Treatment with interleukin-18 binding protein ameliorates Toxoplasma gondii-induced small intestinal pathology that is induced by bone marrow cell-derived interleukin-18.

Peroral infection with Toxoplasma gondii results in a Th1-type immunopathology characterized by small intestinal necrosis and is dependent on IL-18. In the present study, we investigated whether treatment with IL-18 binding protein (IL-18bp) prevents ileal pathology. We observed increased expression of IL-18bp in intestinal biopsies of mice following infection. Whereas small intestines of control mice showed severe necrosis with complete destruction of the small intestinal architecture, mice treated with IL-18bp daily displayed only mild inflammatory changes including flattening of villi and edema in the space between the epithelium and lamina propria. Small intestinal parasite loads and concentrations of pro-inflammatory cytokines did not differ in control and IL-18bp-treated mice. Binding of IL-18 to immobilized IL-18bp revealed a remarkably slow dissociation rate, indicating high affinity. Using chimeric mice we observed that bone marrow-derived rather than stromal cells were the primary source of IL-18 that resulted in small intestinal pathology following peroral infection with T. gondii. In conclusion, the results presented here suggest that IL-18bp may be an effective and safe treatment for small intestinal inflammation. Antigen-presenting rather than epithelial cells appear to be the main source of IL-18 in T. gondii-induced small intestinal inflammation.

Local mechanical properties of the head articulation cuticle in the beetle Pachnoda marginata (Coleoptera, Scarabaeidae).

Insect exoskeleton (cuticle) has a broad range of mechanical properties depending on the function of a particular structure of the skeleton. Structure and mechanical properties of the specialised cuticle of insect joints remain largely unknown to date. We used scanning (SEM) and transmission electron microscopy (TEM) to obtain information about the material structure of the gula plate, the head part of the head-to-neck articulation system in the beetle Pachnoda marginata. The surface of this cuticle appears rather smooth in SEM. The fibers of the exocuticle are partly oriented almost perpendicular to the surface, which is rather unusual for arthropod cuticle. Nanoindentation experiments were performed to determine the local mechanical properties (hardness and elastic modulus) of the gula material. To understand the effect of desiccation and the influence of an outer wax layer on the mechanical behavior of the material, the samples were tested in fresh, dry and chemically treated (lipid extraction in organic solvents) conditions. Nanoindentation results were found to be strongly influenced by desiccation but only slightly by lipid extraction. Decreasing water content ( approximately 15-20% of the cuticle mass) led to an increase in hardness (from 0.1 to 0.49 GPa) and elastic modulus (from 1.5 to 7.5 GPa). The lipid extraction caused a slight further hardening (to 0.52 GPa) as well as stiffening (to 7.7 GPa) of the material. The results are discussed in relation to the mechanical function of the gula plate.

Composite structure of the crystalline epicuticular wax layer of the slippery zone in the pitchers of the carnivorous plant Nepenthes alata and its effect on insect attachment.

The slippery zone situated below the peristome inside pitchers of most carnivorous plants from the genus Nepenthes is covered with a thick layer of epicuticular wax. This slippery zone is reported to play a crucial role in animal trapping and prey retention. In N. alata, the wax coverage consists of two clearly distinguished layers. These layers differ in their structure, chemical composition and mechanical properties, and they reduce the insect attachment in different ways. The lower layer resembles foam, composed of interconnected membraneous platelets protruding from the surface at acute angles. The upper layer consists of densely placed separate irregular platelets, located perpendicular to the subjacent layer. Crystals of the upper layer bear small stalks, directed downwards and providing connections to the lower layer. These morphological distinctions correlate with differences in the chemical composition of waxes. The compound classes of alkanes, aldehydes, primary alcohols, free fatty acids, esters and triterpenoids occurred in extracts from both wax layers, but in different proportions. Chain length distributions in aliphatics were different in extracts from the lower and the upper wax layers. Waxes of the upper and lower layers exhibited different mechanical properties: wax of the lower layer is harder and stiffer than that of the upper layer. Moreover, crystals of the upper layer are brittle and may be easily exfoliated or broken to tiny pieces. Laboratory experiments using tethered insects showed that both wax layers reduce the attachment force of insects. It is assumed that a decrease in insect attachment on the two distinct wax layers is provided by the two different mechanisms: (1) crystals of the upper wax layer contaminate insects' adhesive pads; (2) the lower wax layer leads to a reduction of the real contact area of insects' feet with the plant surface.

