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ID PMID Title PublicationDate abstract
9662754 Alpha-interferon-induced arthritis: clinical presentation treatment, and prevention. 1998 Jun OBJECTIVE: The therapeutic applications of alpha-interferon (IFN) have expanded greatly to include chronic viral hepatitis and malignant disorders. Autoimmune phenomena occur frequently with IFN therapy, but arthritis is uncommon. We describe the clinical features and treatment of IFN-induced arthritis. METHODS: A patient with chronic myelogenous leukemia who developed arthritis secondary to IFN therapy is presented. The clinical features and treatment of this condition in 37 additional cases are reviewed. RESULTS: The most common clinical presentation was symmetric polyarthritis. This was associated with antinuclear antibodies in 72% of patients and rheumatoid factor in 34%. Cessation of IFN, with or without the addition of antiinflammatory or remittive agents, resulted in remission of arthritis in 89% and 71% of the cases, respectively. Restarting IFN therapy resulted in recurrence of arthritis in 63%. In the patient described in this report, recurrence of arthritis was prevented by coadministration of hydroxychloroquine (HCQ) and prednisone. CONCLUSION: Arthritis is an uncommon complication of IFN therapy; but it may lead to cessation of this treatment modality. In such cases, coadministration of a remittive agent such as HCQ may enable reinstitution of IFN therapy without recurrence of arthritis.
10798602 Stem cell transplantation in experimental models of autoimmune disease. 2000 Jan A review of the experiments with animal models of autoimmune disease (AID) that have provided the rationale for the present clinical investigations on the use of autologous stem cells for treating patients with severe refractory AID. The various types of AID in laboratory animals and the recognition of the key-role of hematopoietic stem cells (HSC) in AID are discussed. Two animal models were employed for translational research on autologous bone marrow transplantation (BMT): adjuvant arthritis (AA) as model for rheumatoid arthritis (RA) and experimental allergic encephalomyelitis (EAE) as model for multiple sclerosis (MS). The principal aspects of the treatment, i.e., conditioning agents and doses and T cell depletion of the autograft, were investigated in relation to remission induction and the incidence of relapses.
10673451 Sweet's syndrome (acute febrile neutrophilic dermatosis). 1999 May Sweet's syndrome, or acute febrile neutrophilic dermatosis, is a condition characterized by the sudden onset of fever, leukocytosis, and tender,erythematous, well-demarcated papules and plaques which show dense neutrophilic infiltrates on histologic examination. Although it ma occur in the absence of other known disease, Sweet's syndrome is often associated with hematologic disease (including leukemia), and immunologic disease (rheumatoid arthritis, inflammatory bowel disease). Treatment with systemic corticosteroids is usually successful. skin, Sweet syndrome, neutrophilic dermatosis, corticosteroids,
17039102 Spontaneous abdominal hemorrhage with AA-amyloidosis and vasculitis in a patient with rheu 2001 Apr Both rheumatoid vasculitis and amyloidosis in rheumatoid arthritis (RA) are uncommon. We describe a patient in whom they occurred together and were associated with fatal intra-abdominal hemorrhage. A 56-year-old Caucasian woman was referred because of increasing lethargy, edema, and proteinuria. She had suffered from seropositive, erosive, nodular RA for 14 years. Previously, she had undergone numerous joint replacements, a thyroidectomy for amyloid-associated (AA) amyloidosis of the thyroid that caused a large goiter and a renal biopsy that showed renal AA-amyloidosis in the context of nephrotic syndrome. As her condition deteriorated, this patient became increasingly reluctant to go to the hospital and to take drugs beyond analgesics. Thus, her RA was chronically under treated. While in the hospital for evaluation, this patient suddenly developed hypotension, tachycardia, and a severe colicky left-sided abdominal pain radiating from the left upper quadrant/epigastric region to the left iliac fossa. Computed tomography (CT) showed a large amount of echogenic free fluid within the abdomen and marked thickening of the omentum. At laparotomy, 2 liters of free blood was found adjacent to a hematoma of the greater omentum, and it was evacuated without identification of a discrete bleeding point. All solid and hollow organs were normal. The omentum was noted to be very friable. She developed a more disseminated bleeding diathesis and persistent peritoneal hemorrhage via her abdominal drains. She succumbed shortly afterward. Histology revealed extensive omental hemorrhage and one large vessel within the area of hemorrhage showed a severe necrotizing vasculitis. Extensive amyloid deposition was also found within the walls of the smaller omental arterioles. Vasculitis in the context of RA is relatively rare and is associated with under treated, seropositive disease. Skin and nerve involvement are most common, but bowel involvement has been reported, with a highly significant morbidity (partly due to late presentation/recognition). Similarly, AA-amyloidosis is a rare but feared long-term concomitant of under treated RA. Early recognition can permit successful anti-inflammatory therapy to affect a clinical and pathological remission; continued inflammatory stimulation is associated with rapid progression and demise. Chronically under treated patients with RA are more prone to rare but potentially devastating complications. Gastrointestinal catastrophes are a feature of both rheumatoid vasculitis and of amyloidosis, here uniquely co-localized.
