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PubMed2006

Enhanced stability of hydrogen peroxide in the presence of subsurface solids.

The stabilization of hydrogen peroxide was investigated as a basis for enhancing its downgradient transport and contact with contaminants during catalyzed H(2)O(2) propagations (CHP) in situ chemical oxidation (ISCO). Stabilization of hydrogen peroxide was investigated in slurries containing four characterized subsurface solids using phytate, citrate, and malonate as stabilizing agents after screening ten potential stabilizers. The extent of hydrogen peroxide stabilization and the most effective stabilizer were solid-specific; however, phytate was usually the most effective stabilizer, increasing the hydrogen peroxide half-life to as much as 50 times. The degree of stabilization was nearly as effective at 10 mM concentrations as at 250 mM or 1 M concentrations. The effect of stabilization on relative rates of hydroxyl radical activity varied between the subsurface solids, but citrate and malonate generally had a greater positive effect than phytate. The effect of phytate, citrate, and malonate on the relative rates of superoxide generation was minimal to somewhat negative, depending on the solid. The results of this research demonstrate that the stabilizers phytate, citrate, and malonate can significantly increase the half-life of hydrogen peroxide in the presence of subsurface solids during CHP reactions while maintaining a significant portion of the reactive oxygen species activity. Use of these stabilizers in the field will likely improve the delivery of hydrogen peroxide and downgradient treatment during CHP ISCO.

Citrates↗
PubMed2006

Natural selection for kinetic stability is a likely origin of correlations between mutational effects on protein energetics and frequencies of amino acid occurrences in sequence alignments.

It appears plausible that natural selection constrains, to some extent at least, the stability in many natural proteins. If, during protein evolution, stability fluctuates within a comparatively narrow range, then mutations are expected to be fixed with frequencies that reflect mutational effects on stability. Indeed, we recently reported a robust correlation between the effect of 27 conservative mutations on the thermodynamic stability (unfolding free energy) of Escherichia coli thioredoxin and the frequencies of residues occurrences in sequence alignments. We show here that this correlation likely implies a lower limit to thermodynamic stability of only a few kJ/mol below the unfolding free energy of the wild-type (WT) protein. We suggest, therefore, that the correlation does not reflect natural selection of thermodynamic stability by itself, but of some other factor which is linked to thermodynamic stability for the mutations under study. We propose that this other factor is the kinetic stability of thioredoxin in vivo, since( i) kinetic stability relates to irreversible denaturation, (ii) the rate of irreversible denaturation in a crowded cellular environment (or in a harsh extracellular environment) is probably determined by the rate of unfolding, and (iii) the half-life for unfolding changes in an exponential manner with activation free energy and, consequently, comparatively small free energy effects can have deleterious consequences for kinetic stability. This proposal is supported by the results of a kinetic study of the WT form and the 27 single-mutant variants of E. coli thioredoxin based on the global analyses of chevron plots and equilibrium unfolding profiles determined from double-jump unfolding assays. This kinetic study suggests, furthermore, one of the factors that may contribute to the high activation free energy for unfolding in thioredoxin (required for kinetic stability), namely the energetic optimization of native-state residue environments in regions, which become disrupted in the transition state for unfolding.

Amino Acid Sequence↗
PubMed2004

Stability and the evolvability of function in a model protein.

Functional proteins must fold with some minimal stability to a structure that can perform a biochemical task. Here we use a simple model to investigate the relationship between the stability requirement and the capacity of a protein to evolve the function of binding to a ligand. Although our model contains no built-in tradeoff between stability and function, proteins evolved function more efficiently when the stability requirement was relaxed. Proteins with both high stability and high function evolved more efficiently when the stability requirement was gradually increased than when there was constant selection for high stability. These results show that in our model, the evolution of function is enhanced by allowing proteins to explore sequences corresponding to marginally stable structures, and that it is easier to improve stability while maintaining high function than to improve function while maintaining high stability. Our model also demonstrates that even in the absence of a fundamental biophysical tradeoff between stability and function, the speed with which function can evolve is limited by the stability requirement imposed on the protein.

