Biomedical subjects

C Weiss

Publications and source records attributed to C Weiss.

At least 55 records · Page 3Linked to original sources

PubMed2001

A protein kinase associated with apoptosis and tumor suppression: structure, activity, and discovery of peptide substrates.

Death-associated protein kinase (DAPK) has been implicated in apoptosis and tumor suppression, depending on cellular conditions, and associated with mechanisms of disease. However, DAPK has not been characterized as an enzyme due to the lack of protein or peptide substrates. Therefore, we determined the structure of DAPK catalytic domain, used a homology model of docked peptide substrate, and synthesized positional scanning substrate libraries in order to discover peptide substrates with K(m) values in the desired 10 microm range and to obtain knowledge about the preferences of DAPK for phosphorylation site sequences. Mutagenesis of DAPK catalytic domain at amino acids conserved among protein kinases or unique to DAPK provided a link between structure and activity. An enzyme assay for DAPK was developed and used to measure activity in adult brain and monitor protein purification based on the physical and chemical properties of the open reading frame of the DAPK cDNA. The results allow insight into substrate preferences and regulation of DAPK, provide a foundation for proteomic investigations and inhibitor discovery, and demonstrate the utility of the experimental approach, which can be extended potentially to kinase open reading frames identified by genome sequencing projects or functional genetics screens and lacking a known substrate.

Amino Acid Sequence↗

PubMed2001

Tumor oxygenation after radiotherapy, chemotherapy, and/or hyperthermia predicts tumor free survival.

PURPOSE: To investigate the influence of different treatment modalities (radiotherapy, chemotherapy, and hyperthermia) on the oxygenation of human tumor xenografts and to correlate it with the tumoricidal effect we conducted this study. METHODS AND MATERIALS: Human-derived head-and-neck squamous cell carcinoma xenografts (implanted in nude mice/nine groups of 10 mice) were treated with various treatment modalities and combinations of them (radiation with 5 x 2 or 10 x 2 Gy, hyperthermia at 41 degrees C or 41.8 degrees C, chemotherapy with ifosfamide [32 mg/kg] or cisplatin [2 mg/kg]). The tumor volume was evaluated 3 times per week until Day 60. Tumor pO(2) was measured at Day 1, 5, 8, and 12 with a polarographic pO(2) histograph. RESULTS: Within treatment time (maximum, 10 days) the median pO(2) increased in all groups (except the control group), concomitantly the fraction of measurements of pO(2) that were less than 10 mm Hg showed a constant decrease (p < or = 0.001). The highest difference between the median pO(2) values and the fraction of measurements of pO(2) that were less than 10 mm Hg at the start and 1 week after the end of therapy occurred in the groups with radiochemothermotherapy (triple-modality therapy; p< or = 0.001). At Day 60, the highest rate of complete remissions was observed in the triple-modality therapy groups. CONCLUSION: Tumor oxygenation under a single or combined cancer treatment is correlated with treatment efficacy in terms of complete remissions at Day 60. The posttherapeutic fraction of measurements of pO(2) that were less than 10 mm Hg correlates even better with the long term tumor free survival than the median pO(2) values or the pretherapeutic fraction of measurements of pO(2) that were less than 10 mm Hg.

Animals↗

PubMed2001

Interleukin 9 promotes influx and local maturation of eosinophils.

The interleukin 9 (IL-9) pathway has recently been associated with the asthmatic phenotype including an eosinophilic tissue inflammation. The mechanism by which IL-9 affects eosinophils (eos) is not known. To investigate whether this cytokine has a direct activity on the development of eos and eosinophilic inflammation, a model of thioglycolate-induced peritoneal inflammation was used in IL-9 transgenic (TG5) and background strain (FVB) mice. In this model, a transient eosinophilic infiltration in the peritoneal cavity was observed in FVB mice 12 to 24 hours after thioglycolate injection that coincided with peak IL-5 and IL-9 release. In contrast, TG5 mice developed a massive eosinophilia that persisted at high levels (81% of total cells) even 72 hours after thioglycolate injection. Release of eosinophilic major basic protein (MBP), IL-4, and IL-5 to the peritoneal cavity of these mice was significantly increased when compared with the control FVB strain. To study the mechanism by which IL-9 exerts its effect on eos, bone marrow or peritoneal cells were cultured in the presence of IL-5, IL-9, or their combination in vitro. IL-5 alone was able to generate significant numbers of eos in TG5 but not FVB mice, whereas a combination of IL-5 and IL-9 induced marked eosinophilia in both strains indicating a synergism between these 2 cytokines. These data suggest that IL-9 may promote and sustain eosinophilic inflammation via IL-5-driven eos maturation of precursors.