28246978 Short- and mid-term results with the STAR total ankle prosthesis. 1999 Sep We evaluated the short- to mid-term results of an unconstrained total ankle prosthesis (S. T. A. R.) with uncemented fixation. Fifty consecutive ankle replacements were performed in 48 patients between 1996 and 1999. The initial diagnosis was posttraumatic osteoarthrosis in 31 cases (62 %), primary osteoarthrosis in 8 cases (16 %), and systemic joint affection in 11 cases (22 %), e. g. rheumatoid arthritis (6 cases), hemochromatosis (2 cases), psoriasis arthritis (1 case), lupus erythematodes (1 case), and sclerodermia (1 case). There were two perioperative complications: one superficial wound dehiscence that healed uneventfully, and one injury to the dorsal foot artery that necessitated primary reconstruction. Seven revisions, all in cases of posttraumatic arthrosis, were necessary: local revision of the fibula for painful lateral impingement (3 cases), posteromedial soft tissue revision for painful restriction of dorsiflexion (2 cases), percutaneous lengthening of the Achilles tendon (1 case), and osteotomy and callus distraction for angular correction after stress fracture of the distal tibia (1 case). At the last follow-up control, 21 patients (62 %) were very satisfied, 10 patients (29 %) were satisfied, and 3 patients (9 %) were satisfied with reservations. The obtained range of motion was 30 ° (range, 15 to 55 °), with a maximal plantarflexion of 25 ° (range, 15 to 45 °) and dorsiflexion of 5 ° (-3 to 20 °). When the AOFAS-Hindfoot-Score was applied, the 34 patients scored 84.1 points (range, 44 to 100 points). After settling of the implants within 6 weeks, no migration was noted in any case, and all implants were considered to be stable. The favorable results were considered to be a result of the mechanical properties of the S. T. A. R. total ankle prosthesis that allows for unconstrained motion of the polyethylene inlay on the tibial component, e. g. anteroposterior translation, mediolateral translation and axial rotation. The success of implantation may depend on exact technique, correct hindfoot alignement, sufficient capsuloligamentous stability of the ankle, and a solid bone stock. Although our first results are very encouraging, a longer follow-up is mandatory to answer the question whether ankle replacement is a viable alternative to ankle arthrodesis.
17984879 Further observations regarding the treatment of the radio-ulnar joint in patients with rhe 2000 Dec 30 The aim of this study was to evaluate the late outcome of synovectomy with different resections of the caput of the ulnar bone. Resection of the ulnar caput causes considerable displacement of the ulna in the radial direction. The degree of ulnar displacement and reduced height of the carpus depends more on the rheumatoid process than on surgical procedure. After 10 years or more, degenerative changes begin to develop in most cases more intensively in the distal radio-ulnar region.
