[Transanal total mesorectal excision-Indications, technique and results]. / Transanale totale mesorektale Exzision ­ Indikation, Technik, Ergebnisse.

Total mesorectal excision (TME) has become the standard treatment for rectal cancer in the middle and lower third. Meanwhile, many international trials have confirmed the noninferiority of laparoscopic TME compared to the open technique. Nevertheless, in the presence of anatomical limitations, such as narrow, obese, male pelvises as well as large rectal tumors, the adequate resection of the lower third of the rectum according to oncological criteria, is still challenging even for specialized colorectal surgeons. Therefore, the implementation of innovative approaches, such as robotic-assisted and transanal TME (TaTME) should shed light on this anatomically complex region and guarantee an oncological radical resection and the best possible preservation of neural structures. The advantages of this technique have so far only been provided by retrospective cohort studies by large international centers. Therefore, international prospective randomized trials are currently recruiting patients to analyze the surgical and oncological outcome of TaTME compared to conventional techniques. This article describes the TaTME technique per se, the fields of application and the current data situation. Practical recommendations for the safe implementation of this operative procedure are also presented. The TaTME procedure is reserved for highly specialized colorectal centers with a high volume of rectal cancer cases and appropriate expertise in minimally invasive visceral surgery.Die totale mesorektale Exzision (TME) ist der Goldstandard im Kontext der multimodalen Behandlung des Rektumkarzinoms im mittleren und unteren Drittel. Der transanale Zugang ist eine Ergänzung des zunehmend laparoskopischen Vorgehens, welcher gerade bei anatomischen Limitationen bei der onkologisch adäquaten Resektion des distalen Rektums Abhilfe schaffen soll. Die Nichtunterlegenheit in chirurgischen und onkologischen Parametern wird gegenüber konventionellen (laparoskopisch/offen) Operationsmethoden derzeit intensiv beforscht. Eine sichere Implementation dieser herausfordernden Technik ist an ein modulares Trainingskurrikulum gebunden.

[Treatment of colorectal and non-colorectal liver metastases: rationale for neoadjuvant therapeutic concepts]. / Therapie kolorektaler und nichtkolorektaler Lebermetastasen: Sinnhaftigkeit neoadjuvanter Therapiekonzepte.

BACKGROUND: Liver metastases represent the most common secondary malignant liver disease. Data regarding the incidence of colorectal and non-colorectal liver metastases are rare due to insufficient documentation in a register. Results regarding neoadjuvant therapy are limited and mostly from retrospective analyses. OBJECTIVE: A summary and rating of the rationale for neoadjuvant therapeutic concepts for colorectal and non-colorectal liver metastases were performed. MATERIAL UND METHODS: The analysis was based on European and American guidelines and included publications in both German and English languages. The results and recommendations were summarized and a review based on the literature is given. RESULTS: Neoadjuvant treatment of liver metastases is performed with heterogeneous intentions. The selection of biologically favorable tumors as well as the conversion of primarily non-operable into resectable metastases of the liver are classical reasons for neoadjuvant treatment. The rationale for neoadjuvant treatment of colorectal and especially for non-colorectal liver metastases cannot be answered in a consistently coherent way with respect to the current status quo of the literature and guidelines. The creation of treatment strategies in clinical settings follows criteria, such as patterns of metastases, complexity of the resection and biological factors (metachronous/synchronous metastases, prognostic factors). CONCLUSION: Neoadjuvant treatment in the context of conversion therapy is the standard procedure for metastasized colorectal cancer. The biological selection of favorable tumors as the basis for neoadjuvant treatment of resectable lesions is not a consistently used standard for colorectal cancer. Non-colorectal liver metastases are resected only as part of individual concepts.

Hepatotoxicity following systemic therapy for colorectal liver metastases and the impact of chemotherapy-associated liver injury on outcomes after curative liver resection.

Patients with colorectal liver metastases (CLM) have remarkably benefited from the advances in medical multimodal treatment and surgical techniques over the last two decades leading to significant improvements in long-term survival. More patients are currently undergoing liver resection following neoadjuvant chemotherapy, which has been increasingly established within the framework of curative-indented treatment strategies. However, the use of several cytotoxic agents has been linked to specific liver injuries that not only impair the ability of liver tissue to regenerate but also decrease long-term survival. One of the most common agents included in modern chemotherapy regimens is oxaliplatin, which is considered to induce a parenchymal damage of the liver primarily involving the sinusoids defined as sinusoidal obstruction syndrome (SOS). Administration of bevacizumab, an inhibitor of vascular endothelial growth factor (VEGF), has been reported to improve response of CLM to chemotherapy in clinical studies, concomitantly protecting the liver from the development of SOS. In this review, we aim to summarize current data on multimodal treatment concepts for CLM, give an in-depth overview of liver damage caused by cytostatic agents focusing on oxaliplatin-induced SOS, and evaluate the role of bevacizumab to improve clinical outcomes of patients with CLM and to protect the liver from the development of SOS.

