Myxovirus-like structures in a case of human chronic polymyositis.

Intranuclear and intracytoplasmic aggregates of filaments with tubular structures and transverse striations occurred in muscle tissues biopsied from a patient with chronic polymyositis. The filamentous tubules bear a close resemblance to the incomplete form of myxovirus in which the envelope is missing. Three biopsies from the same patient, taken during a period of 1(1/2) years, all revealed these structures. This finding provides presumptive evidence that a chronic persistent viral infection may be involved in the pathogenesis of chronic polymyositis.

Externalised locking compression plate as an alternative to the unilateral external fixator: a biomechanical comparative study of axial and torsional stiffness.

OBJECTIVES: External fixators are the traditional fixation method of choice for contaminated open fractures. However, patient acceptance is low due to the high profile and therefore physical burden of the constructs. An externalised locking compression plate is a low profile alternative. However, the biomechanical differences have not been assessed. The objective of this study was to evaluate the axial and torsional stiffness of the externalised titanium locking compression plate (ET-LCP), the externalised stainless steel locking compression plate (ESS-LCP) and the unilateral external fixator (UEF). METHODS: A fracture gap model was created to simulate comminuted mid-shaft tibia fractures using synthetic composite bones. Fifteen constructs were stabilised with ET-LCP, ESS-LCP or UEF (five constructs each). The constructs were loaded under both axial and torsional directions to determine construct stiffness. RESULTS: The mean axial stiffness was very similar for UEF (528 N/mm) and ESS-LCP (525 N/mm), while it was slightly lower for ET-LCP (469 N/mm). One-way analysis of variance (ANOVA) testing in all three groups demonstrated no significant difference (F(2,12) = 2.057, p = 0.171).There was a significant difference in mean torsional stiffness between the UEF (0.512 Nm/degree), the ESS-LCP (0.686 Nm/degree) and the ET-LCP (0.639 Nm/degree), as determined by one-way ANOVA (F(2,12) = 6.204, p = 0.014). A Tukey post hoc test revealed that the torsional stiffness of the ESS-LCP was statistically higher than that of the UEF by 0.174 Nm/degree (p = 0.013). No catastrophic failures were observed. CONCLUSION: Using the LCP as an external fixator may provide a viable and attractive alternative to the traditional UEF as its lower profile makes it more acceptable to patients, while not compromising on axial and torsional stiffness.Cite this article: B. F. H. Ang, J. Y. Chen, A. K. S. Yew, S. K. Chua, S. M. Chou, S. L. Chia, J. S. B. Koh, T. S. Howe. Externalised locking compression plate as an alternative to the unilateral external fixator: a biomechanical comparative study of axial and torsional stiffness. Bone Joint Res 2017;6:216-223. DOI: 10.1302/2046-3758.64.2000470.

The influence of gripping techniques on the tensile properties of tendons.

Gripping is a major challenge faced in the tensile testing of tendons. As soft and aqueous materials, tendons are prone to slip and experience premature failure during mechanical testing. Several gripping methods were attempted and evaluated, including serrated jaw, sandpaper, frozen ends, and air-dried ends. It was found that 1 kN pneumatic grips (Shimadzu Company) lined with cardboard provided an adequate grip without perceptible slip and damage to the tendons. It was found that using the pneumatic grips with cardboard lining the stress concentration at the grip-specimen interface reduced substantially. An analysis of specimens that failed at the grip-specimen interface versus those that failed at mid-substance shows that there was no significant difference in their tensile properties.

Cannulated versus non-cannulated cancellous screw fixation for femoral neck fractures: a synthetic bone biomechanical study.