Biophysics↗
PubMed2002

Differential salt-induced stabilization of structure in the initial folding intermediate ensemble of barstar.

The effects of two salts, KCl and MgCl(2), on the stability and folding kinetics of barstar have been studied at pH 8. Equilibrium urea unfolding curves were used to show that the free energy of unfolding, deltaG(UN), of barstar increased from a value of 4.7 kcalmol(-1) in the absence of salt to a value of 6.9 kcalmol(-1) in the presence of 1M KCl or 1M MgCl(2). For both salts, deltaG(UN) increases linearly with an increase in concentration of salt from 0M to 1M, suggesting that stabilization of the native state occurs primarily through a Hofmeister effect. Refolding kinetics were studied in detail in the presence of 1M KCl as well as in the presence of 1M MgCl(2), and it is shown that the basic folding mechanism is not altered upon addition of salt. The major effects on the refolding kinetics can be attributed to the stabilization of the initial burst phase ensemble, I(E), by salt. Stabilization of structure in I(E) by KCl causes the fluorescence properties of I(E) to change, so that there is an initial burst phase change in fluorescence at 320 nm, during refolding. The structure in I(E) is stabilized by MgCl(2), but no burst phase change in fluorescence at 320 nm is observed during refolding. The fluorescence emission spectra of I(E) show that when refolding is initiated in 1M KCl, the three tryptophan residues in I(E) are less solvent exposed than when folding is initiated in 1M MgCl(2). Stabilization of I(E) leads to an acceleration in the rate of the fast observable phase of folding by both salts, suggesting that structure of the transition state resembles that of I(E). The stabilization of I(E) by salts can be accounted for largely by the same mechanism that accounts for the stabilization of the native state of the protein, namely through the Hofmeister effect. The salts do not affect the rates of the slower phases of folding, indicating that the late intermediate ensemble, I(L), is not stabilized by salts. Stabilization of the native state results in deceleration of the fast unfolding rate, which has virtually no dependence on the concentration of KCl or MgCl(2) at high concentrations. The observation that the salt-induced stabilization of structure in I(E) is accompanied by an acceleration in the fast folding rate, suggests that I(E) is likely to be a productive on-pathway intermediate.

Bacterial Proteins↗
PubMed2001

Trunk posture and spinal stability.

OBJECTIVE: The influence of trunk posture on musculoskeletal stability of the spine was investigated. DESIGN: A biomechanical model was developed to evaluate the influence of posture on spinal stability. Model performance was assessed by comparing predicted muscle recruitment patterns with measured EMG activity from the trunk muscles during static lifting exertions. METHOD: An inverted double-pendulum model of the spine controlled by 12 muscle equivalents of the trunk was implemented to determine spinal load and stability. Model input included trunk posture and lifted mass, output included muscle recruitment patterns necessary to achieve stability of the spine and spinal load. EMG activity recorded from the trunk muscles of 10 subjects were recorded during static exertions in various trunk flexion and asymmetric postures to compare with model output. Stable spinal load was examined as a function of trunk flexion and asymmetry during the lifting exertions. RESULTS: Antagonistic co-contraction was necessary to achieve spinal stability, particularly in upright postures. Stable spinal load was increased in asymmetric postures as a result of antagonistic muscle recruitment, suggesting greater neuromuscular control is necessary to maintain stability in asymmetric lifting postures. As trunk flexion angle increased, stability improved but spinal load was greater. CONCLUSIONS: Results illustrate that muscle recruitment patterns are more accurately explained by stability than by equilibrium alone. Spinal stability is influenced by posture. Specifically, control of spinal stability is reduced in asymmetric postures associated with low-back disorder risk. RELEVANCE: Traditional assessment of low-back disorder risk have focussed on spinal loading. Results illustrate that postural risk factors for low-back pain may be partially attributable to stability considerations.

