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PubMed1997

Arthropathy in Behçet's disease.

We analyzed the incidence, clinical features, and the long-term sequelae of arthropathy in 84 patients with Behçet's disease. After a mean disease duration of 44.7 months, 59 patients (70%) had at least 1 episode of arthropathy. Of these, arthropathy was present at the time of diagnosis in the majority of patients (75%). In the remainder, arthropathy developed 4 to 80 months (mean 29) after the diagnosis of Behçet's disease. Female patients were significantly more likely to have arthropathy than male patients (89 versus 56%, p = 0.006). The pattern of involvement was oligoarticular in 75%, monoarticular in 23%, and polyarticular in 2% of these patients. The most commonly involved site was the knee, followed by the ankle and the wrist. Radiologic examination of the involved site was normal in 80% of the patients. After a mean duration of arthropathy of 43.2 months, by the American College of Rheumatology (ACR) criteria, the functional class of the arthropathy was I-II in 88%, and III-IV in 12%. In conclusion arthropathy is a fairly common manifestation in patients with Behçet's disease, but crippling arthritis is relatively rare.

Adult↗

PubMed1983

Studies of dynamic ligamentous instability of the knee by electrogoniometric means.

Ligamentous injuries to a knee joint increase the risk of post-traumatic degenerative changes. Successful early diagnosis and treatment of such injuries remains a challenging and controversial task. There are a variety of clinical tests available and some of these are difficult to perform and interpret. These clinical tests are really static in nature and may not reveal the presence of what is essentially a dynamic event. A complete assessment would need to be "dynamic" and by its application during ambulation, incorporate the effects of ground-foot forces, joint motions and muscle activities. At the Ontario Crippled Children's Centre (OCCC) a triaxial electrogoniometer system (extensively modified CARS-UBC) has been used, together with complementary gait laboratory instrumentation, in order to study the knees of 16 male subjects. Ten subjects had knees without evidence of injury and six had a variety of cruciate and menisceal tears. The purpose of the study was to investigate if a subject's knee could be classified as "normal" or "unstable" by using just the data provided by the electrogoniometer during walking trials. These data are difficult to interpret in their time series form because they are multidimensional and in all subjects likely to exhibit subtle stride to stride variations. The method described allows the mapping of this data into an abstract two dimensional co-ordinate system, resulting in a set of trajectories which cluster together for data belonging to the "normal" group. Only two subjects, with grossly unstable knees, were judged different from normal using a level walking test protocol. Some potential reasons for this are discussed.

Electrophysiology↗

PubMed1985

Prosthesis with electric elbow and hand for a three-year-old multiply handicapped child.

The usefulness of wisely prescribed powered components in the rehabilitation of upper extremity amputees has long been recognized (Schmidl, 1973). Their value is especially evident in the prosthetic rehabilitation of high level adult and child amputees (Heger et al, 1985). In recent years, manufacturers of prosthetic hardware have provided practitioners with a wide selection of either myo-electrically or switch controlled electromechanical components and systems. As a rule, however, most commercially available components are designed to serve the adult amputee and do not lend themselves for use in the prosthetic rehabilitation of children. One current exception is the availability of child-size electric hands. The availability of the world's first child-size electric hand in 1970 at the Ontario Crippled Children's Centre later known as the Variety Village 105 hand, gave tremendous impetus to the fitting of younger children with externally powered components and myoelectric control systems. However, this trend served to benefit the young below-elbow patient only (Sorbye et al, 1972). The successful fitting of higher amputation levels in this age group stopped at the elbow level. Existing artificial elbows such as the Variety Village and Hosmer elbow with their necessary powerpacks are simply too bulky and too heavy for pre-school age children. The need for a lightweight compact electric elbow, suitable for 3-8 year old children, still has not been addressed. This single case report illustrates an innovative and successful conversion of a 6-3/4 Otto Bock hand into a small electric elbow. The idea was first proposed by Schmidl (1973).

Arm↗

PubMed2001

Expression of B cell receptor-associated signaling molecules in human lupus.