PURPOSE: To compare the compressive strength of cannulated versus non-cannulated cancellous screws for undisplaced femoral neck fractures in synthetic bones. METHODS: 18 synthetic proximal femurs simulating an AO B1 valgus impacted femoral neck fracture in osteoporotic bone were used. The fracture angles were between 55º and 63º (Pauwels grade 2). Fixation was made using 6.5-mm non-cannulated screws (n=6), 6.5-mm cannulated screws (n=6), or 7.3-mm cannulated screws (n=6). A custom-built jig was designed to guide the insertion of the screws in an identical triangular configuration. Screws were tightened by a single operator using a torque-measuring screwdriver. The femoral head was subjected to progressive axial loading at 5 mm/min. The load to failure and displacement were recorded. RESULTS: The 3 groups did not differ significantly except that the load to failure was higher in the construct with 6.5-mm non-cannulated screws than that with 6.5-mm cannulated screws (1222 N vs 1008 N, p=0.003). CONCLUSION: The compressive strength of a synthetic bone hip fracture model fixed with non-cannulated screws was higher than that of cannulated screws of the same diameter.

A new immunoperoxidase marker for microglia in paraffin section.

We tested antisera against monocytic and lymphocytic lineages on 27 formalin-fixed, paraffin-embedded brains, obtained at autopsy, using the avidin-biotin-complex immunoperoxidase method. Patients ranged from one day to 69 years with 12 cases under the age of two. LN-1-positive microglia were present in 22 brains. LN-1 did not stain any other glial or neuronal cells. Five negative brains included two irradiated gliomas, two cases of multiple sclerosis and one normal case. Immunostaining was confined to cells with bipolar processes and rod-shaped nuclei recapitulating the characteristic features of microglia in silver-impregnated sections. LN-1-positive microglia were most prominent in the grey matter and in the grey-white junction with fewer positive cells seen in the white matter. Double immunostaining with LN-1 and glial fibrillary acidic protein (GFAP) clearly distinguished LN-1-positive microglia and GFAP-positive astrocytes. The expression of LN-1, a B-lymphocyte antigen, by microglia contradicts the macrophage derivation theory and supports data indicating a functional role of microglia in immune processes. LN-1, while not specific for microglia, should be considered a useful marker, more reliable than silver impregnation, for detecting microglia in paraffin section.

Facial myokymia. Pathological features.

Pathologic examination in a case of facial myokymia showed edema and mild astroglial proliferation of the ipsilateral seventh nerve nucleus; gliomatous tumor involvement occurred rostral to this nucleus. These findings give circumstantial support to functional deafferentation as the cause of facial myokymia.

Anastomoses of transverse tubules with terminal cisternae in polymyositis.

Abnormal transverse or T tubules spatially continuous with sarcoplasmic reticulum (SR), as visualized with a lanthanum (La) tracer, were found in biopsy specimens from nine patients with polymyositis whose serum enzyme (creatine phosphokinase [CPK]) levels were elevated before the time of biopsy. On comparison with the T system in more than 50 control subjects without CPK elevation, it became apparent that presumed anastomoses of T tubules with SR were the most consistent anatomical correlates of the enzyme leakage. Two types of anastomoses were seen on the basis of passage of La: first, early segmental dilation of T tubules and perpendicular continuations with SR; and second, focal proliferation of T tubules forming "T tubule networks" and then anastomosing with SR at the periphery of the networks. The latter is considered to be a concurrent repair process for the injured triads. Lanthanum did not penetrate freely through the plasma membrane of necrotized muscle fibers. It is concluded that junctional sites between T tubules and SR may be the primary sites of leakage of sarcoplasmic enzymes in polymyositis.

Familial cerebral sarcomas.

Four cases of cerebral fibrosarcomas occurring in two families are reported. To our knowledge, no similar cases have been reported. Evidence that a heritable factor is involved in the genesis of some brain tumors is suggested by these cases.

Magnetic resonance imaging (1.5 tesla) in patients with intractable focal seizures.