Adult↗
PubMed2004

Modeling Gibbs energies of solution for a non-polar solute in aqueous solutions of the protein stabilizers glycerol and ethylene glycol.

The Hydration Shell Chemical Equilibrium Model (HSCE) has been applied to Gibbs energies of solution data for toluene in aqueous solutions of the protein stabilizers glycerol and ethylene glycol. The HSCE model fits the experimental data to nearly experimental uncertainty. This satisfactory rendering of the data provides certainty on the physical significance of the model parameters and allows a description, from the molecular point of view, of the behaviour of a non-polar solute in aqueous solutions of protein stabilizers. The toluene-stabilizer interchange energy is positive indicating a dislike between toluene and the stabilizer molecules. This dislike is, however, much less pronounced than that between the solute and water, i.e. the non-polar solute prefers to be in contact with the stabilizer rather than with water. The cohesion between water molecules is much larger than that between stabilizer molecules and it remains to be the dominant cause of the hydrophobic behaviour of the non-polar solute. Since the solute-stabilizer interactions are energetically favoured over the solute-water ones, in the vicinity of the solute the stabilizer molecules are preferred over water ones. However, there is no specific interaction leading to a distinct chemical entity (a solute-stabilizer complex). Thus, the non-polar solute-stabilizer interaction is better described by the term 'preferential solvation of the solute by the stabilizer'.

Cryoprotective Agents↗
PubMedDate not supplied

Stability of cell-penetrating peptide-morpholino oligomer conjugates in human serum and in cells.

Cell penetrating peptides (CPPs) have been shown to enhance the cellular uptake of antisense oligonucleotides (AOs). However, the effectiveness of the CPPs for cytoplasmic or nuclear delivery of therapeutic AOs must take into account the possible entrapment of the CPP-AO conjugates in endosomes/lysosomes and the overall stability of the CPP-AO conjugates to enzymes. This includes the stabilities of the CPPs and AOs themselves as well as the linkage between them. In this study, we investigated the effects of several structural features of arginine-rich CPPs on the metabolic stability of CPP conjugated to phosphorodiamidate morpholino oligomers (PMOs) in human serum and in cells. Those structural features include amino acid configurations (d or l), incorporation of non-alpha-amino acids, peptide sequences, and types of linkages between CPPs and PMOs. Using matrix-assisted laser desorption ionization time-of-flight mass spectrometry, we found that the stability of the CPP portion was varied although the PMO portion of the conjugate was completely stable both in cells and in human serum. d-Configuration CPPs were completely stable, while l-CPPs were degraded in both serum and HeLa cells. Insertions of 6-aminohexanoic acid residues (X) into an R8 peptide increased the corresponding CPP's serum stability with the degree of stability being dependent upon the positions of X. However, X-containing CPPs were degraded rapidly intracellularly. Insertions of beta-alanines (B) into the R8 peptide increased its serum stability and intracellular stability. An amide or a maleimide linkage was stable in both serum and cells; however, an unhindered disulfide linkage was not stable in either. By using fluorescent microscopy, flow cytometry, and an antisense splice correction assay, the cellular uptakes of an X-containing conjugate and its fragments were compared to their antisense activities. We found that a large fraction of the conjugate was trapped within vesicles and the degraded fragments cannot escape from the vesicles. This study indicates that the incorporation of non-alpha-amino acids into l-CPPs can increase the metabolic stability of CPP-PMOs without using costly d-CPPs. However, the position and type of non-alpha-amino acids affect the degree of stability extracellularly and intracellularly. In addition, this study reveals that the degradation of an X-containing CPP-PMO conjugate is a more rapid process than degradation of a B-containing conjugate. Last, the endosomal/lysosomal trapping limits the effectiveness of a CPP-PMO conjugate, and the stability of the CPP is one of the factors affecting the ability of the conjugate to escape the endosomes/lysosomes.

Cell Membrane↗
PubMed2000

Local cardiac wall stabilization influences the reproducibility of regional wall motion during off-pump coronary artery pass surgery.

