Patients with antinuclear antibody-positive juvenile idiopathic arthritis constitute a homogeneous subgroup irrespective of the course of joint disease

OBJECTIVE: We recently hypothesized that in the International League of Associations for Rheumatology (ILAR) classification of juvenile idiopathic arthritis (JIA), the presumably homogeneous patient group characterized by early onset of disease, a female predilection, the presence of antinuclear antibodies (ANA), asymmetric arthritis, and the risk for iridocyclitis is classified into different categories. We sought to investigate whether ANA-positive patients belonging to the ILAR categories of oligoarthritis and rheumatoid factor (RF)-negative polyarthritis share homogeneous features and to compare these features with those of ANA-negative patients with JIA in the same categories. METHODS: We identified patients who were followed up during a 15-year period. All patients had JIA according to the ILAR criteria, with oligoarticular or polyarticular onset. ANA positivity was defined as 2 or more positive results at a titer of >or=1:160. Demographic and clinical features, including the number of joints involved over time and measures of JIA severity at the last followup visit, were recorded retrospectively. RESULTS: A total of 256 patients were included: 190 were ANA positive (109 had persistent oligoarthritis, 48 had extended oligoarthritis, and 33 had RF-negative polyarthritis), and 66 were ANA negative (35 had RF-negative polyarthritis, and 31 had oligoarthritis). All patients who were positive for ANA were similar in terms of age at disease presentation, female-to-male ratio, and frequency of symmetric arthritis and iridocyclitis. Compared with ANA-positive patients with polyarticular disease, ANA-negative patients with polyarticular arthritis were older at disease presentation and had a lower frequency of iridocyclitis, a higher frequency of symmetric arthritis, a greater cumulative number of joints affected over time, and a different pattern of joint disease, with a greater frequency of shoulder and hip involvement. The strong relationship between the presence of ANA and younger age at disease presentation, asymmetric arthritis, and development of iridocyclitis was confirmed by multivariate regression analysis. CONCLUSION: Our results support the hypothesis that patients with similar characteristics are currently classified into different JIA categories. The value of ANA positivity as a possible modifier of the current classification system deserves consideration.     

Decrease of serum carnitine levels in patients with or without gastrointestinal cancer cachexia

AIM: To evaluate the levels of serum carnitine in patients with cancer in digestive organs and to compare them with other cancers in order to provide new insights into the mechanisms of cachexia. METHODS: Fifthy-flve cachectic patients with or without gastrointestinal cancer were enrolled in the present study. They underwent routine laboratory investigations, including examination of the levels of various forms of carnitine present in serum (i.e., long-chain acylcarnitine, short-chain acylcarnitine, free carnitine, and total carnitine). These values were compared with those found in 60 cancer patients in good nutritional status as well as with those of 30 healthy control subjects. RESULTS: When the cachectic patients with gastrointestinal cancer were compared with the cachectic patients without gastrointestinal cancer, the difference was -6.8μmol/L in free carnitine (P < 0.005), 0.04μmol/ L in long chain acylcarnitine (P < 0.05), 8.7μmol/L in total carnitine (P < 0.001). In the cachectic patients with or without gastrointestinal cancer, the difference was 12.2μmol/L in free carnitine (P < 0.001), 4.60μmol/L in short chain acylcarnitine (P < 0.001), and 0.60μmol/L in long-chain acylcarnitine (P < 0.005) and 17.4μmol/L in total carnitine (P < 0.001). In the cachectic patients with gastrointestinal cancer and the healthy control subjects, the difference was 15.5μmol/L in free carnitine (P < 0.001), 5.2μmol/L in short-chain acylcarnitine (P < 0.001), 1.0 umol/L in long chain acylcarnitine (P < 0.001), and 21.8 umol/L in total carnitine (P < 0.001). CONCLUSION: Low serum levels of carnitine in terminal neoplastic patients are decreased greatly due to the decreased dietary intake and impaired endogenous synthesis of this substance. These low serum carnitine levels also contribute to the progression of cachexia in cancer patients.     