Magnetic resonance (MR) (1.5 tesla) studies were performed in ten patients with temporal lobe epilepsy and two with temporofrontal epilepsy. Two patients with temporal lobe epilepsy and one with temporofrontal epilepsy exhibited areas of increased signal intensity on T2-weighted images in the mesiobasal portion of the temporal lobe shown by electroencephalography to be the epileptogenic focus; no analogous abnormalities had been found in these patients on computed tomographic scans. Pathologic studies have not revealed a specific ultrastructural correlate for the MR findings in this group of patients. We found MR to be a useful, noninvasive diagnostic adjunct in the presurgical assessment of some patients with temporal lobe epilepsy. Where abnormalities were found, they corresponded with the epileptogenic focus as defined by electroencephalography.

Effect of denervation on coxsackie A virus myositis in mice: an electronmicroscopic study.

Myositis induced by Coxsackie A4 and A9 viruses was investigated in the gastrocnemius muscles of suckling mice and adult mice with denervation. Denervation markedly increased the susceptibility of adult mice to Coxsackie A virus infection, and this effect was initiated as early as 1 day after denervation. Light microscopy demonstrated inflammation and necrosis in the denervated gastrocnemius muscle of adult mice, whereas muscle from the contralateral leg showed only infrequent, mild, focal myositis. Ultrastructually, crystalline arrays of virus particles were seen in the infected muscle fibers and in the phagocytes of both suckling and adult mice. Nuclear alterations, especially in the myotubes, and a characteristic compound membrane-vesicle complex (CMVC) in the sarcoplasm, developed simultaneously. Replicating and fusing myoblasts, activated as part of the regenerative process after denervation, appeared to be closely associated with the susceptibility of muscle to Coxsackie A virus infection.

Fusariosis, myasthenic syndrome, and aplastic anemia.

Fusarium, a fungus, produces a potent mycotoxin that, when ingested with contaminated cereal grains, produces a serious illness in man called alimentary toxic aleukia (USSR) and Akakabi-byo (Japan). The illness includes gastrointestinal symptoms and weakness and if ingestion of Fusarium contaminated grain persists, culminates in aplastic anemia. A 66-year-old woman had Eaton-Lambert syndrome and a clinical course similar to alimentary toxic aleukia. Several months before her death, pancytopenia, initially thought guanidine-induced, developed and progressed to aplastic anemia despite discontinuation of guanidine 2 1/2 months before death. Autopsy showed numerous granuloma in the liver, spleen, esophagus, and cecum from which Fusarium oxysporum was isolated. Although the unique finding of systemic fusariosis may relate to altered host resistance terminally, a causal relationship with her defect of neuromuscular transmission and/or aplastic anemia is a distinct possibility.

Involvement of the Onuf nucleus in Werdnig-Hoffmann disease.

Contrary to contention that Onuf nucleus is spared in Werdnig-Hoffmann disease (WHD) as it is in ALS, we found central chromatolysis in the Onuf neurons of the sacral cord from all five WHD patients. They were less depopulated but the central chromatolysis appeared more frequently than in anterior motor neurons. In contrast, the sacral autonomic neurons were not affected in any of the five cases. This argues against the view that the Onuf nucleus is autonomic and is spared with other autonomic neurons.

Progressive multifocal leukoencephalopathy with 10-year survival in a patient with nontropical sprue. Report of a case with unusual light and electron microscopic features.

A 46-year-old man with nontropical sprue had anemia and hypoproteinemia for several years, until his condition was diagnosed and treated with dietary measures. Within a year after the diagnosis, progressive multifocal leukoencephalopathy developed, and the patient had a slightly fluctuating chronic downhill course until he died 10 years later. It is postulated that this patient's immune deficiency was related to his malabsorption syndrome and hypoglobulinemia, and the course became unusually protracted (longest reported course in the American literature) because of restoration of plasma protein levels. Autopsy showed the classic findings of progressive multifocal leukoencephalopathy, with much tissue loss of subcortical white matter and active perivascular inflammatory foci with numerous eosinophilic granulocytes. On electron microscopy, oligodendrocyte nuclei and cytoplasm were crowded with virions, but many myelin sheaths invested by severely infected oligodendrocytic processes were remarkably well preserved. This fact would argue against a direct cause-and-effect relationship between infection of oligodendrocytes and myelin breakdown in progressive multifocal leukoencephalopathy. The likelihood of an autoimmune mechanism at work in this disease is suggested, and the role of eosinophils and other cells in such process is considered.

