Efficacy of a new pressure-sensitive alarm for clinical use in orthopaedics.

The current study evaluated a new pressure alarm and compared the ability of subjects to limit weightbearing to 20 lb with and without the alarm. The 28 subjects were divided into four groups (Group 1, n = 7, mean age, 33 years, with normal sensation; Group 2, n = 7, mean age, 59 years, with normal sensation; Group 3, n = 6, mean age, 56 years, without protective lower limb sensation, and Group 4, n = 8, mean age, 39 years, with transtibial amputation). All subjects were instructed in partial weightbearing ambulation and then practiced weight shifting onto a scale set at 20 lb for 2 minutes. Average peak force was measured using the F-scan in-shoe sensor while subjects ambulated in two trials: one with a deactivated pressure alarm and the other with an activated alarm. Data were analyzed using two-tailed t tests. In Groups 1, 2, and 4, significantly lower average peak force with the activated alarm versus deactivated alarm occurred in 43%, 86%, and 100% of subjects, respectively. Weightbearing was limited to less than 20 lb with the activated alarm in 86%, 57%, 33%, and 38% of subjects versus 71%, 14%, 0%, and 0% of subjects with the deactivated alarm, respectively.

Laparoscopic anterior lumbar interbody fusion with rhBMP-2: a prospective study of clinical and radiographic outcomes.

STUDY DESIGN: To prospectively evaluate the clinical and radiographic outcome of laparoscopic anterior lumbar interbody fusion with rhBMP-2. OBJECTIVES: It was hypothesized that discogenic pain could be treated successfully with an anterior lumbar interbody fusion performed laparoscopically using rhBMP-2 as a replacement for autogenous bone. SUMMARY OF BACKGROUND DATA: The traditional surgical treatment of discogenic pain involves painful incisions of muscles, with potential loss of integrity and strength. Harvesting of bone graft is associated with significant complications including persistent pain at the donor site. METHODS: Twenty-two consecutive patients were studied prospectively with the surgery performed by one surgeon. Patients were evaluated clinically and radiographically at 6 and 12 months after surgery. An unbiased radiologist read postoperative computed tomography scans for evidence of fusion. RESULTS: There were 8 male (36%) and 14 female (64%) patients. The average age was 38 years (range, 21-56 years). At 6 and 12 months after surgery 95% (21 of 22) were available for follow-up; 100% were satisfied with treatment at 12 months. Concerning their symptoms, 100% reported relief of back pain, 100% had improvement of leg pain, and 100% described significant functional improvement. Improvements were seen at 6 and 12 months on Oswestry (P < 0.001), functional testing (P < 0.001), and pain analog scale (P < 0.001). Radiographic analysis showed that all of the patients had evidence of a solid fusion at 6 months after operation. CONCLUSION: Discogenic low back pain can be effectively treated surgically with a laparoscopic anterior lumbar interbody fusion using rhBMP-2 in place of autogenous bone. The fusion occurs quickly and predictably with no adverse effects identified.

Patient outcomes after minimally destabilizing lumbar stenosis decompression: the "Port-Hole" technique.

STUDY DESIGN: A prospective evaluation of the outcome of a decompressive procedure for lumbar spinal stenosis designed to preserve spinal stability. OBJECTIVES: To determine whether decompression could be achieved without subsequent fusion for spinal stenosis with and without degenerative spondylolisthesis. SUMMARY OF BACKGROUND DATA: The traditional surgical decompression of spinal stenosis involves removal of the posterior elements. Success occurs in 64% of cases, on the average, with results deteriorating over time. Concomitant spinal fusion is associated with higher costs and complication rates. METHODS: This prospective study included 54 consecutive patients treated surgically by one surgeon. Patients were contacted 21/2 and 4 years, on the average, after surgery. Patients with spondylolisthesis were evaluated for worsening of the listhesis after surgery. RESULTS: At a mean of 4 years after surgery, all patients were satisfied with their treatment. Concerning their symptoms, 80% reported relief of back pain; 96% had improvement of leg pain; 93% experienced relief of leg numbness; and 97% had relief of lower extremity weakness. Before surgery, only 1 patient could walk for longer than 15 minutes. After surgery, 98% (47/48) could walk for more than 15 minutes. Overall clinical results were graded as good to excellent (88%), fair (8%), or poor (4%). Clinical outcomes were comparable between those with and without degenerative spondylolisthesis (P = 0.08). Patients with degenerative spondylolisthesis showed no change in the amount of slip in 13/15 patients (87%). CONCLUSIONS: Degenerative spinal stenosis, even with nonlytic spondylolisthesis, can be decompressed effectively without violating the integrity of the posterior elements.