Adoptive Transfer↗

PubMed2001

Strong acceleration of murine lupus by injection of the SmD1(83-119) peptide.

OBJECTIVE: The mechanisms of IgG anti-double-stranded DNA (anti-dsDNA) antibody induction are incompletely understood. We recently demonstrated a high prevalence of autoantibodies to the C-terminus of SmD1 in patients with systemic lupus erythematosus (SLE) that was closely associated with anti-dsDNA reactivity. The aim of the present study was to analyze the influence of the SmD1 C-terminus on the generation of pathogenic anti-dsDNA antibodies in a murine model of SLE. METHODS: Female lupus-prone prenephritic (NZB x NZW)F1 mice (NZB/NZW mice) as well as female control BALB/c, NZW, and (BALB/c x NZW)F, mice (CWF1 mice) were subcutaneously injected with keyhole limpet hemocyanin (KLH)-coupled SmD1(83-119). Controls received injections of recombinant SmD1 (rSmD1), KLH-rSmD1, KLH-coupled randomized peptide of SmD1(83-119), ovalbumin, or saline. Animals were monitored for survival and proteinuria and for levels of plasma creatinine, urea, and autoantibodies. In addition, histologic examinations were performed and T cell responses against SmD1(83-119) peptide and rSmD1 protein were determined in SmD1(83-119)-treated and -untreated NZB/NZW mice. RESULTS: Immunization with KLH-SmD1(83-119), but not with control peptide, significantly accelerated the natural course of lupus in NZB/NZW mice, with premature renal failure and increased development of anti-dsDNA antibodies. Control strains of mice remained healthy, with no relevant anti-SmD1(83-119) antibodies detectable even after immunization. In contrast to findings in control mice, a T cell response against SmD1(83-119) was already present in unmanipulated NZB/NZW mice, and this response was further amplified after immunization. CONCLUSION: The SmD1(83-119) peptide can influence the pathogenic anti-dsDNA response in the NZB/NZW murine lupus model. The data suggest that an SmD1(83-119)-specific T cell response is critical. Therefore, modulation of these autoantigen-specific T cells by tolerance induction may provide a therapeutic approach to specific immunosuppression in lupus.

Animals↗

PubMed2001

Intracellular delivery mediated by an ethosomal carrier.

The goal of this work was to investigate the efficiency of transcellular delivery into Swiss albino mice 3T3 fibroblasts of molecules with various physico-chemical characteristics from ethosomes, phospholipid vesicular carriers containing ethanol. The probes chosen were: 4-(4-diethylamino) styryl-N-methylpyridinium iodide (D-289), rhodamine red dihexadecanoylglycerophosphoethanolamine (RR) and fluorescent phosphatidylcholine (PC*). The penetration of these fluorescent probes into fibroblasts and nude mice skin was examined by CLSM and FACS. CLSM micrographs showed that ethosomes facilitated the penetration of all probes into the cells, as evident from the high-intensity fluorescence. In comparison, when incorporated in hydroethanolic solution or classic liposomes, almost no fluorescence was detected. The intracellular presence of each of the three probes tested, was evident after 3 min of incubation. Furthermore, with ethosomal D-289, fluorescence was also seen in the fibroblast nucleus. Enhanced delivery of molecules from the ethosomal carrier was also observed in permeation experiments with the hydrophilic calcein and lypophilic RR to whole nude mouse skin. Calcein penetrated the skin to a depth of 160, 80 and 60 microm from ethosomes, hydroethanolic solution and liposomes, respectively. Maximum fluorescence intensities measured for RR delivered from ethosomes, hydroethanolic solution and liposomes were 150, 40 and 20 AU, respectively. Fibroblast viability tests showed that the ethosomal carrier is not toxic to the cultured cells.

