Injection of vascular endothelial growth factor into knee joints induces osteoarthritis in mice.

UNLABELLED: Osteoarthritis (OA) is a common joint disorder affecting circa 2% of the population. OBJECTIVES: It has been suggested that secretion of vascular endothelial growth factor (VEGF) could play a role in the chain of events leading to OA. METHODS: In the present study, healthy mice were injected intra-articularly with VEGF. RESULTS: Shortly after the administration of VEGF, synovial hyperplasia, increased calcification of the articular cartilage and bone sclerosis were observed. Consequently, cartilage degradation characteristic of OA was found. These changes were seen to a lesser degree in the opposite knees of VEGF-injected mice and did not occur in the control mice. CONCLUSIONS: The findings suggest an active role of VEGF in the pathogenesis of OA and render support to a possible role for subchondral bone sclerosis in the pathogenesis of cartilage degradation.

'Adaptable condylectomy' for acquired facial asymmetry and malocclusion caused by temporomandibular joint condylar hyperplasia.

This article describes the 'adaptable condylectomy' and highlights two innovative treatment protocols for the variety of acquired facial asymmetry and associated malocclusion caused by condylar hyperplasia, as illustrated by the cases of seven patients presenting different manifestations of condylar hyperplasia. Protocol I (three cases) is applied for condylar hyperplasia with a normal occlusion and involves a high condylectomy, with the goal of guiding the mandible back to the original occlusion. Protocol II (four cases) is applied for condylar hyperplasia with diverse acquired malocclusions and involves condylectomy at a level adapted to the malocclusion, allowing the mandible to be guided back to the occlusion that pre-existed the active change caused by the condylar hyperplasia, or to a position as close to the midline as possible. Both protocols are followed by gradual self-correction of the acquired facial asymmetry. These protocols often obviate the need for further surgical intervention and, if further correction is needed, it is much simpler.

Limited mouth opening of unknown cause cured by diagnostic coronoidectomy: a new clinical entity?

Limited mouth opening is a constant annoyance and can be life-threatening should intubation be needed. The causes are numerous and are categorised as intra-articular or extra-articular, which are often difficult to distinguish. We present what we regard as a new clinical entity - long-standing limited mouth opening of unknown cause - and describe our treatment. Four female patients presented with limited mouth opening and lateral and protrusive movements within normal limits, which were typical of restriction of extra-articular origin. However, the radiological findings were within normal limits, with no visible cause of the restriction. All four were treated by bilateral coronoidectomy that resulted in the immediate return of mouth opening to within normal limits that was preserved over subsequent years. Histopathological examination showed atrophy and degenerative changes in the temporalis band that had been attached to the coronoid, which accounts for the stiffness of the temporalis muscle but does not explain the pathogenesis. In the light of this "diagnostic coronoidectomy" further studies are required to document the underlying pathological changes and to develop more accurate imaging that will enable correct diagnosis in future.

H2O2 renders cells accessible to lysis by exogenous phospholipase A2: a novel mechanism for cell damage in inflammatory processes.

Phospholipase A2 (PLA2) and H2O2, secreted from activated inflammatory cells, play a central role in the tissue damage occurring in inflammatory processes. However, while exogenous PLA2 alone does not cause cell lysis, it readily does so when acting with H2O2. We have found that H2O2 degrades cell surface proteoglycans, thus rendering the membrane PL accessible to hydrolysis by exogenous PLA2. This novel mechanism introduces a role for cell surface proteoglycans in protection of cells from damage by pro-inflammatory agents, and may assign a central role for the combined action of H2O2 and PLA2 in inflammatory and bacteriocidal processes.

Salivary gland transplantation: a canine model.

