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UNLABELLED: This study assessed the success of splintage for traumatic and atraumatic sagittal band incompetence and its relationship to the duration of symptoms before treatment. A retrospective review of all patients with sagittal band incompetence treated with splintage was performed. All patients had extensor tendon subluxation on physical examination. Ninety-two patients were included: 68 traumatic and 24 atraumatic. Subluxation resolved with splintage in 77 patients. Traumatic tendon subluxation resolved in 95% of acute injuries, 100% of subacute injuries, and 67% of chronic injures. Atraumatic tendon subluxation resolved in 100% of patients with acute presentation, 67% of patients with subacute presentation, and 57% of patients with chronic presentation. Surgery was rarely required. Splintage proved very effective for acute sagittal band incompetence, regardless of causation, but decreased in efficiency with chronicity. LEVEL OF EVIDENCE: Level 4.

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PURPOSE: Hemi-hamate resurfacing arthroplasty is a treatment alternative for the management of severe acute and chronic dorsal proximal interphalangeal (PIP) fracture-dislocations. This study was designed to determine whether this procedure would successfully restore function after such injuries. METHODS: Hemi-hamate reconstructions were performed on 33 patients (mean age, 34 years) who presented to 1 hand surgery practice with dorsal PIP fracture-dislocations. Eligible patients experienced unstable dislocations with comminuted metaphyseal fractures involving at least 50% of the volar middle phalangeal surface that was not amenable to open reduction and internal fixation. We evaluated 22 patients with 14 acute (<6 weeks) and 8 chronic (mean, 30 weeks) injuries at a mean of 4.5 years (range, 1-7 years). Functional outcomes were assessed by objective and subjective measures: joint alignment/motion/stability, grip strength, Disabilities of the Arm, Shoulder, and Hand (DASH) scores, and visual analog scales (VAS) of pain and function. RESULTS: After hemi-hamate reconstruction, active PIP motion averaged 70 degrees (acute 71 degrees , chronic 69 degrees ) with a mean flexion contracture of 19 degrees (range, 0 degrees to 80 degrees ). Active distal interphalangeal motion averaged 54 degrees (acute 56 degrees , chronic 51 degrees ). The mean VAS score for digit pain was 1.4 (acute 0.7, chronic 2.5). The mean DASH score of 5 (acute 2, chronic 9) and VAS functional score of 1.9 (acute 1.4, chronic 2.6) indicated little functional impairment (acute 2, chronic 9). Grip strength averaged 95% of the opposite hand. Mean coronal plane angulation at the PIP joint was 3 degrees . Ten patients reported aching with cold temperatures. One dissatisfied patient underwent revision surgery. Chronic reconstructions were associated with increased VAS pain ratings (p = .02) and higher DASH scores (p = .06). CONCLUSIONS: Hemi-hamate reconstruction represents a valuable surgical procedure to address severe PIP joint fracture-dislocations. Reconstruction of chronic injuries by this method restores PIP function, albeit with more modest outcome performance. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic IV.

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Photo-excited xanthone is known to undergo ultrafast intersystem crossing (ISC) in the 1 ps time domain. Correspondingly, its fluorescence quantum yield in most solvents is very small ( approximately 10(-4)). Surprisingly, the quantum yield in water is 100 times larger, while ISC is still rapid ( approximately 1 ps), as seen by ultrafast pump probe absorption spectroscopy. Temperature dependent steady state and time resolved fluorescence experiments point to a delayed fluorescence mechanism, where the triplet (3)npi* state primarily accessed by ISC is nearly isoenergetic with the photo-excited (1)pipi* state. The delayed fluorescence of xanthone in water decays with a time constant of 700 ps, apparently by internal conversion between the (3)npi* state and the lowest lying triplet state (3)pipi*.

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This retrospective study evaluated the results of the Darrach procedure and the Sauve-Kapandji procedure for the treatment of distal radio-ulnar joint derangement following malunion of dorsally displaced, unstable, intraarticular fractures of the distal radius in patients under 50 years of age. Twelve of 18 possible patients in the Sauve-Kapandji group completed the disabilities of the arm, shoulder, and hand survey at a mean of 4 years postoperatively and nine of the 18 returned for a follow-up examination at a mean of 2 years. Twenty-one of 30 possible patients in the Darrach group completed the disabilities of the arm, shoulder, and hand survey at a mean of 6 years postoperatively and 13 of these 30 returned for follow-up examination at a mean of 4 years. The Darrach procedure and the Sauve-Kapandji procedure yielded comparable and unpredictable results with respect to both subjective and objective parameters.

