[Total ankle arthroplasty with simultaneous subtalar fusion]. / Endoprothese des oberen Sprunggelenks mit simultaner Subtalararthrodese.

OBJECTIVE: Pain free weight bearing ability with orthograde hindfoot position and preserved tibiotalar motion. INDICATIONS: Symptomatic arthritis of the ankle and subtalar joint, additional subtalar hindfoot malalignment. CONTRAINDICATIONS: Absolute: acute infection, noncorrectable ligamentous instability or bony defects, restricted perfusion, diabetic foot syndrome. Relative: inability to comply with postoperative partial weight bearing, only moderate symptoms of subtalar arthritis, smoking, intricate soft tissue situation. SURGICAL TECHNIQUE: Lateral approach to the subtalar joint. Removal of residual cartilage. The joint surfaces are deeply feathered while preserving anatomic congruency. Now tibia and talus are prepared for implantation of a total ankle arthroplasty via an anterior approach. With trial implants in the ankle joint, hindfoot position is evaluated and, if necessary, corrected. Definite fixation of the subtalar joint with 5-10° valgus by one or more compression screws. Final check of ligamentous balance of the ankle and implantation of the definite components. POSTOPERATIVE MANAGEMENT: Immobilization in a cast for 1 week, then removable walker boot for another 5 weeks with partial weight bearing (15 kg) and mobilization in the sagittal plane under physiotherapeutic instruction. With radiologic proof of consolidation weight bearing can be allowed after 6 weeks, with cortical iliac crest bone graft after 8 weeks. RESULTS: From 1998-2016, 41 total ankle replacements with simultaneous isolated subtalar fusion were performed. The consolidation rate was 92.6%. The mean AOFAS Ankle-Hindfoot Score rose from 51.6 preoperatively to 79.7 one year postoperatively. The mean total range of motion (ROM) was 32.3° (range 14-50°) one year after surgery.

A functional outcome study comparing total ankle arthroplasty (TAA) subjects with pain to subjects with absent level of pain by means of videofluoroscopy.

BACKGROUND: Total ankle arthroplasty (TAA) subjects often suffer pain on the anteromedial side of their ankle joint. Whether this prevalent pain is caused by a changed motion pattern of the TAA is unclear. Therefore, this study assessed the kinematic differences in the motion of the TAA components during gait, comparing TAA subjects with elevated versus absent levels of pain. METHODS: Eleven TAA subjects (5 with pain vs. 6 without pain), all with unilateral Mobility™ TAA and at least two years post-operation, were recruited and stratified based on standard clinical assessed patient data. The 3D motion of the TAA was assessed by means of videofluoroscopy during level, uphill and downhill walking. RESULTS: The hypothesis that the pain group shows a different kinematic motion pattern than the no pain group could not be confirmed. CONCLUSIONS: The same kinematic motion pattern causes pain in some patients, but not in others. Further investigation concerning ligament stresses is needed.

[Total ankle replacement in rheumatoid arthritis]. / Sprunggelenkprothese bei chronischer Polyarthritis.

Rheumatoid arthritis is a systemic disease directly involving multiple joints and indirectly damages bone due to specific medicinal therapy. When deciding on the optimal surgical treatment of inflammatory ankle arthritis (fusion versus arthroplasty), specific factors have to be considered. This review discusses the advantages and disadvantages of total ankle arthroplasty for patients with rheumatoid arthritis and highlights important surgical aspects related to this disease.

Loss of the Parkinson's disease-linked gene DJ-1 perturbs mitochondrial dynamics.