Impaired salivary function with resultant severe dryness of the mouth, or xerostomia, may occur in association with a variety of systemic disorders or therapies. No adequate treatment exists for this debilitating condition, which impedes normal oral function, in particular alimentation and phonation. This study explores the feasibility of salivary gland autotransplantation, using a canine model. A salivary gland with its duct and surrounding blood vessels still attached was excised and reimplanted in the dog's thigh by anastomosing the graft's blood vessels to the femoral artery and vein. The duct was sutured to an artificial orifice cut in the thigh's skin, from which the saliva was collected. Salivary secretion was induced by a single intravenous bolus of pilocarpine (5 mg). Preoperative (normal) salivation was measured by collecting saliva from the gland in situ. Periodic functional studies showed normal saliva production during the first month after grafting, after which the salivary flow was reduced by 35% over the next 2 months. This reduction was interpreted as a sign of disuse atrophy resulting from the lack of autonomic innervation. To overcome this impediment, oral pilocarpine (5 mg/day) was administered to the recipient dog, after which normal levels of saliva were excreted through the graft during the 3-month follow-up period. The quality of the graft saliva was assessed by its protein and electrolyte levels, which showed close to normal values.

Primary lymphoma of the parotid gland: a report of twelve cases with a review of the literature.

Primary extranodal lymphoma of the salivary gland is an extremely rare disease. In this report we describe twelve cases of primary lymphoma of the parotid gland seen at a single centre, and review the relevant literature. The 12 cases were treated in different departments and did not receive a uniform therapeutic approach. All three patients with Hodgkin's disease are still alive and two are in complete remission after initial radiotherapy. One of these cases developed stage 4 disease and had to receive combination chemotherapy subsequently. Of the 9 non-Hodgkin's lymphoma (NHL) patients, four had low grade NHL and 5 intermediate or high grade NHL. Of these, 2 died with disseminated disease. However, 6 are still alive and well from 1 to 5 years after therapy. These cases were treated with surgery alone, radiotherapy alone or combination chemotherapy with an anthracycline-bearing regimen. Consequently, we are unable to draw any conclusions relating the success of therapy in these cases, nor can we suggest therapeutic guidelines on the basis of this study alone. The treatment of parotid lymphoma is discussed briefly in the light of the available literature. In most cases, symptoms related to an enlarging mass in the parotid region, were evident. In the light of the above data, we suggest that, despite its rarity, lymphoma of the salivary gland should always be considered in the differential diagnosis of a parotid mass. No correlation between lymphoma and Sjogren's syndrome was noted in the present study.

Severe limitation in mouth opening following transtemporal neurosurgical procedures: diagnosis, treatment, and prevention.

Five new patients and six previously described patients with severe limitation in maximum mouth opening following transtemporal neurosurgical procedures are described. Six patients underwent an operation for epidural hematoma and three for skull-base meningloma; two were treated with a pterional craniotomy for an aneurysm. Limited maximum mouth opening in these circumstances is caused by temporal muscle scarring and shortening. Aggressive physiotherapy is potentially beneficial if started early. If, however, diagnosis is delayed, the efficacy of physiotherapy declines, and surgical treatments such as temporal muscle detachment and coronoidectomy are fully indicated. The differential diagnosis, prevention, and treatment of limited maximum mouth opening following neurosurgical procedures are discussed.

Modulation of locomotor activity of polymorphonuclear cells by cationic substances and cationic lysosomal fractions from human neutrophils.

Seven cationic substances--human and egg-white lysozyme, RNase, protamine, histone, poly-L-lysine and poly-L-arginine; five cationic lysosomal fractions from human polymorphonuclears (PMNs); RNA; poly-L-glutamic acid; DNA; heparin; endotoxin; mastocytotropic agent compound 48/80; and cytochalasin B were tested for the influence on chemotaxis and random migration of human PMNs using under-agarose migration and Boyden chambers with two filters and [51Cr]PMNs. The above substances were either preincubated with PMNs, added to chemoattractants, or used instead of chemoattractants. In under-agarose migration method chemotaxis was inhibited by 11-35% when egg-white lysozyme, protamine, heparin, endotoxin, or compound 48/80 was added to the cells. High concentration of cytochalasin B inhibited chemotaxis by 73%. Cationic fractions I and V and low concentration of cytochalasin B enhanced chemotaxis by 11%, 41%, and 30%, respectively. When human and egg-white lysozyme, DNA, or cytochalasin B was added to the chemoattractants, motility of PMNs was inhibited. Cationic fractions II and V from human PMNs, when used as chemoattractants, enhanced cellular motility by 143-167%. Random migration was enhanced by heparin and inhibited by cytochalasin B and by cationic fractions from human PMNs. These findings suggest that various cationic and anionic substances and cationic fractions from human PMNs have heterogeneous influence on random migration and chemotactic activity of human PMN. Analysis relating chemotaxis to phagocytosis and to intracellular bactericidal activity (ICBA) has shown several patterns. Protamine, poly-L-lysine, poly-L-arginine, and agent compound 40/80 all inhibit chemotaxis and enhance phagocytosis and ICBA; cationic fractions II and V enhanced all three functions, whereas cytochalasin B suppressed phagocytosis and ICBA and had concentration-dependent modulatory influence on chemotaxis. It implies diverse mechanisms of action and possible impact on inflammatory reactions.

