Subject: hormone/osteo/iron/arthritis

   
   Arthritis Rheum 1999 Apr;42(4):799-806
   
Elevated parathyroid hormone 44-68 and osteoarticular changes in patients with
genetic hemochromatosis.

    Pawlotsky Y, Le Dantec P, Moirand R, Guggenbuhl P, Jouanolle AM, Catheline
    M, Meadeb J, Brissot P, Deugnier Y, Chales G
    
   Centre Hospitalier et Universitaire, Rennes, France.
   
   OBJECTIVE: To determine whether the osteoarticular changes associated
   with genetic hemochromatosis could be explained by metabolic
   parathyroid hormone (PTH) disorders. METHODS: The study involved 210
   patients with liver iron overload syndromes. Osteoarticular changes
   were numerically scored as the number of damaged joints. PTH 1-84 and
   44-68 were assayed. RESULTS: An increase in serum PTH 44-68 levels was
   found in one-third of untreated patients who had no calcium or PTH
   1-84 abnormalities. Serum PTH 44-68 levels correlated positively with
   serum ferritin levels. In multivariate analyses, the number of
   affected joints correlated positively with age, serum PTH 44-68
   levels, and serum ferritin levels. CONCLUSION: Liver iron overload
   syndromes, especially genetic hemochromatosis, are associated with
   elevated circulating levels of PTH fragments containing the 44-68
   region, which appears to play a role in osteoarticular changes. This
   increase seems to be a consequence of iron overload.
   
   PMID: 10211896, UI: 99226878
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Subject: arthritis/iron

   
   Free Radic Res 1999 May;30(5):395-405
   
Aggrecan degradation in chondrocytes is mediated by reactive oxygen species and
protected by antioxidants.

    Tiku ML, Gupta S, Deshmukh DR
    
   Department of Medicine, UMDNJ-Robert Wood Johnson Medical School, New
   Brunswick, NJ 08903-0019, USA.
   
   Reactive oxygen species (ROS) are implicated in aging of cartilage and
   in the pathogenesis of osteoarthritis. However, the biological role of
   chondrocytes-derived ROS has not been elucidated. An in-vitro model
   was developed to study the role of chondrocyte-derived ROS in
   cartilage matrix degradation. The primary articular chondrocytes were
   cultured and the aggrecan matrix was radiolabeled with 35-sulfate. The
   labeled aggrecan matrix was washed to remove unincorporated label and
   chondrocytes were returned to serum free balanced salt solution. The
   cell-monolayer-matrix sensitivity to oxidative damage due to either
   hydrogen peroxide or glucose oxidase was established by monitoring the
   release of labeled aggrecan into the medium. Lipopolysaccharide (LPS)
   treatment of chondrocyte-monolayer enhanced the release of labeled
   aggrecan. Catalase significantly prevented the release of labeled
   aggrecan in LPS-chondrocyte cultures, suggesting a role for
   chondrocyte-derived hydrogen peroxide in aggrecan degradation.
   Superoxide dismutase or boiled catalase had no such inhibitory effect.
   The effect of several antioxidants on LPS-chondrocyte-dependent
   aggrecan degradation was examined. Hydroxyl radical scavengers
   (mannitol and thiourea) significantly decreased aggrecan degradation.
   A spin trapping agent N-tert-butyl-phenylnitrone (but not its inactive
   analog tert-butyl-phenylcarbonate) significantly decreased aggrecan
   degradation. Butylated hydroxytoluene also inhibited aggrecan
   degradation, whereas the other lipophilic antioxidant tested, propyl
   gallate, had a marked dose-dependent inhibitory effect. These data
   indicate that general antioxidants, hydroxyl radical scavengers,
   antioxidant vitamins, iron chelating agents, lipophilic antioxidants,
   and spin trapping agents can influence chondrocyte-dependent aggrecan
   degradation. These studies support the role of a chondrocyte-dependent
   oxidative mechanism in aggrecan degradation and indicate that
   antioxidants can prevent matrix degradation and therefore may have a
   preventive or therapeutic value in arthritis. The enhancement of
   oxidative activity in chondrocytes and its damaging effect on matrix
   may be an important mechanism of matrix degradation in osteoarthritis.
   