Cervical manifestation of a borderline type ovarian cancer with pseudomyxoma peritonei - a case report.

Borderline tumours of the ovary (BOTs) are rare tumour entities that do not show any destructive or invasive growth in the majority of cases, even though they can display characteristics of malignant tumours The mucinous subtype can also originate from the appendix, and ovarian metastases can mimic primary ovarian BOTs, often accompanied by peritoneal manifestation in terms of pseudomyxoma peritonei. In cases where a concomitant appendiceal tumour is present, it may prove difficult to determine the primary tumour. This report describes a special case of BOT with a specific example of the complexity of the differential diagnosis of pseudomyxoma peritonei. Especially the case was simultaneously linked to appendiceal and ovarian cancer. Moreover, this case was exceptional for its unusual manifestation of BOT in the cervix.

Effects of a chronic dietary exposure of the honeybee Apis mellifera (Hymenoptera: Apidae) to imidacloprid.

Previous studies have shown that imidacloprid and insecticidally active imidacloprid plant metabolites are rapidly metabolized by honeybees. Accordingly, no striking differences were expected between the acute and the chronic dietary toxicity of imidacloprid to honeybees. More recently, however, an unexpectedly high chronic dietary toxicity to honeybees was reported for imidacloprid and imidacloprid plant metabolites, and a novel pharmacologic mechanism unrelated to the parent toxophor was postulated. In an extensive literature survey, no further evidence was found for the reported high difference between the acute and the chronic dietary toxicity of imidacloprid and its plant metabolites to honeybees. The majority of data indicated a dietary no observed lethal-effect concentration >0.04 and 0.02 mg/L 50% sucrose solution, respectively, for an acute and a chronic dietary exposure of honeybees to either imidacloprid or its plant metabolites. Findings of chronic feeding studies with those plant metabolites where the toxophor had already been cleaved did not support the hypotheses of a novel pharmacologic mechanism unrelated to the parent toxophor. No increased treatment-related mortality or behavioral abnormalities were recorded in four independent research facilities during a 10-day dietary exposure of honeybees of different ages to sucrose solutions spiked with the respective metabolites at 0.0001, 0.001, and 0.010 mg/L 50% sucrose solution.

Risk posed to honeybees (Apis mellifera L, Hymenoptera) by an imidacloprid seed dressing of sunflowers.

In a greenhouse metabolism study, sunflowers were seed-treated with radiolabelled imidacloprid in a 700 g kg-1 WS formulation (Gaucho WS 70) at 0.7 mg AI per seed, and the nature of the resulting residues in nectar and pollen was determined. Only the parent compound and no metabolites were detected in nectar and pollen of these seed-treated sunflower plants (limit of detection < 0.001 mg kg-1). In standard LD50 laboratory tests, imidacloprid showed high oral toxicity to honeybees (Apis mellifera), with LD50 values between 3.7 and 40.9 ng per bee, corresponding to a lethal food concentration between 0.14 and 1.57 mg kg-1. The residue level of imidacloprid in nectar and pollen of seed-treated sunflower plants in the field was negligible. Under field-growing conditions no residues were detected (limit of detection: 0.0015 mg kg-1) in either nectar or pollen. There were also no detectable residues in nectar and pollen of sunflowers planted as a succeeding crop in soils which previously had been cropped with imidacloprid seed-treated plants. Chronic feeding experiments with sunflower honey fortified with 0.002, 0.005, 0.010 and 0.020 mg kg-1 imidacloprid were conducted to assess potential long-term adverse effects on honeybee colonies. Testing end-points in this 39-day feeding study were mortality, feeding activity, wax/comb production, breeding performance and colony vitality. Even at the highest test concentration, imidacloprid showed no adverse effects on the development of the exposed bee colonies. This no-adverse-effect concentration of 0.020 mg kg-1 compares with a field residue level of less than 0.0015 mg kg-1 (= limit of detection in the field residue studies) which clearly shows that a sunflower seed dressing with imidacloprid poses no risk to honeybees. This conclusion is confirmed by observations made in more than 10 field studies and several tunnel tests.

Toxicity and nicotinic acetylcholine receptor interaction of imidacloprid and its metabolites in Apis mellifera (Hymenoptera: Apidae).

