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ID PMID Title PublicationDate abstract
12193907 Parotid sialography for diagnosing Sjögren syndrome. 2002 Jul OBJECTIVE: Despite the availability of many new imaging procedures, sialography has, after decades of use, maintained its status as the imaging procedure of choice for evaluating the oral component of Sjögren syndrome (SS). In this study, the clinical value of sialography as a diagnostic tool in SS was explored by assessing its diagnostic accuracy, observer bias, and staging potential. METHODS: One hundred parotid sialograms were interpreted independently in a blinded fashion by 2 trained and 2 expert observers. Sialograms were derived from a group of consecutive patients referred for diagnostics of SS. Patients were categorized as SS and non-SS by the revised European classification criteria. RESULTS: Trained observers reached a sensitivity of 95 and a specificity of 33% for SS by sialogram, whereas expert observers reached a sensitivity of 87 and a specificity of 84%. There was only "fair" interobserver agreement between trained and expert observers, whereas both expert observers showed "good" agreement with one another, according to Cohen's kappa. Intraobserver agreement was "good" to "very good" for all observers. The 4 different gradations of sialectasia, ie, punctate, globular, cavitary, and destructive, showed a weak but significant correlation with the duration of oral symptoms. CONCLUSIONS: This study markedly shows that the diagnostic value of parotid sialography for diagnosing SS greatly depends on the skills of the observer, implying that sialography lacks general applicability as a diagnostic tool in SS and requires specific expertise. Nevertheless, given its potentially high sensitivity and specificity in diagnosing SS as well as its useful staging potential, sialography still has its use in the evaluation of the oral component of SS.
11919437 The effect of artificial tears on corneal surface regularity in patients with Sjögren syn 2002 Mar PURPOSE: To evaluate the effect of artificial tears on the topographic parameters associated with corneal surface regularity in patients with Sjögren syndrome. METHODS: A total of 38 eyes of 20 patients with Sjögren syndrome were evaluated prospectively. The mean age of the patients was 50.5 +/- 15.3 years (range, 28-76). Corneal topography with the Topographic Modeling System (TMS-2, Tomey) was performed before and after the instillation of artificial tears. The surface regularity index (SRI), surface asymmetry index (SAI), potential visual acuity (PVA) and mean astigmatism were compared in dry eyes before and after the instillation of artificial tears. RESULTS: Before the instillation of artificial tears SAI, SRI, PVA and mean antigmatism values were found to be 1.37 +/- 1.47, 0.74 +/- 0.42, 20/30.92 +/- 20/8.12 and 1.53 +/- 1.47 D, respectively. In corneal topography performed after the instillation of artificial tears SAI, SRI, PVA and mean astigmatism values were 0.71 +/- 0.82, 0.43 +/- 0.36, 20/25.92 +/- 20/5.55 and 1.08 +/- 1.18, respectively. When compared statistically, the SRI, SAI, and mean astigmatism all decreased significantly and the PVA improved (p = 0.0001). CONCLUSION: Irregular corneal surface in dry eye patients affects optical quality. The statistically significant improvement observed in SRI and SAI values after the instillation of artificial tears also improves the PVA that is especially related to SRI.
11830428 Spectral analysis of heart rate and blood pressure variability in primary Sjögren's syndr 2002 Mar BACKGROUND: Autonomic dysfunction has been described in primary Sjögren's syndrome (SS). OBJECTIVE: To investigate the circulatory autonomic regulation in patients with primary SS by power spectral analysis of heart rate and blood pressure variability. METHODS: Forty three (42 female) patients with primary SS, mean age 52 years (range 23-80), with a mean disease duration of eight years (range 1-30) and 30 (15 female) healthy controls, mean age 43 years (range 21-68) were studied. In each patient blood pressure, heart rate, and respiration were measured continuously during supine rest and orthostatic challenge (60 degrees head-up tilt). Power spectral analysis was performed to determine possible differences in short term sympathetic and parasympathetic autonomic regulation between patients and controls. Furthermore, spectral parameters were studied in relation to illness severity and disease duration of the patients with primary SS. RESULTS: After controlling for differences in age, heart rate variability of the mid-frequency band and the variation coefficient of systolic blood pressure were significantly lower in patients with primary SS than in controls during supine rest. During 60 degrees tilt patients with primary SS showed a significantly higher mean heart rate, mean systolic blood pressure, and variation coefficient of diastolic blood pressure, and a significantly lower baroreflex index than controls. After controlling for age, no differences were found either in heart rate variability, blood pressure results, and baroreflex sensitivity during supine rest and tilt between the subgroups divided according to disease duration, Schirmer test results, or between the subgroups with different fatigue scores. No differences were found in spectral data between the groups with and without positive antinuclear antibody serology. CONCLUSION: For the group no differences in sympathetic and parasympathetic cardiac control were seen between patients with primary SS and controls, as assessed by spectral techniques, although some cardiovascular differences were found, particularly during orthostatic challenge.