Growing evidence highlights a role for mitochondrial dysfunction and oxidative stress as underlying contributors to Parkinson's disease (PD) pathogenesis. DJ-1 (PARK7) is a recently identified recessive familial PD gene. Its loss leads to increased susceptibility of neurons to oxidative stress and death. However, its mechanism of action is not fully understood. Presently, we report that DJ-1 deficiency in cell lines, cultured neurons, mouse brain and lymphoblast cells derived from DJ-1 patients display aberrant mitochondrial morphology. We also show that these DJ-1-dependent mitochondrial defects contribute to oxidative stress-induced sensitivity to cell death since reversal of this fragmented mitochondrial phenotype abrogates neuronal cell death. Reactive oxygen species (ROS) appear to play a critical role in the observed defects, as ROS scavengers rescue the phenotype and mitochondria isolated from DJ-1 deficient animals produce more ROS compared with control. Importantly, the aberrant mitochondrial phenotype can be rescued by the expression of Pink1 and Parkin, two PD-linked genes involved in regulating mitochondrial dynamics and quality control. Finally, we show that DJ-1 deficiency leads to altered autophagy in murine and human cells. Our findings define a mechanism by which the DJ-1-dependent mitochondrial defects contribute to the increased sensitivity to oxidative stress-induced cell death that has been previously reported.

Promyelocytic leukaemia-immunoreactive neuronal intranuclear rodlets in the human brain.

In a previous study, we demonstrated immunoreactivity of a subset of neuronal intranuclear rodlets (INRs) in the human substantia nigra for promyelocytic leukaemia (PML) protein, the signature protein of PML bodies. In the present study, we extend these observations and describe the ultrastructural features, immunohistochemical staining characteristics, and topographical pattern of distribution of PML-immunoreactive intranuclear rodlets (PML-INRs). Consistent with a purported role for PML bodies in nuclear proteolysis and/or transcriptional regulation, PML-INRs are immunoreactive for components of the ubiquitin-proteasome system, the transcriptional regulator CREB-binding protein, acetylated histone H4, and the eukaryotic translation initiation factor eIF4E. Immunoelectron microscopy reveals that they all possess a filamentous core and, in some, this is surrounded by a granular shell. We further demonstrate that a proportion of INRs in extranigral sites also show partial immunoreactivity for PML. These observations indicate an intimate association between two neuronal nuclear bodies, PML bodies and INRs. Because both of these structures have been implicated in neurodegenerative disease, PML-INRs may provide a tool with which to study changes in nuclear substructure in disease.

Light and electron microscopy of the pagetoid spread of germ cell carcinoma in the rete testis: morphologic evidence suggestive of field effect as a mechanism of tumor spread.

The purpose of this study is to investigate the mechanism of tumor spread in the pagetoid spread of germ cell tumors in the rete testis (PSRT). Twenty consecutive cases of germ cell tumor of the testis (9 seminomas, 3 embryonal carcinomas, and 8 teratocarcinomas) were retrieved to identify the cases with PSRT. The areas of pagetoid spread were examined by the serial sectioning of the entire thickness of the tissue block. Available fresh tissue was submitted for electron microscopic study. Ten cases were associated with PSRT and had focal or extensive areas of intratubular germ cell neoplasia (IGCN) in the proximity of the tumor and the rete testis (RT). In the remaining 10 cases, 6 were associated with IGCN distant from the RT and the last 4 were not associated with IGCN. Seminiferous tubules with IGCN were seen connecting with the RT with pagetoid spread. Isolated single intraepithelial tumor cells also were identified at the periphery of the areas with PSRT. Electron microscopic study of the RT of 4 cases with PSRT (2 seminomas, 1 embryonal carcinoma, and 1 teratocarcinoma) revealed desmosome-type junctions between tumor cells with RT epithelial cells. Direct tumor expansion and cell motility as mechanisms of tumor spread in PSRT does not explain the presence of isolated cells and desmosome-type junctions of the tumor cells as demonstrated in this study. The authors believe that the field effect plays an important part in the pathogenesis of this pagetoid spread in the RT. It is likely that this field effect is induced by the germ cell tumor and is operated through the immature germ cells or undifferentiated epithelial cells in the RT adjacent to the tumor cells.

Angiogenic histogenesis of stromal cells in hemangioblastoma: ultrastructural and immunohistochemical study.

