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Diagnostic imaging of the diabetic foot.

Diagnostic imaging plays a major role in the osteoarticular disease of the foot in diabetics, allowing the diagnosis and evaluation of alterations for therapy planning. To-date conventional radiology is still of first choice in the study of the diabetic foot with the evaluation of osteoarticular damage caused by neuropathy and vascular disease. Major radiographic patterns are neuroarthropathy and osteomyelitis. Main locations are at the level of forefoot and less frequently of tarsus and tibiotarsal joint. Second choice procedures as US, CT and MRI are useful for a more accurate evaluation of soft tissue lesions and articular structures. US is the first choice procedure in soft tissue evaluation to rule out the presence of abscesses which require surgery. MRI with some limitations represents the gold standard for the study of joints and medullary disease. Spiral CT though less specific and sensitive than MRI for soft tissue and bone marrow study is still the exam of reference for the study of bone structures with three-dimensional reconstructions useful to plan orthopedic surgery.

Diabetic Foot↗

[Thyroid-associated ophthalmopathy].

Thyroid-associated ophthalmopathy is a local autoimmune reaction in the orbit. Typical signs are retraction of the eyelid, periorbital oedema, proptosis and impaired eye motility. Exposure keratopathy or compression of the optic nerve may be a complication. Patients with severe proptosis or progressive loss of vision need an efficient and safe treatment modality. Immunosuppression may be the first choice, followed by surgical decompression of the orbit. We describe a combined external and endoscopic approach with resection of the lateral, inferior and medial orbital walls. In this way, the increased intraorbital pressure is relieved. Retraction of the upper eyelid is corrected by transconjunctival approach and the release of muscles from the tarsus.

Aged↗

The Asian lower eyelid: a comparative anatomic study using high-resolution magnetic resonance imaging.

Asian upper and lower eyelids are typically characterized by a fuller appearance than the lids of whites. Inferior extension of preaponeurotic fat and brow fat into the Asian upper lid explain the upper lid fullness and its difference from the upper lid of whites. Analogous structures in the Asian lower lid may exist to explain its full appearance. High-resolution magnetic resonance imaging (MRI) of 24 normal Asian and white lower lids was performed to evaluate differences in Asian and white lower lid anatomy. Magnetic resonance images revealed two major differences. First, the orbital fat projected further anteriorly with respect to the orbital rim in all Asian lower lids studied. No analogy with the upper lid exists for this difference. Second, the orbital fat extended further superiorly, to the inferior border of tarsus, in those Asian lower lids that did not have well defined creases. This was analogous to the preaponeurotic fat location of the Asian upper lid and different from the white lower lid. The suborbicularis oculi fat in the lower lid, the analogous structure of the brow fat pad in the upper lid, was not different in location in Asian and white lower lids. Therefore, the Asian lower lid appearance is explained by the difference in orbital fat location, which is only partly analogous to the anatomical differences between the Asian and white upper lids.

Adipose Tissue↗

[Diseases of the Achilles tendon in dogs and cats].

Dogs and cats rarely have problems with the Achilles tendon and if so, it usually results from a direct trauma. Prime area for injuries is the insertion on the tuber calcanei or directly proximal. One defers between complete and partial ruptures, acute and chronic injuries as well as displacement of the tendon of the superficial digital flexor muscle. In 38 cases (33 dogs and five cats) the clinical examination, radiology, ultrasonography and therapy are shown. Usually the clinical examination is sufficient for a diagnosis (hyperflexion of the hock and weight-bearing on the plantar surface of the metatarsus). The radiology primarily shows up abnormalities on the calcaneus, mineralisations of the tendon and allows the assessment of implants. Ultrasonography is the diagnostic imaging of choice for judgement of tendon diseases as well as the progress of their healing. Tendon suture is advisable if the rupture is open, fresh and/or complete and in cases of luxation of the superficial digital flexor muscle. Immobilisation of the tarsus in hyperextension seems to be of utmost importance no matter if an operative or conservative therapy is chosen.