Fast axonal transport in amyotrophic lateral sclerosis: an intra-axonal organelle traffic analysis.

Fast transport of intra-axonal organelles was studied in motor nerve from amyotrophic lateral sclerosis (ALS) patients. Organelle traffic in ALS nerves demonstrated a significant increase in anterograde mean speed, while retrograde mean speed was decreased compared with that of controls. Retrograde traffic density (organelles per unit time) was also significantly decreased in the ALS specimens. Anterograde transport machinery is therefore intact and may be responding to the increased physiologic demand of larger motor units. Diminished retrograde speed and organelle traffic density are consistent with a defect in retrograde transport and could impair communication between axon terminals and perikarya.

Chloroquine neuromyotoxicity. Clinical and pathologic perspective.

Six cases of toxic myopathy and/or neuropathy with chloroquine and/or hydroxychloroquine therapy are described. Two patients had unique clinical and pathologic evidence of cardiomyopathy secondary to chloroquine or hydroxychloroquine therapy. One patient had polyneuropathy secondary to chloroquine toxicity. This may be the first documentation of several features of chloroquine/hydroxychloroquine toxicity: morphologic changes in human peripheral nerve in chloroquine toxicity; chloroquine/hydroxychloroquine cardiomyopathy diagnosed by endomyocardial biopsy; and hydroxychloroquine myotoxicity. Chloroquine is a neuromyotoxin that affects nerves and cardiac and skeletal muscles. Discontinuation of chloroquine and hydroxychloroquine resulted in marked improvement in most cases. The reversibility of the symptoms emphasizes the importance of recognizing potential signs of nerve, muscle, and cardiac toxicity in patients being treated with chloroquine or hydroxychloroquine.

Interferon-beta impairs induction of HLA-DR antigen expression in cultured adult human astrocytes.

We studied the effect of interferons on the expression of class II histocompatibility (HLA-DR) antigens by cultured adult human astrocytes. Cultures were derived from brain tissue resected for surgical treatment of intractable epilepsy. Cultured astrocytes did not spontaneously display HLA-DR antigen as determined by immunocytochemistry and flow cytometry with antibody to HLA-DR. Astrocytes cultured for 72 h with recombinant or natural interferon-gamma (IFN gamma) demonstrated a dose-dependent increase in HLA-DR expression with optimal stimulation by 100 U/ml IFN gamma. HLA-DR expression was not detectable in astrocytes cultured with IFN gamma for less then 48 h, and peak HLA-DR expression (over 80% of cells) was seen at 120 h of culture. Optimal HLA-DR expression required continuous presence of IFN gamma. Exposure of astrocytes to recombinant or natural interferon-beta (IFN beta) did not induce HLA-DR and pretreatment of astrocytes with IFN beta or interferon-alpha (IFN alpha) significantly inhibited subsequent induction of HLA-DR expression by IFN gamma. These observations suggest that interferons may function in regulating human astrocyte HLA-DR expression within the central nervous system.

Enhanced DNA synthesis of human glial cells exposed to human leukocyte products.

DNA synthesis was studied in primary glial cell cultures derived from adult human non-neoplastic and neoplastic brain tissues. Enhanced DNA synthesis occurred in 5/5 non-neoplastic astrocyte, one oligodendroglioma, and 2/5 astrocytoma cultures after exposure to medium containing 1.25-12.5% supernatant fluid (SF) from insoluble concanavalin A (Con A) stimulated unseparated or T lymphocyte-enriched human mononuclear leukocytes (MNL). Analyses of SF indicated that the presence of platelet-derived growth factor (PDGF) could not account for glial cell stimulation, and exposure to semi-purified interleukin-2 (IL-2) in amounts comparable to those in SF from Con A-stimulated MNL had no effect on glial cells. These data indicate that non-neoplastic astrocytes and other human glial cells are stimulated by products of human MNL.

