Search PubMed⌕ Search

Biomedical subjects

Frederick A Matsen

Publications and source records attributed to Frederick A Matsen.

At least 19 recordsLinked to original sources
PubMed2025

Increased immunogen valency improves the maturation of vaccine-elicited HIV-1 VRC01-like antibodies.

Antibodies belonging to the VRC01-class display broad and potent neutralizing activities and have been isolated from several people living with HIV (PLWH). A member of that class, monoclonal antibody VRC01, was shown to reduce HIV-acquisition in two phase 2b efficacy trials. VRC01-class antibodies are therefore expected to be one component of an effective HIV-1 vaccine elicited response. In contrast to the VRC01-class antibodies that are highly mutated, their unmutated forms do not engage HIV-1 envelope (Env) and do not display neutralizing activities. Hence, specifically modified Env-derived proteins have been designed to engage the unmutated forms of VRC01-class antibodies, and to activate the corresponding naïve B cells. Selected heterologous Env must then be used as boost immunogens to guide the proper maturation of these elicited VRC01-class antibodies. Here we examined whether and how the valency of the prime and boost immunogens influences VRC01-class antibody-maturation. Our findings indicate that, indeed the valency of the immunogen affects the maturation of elicited antibody responses by preferentially selecting VRC01-like antibodies that have accumulated somatic mutations present in broadly neutralizing VRC01-class antibodies isolated from PLWH. As a result, antibodies isolated from animals immunized with the higher valency immunogens display broader Env cross-binding properties and improved neutralizing potentials than those isolated from animals immunized with the lower valency immunogens. Our results are relevant to current and upcoming phase 1 clinical trials that evaluate the ability of novel immunogens aiming to elicit cross-reactive VRC01-class antibody responses.

AIDS Vaccines↗
PubMed2006

Direct injection of blood into the labrum enhances the stability provided by the glenoid labral socket.

We tested the hypothesis that the stabilizing function of the labrum can be enhanced by inflating it with blood. In 6 fresh cadaveric glenoids, the anteroinferior stability provided by the glenoid was quantitated by measuring the maximal angle between the glenoid centerline and the direction of the force applied via a ball in the glenoid before the ball dislocated from the glenoid. This stability angle was measured for each of 4 different applied loads. These measurements were repeated after the anteroinferior labrum was augmented by the injection of fresh blood. Injection augmentation of the labrum significantly increased the measured stability angles in 5 of 6 specimens. The 1 outlier had a partial labral tear. The mean increase in stability for all 6 glenoids ranged from 19% to 30% for the different test loads. Labral injection with blood may be a useful adjunct in the surgical management of glenohumeral instability.

Aged↗
PubMed2006

The effect of total shoulder arthroplasty on self-assessed deficits in shoulder function in patients with capsulorrhaphy arthropathy.

The objective of this study was to characterize self-assessed functional deficits before and after total shoulder arthroplasty (TSA) in a consecutive series of 24 patients treated for capsulorrhaphy arthropathy. Deficits were determined by use of the Simple Shoulder Test. The effects of age, type of original stabilization surgery, duration of time since the initial repair, and pattern of glenoid erosion were analyzed. Deficits were significantly reduced from 8.5 to 4 of 12 SST items after TSA (P = .003). Items related to motion and function had the largest effect on improvement. Age did not affect results. There was a trend toward greater improvement in patients whose original stabilization was less than 20 years previously (P = .06) and in those with concentric glenoid erosion (P = .06). A prior Bristow procedure was associated with the least improvement. Overall, TSA was an effective treatment for capsulorrhaphy arthropathy at midterm follow-up. Restoring range of motion appears to have the largest impact on improvement in function.

Adult↗
PubMed2006

Using a freeze substitution fixation technique and histological crimp analysis for characterizing regions of strain in ligaments loaded in situ.