Achilles Tendon↗

Appearance of ossification centers of the lower arm, wrist, lower leg, and ankle in immature orangutans and chimpanzees with an assessment of the relationship of ossification to dental development.

This study examines the appearance of the secondary ossification centers in the lower arms, wrists, lower legs, and ankles of a cross-sectional sample of 20 infant orangutans and chimpanzees (15 of known age). The number of tarsal and carpal centers is analyzed relative to the degree of M1 development and the weight of individual animals. Variation in the appearance of these ossification centers is discussed relative to these variables and others. In addition, a sequence of appearance is established for the carpal and tarsal ossification centers in the orangutan and data is presented on the status of these centers in a fetal and newborn gorilla. Study results indicate that 1) there is variation in the number of secondary epiphyses present in animals of similar ages; 2) tarsal ossification is completed prior to carpal ossification in the orangutan; 3) there are indications of a relationship between weight and the number of ossification centers present in animals of similar age; and 4) there appears to be no evidence of specific relationships between carpal and tarsal development and M1 development.

Animals↗

Horseradish peroxidase study of the spatial and electrotonic distribution of group Ia synapses on type-identified ankle extensor motoneurons in the cat.

Eight functionally identified group Ia muscle afferents from triceps surae or plantaris muscles were labeled intraaxonally with horseradish peroxidase (HRP) in seven adult cats. Subsequently, HRP was injected into two to six homonymous or heteronymous alpha-motoneurons per animal (total = 22), each identified by motor unit type and located near the site of afferent injection. The complete trajectories of labeled afferents were reconstructed, and putative synaptic contacts on HRP-labeled motoneurons were identified at high magnification. Dendritic paths from each contact were also mapped and measured. A total of 24 contact systems (the combination of a group Ia afferent and a postsynaptic motoneuron) were reconstructed, of which 17 were homonymous, and seven were heteronymous. Overall, homonymous contact systems had an average of 9.6 boutons, whereas heteronymous contact systems had an average of 5.9 boutons. The average number of boutons found on type S motoneurons in homonymous contact systems was smaller (6.4, range 3-17) than in systems involving types FF or FR motoneurons (FF: 10.4, range 4-18; FR: 11.3, range 4-32). Neither of these differences were statistically significant. In contrast to earlier reports, a majority (15/24) of contact systems included more than one collateral from the same Ia afferent. The complexity (number of branch points) in the arborization pathway leading to each contact (overall mean 8.4 +/- 3.3) was virtually identical in all contact systems, irrespective of the type of postsynaptic motoneuron. The three-dimensional distribution of group Ia contacts was not coextensive with the radially organized dendrites of motoneurons: Dendrites oriented in the ventromedial to dorsolateral axis had the fewest (8%) contacts, whereas rostrocaudal dendrites had the most (63%) contacts. Nevertheless, contacts were widely distributed on the motoneuron surface, with few on and near the soma (< or = 200 microns radial distance from the soma) or on the most distal parts of the tree (> or = 1,000 microns). The boutons in individual contact systems also showed wide spatial and estimated electrotonic distributions; only 3/24 systems had all contact located within a restricted spatial/electrotonic region. The relations between these anatomical results and existing electrophysiological data on group Ia synaptic potentials are discussed.

Animals↗

Evaluating motor end-plate-targeted injections of botulinum toxin type A in a canine model.

Tarsal joint forces were measured in dogs over 70 days following botulinum toxin type A (BTX-A) injections. Three dogs were injected at motor end-plates located by electromyography (EMG), while 3 dogs were similarly injected, but without EMG guidance. Extension forces were significantly (P < 0.05) smaller in limbs injected at motor end-plates than in corresponding limbs on days 14 and 35. There were no significant differences at other times. Using these techniques, EMG end-plate targeting potentiates effects of BTX-A.

Animals↗

Transmission of antibody-induced arthritis is independent of complement component 4 (C4) and the complement receptors 1 and 2 (CD21/35).