   PMID: 10342332, UI: 99271760
     _________________________________________________________________
   
   Clin Orthop 1998 Apr;(349):108-15
   
Hemochromatosis of the foot and ankle. Report of three cases and review of the
literature.

    Bailey EJ, Gardner AB
    
   Emory University School of Medicine, Atlanta, GA 30322, USA.
   
   Genetic hemochromatosis is a disorder of iron metabolism that results
   in deposition of massive amounts of iron in the tissues. Arthropathy
   is one of numerous clinical manifestations associated with this
   disease. Characteristic radiographic features have been reported in
   the hand and wrist, and the hip; however, there is no mention in the
   literature of joint manifestations in the foot and ankle. In this
   report, the authors present three patients with hemochromatosis
   arthropathy of the foot and ankle. Two patients presented primarily
   with foot pain and were treated initially with orthoses. One of these
   patients went on to have to midfoot arthrodesis performed. The third
   patient presented with ankle joint symptoms, and was treated
   successfully with an ankle foot orthosis. The arthritis of
   hemochromatosis has classic radiographic findings. However, the
   arthritis of hemochromatosis may be difficult to differentiate from
   several other joint diseases. Characteristic features of this disease
   in the foot and ankle are discussed.
   
   Publication Types:
     * Review
     * Review literature
       
   PMID: 9584373, UI: 98245352
     _________________________________________________________________


Subject: arthritis/chelator

   
   Ann Rheum Dis 1989 May;48(5):382-8
   
Investigation of the anti-inflammatory properties of hydroxypyridinones.

    Hewitt SD, Hider RC, Sarpong P, Morris CJ, Blake DR
    
   Cancer Research Unit, University of York, Heslington.
   
   Synovial iron deposition associated with rheumatoid disease may result
   in the production of highly reactive oxygen free radicals, leading to
   tissue damage. This chain of events can be interrupted by iron
   chelation. Families of strong iron (III) chelators have been tested
   for their iron scavenging properties in vitro and their effects
   assessed in vivo using a rat model of inflammation. All the chelators
   competed successfully for iron with apotransferrin, and some removed
   up to 34% of iron from ferritin. The best anti-inflammatory effects
   were achieved with the most hydrophilic chelators and those which
   chelated iron most avidly. Activity was dependent on dose. The route
   of administration was also an important factor with lower affinity
   chelators. This work introduces a range of simple bidentate iron
   chelators, which under certain conditions exceed desferrioxamine in
   their iron scavenging abilities, and some of which, in this simple
   animal model, approach indomethacin in their anti-inflammatory
   capabilities.
   
   Comments:
     * Comment in: Ann Rheum Dis 1990 Nov;49(11):956-7
       
   PMID: 2730166, UI: 89272259
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Subject: bacteria/iron

   
   Clin Microbiol Rev 1996 Oct;9(4):435-447
   
Mycobacterium haemophilum: microbiology and expanding clinical and geographic
spectra of disease in humans.

    Saubolle MA, Kiehn TE, White MH, Rudinsky MF, Armstrong D
    
   Department of Pathology, Good Samaritan Regional Medical Center,
   Phoenix, Arizona 85006, USA.
   