Adhesive force: the underlying cause of the disc anchorage to the fossa and/or eminence in the temporomandibular joint--a new concept.

The commonly held cause for using the closed lock technique is the prevention of disc sliding by using the non-reducible disc. The purpose of this study was to re-evaluate the pathogenesis of sudden and persistent severely limited mouth opening associated with a total lack of disc sliding in view of the fact that it is promptly released by lavage of the upper compartment of the temporomandibular joint (TMJ). The proposed pathogenesis is based upon earlier clinical and laboratory findings of the first author coupled with pertinent information culled from the literature. It is suggested that sliding of the disc in the TMJ is enabled due to the presence of phospholipids protected by hyaluronic acid (HA) that constitute an efficient lubrication system. Joint overloading may be associated with uncontrolled production of reactive oxygen species (ROS) that causes degradation of the HA, followed by the exposure of the phospholipids to lysis by phospholipase A2 (PLA2). The denuded, smooth and elastic articular surfaces that possess high surface energy become strongly adherent when placed in direct physical contact with each other. The presence of an extremely thin film of fluid (sub-boundary lubrication) between the mating surfaces may cause even higher adhesion. These adhesive forces are probably responsible for the flexible disc anchorage to the fossa and/or eminence. They also explain the immediate release of the disc and rehabilitation of its sliding following arthrocentesis. Since it is uncommon for two opposing surfaces to be stripped bare and to become adherent, the likelihood of anchored disc phenomenon (ADP) occurring and recurring is very low.

Inflammatory cells and bacteria in pericoronal exudates from acute pericoronitis.

The present work is one in a series of studies carried out to verify the relationship between bacteria and gingival tissues in pericoronitis. Exudates from 6 cases of acute pericoronitis were examined by light and electron microscopy, including ultrathin sections and negative staining. While bacterial phagocytosis was prevalent in all the exudates studied, spirochetes, which were the predominant microorganisms, were not observed being phagocytized by PMNs or macrophages. The presence of spirochetes in pericoronitis as compared with acute necrotizing ulcerative gingivitis is discussed.

The use of monoclonal anti-CEA antibody immunohistochemistry in detecting the origin of oral cavity metastasis.

A 75-year-old woman presented with a painless swelling in the right mandibular retromolar area and numbness of the left lower lip. Radiographic examination of the mandible demonstrated an osteolytic lesion of the ascending ramus. Biopsy revealed adenocarcinoma of obscure origin. Staining of the specimen with a monoclonal antibody specific to colon carcinoma revealed its origin. On subsequent examinations, a primary tumor in the rectosigmoid region with extensive lung, liver and skeletal metastases were diagnosed. This unusual case of colonorectal carcinoma, presenting as a metastatic lesion of the mandible, was readily diagnosed by a novel immunohistochemical technique that utilizes highly specific monoclonal antibodies.

The diagnostic value of computed tomography in temporomandibular joint synovial chondromatosis.

Synovial chondromatosis of the temporomandibular joint was diagnosed and location of dens particles was assessed by means of computed tomography. Based upon the data collected, the joint was operated conservatively and most of the calcifications were removed leaving the patient symptom free. The importance of an accurate preoperative diagnosis of synovial chondromatosis by use of CT scan is stressed in view of numerous unnecessary condylectomies and parotidectomies reported in the literature.