OBJECTIVE: Myocardial ischemia is a risk factor during off-pump coronary artery bypass procedures. The development of new regional wall motion abnormalities assessed by transesophageal echocardiography (TEE) is a very sensitive sign of myocardial ischemia. To facilitate anastomosis, the epicardial area of the anastomosis site is often immobilized by a "stabilizer." This study was designed to investigate whether cardiac wall stabilization with an epicardial stabilizer could affect the interpretation of wall motion during coronary anastomosis without cardiopulmonary bypass. METHODS: The TEE videotapes of 15 adult patients were investigated. Left ventricular (LV) transgastric short and long axis views were divided according to a modified 16-segment method. LV wall motion was scored using a 5-grade scale by two independent blinded investigators during pre-occlusion, occlusion, and reperfusion of anastomosed coronary arteries. The wall motion scores of a stabilized segment combined with two adjacent segments were compared with those of non-stabilized segments. Interobserver agreement was assessed using the weighted kappa statistic. RESULTS: A total of 216 segments were analyzed by two investigators. The interobserver kappa coefficient in pre-occlusion and reperfusion periods was 0.87, 0.87 and 0.86, 0.87, respectively, indicating high agreements without stabilizer. During the occlusion period in stabilized and non-stabilized segments, it was 0.59 and 0.76, respectively, showing significantly less reproducibility in the presence of stabilizer. CONCLUSION: Cardiac wall stabilization affects the reproducibility in the interpretation of regional wall motion during off-pump coronary artery bypass surgery. Caution should be used when monitoring for myocardial ischemia using TEE during coronary artery bypass surgery with epicardial stabilizer.

Coronary Artery Bypass↗
PubMedDate not supplied

A biomechanical comparison of screw and wire fixation with and without polymethylmethacrylate re-enforcement for acetabular osteotomy stabilization in dogs.

OBJECTIVE: Compare the biomechanical characteristics of screw and wire fixation with and without polymethylmethacrylate (PMMA) re-enforcement for acetabular osteotomy stabilization in dogs. ANIMALS: Pelves removed from 8 adult mixed breed dogs weighing between 25 and 30 kg. PROCEDURE: The pubic symphysis of each pelvis was split and a central transverse acetabular osteotomy was performed. One hemipelvis from each dog was stabilized with the composite fixation (interfragmentary Kirschner wire, two screws and a figure-of-eight orthopedic wire with PMMA). The contralateral hemipelves was stabilized with an interfragmentary Kirschner wire, two screws, and a figure-of-eight orthopedic wire without PMMA. All hemipelves were tested in bending by using a materials testing machine at a cross head speed of 5 mm/min. An extensometer was placed on the dorsomedial surface of the hemipelves centered over acetabular osteotomy to record distraction of the osteotomy during loading. A load/deformation curve and a load/distraction curve was produced for each hemipelvis. The slope for the initial linear portion of the load/deformation curve and the load/distraction curve, yield load and maximum load sustained were compared between repair groups using a paired t-test with P < .05 considered significant. RESULTS: The slope of the load/deformation curve was significantly greater (P = .001) for hemipelves stabilized with the composite fixation (mean +/- SD: 69 +/- 18 N/mm) compared with hemipelves stabilized without PMMA (mean +/- SD: 39 +/- 8 N/mm). There was no significant difference (P = .593) between repair groups in the slope of the load/distraction curves as measured on the extensometer. Yield load was significantly greater (P = .0002) for hemipelves stabilized with the composite fixation (mean +/- SD: 184 +/- 25 N) compared to hemipelves stabilized without PMMA (mean +/- SD: 74 +/- 12 N). Maximum load sustained was also significantly greater (P = .013) for hemipelves stabilized with the composite fixation (mean +/- SD: 396 +/- 71 N) compared to hemipelves stabilized without PMMA (mean +/- SD: 265 +/- 94 N). Failure of hemipelves stabilized with the composite fixation occurred primarily by ventrolateral bending of the cranial and caudal pelvic segments at the osteotomy site. Failure of hemipelves stabilized without PMMA occurred by ventrolateral bending of the cranial and caudal pelvic segments at the osteotomy site with pronounced concurrent ventrolateral rotation of the cranial pelvic segment. CONCLUSION: PMMA improves the mechanical characteristics of acetabular fracture fixation, at least in part by neutralization of rotational forces. The results of this study justify use of PMMA as a component of the composite fixation when repairing acetabular fractures.

