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Biomedical subjects

R P Baker

Publications and source records attributed to R P Baker.

At least 19 recordsLinked to original sources
PubMed2006

Treatment of the young active patient with osteoarthritis of the hip. A five- to seven-year comparison of hybrid total hip arthroplasty and metal-on-metal resurfacing.

We compared the five- to seven-year clinical and radiological results of the metal-on-metal Birmingham hip resurfacing with a hybrid total hip arthroplasty in two groups of 54 hips, matched for gender, age, body mass index and activity level. Function was excellent in both groups, as measured by the Oxford hip score, but the Birmingham hip resurfacings had higher University of California at Los Angeles activity scores and better EuroQol quality of life scores. The total hip arthroplasties had a revision or intention-to-revise rate of 8%, and the Birmingham hip resurfacings of 6%. Both groups demonstrated impending failure on surrogate end-points. Of the total hip arthroplasties, 12% had polyethylene wear and osteolysis under observation, and 8% of Birmingham hip resurfacings showed migration of the femoral component. Polyethylene wear was present in 48% of the hybrid hips without osteolysis. Of the femoral components in the Birmingham hip resurfacing group which had not migrated, 66% had radiological changes of unknown significance.

Adolescent↗
PubMed2006

Total hip arthroplasty and hemiarthroplasty in mobile, independent patients with a displaced intracapsular fracture of the femoral neck. A randomized, controlled trial.

BACKGROUND: Hemiarthroplasty and total hip arthroplasty are commonly used to treat displaced intracapsular fractures of the femoral neck, but each has disadvantages and the optimal treatment of these fractures remains controversial. METHODS: In the present prospectively randomized study, eighty-one patients who had been mobile and lived independently before they had sustained a displaced fracture of the femoral neck were randomized to receive either a total hip arthroplasty or a hemiarthroplasty. The mean age of the patients was seventy-five years. Outcome was assessed with use of the Oxford hip score, and final radiographs were assessed. RESULTS: After a mean duration of follow-up of three years, the mean walking distance was 1.17 mi (1.9 km) for the hemiarthroplasty group and 2.23 mi (3.6 km) for the total hip arthroplasty group, and the mean Oxford hip score was 22.3 for the hemiarthroplasty group and 18.8 for the total hip arthroplasty group. Patients in the total hip arthroplasty group walked farther (p=0.039) and had a lower (better) Oxford hip score (p=0.033) than those in the hemiarthroplasty group. Twenty of thirty-two living patients in the hemiarthroplasty group had radiographic evidence of acetabular erosion at the time of the final follow-up. None of the hips in the hemiarthroplasty group dislocated, whereas three hips in the total hip arthroplasty group dislocated. In the hemiarthroplasty group, two hips were revised to total hip arthroplasty and three additional hips had acetabular erosion severe enough to indicate revision. In the total hip arthroplasty group, one hip was revised because of subsidence of the femoral component. CONCLUSIONS: Total hip arthroplasty conferred superior short-term clinical results and fewer complications when compared with hemiarthroplasty in this prospectively randomized study of mobile, independent patients who had sustained a displaced fracture of the femoral neck.

Aged↗
PubMed2005

The use of the long gamma nail in proximal femoral fractures.

The results of 100 'Long Gamma Nails' (LGN) inserted in 97 patients, for the treatment of complex proximal femoral fractures and pathological lesions, are reported. The mean patient age was 74 (16-98). Seven significant complications occurred; four lag screws cut out, one broken nail, one infected non-union and one peri-prosthetic fracture. Five patients underwent revision either to total hip arthroplasty or exchange nailing. Seventy patients had follow-up of greater than 2 months (mean 10.8 months). Success was defined as stability of the fracture until union or death; this was achieved in 85% of cases. The mortality was 10% at 30 days and 25% at 1 year. The complication rate fell with increasing experience. Complex proximal femoral fractures are difficult to treat with all implants demonstrating high complication rates. The long gamma nail allowed early weight bearing and was effective in 85% of cases. Malpositioning of the implant should be avoided, as this was the leading cause of failure. Surgeon experience is an important factor but training of surgeons does not adversely affect outcome.

Adolescent↗
PubMed2004

Improvement in cognitive function after right temporal arteriovenous malformation excision.

A patient is presented in whom right temporal AVM excision led to improved cognitive function. Neuropsychological assessment showed a significant postoperative improvement in Performance IQ (p = < 0.05), Full Scale IQ (p = < 0.05), and clinically in visual memory (p = < 0.10). Reversal of vascular steal may lead to increases in cognitive function. We recommend that patients undergoing AVM excision have a complete neuropsychological evaluation.

