Predicting the Responses of Mechanoreceptor Neurons to Physiological Inputs by Nonlinear System Identification

The nonlinear dynamic properties of action potential encoding were studied in mechanosensory neurons innervating the slits of a slit-sense organ in the tropical wandering spider, Cupiennius salei. The organ contains two types of neurons that are morphologically similar but have different dynamic properties. Type A neurons produce only one or two action potentials in response to a mechanical or electrical stimulus of any suprathreshold amplitude, while type B neurons can fire prolonged bursts of action potentials in response to similar stimuli. Neurons were stimulated with pseudorandomly modulated intracellular current while recording the resultant fluctuations in membrane potential and action potentials. A parallel cascade method was used to estimate a third-order Volterra series to describe the nonlinear dynamic relationship between membrane potential and action potentials. Kernels measured for the two types of neurons had reproducible forms that showed differences between the two neuron types. The measured kernels were able to predict the responses of the neurons to novel pseudorandomly modulated inputs with reasonable fidelity. However, the Volterra series did not adequately predict the difference in responses to step depolarizations. © 2001 Biomedical Engineering Society. PAC01: 8719Bb, 8717Nn, 8719La, 8719Nn, 8716Uv