14991851 Clinicopathological features of pure mica pneumoconiosis associated with Sjögren syndrome 2004 Mar BACKGROUND: There are few reports on the clinical, radiologic, and pathologic features of pure mica pneumoconiosis. METHODS: A case of definite pure mica pneumoconiosis in a rubber factory worker is reported with the clinicopathological findings. RESULTS: Chest HRCT demonstrated subpleural and peribronchovascular interstitial thickening. The characteristic histologic features were pulmonary fibrosis accompanied by prominent histiocytic granulomas containing giant cells. CONCLUSIONS: Pure mica pneumoconiosis can be identified by specific radiologic and pathologic findings.
12352083 Use of the dry eye questionnaire to measure symptoms of ocular irritation in patients with 2002 Oct PURPOSE: To demonstrate the ability of the Dry Eye Questionnaire (DEQ) to characterize the frequency of ocular surface symptoms and their diurnal intensity in patients with Sjögren's syndrome (SS), keratoconjunctivitis sicca (KCS), and age-matched controls. METHODS: One hundred patients with tear-deficient dry eye from Toronto Western Hospital were mailed the DEQ and the McMonnies' questionnaire (MQ). Age- and gender-matched controls were selected from an historical data set. The DEQ measured the habitual frequency, intensity, and impact of common ocular surface symptoms and asked questions about computer use, medications, and allergies. RESULTS: Sixty-two dry eye subjects responded; 30 with SS and 32 with KCS. Compared with controls, SS subjects consistently reported the highest frequency and intensity of symptoms, followed by non-KCS subjects. The intensity of symptoms was significantly greater in the evening than in the morning among SS subjects for all symptoms except dryness and light sensitivity (p < 0.05). Sixty percent of SS subjects reported the need to stop daily activities and close their eyes due to dryness, burning, and light sensitivity. CONCLUSIONS: Symptoms of ocular irritation were frequent and intense among SS and KCS subjects. These symptoms often increased in intensity over the day, suggesting that open-eye conditions affect the progression of symptoms. Measurement of symptom frequency and diurnal intensity by the DEQ provides a sensitive tool that may be useful in clinical treatment trials for dry eye.
12298431 Lymphocytic interstitial pneumonitis associated with Epstein-Barr virus in Systemic Lupus 2002 Sep Lymphocytic interstitial pneumonitis (LIP) is characterized by diffuse bilateral pulmonary infiltrations in both lower lobes. Pleomorphic lymphohistiocytes including mature lymphocytes, variable admixture of plasma cells and other mononuclear cells infiltrate within the pulmonary interstitium, ranging from widened septa to confluent masses. We report a case of LIP associated with Epstein-Barr virus in a patient with SLE and Sjögren's syndrome. A 50-year-old woman was admitted with insidious onset of progressive dyspnea for 20 days. She suffered from arthritis 10 years earlier without specific diagnosis. A radiography of chest has showed bilateral consolidative infiltrations with pleural effusion in both lower lung fields. Open lung biopsy documented lymphocytic interstitial pneumonitis which expressed Epstein-Barr virus genome in situ hybridization study. Following corticosteroid and cyclophosphamide therapy, clinical symptoms and radiologic infiltrations gradually remitted.