10761518 [Mycobacterium xenopi osteoarthritis of the ankle in a patient followed for psoriatic rheu 2000 Mar 18 BACKGROUND: Mycobacterium xenopi is an uncommon cause of osteoarticular sepsis. However, a recent series of M. xenopi spondylodiscitis emphasizes the potential risk after invasive procedures. CASE REPORT: A 33-year-old woman was followed for psoriasis rheumatoid arthritis. She had undergone several exploratory procedures including arthroscopy of the left ankle for invalidating joint disease. In 1999, M. xenopi arthritis and osteomyelitis was diagnosis in this joint. DISCUSSION: Sterilization and maintenance of surgical instruments must abide by rigorously controlled strict protocols. The benefit/risk ratio of invasive procedures in debilitated joints should be more precisely evaluated. Specific and repeated sample cultures should be performed to search for mycobacteria in all bone and joint infections, particularly in case of prior invasive procedures.
9676907 Immunologic and clinical evaluation of postsurgical necrotizing sclerocorneal ulceration. 1998 Jul PURPOSE: To perform a clinical, laboratory and pathologic evaluation in patients who had developed a postsurgical necrotizing sclerocorneal ulceration to detect a serious associated autoimmune disorder and to treat the ocular disease early. METHODS: Nine patients with postsurgical necrotizing sclerocorneal ulceration after uneventful cataract extraction were studied by means of immunohistochemical techniques on conjunctival resections, immunologic serologic studies, and rheumatologic evaluation. Nine healthy subjects who underwent uneventful cataract surgery were used as controls. RESULTS: The pathologic studies showed a local immunoglobulin M (IgM) and IgG deposition, increased human leukocyte antigen (HLA-DR) expression, and a significant T-helper cell participation in conjunctival biopsies in the most severe ulcerations, which were detected in four patients with underlying autoimmune systemic disorder (rheumatoid arthritis, 45%) and only a macrophagic infiltration in the mildest ulcers in patients (55%) without immune disorders. Serologic features included high titers of rheumatoid factor in the four (45%) patients with rheumatoid arthritis, nonspecific serologic immune alteration in three (33%) patients, and were unremarkable in two (22%) patients. The medical and immunologic evaluations were negative in the control cases. Topically administered cyclosporin A healed the ocular disease. CONCLUSION: A surgically induced local autoimmune reaction could occur in the incision area in patients with systemic vasculitic disease. There was no underlying systemic disorder in the mildest ulcers, and these ulcers could be due to a defect in the surgical technique. Our results suggest the need for a detailed systemic evaluation in patients with severe postsurgical necrotizing ulceration. Early diagnosis and aggressive medical treatment of the ocular disorder improves the visual outcome.
11207399 Bee venom injection into an acupuncture point reduces arthritis associated edema and nocic 2001 Feb 15 Bee venom (BV) has traditionally been used in Oriental medicine to relieve pain and to treat inflammatory diseases such as rheumatoid arthritis (RA). While several investigators have evaluated the anti-inflammatory effect of BV treatment, the anti-nociceptive effect of BV treatment on inflammatory pain has not been examined. Previous studies in experimental animals suggest that the therapeutic effect of BV on arthritis is dependent on the site of administration. Because of this potential site specificity, the present study was designed to evaluate the anti-nociceptive effect of BV injections into a specific acupoint (Zusanli) compared to a non-acupoint in an animal model of chronic arthritis. Subcutaneous BV treatment (1 mg/kg per day) was found to dramatically inhibit paw edema caused by Freund's adjuvant injection. Furthermore, BV therapy significantly reduced arthritis-induced nociceptive behaviors (i.e. the nociceptive scores for mechanical hyperalgesia and thermal hyperalgesia). These anti-nociceptive/anti-inflammatory effects of BV were observed from 12 days through 21 days post-BV treatment. In addition, BV treatment significantly suppressed adjuvant-induced Fos expression in the lumbar spinal cord at 3 weeks post-adjuvant injection. Finally, injection of BV into the Zusanli acupoint resulted in a significantly greater analgesic effect on arthritic pain as compared to BV injection in to a more distant non-acupoint. The present study demonstrates that BV injection into the Zusanli acupoint has both anti-inflammatory and anti-nociceptive effects on Freund's adjuvant-induced arthritis in rats. These findings raise the possibility that BV acupuncture may be a promising alternative medicine therapy for the long-term treatment of rheumatoid arthritis.