Controversy regarding the origin of characteristic stromal cells (SC) is responsible for the placement of hemangioblastoma as a single entity in the category of "tumors of uncertain histogenesis" in the current WHO classification of brain tumors. This subclassification of hemangioblastoma is, to a large extent, a consequence of a remarkable antigenic heterogeneity of SC demonstrated in many, often contradictory immunohistochemical studies. In contrast, most of the electron microscopic studies demonstrated a number of features indicating angiogenic nature of SC and, therefore, hemangioblastoma. This study reevaluated the histogenesis of SC, applying immunohistochemistry as well as electron microscopy and immunoelectron microscopy. Immunohistochemical studies confirmed most of the previous results indicating a very frequent expression of vimentin, S-100 protein, neuron-specific enolase, and cytokeratins. SC were less commonly immunoreactive for desmin, factor XIIIa, and Ricinus communis lectin receptors, and only occasionally for factor VIII and Ulex europeus lectin. They were negative for other markers of endothelial, neuronal, glial, neuroendocrine, and smooth muscle differentiation. Approximately 1% of SC showed Ki67 immunoreactivity, indicating their slight proliferative activity, consistent with the benign nature of the tumor. In contrast to the inconclusive results of the immunohistochemistry, electron microscopy demonstrated a clear relationship of SC to endothelial cells, smooth muscle cells, and pericytes. Occasional SC were found within the vascular lumina. SC often showed intracellular caveolae consistent with the formation of early capillary lumina. Moreover, occasional SC contained small Weibel-Palade bodies positive for factor VIII in immunoelectron microscopy. SC represent a heterogeneous population of abnormally differentiating mesenchymal cells of angiogenic lineage, with some morphological features of endothelium, pericytes, and smooth muscle cells. Occurrence of SC in hemangioblastoma could be related to a limited ability of angioformative stromal cells to develop an architecture of capillary lumina integrated with the vascular network of the tumor. Hemangioblastoma should be reclassified and included together with other vascular tumors of the central nervous system.

Myopathy with hexagonally cross-linked tubular arrays: a new autosomal dominant or sporadic congenital myopathy.

We describe a slowly progressive myopathy with unique crystalloid inclusions in type 2 muscle fibers in a father and his son, as well as one more unrelated individual. The inclusions were strongly eosinophilic and purple by the Gomori method. They were composed of vesicular profiles, approximately 20 nm in cross-diameter, connected by radially arranged double spokes arising at 60 degrees angles. The inclusions were not related to any normal cellular organelle. Extensive immunohistochemical studies failed to reveal their chemical nature. It is suggested that this is a new congenital myopathy with characteristic intracytoplasmic inclusions, occurring sporadically or with an autosomal dominant pattern of inheritance.

Evaluation of apoptosis in four human tumour cell lines with differing sensitivities to cisplatin.

Four human tumour cell lines were evaluated for their ability to undergo apoptosis when subjected to cisplatin or hyperthermia treatment. In an ovarian carcinoma line (A2780s) and its derivative cisplatin resistant line (A2780cp) the variation in response was expressed for both the colony survival endpoint and the apoptosis endpoint. Apoptosis was measured by the number of floating cells, DNA agarose gels, and electron microscopy. In fact, cisplatin resistance was expressed to a higher level for apoptosis, than colony survival in the A2780cp cell line compared to the A2780s line. The melanoma cell line (Sk Mel-3) also showed induced apoptosis by cisplatin treatment while the glioma line (U87MG) showed little to no apoptosis in response to cisplatin treatment. Hyperthermia (43 degrees C for 1 hour) induced apoptosis in the human melanoma cell line but not in the glioma cell line. These data indicate that, while both cisplatin and hyperthermia can induce apoptosis in human tumour cell lines, the degree of induction is highly cell line dependent.

Induction of apoptosis in equine chorionic gonadotropin (eCG)-primed rat ovaries by anti-eCG antibody.

We have established a model to examine the early events of apoptosis in small antral follicles in vivo. Immature female rats injected with 15 IU eCG, and subsequently (24 h later) with an anti-eCG antibody to induce gonadotropin withdrawal, displayed a significantly lower ovarian weight and increased incidence of follicular atresia and granulosa cell death, especially in small- to medium-sized follicles. Evidence of apoptosis was apparent in a significantly higher proportion of granulosa cells from antibody-treated rats, which exhibited membrane blebbing, nuclear and cytoplasmic condensation, fragmentation, and phagocytosis. In addition, there was a loss of the regular organization of the lamina densa in the follicular basement membrane. Degradation of DNA was consistently found by 24 h in the antibody-treated group, and ladders could be observed as early as 1 h after treatment. Although cell death was observed after antibody treatment in some larger antral follicles, the occurrence of apoptosis was less frequent. These results demonstrate that gonadotropin withdrawal in vivo rapidly induces apoptosis in small- to medium-sized antral follicles at the critical stage of development when atresia is commonly observed, suggesting that this model is ideal for studying apoptosis in the ovary.