Palliative education: a didactic and experiential approach to teaching end-of-life care.

BACKGROUND: The training in palliative care that health professionals receive is inadequate. An aging population, changing systems of health care delivery, and the debate about euthanasia and physician-assisted suicide increase the importance of ongoing education about palliative care. METHODS: Three modules are offered by the University of California, Davis, West Coast Center for Palliative Education (WCCPE). Module 1, offered on-site, blends didactic and field learning using lectures, case studies, patient contact, and role modeling. Module 2 programs, held off-site, are customized in collaboration with the sponsor to address local needs and concerns. This module emphasizes group discussion and problem solving. Module 3 trains health care and custody staff and volunteer inmates at correctional facilities. Inmate training focuses on developing communication skills and a capacity to empathize through experiential exercises, dialog, and role-playing. RESULTS: Off-site training significantly improved self-assessed knowledge about pain management and attitudes towards end-of-life care. Qualitative measures showed enhanced care-delivery skills for participants in all three modules. CONCLUSIONS: Palliative care education can be enhanced when delivered close to the point of care using multimodal techniques that influence attitudes as well as knowledge.

Laser catheter coagulation of normal and scarred ventricular myocardium in dogs.

BACKGROUND AND OBJECTIVE: Larger lesions would increase success rates of catheter ablation of ventricular arrhythmias. Therefore, improved radio frequency current application techniques, but also alternative energy sources, are being investigated. The purpose of this study was to determine morphology and dimensions of ventricular lesions induced by transcatheter application of laser energy. MATERIAL AND METHODS: A total of 244 lesions were produced by Nd:YAG laser pulses, 1,064 nm, 10-30 W, 15-60 s, percutaneously (endocardial approach, n = 124) and under visual control (epicardial approach, n = 120) in the left ventricular walls of 24 anesthetized dogs. RESULTS: Dimensions of lesions increased with the amount of energy applied. Maximal values were obtained at 20 W, 60 s: depth = 12.6 +/- 1.1 mm (transmural); width = 15.0 +/- 2.8 mm; volume = 1,582 +/- 777 mm3. Volumes of lesions did not change significantly when induced through previously scarred myocardium. Histologically, lesions were clear-cut, without crater or thrombus formation. Procedures and follow-up periods of up to 22 months were without complications. CONCLUSION: Nd:YAG laser pulses at 10-20 W and 15-60 s produce homogeneous myocardial lesions of coagulation necrosis of reproducible sizes, in a controllable manner, without unwanted effects on the ventricular walls, in normal and through scarred myocardium of dogs. The laser method is a promising alternative for ablation of ventricular arrhythmias including candidates with ischemic heart disease.

Laser versus radiofrequency catheter ablation of ventricular myocardium in dogs: a comparative test.

To compare the effects of laser light with those of radiofrequency (RF) current on ventricular myocardium, a total of 36 lesions (endocardial approach n = 10 each and epicardial approach n = 8 each) were produced by either transcatheter laser (Nd:YAG, 1,064 nm, 30 W, 30 s) or RF (70 degrees C, 30 s) catheter applications in the beating hearts of 4 dogs. Volumes of coagulated myocardium in endo-/epicardial approaches were 996 +/- 73/1,075 +/- 82 (laser) and 111 +/- 38/44 +/- 5 mm3 (RF). RF lesions showed intramural bleeding, rupture and dissociation of myocardial fibers, tissue vaporization with crater and thrombus formation. Transcatheter application of laser light produced significantly larger and better reproducible lesions than RF current, without undesirable effects on the ventricular walls.