2-Butoxyethanol model of haemolysis and disseminated thrombosis in female rats: a preliminary study of the vascular mechanism of osteoarthritis in the temporomandibular joint.

Female rats develop haemolytic anaemia and disseminated thrombosis and infarction in multiple organs, including bone, when exposed to 2-butoxyethanol (BE). There is growing evidence that vascular occlusion of the subchondral bone may play a part in some cases of osteoarthritis. The subchondral bone is the main weight bearer as well as the source of the blood supply to the mandibular articular cartilage. Vascular occlusion is thought to be linked to sclerosis of the subchondral bone associated with disintegration of the articular cartilage. The aim of this study was to find out whether this model of haemolysis and disseminated thrombosis supports the vascular hypothesis of osteoarthritis. Six female rats were given BE orally for 4 consecutive days and the two control rats were given tap water alone. The rats were killed 26 days after the final dose. The mandibular condyles showed histological and radiological features consistent with osteoarthritis in three of the four experimental rats and in neither of the control rats. These results may support the need to explore the vascular mechanism of osteoarthritis further.

Intraarticular pressure in the functioning human temporomandibular joint and its alteration by uniform elevation of the occlusal plane.

Intraarticular pressure (IAP) was measured at the posterior slope of the eminence in the upper compartment of the temporomandibular joint (TMJ) of 35 individuals (28 females and 7 males) under local anesthesia. Pressure measurements were obtained with the jaw in rest position, during maximal mouth opening (MMO), and while clenching. During MMO, IAP decreased to levels ranging between -130 and -5 mm Hg (mean, -53.82 +/- 34.40 mm Hg), whereas during clenching the pressure was always positive (range, +8 to +200 mm Hg; mean, 63.90 +/- 52.25 mm Hg). The significance of the fluctuating pressures with respect to the joint's maintenance and performance, as well as the potentially harmful effect of the positive pressure, especially when it is high and prolonged, are discussed. Females generated significantly higher pressures than males (73.70 +/- 61.06 mm Hg vs 31.42 +/- 11.47 mm Hg, P = .017). This gender difference regarding IAP may help elucidate the enigma of the considerably higher proportion of women with TMJ problems. In 22 of the patients IAP also was measured while clenching on a specifically constructed interocclusal appliance (IOA), which uniformly elevated the occlusal plane so as to reduce the force directed toward the TMJ. During clenching without the IOA, pressures ranged from 20 to 200 mm Hg (mean, 68.8 +/- 49.1), decreasing by 81.2% to IAP levels ranging from 0 to 40 mm Hg (mean, 7.9 +/- 10.9; P < .001) with the appliance in place. The use of an IOA as a palliative treatment for symptomatic TMJs is discussed.

'Friction and adhesive forces'--possible underlying causes for temporomandibular joint internal derangement.

Since normal temporomandibular joint (TMJ) movements depend primarily on the disc freely sliding down the slope of the eminence, understanding how aberrations in the lubrication system contribute to TMJ dysfunction is clearly critically important. It provides a possible explanation for the genesis of disc displacement and helps make us familiar with the clinical appearance and ways of treating limited mouth opening caused by the anchored disc phenomenon (ADP) versus disc displacement without reduction, TMJ open lock versus dislocation and osteoarthritis. This understanding clarifies the efficiency of procedures such as joint hydraulic pump, arthrocentesis and arthroscopic lavage and lysis particularly in ADP, open lock and osteoarthritis.

On the genesis of "dry socket".

One major school of thought regarding the pathogenesis of a dry socket occurring following tooth extraction is based on the concept that a blood clot fails to form, a concept that is, however, refuted by the clinical symptoms associated with the phenomena of a dry socket. A second theory maintains that, initially, clot formation takes place, but that the clot is subsequently lysed, bringing about the severe symptoms of a dry socket. Fibrinolysis generated by tissue activators only partly explains the occurrence of a dry socket. Based on the data accumulated in the literature, it is postulated that bacterial agents are involved in the fibrinolysis and that Treponema denticola may play a leading part in this process.