   Reports of the association of Mycobacterium haemophilum with disease
   in humans have greatly increased. At least 64 cases have now bee (HOME) n
   reported, with symptoms ranging from focal lesions to widespread,
   systemic disease. The organism is now known to cause primarily
   cutaneous and subcutaneous infection, septic arthritis, osteomyelitis,
   and pneumonitis in patients who are immunologically compromised and
   lymphadenitis in apparently immunocompetent children. Underlying
   conditions in the compromised patients have included AIDS; renal, bone
   marrow, and cardiac transplantation; lymphoma; rheumatoid arthritis;
   marrow hypoplasia; and Crohn's disease. Reports have originated from
   diverse geographic areas worldwide. The epidemiology of M. haemophilum
   remains poorly defined; there appears to be a genetic diversity
   between strains isolated from different regions. The organism is
   probably present in the environment, but recovery by sampling has not
   been successful. M. haemophilum has several unique traits, including
   predilection for lower temperatures (30 to 32 degrees C) and
   requirement for iron supplementation (ferric ammonium citrate or
   hemin). These may in the past have compromised recovery in the
   laboratory. Therapy has not been well elucidated, and the outcome
   appears to be influenced by the patient's underlying
   immunosuppression. The organisms are most susceptible to
   ciprofloxacin, clarithromycin, rifabutin, and rifampin. Timely
   diagnosis and therapy require communication between clinician and the
   laboratory.
   
   Publication Types:
     * Review
     * Review, academic
       
   PMID: 8894345, UI: 97049617
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 Subject: Ovid Citations


Arthropathy article

Arthritis & Rheumatism
American College of Rheumatology

Musculoskeletal Disorders and Iron Overload Disease: Comment on the American
College of Rheumatology Guidelines for the Initial Evaluation of the Adult
Patient with Acute Musculoskeletal Symptoms
[Letter]
Vasquez, Alex DC
Seattle, WA
Outline

REFERENCES

----------------------------------------------

Musculoskeletal disorders and iron overload disease: comment on the American
College of Rheumatology guidelines for the initial evaluation of the adult
patient with acute musculoskeletal symptoms.

To the Editor:

The recent clinical guidelines for the initial evaluation of the adult
patient
with acute musculoskeletal symptoms, proposed by the American College of
Rheumatology ([1]), provide useful information and a good review for
clinicians. However, there is one important omission in these guidelines.
Nowhere in the guidelines is hemochromatosis mentioned. Such a prevalent and
potentially
life-threatening disease certainly deserves to be considered in the
evaluation of patients with musculoskeletal disorders.

Hereditary hemochromatosis is now thought to be the most common genetic
disorder in the white population ([2]). Approximately 1 in 250 persons is
homozygous for
this disorder and will develop the characteristic clinical manifestations
such as diabetes, cardiomyopathy, liver disease, endocrine dysfunction, and,
most notable for this discussion, arthropathy or other musculoskeletal
disorders ([2]). Although hereditary iron overload disorders have
traditionally been thought of as occurring exclusively in whites, recent
research by Barton et al
([3]) indicates that approximately 1 in 67 African-Americans is affected by
an etiologically distinct and severe form of iron overload. Hereditary iron
overload disorders have been detected in persons of every ethnic background.

Arthropathy affects up to 80% of iron-overloaded patients and is often the
only manifestation of this disease ([4]). Joint pain is a common and early
symptom of iron overload, and "bone pain" has also been described as a
common initial complaint ([5]). Clinically and radiographically,
hemochromatoic arthropathy can
resemble osteoarthritis, calcium pyrophosphate dihydrate deposition disease,
pseudogout, rheumatoid arthritis, ankylosing spondylitis, or generalized
osteopenia with osteoporotic fractures ([4,6,7]). Since iron overload can
cause such a wide array of musculoskeletal manifestations and because
definitive
clinical differentiation of iron overload from other arthropathies is very
difficult, patients with peripheral arthropathy should be screened for iron
overload. Indeed, recent research by Olynyk et al ([8]) indicates that the
prevalence of iron overload is 5 times higher in patients with peripheral
arthropathy than in the general population. Therefore, screening of patients
with peripheral arthropathy for the possible presence of iron overload is
justified.

Thus, since iron overload affects such a large portion of the population and
arthropathy is a common manifestation of this disorder, patients with
musculoskeletal symptoms should be screened for iron overload ([4,8]). The
current literature suggests that everyone should be screened for iron
overload even if there are no symptoms ([8-10]).

