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Following severance of the blood supply to the left femoral head of 6-month-old rats by incising the periosteum of the neck and cutting the ligamentum teres, a 21-gauge needle, inserted into the foveola, was pushed forward in the direction of the neck up to the opposite cortical bone. Femora were obtained for histological examination on postoperative days 32 and 42, from 22 and 12 rats, respectively. The right femoral heads were normal. In addition to the usual reparative and regressive changes characteristic of the second month after induction of osteonecrosis, the left femoral heads showed, compared to the femoral heads of otherwise untreated rats, lavish ingrowth of blood vessels and proliferation of mesenchymal cells. Moreover, 16 of the 34 femoral heads disclosed additional distinctive lesions, namely, partial fibrous replacement, surface depression, intraosseous tunneling, and subtotal destruction of the epiphysis. The results of this experiment, an attempt at modeling core decompresssion in man, parallel the frequently reported unsatisfactory outcome of the procedure in patients with osteonecrosis of the femoral head. They as well indicate that any therapeutic effects of producing an epiphyseal-metaphyseal conduit for the ingrowth of vessels and cells may only be achieved at the cost of a reduction in the mechanical load-bearing capacity of the femoral head. [ABSTRACT FROM AUTHOR]

Osteonecrosis of the femoral head was produced in rats by cutting the ligamentum teres and incising the cervical periosteum. As of the second postoperative week, fibrous tissue pervaded the necrotic epiphyses, macrophages and osteoclasts removed the debris, osteoblasts deposited lamellar-fibred and woven-fibred intramembranous bone, and remodeling began. In 16% of the rats killed during the 2nd postoperative week, the epiphyses contained big fragments of necrotic bone enclosed by densely packed, capillary-sized vessels. Ingrowth of this hypervascularized, pyogenic granuloma-like tissue is presumably due to the presence of excessive growth factors, reflecting an exaggerated pathophysiological reaction within the framework of organization of the necrotic epiphyses.

A 28-year-old man presented with a clinical picture suggestive of complex regional pain syndrome type I following a blow to the thenar eminence and thumb. Symptoms, including swelling of the hand and distal forearm, progressed until an amputation was carried out to rid the patient of an unendurable painful and nonfunctioning wrist and hand. The histologic evaluation of the amputation specimen showed: 1) dermal edema, perivascular dermatitis, and epidermal hyperkeratosis; 2) subcutaneous chronic inflammation with subtotal replacement of the adipose lobules by fibrous tissue associated with thickening of the muscular fascia, implying the fasciitis-panniculitis reaction pattern; 3) atrophy, degeneration, necrosis, and focal calcifications of the skeletal muscles; 4) phlebosclerosis, phlebectasias and lymphocytic arteritis; and 5) increased cortical porosity of the bones. It seems that the pathogenetic process underlying the fasciitis-panniculitis syndrome may rarely manifest as a complex regional pain syndrome-like disorder.

The authors describe the serendipitous discovery of clustered erythrocytes within myocytes in a biopsy obtained during repair of a torn tendon. Their perusal of the literature failed to uncover an analogous observation.

The expedited revascularization of the rats' avascular, necrotic femoral heads suggests the operation of angiogenic factor(s). The blood circulation of the epiphysis was interrupted by cutting the cervical periosteum and the ligamentum teres of rats' femoral heads. Three days postoperatively, the marrow was necrotic. Seven days postoperatively, the subchondral bony plate and trabecular bone were necrotic as well. The joint capsule was distended by myriad, so-called synovial fibroblasts, all of which were virtually immunoreactive with an antibody to vascular endothelial growth factor. The expression of this factor in the synovial membrane of non-operated rats was limited to preexisting blood vessels. Revascularization of necrotic, avascular femoral heads makes up the essential step in the chain of events terminating in the repair processes, that is, resorption of the necrotic debris and its substitution by newly formed bony and hematopoietic-fatty tissues. Synthesis and release of excessive amounts of vascular endothelial growth factor by these fibroblasts explain the lively angiogenesis in the necrotic intertrabecular spaces of the femoral heads.