9690855 Effect of the peripherally selective kappa-opioid agonist, asimadoline, on adjuvant arthri 1998 Jun 1. Opioids, though widely used as analgesics, have not been seriously considered as therapy for rheumatoid arthritis. The present study evaluated the dose-effect and time-dependence relationships of a new peripherally selective kappa agonist, asimadoline, in rats with adjuvant arthritis. 2. The arthritis was assessed by a pooled severity index combining the comprehensive criteria of oedema, radiography and histological changes, in the hind limbs. Asimadoline was extremely effective in attenuating joint damage (by up to 80%) when administered parenterally (0.5 to 10 mg kg(-1) day(-1), i.p.) throughout the disease or during its early phase; treatment was less successful if confined to the latter stages. Ten fold higher doses were effective orally. 3. Equimolar doses of a peripherally-selective antagonist, naloxone methiodide, and the kappa-selective antagonist, MR2266, fully reversed the peripheral anti-arthritic effects of asimadoline (5 mg kg(-1) day(-1)), indicating that asimadoline acts through peripheral kappa-opioid receptors. However, an equivalent dose of MR2266 did not fully reverse the anti-arthritic effects of the highest dose of asimadoline (40 mg kg(-1) day(-1)), suggesting a loss of kappa-selectivity at this dose. 4. Asimadoline also exhibited analgesic effects (mechanical nociceptive thresholds) in arthritic but not non-arthritic rats, indicating that inflammation is necessary for asimadoline-induced analgesia. 5. These data confirm our previous findings that kappa-opioids possess anti-arthritic properties and that these effects are mediated via peripheral kappa-receptors. The present results are new in showing that the peripherally acting kappa-opioid agonist, asimadoline, is a potent anti-arthritic agent. Such novel drugs, essentially lacking central side effects, herald new treatments for rheumatoid arthritis.
27645003 Juvenile rheumatoid arthritis: A clinical approach and pharmacological management. 1999 Nov Full text is available as a scanned copy of the original print version.
18020527 High dose intravenous immunoglobulin in autoimmune rheumatic disorders. 1997 Nov Since the effectiveness of high dose intravenous immunoglobulin (IVIg) was first demonstrated in autoimmune thrombocytopenia, IVIg has been investigated in the treatment of various autoimmune rheumatic disorders. Controlled randomised studies have established the efficacy of IVIg in Kawasaki's syndrome, for which combined IVIg and aspirin (acetylsalicylic acid) now constitutes the standard treatment. Another controlled study has demonstrated the benefit of IVIg in dermatomyositis. IVIg treatment in juvenile rheumatoid arthritis has produced contradictory results. Uncontrolled studies and case reports on the application of IVIg in systemic lupus erythematosus, ANCA-associated vasculitides and adult rheumatoid arthritis generally describe short term positive effects. Various mechanisms are thought to underlie the effect of IVIg on autoimmune rheumatic diseases, such as: blockade of Fc receptors;immunomodulation via anti-idiotypic interactions;inhibition of complement-mediated tissue damage;modulation of cytokine expression by leucocytes and endothelial cells; andinhibition of superantigen-mediated T cell activation. IVIg is considered to be a low-risk form of treatment. Reported adverse effects include headache, aseptic meningitis and transient impairment of renal function. Haemolysis and anaphylactic reactions are rare. The effect profile of IVIg makes it a relevant, although still experimental, form of treatment in autoimmune rheumatic disorders, but its high cost renders it unsuitable as a first-line treatment. Because IVIg does not weaken patients' resistance to infection, it might serve as a therapeutic option in bridging clinical situations where immunosuppressive or cytotoxic approaches are contraindicated in patients with autoimmune disorders, such as intercurrent infection or in the period immediately before and after surgery.