Type I collagen fibrils in tendons and ligaments assume a sinusoidal wave shape, or crimp, which straightens only with tensile load. The load response of crimp has been studied primarily in isolated subunits and not in complex, intact structures. The purpose of our study was to determine if freeze substitution fixation of an entire ligament could preserve changes in crimp morphology induced by functionally relevant loading conditions. We hypothesized that, in ligaments prepared by freeze-substitution fixation under load, crimp would progressively extinguish with increasing loads, and nonuniform strain following partial section could be detected from crimp morphology. Tensile loads ranging from 0 to 220 N were applied to patellar ligaments of 16 fresh rabbit stifle joints using simulated isometric quadriceps pull through the patella. The loaded joints were flash frozen with isopentane cooled in liquid nitrogen, then fixed using freeze substitution. Another six ligaments were loaded to 150 N following incision of the anterior third and evaluated under polarized light microscopy for crimp distribution. Ligaments with no or low loads could be identified by the presence of crimp on mid-sagittal sections. Strain distribution was inhomogeneous, in that the ligament displayed a consistent pattern of collagen fiber recruitment among three morphologically distinct bands seen on coronal sections. At very low loads (about 18 N), the fibers in a central band were uncrimped; anterior and deep bands uncrimped at higher loads. The crimp in the entire specimen was extinguished at about 67 N, which correlates closely with the previously reported toe-region of the stress-strain curve of the rabbit patellar ligament. When the anterior third was transected, fibers within that segment retained a crimp in ligaments prepared under loads that ordinarily would ablate all crimp. These findings suggest that freeze fixation could be used to map the functional microstructure of ligaments or tendons.

Animals↗
PubMed2006

Alterations in surface geometry in retrieved polyethylene glenoid component.

This study characterized and quantified the changes found in retrieved glenoid polyethylene components found at revision total shoulder arthroplasty (TSA). Twenty components obtained at revision TSA were evaluated, all from a system (Global, DePuy, Warsaw, IN) with a glenoid radius of curvature 3 mm greater than that of the humeral head. Laser surface scanning provided three-dimensional analysis of the surface of the glenoid component. Scans of unused components of similar sizes enabled determination of the changes occurring after implantation. Alterations in radius of curvature were noted in every glenoid. All showed loss of the balance stability angle (BSA, the maximal angle that the net humeral joint reaction force can make with the glenoid center line before the humeral head would dislocate) of at least 5 degrees in one or more directions. Increase in BSA in one direction was seen in 11 of the components. In five of these, the increase was associated with a reduction of the local radius to match that of the humeral component. Glenoid surface morphology and stability can be changed by in vivo use. While correlation with clinical instability in the patients from whom the implants were obtained was not possible, many of the observed changes in surface morphology are of sufficient magnitude to compromise the contribution of the glenoid surface to shoulder stability. Three patterns of wear were identified: "humeral" that showed loss of the mismatch between the humeral and glenoid radii of curvature (5 of 20 components), "diffuse" that showed broad surface irregularity (18 of 20), and "rim" wear with loss of the polyethylene rim of the component (14 of 20). More than one type of wear was possible within a single glenoid.

Arthroplasty, Replacement↗
PubMed2006

A geometric approach to tree shape statistics.

This article presents a new way to quantify the descriptive ability of tree shape statistics. Where before, tree shape statistics were chosen by their ability to distinguish between macroevolutionary models, the resolution presented in this paper quantifies the ability of a statistic to differentiate between similar and different trees. This is termed the geometric approach to differentiate it from the model-based approach previously explored. A distinct advantage of this perspective is that it allows evaluation of multiple tree shape statistics describing different aspects of tree shape. After developing the methodology, it is applied here to make specific recommendations for a suite of three statistics that may prove useful in applications. The article ends with an application of the statistics to clarify the impact of taxa omission on tree shape.

Classification↗
PubMed2005

Convergence to the island-model coalescent process in populations with restricted migration.