Myriad Liesegang rings were encountered in the urine of a 43-year-old patient who was diagnosed as having idiopathic hematuria, emanating from the left ureter or kidney. Erythrocytes and the Liesegang rings spontaneously disappeared from the urine within 4 weeks. We are unaware of a report of a similar observation. Lack of descriptions may be due to underreporting or reflect true rarity of Liesegang rings in the urine. It is suggested that Liesegang rings may precipitate in the hemorrhagic urine as they do in diverse blood-imbibed tissues.

An impeded blood flow through the femoral head is incriminated in the etiopathogenesis of osteonecrosis of the femoral head. The disorder is either primary (idiopathic avascular osteonecrosis) or secondary to one condition or another, say, corticosteroid medication, fracture of the neck, coagulation defects, physical or thermal damage, storage disorders, alcoholism, and infectious, autoimmune as also marrow infiltrating diseases. In the wake of the necrosis, several mediators are released in increased amounts, prime among which is the vascular endothelial growth factor. The intermediates recruit endothelial progenitor cells, macrophages, osteoclasts, fibroblasts, and osteoblasts, which, pervading throughout the necrotic areas, initiate the reparative processes. The dead, soft and hard tissular debris is substituted by fibrous - later on by hematopoietic-fatty tissue - and bone. The newly formed, appositional and intramembranous bone is deficient in its mechanical properties. The ordinary load-carrying functions suffice to deform these weakened femoral heads so that osteoarthritic changes develop. Considering contemporary assumptions of the causes of osteonecrosis, oxygenation, revascularization, and core decompression are the realistic therapeutic interventions. Necrosis of rats' femoral heads is studied as a model of osteonecrosis in both adults and children. In view of rodents' lifelong persisting physeal cartilage, vascular deprivation-induced osteonecrosis in rats mimics children's Perthes disease. The experimental model, which is well suited to test treatment modalities, has been used to investigate the effects of exposure to hyperbaric oxygen with and without non-weight bearing, medication of enoxaparin, and creation of an intraosseous conduit on the remodeling of the avascular necrotic femoral head. Intriguingly, the shape of treated rats' femoral heads is disfigured to a greater degree than that of untreated animals. This is most likely due to the reduced yield strength and elastic modulus as well as the raised strain-to-failure of the recently formed bone making up the post-necrotic femoral heads. It follows that expedited osteogenesis is, counter intuition, detrimental to maintaining the hemispherical shape of the femoral head, and thus to an articulation with congruent load-bearing surfaces. If this is indeed the case, the remodeling of the necrotic femoral head should be delayed, rather than sped up, as the present day paradigm would have it. Bearing in mind that the dead osseous structures keep their mechanical attributes for quite a while, a slowed down new bone formation would favor the gradual replacement of the necrotic by living bone. Therefore, management of the adult patients with osteonecrosis and children with Perthes disease should focus on a slowly progressive substitution so that the decline of the bone's mechanical properties is kept to a minimum. One viable therapeutic mode is a medication of inhibitors of the vascular endothelial growth factor.

In this study, we investigated the sensitivity, specificity, and predictive values of morphometric parameters of thyroideal follicular neoplasms based on concepts of fractal geometry. Thirty-seven follicular adenomas and 36 well-differentiated follicular carcinomas were assessed morphometrically. The nuclear area, nuclear area fraction, nuclear regularity factor, nuclear elongation factor, and slope setting (representing the ratio between the nuclear perimeter and nuclear regularity factor) were subjected to fractal dimensions analysis. By univariate analysis, the nuclear area, nuclear area fraction, nuclear regularity factor and slope values discriminate between adenomas and carcinomas. By multivariate analysis, the nuclear area, nuclear area fraction and slope values possess significant discriminatory powers in distinguishing between adenomas and carcinomas. Incorporating the nuclear area, nuclear area fraction, and slope values leads to a discriminatory power with 92% specificity and 83% sensitivity. The reciprocal relationships between the nuclear area, nuclear perimeter, and nuclear regularity factor of the cells of thyroideal adenomas and carcinomas may be expressed by fractal dimensions. Analysis limited to one parameter provides incomplete data. Expressing variations of the nuclear perimeter as a function of the nuclear regularity factor, the slope values constitute an independent attribute that significantly differentiates thyroideal adenomas from carcinomas.