Adolescent↗
PubMed2001

Interaction between Ran and Mog1 is required for efficient nuclear protein import.

Mog1 is a nuclear protein that interacts with Ran, the Ras family GTPase that confers directionality to nuclear import and export pathways. Deletion of MOG1 in Saccharomyces cerevisiae (Deltamog1) causes temperature-sensitive growth and defects in nuclear protein import. Mog1 has previously been shown to stimulate GTP release from Ran and we demonstrate here that addition of Mog1 to either Ran-GTP or Ran-GDP results in nucleotide release and formation of a stable complex between Mog1 and nucleotide-free Ran. Moreover, MOG1 shows synthetic lethality with PRP20, the Ran guanine nucleotide exchange factor (RanGEF) that also binds nucleotide-free Ran. To probe the functional role of the Mog1-Ran interaction, we engineered mutants of yeast Mog1 and Ran that specifically disrupt their interaction both in vitro and in vivo. These mutants indicate that the interaction interface involves conserved Mog1p residues Asp(62) and Glu(65), and residue Lys(136) in yeast Ran. Mutations at these residues decrease the ability of Mog1 to bind and release nucleotide from Ran. Furthermore, the E65K-Mog1 and K136E-Ran mutations in yeast cause temperature sensitivity and mislocalization of a nuclear import reporter protein, similar to the phenotype observed for the Deltamog1 strain. Our results indicate that a primary function of Mog1 requires binding to Ran and that the Mog1-Ran interaction is necessary for efficient nuclear protein import in vivo.

Crystallography, X-Ray↗
PubMed2001

Molecular mechanism of translocation through nuclear pore complexes during nuclear protein import.

The trafficking of macromolecules between cytoplasm and nucleus through nuclear pore complexes is mediated by specific carrier molecules such as members of the importin-beta family. Nuclear pore proteins (nucleoporins) frequently contain sequence repeats based on FG cores and carriers appear to move their cargo through the pores by hopping between successive FG cores. A major question is why some macromolecules are transported while others are not. This selectivity may be generated by the ability to bind FG repeats, a local concentration of carrier-cargo complexes near the entrance to the pore channel, and steric hindrance produced by high concentrations of nucleoporins in the channel.

Active Transport, Cell Nucleus↗
PubMed2000

1.9 A resolution crystal structure of the Saccharomyces cerevisiae Ran-binding protein Mog1p.

The 1.9 A resolution X-ray crystal structure of Ran-binding protein Mog1p shows that it has a unique fold based on a six-stranded antiparallel beta-sheet backed on both sides by an extensive alpha-helix. The topology of some elements of Mog1p secondary structure resemble a portion of nuclear transport factor 2 (NTF2), but the hydrophobic cavity and surrounding negatively charged residues that are important in the NTF2-RanGDP interaction are not conserved in Mog1p. In addition to binding RanGTP, Mog1p forms a 1:1 complex with RanGDP and so binds Ran independent of its nucleotide state. Mog1p and NTF2 compete for binding to RanGDP indicating that their binding sites on RanGDP are sufficiently close to prevent both proteins binding simultaneously. Although there may be some overlap between the Mog1p and NTF2 binding sites on RanGDP, these sites are not identical. Sequence analysis of Mog1p homologues from Schizosaccharomyces pombe, human, and Caenorhabditis elegans in the context of the Mog1p crystal structure indicates the presence of a cluster of highly conserved surface residues consistent with an interaction site for Ran.

Alleles↗
PubMed2000

Crystallization and preliminary X-ray diffraction analysis of the Saccharomyces cerevisiae ran-binding protein Mog1p.

Mog1p binds the Ras-family GTPase Ran/Gsp1p, which has a central role in nucleocytoplasmic transport and cell-cycle progression. Overexpression of MOG1 is able to suppress temperature-sensitive gsp1 mutants in yeast; Deltamog1 null mutants display temperature-sensitive defects in nuclear trafficking. Orthorhombic crystals of bacterially expressed Mog1p that diffract to beyond 2 A resolution using synchrotron radiation have been obtained. The crystals have P2(1)2(1)2(1) symmetry, with unit-cell parameters a = 39.67, b = 51.96, c = 112.23 A, a Matthews coefficient of 2.44 A(3) Da(-1), an estimated solvent content of 49.5% and one chain in the asymmetric unit.

Crystallization↗
PubMed1998

The proofreading pathway of bacteriophage T4 DNA polymerase.