Inclusion body myositis: a chronic persistent mumps myositis?

Among the generalized chronic idiopathic inflammatory myopathies, inclusion body myositis (IBM) has emerged as a clinico-pathologic variant during the past two decades. It occurs primarily in elderly persons (in approximately the sixth decade of life), but young adults (in approximately the second decade of life) may also be affected. Slowly progressive weakness of distal as well as proximal muscle groups in IBM is usually not associated with skin rash, malignancy or collagen-vascular disease, and is refractory to treatment with steroids or other immunosuppressants. Exceptions to each of these general rules have been found. Muscle biopsy and electromyography may suggest a neurogenic process mixed with myopathic features. Rimmed vacuoles with basophilic granules in cryostat sections stained with hematoxylin-eosin are strongly suggestive of IBM if accompanied by the histopathologic triad of polymyositis. The presence of eosinophilic intranuclear or cytoplasmic inclusions in affected myofibers is further suggestive of IBM. The ultimate diagnosis, however, depends on ultrastructural demonstration of characteristic microtubular filaments resembling the nucleocapsids of the paramyxovirus group. Recent reports of immunostaining of the inclusions for mumps virus antigen strongly suggest a chronic persistent mumps virus infection as the cause of IBM. IBM is considered to be pathologically related to both distal myopathy (DM) and oculopharyngeal muscular dystrophy (OPMD).

Occlusive hypertrophic arteritis as the cause of discrete necrosis in CNS toxoplasmosis in the acquired immunodeficiency syndrome.

Brain specimens from five immunocompromised patients with CNS toxoplasmosis were studied with immunostaining for toxoplasma antigens and electron microscopy. The tachyzoites or toxoplasma antigens were predominantly localized in walls of hypertrophic, often thrombosed, arteries and adjacent brain tissue at the hyperemic rims of centrally necrotic lesions. This study suggests that in CNS toxoplasmosis of immunocompromised hosts, the organisms primarily invade and spread along segments of small artery walls, causing hypertrophy of arterial walls, thrombotic occlusion of lumens, circumscribed but expansive ischemic necrosis, and extravasation of organisms. Rapid response to chemotherapy can be explained by this preferential parasitism to the arterial walls. Early definitive diagnosis on brain biopsy specimens can be attained by immunostaining.

Colocalization of NOS and SOD1 in neurofilament accumulation within motor neurons of amyotrophic lateral sclerosis: an immunohistochemical study.

Peroxynitrite, formed from nitric oxide and superoxide, may affect neurofilament assembly and cause neurofilament accumulation in motoneurons. This hypothesis may reconcile the mutations of two genes: superoxide dismutase-1 in some patients with familial amyotrophic lateral sclerosis, and the gene for the heavy neurofilament in some patients with sporadic amyotrophic lateral sclerosis previously reported. We found colocalization of superoxide dismutase-1 and nitric oxide synthase in the foci of neurofilament accumulation as 'conglomerates' in upper motor neurons and 'axonal spheroids' in lower motor neurons. In addition, all the specific molecules related to the reactions, including calmodulin, 3', 5'-cyclic guanosine-monophosphate, citrulline, and nitrotyrosine were found strongly immunopositive in the site of neurofilament accumulation. Our data support the view that the neurofilament aggregates are tightly linked with superoxide dismutase-1 and nitric oxide synthase activities. Both enzymes may focally contribute to peroxynitrite formation at light neurofilament, which is rich in both tyrosine and arginine residues and hence considered as the vulnerable site for nitrotyrosine formation. Nitrotyrosine is known to inhibit phosphorylation and if it impairs phosphorylation of neurofilament subunits, either light or heavy, may alter the slow axonal transport culminating in proximo-distal accumulation of NF and slowly progressive motoneuron death.