Mapping guided laser catheter ablation of the atrioventricular conduction in dogs.

Safety and efficacy of mapping guided laser catheter ablation of the AV junction was tested in a canine model. A total of 43 laser pulses (continuous wave, Nd:YAG, 1,064 nm, 30 W, irradiated spot diameter 2.0-2.5 mm) were delivered in 15 dogs (2-5 per dog) via a novel laser catheter system. Pulses were selectively aimed at: (1) the AV node; (2) the His bundle; and (3) the bundle branches. Laser pulses of 9.7 +/- 1.1 seconds (n = 31) produced reversible conduction disturbances in the targeted segment of the AV conduction system, while pulses of 28.6 +/- 7.9 seconds (n = 9) resulted in chronic block. The dogs survived the procedure without complications. Follow-up was 6.5-10.5 months. Histopathologically, lesions showed clear-cut oval-shaped areas of fibrosis of 0.5-18.0 mm in diameter and 0.5-3.5 mm (transmural) in depth, depending on the irradiation time. Pervenous mapping guided laser catheter irradiation of the AV junction can produce AV block consistently and selectively in the targeted segment of the right ventricular conduction system in dogs. The method is safe and can be performed in a controllable manner by using the catheter system presented.

Megestrol acetate in patients with AIDS and cachexia.

OBJECTIVE: To study the effects of a megestrol acetate liquid formulation (800 mg/d) on body weight, body composition, caloric intake, and mental outlook in patients with the acquired immunodeficiency syndrome (AIDS) who had cachexia. DESIGN: Twelve-week, multicenter, randomized, double-blind, placebo-controlled trial. SETTING: Multiple clinical centers. PATIENTS: 100 patients with AIDS who had weight loss of 10% or more of ideal body weight were randomly assigned to placebo (n = 48) or megestrol acetate (n = 52). MEASUREMENTS: Caloric intake, body weight, body composition, and sense of well-being. RESULTS: Most patients receiving megestrol acetate had increased caloric intake resulting in body weight gain (mainly fat mass). From baseline to week 8, the megestrol acetate group increased their daily caloric intake by 608 calories, whereas the placebo group increased intake by 134 calories (difference, 474 calories; 95% CI, -68 to 880 calories). Body weight in the megestrol acetate group increased by 3.86 kg from baseline to week 8, although it decreased by 0.46 kg in the placebo group (difference, 4.32 kg; CI, 2.42 to 6.22 kg). At week 8 in the megestrol acetate group, patients gained 3.68 kg in fat mass and those in the placebo group lost 0.28 kg (difference, 3.96 kg; CI, 2.49 to 5.43 kg). Body water, lean mass, and patient survival were not statistically different between treatment groups. Patients treated with megestrol acetate had an increased sense of well-being when compared with patients who received placebo. CONCLUSIONS: This megestrol acetate liquid formulation is well tolerated, increases food intake, results in body weight gain, and improves the sense of well-being in cachectic patients with AIDS.

Catheter-directed laser coagulation of atrial myocardium in dogs.

The feasibility of transcatheter laser coagulation of atrial myocardium was tested in a canine model by using a combined electrode-laser catheter. In 17 anaesthetized beagles a total of 264 lesions, 12-19 per dog, and 3-5 in each area were produced in: (1) the lateral walls, (2) the posterior right atrial walls, (3) the inter-atrial septum, and (4) the atrial appendage. The power source was a continuous wave Nd:YAG laser. Irradiance was 1 kW.cm-2, at a wave length of 1064 nm, the irradiated spot diameter was 2.0-2.5 mm, and the pulse duration 5-60 s. Local intra-cardiac atrial potentials recorded from the targeted areas during laser irradiation dwindled after onset of the laser pulse, and their amplitude was reduced persistently by pulses of 15 s or longer. Histopathologically, the acute lesions showed intramural haemorrhage and coagulation necrosis, but there was no tissue vaporization or crater formation. Chronic lesions showed clear-cut oval-shaped areas of transmural fibrosis. Diameters of lesions, dependent on the amount of laser energy applied, measured from 4.6 +/- 0.5 mm (450 J) to 7.8 +/- 1.4 mm (1800 J). Follow-up lasted 6-25 months (average 10.5). All the animals survived the procedure without complications. Transcatheter laser coagulation of atrial myocardium is safe and can be performed in a controllable manner by using the catheter system presented.