Compression arthrodesis of the rheumatoid ankle and hindfoot.

The reported frequency of involvement of the rheumatoid ankle and hindfoot varies between 9% and 70%. Fusion of the ankle joint, the subtalar, talonavicular, or calcaneocuboidal joint (Chopart's joint) or all of them is the preferred method of treatment for severe rheumatoid involvement causing pain, instability, and/or severe deformity. Ankle arthroplasty is indicated rarely. Pantalar arthrodesis is performed more frequently than talonavicular fusion or ankle fusion. Reported rates of fusion after compression arthrodesis of the ankle joint vary from 65% to 90%, averaging 80% to 85%. Higher success rates of as high as 95% were obtained with internal lag screw fixation as proposed by Wagner. The result of various combinations of arthrodesis (n = 54) of the ankle joint, the subtalar joint, and Chopart's joint in 43 patients with rheumatoid arthritis operated on in a 10-year period from 1984 through 1993 are presented. In all cases internal fixation by lag screws according to Wagner was used with a modified lateral approach incorporating osteotomy of the distal fibula. The technique is described in detail. Solid fusion was obtained in 21% of the cases after 8 weeks, in 9% of the cases after 12 weeks, and in 92% of the cases after 16 weeks. In 8% (3 patients) revision because of delayed union or nonunion eventually led to bony fusion. Postoperative pain, walking capacity, gait, and the subjective outcome were assessed. Complications occurred in 16%, revision was performed in 11.6% of the cases; in all cases healing was obtained. Overall patient satisfaction was 93%.

Differentiating neuroblastoma of pituitary gland: neuroblastic transformation of epithelial adenoma cells. Case report.

The authors report the case of a 40-year-old woman with a 12-year history of irregular menses, amenorrhea, infertility, galactorrhea, a slightly elevated prolactin level, and a slowly growing pituitary adenoma. She developed recent onset of visual symptoms, prompting craniotomy for removal of an intrasellar tumor. Following surgery, her vision and prolactin levels returned to normal. Light microscopic and immunohistochemical examination of the tumor revealed it to be a neuroblastoma, which was immunohistochemically positive for synaptophysin, S-100 protein, and oxytocin. The neoplasm contained prolactin-positive neuroblastic and pituitary epithelial cells. No other pituitary hormones were found. Electron microscopy demonstrated two cell types: one with frequent neuritic processes containing neurosecretory granules and showing synaptic specialization, and another one compatible with epithelial adenohypophyseal cells. A few cells had ultrastructural features that were transitional between neuronal cells and granulated epithelial cells. Agranular folliculostellate cells were also identified. Immunoelectron microscopy demonstrated prolactin granules in the cytoplasm of the epithelial cells, in a few transitional cells, and in scattered neuritic processes. Ultrastructural and immunohistochemical features of the tumor suggested a transformation of pituitary epithelium to neuroblastic cells. Hyperprolactinemia and associated clinical symptoms may in part be attributed to selective prolactin secretion by neoplastic cells that were differentiating into adenomatous pituitary cells and, to a lesser extent, to cells differentiating into a neuroblastic line. Compression of pituitary stalk might also have been a contributory factor to the increased prolactin levels. Moreover, the oxytocin produced by the neuroblastic cells was considered an additional stimulus for prolactin secretion by neoplastic cells or by the normal pituitary.

Giant desmosomes in tumors.