Alex Vasquez, DC

Seattle, WA

REFERENCES

1. American College of Rheumatology Ad Hoc Committee on Clinical Guidelines:
Guidelines for the initial evaluation of the adult patient with acute
musculoskeletal symptoms. Arthritis Rheum 39:1-8, 1996

2. Olynyk JK, Bacon BR: Hereditary hemochromatosis: detecting and correcting
iron overload. Postgrad Med 96:151-165, 1994  [Medline Link]

3. Barton JC, Edwards CQ, Bertoli LF, Shroyer TW, Hudson SL: Iron overload
in African Americans. Am J Med 99:616-623, 1995  [Medline Link]

4. Faraawi R, Harth M, Kertesz A, Bell D: Arthritis in hemochromatosis. J
Rheumatol 20:448-452, 1993  [Medline Link]

5. Adams PC, Kertesz AE, Valberg LS: Clinical presentation of
hemochromatosis: a changing scene. Am J Med 90:445-449, 1991  [Medline Link]

6. Bywaters EGL, Hamilton EBD, Williams R: The spine in idiopathic
hemochromatosis. Ann Rheum Dis 30:453-465, 1971  [Medline Link]

7. Eyres KS, McCloskey EV, Fern ED, Rogers S, Beneton M, Aaron JE, Kanis JA:
Osteoporotic fractures: an unusual presentation of hemochromatosis, Bone
13:431-433, 1992

8. Olynyk J, Hall P, Ahern M, Kwiatek R, Mackinnon M: Screening for
hemochromatosis in a rheumatology clinic. Aust N Z J Med 24:22-25, 1994
[Medline Link]

9. Baer DM, Simmons JL, Staples RL, Runmore GJ, Morton CJ: Hemochromatosis
screening in asymptomatic ambulatory men 30 years of age and older. Am J Med
98:464-468, 1995  [Medline Link]

10. Adams PC, Gregor JC, Kertesz AE, Valberg LS: Screening blood donors for
hereditary hemochromatosis: decision analysis model based on a 30-year
database.
Gastroenterology 109:177-188, 1995  [Medline Link]


[INLINE] TEKTRAN
     _________________________________________________________________
   
IRON DEPOSITION IN THE JOINTS OF CHILDREN WITH JUVENILE RHEUMATOID ARTHRITIS

   Author(s): 
          SHYPAILO ROMAN J
          ELLIS KENNETH J
          PEREZ MARIA
          ABRAMS STEVEN A
          
   Interpretive Summary: 
          We wanted to develop an accurate and noninvasive way of
          determining the amount of iron deposited in the joints of
          patients with juvenile rheumatoid arthritis. Children with JRA
          often develop excess iron in their joints, so doctors need a
          way of monitoring the iron level, particularly when prescribing
          iron supplements for the common problem of anemia. However, the
          only method currently available is to take a biopsy. We adapted
          a machine called a gamma counter to measure the iron in eight
          patients' joints after giving them an iron isotope by vein.
          Then we compared the results with the total amount of iron in
          their bodies, measured by a whole-body counter. We found that
          we had developed an accurate new way of measuring iron in these
          patients' joints. We also found that six of the eight subjects
          had excess uptake of the iron isotope in their joints. That
          provided a signal that a preponderance of JRA patients are
          prone to have this problem, and clinicians should take special
          care to monitor them for it. Moreover, this is the first time a
          noninvasive way of performing this measurement has been
          available.
          
   Keywords: 
          energy reproduction growth body composition women infants
          children water potassium bioelectrical impedance conductance
          bromide space lactating iron adipose tissue lipid motabolism
          beta-adrenergic receptor cell culture neutron activation
          nitrogen carbon calcium sodium chlorine phosphorus hormonal
          changes differentiation adipocyte hnrim021125
          
   Contact: 
          USDA/ARS CHILDREN'S NUTR
          1100 BATES ST.
          HOUSTON
          TX 77030
          FAX: (713)798-7130
          Email: kellis@bcm.tmc.edu
          
   Approved Date: 1999-01-07
   ______________________________________________________________________
   
   
    TEKTRAN
    United States Department of Agriculture
    Agricultural Research Service
    
   Updated: 1999-01-16

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