Numerical abnormalities of chromosome 7 in human prostate cancer detected by fluorescence in situ hybridization (FISH) on paraffin-embedded tissue sections with centromere-specific DNA probes.

Fluorescence in situ hybridization (FISH) using chromosome-specific alpha-satellite DNA probes for chromosomes 7, 8, and 12 was performed on paraffin-embedded tissue sections and touch imprint preparations of 53 cases of human prostate cancer. Subsequent haematoxylin and eosin (H & E) staining of the hybridized tissue sections allowed unambiguous assignment of hybridization signals either to tumour or to non-tumorous parenchyma. Fifty-three cases of human prostate cancer were evaluated for numerical aberrations of chromosome 7. Scoring 200 cells of tumour and non-tumorous parenchyma in each case revealed abnormalities exclusively in tumour parenchyma in 41 cases (77 per cent). Ten of 41 cases (24 per cent) showed trisomy 7, and 15 cases (37 per cent) monosomy 7 or trisomy 7 in combination with monosomy 7, respectively. Sixteen cases (39 per cent) exhibited polysomy 7 in cells of the tumour parenchyma. In the tumour tissue in one case, different polyploid clones (triploid, tetraploid) and polysomy 7 could be identified by double hybridization with chromosome-specific DNA probes for chromosome 7, plus 8 or 12. The indicated numerical aberrations of chromosome 7 were correlated with 78 per cent of advanced pathological stages or poorly differentiated tumours (pT3/4 or G3) of prostate carcinomas. A statistical analysis of the data revealed significant relationships of particular numerical abnormalities of chromosome 7 to different pathological categories (pT, G, pN) of tumour classification. For the T-classification, the frequency of cells carrying polysomy 7 and polysomy 7/+7 increases significantly from pT1 to pT3/4 (P = 0.022).(ABSTRACT TRUNCATED AT 250 WORDS)

Transcatheter laser atrial septostomy in rabbits.

The feasibility of percutaneous transluminal catheter-directed laser (Argon multiline 488/514 nm) atrial septostomy under echocardiographic guidance was studied in eight rabbits. In five animals the interatrial septum was exposed to laser energy for 30 s (n = 1) or for 10 s (n = 4) by using the continuous wave (cw) mode of irradiation. In the other three animals chopped mode of irradiation was applied for 10 s at 7 W. Echocardiography allowed visualization of both atrial cavities and the interatrial septum, the tip of the catheter including the optical fiber tip as well as the flow direction of contrast echoes during the laser firing. Blood clotting with thrombus formation was present following the cw mode of irradiation. The defects created in the interatrial septa of < or = 0.3 mm in diameter had irregular black borders and, histopathologically, were surrounded by a zone of coagulation necrosis of < or = 0.2 mm and vacuolization (vacuoles of < 0.1 mm in diameter). After 30 s of lasering a huge defect was conspicuous in the interatrial septum which extended up to the right and left atrial roof. The chopped mode of irradiation induced less blood clotting and narrow channels of < or = 0.08 mm through the interatrial septa with a small zone of coagulation necrosis of < or = 0.05 mm and without carbonization and vacuolization. This study demonstrates that laser atrial septostomy is technically feasible. However, prior to the extension of the method to humans, further investigation especially considering other laser power sources, possibly more suitable for this application such as Neodymium-YAG or Excimer lasers is warranted.

Thermal effects and histologic changes from Nd:YAG laser irradiation on normal and diseased aortic tissue using a novel angioplasty catheter with a mobile optical fiber: an in vitro assessment.