Acute oral and contact toxicity tests of imidacloprid, an insecticide acting agonistically on nicotinic acetylcholine receptors (nAChR), to adult honeybees, Apis mellifera L var carnica, were carried out by seven different European research facilities. Results indicated that the 48-h oral LD50 of imidacloprid is between 41 and > 81 ng per bee, and the contact LD50 between 49 and 102 ng per bee. The ingested amount of imidacloprid-containing sucrose solution decreased with increasing imidacloprid concentrations and may be attributed to dose-related sub-lethal intoxication symptoms or to antifeedant responses. Some previously reported imidacloprid metabolites occurring at low levels in planta after seed dressing, i.e. olefine-, 5-OH- and 4,5-OH-imidacloprid, showed lower oral LD50 values (> 36, > 49 and 159 ng per bee, respectively) compared with the concurrently tested parent molecule (41 ng per bee). The urea metabolite and 6-chloronicotinic acid (6-CNA) exhibited LD50 values of > 99,500 and > 121,500 ng per bee, respectively. The pharmacological profile of the [3H]imidacloprid binding site in honeybee head membrane preparations is consistent with that anticipated for a nAChR. IC50 values for the displacement of [3H]imidacloprid by several metabolites such as olefine, 5-OH-, 4,5-OH-imidacloprid, urea and 6-CNA were 0.45, 24, 6600, > 100,000, and > 100,000 nM, respectively. Displacement of [3H]imidacloprid by imidacloprid revealed an IC50 value of 2.9 nM, thus correlating well with the observed acute oral toxicity of the compounds in honeybees. Neurons isolated from the antennal lobe of A mellifera and subjected to whole-cell voltage clamp electrophysiology responded to the application of 100 microM acetylcholine with a fast inward current of between 30 and 1600 pA at -70 mV clamp potential. Imidacloprid and two of the metabolites (olefine- and 5-OH-imidacloprid) acted agonistically on these neurons, whereas the others did not induce currents at test concentrations up to 3 mM. The electrophysiological data revealed Hill coefficients of approximately 1, indicating a single binding site responsible for an activation of the receptor and no direct cooperativity or allosteric interaction with a second binding site.

Molecular cloning, sequency, and expression of the heat-labile uracil-DNA glycosylase from a marine psychrophilic bacterium, strain BMTU3346.

The gene encoding a heat-labile uracil-DNA glycosylase (UDG) from a psychrophilic, gram-positive marine strain (BMTU3346) has been cloned, sequenced, and expressed in Escherichia coli. The UDG is a cold-active enzyme with an apparent temperature optimum of 35 degrees C and a half-life of 2min at 40 degrees C. The amino acid sequence shows an identity of 39.1%-46.2% to UDGs from mesophilic bacteria. The primary structure was examined for features that could be related to the thermolability of the enzyme. The amino acid sequence of the heat-labile UDG shows 22 differences with respect to the consensus sequence derived from bacterial UDGs. Features previously recognized in cold-active enzymes such as extended surface loops or a decrease in the number of arginine residues or proline residues in loops were not observed. Because dominant features that could be related to the thermolability of the UDG from BMTU3346 cannot be identified, more subtle modifications of the conformation seem to be responsible for its thermolability.

Impact of Vairimorpha sp. (Microsporidia: Burnellidae) on Trichogramma chilonis (Hymenoptera, Trichogrammatidae), a hymenopteran parasitoid of the cabbage moth, Plutella xylostella (Lepidoptera, Yponomeutidae).

A multi-generation mass breeding colony of the cabbage moth, Plutella xylostella, was found to be infected with a microsporidium, Vairimorpha sp., which is passed transovarially between generations. The microsporidian infection had little impact on the fitness of this lepidopteran pest. However, when Trichogramma chilonis parasitized such infected host eggs, the offspring of this parasitoid species suffered from severe deficiencies. Microsporidian spores, ingested by parasitoid larvae together with the host egg nutrients, gave rise to stages which developed in various tissues of the parasitoid, such as the flight muscle and the nervous system. This infection resulted in a significantly increased rate of metamorphosis failure (related to host age) and reduced longevity and reproductive performance of the parasitoids. There are two main consequences arising from our findings if T. chilonis is to be used in an integrated control strategy against P. xylostella: (1) T. chilonis must be raised on Vairimorpha-free host eggs to receive viable and efficaceous parasitoids for release and (2) if natural populations of the cabbage moth in cruciferous crops are infected with Vairimorpha to a significant extent, the parasitoid must be released repeatedly within infested crop areas.

Regulation of body water balance in reedfrogs (superspecies Hyperolius viridiflavus and Hyperolius marmoratus: Amphibia, Anura, Hyperoliidae) living in unpredictably varying savannah environments.