12023386 Possible involvement of the vascular endothelial growth factor-Flt-1-focal adhesion kinase 2002 Jun 1 Vascular endothelial growth factor (VEGF) plays a crucial role in the pathogenesis of inflammatory joint disease, including angiogenesis and synovitis. Rheumatoid arthritis is a chronic inflammatory disease characterized by progressive synovitis and subsequent bone destruction mediated by osteoclasts (OCs). In this study, we investigate the effects of VEGF on OC precursor cells (pOCs) using Raw cells and adjuvant-induced arthritis in rats. OCs and pOCs in the arthritic joints express VEGF and VEGF receptor type I (Flt-1). Raw cells also express Flt-1, and VEGF treatment stimulated chemotaxis, cell proliferation, the association of Flt-1 with focal adhesion kinase (FAK), and the tyrosine phosphorylation of FAK in Raw cells. The tyrosine phosphorylation of FAK was also observed in pOCs in the arthritic joints of adjuvant-induced arthritis. Adenovirus-mediated expression of FAK-related nonkinase in Raw cells inhibited the effects of VEGF in a dominant negative manner. Furthermore, intra-articular injection of the FAK-related nonkinase virus suppressed the recruitment of pOCs and bone destruction. Our results suggest the possible involvement of the VEGF-Flt-1-FAK pathway in inflammatory disease-induced joint destruction.
12610805 Frequency of adverse drug reactions in patients with systemic lupus erythematosus. 2003 Mar OBJECTIVE: The literature suggests that patients with systemic lupus erythematosus (SLE) have a higher frequency of adverse drug reactions (ADR). We performed this case control study to compare the prevalence of ADR in patients with SLE and controls with inflammatory arthritis. METHODS: We surveyed 249 patients, 145 with SLE and 104 age and sex matched controls with other types of inflammatory arthritis, such as rheumatoid arthritis (RA), probable RA, and psoriatic arthritis. We asked about exposure and ADR to the following classes of drugs: (1) beta-lactam antibiotics, (2) sulfonamides, (3) other antibiotics, (4) disease modifying antirheumatic drugs (DMARD), and (5) nonsteroidal antiinflammatory drugs (NSAID). Personal and family atopic histories were obtained. The 2 groups were obtained from a single rheumatologic practice and had similar characteristics and drug exposures. RESULTS: The response rate was 63% in the SLE patients and 64% in the control group. The mean age was 47.8 +/- 1.5 years in patients with SLE and 46.1 +/- 1.7 years in controls (p < 0.51). Ninety-two percent of SLE patients and 88% of controls were female (p < 0.42). Both groups had been exposed similarly to all antibiotics, as there were no significant differences between groups (exposure to sulfa antibiotics 53% in SLE patients vs 46% in controls), and to NSAID (84% SLE group vs 93% controls). Few patients from the SLE group had DMARD exposure, with the exception of plaquenil (65% SLE group vs 30% controls; p < 0.0001) and azathioprine (18% SLE group vs 4% controls; p < 0.006). There were between-groups differences with respect to total number of ADR with sulfa antibiotics (exposed had 25/48 reactions in SLE group vs 6/31 in controls; p < 0.003), but not with other drugs. Most ADR to sulfa antibiotics were cutaneous (rash). Subjects with an allergic or atopic history had more ADR (p < 0.0005). There were no differences between SLE patients and controls in having an allergic history (p < 0.88). Subjects with a positive family history of allergies were more likely to have ADR (p < 0.0043). SLE patients and controls with a personal versus family history of environmental allergies did not differ in having ADR (p < 0.16 and p < 0.83, respectively). CONCLUSION: Both intolerances and true allergic reactions were not dissimilar in patients with SLE compared to controls with inflammatory arthritis, with the exception of cutaneous reactions to sulfa antibiotics in SLE patients. This has not been the experience of other investigators (with increased ADR with several antibiotics in SLE groups) who used healthy, best friend, and relative controls with dissimilar frequencies of drug exposures. Perhaps differences observed in the past (where SLE patients have more ADR than healthy controls) are true of other inflammatory arthritis subjects (who have different drug exposures than healthy individuals) rather than just SLE. Differences could also exist in the pharmacogenetics, as our sample population was mostly Caucasian.