Although various laser angioplasty devices are currently being examined, thermal damage and perforation of the vessel wall remains the major acute complication of vascular laser recanalization. Consequently, the aim of this study was to investigate the thermal effects and histologic changes from laser irradiation (Nd:YAG, 1064 nm) on normal and diseased aortic tissue using a novel angioplasty device. During laser emission the coaxially guided optical fiber tip was positioned in reference to the end hole of the metallic capped probe as follows: (1) at the end hole (metal-cap position), (2) protruding 10 mm from that end hole (bare-fiber position), (3) withdrawn 5 mm into the metal cap's lumen (hot-tip position). In total, 96 laser impacts (25 joule: 5 W, 5 s, each) were produced on normal and atherosclerotic aorta in air through a 0.2-mm-core-diameter silica quartz fiber, with direct contact on the intimal surface of the target tissue by both the fiber and the metal cap and by either the fiber or the metal cap (n = 32 each). Tissue temperature was measured by means of special sensors positioned opposite the irradiated intimal spot in direct contact with the adventitial surface. Morphohistologic evaluation of lesions was performed and injury indexes were determined.

Human atherosclerotic coronary artery xenografts: a model for investigation of transluminal recanalization.

A model for testing transluminal recanalization techniques was developed. Fragments of human atherosclerotic coronary arteries were transplanted into carotid arteries of dogs and evaluated by angiographic, angioscopic, and histologic study within a three-month period. An inflammatory response was most intense within the first week. By two weeks no inflammation was noted. Total occlusion (n = 13) and stenosis (n = 11) of the carotid arteries were achieved without complications. The model is easy to produce within a short period and the arterial occlusion resembles human vascular disease. This model has been used to evaluate laser recanalization of vascular obstructions.

Laser balloon angioplasty: technical realization and vascular tissue effects of a modified concept.

A modified concept using a movable fiber with radial light dispersion was developed for combining mechanical balloon dilatation and intraluminal circumferential Nd-Yag laser irradiation of the arterial wall. The aims of the study were the technical feasibility and the acute and chronic vascular tissue effects of laser-assisted balloon dilatation. The carotid arteries (n = 9 dogs) and femoral arteries (n = 5 dogs) of dogs were mechanically dilated and simultaneously circumferentially irradiated through the balloon by 1,064 nm Nd-Yag laser (20-25 W). Temperature at the adventitial surface was kept constant at 50 degrees C, 60 degrees C, 70 degrees C, or 80 degrees C for either 8 or 15 seconds by a computerized feedback system for temperature control. Angiographic and histological results were available acutely, subacutely (2 days), and at 3 months. Angiographically, stable and smooth enlargement of the lumen was demonstrated acutely. At 3 months, occlusions, probably thrombotic in origin, had occurred in 5 of the carotid arteries and none of the femoral arteries. Histologically, laser-induced coagulation of the arterial wall with loss of cellular elements was demonstrated. Collagen and elastic fibers remained relatively intact. In two carotid arteries intimal proliferation was observed at the treated site. Thus, this technique appears to be technically feasible, yet further study is needed to assess its potential to reduce or repair acute vascular complications (dissections) and to reduce restenoses after percutaneous transluminal coronary angioplasty (PTCA). However, the clinical value of this technique appears to be limited in view of the thromboses and reactive proliferations observed in this preliminary study.

Effects of Nd: YAG laser coagulation of myocardium on coronary vessels.