3T3 Cells↗

PubMed2001

Regulation of chromogranin biosynthesis by neurotrophic growth factors in neuroblastoma cells.

Polypeptide growth factors secreted from the target tissue determine the choice of transmitter synthesis in the innervating nerves. We have investigated whether they also influence the expression of chromogranins and neuropeptide Y, components co-stored with the neurotransmitters within large dense-core vesicles. IMR-32 and SH-SY5Y human neuroblastoma cells were treated for up to six days with various neurotrophic growth and differentiation factors. For chromogranins A and B, no significant changes at the mRNA level were observed and for chromogranin A this was confirmed at the protein level. The expression of secretogranin II/pro-secretoneurin mRNA, however, was considerably enhanced in both cell lines after basic fibroblast growth factor treatment. In IMR-32 cells we determined a fast and continuous induction, whereas the up-regulation in SH-SY5Y cells was more delayed. A transient elevation of secretogranin II/pro-secretoneurin mRNA levels was seen in SH-SY5Y cells in response to epidermal growth factor. In these cells we also measured the amounts of secretogranin II/pro-secretoneurin protein which were increased by both growth factors. In addition to the above described changes in secretogranin II/pro-secretoneurin biosynthesis we extended and confirmed data available on neuropeptide Y. We found a qualitatively similar pattern of biosynthesis regulation as for secretogranin II/pro-secretoneurin, indicating that the ultimately increased expression of the two proteins may be characteristic of the phenotypic differentiation after growth factor treatment. Moreover, this finding of a concomitant regulation further emphasizes the concept of secretogranin II/pro-secretoneurin being a neuropeptide precursor from which the functional peptide secretoneurin is proteolytically liberated.

Cell Differentiation↗

PubMed2001

Optimized mapping of slow pathway ablation guided by subthreshold stimulation: a randomized prospective study in patients with recurrent atrioventricular nodal re-entrant tachycardia.

OBJECTIVES: This randomized prospective study sought to assess the value of slow pathway (SP) mapping and ablation guided by subthreshold stimulation (STS) in comparison with a strategy based on conventional criteria. BACKGROUND: Previous studies have demonstrated that STS can be used as a highly specific and sensitive marker for successful SP ablation in the setting of atrioventricular nodal re-entrant tachycardia (AVNRT). Nonetheless, thus far this mapping strategy has not been investigated in contrast with the conventional approach. METHODS: One hundred patients with sustained AVNRT were included. Fifty patients (group A) were randomly assigned to endocardial mapping and SP ablation using currently established criteria. In the other 50 patients (group B), SP ablation was guided by STS mapping. In group B patients, only radiofrequency current (RFC) was applied if additionally constant current STS (up to 5 mA) during AVNRT interrupted the tachycardia due to selective block within the SP. RESULTS: Termination of AVNRT without apparent capture was observed during STS in 47 of 50 group B patients (94%). In all cases, this effect was indicative for successful subsequent SP ablation. The mean number of RFC pulses required for successful SP ablation was significantly lower in patients assigned to the STS-guided strategy (1.6 +/- 1.3 vs. 3.9 +/- 3.4; p = 0.0003). Similarly, the mean procedure duration was shorter in the STS group (156.9 +/- 33.5 vs. 173.2 +/- 49.7 min; p = 0.0221); the fluoroscopy time was comparable between both groups (14.1 +/- 8.7 vs. 16.9 +/- 10.6 min; p = 0.1278). CONCLUSIONS: Subthreshold stimulation is an effective method for detection of target sites for selective SP ablation. This technique helps to minimize the number of RFC pulses without prolongation of the overall procedure and fluoroscopy time required for SP ablation.

Aged↗

PubMed2001

Electroanatomical Mapping (CARTO) of ectopic atrial tachycardia: impact of bipolar and unipolar local electrogram annotation for localization the focal origin.