In this article we apply some graph-theoretic results to the study of coalescence in a structured population with migration. The graph is the pattern of migration among subpopulations, or demes, and we use the theory of random walks on graphs to characterize the ease with which ancestral lineages can traverse the habitat in a series of migration events. We identify conditions under which the coalescent process in populations with restricted migration, such that individuals cannot traverse the habitat freely in a single migration event, nonetheless becomes identical to the coalescent process in the island migration model in the limit as the number of demes tends to infinity. Specifically, we first note that a sequence of symmetric graphs with Diaconis-Stroock constant bounded above has an unstructured Kingman-type coalescent in the limit for a sample of size two from two different demes. We then show that circular and toroidal models with long-range but restricted migration have an upper bound on this constant and so have an unstructured-migration coalescent in the limit. We investigate the rate of convergence to this limit using simulations.

Algorithms↗
PubMed2005

PEG-grafted chitosan as an injectable thermosensitive hydrogel for sustained protein release.

Thermosensitive polymer hydrogels that undergo a sol-to-gel transition in response to temperature changes are of great interest in therapeutic delivery and tissue engineering as injectable depot systems. A chitosan-based, injectable thermogel was prepared by grafting an appropriate amount of PEG onto the chitosan backbone and studied for drug release in vitro using bovine serum albumin (BSA) as a model protein. When more than approximately 40 wt.% of PEG was grafted to chitosan chains via covalent bonding, the aqueous solution of the resultant copolymer was an injectable liquid at low temperature and transformed to a semisolid hydrogel at body temperature. After an initial burst release in the first 5 h, a steady linear release of protein from the hydrogel was achieved for a period of approximately 70 h. Prolonged quasi-linear release of protein up to 40 days was achieved by crosslinking the hydrogel with genipin in situ, in a fashion suitable for protein encapsulation while maintaining the injectability of the hydrogel. The crosslinkage transformed the copolymer from a physical gel to an insoluble chemical gel and substantially reduced the initial burst release of protein. Both high performance liquid chromatography (HPLC) and gel electrophoresis indicated that the primary structure of BSA released from the hydrogels with or without genipin-crosslinking was generally conserved. The hydrogel can be prepared in solutions with a physiological pH, allowing the safe incorporation of bioactive molecules for a broad range of medical applications, particularly for sustained in vivo drug release and tissue engineering.

Chitosan↗
PubMed2005

PEG-grafted chitosan as an injectable thermoreversible hydrogel.

PEG-grafted chitosan was formulated such that its solution undergoes a thermally reversed phase transition from an injectable free-flowing solution at low temperature to a gel at body temperature. Aqueous solutions of PEG-grafted chitosan can be prepared at physiological pH values, thereby allowing safe incorporation of bioactive molecules. This injectable thermoreversible hydrogel is potentially suitable for a wide range of biomedical applications, particularly in sustained in vivo drug release and tissue engineering. An aqueous solution of PEG-grafted chitosan polymer is injectable at low temperatures but forms a gel at body temperature.

Chitosan↗
PubMed2005

Electrospun chitosan-based nanofibers and their cellular compatibility.

Chitosan-based nanofibers with an average fiber diameter controllable from a few microns down to approximately 40 nm and a narrow size distribution were fabricated by electrospinning solutions containing chitosan, polyethylene oxide (PEO), and Triton X-100. Rheological study showed a strong dependence of spinnability and fiber morphology on solution viscosity and thus on chitosan-to-PEO ratio. The nanofibers can be deposited either as a nonwoven mat or as a highly aligned bundle of controllable size. Potential use of this nanofibrous matrix for tissue engineering was studied by examining its integrity in water and cellular compatibility. It was found that the matrix with a chitosan/PEO ratio of 90/10 retained excellent integrity of the fibrous structure in water. Experimental results from cell stain assay and SEM imaging showed that the nanofibrous structure promoted the attachment of human osteoblasts and chondrocytes and maintained characteristic cell morphology and viability throughout the period of study. This nanofibrous matrix is of particular interest in tissue engineering for controlled drug release and tissue remodeling.

Biocompatible Materials↗
PubMed2005

Healing of reamed glenoid bone articulating with a metal humeral hemiarthroplasty: a canine model.