The femoral heads of 15 rats were studied histologically 3 months after the induction of ischaemic necrosis by incising the cervical periosteum and cutting the ligamentum teres. The epiphyses consisted of immature disorganized subchondral and trabecular bone. The inter-trabecular spaces contained fibrous or haematopoietic tissue. Residual necrotic bone was rare. There was marked osteoblastic and osteoclastic activity. The articular aspect of the heads showed a spectrum of changes, ranging from cartilaginous degeneration with fibrillation and loss of glycosaminoglycans to an eburnated and polished bony surface. In seven rats, transphyseal bridges connected the epiphyseal and metaphyseal bony trabeculae to each other. It is suggested that the postnecrotic reparative processes, including the resorption of the necrotic debris and its replacement by newly formed, weak bone, led to an osteoarthritis-like disorder. This healing pattern of the necrotic femoral head was reminiscent of the progressive remodelling that occurs in rings in femoral capital osteonecrosis of adult human patients and in Perthes's disease of children.

Animal models of osteonecrosis of the femoral head are indispensable to the understanding of successful treatment modalities for avascular necrosis of the femoral head in adults and in children with Legg-Calvé-Perthes disease. Many of these models adequately reflect the current "vascular deprivation" theory regarding the etiology of the disease. In addition to spontaneous occurrence, surgical- and corticosteroid-induced models are suitable, common experimental ones. Osteonecrosis of spontaneously hypertensive rats appears to be due to defective bone formation and compression of the arteries entering the femoral head at its lateral facets by daily weight-bearing loads. Successful modeling of surgical-induced femoral capital necrosis can be a challenge in animals with a dual epiphyseal blood supply. High doses of corticosteroids are a pivotal risk factor in the development of osteonecrosis. The pathogenesis of corticosteroid-induced osteonecrosis likely resides in reduced blood flow. Steroids may reduce blood flow by numerous mechanisms, including marrow adipocytic hypertrophy leading to sinusoidal compression, venous stasis and, eventually, obstruction of the arteries, and arterial occlusion by fat emboli and lipid-loaded fibrin-platelet thrombi. Other, less common varieties of osteonecrosis include those secondary to endotoxin-induced disseminated intravascular coagulation, immune reactions, immoderately low or high temperatures, and high-impact-related injuries. Common to these diverse forms of osteonecrosis are fibrin thrombi clogging arterioles and small arteries.

The blood supply of one femoral head of 6-month-old rats was severed by incising the periosteum of the neck and cutting the ligamentum teres. The rats were killed on the 30th postoperative day and the femoral bones were obtained for semiquantification of the reparative processes in the necrotic heads. Fourteen rats were treated with enoxaparin and 14 untreated animals served as controls. Statistically, the amounts of necrotic bone in the epiphysis were less, the extent of remodeling of the femoral heads was milder, and the articular cartilage degeneration was slighter in the enoxaparin-treated than untreated rats. There was no significant difference in the quantities of newly formed bone in femoral heads of treated and untreated rats. These findings are in agreement with the known effects of unfractionated and low-molecular-weight heparins which enhance osteoclastic bone resorption and angiogenesis and decrease osteoblastic bone formation. The former activities, operative in minimizing the structural distortion of the femoral head, oppose the crucial event in the pathogenesis of post-osteonecrotic osteoarthritis.

Response of breast carcinomas to tamoxifen treatment depends, among others, on the estrogen receptor status. The estrogen receptor content was semiquantitatively determined in immunostained sections of stage 1 and 2 cancers of patients who had undergone tumor excision, tamoxifen treatment, adjuvant chemotherapy and radiotherapy. Weighted scores of the estrogen receptor content of the tumors were established by calculating the arithmetic means of the intensity of stained nuclei and the number of positively stained nuclei. Statistically, a cut-off value of > or = 2.1 signified a good prognosis; all patients whose tumors disclosed a weighted score of > or = 2.1 were alive and free of disease at the 10-year postoperative follow-up examination. On the other hand, one third of the patients whose carcinomas had a weighted score of < 2.1 presented with locally recurrent cancer, distant metastases, or both during the follow-up observation period. The statistically significant association between the patients' 10-year event-free survival and carcinomas with a weighted score of > or = 2.1 may serve oncologists in their decision making with respect to hormonal treatment.

