Charles N. Bertolami

Use of sodium hyaluronate in treating temporomandibular joint disorders: A randomized, double-blind, placebo-controlled clinical trial

This study assessed the efficacy of high-molecular-weight sodium hyaluronate as a treatment for certain intracapsular temporomandibular joint (TMJ) disorders. One hundred twenty-one patients were studied at three test sites using a randomized, double-blind, placebo-controlled experimental design. Patients were selected on the basis of 1) confirmed diagnosis of either degenerative joint disease (DJD), reducing displaced disc (DDR), or nonreducing displaced disc (DDN); 2) nonresponsiveness to nonsurgical therapies; and 3) severe dysfunction as established by the Helkimo indices (HI), visual analog scales (VASs), and physical measurements of joint movement and joint noise (arthrophonometry [APM]). Subjects received a unilateral upper joint space injection of either 1) 1% sodium hyaluronate in physiologic saline (MedChem Products, Woburn, MA) or 2) USP physiologic saline. Clinical evaluations were performed using HI, VAS, and APM at weekly intervals for the first month and then at monthly intervals up to 6 months postinjection. Statistical analyses for both categorical and continuous variables were performed for each diagnostic category at each examination interval. For DJD, no difference in outcome was seen between treatment groups. For DDN, significant between-group differences were seen through 1 month; however, beyond this time point, the number of DDN patients was insufficient to draw meaningful conclusions concerning efficacy. For DDR, statistically significant within-group and between-group improvement in all three measures (HI, VAS, APM) was seen for the hyaluronate group compared to the saline group throughout the 6-month test period. At the month-2 and month-3 examination intervals, twice as many patients treated with hyaluronate (90%) showed improvement compared to patients given placebo. Further, only 3% of patients with DDR who were treated with hyaluronate relapsed compared with 31% of patients with DDR given placebo.

Effect of chitosan on lingual hemostasis in rabbits.

Bleeding times were measured for bilateral (15 mm x 2 mm) tongue incisions in 14 New Zealand white rabbits. Using a randomized, blinded experimental design, one incision in each animal was treated with chitosan and the other was treated with control vehicle without chitosan. Extraoral bleeding and coagulation times were also measured for each animal preoperatively, postoperatively, and prior to killing to verify normal bleeding parameters and to evaluate possible systemic effects associated with topical application. Comparison of lingual incisions receiving the experimental substance versus those receiving control solution showed enhanced hemostasis manifested by a 32% (P less than .05) decrease in bleeding time.

The acoustical characteristics of the normal and abnormal temporomandibular joint

This paper describes the results of a clinical study that recorded and analyzed sounds emitted from the temporomandibular joint (TMJ) during simple function as a means for differentially diagnosing disorders of the joint. The technique is based on the principle that each different disorder of the TMJ produces a different effect on the mechanical relationship between the articulating surfaces of the joint, and that these mechanical effects can be determined by analyzing joint sounds in relation to joint movement. A total of 79 patients (101 joints) were studied; 32 (46 joints) were diagnosed as having extracapsular disorders, (primarily MPD), 27 (32 joints) were diagnosed as having a displaced disc with reduction, nine (10 joints) were diagnosed as having a displaced disc without reduction, and 11 (13 joints) were diagnosed as degenerative disease (osteoarthritis/arthrosis). In addition, 25 adults (50 joints) with normal TMJs were included as controls. The results of this study demonstrated that each specific disease of the TMJ is characterized by a unique relationship between the sounds propagated by the joint and the movement of the joint. Essentially, an extracapsular disease was characterized by acoustic quiescence during natural (as opposed to maximal) jaw movement, an internal derangement by a usually symmetrical short duration click/reciprocal click, or random click complex, depending on the subcategory of the disorder, and a degenerative disease by a long duration noise during either or both jaw opening and closing. The data further suggest that the technique serves to reflect the mechanical events (and abnormalities) that are involved in function of the diseased joint and has potential for use as a clinical diagnostic tool.