17638136 Rheumatoid arthritis antirheumatic drug trials: effects of a standardized instructional vi 1997 AIMS: A study was designed to assess the effects of a standardized instructional videotape on reducing interobserver variability for several commonly used observer-dependent outcome measures. METHODS: During a single day, six rheumatologists independently examined six patients with rheumatoid arthritis (RA) in a predetermined order using a Latin square design, before and after viewing a standardized videotape demonstrating 13 examination techniques. Reliability coefficients were calculated based on the variance components of the analysis of variance (ANOVA) table. RESULTS: Prestandardization reliability coefficients were >0.80 for all measures and remained above 0.80 following standardization. CONCLUSIONS: It is usually assumed that serial measurement in clinical trials should be performed by the same assessor because of concern regarding interobserver variability. However, the high levels of prestandardization interobserver reliability observed in this study indicate that, for these variables, serial measurements in a clinical trial could be made by different assessors, assuming they were equally skilled. This observation has important implications for outcome measurement in RA clinical trials. Although high levels of prestandardization reliability precluded the demonstration of any significant effect, we speculate that the videotape might be effective in training less-experienced assessors. Reductions in observer variability have the potential to diminish sample size requirements for RA antirheumatic drug studies. The use of a videotape to achieve this goal offers cost and convenience advantages over one-on-one training procedures, and this method should be further assessed in less-experienced assessors.
18597154 An evaluation of the effectiveness of a videotape programme on interobserver reliability i 1999 AIMS: A study was designed to assess the effects of a standardized instructional videotape on training senior medical students to acceptable levels of reliability in performing several commonly used observer dependent outcome measures in patients with rheumatoid arthritis (RA). METHODS: During a single day, six third-year medical students independently examined six patients with RA in predetermined order using a Latin Square design, before and after viewing a standardized videotape demonstrating 15 examination techniques. Reliability coefficients were calculated based on the variance components of the analysis of variance (ANOVA) table. RESULTS: Prestandardization reliability coefficients were >0.80 for all measures and remained above 0.80 following standardization except for one measure. CONCLUSIONS: High levels of interobserver agreement were noted prior to viewing the instructional videotape. This may represent the success of undergraduate clinical skills training programmes or it may be me result of the students having reviewed an illustrated instructional text just prior to the initial patient examinations. High levels of prestandardization reliability, by necessity, precluded the demonstration of significant effects from viewing the videotape. Nevertheless, the data indicate that senior medical students are capable of reliably performing quantitative measurement in RA. Recent surveys in Canada and Australia, showing a general lack of quantitative clinical measurement in the longitudinal follow up of RA outpatients by rheumatologists, suggest that the lack of standardization is not due to inability to reliably perform the measurements.
12687096 Clinico-Immunologic Peculiarities of Different Forms of Rheumatoid Arthritis. 1998 Jul The problem of searching different immunologic, clinical and laboratory signs and parameters characterizing evaluation of the rheumatoid arthritis (RA) and the early prognosis of its outcome cause interest to studying peculiarities of immunologic status and changes of some serologic markers in different RA forms. The comparison of clinico-immunologic data in seropositive and seronegative patients revealed the most pronounced changes in patients with extraarticular manifestations (EAM), positive to IgM-RF. In this case the direct correlation with RA severity was seen in the both RA forms. The comparison analysis of the data obtained revealed the most pronounced changes in seropositive patients with EAM. This allowed us to consider this RA variant as the most unfavorable. EAM RA together with progression of articular process provided the RA severity and could cause patients' lethality. In seronegative RA form the level of ESR, CIC, Abs to nucleic acids enabled to stipulate the articular form (AF) as the most unfavorable that was accompanied with the most rapid progression of destruction events. One of the heights levels of anticardiolipin antibodies (aCL) and factor VIII-related von Willebrand polymers (factor VIII:vWF) were associated with EAM. Additionally, the indices' shifts were increased in seronegative RA that corresponded to vascular disturbances. The RA activity correlated with quantitative and/or qualitative parameters of CD3, CD4, CD8 lymphocytes, IgM-RF and immunoglobulins. Thus, the present study revealed two forms of RA associated with rapid development of articular destruction and extraarticular complications: seropositive EAM and seronegative AF forms. Additionally, the association of elevated aCL, and factor VIII:vWF with development of different EAM in RA in the both RA forms was found out.