Importance of the beta12-beta13 loop in protein phosphatase-1 catalytic subunit for inhibition by toxins and mammalian protein inhibitors.

Type-1 protein serine/threonine phosphatases (PP1) are uniquely inhibited by the mammalian proteins, inhibitor-1 (I-1), inhibitor-2 (I-2), and nuclear inhibitor of PP1 (NIPP-1). In addition, several natural compounds inhibit both PP1 and the type-2 phosphatase, PP2A. Deletion of C-terminal sequences that included the beta12-beta13 loop attenuated the inhibition of the resulting PP1alpha catalytic core by I-1, I-2, NIPP-1, and several toxins, including tautomycin, microcystin-LR, calyculin A, and okadaic acid. Substitution of C-terminal sequences from the PP2A catalytic subunit produced a chimeric enzyme, CRHM2, that was inhibited by toxins with dose-response characteristics of PP1 and not PP2A. However, CRHM2 was insensitive to the PP1-specific inhibitors, I-1, I-2, and NIPP-1. The anticancer compound, fostriecin, differed from other phosphatase inhibitors in that it inhibited wild-type PP1alpha, the PP1alpha catalytic core, and CRHM2 with identical IC(50). Binding of wild-type and mutant phosphatases to immobilized microcystin-LR, NIPP-1, and I-2 established that the beta12-beta13 loop was essential for the association of PP1 with toxins and the protein inhibitors. These studies point to the importance of the beta12-beta13 loop structure and conformation for the control of PP1 functions by toxins and endogenous proteins.

Human tyrosyl-tRNA synthetase shares amino acid sequence homology with a putative cytokine.

To test the hypothesis that tRNATyr recognition differs between bacterial and human tyrosyl-tRNA synthetases, we sequenced several clones identified as human tyrosyl-tRNA synthetase cDNAs by the Human Genome Project. We found that human tyrosyl-tRNA synthetase is composed of three domains: 1) an amino-terminal Rossmann fold domain that is responsible for formation of the activated E.Tyr-AMP intermediate and is conserved among bacteria, archeae, and eukaryotes; 2) a tRNA anticodon recognition domain that has not been conserved between bacteria and eukaryotes; and 3) a carboxyl-terminal domain that is unique to the human tyrosyl-tRNA synthetase and whose primary structure is 49% identical to the putative human cytokine endothelial monocyte-activating protein II, 50% identical to the carboxyl-terminal domain of methionyl-tRNA synthetase from Caenorhabditis elegans, and 43% identical to the carboxyl-terminal domain of Arc1p from Saccharomyces cerevisiae. The first two domains of the human tyrosyl-tRNA synthetase are 52, 36, and 16% identical to tyrosyl-tRNA synthetases from S. cerevisiae, Methanococcus jannaschii, and Bacillus stearothermophilus, respectively. Nine of fifteen amino acids known to be involved in the formation of the tyrosyl-adenylate complex in B. stearothermophilus are conserved across all of the organisms, whereas amino acids involved in the recognition of tRNATyr are not conserved. Kinetic analyses of recombinant human and B. stearothermophilus tyrosyl-tRNA synthetases expressed in Escherichia coli indicate that human tyrosyl-tRNA synthetase aminoacylates human but not B. stearothermophilus tRNATyr, and vice versa, supporting the original hypothesis. It is proposed that like endothelial monocyte-activating protein II and the carboxyl-terminal domain of Arc1p, the carboxyl-terminal domain of human tyrosyl-tRNA synthetase evolved from gene duplication of the carboxyl-terminal domain of methionyl-tRNA synthetase and may direct tRNA to the active site of the enzyme.