B cell receptor (BcR) signaling requires a tight regulation of several protein tyrosine kinases and phosphatases, and associated co-receptors. Mounting evidence indicates that abnormal BcR signaling, such as occurs in SHP-1 and Lyn-deficient mice, results in production of pathogenic autoantibodies and lupus-like glomerulonephritis, suggesting that altered signaling thresholds could underlie the development of systemic autoimmunity. To test this hypothesis, we investigated expression of BcR-associated signaling molecules in lymphocytes from patients with systemic lupus erythematosus (SLE) during inactive phases of the disease. We found that the transmembrane regulatory protein tyrosine phosphatase CD45 is expressed at abnormal levels. Strikingly, this reduction persisted during four months of follow-up. By contrast, despite its potent role as a regulator of thymus-independent immune responses and of B cell life span, the CD22 co-receptor is expressed at normal levels in B lymphocytes isolated ex vivo from SLE patients. We also noted unusual levels of the cytosolic protein tyrosine kinase Lyn and the protein tyrosine phosphatase SHP-1 in the lymphocytes of the patients. Since in normal B cells Lyn and SHP-1 act in concert within a common negative pathway in which CD45 counteracts SHP-I regulatory role, we propose that this feedback regulatory pathway is crippled to different degrees in human SLE B cells. Break of the balance between positive and negative signaling molecules likely modifies the BcR signaling thresholds. Such alterations, together with other factors, may contribute to the disruption of self-tolerance in this disease.

Animals↗

PubMed1991

Cyclosporine-induced autoimmunity and immune hyperreactivity.

Cyclosporine (CS) is a potent immunosuppressive agent which under some circumstances paradoxically augments DTH responses, aggravates some autoimmune diseases, and induces specific forms of autoimmunity. The enhancement of DTH and other immune responses is closely related to the timing of CS administration relative to immunization. CS inhibits IL-2 production (and several other lymphokines) at a pretranscriptional level, but does not usually prevent the antigen-specific priming of T cells, such that T cells may be poised to respond as soon as CS is withdrawn. Thus, accelerated GVHD and allograft rejection may occur after withdrawal of CS. CS has been shown to aggravate and/or induce relapse in several autoimmune diseases including collagen-induced arthritis, EAE, autoimmune thyroiditis, uveitis in SDA chickens, and an autoimmune form of myocarditis in mice. CS may enhance immune responses by inactivating suppressor cells, by altering Th1/Th2 antagonism (e.g., CS promotes a protective Th1-type response in BALB/c mice infected with Leishmania major), or by promoting T cell activation through a CS-resistant IL-2-independent T cell activation/differentiation pathway. At least three forms of CS-induced autoimmunity have been described: Syngeneic or autologous GVHD which occurs in CS-treated syngeneic or autologous bone marrow transplant recipients after CS is withdrawn in rats, mice, and humans; a systemic autoimmune disease with polyarthritis and glomerulonephritis which occurs in irradiated CBA/N mice treated with CS; and organ-specific autoimmune diseases which occur in mice treated with CS during the neonatal period. The precise mechanisms by which CS induces these autoimmune diseases are not clear, however, CS affects immune tolerance at three levels. CS induces thymic medullary involution with loss of medullary Ia+ cells, and appears to at least partially block the transition from double positive (CD4+CD8+) to single positive (mature type) thymocytes. In syngeneic bone marrow chimeras, CS appears to inhibit the intrathymic deletion of clones with relatively low affinity, but not those with high affinity, to self antigens. CS appears to inhibit the action of suppressor T cells which normally maintain an innate form of resistance to autoimmunity. Finally, CS has been shown to prevent the development of T cell clonal anergy. There is redundancy in immune tolerance mechanisms, i.e., clonal deletion, clonal anergy, and suppressor cells can each maintain tolerance to similar antigens, such that it is likely that CS must cripple more than one tolerance mechanism for autoimmunity to occur.

Adjuvants, Immunologic↗

PubMed1979

Myositis ossificans progressiva. Clinical and metabolical observations in a case treated with a diphosphonate (EHDP) and surgical removal of ectopic bone.

A 20-year-old woman with a severely crippling myositis ossificans progressiva was treated with a diphosphonate (EHDP), 10-20 mg/kg/day. While being treated with this drug, surgical removal of ectopic bone was performed. Although ectopic calcification recurred postoperatively, considerable functional improvement was achieved. At the highest dosage of EHDP, hypercalcaemia gradually appeared, but was reversible upon cessation of drug treatment. It is probably related to a direct effect of EHDP on the bone.