UNLABELLED: Electroanatomical Mapping (CARTO) allows a tridimensional localization of ectopic atrial tachycardia (EAT). No standardized recommendation exists for annotation the local activation time in EAT using this new technology. In the present study bipolar local electrogram were used for CARTO guided RF ablation of EAT. In comparison the same maps were retrospectively analyzed by annotation the unipolar local electrogram. METHODS: In 15 consecutive patients (6m, 51+/-14 y) with EAT CARTO mapping was guided by annotation the earliest onset of the bipolar local electrogram. Following successful RF ablation the obtained EAT maps were subsequently evaluated by annotation of the earliest steepest negative intrinsic deflection of the unipolar local electrogram. Both CARTO maps were compared with regard to the region of focal EAT origin. RESULTS: RF ablation of all 15 EAT foci guided by annotation the bipolar local electrogram with CARTO was successful with a median of 3 [1-18] pulses and a median fluoroscopy time of 10 min [4-25]. All but one focus was located in the right atrium: posterior to posteroinferior region of the terminal crest in 6, septal region in 5, anterior superior region in 3 cases. One left sided EAT was located at the septum. The bipolar CARTO map demonstrated a "small territory" location of earliest activation (extension of the focus < or =0.4 cm(2)) in 14 out of 15 patients. In a single patient the bipolar map showed several sites of earliest local activation (extension >0.4 cm(2)). On the other side the retrospectively achieved unipolar maps demonstrated an extended region of earliest local activation in 6 out of 15 patients (>0.4 cm(2)). CONCLUSIONS: CARTO maps of EAT by annotation the earliest onset of the bipolar local electrogram provide an efficacious guide for location the focal origin. Extended regions of earliest local activation in EAT might be rather determined by annotation the unipolar in comparison to the bipolar local electrogram.

Adult↗

PubMed2001

Eyeblink conditioning in the rabbit (Oryctolagus cuniculus) with stimulation of the mystacial vibrissae as a conditioned stimulus.

Eyeblink conditioning is a well-understood paradigm for the study of learning and memory and has been successfully employed with the use of auditory and visual conditioned stimuli (CSs). In this study, vibrotactile stimulation of the mystacial vibrissae was examined as an alternative CS in the rabbit (Oryctolagus cuniculus). The technique is described and acquisition of eyeblink conditioning (EBC) with stimulation of a single row of vibrissae in a delay paradigm is reported. Extinction of EBC with presentation of the CS alone is demonstrated, as well as reacquisition with stimulation of a single whisker. Finally, control experiments ensure that the CS has no auditory components. Ipsilateral presentation of the CS and airpuff is a more effective combination for training than contralateral presentations. Vibrotactile stimulation of the vibrissae as a CS will enable further examination of the neural correlates of learning in a well-characterized sensory system.

Animals↗

PubMed2001

The effect of nucleotides and mitochondrial chaperonin 10 on the structure and chaperone activity of mitochondrial chaperonin 60.

Mitochondrial chaperonins are necessary for the folding of newly imported and stress-denatured mitochondrial proteins. The goal of this study was to investigate the structure and function of the mammalian mitochondrial chaperonin system. We present evidence that the 60 kDa chaperonin (mt-cpn60) exists in solution in dynamic equilibrium between monomers, heptameric single rings and double-ringed tetradecamers. In the presence of ATP and the 10 kDa cochaperonin (mt-cpn10), the formation of a double ring is favored. ADP at very high concentrations does not inhibit malate dehydrogenase refolding or ATP hydrolysis by mt-cpn60 in the presence of mt-cpn10. We propose that the cis (mt-cpn60)14.nucleotide.(mt-cpn10)7 complex is not a stable species and does not bind ADP effectively at its trans binding site.

Adenosine Diphosphate↗

PubMed2001

Radiofrequency catheter ablation using long coiled electrodes: impact of irrigation on lesion dimensions and incidence of coagulum formation.