Acetabulum↗
PubMed2000

The contribution of individual interchain interactions to the stabilization of the T and R states of Escherichia coli aspartate transcarbamoylase.

Stabilization of the T and R allosteric states of Escherichia coli aspartate transcarbamoylase is governed by specific intra- and interchain interactions. The six interchain interactions between Glu-239 in one catalytic chain of one catalytic trimer with both Lys-164 and Tyr-165 of a different catalytic chain in the other catalytic trimer have been shown to be involved in the stabilization of the T state. In this study a series of hybrid versions of aspartate transcarbamoylase was studied to determine the minimum number of these Glu-239 interactions necessary to maintain homotropic cooperativity and the T allosteric state. Hybrids with zero, one, and two Glu-239 stabilizing interactions do not exhibit cooperativity, whereas the hybrids with three or more Glu-239 stabilizing interactions exhibit cooperativity. The hybrid enzymes with one or more of the Glu-239 stabilizing interactions also exhibit heterotropic interactions. Two hybrids with three Glu-239 stabilizing interactions, in different geometric relationships, had identical properties. From this and previous studies, it is concluded that the 239 stabilizing interactions play a critical role in the manifestation of homotropic cooperativity in aspartate transcarbamoylase by the stabilization of the T state of the enzyme. As substrate binding energy is utilized, more and more of the T state stabilizing interactions are relaxed, and finally the enzyme shifts to the R state. In the case of the Glu-239 stabilizing interactions more than three of the interactions must be broken before the enzyme shifts to the R state. The interactions between the catalytic and regulatory chains and between the two catalytic trimers of aspartate transcarbamoylase provide a global set of interlocking interactions that stabilize the T and R states of the enzyme. The substrate-induced local conformational changes observed in the structure of the isolated catalytic subunit drive the quaternary T to R transition of aspartate transcarbamoylase and functionally induced homotropic cooperativity.

Adenosine Triphosphate↗
PubMed2002

Effects of the abdominal belt on muscle-generated spinal stability and L4/L5 joint compression force.

The goals of this study were (1) to determine the effects of abdominal belts on muscle-generated active lumbar spine stability, (2) to determine their effect on the subsequent joint compression force at L4/L5 and (3) to determine whether the effective stability of the spine could be predicted by the active spine stability and belt condition. Electromyographic (EMG) and trunk stiffness data from a previously reported experiment in which 10 subjects performed quick-release tasks (perturbation) with and without an abdominal belt were used as inputs to biomechanical models to estimate the active spine stability and effective stability of the spine, respectively. The subjects exerted isometric trunk flexion, extension and lateral bending trials at 0 and 80% of maximum intra-abdominal pressure when the resisted force was suddenly released. Wearing an abdominal belt had no significant effect on either the muscle-generated lumbar spine stability or the L4/L5 joint compression force in any direction. The effective stability of the spine was adequately predicted by the active spine stability and the effect of the belt, which accounted for approximately 34% of the effective spine stability. The study demonstrated that the abdominal belt contributed to the passive stability of the lumbar spine and did not change the active stability for tests performed within the same experimental session.

Adult↗
PubMed1986

Erythrocyte membrane deformability and stability: two distinct membrane properties that are independently regulated by skeletal protein associations.