The K/BxN murine model of rheumatoid arthritis (RA) is dependent on the specificity of the KRN alpha beta-TCR, to recognize glucose-6-phosphate-isomerase (GPI) on the NOD MHC class II A(g7) allele and production of GPI-specific autoantibodies. Transfer of K/BxN serum into MHC-unrelated and lymphocyte-deficient mice induces RA. To investigate whether K/BxN serum-induced RA involves complement activation and/or the complement receptors (CR) 1 and 2, we analyzed the role of complement C4 and of CR1 and CR2. For this purpose we used C4(-/-) mice impaired in the classical and the lectin complement pathways; Cr2(-/-) mice lacking CR1 and CR2 and, as control strains, BALB/c, C57BL/6, KRN and NOD. RA was assessed by caliper measurement of ankle thickness, clinical index and joint histology. We found that all mouse strains except NOD developed RA. The lack of protection in C4(-/-) mice suggests that antibody-mediated RA is independent of the classical as well as the lectin complement pathways and the split complement product C4b. The lack of protection in Cr2(-/-) mice suggests that absence of CR1 had no significant affect, considering its role in immune complex clearance, inhibition of C3 and C5 convertase and as receptor for C3b/C4b. Also, CR2 lacks a role in disease as analyzed here, in its possible functions as receptor for C3dg, germinal center reaction and activation of alternative pathway on binding iC3. Hence we conclude that the transmission of K/BxN serum-induced RA is independent of the classical and the lectin complement pathways and CR1 and CR2. The crucial role of complement C5, while neither classical nor lectin pathway is necessary, indicates that the alternative complement pathway may have a role in the K/BxN serum-induced RA model.

Animals↗

Disease-modifying activity of SB 242235, a selective inhibitor of p38 mitogen-activated protein kinase, in rat adjuvant-induced arthritis.

OBJECTIVE: To evaluate the effects of SB 242235, a potent and selective inhibitor of p38 mitogen-activated protein (MAP) kinase, on joint integrity in rats with adjuvant-induced arthritis (AIA). METHODS: Male Lewis rats with AIA were orally treated either prophylactically (days 0-20) or therapeutically (days 10-20) with SB 242235. Efficacy was determined by measurements of paw inflammation, dual-energy x-ray absorptiometry for bone-mineral density (BMD), magnetic resonance imaging (MRI), microcomputed tomography (CT), and histologic evaluation. Serum tumor necrosis factor alpha (TNFalpha) in normal (non-AIA) rats and serum interleukin-6 (IL-6) levels in rats with AIA were measured as markers of the antiinflammatory effects of the compound. RESULTS: SB 242235 inhibited lipopolysaccharide-stimulated serum levels of TNFalpha in normal rats, with a median effective dose of 3.99 mg/kg. When SB 242235 was administered to AIA rats prophylactically on days 0-20, it inhibited paw edema at 30 mg/kg and 10 mg/kg per day by 56% and 33%, respectively. Therapeutic administration on days 10-20 was also effective, and inhibition of paw edema was observed at 60, 30, and 10 mg/kg (73%, 51%, and 19%, respectively). Significant improvement in joint integrity was demonstrated by showing normalization of BMD and also by MRI and micro-CT analysis. Protection of bone, cartilage, and soft tissues was also shown histologically. Serum IL-6 levels were decreased in AIA rats treated with the 60 mg/kg dose of compound. CONCLUSION: Symptoms of AIA in rats were significantly reduced by both prophylactic and therapeutic treatment with the p38 MAP kinase inhibitor, SB 242235. Results from measurements of paw inflammation, assessment of BMD, MRI, and micro-CT indicate that this compound exerts a protective effect on joint integrity, and thus appears to have disease-modifying properties.

Absorptiometry, Photon↗

Fractalkine, a novel chemokine in rheumatoid arthritis and in rat adjuvant-induced arthritis.