Treatment of esophageal varices: a randomized controlled trial comparing endoscopic sclerotherapy and EUS-guided sclerotherapy of esophageal collateral veins

BACKGROUND: Endoscopic sclerotherapy (ES) and band ligation are standard treatments for esophageal varices. Unfortunately, recurrence is common and seems to be related to esophageal collateral vessels, easily identified by EUS. Eradication of these vessels might lead to a more durable therapeutic effect. OBJECTIVE: To compare ES with EUS-guided sclerotherapy of collateral vessels (EUS-ES). DESIGN: Randomized controlled trial. SETTING: Endoscopy Unit, Division of Gastroenterology. Universidade Federal de S?o Paulo, S?o Paulo, Brazil. PATIENTS AND INTERVENTIONS: Fifty cirrhotic patients with esophageal varices were randomized into 2 groups: ES (n = 25) and EUS-ES (n = 25). EUS-ES was targeted at collateral veins. Patients were followed-up for at least 6 months after eradication. MAIN OUTCOME MEASUREMENTS: Efficacy in eradication, complications, and recurrence of varices. RESULTS: Varices were eradicated in 48 patients who adhered to the study protocol. The mean (SD) number of sessions until eradication was 4.3 (1.5) for the ES group and 4.1 (1.2) for the EUS-ES group. In ES group, 4 patients had mild bleeding. In EUS-ES group, 4 patients had pain. The mean (SD) length of the follow-up period was 22.6 (6.9) months for the ES group and 24.9 (8.1) months for the EUS-ES group. Recurrence was seen in 4 patients after ES and in 2 after EUS-ES (P = .32). The presence of collateral vessels was associated with recurrence (P = .003). CONCLUSION: EUS-ES is as safe and effective as ES in variceal eradication. Recurrence tends to be less frequent and occurs later. Persistence of esophageal collateral vessels after sclerotherapy is a risk factor for recurrence.     

Histologic Risk Factors and Clinical Outcome in Colorectal Malignant Polyp: A Pooled-Data Analysis

PURPOSE The malignant polyp carries a significant risk of lymphohematic metastasis and mortality. Clinical usefulness of histologic risk factors is still controversial. The study was designed to compute the association between the main histologic risk factors and the occurrence of unfavorable outcomes in patients with malignant polyps.METHODS A MEDLINE search regarding malignant polyps was performed. Three histologic risk factors (positive resection margin, poor differentiation of carcinoma, vascular invasion) and five (residual disease, recurrent disease, lymph node metastasis, hematogenous metastasis, mortality) unfavorable clinical outcomes were evaluated. Further analysis was performed by subgrouping polyps in high-risk and low-risk groups.RESULTS Thirty-one studies enrolling 1,900 patients with malignant polyp were selected. Positivity of resection margin was significantly predictive of the presence of residual disease (odds ratio, 22; P < 0.0001), poorly differentiated carcinoma was associated with an increased mortality (odds ratio, 9.2; P < 0.05), and vascular invasion with a higher lymph node metastasis risk (odds ratio, 7; P < 0.05). Patients with high-risk polyps showed a significantly worse outcome than those with low-risk, especially for mortality (odds ratio, 11; P < 0.05). Surgical-related death was as low as 0.8 percent.CONCLUSIONS All three histologic risk factors are significantly associated with the clinical outcome. Classification in low-risk and high-risk patients may be regarded as a meaningful staging procedure.     

Natural Course of Functional Dyspepsia After <Emphasis Type="Italic">Helicobacter pylori</Emphasis>Eradication: A Seven-Year Survey