Skeletal proteins play an important role in determining erythrocyte membrane biophysical properties. To study whether membrane deformability and stability are regulated by the same or different skeletal protein interactions, we measured these two properties, by means of ektacytometry, in biochemically perturbed normal membranes and in membranes from individuals with known erythrocyte abnormalities. Treatment with 2,3-diphosphoglycerate resulted in membranes with decreased deformability and decreased stability, whereas treatment with diamide produced decreased deformability but increased stability. N-ethylmaleimide induced time-dependent changes in membrane stability. Over the first minute, the stability increased; but with continued incubation, the membranes became less stable than control. Meanwhile, the deformability of these membranes decreased with no time dependence. Biophysical measurements were also carried out on pathologic erythrocytes. Membranes from an individual with hereditary spherocytosis and a defined abnormality in spectrin-protein 4.1 association showed decreased stability but normal deformability. In a family with hereditary elliptocytosis and an abnormality in spectrin self-association, the membranes had decreased deformability and stability. Finally, membranes from several individuals with Malaysian ovalocytosis had decreased deformability but increased stability. Our data from both pathologic membranes and biochemically perturbed membranes show that deformability and stability change with no fixed relationship to one another. These findings imply that different skeletal protein interactions regulate membrane deformability and stability. In light of these data, we propose a model of the role of skeletal protein interactions in deformability and stability.

Cytoskeletal Proteins↗
PubMed2001

Pedicle screw adjustments affect stability of thoracolumbar burst fracture.

STUDY DESIGN: An in vitro biomechanical study of the stabilizing effect of pedicle screw instrumentation on experimental thoracolumbar burst fractures. OBJECTIVES: To evaluate the effects of different adjustments applied by the pedicle screw fixation device on the stability of the spine-device construct. SUMMARY OF BACKGROUND DATA: Pedicle screw devices are widely used to accomplish spinal reduction and provide stability to an injured spine. In previous biomechanical studies the stability of the spine-device constructs has been examined for many devices. However, no study has quantitatively assessed the associations between the device adjustments and the stability of the construct. METHODS: Five-vertebrae human cadaveric specimens with burst fracture at L1 vertebra were studied. Pedicle screw fixation device was attached to the T12 and L2 vertebrae. Five device adjustments (pure compression, pure distraction, pure extension, a combination distraction-extension, and neutral posture) were studied. Multidirectional flexibility test was performed when intact, after burst fracture, and after each device adjustment to document spinal stability. RESULTS: The construct stability had a complex association to the device adjustment. For example, the maximum flexion and extension stabilities were achieved by pure compression and distraction-extension combination adjustments, respectively. Pure distraction and pure extension adjustments decreased the construct stability. CONCLUSIONS: The device adjustments affected the spinal construct stability differently in different directions. Although pure compression provided the most stability in most directions, the combined distraction-extension adjustment may be more suitable considering the neural decompression also.

Adult↗
PubMed2005

High NaCl increases TonEBP/OREBP mRNA and protein by stabilizing its mRNA.

Hypertonicity increases mRNA and protein abundance of the transcription factor tonicity-responsive enhancer/osmotic response element binding protein (TonEBP/OREBP), contributing to increased transcription of downstream osmoprotective genes. Previously, this was attributed to increased transcription of TonEBP/OREBP because no change was found in its mRNA stability. However, there is no direct evidence for increased transcription, and the 3'-untranslated region (UTR) of TonEBP/OREBP contains numerous adenylate/uridylate-rich elements, which can modulate RNA stability. Therefore, we have reinvestigated the effect of hypertonicity on TonEBP/OREBP mRNA stability. We find that, in mouse inner medullary collecting duct cells, raising osmolality from 300 to 500 mosmol/kgH(2)O by adding NaCl increases TonEBP/OREBP mRNA to a peak of 2.3-fold after 4 h, followed by a decline. TonEBP/OREBP protein increases to a sustained peak of 3.0-fold at 8 h. To determine the stability of TonEBP/OREBP mRNA, we measured the rate of its decrease after inhibiting transcription with actinomycin D, finding that it is stabilized for 6 h after addition of NaCl. This stabilization is sufficient to explain the increase in mRNA without any change in transcription. To investigate how hypertonicity stabilizes TonEBP/OREBP mRNA, we tested luciferase reporters containing parts of the TonEBP/OREBP mRNA UTR. Inclusion of both the 5'- and 3'-UTR increases reporter activity, consistent with mRNA stabilization. Surprisingly, however, it is the 5'-UTR that stabilizes; the 3'-UTR, by itself, decreases reporter activity. We concluded that 1) hypertonicity stabilizes TonEBP/OREBP mRNA, contributing to its increase, and 2) stabilization depends on the presence of the 5'-UTR.