Effect of chitosan on lingual hemostasis in rabbits with platelet dysfunction induced by epoprostenol

Chitosan, a complex carbohydrate derivative of shellfish exoskeleton, is shown to enhance lingual hemostasis in rabbits treated with a known antagonist of platelet function, epoprostenol (prostacyclin or PGI2). Bleeding times were measured for bilateral (15 mm x 2 mm) tongue incisions in 10 New Zealand white rabbits. Using a randomized, blinded experimental design, one incision in each animal was treated with chitosan and the other was treated with control vehicle without chitosan. Extraoral bleeding and coagulation times were measured for each animal before, during, and after infusion of epoprostenol. Continuous infusion of epoprostenol increased mean systemic bleeding time 95%. In this platelet dysfunction animal model, lingual incisions receiving the experimental substance showed a 56% improvement in bleeding time in comparison with lingual incisions receiving control solution (P = .003).

Hyaluronidase activity during open wound healing in rabbits: a preliminary report.

Abstract The presence of an enzyme with hyaluronidase activity has been established for open wound granulation tissue in rabbits. Such activity was unrelated to the presence of inflammatory cells and, in fact, was absent in early wounds. Activity increased 7 days after wounding and remained elevated through the 19-day term of the study. The approximate hyaluronic acid content of granulation tissue during healing decreased markedly during this period. The relationship of hyaluronidase to hyaluronic acid in the process of open would healing is discussed.

The Spectral Properties of Temporomandibular Joint Sounds

Spectral analyses were performed on sounds recorded from TMJs that had previously been classified into different intracapsular categories, in an attempt to determine whether the inherent properties of these sounds were unique for each different disorder. A total of 55 joints was studied: 32 were diagnosed as displaced disc with reduction [DDR], 10 were diagnosed as displaced disc without reduction [DDN], and 13 were diagnosed as degenerative joint disease [DJD]. The spectral analysis for each recorded joint sound was performed using a Fast Fourier transform routine, the results of which were plotted as a frequency vs. amplitude envelope. These analyses showed that different intracapsular TMJ disorders were characterized by sounds whose energy distribution patterns, while showing certain across-group differences, usually shared significant common spectral properties. The joint-propagated noises associated with DDR, DDN, and DJD were each characterized by a spectral envelope whose primary band of energy was centered around a peak at approximately 1 kHz, and which dropped off from that point to background levels. These patterns presumably reflect the resonance characteristics of the disordered joint as defined by the mass and stiffness of its articulating surfaces. Based on the findings of this study, it would appear that comparisons of the spectral envelopes of joint-propagated sounds would have only limited application in the differential diagnosis of intracapsular TMJ disorders.

Advances in diagnostic and surgical arthroscopy of the temporomandibular joint

Part 1 Diagnosis: terminology for normal findings intracapsular fibrosis related to pain and dysfunction intraarticular adhesions of the temporomandibular joint arthroscopic evaluation of patients with temporary silastic implants. Part 2 Treatment: a 5-year experience with arthroscopic lysis and lavage for the treatment of painful temporomandibular joint hypomobility arthroscopic surgery for the treatment of restrictive temporomandibular joint disease effectiveness of arthroscopy a retrospective study comparing arthroscopic surgery with arthrotomy and disk repositioning temporomandibular joint arthroscopic surgery arthroscopic temporomandibular joint lysis, lavage and manipulation and chemical sclerotherapy for painful hypermobility and recurrent mandibular dislocation arthroscopic treatment of the human temporomandibular joint. Part 3 Technology: temporomandibular joint arthroscopic photography and documentation arthroscopic laser surgery and suturing for temporomandibular joint disorders arthroscopic traction suturing arthroscopic laser procedures. Part 4 Research: development of the canine model for investigative temporomandibular joint arthroscopy the structure and function of sodium hyaluronate and its use as a biomaterial to treat temporomandibular joint dysfunction sodium hyaluronate injections in synovial joints the histologic basis and clinical implications for temporomandibular joint adaptation synovial fluid pressure.

Modulation of fibroblast growth and glycosaminoglycan synthesis by interleukin-1.