Ablation catheters with multiple long coiled electrodes have been recently developed to induce continuous linear lesions for the treatment of atrial fibrillation. The efficacy and safety of ablation catheters with multiple long coiled electrodes has not been evaluated. The aim of the present in vivo study was to investigate the influence of saline irrigation on lesion dimensions and coagulum formation during RF current ablation using those ablation catheters. In 14 anesthetized sheep, the thigh muscle was prepared as a cradle and filled with heparinized blood (37 degrees C). The quadripolar coiled ablation catheter (electrode length 7 mm, electrode distance 2 mm) was placed parallel to the muscle with standardized 10-g contact pressure. RF current energy was delivered sequentially temperature-(70 degrees C) or power-controlled (10, 20, 30, or 40 W) with additional irrigation of the electrode (10 mL/min normal saline) for 90 seconds. Forty-two of 129 RF current lesions were induced by temperature-controlled and 87 by irrigated ablation. Except for three lesions following low energy irrigated application (10 W), all lesions were continuous. Significantly larger lesions following irrigated RF current applications were produced with a power output of 30 W (depth 0.74 +/- 0.13 cm, width 0.78 +/- 0.13 cm) and 40 W (depth 0.75 +/- 0.16 cm, width 0.92 +/- 0.28 cm) as compared to 20 W (depth 0.47 +/- 0.13 cm, width 0.82 +/- 0.22 cm). Coagulum formation adherent to the electrode was exclusively observed following 18 of 42 nonirrigated RF current ablations. In conclusion, irrigated coiled ablation electrodes induce continuous linear lesions with a power output of 20-40 W. The risk of coagulum formation at the coiled electrode can be avoided by irrigation.

Animals↗

PubMed2001

Subthreshold stimulation at the focal origin of para-Hisian-located ectopic atrial tachycardia.

The focal origin of ectopic atrial tachycardia (EAT) is occasionally located in the superoparaseptal region adjacent to the bundle of HIS. Radiofrequency catheter ablation (RFCA) of EAT in this anatomic location implies the potential hazard of adverse impairment of the AV conduction. Therefore, careful precise mapping is mandatory. Subthreshold stimulation as defined as the delivery of noncaptured low energy pulses has been introduced as an additional mapping technique for slow pathway ablation in the setting of AV nodal reentrant tachycardia and other reentrant tachycardia. A patient with a right superoparaseptal EAT focus, in which subthreshold stimulation (STS) could determine the site of successful subsequent RFCA is described. During STS with EAT termination no AV conduction disturbances, junction-escape rhythms or atrial capture could be recorded. Thus STS may be used as an additional mapping tool to identify successful ablation sites in EAT.

Body Surface Potential Mapping↗

PubMed2001

Role of contact system activation in hemodialyzer-induced thrombogenicity.

BACKGROUND: The contact system is generally believed to be the main trigger of the coagulation cascade during extracorporeal circulation. However, the extent of contact activation, its role for intradialytic thrombin generation as well as the influence of different dialyzer membranes have not been well established. METHODS: In a novel full-scale ex vivo recirculation dialysis model, we investigated the thrombogenicity of three widely used hemodialyzers (Cuprophan Renak RA15-U, Polysulfone F6HPS and AN69XT Nephral 200). The activation of the contact system was evaluated using a newly developed ELISA for factor XIIa-C1-inhibitor complexes. Additionally, we determined free FXIIa (ELISA), thrombin-antithrombin (TAT) complexes, platelet factor 4 (PF4), complement activation (C5a), granulocyte elastase and blood cell counts. The findings in blood from normal volunteers were compared with factor XII-deficient blood. RESULTS: With normal blood AN69 exhibited the highest thrombogenicity in comparison to Cuprophan and Polysulfone, as assessed by TAT generation and platelet consumption. AN69 caused a rapid increase of the FXIIa-C1-inhibitor complexes and of free FXIIa. Despite significant TAT generation with Cuprophan and Polysulfone free FXIIa remained unchanged and the FXIIa-C1-inhibitor complexes stayed below the detection limit. With factor XII-deficient blood Polysulfone exhibited the same TAT generation, whereas the thrombogenicity of AN69 was greatly reduced. CONCLUSIONS: Our data challenge the common assumption that activation of the contact system with generation of FXIIa is the main trigger for coagulation and thrombus formation in hemodialysis. Only the negatively charged AN69 membrane with enhanced thrombogenicity strongly induced contact activation.