3' Untranslated Regions↗
PubMed1986

Restoration of normal membrane stability to unstable protein 4.1-deficient erythrocyte membranes by incorporation of purified protein 4.1.

Protein 4.1, a principal component of the erythrocyte membrane skeleton, is thought to be important in regulating membrane stability through its interaction with spectrin and actin. A key role for protein 4.1 has been indicated in studies in which deficiency of this protein was shown to result in marked instability of the membrane. In order to obtain direct evidence for the functional role of protein 4.1, we reconstituted protein 4.1-deficient membranes with purified protein 4.1 and showed restoration of membrane stability. Erythrocyte membranes totally and partially deficient in protein 4.1 were reconstituted by exchange hemolysis with various concentrations of purified protein 4.1, and their stability measured using an ektacytometer. Native erythrocyte membranes totally deficient in protein 4.1 were markedly unstable, while those partially deficient had intermediate reductions in membrane stability. Reconstitution with increasing concentrations of purified protein 4.1 resulted in progressive restoration of membrane stability. Near-normal membrane stability could be restored to both totally and partially protein 4.1-deficient membranes. In contrast, the addition of protein 4.1 to resealed membranes did not improve membrane stability. This implies that the added protein 4.1 must have access to the cell interior in order to affect membrane stability. Furthermore, in control experiments, the addition of protein 4.1 to normal membranes did not increase their stability. Also, the addition of purified spectrin and human serum albumin during resealing did not improve stability of protein 4.1-deficient membranes. These results provide direct evidence for the crucial role of protein 4.1 in regulating erythrocyte membrane stability.

Actins↗
PubMed1997

Association between mood-stabilizing medication and mental health resource use in the management of acute mania.

OBJECTIVE: To better understand how mood-stabilizing agents other than lithium have changed treatment and outcomes in bipolar disorder, this study examined health service utilization among patients with acute mania who were being treated with a variety of regimens using mood stabilizers. METHODS: Demographic, clinical, and resource utilization data were collected from the records of 96 inpatients with a discharge diagnosis of bipolar mania. Patients were categorized into four major treatment groups: lithium monotherapy, anticonvulsant monotherapy, treatment with multiple mood stabilizers, and treatment with no mood stabilizers. RESULTS: The mean +/- SD age of the sample was 50 +/- 12.3 years. Lithium was the most commonly prescribed antimanic agent, with 29 of the 96 patients on lithium monotherapy, 17 on anticonvulsant monotherapy, 42 taking multiple mood stabilizers, and eight taking no mood stabilizers. The mean inpatient stay was significantly longer for patients on multiple mood stabilizers (30.3 +/- 20.7 days) than for those on lithium monotherapy (20.7 +/- 14.4 days), anticonvulsant monotherapy (17 +/- 9.3 days), and no mood stabilizers (17.3 +/- 14.4 days). Patients who were not taking a mood stabilizer had a higher rate of leaving the hospital against medical advice than the other groups. Patients on anticonvulsant monotherapy had significantly more comorbid psychiatric illnesses than patients taking multiple mood stabilizers. Inpatient use of seclusion or restraint and of concurrent antipsychotic medications did not differ significantly between the treatment groups. Compliance with outpatient follow-up was poor in all treatment groups, and almost absent in the group taking no mood stabilizers. CONCLUSIONS: Changes in the pharmacological management of acute mania will have an impact on clinical outcomes and health resource utilization.