This study characterizes the healing response of the glenoid after spherical reaming and prosthetic humeral head replacement in a canine model of glenohumeral hemiarthroplasty. The right glenoid of twelve skeletally mature female dogs was reamed to a uniform radius of curvature, removing all cartilage down to bleeding subchondral bone. The glenoid was not resurfaced. The humeral head was replaced with a stemmed metal prosthesis. Post-surgery, the operated limbs were immobilized for seven days, with motion allowed ad libitum thereafter. Fluorescent bone labels were administered to identify bone formation. These procedures were not complicated by instability, infection or death. Six animals were euthanized at 10 week and six more at 24 week. The intact glenohumeral joints were evaluated by gross examination, assessment of glenoid concavity, and light microscopy of methylmethacrylate sections. At 10 week, vascular fibrous tissue partially covered the glenoid, maintaining a concave surface congruent with the prosthetic humeral head. New bone formed at the margin of the glenoid, and the density of the periarticular trabecular bone increased. At 24 week, the healing was more advanced; thick fibrocartilaginous tissue covered the entire glenoid surface. These results demonstrate that spherical glenoid reaming produced a consistent healing response characterized by remodelling of the reamed bony concavity to a congruent, living, smooth, securely attached interface articulating with the humeral prosthesis.

Animals↗
PubMed2005

Open rotator cuff repair without acromioplasty.

BACKGROUND: In most clinical reports on rotator cuff repair, acromioplasty was done as part of the procedure. In this prospective study, we evaluated the hypothesis that rotator cuff repair without acromioplasty would result in a substantial improvement in shoulder comfort and function. METHODS: Ninety-six consecutive primary repairs of full-thickness tears of the rotator cuff were performed through a deltoid-muscle-splitting incision that preserved the integrity of the coracoacromial arch and the deltoid insertion. All patients were invited to participate in a prospective study involving periodic self-assessment of shoulder function with the Simple Shoulder Test and general health status with the Short Form-36 (SF-36) questionnaire, both of which are validated instruments. Sixty-one patients provided follow-up information for at least two years postoperatively, and the average duration of follow-up was five years. Thirty-four of the tears involved the supraspinatus tendon alone; sixteen involved the supraspinatus and infraspinatus tendons; and eleven involved the supraspinatus, infraspinatus, and subscapularis tendons. RESULTS: The percentage of shoulders that could be used to perform each of the twelve functions on the Simple Shoulder Test was significantly increased postoperatively (p < 0.002). Men and women had different degrees of function preoperatively (p < 0.00000001) and postoperatively (p < 0.001), but the improvement in function was essentially identical for the two genders. The mean improvement in the number of shoulder tests that could be performed was best for the patients with one-tendon tears (4.9 tests), next best for those with two-tendon tears (3.6 tests), and worst for those with three-tendon tears (3.3 tests). SF-36 scores for physical role (p < 0.003) and comfort (p < 0.0001) were significantly improved postoperatively. CONCLUSIONS: Significant improvement in self-assessed shoulder comfort and in each of the twelve shoulder functions was observed after rotator cuff repairs performed without acromioplasty. The technique that we used is very similar to that described by Codman almost seventy years ago.

Acromion↗
PubMed2005

Anteroinferior bone-grafting can restore stability in osseous glenoid defects.