The base analog, 2-aminopurine (2AP), was used as a fluorescent reporter of the biochemical steps in the proofreading pathway catalyzed by bacteriophage T4 DNA polymerase. "Mutator" DNA polymerases that are defective in different steps in the exonucleolytic proofreading pathway were studied so that transient changes in fluorescence intensity could be equated with specific reaction steps. The G255S- and D131N-DNA polymerases can hydrolyze DNA, the final step in the proofreading pathway, but the mutator phenotype indicates a defect in one or more steps that prepare the primer-terminus for the cleavage reaction. The hydrolysis-defective D112A/E114A-DNA polymerase was also examined. Fluorescent enzyme-DNA complexes were preformed in the absence of Mg2+, and then rapid mixing, stopped-flow techniques were used to determine the fate of the fluorescent complexes upon the addition of Mg2+. Comparisons of fluorescence intensity changes between the wild type and mutant DNA polymerases were used to model the exonucleolytic proofreading pathway. These studies are consistent with a proofreading pathway in which the protein loop structure that contains residue Gly255 functions in strand separation and transfer of the primer strand from the polymerase active center to form a preexonuclease complex. Residue Asp131 acts at a later step in formation of the preexonuclease complex.

2-Aminopurine↗
PubMed1998

Identification of a transient excision intermediate at the crossroads between DNA polymerase extension and proofreading pathways.

DNA polymerases achieve accurate DNA replication through a delicate balance between primer elongation and proofreading. While insufficient proofreading results in DNA replication errors, indiscriminate removal of correct along with incorrect nucleotides is wasteful and may prevent completion of DNA synthesis. The transition between polymerization and proofreading modes is proposed to be governed by a kinetic barrier that prevents proofreading unless the rate of primer elongation is significantly reduced by the presence of an incorrect base pair at the primer-terminus. We have used mutational analysis, coupled with a sensitive, fluorescence-based assay to characterize intermediate steps in the proofreading pathway. A highly fluorescent complex forms between the bacteriophage T4 DNA polymerase and DNA primer-templates labeled at the 3' terminus with the base analog 2-aminopurine. Formation of the fluorescent complex appears to be a rate-determining step in the proofreading pathway and is impaired for several mutator T4 DNA polymerases with amino acid substitutions in the exonuclease domain. Although these mutant DNA polymerases are proficient in hydrolysis, their reduced ability to form the fluorescent complex imposes a higher kinetic barrier. As a consequence, the mutant DNA polymerases proofread less frequently, resulting in more DNA replication errors.

Bacteriophage T4↗
PubMed1989

Head injury at the southeastern Georgia Regional Trauma Center: a three-year review.

The impact of head injury on our trauma center is significant because of the large number of cases with their heavy utilization of trauma center resources. Head injury also exerts a major influence on the Trauma Center in a rural area since it serves as a major provider of care for the head injured over a wide geographical area. Mortality rates seen in this population compare favorably with contemporary data from other studies using GCS and Head AIS as indicators of level of injury.

Craniocerebral Trauma↗
PubMed1987

Pharmacokinetic comparison of three clindamycin phosphate dosing schedules.

In a randomized, three-way crossover study, six male volunteers received clindamycin phosphate 600 mg iv q6h (treatment A), 600 mg iv q8h (treatment B), or 900 mg iv q8h (treatment C). Plasma clindamycin concentrations were determined periodically for eight hours after achieving steady state. The results indicate that treatment C yielded significantly higher peak plasma clindamycin concentrations than treatments A or B. There were no significant differences in minimum plasma clindamycin concentrations (Cmin) or area under the plasma concentration versus time curve (AUC24) between treatments A and C. However, both treatments A and C yielded significantly greater Cmin and AUC24 values than treatment B. There were no significant differences among treatments for clindamycin clearance. It is concluded that clindamycin phosphate 900 mg q8h is a pharmacokinetically acceptable alternative to clindamycin phosphate 600 mg q6h.

Adolescent↗
PubMed1987

Experience with the neodymium:yttrium-aluminum-garnet laser in forty-two cases.

The neodymium:yttrium-aluminum-garnet (Nd:YAG) laser has been utilized in the treatment of 42 cases during the past 2 years at two institutions. The laser was used under investigational permits from the Food and Drug Administration. It was found to be of particular value in the treatment of vascular intracranial tumors, especially meningiomas, and metastatic tumors of the spine. The ability of the laser to shrink and devascularize these tumors was efficacious as a surgical adjunct. Laser treatment of tumor attachments, especially those of meningiomas to the skull base, seemed to be effective in eradication of residual tumor. Long term benefits of such therapy, however, remain unproven. Because of the penetrating ability of the Nd:YAG laser beam, this device must be used with care by surgeons experienced in its use to prevent injury to adjacent structures.

Humans↗