OBJECTIVE: To examine the expression of the novel CX3C chemokine fractalkine (Fkn) and its receptor (CX3CR1) in rheumatoid arthritis (RA) and rat adjuvant-induced arthritis (AIA), a model of RA. METHODS: Immunohistochemistry, flow cytometry, enzyme-linked immunosorbent assay (ELISA), reverse transcriptase-polymerase chain reaction (RT-PCR), and chemotaxis assays were used. RESULTS: In rat AIA, synovial tissue (ST) macrophages, fibroblasts, endothelial cells, and dendritic cells were Fkn immunopositive, whereas lymphocytes did not significantly express Fkn. Significant staining for CX3CR1 was found in ST macrophages, fibroblasts, and dendritic cells, whereas only a small percentage of endothelial cells stained for CX3CR1 in rat AIA. We immunolocalized Fkn to RA ST macrophages, fibroblasts, endothelial cells, and dendritic cells. We also found intense ST macrophage and dendritic cell staining for CX3CR1 in RA ST. Flow cytometry analysis of RA synovial fluid (SF) and peripheral blood revealed a greater percentage of monocytes expressing Fkn and CX3CR1 compared with T cells. By ELISA, we found significantly elevated soluble Fkn (sFkn) levels in RA SF compared with SF from patients with osteoarthritis or other forms of arthritis. By RT-PCR, we found enhanced expression of Fkn and CX3CR1 mRNA on day 18 in rat AIA, a time of pronounced inflammation in the rat joint. Soluble Fkn-depleted RA SF showed significantly decreased chemotactic activity for monocytes compared with sham-depleted RA SF. CONCLUSION: These results indicate that Fkn and its receptor are both expressed in RA and in rat AIA, and that sFkn is up-regulated in RA SF. Furthermore, our data suggest a new role for Fkn in monocyte chemotaxis in the inflamed RA joint.

Adult↗

Lesions in the rat soleus muscle following eccentrically biased exercise.

Morphological changes in skeletal muscle related to lengthening (eccentric) contractions have been noted by several laboratories. However, a systematic examination of skeletal muscle following repetitive eccentric contractions is lacking. This study was undertaken to study lesions and determine their relative densities in rat soleus muscle 30 min following level or downhill treadmill exercise. Following fixation in situ by vascular perfusion, toluidine-blue-stained 1-micron sections of the muscle samples selected at 73-micron intervals were scanned with a light microscope. Three types of lesions were noted: focal disruptions in the A-band, localized dissolution of Z-lines, and clotting of muscle fibers. Soleus muscle from the caged controls and the tibialis anterior muscle from downhill-exercised rats were essentially free of lesions. Eighty-nine percent of the soleus m. lesions in the downhill runner group and 97% of those in the level runner group were A-band disruptions. A-band lesion density was significantly higher in the soleus muscle of the downhill runners compared to level runners with the highest incidence in the distal half. A-band lesion density was lower in soleus muscles from level runners; however, the highest intramuscular incidence was in the proximal rather than the distal end. The results indicate that a disruption of the A-band is a principal change within some skeletal muscle fibers 30 min following repetitive eccentric contractions.

Animals↗

Hindlimb proportions, allometry, and biomechanics in Old World monkeys (primates, Cercopithecidae).

The traditional focus on morphological rather than mechanical units has obscured some significant functional differences in the hindlimbs of primates. This paper examines the allometric and biomechanical basis for some distinctive proportional differences among pairs of morphological units in the hindlimb, and especially the foot, of cercopithecid primates. Five major conclusions are reached. First, many hindlimb dimensions scale allometrically with body mass to maintain mechanical similarity within taxonomic and locomotor groups. Therefore, the majority of traditional indices which describe the shape of the foot within cercopithecids reveal differences which are primarily a function of size. Second, the hindlimb segments in colobines, and especially in Presbytis, are relatively long, probably to enhance leaping. Third, the major distinction of terrestrial cercopithecines among the features analysed is reduction in the length of the phalanges, due to the reduced importance of grasping during locomotion and the assumption of digitigrady. Fourth, Theropithecus and male Erythrocebus have high crural indices, relative to their body masses, which can facilitate curosoriality. Female E. patas already has a high crural index as a function of its body mass. Fifth, macaques form a distinctive group among cercopithecines, characterized by relatively short hindlimbs. Relatively very short hindlimbs in Macaca fuscata and M. thibetana suggest that climatic conditions can have an added effect on the lengths of the hindlimb segments. In summary, this analysis of the lengths of the hindlimb segments relative to body size reveals taxonomic differences which are due in part to phylogeny, to differences in locomotor behavior, and to substrate use.