Adult↗

PubMed2001

Dacron vs. polytetrafluoroethylene grafts for femoropopliteal bypass: a prospective randomised multicentre trial.

OBJECTIVES: To compare the patency of PTFE (Polytetrafluoroethylene) and unsealed knitted Dacron femoro-popliteal bypasses. DESIGN: Multi-centre prospective randomised trial. MATERIALS AND METHODS: Of 203 patients randomised, 194 were included in the final analysis (103 Dacron grafts and 91 PTFE grafts). The median follow-up was 36 months (range: 6-72 months); the distal anastomosis was above-knee in 141 and below-knee in 53 cases. Univariate comparisons of patency were made by the Kaplan-Meier method, multivariate calculations on the effects of covariables by a Cox regression analysis. RESULTS: There was no difference regarding primary and secondary patency or limb salvage between Dacron and PTFE. The primary 3-year patency for Dacron grafts was 64% (95% confidence interval [C.I.] 55-74%) and for PTFE grafts 61% (C.I. 49-72%). The corresponding 3-year secondary patency was 81% (C.I. 73-89%) and 75% (C.I. 65-86%) respectively, the limb salvage rate 90% (C.I. 84-96%) and 91% (C.I. 84-97%). Upon multivariate analysis below-knee anastomosis was the principal independent predictor of primary graft failure (risk ratio 1.7 [C.I. 1.05-2.8]), impaired secondary patency was associated with infragenicular bypass (risk ratio 3.3 [C.I. 1.8-6.3]) and distal gangrene (risk ratio [C.I. 1.01-3.8]p=0.048), major amputation was independently predicted by below-knee bypass, tissue necrosis, and poor run-off index. CONCLUSIONS: PTFE and Dacron are equally suitable for femoro-popliteal bypass.

Adult↗

PubMed2001

Characterization of a calcium-activated chloride channel as a shared target of Th2 cytokine pathways and its potential involvement in asthma.

Interleukin (IL)-9 is a T helper (Th) 2 cytokine recently implicated as an essential factor in determining susceptibility to asthma. Transgenic mice overexpressing IL-9 exhibit many features that are characteristic of human asthma. To better understand the mechanism by which IL-9 mediates the various biologic activities in asthma, we performed suppressive subtraction hybridization with whole lung from IL-9 transgenic and control mice. Here we report the identification of mCLCA3, a calcium-activated chloride channel that was specifically induced in the lung epithelium of IL-9 transgenic mice. Expression of mCLCA3 could also be induced by intratracheal administration of IL-9 or other Th2 cytokines (IL-4, IL-13), but not by interferon-gamma. Moreover, expression of mCLCA3 was induced in the lung of antigen-exposed mice, and this induction could be suppressed by neutralizing IL-9 antibody treatment, indicating IL-9 is both necessary and sufficient to induce mCLCA3 in this experimental model of asthma. Finally, we demonstrate that hCLCA1 is the human counterpart to mCLCA3 and is also induced in vitro in human primary lung cells by Th2 cytokine treatment. Together, these data strongly implicate the involvement of mCLCA3 (in mice) and hCLCA1 (in humans) in the pathogenesis of Th2 cytokine-mediated asthmatic disorders.

Amino Acid Sequence↗

PubMed2001

Cost implications of introducing an alternative treatment for patients with osteoarthritis of the knee in a managed care setting.