Adult↗

PubMed1987

Calcium--osteoporosis and blood pressure.

Calcium is the main essential mineral for building strong bones and sound teeth. Bone remodeling occurs throughout life; new bone is deposited and existing bone is replaced. Peak bone mass development is obtained up to 35 yr of age after which bone resorption is increased. It is therefore imperative that Ca intake meet the recommended dietary allowances not only during the growing period but throughout life. Milk and dairy products are the major food source of Ca in the US diet, supplying about 61% of our intake while other food groups supply the rest. It is almost impossible to supply the recommended dietary allowances of Ca without consuming milk in some form, as most other food groups are low in Ca content. The Ca in dairy products is bioavailable and readily absorbed by the body whereas Ca in other food sources may be less so. Several government surveys have shown that a large proportion of the US population, especially females 11 yr of age and older, have very low Ca intakes that do not meet the recommended dietary allowances for Ca. Recent developments in osteoporosis (porous, brittle, and fragile bones) have indicated that low Ca intake or bioavailability of this mineral is one of the major factors involved in this crippling bone disease. Osteoporosis affects 15 to 20 million middle-aged and elderly persons, especially postmenopausal women who are susceptible to bone fractures. Recent studies on nutrient intake and high blood pressure have reported an inverse relationship between dietary Ca intake and blood pressure levels.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

PubMed1998

Insulin-like growth factors and bone: the osteoporosis connection revisited.

Tremendous advances have been made in knowledge about the pathogenesis and treatment of osteoporosis, a disease that affects more than 25 million Americans. In particular, it has been determined that two major processes are responsible for osteoporotic fractures. These are: 1) bone mass acquisition during adolescence; and 2) bone loss beyond the sixth decade. The former, and possibly the latter, are regulated by genetic and environmental factors. Insulin-like growth factor-I (IGF-I), a ubiquitous polypeptide, assumes a critical role in both of these processes. Very recent studies have elucidated a complex multifaceted IGF regulatory system in bone and have allowed investigators to consider site-directed approaches to therapy. Even more exciting is the prospect that the genetic regulation of peak bone mass may be controlled by components of the IGF regulatory system. Within the last half decade, tremendous strides have been made in defining the regulatory circuits that determine the expression of skeletal and serum IGF-I. These heritable modulators may be similar or identical to regulators of bone mineral density, thereby joining two distinct phenotypes. This minireview highlights some of the new investigations into the role IGF-I plays in the pathogenesis of osteoporosis. Although recent clinical trials with growth hormone and IGF-I in this disease have been relatively disappointing, advances on other fronts have generated considerable excitement, and these promise new and innovative approaches to this crippling disease.

Adolescent↗

PubMed1977

Spontaneous spondylolisthesis in embryonic and adult chick.

The incidence of spontaneous avian spondylopathy was maintained between 58 and 66% in the progeny of one flock (Flock A) and less than 40% in the progeny of another (Flock B), by proper selection and breeding for 4 generations. Spondylolisthesis, the major type of spondylopathy present, was observed at the first and sixth vertebral levels. Spondylolisthesis was progressive in nature and consisted of a ventrodorsal rotation of the 1st and/or 6th thoracic vertebrae leading to spinal cord injury and paraplegia or partial crippling in some birds. There was occasionally extensive muscle degeneration and connective tissue proliferation around the distorted vertebrae and the spinous ligaments bridging the defect were stretched and appeared heavier than normal. Spondylopathy was also observed in 20-day chick embryos. Spondylolisthesis was observed in 33% of the embryos examined from Flock A-G2 and the other conditions present consisted of scoliosis and abnormal lordosis and kyphosis. Using a grading scale of +1 (mild) to +3 (severe), all cases of embryonic spondylopathy were graded as +1. The back defects present in Flock B-G2 embryos were entirely due to abnormal kyphosis.

Animals↗

PubMed1989

Pitfalls in diagnosis: the hip.

The hip joint is unique anatomically, physiologically, and developmentally. Because of these features, diagnosis of pathologic conditions is more difficult than for most joints. Because delay in diagnosis and treatment may result in crippling osteoarthritis, it is imperative that diagnostic pitfalls be avoided.