Osteonecrosis of rat femoral heads was induced by stripping the periosteum of the neck and cutting the ligamentum teres. The epiphyseal marrow and bone were necrotic on the 5th postoperative day. Specimens obtained 18 and 36 days postoperatively showed fibrous and hematopoietic-fatty tissue in the intertrabecular spaces, osteoclastic bone resorption, osteogenesis, and degeneration of the joint cartilage. Morphometrically, the means of the height-to-length ratios of the control, 6-day, 18-day, and 36-day femoral heads were 0.26, 0.28, 0.48, and 0.29, respectively. The shape factor of the femoral heads of the control rats was higher than 0.81 in 80% of the cases, while those of rats killed on the 6th, 18th, and 36th postoperative day were higher than 0.81 in 65, 60, and 50% of cases, respectively. Statistically, the means of the height-to-length ratios and the values of the shape factors of the femoral heads of the rats killed 18 days postoperatively differed significantly from those of the other three groups of rats. The quantitatively gauged data of the remodeled epiphyses negate the authors' subjective impression concerning early flattening of the femoral heads after surgically produced osteonecrosis., (Copyright 2001 Elsevier Science.)

A 52-year-old patient underwent excision of a parotid lump which was fond to consist of a Warthin's tumor coexistent with a lymph node involved in dermatopathic lymphadenopathy. A preoperative fine-needle aspiration specimen contained brown pigment-granule-laden macrophages within the background of many lymphocytes. Failure to correctly diagnose the parotid tumor was likely due to a sampling error., (Copyright 2001 S. Karger AG, Basel)

Gastrointestinal autonomic nerve (GAN) tumours form a distinct subcategory of gastrointestinal stromal tumours, and are thought to originate from the enteric autonomic plexus. To date, a total of 45 cases have been documented in the literature; a few of these cases were associated with neurofibromatosis type 1 (NF-1). Bowel perforation due to other gastrointestinal stromal tumours has been reported only twice, but never in association with a GAN tumour. We describe a 40-year-old woman with NF-1 who had bowel perforation due to a GAN tumour. The patient underwent radical surgical resection and remained tumour free for at least 4 years, which may indicate a good prognosis.

An elderly patient with paraneoplastic cutaneous leukocytoclastic vasculitis (CLV) leading to the discovery of an as-yet asymptomatic, potentially surgically curable squamous cell carcinoma of the lung is presented. This type of vasculitis has not been previously described in association with this type of lung cancer. Since vasculitic paraneoplastic syndromes, including CLV, may develop before the clinical presentation of malignant tumors, the present case and others previously reported strongly suggest that in apparently idiopathic CLV, patients should be evaluated for the presence of occult malignancy that could be curable by early detection.

We examined the role of hyperbaric oxygenation (HBO2) combined with non-weight bearing (NWB) in the treatment of vascular deprivation-induced osteonecrosis of the femoral head in the rat. Group 1 included 16 rats treated by a combination of NWB and HBO2. Twenty animals treated by NWB alone (group 2), and 18 rats which received no treatment (group 3), served as the control groups. Maximal benefit of HBO2 was observed on Day 30 of the study. The femoral heads were less deformed in group 1 animals (P = 0.07). Preservation of the femoral heads was observed in a larger proportion of the HBO2-treated animals (P = 0.06). A smaller proportion of high-grade new bone formation was observed, and more animals demonstrated well-regenerated hematopoietic tissue (P = 0.08). The tendency for less deformation of the femoral head in the HBO2-treated group might be a predictor of better function of the hipjoint.

In view of the lifelong persistence of the physis, the femoral head of rats may serve to model Perthes disease and slipped capital femoral epiphysis. To produce osteonecrosis, the blood supply of one femoral head of 133, 6-month-old animals was severed by circumferentially incising the periosteum of the neck and cutting the ligamentum teres. The rats were killed 7 days to 90 days postoperatively. Associated with resorption of the necrotic bone and marrow, remodeling of the epiphysis was characterized by an ingrowth of vascularized fibrous tissue, formation of new bone and some cartilage, architectural deformation and flattening of the head. In 22 of 83 rats killed 30 days or more postoperatively, gaps in the continuity of the physeal cartilage were occupied by osseous bridges, connecting newly formed epiphyseal bony trabeculae with either the preexisting or newly formed metaphyseal osseous trabeculae. This healing mode may follow ischemic death of physeal chondrocytes or be owing to another mechanism, e.g., release of mediatory substances of inflammation. These findings raise the possibility that fixation of the healing epiphysis of a child's previously necrotic femoral head to the metaphysis occurs by transphyseal osseous growth in cases in which the physis is involved in the necrotic process.