The role of Helicobacter pylori(Hp) in functional dyspepsia (FD) is controversial and previously published data do not help to clarify whether Hp eradication affects the natural course of FD. The aim of this study was to assess the clinical course of FD during a long follow-up period of 7 years in a homogeneous sample of Hp-eradicated patients. Among patients referred between 1991 and 1996, patients with FD and infected with Hp were enrolled. Patients were administered a structured symptom questionnaire and evaluated after Hp eradication at each 12-month time points. Patients were divided into three FD subgroups: predominantly ulcer-like, dismotility-like, and reflux-like symptom clusters. A composite symptom score ranging from 0 (no symptom) to 3 (severe symptoms) was assigned to each FD cluster. Of the 1685 screened patients, 405 had FD and 211 of them (52.1%) were also Hp-positive. During the follow-up, the amount of missing information varied from 10% to 17.5% within the first 6 years and was 30.8% at 7 years. The rates of improved patients ranged from 33% (reflux-like) to 34.9% (dismotility-like) to 47.3% (ulcer-like). However, only a proportion of 10%–50% of them was symptom-free after eradication and also at each 12-month evaluation, whereas the other patients became symptomatic at different times. FD symptoms slightly improve after Hp eradication over a long period of time but a large percentage of these improved patients may experience FD symptoms again, even after some years of well-being after Hp eradication. This study was not supported by any pharmaceutical company, government agency, or other grants: under the auspices of Roberto Farini Foundation for Gastroenterological Research. The data were analyzed by G. Leandro, MD. Preliminary versions of this paper were presented in abstract form at the 16th International Workshop of Gastrointestinal Pathology and Helicobacter, September 3–6, 2003, Stockholm Sweden; the 11th United European Gastroenterology Week, November 1–5, 2003, Madrid, Spain; the 10th National Congress on Digestive Diseases, March 27–31, 2004, Torino, Italy; and Digestive Disease Week, May 15–20, 2004, New Orleans, Louisiana, USA.     

Comparison between the two systems to evaluate the appropriateness of endoscopy of the upper digestive tract

OBJECTIVES: The aim of this study was to compare the diagnostic performance of the two systems for the evaluation of the appropriateness of upper digestive endoscopy suggested by the American Society of Gastrointestinal Endoscopy (ASGE) and by the European Panel on the Appropriateness of Gastrointestinal Endoscopy (EPAGE). METHODS: Patients referred for the upper digestive endoscopy (EGD) to a University Outpatients Clinic of Northeastern Italy were consecutively included in this prospective observational study. Before the EGD, the endoscopist assigned the patients to one of the ASGE appropriateness classes; another endoscopist then identified the detailed clinical scenario for the patients, which corresponds to scenarios examined by EPAGE by using a nine-point scale: 1-3 inappropriate; 4-6 uncertain; and 7-9 appropriate. The relationship between the appropriateness of use and the presence of relevant endoscopic lesions (neoplasms, ulcers, esophagitis, erosive gastritis/duodenitis, stenosis, and varices) was assessed, calculating the sensitivity and the specificity for each of the ASGE criteria, and each of the EPAGE scores, and plotting them to form a receiver operating characteristic (ROC) curve. The area under the ROC curve (AUC) provides a summary measure of test performance, and can vary from a minimum of 0.5 to a maximum of 1.0. We compared the AUC of the ROC curve derived from the ASGE criteria against that derived from the EPAGE criteria. RESULTS: A total of 2,300 consecutive patients were included in the study (42% men; mean age: 57.3; range: 12-99); comparison of appropriateness criteria according to the ASGE and EPAGE could be made for 2,000 patients. The AUC of the ROC curve derived from the ASGE criteria was 0.553 (95% CI: 0.527-0.579), significantly higher than the AUC of the ROC curve derived from the EPAGE score: 0.523 (95% CI: 0.497-0.549; p < 0.05). CONCLUSIONS: We suggest that the diagnostic yield for relevant endoscopic findings obtained by both the systems (ASGE and EPAGE) is low; slightly better results could be accomplished by the ASGE criteria.     