9218084 The absorption of low-dose methotrexate in patients with inflammatory bowel disease. 1997 Jun BACKGROUND: Recent clinical trials have demonstrated that methotrexate may have an important therapeutic role in the treatment of patients with inflammatory bowel disease, who are either refractory or intolerant to traditional medical therapy. The aim of this study was to evaluate the pharmacokinetics of low-dose oral methotrexate in patients with inflammatory bowel disease. METHODS: Methotrexate (12.5 mg) was given orally to nine patients with inflammatory bowel disease: five with Crohn's disease, and four with ulcerative colitis, and to six patients with rheumatoid arthritis who served as a control group. Blood samples were drawn at specific intervals to evaluate methotrexate plasma levels. RESULTS: Methotrexate was rapidly absorbed in all patients. Peak concentrations (Cmax) varied considerably, ranging from 0.25-0.87 micro M. The mean Cmax values were similar in all patient groups (0.59 +/- 0.12, 0.69 +/- 0.16 and 0.54 +/- 0.18 micro M, P not significant) for Crohn's disease, ulcerative colitis and rheumatoid arthritis, respectively. The mean area under curve in 120 min (AUC0-120) was also similar in all patient groups (32.9 + 11.3, 43.6 + 9.9 and 41.8 + 14.9 ng.min/mL, P not significant) for Crohn's disease, ulcerative colitis and rheumatoid arthritis, respectively. The mean time to reach Cmax, (tmax), varied between patient groups (84, 112 and 95 min, respectively, with a significant difference, P < 0.02, between the Crohn's disease and ulcerative colitis groups. A negative correlation was found between methotrexate dosage/kg and Cmax (r = -0.74) only in Crohn's disease patients but not in the other patient groups. CONCLUSIONS: Orally administered methotrexate is well absorbed in patients with inflammatory bowel disease including those with severe small bowel disease or resection. If methotrexate is proven to be effective in inflammatory bowel disease, it should be administered orally.
9350035 Salubrious effect of Semecarpus anacardium against lipid peroxidative changes in adjuvant 1997 Oct Oxygen derived free radicals are known to play an important role in the etiology of tissue injury in rheumatoid arthritis. The effect of milk extract of Semecarpus anacardium nuts at the dose level of 150 mg/kg body weight for 14 days on adjuvant arthritis was studied for gaining insight into the intrigue disease in relation to the lipid peroxidation and antioxidant defence system. Increased lipid peroxides' levels in both plasma and tissues (liver, kidney and heart) of adjuvant arthritis was significantly decreased by the administration of the drug. The antioxidant defence system studied in tissues of arthritic animals were altered significantly as evidenced by the decreased level of non-enzymatic antioxidants (GSH, vitamin E, vitamin C, NPSH and TSH) and enzymatic antioxidants (catalase and GPx except SOD). Administration of Semecarpus anacardium nut extract brings back the altered antioxidant defence components to near normal levels. These observations suggest that the diseased state of adjuvant arthritis may be associated with augmented lipid peroxidation and the administration of the drug may exert its antiarthritic effect by retarding lipid peroxidation and causing a modulation in cellular antioxidant defence system.
18597156 Elevated urinary nitrite and citrulline levels in patients with rheumatoid arthritis. 1999 The objective of this research was to determine, if NO production, as measured in the serum and urine, is increased in patients with rheumatoid arthritis. Forty-seven patients with RA were recruited in the study and subdivided into inactive and active disease (24 and 23 patients, respectively). Twenty-eight healthy individuals served as controls and nine patients with gastroenteritis were studied to validate the technique of measurement of NO production. Nitrite and citrulline were measured by spectrophotometry, as surrogate markers of NO production. It was found that serum nitrite and citrulline levels of patients with gastroenteritis were not significantly different from controls and the two subgroups of RA. Urine nitrite and citrulline levels were significantly higher in patients with gastroenteritis as compared to the two subgroups of RA and controls (p > 0.001). Serum and urine nitrite levels of patients with active RA were higher than controls and patients with inactive disease (p > 0.05). Serum citrulline levels were not significantly different among the two subgroups of patients with RA. However, they were significantly higher in patients with active disease as compared with controls (p > 0.05). Urinary citrulline levels were significantly higher among patients with active disease as compared to controls and patients with inactive RA (p > 0.05). It is therefore suggested that urinary nitrite and citrulline levels can be useful for the measurement of NO production and are associated with active disease in patients with RA.