Analysis of Variance↗

Hindlimb adaptations in Ourayia and Chipetaia, relatively large-bodied omomyine primates from the Middle Eocene of Utah.

North American omomyids represent a tremendous Eocene radiation of primates exhibiting a wide range of body sizes and dietary patterns. Despite this adaptive diversity, relatively little is known of the postcranial specializations of the group. Here we describe hindlimb and foot bones of Ourayia uintensis and Chipetaia lamporea that were recovered from the Uinta B member (early Uintan Land Mammal Age), Uinta Formation, Utah. These specimens provide insights into the evolution of postcranial adaptations across different body sizes and dietary guilds within the Eocene primate radiation. Body mass estimates based on talar measurements indicate that Ourayia uintensis and Chipetaia lamporea weighed about 1,500-2,000 g and 500-700 g, respectively. Skeletal elements recovered for Ourayia include the talus, navicular, entocuneiform, first metatarsal, and proximal tibia; bones of Chipetaia include the talus, navicular, entocuneiform, and proximal femur. Both genera had opposable grasping big toes, as indicated by the saddle-shaped joint between the entocuneiform and first metatarsal. Both taxa were arboreal leapers, as indicated by a consistent assemblage of characters in all represented bones, most notably the somewhat elongated naviculars, the high and distinct trochlear crests of the talus, the posteriorly oriented tibial plateau (Ourayia), and the cylindrical head of the femur (Chipetaia). The closest resemblances to Ourayia and Chipetaia are found among the Bridger omomyines, Omomys and Hemiacodon. The results of our comparisons suggest that the later, larger, more herbivorous omomyines from Utah retained a skeletal structure characteristic of earlier, smaller North American omomyids.

Adaptation, Physiological↗

Ultrastructural and biochemical changes in rat soleus muscle following tenotomy.

This study was designed to correlate changes in the rate-limiting enzymes of glycogen synthesis (glycogen synthase) and glycogen breakdown (glycogen phosphorylase) with the ultrastructural changes which occur in the soleus muscle following tenotomy. Soleus muscles were removed at 1, 2, 3, 7, 14, 21, and 63 days after tenotomy and were prepared for electron microscopy or frozen for enzyme analysis. In the first 7 days posttenotomy, soleus muscle fibers underwent a series of degenerative changes, while both synthase and phosphorylase activities decreased. Over the next 8 weeks the histological appearance of the soleus muscle eventually returned to normal while synthase and phosphorylase activities increased. We suggest that recovery from tenotomy involves an increase in the energy demands of the muscle, resulting in the increased activity of the key rate-limiting enzymes of muscle glycogen metabolism from the drastically reduced levels observed in the period before recovery begins.

Animals↗

Immunohistochemical localization of type X collagen in the proximal tibiotarsi of broiler chickens and turkeys.

Type X collagen is a prominent component of the extracellular matrix in cartilage destined to mineralize during endochondral ossification, yet its role is only now being determined. As a prelude to determining what, if any, alterations occur in the distribution of type X collagen in growth plates of poultry with rickets or tibial dyschondroplasia, our objective in the current study was to determine the distribution of type X collagen in the proximal tibiotarsi of broiler chickens and turkeys from 1 day of age through physeal closure. Proximal tibiotarsi from five male broiler chickens, five female broiler chickens and five male turkeys were collected at 1, 7, 14, 28, 56, and 98 days of age and processed for immunohistochemistry; a monoclonal antibody for type X collagen was used to demonstrate type X collagen distribution. Our findings indicate that type X collagen is produced in the prehypertrophic and early hypertrophic zones of the avian growth plate and is incorporated into the extracellular matrix in these zones. Furthermore, intracellular type X collagen is markedly decreased in more mature areas of the growth plate, although type X collagen remains a prominent component of the extracellular matrix until the matrix is completely resorbed. In addition, the distribution of type X collagen is similar in the proximal tibiotarsi of broiler chickens and turkeys at comparable stages of endochondral ossification and distribution of type X collagen in the secondary center of ossification parallels that in the physis.