15574234 Subtalar joint arthrodesis using a single lag screw. 2004 Nov BACKGROUND: This study tested the hypotheses that fusing the subtalar joint with a single lag screw from the posteroinferior calcaneus to the anterior talar neck is an effective technique and that factors affecting the time to fusion can be identified. METHODS: Between October, 1995, and July, 2002, the senior author (RAM) performed 101 isolated subtalar arthrodeses using a technique of single lag-screw fixation from posteroinferior to anterosuperior across the posterior facet of the subtalar joint combined with the application of an autograft taken from the floor of the sinus tarsi and anterior process. The average patient age was 52 (range 17 to 82) years. There were 52 women (53 arthrodeses) and 48 men (48 arthrodeses). Eight of 101 (8%) arthrodeses were revisions. The indications included posttraumatic arthritis (45), posterior tibial tendon dysfunction (18), failed prior ankle joint fusion (14), idiopathic disorders (12), hindfoot coalition (7), rheumatoid arthritis (3), and Charcot-Marie-Tooth disease (2). Fifteen of 101 patients (15%) smoked an average of 0.9 +/- 0.5 pack of cigarettes per day. RESULTS: Two of 101 joints did not fuse, resulting in an overall fusion rate of 98%. The average time to fusion was 12.3 +/- 3.4 weeks. The presence of a prior ankle fusion significantly prolonged the time to fusion of the subtalar joint (11.9 +/- 2.3 vs. 14.9 +/- 7.0, p = .003). Other factors, including smoking, revision surgery, patient age, and patient sex, did not affect time to fusion. The fixation screw was removed in 13 of 101 (13%) joints at an average of 8.8 +/- 0.5 months. CONCLUSIONS: Using a single 7.0-mm lag screw across the posterior facet of the subtalar joint results in fusion of the subtalar joint in 98% of patients. A prior ankle arthrodesis delays the time to fusion of the subtalar joint by 3 weeks. This is a simple and reliable technique for achieving fusion of the subtalar joint.
15280347 Clinical implications of the osteoprotegerin/RANKL/RANK system for bone and vascular disea 2004 Jul 28 Bone resorption by osteoclasts is coupled with bone formation by osteoblasts, and this balanced process continuously remodels and adapts the skeleton. The receptor activator of nuclear factor kappaB ligand (RANKL) has been identified as an essential cytokine for the formation and activation of osteoclasts. The effects of RANKL are physiologically counterbalanced by the decoy receptor osteoprotegerin (OPG). Estrogen deficiency, glucocorticoid exposure, T-cell activation (eg, rheumatoid arthritis), and skeletal malignancies (eg, myeloma, metastases) enhance the ratio of RANKL to OPG and, thus, promote osteoclastogenesis, accelerate bone resorption, and induce bone loss. Moreover, alterations of the OPG/RANKL/RANK system have been implicated in vascular diseases. RANKL blockade (using OPG or RANK fusion proteins or RANKL antibodies) has prevented bone loss caused by osteoporosis, chronic inflammatory disorders, and malignant tumors in animal models and may emerge as a therapy in humans based on studies in postmenopausal osteoporosis, myeloma bone disease, and osteolytic metastases. This review summarizes the clinical implications of the OPG/RANKL/RANK system for bone and vascular diseases.
