Sarcoid-related uveitis occurring during etanercept therapy.

We report the case of a 7-year-old boy who was initially diagnosed as having polyarticular juvenile idiopathic arthritis. Clinical and laboratory features of overt sarcoidosis became evident early during etanercept therapy when he developed acute panuveitis, papular skin rash and elevated levels of angiotensin-converting enzyme. Non-caseating granulomas were present in the liver. Uveitis resolved upon discontinuation of etanercept and systemic administration of corticosteroids. In rare cases expression of autoimmune disorders or expanded clinical features of these disorders may occur during etanercept treatment.

Treatment of experimental mouse bladder tumour by LPS-induced epithelial cell shedding.

The purpose of the present study was to explore the therapeutic potential of serial administration of shedding-inducing endotoxin in a mouse tumour bladder model. The studies were conducted with two variants derived from the MBT-2 tumour namely, T5 and T50, the latter being far more aggressive than the former. It was found that T5 tumours responded to intravesical lipopolysaccharides (LPS) instillation by a considerable reduction in their pace of growth (P < 0.0001) when treatment was initiated 3 days after tumour implantation, but not when started after 7 days. The T50 variant did not respond to LPS when treated 3 days after implantation, but a considerable reduction in rate of growth occurred when treatment was started after 1-2 days. Shedding induced by intravesically instilled LPS was found to retard considerably the progression rate of experimental bladder tumour.

The relativity of biocompatibility. A critique of the concept of biocompatibility.

The concept of biocompatibility of the materials used in surgical reconstruction of joints, ligaments, and tendons is controversial, as evinced by the conflicting definitions proposed by the many authors who have studied the host reaction to the presence of implants and their breakdown products. We propose that biocompatibility of contemporary medical implants is not a property of the chemical composition of the biomaterials but depends rather on their physical attributes. The histological reaction patterns of tissue to the presence of polyethylene in diverse physical states are described. The inflammatory response evoked by the implants is laudable in so far as it precedes and accompanies the adequate tissular incorporation of the devices used. On the other hand, the granulomatous reaction induced by small, irregularly shaped and edgy breakdown products adversely affects the life span of the implants. Thus the manner in which the host handles the biomaterials is determined primarily by the physical state of the biomaterials (rather than their chemical composition), which in turn determines the success or failure of reconstructive surgery. It logically follows that biocompatibility constitutes a relativistic concept.

Secondary hyperparathyroidism and nonmedullary thyroid cancer.

Nonmedullary thyroid carcinoma is known to occur in association with primary hyperparathyroidism. A combination of secondary, uremic, hyperparathyroidism and non-medullary thyroid carcinoma is rare and was hitherto reported in only 12 cases. We report another three patients with this parathyroid/thyroid disease combination, suggesting that it may represent not merely a coincidence. A number of factors active in secondary hyperparathyroidism may play a role in the induction and/or promotion of the thyroid cancer. These include parathyroid endocrinopathy, goiterogenic effect of prolonged hypercalcemia, and uremia. During surgery on the parathyroid glands, associated thyroid lesions demand special considerations.

Remodeling of the calcaneus apophysis in the growing child.

Radiography and computer-aided analysis of tomography of the os calcis in 35 children with Sever's disease and of 52 control children were concurrently evaluated with histologic appearance of six calcanei of victims of road accidents, which were radiographically compatible with the same syndrome. Histology showed abrupt interruption in continuity of the apophysis of perpendicular fibrous plates with evidence of an ongoing reparative process. Computer-aided analysis of orientation of the "fragmentation" lines and histologic data both support the hypothesis of a stress remodeling process owing to excessive bending forces acting on the calcaneal apophysis.

The malignant potential of postchemotherapy residual mature teratoma for disseminated nonseminomatous testicular tumors.

Flow cytometric nuclear DNA ploidy analysis was used to study 7 paraffin-embedded tissue blocks from 3 patients with postchemotherapy residual mature teratomas. All specimens contained abnormal DNA and were classified as DNA aneuploid. These findings indicate that despite the benign appearance of postchemotherapy mature teratomas, these lesions are susceptible to resume malignant behavior. Therefore, complete surgical removal is recommended.

The nature of the bone-implant interface. The lessons learned from implant retrieval and analysis in man and experimental animal.