Adolescent↗

PubMed1994

Compartment syndrome of the upper arm.

Compartment syndromes of the upper arm are reported rarely in the literature. The diagnosis requires a high index of suspicion. As with compartment syndromes elsewhere, prompt aggressive treatment is crucial in avoiding possible crippling sequelae.

Adolescent↗

PubMedDate not supplied

Management of superior oblique palsy after surgery for true Brown's syndrome.

Thirty patients requiring surgery for true Brown's syndrome were examined postoperatively. Follow-up ranged from three months to 20 years. Eight-five percent of patients demonstrated some degree of superior oblique palsy, with 54% having a decompensated condition and 30% requiring a second surgical procedure. Patients with marked preoperative restriction appear to be at increased risk for developing a decompensated superior oblique palsy postoperatively. Solutions to this problem are suggested: 1) perform tenotomy at insertion and preserve the adjacent intermuscular septum so a less crippling effect is seen; 2) combine tenotomy with inferior oblique weakening initially in those patients with marked preoperative restriction.

Child↗

PubMedDate not supplied

Synergistic divergence: saccadic velocity analysis and surgical results.

The clinical findings are described in four patients with synergistic divergence (SD), an ocular motility disorder which is considered to be a variant of Duane retraction syndrome (DRS). Saccadic velocity studies in three patients demonstrated preserved abducting saccades in the affected eye with equally reduced amplitudes on both attempted abduction and adduction. The preserved saccades on attempted abduction of the affected eye, coupled with electromyographic evidence that shows maintenance of normal reciprocal innervation with respect to gaze on attempted abduction as dictated by Sherrington's law, strongly suggest that the abducens nerve is not necessarily absent or severely hypoplastic in this condition. One patient showed typical DRS in the contralateral eye and had a son with bilateral DRS, attesting to a possible genetic and etiologic relationship between SD and DRS. Three patients underwent strabismus surgery. Review of our surgical results and an analysis of the literature indicate that a crippling procedure to the ipsilateral lateral rectus muscle, such as extirpation, may be necessary to eliminate simultaneous abduction. Overcorrection did not occur following lateral rectus extirpation.

Adolescent↗

PubMedDate not supplied

Prevalence of uveitis in an outpatient juvenile arthritis clinic: onset of uveitis more than a decade after onset of arthritis.

PURPOSE: To determine the prevalence and severity of uveitis in an outpatient pediatric arthritis clinic in the midwestern United States during the 1990s. METHODS: The prevalence and clinical characteristics of uveitis were studied retrospectively for all children diagnosed with arthritis at Shriner's Hospital for Crippled Children and followed by the pediatric rheumatology and ophthalmology units of the St Louis Children's Hospital between 1992 and 1995. RESULTS: Seven children (9%) developed uveitis in a population of 78 patients with juvenile arthritis. Six of the seven children were female, and all six females had anti-nuclear antibody (ANA)-positive, juvenile rheumatoid arthritis (JRA). The prevalence of anterior uveitis in females with ANA-positive, pauciarticular JRA was 20%, and in polyarticular JRA, 17%. One of the girls with uveitis had combined JRA and sarcoidosis; the boy with uveitis had juvenile spondylitis. Arthritis preceded the onset of uveitis in each child by 1 to 13 years (average, 6.4 years). Progression of the uveitis in three of the children resulted in band keratopathy and cataract, causing significant visual loss in two (i.e., in 29% of the children who developed uveitis). CONCLUSION: The prevalence and ocular morbidity of uveitis in juvenile arthritis appears to have remained relatively stable over the last 2 decades. Onset of the uveitis in several of the children in our study population occurred more than a decade after the diagnosis of arthritis. Girls with ANA-positive JRA and boys with juvenile spondylitis may need to be followed by periodic slit-lamp examination for longer periods than recommended previously.

Adolescent↗

PubMed1997

[The chronological changes in the size of maxillary defect].