Laser coagulation of arrhythmogenic myocardium proved to be an effective surgical therapy for refractory arrhythmias. To determine the influence of Nd: YAG laser coagulation of myocardium on coronary vessels, a total of 48 transcatheter laser impacts (10 W, 10 sec, 7 W mm2) were directed to the left ventricular free wall via endocardial (24 lesions in 2 dogs) or epicardial (24 lesions in 2 dogs) approach. In 8 of 24 endomyocardial lesions (2 and 6 months old) coronary vessels with a diameter of greater than 50 microns were found within the coagulation zones. The volume of these lesions was significantly (P less than 0.01) smaller (139 +/- 43 mm3) than those (n = 16) with coronary vessels measuring less than 50 microns (311 +/- 87 mm3). Volumes of epimyocardial lesions (1-2 hours old) produced by transcoronary irradiation with normal coronary blood flow were significantly (P less than 0.01) smaller (31 +/- 17 mm3) than with reduced (73 +/- 22) or interrupted (119 +/- 34 mm3) blood flow (n = 8, each). Both directly irradiated coronary vessels and those found within the coagulation zones and scars appeared histologically normal through all layers with an intact intima without fibrosis or thrombosis. The ultrastructure of irradiated arteries, even with total interruption of blood flow, was no different from that of non-irradiated controls. Thus, coronary artery blood flow significantly reduces the volume of coagulated myocardium, whereas the vessels themselves appear to remain undamaged by laser irradiation as used for myocardial coagulation.

[Use of the thermal laser effect of laser irradiation for cardiovascular applications exemplified by the Nd:YAG laser]. / Die Nutzung der thermischen Wirkung von Laserstrahlung für kardiovaskuläre Anwendungen am Beispiel des Nd:YAG-Lasers.

Techniques of percutaneous transluminal application of laser energy for vessel recanalization have been used clinically since 1983. The commonly used Nd:YAG and argon lasers achieve ablation of atherosclerotic plaques by thermal action (vaporization). In order to reduce undesirable thermal damage in the neighborhood of the target tissue and to avoid vessel perforation, optimal irradiation parameters, modified (atraumatic) fiber tips (hot tips, sapphires), and steerable catheter systems needed to be implemented. Favorable results from peripheral application have encouraged use in the coronary circulation. More recently, coagulative tissue effects of circumferential irradiation of the vessel wall during balloon dilatation have been used for stabilization of acute and late results after mechanical balloon angioplasty. Enhancement of the differential light absorption of atherosclerotic plaque by use of biological dyes may further improve selective intravascular laser application. Intraoperative ECG-guided laser coagulation of arrhythmogenic areas of myocardium is a method for treatment of malignant arrhythmias. Transluminal non-operative application of myocardial laser photocoagulation has now been tested experimentally and shown to be safe and effective. There was no arrhythmogenicity or thermal damage of coronary arteries associated with this method. Innovative techniques such as nanosecond pulsed excimer lasers (athermal action) and development of "intelligent" lasers--which are equipped with spectroscopy-guided feedback systems for plaque recognition--have opened new perspectives and will further improve safety and efficacy of clinical laser application. However, according to current experience, the thermally acting Nd:YAG laser is an effective and versatile mode of laser therapy for selected cardiovascular indications.

Percutaneous Nd:YAG laser coagulation of ventricular myocardium in dogs using a special electrode laser catheter.

A novel catheter system was used for intracardiac electrogram recordings, ventricular pacing and continuous-wave Nd:YAG laser (1,064 nm) irradiation of ventricular myocardium in eight dogs. Radiation at a power of 10 W for 3, 5, and 10 seconds was delivered through a 400 microns optical fiber. Power density was 15 W/mm2. A total of 96 laser injuries (12 per dog) were produced in selected sites in both the right and the left normal canine ventricle. Ventricular arrhythmias were noted during 12 of 96 (12.5%) laser pulses. Programmed electrical stimulation performed during control study immediately (all dogs) at 2 days (two dogs), and 4 months (4 dogs) following the experiments showed no episodes of sustained or nonsustained ventricular tachycardia. Radiation energies up to 50 J (10 W over 5 s) caused focal injuries of homogeneous coagulation/fibrosis localized to the target area, without vaporizing tissue and forming craters. Morphometrically and histologically there was a direct relationship between the energy of radiation delivered, and the extent and severity of the injury produced. The maximum size of lesions measured 7/11 mm (diameter/depth). Using a special catheter system laser coagulation of myocardium can be accomplished percutaneously. This method can create controlled subendocardial injuries without major side effects and appears to overcome most disadvantages of transcatheter high energy direct-current shocks when used as a regular course of procedure in ablation of arrhythmogenic tissue in the heart.