The morphological appearances of the interface between the bone and the components of arthroplasties depend on multiple factors. Present-day biomaterials being biocompatible when in bulk form, a host reaction consequent upon untoward effects of the implants as such is not expected. Thus, osseointegration, i.e., the direct apposition of bone to the surface of a foreign material at the light microscopical level, occurs, under favorable biomechanical circumstances, irrespective of the chemical composition of the implant. Osseointegration is a multifaceted phenomenon. First and foremost, it evolves when an initially rigid fixation of the component is surgically attained. Interfacial motions are associated with resorption of the bony bed, macrophagic activation and production of wear particles, the close bone-implant apposition is lost and the formation of an interfacial membrane (IM) ensues. The histological features of the IM coincide with the context of its formation and evolution. The quiescent IM is composed of a thin layer of fibrous tissue and its occurrence is compatible with the biofunctionality of the implant. The aggressive or lytic IM (LIM) develops when tissue-irritating, small, irregularly shaped and edgy breakdown products are deposited at the interface. The thick LIM consists of an inflamed fibrous tissue, scattered within which are myriad granulomas, and its surface facing the implant displays a synovial-like aspect. The mono- and polykaryonic macrophages, constituting the granulomatous response, ingest and abut on the wear particles. Amongst the intermediary substances of inflammation elaborated by the lymphocytes and macrophages of the LIM, factors which stimulate the osteoclasts play the pivotal role in as much as progressive bone resorption is associated with progressive growth of the IM and, hence, with incremental interfacial motion, interfacial deposition of wear particles and inflammatory-granulomatous response. The ensuing vicious circle culminates in aseptic loosening of the arthroplasty. The morphological features of the LIM, though characterized by a stereotypical reaction pattern, are, in their details, closely linked with the nature of the diverse components of the composite joint replacement. The histological appearances of the bone-implant interface of stable and loose arthroplasties, the tissular reactions to polymethylmethacrylate, polyethylene, polyacetal, metals and hydroxyapatite as well as the characteristics of cemented and cementless porous-coated, press-fit and hydroxyapatite-coated prostheses are described.

Cancer-associated fasciitis panniculitis.

BACKGROUND: Eosinophilic fasciitis and the related fasciitis panniculitis syndrome (FPS) are the clinical and morphologic expression of a variety of disorders, of which chronic inflammation and fibrous thickening of the subcutaneous septa, fascia, and perimysium are common. FPS in patients with cancer has been reported sporadically. METHODS: In the course of our studies of FPS we have encountered three patients who had an associated neoplasia. Nine reports of patients have been taken from the literature. The clinical and histologic data of FPS in the 12 patients were analyzed in the search of distinctive features from FPS in patients with no evidence of malignancy. RESULTS: Among patients with cancer-associated FPS there was a female predominance (8 patients), predilection for hematolymphatic malignancies (9 patients), precedence of the FPS to cancer diagnosis (10 patients) by a median lag time of 1 year, and unresponsiveness to prednisone therapy in most patients (7 of 8 patients). CONCLUSIONS: Cancer-associated FPS has several characteristics of a paraneoplastic syndrome: it occurs at a distance from the tumor, certain types of tumors are overrepresented among patients with FPS, it evolves in concert with the neoplasia, and it sometimes remits after successful cancer surgery. In contrast to idiopathic FPS, cancer-associated FPS shows a female predominance, and it usually fails to respond to corticotherapy.

Bone defect healing in the absence and presence of a plastic catheter: an experimental study in the rabbit.

The healing pattern of small, round, cortical defects, drilled in the upper tibial diaphysis of rabbits, was studied histologically and histomorphometrically. Group I rabbits were not further handled. In groups II and III animals, a polyethylene catheter was introduced into the medullary cavity by way of a second cortical hole and driven forward until its tip was close to the first cortical defect. Group II rabbits were not further handled. The cortical defect of group III animals was irradiated from a diode source via a fiber optic cable in the catheter. Assessment of the osseous healing of the cortical defects revealed neither qualitatively nor quantitatively significant differences among the three groups. The morphological catheter, which abuts on a cortical defect, does not hinder the normal progression of osseous bridging of the gap.

Studies on a novel anterior cruciate ligament polyethylene fiber prosthesis: the histomorphological pattern of organization and bony anchorage of a polyethylene fiber prosthesis in the stifle of the goat.

The anterior cruciate ligament of goats was substituted by a high-tensile polyethylene fiber prosthesis. The animals were sacrificed after 6-12 months. Histologically, the implants were separated from a newly formed bony shell by a thick fibrous interface membrane, which was anchored to the bone by Sharpey-like fibers. Within the joint cavity, the implants were enclosed in thick fibrous sheaths, which were continuous with the intra-osseous interface membranes. While the inner granulomatous layer of the interface membrane extended in between the polyethylene fibrils for a short distance, the bulk of the prosthesis was poorly organized. A thick central fibrous band accompanied the intra-osseous and intra-articular portions of the implants throughout their entire lengths. Oblique fibrous tracks linked the interface membranes with the central fibrous bands. The intra-osseous tunnels were considerably expanded when compared to the initially drilled tunnels.

Pathogenesis of lipodermatosclerosis of venous disease: the lesson learned from eosinophilic fasciitis.

The histological features of lipodermatosclerosis and eosinophilic fasciitis and its variants were compared in a prospective study of outpatients attending the vascular clinic and inpatients in the Department of Medicine of a regional university hospital. Main outcome measures examined were swelling and induration of the subcutaneous layers with a stocking distribution in the calves. The inflammatory and fibrosing alterations involving the panniculus adiposus, superficial fascia and perimysium were essentially indistinguishable histologically in patients with lipodermatosclerosis or eosinophilic fasciitis and its variants. The intensity of the subcutaneous induration was related to the underlying nosological entity and the duration of the process. Infectious cellulitis was found to aggravate the clinical symptoms of lipodermatosclerosis. Since the stereotypical inflammatory and fibrosing processes in lipodermatosclerosis and eosinophilic fasciitis and its variants are similar irrespective of the initiating factors, it is suggested that there is a common final pathway in the pathogenesis of both disorders.