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BACKGROUND: There has been considerable controversy regarding the procedure of choice for treatment of any given stage of osteoarthritis of the thumb carpometacarpal joint. This study was designed to directly compare the clinical results of two common surgical procedures for this condition, trapeziometacarpal arthrodesis and trapezial excision with ligament reconstruction and tendon interposition, in similar patient populations. METHODS: Between 1988 and 1998, 109 patients (141 thumbs) who were less than sixty years old were treated with one of the two procedures. In a retrospective review, forty-two patients (fifty-eight thumbs) treated with arthrodesis completed an outcome questionnaire and twenty-nine patients (forty-four thumbs) treated with arthrodesis completed the questionnaire and were examined. In the group treated with trapezial excision with ligament reconstruction and tendon interposition, thirty-nine patients (forty-nine thumbs) completed the questionnaire and thirty patients (thirty-eight thumbs) completed the questionnaire and were examined. The average duration of follow-up was sixty-nine months. The groups were similar with regard to age, gender, hand dominance, and duration of follow-up. RESULTS: Subjective evaluation of pain, function, and satisfaction demonstrated no significant difference between the two groups, with >90% of patients satisfied following either procedure. Although grip strength did not differ between the groups, the arthrodesis group had significantly stronger lateral pinch (p < 0.001) and chuck pinch (p < 0.01). The group treated with ligament reconstruction and tendon interposition had a better range of motion with regard to opposition (p < 0.05) and the ability to flatten the hand (p < 0.0001). There was a higher complication rate in the arthrodesis group, with nonunion of the fusion site accounting for the majority of the complications. However, despite a persistent nonunion in six thumbs, those thumbs and the thumbs in which union was obtained did not differ with regard to pain; all of the patients with nonunion had improvement in their pain status compared with preoperatively, and all were very satisfied with the outcome. Peritrapezial arthritis developed in nine patients (fourteen thumbs). This finding was not related to age and did not affect overall pain, function, or satisfaction. CONCLUSIONS: Although traditionally arthrodesis and ligament reconstruction and tendon interposition have been indicated in two different patient populations, we compared them in a homogeneous group and found that the two procedures had similar results with regard to pain, function, and satisfaction despite minimal differences in strength and motion. Although complications were more frequent following arthrodesis, most did not affect the overall outcome.

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Folding of lysozyme at pH 5.2 is a complex processes. After rapid collapse (<1 ms) kinetic partitioning into a slow and fast folding pathway occurs. The fast pathway leads directly to the native structure (N), whereas the slow pathway goes through a partially folded intermediate (I(1)) with native-like secondary structure in the alpha-domain. This mechanism is in agreement with data from a large number of spectroscopic probes, from changes in the radius of gyration and from measurements on the time-course of the populations of the different species. Results from pulsed hydrogen exchange experiments, in contrast, revealed that the secondary structure of I(1) and of N is formed significantly faster than changes in spectroscopic properties occur and showed large variations in the protection kinetics of individual amide sites. We investigated the molecular origin of the rapid amide protection by quantitatively simulating all kinetic processes during the pulse-labeling experiments. Absorbance and fluorescence-detected folding kinetics showed that the early events in lysozyme folding are accelerated under exchange conditions (pH 9.2) and that a change in folding mechanism occurs due to the transient population of an additional intermediate (I(2)). This leads to kinetic competition between exchange and folding during the exchange pulse and to incomplete labeling of amide sites with slow intrinsic exchange rates. As a result, apparently faster and non-exponential kinetics of amide protection are measured in the labeling experiments. Our results further suggest that collapsed lysozyme (C) and I(1) have five and ten-times reduced free exchange rates, respectively, due to limited solvent accessibility.

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Folding of tendamistat, an inhibitor of alpha-amylase, is a fast two-state process accompanied by two minor slow reactions, which were assigned to prolyl isomerization. In a proline-free variant, 5% of the molecules still fold slowly with a rate constant of 2.5 s(-1). This reaction is caused by a slow equilibrium between two populations of unfolded molecules. The time constant for this equilibration process, its sensitivity to LiCl and its temperature dependence identify it as a cis-trans isomerization of nonprolyl peptide bonds. Although nonprolyl peptide bonds have the cis conformation populating only approximately 0.15% in unfolded proteins, their large number generates a significant fraction of slow-folding molecules. This emphasizes that heterogeneous populations in an unfolded protein can induce complex folding kinetics on various time scales.

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The small all-beta-sheet protein tendamistat folds and unfolds rapidly in apparent two-state reactions. Kinetic measurements of two tendamistat variants under various solvent conditions reveal, however, that folding occurs in at least two sequential steps through a metastable obligatory intermediate. Depending on the solvent conditions either step can become rate limiting. The activation parameters indicate that the first step represents an enthalpic barrier whereas the second step is an entropic barrier at 25 degrees C. Our results suggest that initial non-specific collapse precedes formation of native secondary and tertiary structure in tendamistat folding. This points at a distinct route in tendamistat folding and indicates that partially folded metastable intermediates might play an important role in the mechanism of apparent two-state folding.