Acute Disease↗
PubMed2006

Arthroscopic versus open shoulder stabilization for recurrent anterior instability: a prospective randomized clinical trial.

BACKGROUND: Arthroscopic stabilization for anterior shoulder instability has been reported to result in a higher rate of recurrent instability compared to traditional open techniques. PURPOSE: To test the null hypothesis that there is no difference in the clinical outcomes in patients with recurrent anterior shoulder instability treated with open or arthroscopic stabilization. STUDY DESIGN: Randomized controlled trial; Level of evidence, 1. METHODS: A consecutive series of 64 patients with recurrent anterior shoulder instability were randomized to receive either arthroscopic or open stabilization by a single surgeon. Magnetic resonance arthrogram studies were obtained preoperatively. These findings were compared to arthroscopic findings. Postoperative evaluations included range of motion, stability, and subjective assessments including Single Assessment Numeric Evaluation, Simple Shoulder Test, Western Ontario Instability Index, and University of California, Los Angeles evaluation. Failure was defined as a second dislocation, recurrent subluxation, or symptoms precluding return to previous work or unrestricted active military duty. RESULTS: Sixty-one patients, 29 who received open stabilization and 32 who received arthroscopic stabilization, were evaluated at a mean of 32 months postoperatively (range, 24-48 months). Patient demographics were equivalent. Preoperative magnetic resonance arthrogram findings were confirmed at arthroscopic examination. The mean operative time was significantly shorter for the arthroscopic repairs (59 vs 149 minutes; P < .001). There were 3 clinical failures (2 open stabilizations, 1 arthroscopic stabilization) by the established criteria. There was a statistically significant improvement from preoperative to postoperative Single Assessment Numeric Evaluation scores in both groups (P < .001). The mean loss of motion (compared to the contralateral shoulder) was greater in the open shoulders. Subjective evaluations were equal in both groups. CONCLUSION: Clinical outcomes after arthroscopic and open stabilization were comparable. Preoperative magnetic resonance arthrograms in shoulders with anterior instability allow an accurate diagnosis of intra-articular abnormality that correlates well with operative findings. Arthroscopic stabilization for recurrent anterior shoulder instability can be performed safely; the clinical outcomes are comparable to those after traditional open stabilization.

Adult↗
PubMed2005

Biomechanical comparison of two stabilization techniques of the atlantoaxial joints: transarticular screw fixation versus screw and rod fixation.

OBJECTIVE: To compare the biomechanical stability imparted to the C1 and C2 vertebrae by either transarticular screw fixation (TSF) or screw and rod fixation (SRF) techniques in a cadaver model. METHODS: Ten fresh ligamentous human cervical spine specimens were harvested from cadavers. The specimens were tested sequentially in the intact state, after injury and stabilization (unilateral left side and bilateral), and after fatiguing to 5000 cycles (0.5 Hz) at +/-1.0 N.m of flexion and extension. The specimens were stabilized by use of TSF in 5 spines or SRF in the other 5 spines. The data were converted to angular displacements, and the stabilized cases were compared with intact states for evaluating the efficacies of the two techniques in stabilizing the C1-C2 segments. RESULTS: In the TSF group, the unilateral fixation using one screw imparted a significant stability in only the axial rotation mode. The unilateral procedure in the SRF group was effective in stabilization in all modes except in extension. The bilateral procedure in both of the groups was effective across the C1-C2 segment. However, the SRF group afforded higher stability than the corresponding TSF group in the flexion and extension modes. The degree of stability did not change after fatigue compared with the prefatigue data. CONCLUSION: In general, a surgeon should undertake a bilateral fixation to achieve sufficient stability across the atlantoaxial complex, and either technique will provide satisfactory results, although the SRF technique may be better in the flexion and extension modes. One should use the SRF procedure while trying to achieve stability with a unilateral system.

Aged↗