The lengths of desmosomal profiles were measured in sections of tumor tissue from cases of mesothelioma, adenocarcinoma, squamous cell carcinoma, thymoma, and meningioma. Giant desmosomes (length of profile 1 micron or greater than 1 micron) were found in all the above-mentioned tumors except adenocarcinomas. The largest desmosomal profile in adenocarcinoma was approximately 0.8 micron long; the largest in mesothelioma was approximately 2 microns long. Our observations suggest that one of the ways in which giant desmosomes arise is by growth and fusion of adjacent desmosomes. Giant desmosomes may at times help in distinguishing mesothelioma from adenocarcinoma, but this is a rather rare phenomenon. In this study giant desmosomes were found in only 2 out of 10 cases of mesothelioma.

Primary intracranial pleomorphic angioleiomyoma--a new morphologic variant. An immunohistochemical and electron microscopic study.

BACKGROUND: Angioleiomyomas usually are benign subcutaneous neoplasms that occur most often in extremities of middle-aged individuals. Very few cases have been described in other locations; none along the neuroaxis. An intracranial example of angioleiomyoma displaying unusual morphologic features not seen in the typical peripheral variants of this tumor is described. METHODS: The tumor was studied with conventional histology, immunohistochemistry with morphometric calculation of proliferation index, immunoelectron microscopy, and DNA flow cytometry. RESULTS: The tumor was composed of large epithelioid and pleomorphic cells filled with intermediate filaments positive for desmin and vimentin. Scattered cells also expressed myosin and muscle-specific actin. Smooth muscle cell differentiation was confirmed by ultrastructural demonstration of subplasmalemmal dense bodies, attachment plaques, and discontinuous basal lamina. The proliferation index with proliferating cell nuclear antigen (PCNA) monoclonal antibody was 75.78%, whereas it was only 4.22% with Ki67 monoclonal antibodies adopted to paraffin material (MIB-1). CONCLUSION: The tumor represents a unique morphologic variant of a pleomorphic angioleiomyoma. Cellular pleomorphism and a strong reaction for PCNA in numerous cells suggested that the lesion was malignant. However, the absence of mitotic figures, a small number of Ki-67-positive cells, a diploic DNA pattern, and a low proliferation index in flow cytometry all supported the concept that this neoplasm represented an unusual histologic variant of benign angiogenic leiomyoma. Encapsulation and demarcation of the surgical specimen and the survival of the patient for more than 4 years without recurrence after resection support this interpretation.

Unusual immunostaining pattern of chromogranin in normal urothelium and in transitional cell neoplasms.

We report an unusual pattern of immunostaining for chromogranin A in 24 transitional cell carcinomas (TCC). Positive immunostaining was seen with chromogranin A antisera in 10 of 16 urinary bladder TCC, neither of 2 prostatic TCC, 3 of 3 ureteral TCC and 2 of 3 metastatic TCC. This staining was demonstrated within the cytoplasm of transitional cells at all levels of the neoplastic epithelium, including cells near the basement membrane and at the free surface (umbrella cells). In 5 of 7 cases there was also immunoreactivity of the non-neoplastic urothelium. Immunostaining with neuron-specific enolase and synaptophysin was negative in all of these cases and no neuro-secretory granules were identified in 7 cases examined by electron microscopy. This pattern of immunostaining is probably due to reactivity with chromogranins or certain chromogranin-like proteins in the transitional cells, particularly in the umbrella cells.

Intracisternal collagen fibrils in proliferative fasciitis and myositis of childhood.

During ultrastructural examination of a difficult to diagnose tumor, short spacing collagen fibrils (periodicity of banding, approximately 43.2 nm) and native collagen fibrils (periodicity of banding, approximately 53 nm) were found in dilated and vacuolated cisternae of rough endoplasmic reticulum and the perinuclear cistern. Original diagnoses from several histopathologists included alveolar soft part sarcoma, malignant fibrous histiocytoma, atypical fibroxanthoma, and myogenic tumor. The finding of intracisternal collagen (which is but a variety of intracellular collagen) led to the conclusion that this was a fibroblastic neoplasm. This, plus a review of the histologic findings, led to the diagnosis of proliferative fasciitis and myositis of childhood.

Reliability of criteria for ultrastructural identification of neuroendocrine granules.