Neuropilin-2 (np-2) is a receptor for semaphorin-3F (sema-3F) and semaphorin-3C (sema-3C). These semaphorins repel tips of growing axons that express np-2. In addition, np-2 functions as a receptor for heparin binding forms of the angiogenic factor vascular endothelial growth factor (VEGF) such as VEGF145 and VEGF165. We report that np-2 is strongly expressed in neuroendocrine cells located all along the human digestive tract. Confocal fluorescent microscopy revealed that np-2 is concentrated in vesicle-like structures located near the nucleus at the basolateral side of these cells. In the colon, the np-2-expressing subpopulation of neuroendocrine cell is almost identical with the serotonin-producing subpopulation of neuroendocrine cells. Gastrointestinal carcinoid tumors are digestive tract tumors that develop from neuroendocrine cells. Interestingly, most of the carcinoid tumors derived from the colon and the appendix did not contain np-2-producing cells. However, some carcinoid tumors derived from the small intestine and stomach did express low levels of np-2 in isolated foci of cells. By contrast, strong serotonin and chromogranin-A expression was observed in all of the carcinoid tumors that were examined. These results suggest that loss of np-2 expression may accompany tumor progression in carcinoid tumors., (Copyright 2001 Academic Press.)

The patellae of 6 male and 2 female, 40 to 70 year-old individuals, who were healthy at the time of their violent death, were assessed by computer-assisted image analysis. The means of the bone density (percentage of bone in the respective field of interest) ranged from approximately 20% to approximately 30% in the central spongiotic zones, from approximately 40% to approximately 80% in the superior and inferior peripheral zones, and approximately 40% to approximately 60% in the subchondral zone. Bone densities were greatest in the lateral parts of the subchondral and spongiotic territories. The bony trabeculae were haphazardly distributed in the central spongiotic zones. They were commonly oriented vertically or parallel to the surface of the patella in the peripheral and subchondral zones. In conclusion, the histomorphometric data presented validate the rationale of reaming the articular aspect of the patella into a dome-shaped configuration with preservation of a circumferential bony bulwark in the preparation for the implantation of a thick polyethylene-based component with a concave undersurface.

Purpose: The aim of this work was to detect nuclear parameters related to the prognosis of patients with stage III, IV or DS neuroblastomas., Methods: Histological sections of 25 operation specimens obtained from children with advanced-stage neuroblastomas were subjected to computer-assisted image analysis. Statistical relationships between nuclear descriptors of the tumor cells and patients' clinical outcome were determined., Results: The coefficient of variability of the mean nuclear area the mean nuclear elongation factor, and the mean nuclear averaged Feret diameter of the neuroblastoma cells were ascertained to be discriminators separating high-grade from low-grade tumors., Conclusions: The histomorphometrically gauged nuclear parameters may help oncologists to assess the prognosis of patients with advanced-stage neuroblastoma.

Analysis of retrieved woven carbon filamentous pads, used for resurfacing of the patellar joint surface, disclosed a 4-zonal organizational pattern. Zone 1, facing the articular cavity, was devoid of carbon filaments and consisted of fibrous tissue. Foreign body granulation tissue and fibrous tissue occupied about one-third and approximately 50%-60% of the interfilamentous space in zones 2 and 3, respectively. Carbon filaments formed 2%-9% of zone 2 and 14%-16% of zone 3. An interfacial membrane-like zone 4 separated the carbon filamentous pads from a trabecular bony shell. The bone volume within the latter was approximately 25%. Given that the purpose of articular resurfacing with implants is repopulation of the defect by chondrocytes producing a cartilaginous matrix, the woven carbon filamentous pads did not fulfill this expectation. In an environment of an ongoing foreign body-induced granulomatous reaction, the stem cells permeating the interstices of the woven carbon filamentous pad are apparently incapable of maturing into highly differentiated cells (chondrocytes) synthesizing a highly complex (cartilaginous) matrix.