Use of a maxillary prosthesis is now considered one of the good methods to ameliorate the crippling caused by the defect in the maxillary palate area after an ablative procedure for a maxillary tumor and it consumes no physical resources from the patient. There has been debate on whether the prosthesis should be made in the very early postoperative days or after the wound is stabilized. In this study, changes in the area of the defect in the palate after surgery were investigated by using plaster models from clinical cases we have experienced. Twenty-one cases were investigated according to the following features: "maxillary sinus cancer "+" more than 1.5 years of follow-up for maxillofacial prosthetics "+" presence of more than two casts of the case". These casts were photographed from a distance of 1.5 m, and the photographs were enlarged to the original size of the cast, then the defect area was measured with a Planimeter (Uchida Co. Ltd). The area of the defect had shrunk in 16 cases. It took over 1 year to get stabilized in 80% of the cases. It is believed to take around 3.5 years for all cases to become stable. This tendency had no relationship with the pattern of the defect, the stroke of the mouth opening, the pattern of the rest of the teeth, or the defect area itself. These findings suggest that it may be advisable to start the prosthetic work as early as possible rather than waiting for stability of the defect wound, to improve the patients's QOL.

Adult↗

PubMed2001

The human endoplasmic reticulum molecular chaperone BiP is an autoantigen for rheumatoid arthritis and prevents the induction of experimental arthritis.

Rheumatoid arthritis (RA) is the most common, crippling human autoimmune disease. Using Western blotting and tandem mass spectroscopy, we have identified the endoplasmic reticulum chaperone BiP, a 78-kDa glucose-regulated protein, as a possible autoantigen. It preferentially stimulated increased proliferation of synovial T cells from patients with RA but not from patients with other arthritides. Mice with established collagen- or pristane-induced arthritis developed IgG Abs to BiP. Although BiP injected in CFA failed to induce arthritis in several strains of rats and mice, including HLA-DR4(+/-)- and HLA-DR1(+/+)-transgenic animals, it completely inhibited the development of arthritis when given i.v. 1 wk before the injection of type II collagen arthritis. Preimmunization with BiP suppressed the development of adjuvant arthritis in Lewis rats in a similar manner. This is the first report of a mammalian chaperone that is an autoantigen in human RA and in experimental arthritis and that can also prevent the induction of experimental arthritis. These findings may stimulate the development of new immunotherapies for the treatment of RA.

Adult↗

PubMed2001

Toxoplasma gondii tachyzoites inhibit proinflammatory cytokine induction in infected macrophages by preventing nuclear translocation of the transcription factor NF-kappa B.

Control of microbial infection requires regulated induction of NF-kappaB-dependent proinflammatory cytokines such as IL-12 and TNF-alpha. Activation of this important transcription factor is driven by phosphorylation-dependent degradation of the inhibitory IkappaB molecule, an event which enables NF-kappaB translocation from the cytoplasm to the nucleus. In this study, we show that intracellular infection of macrophages with the protozoan parasite Toxoplasma gondii induces rapid IkappaB phosphorylation and degradation. Nevertheless, NF-kappaB failed to translocate to the nucleus, enabling the parasite to invade cells without triggering proinflammatory cytokine induction. Infected cells subsequently subjected to LPS triggering were severely crippled in IL-12 and TNF-alpha production, a result of tachyzoite-induced blockade of NF-kappaB nuclear translocation. Our results are the first to demonstrate the ability of an intracellular protozoan to actively interfere with the NF-kappaB activation pathway in macrophages, an activity that may enable parasite survival within the host.

Active Transport, Cell Nucleus↗

PubMed2005

Staphylococcal protein a deletes B-1a and marginal zone B lymphocytes expressing human immunoglobulins: an immune evasion mechanism.

Protein A (SpA) of Staphylococcus aureus is endowed with the capacity to interact with the H chain variable region (V(H)) of human Abs and to target >40% of B lymphocytes. To investigate whether this property represents a virulence factor and to determine the in vivo consequences of the confrontation of SpA with B lymphocytes, we used transgenic mice expressing fully human Abs. We found that administration of soluble SpA reduces B-1a lymphocytes of the peritoneal cavity and marginal zone B lymphocytes of the spleen, resulting in a markedly deficient type 2 humoral response. Single-cell PCR analysis and sequencing of the Ab V(H) gene repertoire revealed a significant reduction of V(H)3+ marginal zone B cells. Since the two B lymphocyte subsets targeted are involved in innate immune functions, our data suggest that crippling of humoral immunity by S. aureus represents an immune evasion mechanism that may aggravate recurrent infections.

Animals↗