12483722 Nonrandom evolution of end-stage osteoarthritis of the lower limbs. 2002 Dec OBJECTIVE: Patients with unilateral hip or knee replacements for end-stage osteoarthritis (OA) are at high risk for future progression of OA in other joints of the lower extremities, often requiring additional joint replacements. Although the risks of future surgery in the contralateral cognate joints (i.e., contralateral hip replacement after an initial hip replacement) have been evaluated, the evolution of end-stage hip OA to OA involving the knee joints, and vice versa (i.e., noncognate progression) has not been investigated. Because characterization of OA progression in noncognate joints may shed light on the pathogenesis of multijoint OA, we investigated the pattern of evolution of end-stage lower extremity OA in a large, clinical cohort. METHODS: Total joint replacement (TJR) was selected as a marker of end-stage OA, and a database comprising all lower extremity TJRs performed at a large referral center between 1981 and 2001 was accessed. Of the 5,894 patients identified, 486 patients with idiopathic OA who underwent hip replacement and 414 who underwent initial knee replacement were analyzed to determine the relative likelihood of subsequent TJRs. Patients with the systemic inflammatory arthropathy, rheumatoid arthritis (RA), were evaluated as a control population because RA progression is not considered to be a primarily mechanically mediated process. RESULTS: The contralateral cognate joint was the most common second joint to undergo replacement in both the OA and the RA groups. However, in OA patients for whom the second TJR was in a noncognate joint, that joint was >2-fold more likely to be on the contralateral limb than on the ipsilateral limb (hip to knee P < 0.001; knee to hip P = 0.013). In contrast, among the RA cohort, the evolution was random and no laterality for noncognate TJR was observed at either the hip or the knee (P = 0.782). CONCLUSION: This characterization of end-stage lower extremity OA demonstrates that the disease evolves nonrandomly; after 1 joint is replaced, the contralateral limb is significantly more likely to show progression of OA than is the ipsilateral limb. Thus, OA in 1 weight-bearing joint appears to influence the evolution of OA in other joints. The absence of such laterality in RA suggests that OA progression may be mediated by extrinsic factors such as altered joint loading.
11940616 Rate of and risk factors for acute inpatient mortality after orthopaedic surgery. 2002 Apr BACKGROUND: Orthopaedic surgeons operate on a diverse group of patients, and many of these patients have concomitant medical problems. The purpose of this study was to identify the rate of mortality and to evaluate the risk factors associated with mortality after orthopaedic surgery. METHODS: Data from the National Hospital Discharge Survey, a nationwide sample of hospital admissions, were obtained for the years 1995 through 1997. The study was limited to hospital admissions. Univariate and multivariate analyses were performed. RESULTS: The 43,215 inpatient orthopaedic operations that we evaluated were associated with a mortality rate of 0.92%. Seventy-seven percent of all deaths occurred after procedures performed for patients who were more than seventy years old, and 50% of all deaths occurred after operations performed for the treatment of hip fractures. The independent preoperative medical risk factors for death included chronic renal failure, congestive heart failure, metastasis to bone, atrial fibrillation, chronic obstructive pulmonary disease, and osteomyelitis. The risk factors of diabetes, coronary artery disease, peripheral vascular disease, septic arthritis, and rheumatoid arthritis did not achieve significance. Among orthopaedic subspecialty categories, operations for tumors, trauma, and infection were associated with elevated mortality rates. In a predictive model, five critical risk factors were identified as most helpful in identifying patients at risk for death: chronic renal failure, congestive heart failure, chronic obstructive pulmonary disease, hip fracture, and an age of greater than seventy years. The mortality rate was 0.25% for patients with no critical risk factors. A linear increase in mortality was seen with increasing numbers of critical risk factors (p < 0.005). CONCLUSION: Death is rare after orthopaedic operations. In the United States, the rate of acute mortality after inpatient orthopaedic surgical procedures is approximately 1% for all patients, 3.1% for patients with a hip fracture, and 0.5% for patients without a hip fracture. These data will aid orthopaedic surgeons in predicting operative mortality for their patients.
15389210 Aggressive cutaneous T-cell lymphomas after TNFalpha blockade. 2004 Oct Pharmacologic blockade of TNFalpha has been a highly effective approach to treating several immunologically mediated diseases, including rheumatoid arthritis, Crohn's disease, and psoriatic arthritis. 1,2,3 Both etanercept, the recombinant extracellular domain of the tumor necrosis factor receptor 2 (TNFR2), and infliximab, a humanized murine antibody, bind TNFalpha and block its interaction with cell surface receptors. Recently, it has become clear that blockade of TNFalpha action is profoundly immunosuppressive, and may result in reactivation of tuberculosis and histoplasmosis, as well as the emergence of B-cell lymphomas. 4,5,6 In this report, we describe two cases of cutaneous and systemic T-cell lymphoma that progressed rapidly in the setting of TNFalpha blockade. Both cases were characterized by rapid onset, a fulminant clinical course with extensive cutaneous and systemic involvement, and death within months of diagnosis.