Animals↗

Suppression of autoimmune arthritis in interleukin-1-deficient mice in which T cell activation is impaired due to low levels of CD40 ligand and OX40 expression on T cells.

OBJECTIVE: To elucidate the roles of interleukin-1 (IL-1) in the development of 2 etiologically different rheumatoid arthritis (RA) models: the type II collagen (CII)-induced arthritis (CIA) model and the human T cell leukemia virus type I transgenic (HTLV-I Tg) mouse model. METHODS: For the CIA model, DBA/1J-background IL-1alpha-/-, IL-1beta-/-, IL-1alpha/beta-/-, and wild-type littermate mice were immunized with CII. For the HTLV-I Tg model, BALB/c IL-1beta-/- or IL-1alpha/beta-/- mice were crossed with HTLV-I Tg mice. The effects of IL-1 deficiency were assessed as follows: Development of arthritis was assessed both macroscopically and microscopically. Serum antibody titer was measured by enzyme-linked immunosorbent assay. Proliferative response of lymph node cells was assayed by measurement of (3)H-thymidine incorporation. Expression of T cell surface molecule CD40 ligand (CD40L) and OX40 was determined by multicolor flow cytometric analysis. RESULTS: The development of arthritis was markedly suppressed in IL-1alpha/beta-/- mice in both models, although the effect was less prominent in HTLV-I Tg mice. Deficiency of only IL-1alpha or only IL-1beta was also associated with disease suppression. Antibody production after immunization with CII was normal in IL-1alpha/beta-/- mice, while autoantibody production was suppressed in IL-1alpha/beta-/- HTLV-I Tg mice. In IL-1alpha/beta-/- mice, the T cell proliferative response against CII was greatly reduced in both the CIA and the HTLV-I Tg models, suggesting inefficiency of T cell activation. Furthermore, expression of CD40L and OX40 on T cells was greatly reduced in IL-1alpha/beta-/- mice. CONCLUSION: These observations suggest that T cell activation by IL-1 is important for the development of autoimmunity and arthritis in these mice.

Animals↗

Projections of ankle joint afferents to the spinal cord and brainstem of the chicken (Gallus g. domesticus).

The projections of the ankle joint capsule afferents were studied by transganglionic transport of horseradish peroxidase injected directly into the ankle joint. The number and size of the labelled dorsal root ganglion cells were measured from synsacral nerves 2-9. In the dorsal root ganglia, all sizes of sensory neurones were labelled, and the largest number of labelled cells was in ganglia 5-7. The extensive sympathetic innervation of the ankle joint was identified by the large number of cell bodies labelled in the sympathetic ganglia of the paravertebral chain. Labelled afferent fibres projected to the spinal cord from the 2nd to the 8th synsacral nerves, with the rostral projection mainly via Lissauer's tract and the dorsal funiculus. Terminal labelling in the dorsal horn was identified in laminae I-III and VI, with a slight projection to V. Two areas of dense labelling, which did not correspond with the largest number of labelled dorsal root ganglion cells, were identified. A rostral area with the highest density of label was observed at the level of synsacral nerves 3-4 and a second slightly less dense area between synsacral nerves 7-8. In the caudal medulla, diffuse terminal labelling was observed in the nucleus gracilis et cuneatus, nucleus of the tractus solitarius, and the nucleus cuneatus externus. These results are discussed in a comparative context to identify similarities and differences between different primary afferent projections in birds and mammals and to highlight the possible functional significance of the avian articular afferent projection.

Afferent Pathways↗