9755705 Functional MR imaging of the cervical spine in patients with rheumatoid arthritis. 1998 Sep PURPOSE: To evaluate functional MR imaging in patients with rheumatoid arthritis (RA) involving the cervical spine. MATERIAL AND METHODS: We used a device that allows MR examination to be made of the cervical spine in infinitely variable degrees of flexion and extension. Dynamic functional MR imaging was performed on 25 patients with RA. RESULTS: Functional MR imaging was able to show the degree of vertebral instability of the occipito-atlantal or atlanto-axial level as well as the subaxial level. By performing functional MR imaging, we were able to demonstrate the extent of synovial tissue around the dens, and the impingement and displacement of the spinal cord during flexion and extension. The basilar impression, the cord impingement into the foramen magnum, the cord compression, the slipping of vertebrae, and the angulation of the cord were all much more evident in functional than in static MR imaging. CONCLUSION: Functional MR imaging provided additional information in patients with RA, and is valuable in patients who have a normal MR study in the neutral position and yet have signs of a neurological deficit. Functional MR imaging is important in the planning of stabilizing operations of the cervical spine.
10503812 Cyclosporin pharmacokinetics in the elderly. 1999 Sep Cyclosporin is an immunosuppressant used in organ transplantation and selected autoimmune diseases such as rheumatoid arthritis. In both these indications, the elderly represent an important and growing segment of the patient population. Cyclosporin is primarily eliminated via biotransformation by cytochrome P450 (CYP)3A in the gut wall and liver. Additionally, P-glycoprotein (mdr-1) located in the gastrointestinal epithelium can affect affect blood drug concentrations after oral administration of cyclosporin, presumably by counter-transporting the drug from the systemic circulation back into the gastrointestinal lumen. Theoretically, age-related alterations in either of these pathways could affect cyclosporin disposition in the elderly. These general pharmacological considerations together with the narrow therapeutic index of cyclosporin between minimally immunosuppressive concentrations and those associated with adverse events, underscore the need for dedicated pharmacokinetic studies in the elderly. Single dose studies have demonstrated that cyclosporin pharmacokinetics are not different in healthy elderly individuals compared with healthy young adults, nor is the between-subject variability in pharmacokinetic parameters more heterogenous in healthy elderly individuals. Similarly, there were no apparent differences in cyclosporin disposition in elderly patients with rheumatoid arthritis compared with healthy young and elderly individuals. Whether pharmacokinetic variability may be increased in elderly patients has not been rigorously addressed and requires investigation in a larger patient population for a definitive conclusion. A population pharmacokinetic study of cyclosporin in organ transplant patients, including elderly allograft recipients up to 75 years of age, did not identify age as a covariable influencing cyclosporin pharmacokinetics. Hence, the available pharmacokinetic data in the elderly do not reveal any major differences from the disposition characterised in younger individuals. It is generally recognised that the elderly are more prone to drug-related adverse experiences and are at greater risk for drug-drug interactions secondary to polypharmacy. The former factor may underlie, in part, the increased incidence of renal adverse events reported in patients with rheumatoid arthritis over 65 years of age receiving cyclosporin. Clinical experience with cyclosporin in elderly organ transplant recipients has not revealed a tolerability profile remarkably different from those in younger patients. Polypharmacy may have specific relevance for elderly patients treated with cyclosporin since this agent is a substrate of both CYP3A and P-glycoprotein, both of which are important in the elimination of many commonly used drugs. This implies that the clinician prescribing cyclosporin for an elderly patient must exercise a heightened awareness for potential drug-drug interactions which could affect the pharmacokinetics of cyclosporin. Based on the available cyclosporin pharmacokinetic data in adults, no age-related administration adaptations appear necessary for its use in the elderly.