Cellular response to inflammatory mediators is central to the regulation of new scar tissue formation. Fibroblasts derived from normal dermis and from 14-day old skin wound granulation tissue were compared with regard to production of non-collagenous extracellular matrix and response to interleukin-1 (IL-1). Following a serum-free 48 hour labeling with [3H]-glucosamine, the cellular, pericellular and medium fractions from the two cell types were collected, precipitated with cetylpyridinium chloride (CPC), and analyzed by cellulose acetate electrophoresis. In addition, susceptibility of precipitates to the polysaccharidases Streptomyces hyaluronidase and chondroitinase ABC was determined. Labeled conditioned medium from both cell types contained dermatan sulfate (DS) and hyaluronate (HA), although the relative amounts of these glycosaminoglycans (GAGs) were different. Medium from normal dermal fibroblasts contained more DS than HA, while 14-day granulation tissue culture medium contained a proportionately larger amount of HA. The amount of HA in the medium fraction of normal dermal fibroblasts was increased approximately 10-fold in the presence of 5 U/ml IL-1, while HA in the medium of wound-derived fibroblasts was quantitatively unaffected by addition of the mediator. Pericellular GAG consisted of heparan sulfate (HS) and chondroitin sulfate (CS), with no observable differences between the two cell types and no effect of IL-1 on this profile for either cell type. Conditioned medium from both cell types contained IL-1 activity (measured by thymocyte proliferation assay), with medium from 14-day granulation tissue fibroblasts containing 10-fold higher activity than normal dermal fibroblast medium.

Distinctive fibroblastic subpopulations in skin and oral mucosa demonstrated by differences in glycosaminoglycan content

SummaryThe glycosaminoglycan (GAG) content of rabbit skin, oral mucosa, and cultured [3H]-glucosamine-labeled dermal and submucosal fibroblasts was compared. Skin contained predominantly dermatan sulfate (DS) and a small amount of hyaluronic acid (HA), whereas mucosa contained primarily keratan sulfate (KS) and smaller quantities of HA and DS. Culture medium from dermal and submucosal fibroblasts contained GAGs co-electrophoresing with DS, HA, and chondroitin sulfate (CS), although the relative proportions of these GAG differed. CS isolated from dermal and mucosal fibroblast culture medium co-electrophoresed with chondroitin 4-sulfate (C4-S) on cellulose acetate, whereas dermal medium CS was resistant to digestion by chondroitinase ABC, and mucosal medium CS was chondroitinase ABC-susceptible. The pericellular matrix of dermal fibroblasts contained primarily DS and C4-S/C6-S, as confirmed by chondroitinase ABC digestion; the corresponding fraction of mucosal fibroblasts contained HS and a GAG co-electrophoresing with a C6-S standard, yet resistant to digestion by chondroitinase ABC. Thus the GAG content of dermal and mucosal fibroblasts differed both qualitatively in terms of the type of GAG secreted into the culture medium and pericellular matrix, and quantitatively, in terms of the relative proportions of these GAGs in both fractions. These differences support the concept of distinctive fibroblastic subpopulations in skin and mucosal tissue, inasmuch as the cells were subjected to identical culturing conditions.

Binding and internalization of hyaluronate by human cutaneous fibroblasts

Hyaluronate is a ubiquitous component of mammalian extracellular matrix. It influences numerous cellular processes and accumulates in fibrotic connective tissue disorders. Recently, hyaluronate catabolism has assumed additional importance because of the introduction into clinical practice of therapeutic procedures which deposit high concentrations of hyaluronate directly into tissues. Relatively little is known about the local metabolism, fate, or long-term effects of either endogenous or exogenous hyaluronate at deposition sites. A capacity for degrading hyaluronate within connective tissues, presumably by fibroblasts, has been inferred but remains controversial because direct proof that human fibroblasts endocytose and degrade hyaluronate has been lacking. In the present study, fibroblasts from normal and fibrotic skin were incubated with [3H]-hyaluronate. Binding and internalization of radiolabeled substrate were then measured: Binding assays revealed a saturable, dose-dependent increase in cell surface-associated [3H]-hyaluronate which was enhanced by pretreatment with hyaluronidase. Similar binding curves were obtained for all cells tested. All the cell lines internalized hyaluronate; however, fibroblasts in confluent cultures internalized 3.5- to 4.2-fold more radioactivity per cell than did fibroblasts from corresponding subconfluent cultures (p less than or equal to 0.002). Normal scar fibroblasts showed greater capacity for generating hyaluronate-derived partial degradation products. This work provides clear evidence that human cutaneous fibroblasts are capable of both binding and internalizing hyaluronate, possibly as a prerequisite for degradation.