15760675 Inflammation, genetics, and ischemic heart disease: focus on the major histocompatibility 2005 Mar 7 BACKGROUND: Increasing data suggest that ischemic heart disease (IHD) shares several characteristics with common inflammatory diseases (such as rheumatoid arthritis), in which the pathogenetic role of inflammatory gene polymorphisms is well established. Variants in the genes for the major histocompatibility complex (MHC) molecules on the short arm of chromosome 6 show profound "linkage disequilibrium", leading to the formation of "haplotypes", i.e., frozen blocks of alleles travelling together through generations. DESIGN: We performed a review of published studies linking IHD with gene polymorphisms of the MHC molecules tumor necrosis factor (TNF)-alpha and -beta, the class II DR human leukocyte antigens, heat shock protein 70-1, hemochromatosis related gene, and complement C4. RESULTS: The emerging data are quite conflicting and do not provide definitive evidence for a role of these gene variants in the pathogenesis of IHD; a possible exception is the G252A and polymorphism in the TNF-beta gene (also known as lymphotoxin-alpha) which, in a comprehensive genome-scan linkage analysis of unrelated Japanese, but not in a smaller German population, was linked to myocardial infarction. However, some important biases appear, e.g. different study design and variable linkage disequilibrium among different populations. CONCLUSIONS: Preliminary positive results should encourage future studies to focus on clinical models of IHD with well-codified inflammatory components, using novel methods (such as haplotype analysis) to assess gene polymorphisms and their clinical effect.
12789686 Protease inhibitors of the sulfonamide type: anticancer, antiinflammatory, and antiviral a 2003 Sep The sulfonamides constitute an important class of drugs, with several types of pharmacological agents possessing antibacterial, anticarbonic anhydrase, diuretic, hypoglycemic, and antithyroid activity among others. A large number of structurally novel sulfonamide derivatives have ultimately been reported to show substantial protease inhibitory properties. Of particular interest are some metalloprotease inhibitors belonging to this class, which by inhibiting several matrix metalloproteases (MMPs) show interesting antitumor properties. Some of these compounds are currently being evaluated in clinical trials. The large number of sulfonamide MMP inhibitors ultimately reported also lead to the design of effective tumor necrosis factor-alpha converting enzyme (TACE) inhibitors, potentially useful in the treatment of inflammatory states of various types. Since both MMPs and TACE contribute synergistically to the pathophysiology of many diseases, such as arthritis, bacterial meningitis, tumor invasion; the dual inhibition of these enzymes emerged as an interesting target for the drug design of anticancer/antiinflammatory drugs, and many such sulfonamide derivatives were recently reported. Human neutrophyl elastase (HNE) inhibitors of the sulfonamide type may also be useful in the treatment of inflammatory conditions, such as emphysema, cystic fibrosis, chronic bronchitis, ischemia reperfusion injury, and acute respiratory distress syndrome. Inhibition of some cysteine proteases, such as several caspase and cathepsin isozymes, may lead to the development of pharmacological agents effective for the management of several diseases, such as rheumatoid arthritis, inflammatory bowel disease, brain damage, and stroke. Another research line that progressed much in the last time regards different sulfonamides with remarkable antiviral activity. Some clinically used HIV protease inhibitors (such as amprenavir) possess sulfonamide moieties in their molecules, which are critical for the potency of these drugs, as shown by means of X-ray crystallography, whereas a very large number of other derivatives are constantly being synthesized and evaluated in order to obtain compounds with lower toxicity or augmented activity against viruses resistant to the such first generation drugs. Other viral proteases, such as those isolated from several types of herpes viruses may be inhibited by sulfonamide derivatives, leading thus to more effective classes of antiviral drugs.