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The small all-beta protein tendamistat folds and unfolds with two-state kinetics. We determined the volume changes associated with the folding process by performing kinetic and equilibrium measurements at variable pressure between 0.1 and 100 MPa (1 to 1, 000 bar). GdmCl-induced equilibrium unfolding transitions reveal that the volume of the native state is increased by 41.4 +/- 2.0 cm(3)/mol relative to the unfolded state. This value is virtually independent of denaturant concentration. The use of a high-pressure stopped-flow instrument enabled us to measure the activation volumes for the refolding (DeltaVo/f) and unfolding reaction (DeltaVo/u) over a broad range of GdmCl concentrations. The volume of the transition state is 60% native-like (DeltaVo/f) = 25.0 +/- 1.2 cm(3)/mol) in the absence of denaturant, indicating partial solvent accessibility of the core residues. The volume of the transition state increases linearly with denaturant concentration and exceeds the volume of the native state above 6 M GdmCl. This result argues for a largely desolvated transition state with packing deficiencies at high denaturant concentrations and shows that the structure of the transition state depends strongly on the experimental conditions.

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This retrospective study assessed the short-term complications and long-term subjective and objective results of operative treatment of acute unstable dorsal proximal interphalangeal joint dislocations treated by 2 methods: open reduction internal fixation and volar plate arthroplasty. Fifty-six patients were included in this study. Twenty-three (41%) were treated by volar plate arthroplasty and 33 (59%) were treated by open reduction internal fixation. Postoperative complications occurred in 10 patients (18%). The most frequent complication was redislocation, which occurred in 6 patients (volar plate arthroplasty, 3 patients; open reduction internal fixation, 3 patients) and necessitated salvage surgery in 4 of these 6 cases. In all 6 cases, the fracture of the base of the middle phalanx involved more than 50% of the articular surface. Twenty-four patients (43%) returned for long-term evaluation at an average follow-up period of 46 months (range, 13-125 months). Twenty of these 24 patients (83%) reported little or no pain despite a high incidence (96%) of posttraumatic degenerative changes. Eighteen (75%) reported no difficulty with work activities; 92% continued leisure activities with little or no modification. Proximal interphalangeal joint flexion contractures and extension lag at the distal interphalangeal joint were common. These data indicate that if reduction is maintained, patients may expect few functional deficits despite radiographic degenerative changes and loss of mobility.

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Lysozyme folds through two competing pathways. A fast pathway leads directly from a collapsed state to the native protein, whereas folding on a slow pathway proceeds through a partially folded intermediate (I(1)). At NaCl concentrations above 100 mM, a second transient intermediate (I(2)) is induced as judged by the appearance of an additional apparent rate constant in the refolding kinetics. Monitoring the time course of native molecules and of both intermediates shows that the NaCl-induced state (I(2)) is located on neither of the two folding pathways observed at low-salt concentrations. These results suggest that I(2) is a metastable high-energy intermediate at low-ionic strength and is located on a third folding pathway. The folding landscape of lysozyme seems to be complex with several high-energy intermediates located on parallel folding routes. However, the experiments show no evidence for partially folded states on the fast direct pathway.

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The mechanism of protein folding is under intense theoretical and experimental investigation. From stopped-flow mixing experiments we have detailed knowledge of processes slower than about 1 ms, but until recently little was known about folding and unfolding reactions on the microsecond to nanosecond time scale. The use of novel techniques allowed to explore the elementary steps in protein folding, such as intrachain diffusion and formation of alpha-helices, beta-hairpins and loop structures. This brief review discusses the time scales of these early elementary events which are crucial for the understanding of how proteins fold.

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A direct measure of intramolecular chain diffusion is obtained by the determination of triplet-triplet energy-transfer rates between a donor and an acceptor chromophore attached at defined points on a polypeptide chain. Single exponential kinetics of contact formation are observed on the nanosecond time scale for polypeptides in which donor and acceptor are linked by repeating units of glycine and serine residues. The rates depend on the number of peptide bonds (N) separating donor and acceptor and show a maximum for the shortest peptides (N = 3) with a time constant (tau = 1/k) of 20 ns. This sets an upper limit for the speed of formation of the first side-chain contacts during protein folding.