For full diagnostic use to be made of the neurosecretory granule, the range of sizes, forms, and staining qualities for this cytoplasmic organelle, along with the extent of its expression in various neoplasms, must be established. Neurosecretory type granules occasionally occur in nonneuroendocrine tumors. A series of carcinoids of the lung provides a model for assessing the morphologic types of cytoplasmic granules identified by antibodies to chromogranin A and immunogold labeling. The results show that granule structure in tumors is pleomorphic. Despite having sizes within the expected range, many labeled and, indeed, unlabeled secretory granules are atypical, particularly in structural form. Cell-to-cell variation in the proportion of even typical neurosecretory granules labeling for chromogranin A is the rule. Studies correlating biochemical, immunohistochemical, electron microscopic, and perhaps in situ hybridization characteristics are required to define better the criteria for unequivocal identification of neurosecretory granules in tumors.

Immunoelectron microscopic localization of monoclonal IgM antibodies in gammopathy associated with peripheral demyelinative neuropathy.

A sural nerve biopsy from a patient with benign monoclonal IgM kappa gammopathy and sensory-motor demyelinative neuropathy, revealed marked loss of myelinated fibers and focal axonal degeneration as well as widespread demyelination and remyelination with onion-skin formation. Almost all myelinated fibers displayed characteristic widening of the myelin lamellae as well as excessive thickness and/or exuberant outfoldings of myelin, reminiscent of that seen in tomaculous neuropathy. Many endoneurial capillaries were lined by fenestrated endothelium, indicating breakdown of a normal blood-nerve barrier. The endoneurium contained large amounts of extracellular proteinaceous material. Immunofluorescence and immunoelectron microscopy performed on the nerve of the patient, demonstrated selective deposition of IgM kappa gammaglobulin, exclusively in the areas of splittings of the myelin lamellae. Schwann cells contained cytoplasmic myelin debris labelled with IgM kappa only. In the indirect immunofluorescence and immunoelectron microscopy, serum of the patient reacted with the whole thickness of compact peripheral myelin of a normal human nerve. There was no immunoreactivity with the central myelin, Schwannoma cells, glial cells, axons or neurons. Demonstration of the selective presence of monoclonal IgM in widened lamellae of myelinated fibers, as well as bound to the internalized myelin debris in Schwann cells and macrophages, indicates a pathogenetic role of monoclonal paraprotein in myelin injury. Demyelination is promoted by development of endothelial fenestrations in the endoneurial capillaries and breakdown of the blood-nerve barrier.

Immunogold localization of actin and cytokeratin filaments in myoepithelium of human parotid salivary gland.

Myoepithelial cells of salivary gland are uniquely specialized cells; their function is unclear, but the considerable complement of muscle-specific actin suggests contractility is one function. By routine transmission electron microscopy myofilament visualization is variable. Some myoepithelial cells appear to have limited and only focal aggregates of myofilaments, while others seem to have readily appreciated myofilaments within a longitudinally oriented cytoplasmic zone at the basal portion of the cell. However, immunogold electron microscopy using the anti-muscle-specific actin antibody, HHF35, while indicating a basal distribution for the muscle-isoform of actin in a platelike fashion in certain myoepithelial cells, also reveals that others associated with both intercalated ducts and acini have a more generalized distribution of myofilaments throughout the cytoplasm. Actin was also noted within tonofilaments and double immunogold labeling using both the HHF35 and AE1/AE3 (anticytokeratins) antibodies confirmed the variable interrelationship of these two filaments. Within any one myoepithelial cell, actin and cytokeratins might colocalize in some areas of the cytoplasm containing filaments, but not in adjacent zones. These results suggest that intermediate filaments and myofilaments are complexly organized in myoepithelial cells, and that quantitative and qualitative differences exist in the expression and distribution of intermediate filaments and myofilaments. These cells are likely structurally, if not functionally, heterogeneous.

Diagnostic value of microvillus-matrix associations in tumors.

Until now microvillus-matrix associations have been reported to occur only in mesotheliomas and hence this phenomenon is thought to be of value in distinguishing mesothelioma from pulmonary adenocarcinoma. We report here the occurrence of microvillus-matrix associations in two pulmonary adenocarcinomas which reduces the value of this phenomenon in the differential diagnosis of these tumors.