12466002 Etoricoxib. 2002 Etoricoxib is a cyclo-oxygenase (COX)-2-selective NSAID with a higher COX-1 to COX-2 selectivity ratio than the other COX-2-selective NSAIDs rofecoxib, valdecoxib or celecoxib. In patients with rheumatoid arthritis, improvements in tender and swollen joint counts and patient and investigator global assessment of disease activity were significantly greater in etoricoxib than in placebo recipients in two studies. Etoricoxib was also significantly more effective than naproxen in one of these studies. In patients with osteoarthritis of the hip or knee, etoricoxib was significantly more effective than placebo and had similar efficacy to naproxen with regards to improvements in pain and physical function scores and patient global assessment of disease status scores in two studies. Etoricoxib had similar efficacy to diclofenac in patients with osteoarthritis of the knee. Single-dose etoricoxib relieved pain in patients with postoperative dental pain in two studies. Similar scores assessing total pain relief over 8 hours (TOPAR8) were reported in etoricoxib and naproxen sodium or ibuprofen recipients, and higher TOPAR8 scores were reported with etoricoxib than with paracetamol (acetaminophen)/codeine. Pain relief was significantly better with etoricoxib than placebo in two studies in patients with chronic low back pain. Etoricoxib had similar efficacy to indomethacin in a study in patients with acute gout, and single-dose etoricoxib had similar efficacy to naproxen sodium in a study in women with primary dysmenorrhoea. Compared with non-COX-selective NSAIDs, etoricoxib was associated with significantly fewer upper gastrointestinal (GI) perforations, ulcers or bleeds, and was significantly less likely to result in treatment discontinuation because of NSAID-type GI symptoms or any GI symptoms.
12171772 Circulating thrombopoietin in clonal versus reactive thrombocytosis. 2002 Feb INTRODUCTION: The aim of this study is to assess circulating thrombopoietin concentrations in patients with both clonal and reactive thrombocytosis (RT), which are two distinct categories of extreme platelet production circumstances. Investigation of the thrombopoietin levels in clonal versus reactive thrombocytosis may help us to understand the interactions of this key regulatory cytokine and the conditions in which abnormally increased platelet formation exist. MATERIALS AND METHODS: Thrombopoietin levels were measured in patients with platelet counts greater than 500 x1 0(3) microl(-1). The study population consisted of 21 patients with RT (13 with iron deficiency anemia, and 8 with rheumatoid arthritis), 24 patients with clonal thrombocytosis (six with essential thrombocytosis, three with myelofibrosis, eight with chronic myelogenous leukemia, and seven with polycythemia vera (PV)) and 16 healthy subjects were used as controls. RESULTS: The median plasma thrombopoietin concentration was 100.5 pg ml(-1) in patients with RT, 467 pg ml(-1) in patients with clonal thrombocytosis and 62.65 pg ml(-1) in the control group. The thrombopoietin concentration was found to be higher in the patients with primary thrombocytosis when compared to the control group (p=0.001), as well as in patients with RT (p=0.002). However, there was no statistically significant difference between the patients with RT and the control group (p=0.14). There was no correlation between thrombopoietin levels and the platelet counts in patients with clonal thrombocytosis, including essential thrombocythemia (ET). CONCLUSIION: Increased levels of thrombopoietin were found in patients with clonal thrombocytosis versus patients with RT and control subjects as well. Defective clearance of thrombopoietin by megakaryocytes and platelets due to a reduced number of thrombopoietin receptors may be the causative mechanism behind this. These results indicate that plasma thrombopoietin levels may be helpful in distinguishing between clonal and reactive thrombocytosis.