OBJECTIVES: To illustrate the current cost of treating osteoarthritis (OA) of the knee and to demonstrate potential savings associated with the new treatment modality of viscosupplementation in a managed care setting. STUDY DESIGN: Pharmacoeconomic model with inputs obtained from peer-reviewed medical literature, clinical trial data, clinical expert opinion, and claims data. METHODS: A spreadsheet-based model was developed to define a treatment pathway for OA of the knee, illustrate the current costs of treating patients with the condition, and demonstrate the potential savings associated with introduction of Hylan G-F 20. A hypothetical cohort of patients categorized as having mild, moderate, or severe OA of the knee was followed over a 3-year time period. The analysis was conducted from the perspective of a managed care plan with a large Medicare population. RESULTS: The 3-year savings associated with adding 1 or more courses of Hylan G-F 20 therapy to the standard treatment pathway for OA of the knee was $8,810,771. The total savings per OA patient receiving Hylan G-F 20 was $4706. The number of total knee replacements (TKRs) avoided was 808. The model was highly sensitive to the durability of Hylan G-F 20; increasing and decreasing durability within a reasonable range resulted in 3-year savings of $9,131,879 and $2,012,082, respectively. CONCLUSIONS: Hylan G-F 20 has proven to be an effective treatment for patients with OA of the knee. Appropriate use of Hylan G-F 20 could delay the need for TKRs and generate savings in the managed care setting.

Adult↗

PubMed2001

Radiofrequency catheter ablation of common-type atrial flutter guided by conventional versus electroanatomical mapping.

Radiofrequency catheter (RF) ablation aiming the complete conduction block of the cavotricuspid isthmus has become treatment of choice for common type atrial flutter. Different approaches to guide the ablation procedure are used. For the conventional approach multipolar catheters in the right atrium and in the coronary sinus are required to detect the induction of conduction block via the isthmus. RF current is applied starting at the ventricular site of the cavotricuspid isthmus under fluoroscopic control to recognise dislocation of the ablation catheter and to avoid potential complications. Three-dimensional electroanatomic (CARTO) activation mapping can be helpful to guide atrial flutter ablation. By the help of a magnetic sensor, embedded in the tip of the mapping catheter, a virtual frame of the cavotricuspid isthmus will be reconstructed. The middle region between the virtual septal and posterolateral border of the cavotricuspid isthmus will be targeted for the ablation lesion line. Both approaches have been shown to be associated with a high acute success rate and a low recurrence rate. The major difference is that the CARTO system leads to a substantial reduction of fluoroscopic time required for atrial flutter ablation. Thus, CARTO-guided ablation directed at the cavotricuspid isthmus represent a modern method for rapid and successful treatment of common-type atrial flutter with low radiation exposure. (Fig. 4, Ref. 16.)

Atrial Flutter↗

PubMed2000

[Increased clinical and economic advantages using PROSIT (proteinuria screening and intervention) in type 2 diabetic patients].

BACKGROUND AND OBJECTIVE: Even though there are simple and cost-effective means for the early diagnosis of diabetic nephropathy, only a small proportion of diabetics in Germany is regularly tests for microalbuminuria. On the basis of evidence-based knowledge and of international guidelines the PROSIT project (proteinuria screening and intervention) aims to make good this deficiency in the German Federal Republic by introducing nephropathy screening and a structured intervention to improve blood sugar and blood pressure regulation, optimizing lipid metabolism and nutritional intake. It was the aim of this study to assess with a computer-aided diabetes model the clinical value and cost-effectiveness of such an intervention. PATIENTS AND METHODS: From data collected for 589 diabetics who participated in the PROSIT project, the short-time effects after one year on HbA1c, systolic blood pressure and lipid levels were obtained and cost-effectiveness compared with that of standard care. Life expectancy, life-time costs to be met by health insurance and event frequency of the diabetic nephropathy stages were calculated with a Markov model for type 2 diabetics. RESULTS: PROSIT improved individual life expectancy by 0.23 years with reduction of life-time costs by DM 9,772 (ca. $4,900). The cumulative incidence of microalbuminuria was lowered by 30.5%, that of terminal renal failure by 55.9%. Even after discounting the results (i.e. the inclusion of time preference for cost and benefit) and stepwise changes of all variables by +/- 10%, PROSIT remained the more cost-effective variant. CONCLUSION: From a health economy viewpoint PROSIT is superior to standard management. Early recognition of albuminuria and the introduction of a multifactorial treatment strategy make it possible to delay progression to terminal renal failure. In addition to its clinical benefits, prevention of dialysis and transplantation would reduce the annual savings of the health care system by several billion DM.

Albuminuria↗