Percutaneous Lumbar Disc Decompression Using the Dekompressor: A Prospective Long-Term Outcome Study.

BACKGROUND DATA: Few studies have investigated the long-term efficacy of percutaneous lumbar disc decompression (PLDD) with Dekompressor (Stryker, Kalamazoo, MI) for discogenic radicular pain that has failed conservative management. OBJECTIVE: Determine long-term outcomes of Dekompressor PLDD for discogenic radicular pain. METHODS: Prospective cohort study at a tertiary academic spine center of consecutive patients (12/2004-11/2005) with discogenic lumbosacral radicular pain who underwent PLDD with Dekompressor. Numerical Rating Scale (NRS) leg pain score and Oswestry Disability Index (ODI) score data were collected at 6 months and 1 year. These two measures, 5-point Likert scale patient satisfaction, and surgical rate data were collected at 8 years. RESULTS: Seventy patients underwent PLDD. Forty and 25 patients were successfully contacted at 1-year and 8-year follow-up, respectively. Using intention to treat analysis, at 1 year and 8 years, NRS leg pain scores were reduced >50% in 47% (95% confidence interval [CI] 35%, 59%) and 29% (95% confidence interval [CI] 18%, 40%) of patients, respectively; ODI score improved >30% in 43% (CI 32%, 55%) and 26% (CI 19%, 41%) of patients, respectively. Of the patients who followed up at 8 years, 36% (CI 17%, 55%) had undergone surgery and the median satisfaction was "4" (interquartile range 2,5). CONCLUSIONS: While limited by loss-to-follow-up, this study suggests that treatment of discogenic lumbosacral radicular pain with Dekompressor results in decreased leg pain and disability and favorable satisfaction at long-term follow-up. Further study with adequate follow-up retention is needed to confirm that Dekompressor spares open spinal surgery.

An investigation on the fuel savings potential of hybrid hydraulic refuse collection vehicles.

Refuse trucks play an important role in the waste collection process. Due to their typical driving cycle, these vehicles are characterized by large fuel consumption, which strongly affects the overall waste disposal costs. Hybrid hydraulic refuse vehicles offer an interesting alternative to conventional diesel trucks, because they are able to recuperate, store and reuse braking energy. However, the expected fuel savings can vary strongly depending on the driving cycle and the operational mode. Therefore, in order to assess the possible fuel savings, a typical driving cycle was measured in a conventional vehicle run by the waste authority of the City of Stuttgart, and a dynamical model of the considered vehicle was built up. Based on the measured driving cycle and the vehicle model including the hybrid powertrain components, simulations for both the conventional and the hybrid vehicle were performed. Fuel consumption results that indicate savings of about 20% are presented and analyzed in order to evaluate the benefit of hybrid hydraulic vehicles used for refuse collection.

High-throughput screening with the Eimeria tenella CDC2-related kinase2/cyclin complex EtCRK2/EtCYC3a.

The poultry disease coccidiosis, caused by infection with Eimeria spp. apicomplexan parasites, is responsible for enormous economic losses to the global poultry industry. The rapid increase of resistance to therapeutic agents, as well as the expense of vaccination with live attenuated vaccines, requires the development of new effective treatments for coccidiosis. Because of their key regulatory function in the eukaryotic cell cycle, cyclin-dependent kinases (CDKs) are prominent drug targets. The Eimeria tenella CDC2-related kinase 2 (EtCRK2) is a validated drug target that can be activated in vitro by the CDK activator XlRINGO (Xenopus laevis rapid inducer of G2/M progression in oocytes). Bioinformatics analyses revealed four putative E. tenella cyclins (EtCYCs) that are closely related to cyclins found in the human apicomplexan parasite Plasmodium falciparum. EtCYC3a was cloned, expressed in Escherichia coli and purified in a complex with EtCRK2. Using the non-radioactive time-resolved fluorescence energy transfer (TR-FRET) assay, we demonstrated the ability of EtCYC3a to activate EtCRK2 as shown previously for XlRINGO. The EtCRK2/EtCYC3a complex was used for a combined in vitro and in silico high-throughput screening approach, which resulted in three lead structures, a naphthoquinone, an 8-hydroxyquinoline and a 2-pyrimidinyl-aminopiperidine-propane-2-ol. This constitutes a promising starting point for the subsequent lead optimization phase and the development of novel anticoccidial drugs.

Inhibition of Eimeria tenella CDK-related kinase 2: From target identification to lead compounds.

Apicomplexan parasites encompass several human- and animal-pathogenic protozoans such as Plasmodium falciparum, Toxoplasma gondii, and Eimeria tenella. E. tenella causes coccidiosis, a disease that afflicts chickens, leading to tremendous economic losses to the global poultry industry. The considerable increase in drug resistance makes it necessary to develop new therapeutic strategies against this parasite. Cyclin-dependent kinases (CDKs) are key molecules in cell-cycle regulation and are therefore prominent target proteins in parasitic diseases. Bioinformatics analysis revealed four potential CDK-like proteins, of which one-E. tenella CDK-related kinase 2 (EtCRK2)-has already been characterized by gene cloning and expression.1 By using the CDK-specific inhibitor flavopiridol in EtCRK2 enzyme assays and schizont maturation assays (SMA), we could chemically validate CDK-like proteins as potential drug targets. An X-ray crystal structure of human CDK2 (HsCDK2) served as a template to build protein models of EtCRK2 by comparative homology modeling. Structural differences in the ATP binding site between EtCRK2 and HsCDK2, as well as chicken CDK3, were addressed for the optimization of selective ATP-competitive inhibitors. Virtual screening and "wet-bench" high-throughput screening campaigns on large compound libraries resulted in an initial set of hit compounds. These compounds were further analyzed and characterized, leading to a set of four promising lead compounds for development as EtCRK2 inhibitors.