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The effect of intermediates on the rate of protein folding is explored by applying Kramers' theory of diffusive barrier crossing in the high friction limit. Intermediates are represented as local minima in the transition barrier. We observe that very large or very small additional barriers created by the intermediates slow down the folding process. The rate of folding markedly increases, however, when the additional barriers become >1 kBT but leave the overall barrier height unchanged. This rate-enhancing effect is caused by a favorable entropic contribution to the free energy of activation, and it increases with the number of intermediates up to a limiting value. From these calculations, we conclude that optimized transition barriers should contain partially folded high energy intermediates.

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We have used synchrotron radiation, together with stopped-flow and continuous-flow mixing techniques to monitor refolding of lysozyme at pH 5.2. From data measured at times which range from 14 ms to two seconds, we can monitor changes in the size, the shape and the pair distribution function of the polypeptide chain during the folding process. Comparison of the results with the properties of native and GdmCl-unfolded lysozyme shows that a major chain collapse occurs in the dead-time of mixing. During this process about 50 % of the change in radius of gyration between the unfolded protein and the native state occurs and the polypeptide chain adopts a globular shape. Time-resolved fluorescence spectra of this collapsed state suggest that the hydrophobic side-chains are still highly solvent accessible. A subsequently formed intermediate with helical structure in the alpha-domain is nearly identical in size and shape with native lysozyme and has a solvent-inaccessible hydrophobic core. Despite its native-like properties, this intermediate is only slightly more stable (DeltaG0=-4 kJ/mol) than the collapsed state and still much less stable than native lysozyme (DeltaDeltaG0=36 kJ/mol) at 20 degrees C.

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The arterial anatomy, coverage area, and potential donor site morbidity of the anconeus muscle flap are described. Using 17 cadaveric upper extremities, we investigated the muscle's arterial anatomy in 12 specimens and defined the coverage area of the anconeus flap in 5 specimens. We also reviewed the records of 9 patients who underwent a pedicle anconeus muscle flap for elbow coverage to assess clinical results of the procedure. The anconeus muscle is supplied from 3 arterial pedicles: the recurrent posterior interosseus artery, the medial collateral artery, and the posterior branch of the radial collateral artery. The recurrent posterior interosseus artery and the medial collateral artery were present in all dissected cadavers and consistently anastomosed with each other underneath the anconeus muscle. By harvesting the muscle on the medial collateral artery, the anconeus muscle flap can be expected to cover a 7.3 cm2 defect over the radiocapitellar joint, a 6.1 cm2 defect over the distal triceps tendon, and a 7.2 cm2 defect over the olecranon. In this series, none of the patients experienced loss of elbow motion, stability, or extension strength. The results of this study indicate that the anconeus can be harvested with minimal risk of morbidity and provides effective coverage for soft tissue defects of the elbow.

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The channel-forming protein OmpF porin from Escherichia coli spans the bacterial outer membrane. Each of the three monomers comprises a hollow, 16-stranded beta-barrel. These are associated to homotrimers which are unusually stable, due mostly to hydrophobic interactions between the beta-barrels. In addition, a loop, L2 connects one subunit to its neighbor by latching into its channel. Residue E71 on loop 2 is integrated into an ionic network and forms salt bridges and hydrogen bonds with R100 and R132 on the channel wall in the adjacent subunit. To examine these contributions quantitatively, six single-site, two double, and one deletion mutant were constructed on the basis of the atomic coordinates of the protein. Differential scanning calorimetric analysis showed that the salt-bridge, E71-R100, contributes significantly to trimer stability: the substitution E71Q causes a decrease of the transition temperature from 72 to 48 degreesC, with DeltaHcal diminishing from 430 to 201 kcal mol-1. A nearby substitution in the loop, D74N, has lesser effects on thermal stability, while the deletion in L2 (Delta69-77) has an effect comparable to that of E71Q. X-ray structure analysis to 3.0 A resolution revealed only local structural differences in the mutants except for the substitution R100A, where another residue, R132, is found to fill the gap left by the truncated side chain of A100. Functional assays in planar lipid bilayers show significantly increased cation selectivities if the charge distribution was affected.

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Overuse injuries are the result of repetitive microtrauma to the musculotendinous unit. Treatment protocols are based on the stage of the inflammatory process that is active at the time of diagnosis. Control of the inflammatory response with rest, elevation, and ice is the treatment objective during the inflammatory stage. Prevention of further injury is the primary treatment goal throughout the proliferative phase. Once the inflammatory process has reached the maturation stage, rehabilitation can begin with flexibility exercises, isometric contractions, and a slow return to strength training. Surgical decompression is frequently necessary if chronic inflammation causes fibrosis of the fibro-osseous tendon sheaths. Anomalous muscle bellies and tendinous interconnections can be contributing factors to overuse syndromes. Properly structured training programs and rehabilitation regimens can prevent tendinitis and overuse syndromes.

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