The regulation of body water balance was examined in the reedfrogs Hyperolius marmoratus taeniatus and Hyperolius viridiflavus ommatostictus. Temperature and stage of post-metamorphic development significantly affected the rate of water uptake. Hydrated reedfrogs prevented hyperhydration by voiding diluted urine when obtaining water. Within 48 hr after rehydration, body fluid osmolality remained at low levels, which may be supportive to counter excessive cutaneous water influx in hydrated frogs. Once evaporative water loss exceeded 10-12% total body mass, reedfrogs became anuric. The rate of water uptake strongly increased with increasing body water deficit. Both the anuric response and the increased rate of water uptake are assumed to strongly enhance the efficacy of using very briefly available water sources during dry-period conditions. Dry-adapted and estivating reedfrogs survived evaporative water losses between 40 and 55% total body mass. Bladder fluid stores contributed substantially to this desiccation tolerance. During a 16-day period of desiccation, H. v. ommatostictus could replace approximately 25% of evaporative water loss from the bladder fluid store. During desiccation, the level of free amino acids selectively increased in the gastrocnemius muscle tissue, which may support cell volume regulation and/or protect cellular structures from osmotic stresses. Even strongly dehydrated reedfrogs rehydrated quickly with no obvious osmoregulatory problem. Rehydration was associated with a higher than expected decrease of free amino acids in the gastrocnemius muscle tissue, a response that may help to protect cells from bursting during fast rehydration.

Adaptations of the reed frog Hyperolius viridiflavus (Amphibia, Anura, Hyperoliidae) to its arid environment : III. Aspects of nitrogen metabolism and osmoregulation in the reed frog, Hyperolius viridiflavus taeniatus, with special reference to the role of iridophores.

Reed frogs of the superspecies Hyperolius viridiflavus occur throughout the seasonally very dry and hot African savannas. Despite their small size (300-700 mg), estivating reed frogs do not avoid stressful conditions above ground by burrowing into the soil, but endure the inhospitable climate relatively unprotected, clinging to mostly dry grass stems. They must have efficient mechanisms to enable them to survive e.g. very high temperatures, low relative humidities, and high solar radiation loads. Mechanisms must also have developed to prevent poisoning by the nitrogenous wastes that inevitably result from protein and nucleotide turnover. In contrast to fossorial amphibians, estivating reed frogs do not become torpid. Reduction in metabolism is therefore rather limited so that nitrogenous wastes accumulate faster in these frogs than in fossorial amphibians. This severely aggravates the osmotic problems caused by dehydration. During dry periods total plasma osmolarity greatly increases, mainly due to urea accumulation. Of the total urea accumulated over 42 days of experimental water deprivation, 30% was produced during the first 7 days. In the next 7 days rise in plasma urea content was negligible. This strong initial increase of urea is seen as a byproduct of elevated amino acid catabolism following the onset of dry conditions. The rise in total plasma osmolarity due to urea accumulation, however, is not totally disadvantageous, but enables fast rehydration when water is available for very short periods only. Voiding of urine and feces ceases once evaporative water loss exceeds 10% of body weight. Therefore, during continuous water deprivation, nitrogenous end products are not excreted. After 42 days of water deprivation, bladder fluid was substantially depleted, and urea concentration in the remaining urine (up to 447 mM) was never greater than in plasma fluid. Feces voided at the end of the dry period after water uptake contained only small amounts of nitrogenous end products. DSF (dry season frogs) seemed no to be uricotelic. Instead, up to 35% of the total nitrogenous wastes produced over 42 days of water deprivation were deposited in an osmotically inert and nontoxic form in iridophore crystals. The increase in skin purine content averaged 150 µg/mg dry weight. If urea had been the only nitrogenous waste product during an estimation period of 42 days, lethal limits of total osmolarity (about 700 mOsm) would have been reached 10-14 days earlier. Thus iridophores are not only involved in colour change and in reducing heat load by radiation remission, but are also important in osmoregulation during dry periods. The selective advantages of deposition of guanine rather than uric acid are discussed.

Superpatriot opposition to community mental health programs.

Superpatriots' concerns about mental health programs are explored. Superpatriots are defined by nationalistic conservatism, the perception of a major internal communist threat in America, and a commitment to action. Their opposition to mental health programs involves the belief that psychological testing invades privacy and that such programs are extensions of federal bureaucracy, encourage immorality, are ideologically biased, and are part of a communist plot to destroy America. Superpatriots who were interviewed werenot disturbed or alienated. They were strongly fundamentalist in religion, dogmatic, moralistic, and informally associated with other superpatriots through neighborhood groups.