11858868 Adverse event reports following vaccination for Lyme disease: December 1998-July 2000. 2002 Feb 22 CONTEXT: The vaccine adverse event reporting system (VAERS) monitors vaccine safety post-licensure. Although events reported to VAERS are not necessarily causally associated with vaccination, VAERS reports can be used to identify possible safety concerns that occur at too low a rate to have been identified prior to licensure. OBJECTIVE: To evaluate adverse events following Lyme disease vaccination reported to VAERS during the first 19 months of the vaccine's licensure. DESIGN, SETTING, AND PARTICIPANTS: Analysis of all VAERS reports of adverse events following vaccination for Lyme disease in the US from 28 December 1998 to 31 July 2000. MAIN OUTCOME MEASURE: We evaluated reported adverse events for unexpected patterns in age, gender, time to onset, dose number, and clinical characteristics and compared them to adverse events observed in clinical trials of this vaccine. RESULTS: Over 1,400,000 doses were distributed and 905 adverse events were reported to VAERS, 440 in men and 404 in women, with ages ranging from 10 to 82 years. The majority (56%) of adverse events occurred after administration of the first dose. The most frequently reported adverse events were arthralgia (250), myalgia (195), and pain (157). There were 59 reports coded as arthritis, 34 as arthrosis, 9 as rheumatoid arthritis, and 12 as facial paralysis. Sixty-six (7.4%) events were classified as serious, involving life-threatening illness, hospitalization, prolongation of hospitalization, persistent or significant disability/incapacity, or death. Twenty-two hypersensitivity reactions were reported. CONCLUSION: Based on reporting to VAERS, we did not detect unexpected or unusual patterns of reported adverse events following Lyme disease vaccine administration, other than hypersensitivity reactions, compared with adverse events observed in clinical trials.
15683037 [Nosology and epidemiology of human toxocarosis--the recent situation in Austria]. 2004 Toxocara canis and T. cati are not only ubiquitously distributed parasites of dogs, foxes and cats, but may also infest humans, causing a great variety of symptoms and sometimes also severe diseases: the visceral larva migrans syndrome, the ocular larva migrans syndrome, covert toxocarosis, common toxocarosis, neurological toxocarosis, and some other clinical pictures (asthma bronchiale, epilepsy, rheumatoid arthritis) are considered to be induced by Toxocara species. Both Toxocara species are also widely distributed in Austrian dog, fox and cat populations; seroepidemiological studies carried out in Austria revealed seroprevalence rates of 3.7% among the normal human population and up to 44% among persons particularly exposed to those parasites (i.e. veterinarians, farmers). Although many Toxocara infestations do not cause severe clinical manifestations, a few dozens of toxocarosis patients have been registered every year during the last years; in reality, however, we have to assume that several hundreds of patients suffer from toxocarosis. This paper tries to give a synoptic overview of the nosology of this (still) largely almost unknown helminthozoonosis, moreover it summarizes the most important epidemiologic parameters, and presents the diagnostic and therapeutic possibilities available today.
14673392 The systemic amyloidoses. 2004 Jan PURPOSE OF REVIEW: Clinical management of the amyloidoses has historically been the province of rheumatologists, because of the relation to long-standing inflammation in rheumatoid arthritis, ankylosing spondylitis, and juvenile chronic arthritis. Currently, nephrologists, hematologist-oncologists, neurologists, and transplant surgeons all have a diagnostic or therapeutic interest. Current advances, using the tools of physical biochemistry, cell biology, and genetics, have begun to impact the diagnosis and clinical management of these disorders and raise questions regarding our notions of protein conformation in vivo and how nonnatively folded proteins may produce disease. RECENT FINDINGS: It appears that all amyloidogenic precursors undergo some degree of misfolding that allows them to populate an immediate precursor pool from which they rapidly aggregate. Depending on the particular protein, a variety of mechanisms appear operative, some of which involve nonphysiologic proteolysis, defective physiologic proteolysis, mutations involving changes in thermodynamic or kinetic properties, and pathways that are yet to be defined. Whatever the particular process, the result is a tendency toward oligomeric aggregation followed by the assembly of higher order structures that become insoluble under physiologic conditions. Detailed analyses have been described for transthyretin (senile systemic amyloidosis and familial amyloid polyneuropathy), immunoglobulin light chains (light-chain amyloid), beta2 microglobulin (dialysis-related amyloid), and apolipoprotein A1, and are in process for others. SUMMARY Therapies have been proposed based on precursor stabilization (transthyretin), elimination of the synthesizing cell (light-chain amyloid), fibril disruption and immunization to induce host-mediated aggregate clearance (Alzheimer disease, light-chain amyloid, prions), and aggressive therapy of a primary inflammatory process (amyloid A). During the next decade, the value of these therapies, and others, suggested by studies on the basic properties of cells and proteins, will become clear.