BACKGROUND: Glenohumeral instability associated with a large osseous defect of the glenoid can be treated with bone graft to restore the glenoid concavity. The shape and positioning of the graft is critical: a graft that encroaches on the extrapolated glenoid curvature can prevent the head from seating completely in the glenoid, whereas a graft that is too far from the curvature does not restore the glenoid concavity. The purpose of the present study was to investigate how the intrinsic stability that is provided by the glenoid is affected by (1) a standardized anteroinferior glenoid defect and (2) different configurations of anteroinferior glenoid bone graft. METHODS: The anteroinferior stability provided by the glenoid was quantitated by measuring the balance stability angle in that direction. The balance stability angle is the maximal angle that the direction of the net humeral joint-reaction force can make with the glenoid centerline before dislocation takes place. The anteroinferior stability was assessed in each of four fresh-frozen, grossly normal cadaveric glenoids in (1) the unaltered state, (2) after the creation of a standardized defect of a magnitude that has been reported by other investigators to be sufficient to require a bone graft, and (3) after each step of a series of bone-grafting procedures involving grafts of varying height and contour. RESULTS: The anteroinferior glenoid defect significantly diminished the anteroinferior stability by almost 50% (p = 0.006). Bone-grafting significantly increased the stability provided by the glenoid. The increase in stability as compared with that of the glenoid with the standardized defect was particularly marked for contoured graft heights of 6 and 8 mm, for which the increases were 150% (p = 0.0001) and 229% (p < 0.00025), respectively. Contouring of the graft minimized the potential for unwanted contact between the ball and the graft. CONCLUSIONS: Anteroinferior shoulder instability caused by an osseous defect in the glenoid can be corrected with bone-grafting. The effectiveness of the graft in restoring the lost stability is related both to its height and to the extent to which it is contoured as long as the graft is not so prominent that it forces the ball posteriorly from the center of the glenoid.

Aged↗
PubMed2005

Humeral component modularity may not be an important factor in the outcome of shoulder arthroplasty for glenohumeral osteoarthritis.

We examined the outcomes of using 3 types of humeral prostheses in total shoulder arthroplasty for osteoarthritis: a modular prosthesis with variable head diameters (MV), a nonmodular prosthesis with variable head diameters (NV), and a nonmodular prosthesis with a fixed head diameter (NF). Patients (N=101) completed self-assessments of shoulder function and health status before surgery and at follow-up between 30 and 60 months after surgery. Outcomes for the MV and NV prostheses did not differ statistically. The NF prosthesis trended toward poorer functional scores. Two Short Form-36 dimensions were statistically significantly lower (P<.05) in the NF group than in the MV and NV groups. These results fail to confirm that humeral component modularity is an important factor in the outcome of shoulder arthroplasty.

Aged↗
PubMed2004

Win-stay, lose-shift in language learning from peers.

Traditional language learning theory explores an idealized interaction between a teacher and a learner. The teacher provides sentences from a language, while the learner has to infer the underlying grammar. Here, we study a new approach by considering a population of individuals that learn from each other. There is no designated teacher. We are inspired by the observation that children grow up to speak the language of their peers, not of their parents. Our goal is to characterize learning strategies that generate "linguistic coherence," which means that most individuals use the same language. We model the resulting learning dynamics as a random walk of a population on a graph. Each vertex represents a candidate language. We find that a simple strategy using a certain aspiration level with the principle of win-stay, lose-shift does extremely well: stay with your current language, if at least three others use that language; otherwise, shift to an adjacent language on the graph. This strategy guarantees linguistic coherence on all nearly regular graphs, in the relevant limit where the number of candidate languages is much greater than the population size. Moreover, for many graphs, it is sufficient to have an aspiration level demanding only two other individuals to use the same language.

Algorithms↗
PubMed2004

Glenoid cementing may generate sufficient heat to endanger the surrounding bone.

Glenoid loosening is a common complication of shoulder arthroplasty. One possible cause is bone necrosis from the exothermic reaction of polymethylmethacrylate. The relationship between the amount of cement used in glenoid fixation and the risk of thermal injury to bone was examined. Glenoid arthroplasty was done on 17 fresh cadaver scapulas, recording the amount of cement used. The bone surface temperature during cement curing was measured using infrared thermography. Using these data and published thresholds for thermal necrosis, the frontal plane area of bone that would be at risk for necrosis in vivo was estimated. The average weight of cement implanted was 5.35 g (2.65-8.08 g). The maximum temperature recorded averaged 64.7 degree C (48.2 degree-76.8 degree C). The area of bone at risk correlated with the amount of cement used. This study indicates that potentially dangerous amounts of heat may be generated during cementing of glenoid components.

Arthroplasty, Replacement↗