The bone-cement interface: histological observations on the interface of cemented arthroplasties within the immediate and late phases.

Undecalcified specimens of cemented arthroplasties obtained during the early and late phases were studied. On the tenth postoperative day, there was excellent interlocking of the cement with the soft and hard tissues of the bone: there was no necrosis of the bed of the implant: a neutrophilic and macrophagic inflammatory response, where present, was mild and focal. Samples of the bone-cement interface of well fixed components obtained (at autopsy or by biopsy) many years after implantation revealed a thin and quiescent fibrous interfacial membrane alternating with bone and osteoid (that is, segmental osseointegration) or a cartilaginous layer abutting on the cement. It is concluded that, firstly, modern cementation techniques are not associated with extensive necrosis of the underlying bone in the immediate postoperative period; secondly, monomeric and polymeric methylmethacrylate as such is not toxic to the tissues; and, thirdly, acrylic cement is osseointegrated when motion at the interface is at its minimum.

Cervical soft tissue metastasis of typical carcinoid tumor preceding diagnosis of ileal primary by 4 years.

A solitary cervical metastasis of a typical carcinoid tumor was found in the subcutaneous tissue of an asymptomatic 38-yr-old woman. Investigations failed to disclose the primary site until the 5th yr, when she presented with carcinoid syndrome. Multifocal ileal carcinoid tumors were resected and debulking of abdominal metastases performed. Interferon and somatostatin analogue treatment resulted in remission. Solitary cervical metastasis is an exceedingly rare initial manifestation of a mid-gut carcinoid tumor, and poses a therapeutic dilemma. There are no directions in the literature as to whether a "wait-and-see" approach or exploration surgery is the preferred management when one is confronted by a cervical metastasis of typical carcinoid tumor of unknown primary site.

The fasciitis-panniculitis syndrome: clinical spectrum and response to cimetidine.

The term fasciitis-panniculitis syndrome (FPS) is proposed as a novel compilation encompassing several disorders, common to which is subcutaneous induration caused by cicatrizing fasciitis as well as septal and lobular panniculitis and perimysial fibrosis. Included herein are Shulman's eosinophilic fasciitis, morphea profunda, lupus profundus, venous lipodermatosclerosis, toxic oil syndrome, altered tryptophane-related eosinophilic myositis, graft-versus-host reaction, and fasciitis reactive to subjacent basal cell carcinoma. FPS should be differentiated from scleroderma, which primarily affects the dermal structures and in which arterioles are injured. In contrast, vasculopathy of the subcutaneous medium-sized veins accompanies the hypodermal lesions of FPS. The importance of recognizing and grouping these disorders lies in their different histopathology, characterization as reactive phenomena, enhanced responsiveness to treatment, and better prognosis than scleroderma. In view of the excellent prognosis of FPS, steroid treatment is not warranted. Long-term therapy with cimetidine appears to benefit the majority of patients.

The phlebopathies of the fasciitis panniculitis syndrome.

The fasciitis-panniculitis syndrome is histologically characterized by fibrous thickening and inflammation of the subcutaneous septa, fascia and perimysium. These morphological features were the common denominator in 13 patients with Shulman's eosinophilic fasciitis, scleroderma profunda, venous lipodermatosclerosis, induration following recurrent erysipelas and erysipeloid erythema nodosum. Small to medium-sized vessel phlebitis was found in the subcutaneous and perimysial tissues of 11 of the patients and subcutaneous phlebosclerosis was encountered in all cases. These data contrast with the low incidence of phlebopathy reported by others in these disorders.

[Partial sensory palsy of median nerve due to neurilemmoma].

A neurilemmoma that developed in the median nerve caused partial sensory loss in a 54-year-old woman. All symptoms disappeared within 3 months of excision of the tumor. This presentation highlights the fact that symptoms of nerve compression can be caused by intraneural tumors.

Intramuscular haemangioma of the forearm.

Intramuscular haemangioma, though benign, may be a serious disorder, because its large size can cause functional impairment, pain and disfigurement, which may require surgical excision. These, as well as the baffling histopathological aspects, are exemplified by this report of an intramuscular haemangioma of the forearm in an adolescent girl. Clinical recognition of a cutaneous angioma overlying a deeply-situated soft tissue tumour may aid the diagnosis of an intramuscular haemangioma.

Histological features of the interface membrane of failed isoelastic cementless prostheses.

The interface membranes of both components from two isoelastic cementless hip arthroplasties, which were revised for aseptic loosening, were examined histologically. The membranes consisted of densely structured fibrous tissue interspersed with giant cell granulomas, sheets of histiocytes and chronic inflammatory infiltrates. The granulomas and the histiocytes contained polymeric and metallic wear products, respectively. The morphological features of these membranes were compared with those of cemented joint replacements. Apart from the deposits of acrylic cement bordered by macrophages, there were no distinctive differences between the membranes of failed cementless and cemented arthroplasties. The release and deposition of wear products, of whatever nature, are apparently responsible for the formation of exuberant interface membranes.