Vascular endothelial growth factor gene polymorphisms in Behçet's disease

OBJECTIVE: To evaluate potential associations of vascular endothelial growth factor (VEGF) gene polymorphisms with Beh?et's disease (BD) and disease expression. METHODS: Case patients were 122 consecutive Italian patients with BD followed at the Rheumatology, Ophthalmology, and Neurology Units in Bologna, Ferrara, Milano, Palermo, Potenza, Prato, Reggio Emilia, and Trento over a 3-year period (1997-99) and who satisfied the International Study Group criteria for BD. Also selected as a control group were 200 healthy age and sex matched blood donors. All patients with BD and controls were genotyped by polymerase chain reaction and allele-specific oligonucleotide techniques for +936 C/T (rs3025039) and -634 C/G (rs2010963) mutations and for an 18 base pair (bp) insertion/deletion (I/D) polymorphism at -2549 of the the VEGF promoter region. In vitro release of VEGF by peripheral blood mononuclear cells (PBMC) was investigated by ELISA in healthy controls homozygous for the polymorphisms studied. RESULTS: The carriage rates of the alleles I and -634C were significantly more frequent in patients with BD than in healthy controls [p corr = 0.036, OR 1.8 (95% CI 1.1-2.9) and p corr = 0.05, OR 1.8 (95% CI 1.1-3.0), respectively]. While the distribution of allele +936T was similar in patients with BD and healthy controls, its frequency was significantly higher in BD patients with posterior uveitis/retinal vasculitis than in those without (p = 0.022, OR 2.4, 95% CI 1.1-5.0). Lipopolysaccharide-stimulated VEGF production from PBMC of healthy subjects was higher in II homozygous than in DD homozygous. CONCLUSION: Our data indicate that carriers of -634C and I alleles are associated with susceptibility to developing BD.     

The effect of cardiac genetic testing on psychological well-being and illness perceptions

Objective

To assess the effects of positive cardiac genetic diagnoses, ICD discharges, and arrhythmias on measures of psychological well-being.

Methods

Fifty-eight adults with prior cardiac genetic testing were enrolled. Patient well-being was determined using the SF-36 (QoL), HADS-A and HADS-D (anxiety/depression), and IPQ-R (patients' perceptions of illness). Patients with positive and negative cardiac genetic test results were compared using non-parametric statistics.

Results

Genetic testing yielded 76% with a positive diagnosis and 29% reported an ICD shock. QoL assessments (n = 33) were within normal ranges (mean of 50) with the exceptions of general health (44.1 ± 12.2, p < 0.01) and bodily pain (55.1 ± 9.1, p < 0.01) domains, but only the bodily pain domain showed differences between those with positive and negative cardiac genetic test results. Subjects with ICD discharges had higher scores than those without shocks in consequential and emotional IPQR subscales as well as greater perceived risks of experiencing a serious cardiac event, developing additional symptoms, or limitations in daily activities.

Conclusion

Positive genetic results did not negatively impact patient well-being with the exception of the bodily pain domain of the SF-36.     

Pharmacological characterization of 2NTX-99 [4-methoxy-N1-(4-trans-nitrooxycyclohexyl)-N3-(3-pyridinylmethyl)-1,3-benzenedicarboxamide], a potential antiatherothrombotic agent with antithromboxane and nitric oxide donor activity in platelet and vascular preparations

Thromboxane (TX) A(2), prostacyclin (PGI(2)), and nitric oxide (NO) regulate platelet function and interaction with the vessel wall. Inhibition of TXA(2), implemented synthesis of PGI(2), and supply of exogenous NO may afford therapeutic benefit. 2NTX-99 [4-methoxy-N(1)-(4-trans-nitrooxycyclohexyl)-N(3)-(3-pyridinylmethyl)-1,3-benzenedicarboxamide], a new chemical entity related to picotamide, showed antithromboxane activity and NO donor properties. 2NTX-99 relaxed rabbit aortic rings precontracted with norepinephrine or U46619 (9,11-dideoxy-9alpha,11alpha-methanoepoxy-prosta-5Z,13E-dien-1-oic acid; EC(50), 7.9 and 17.1 microM, respectively), an effect abolished by 10 microM 1H-(1,2,4)oxadiazolo(4,3-a)quinoxalin-1-one (ODQ). 2NTX-99 inhibited arachidonic acid (AA)-induced washed platelet aggregation (EC(50), 9.8 microM) and TXB(2) formation (-71% at 10 microM), and its potency increased in the presence of aortic rings (EC(50), 1.4 microM). In whole rabbit aorta incubated with homologous platelets, AA caused contraction and TXA(2) formation, reduced by 2NTX-99 (10-40 microM): contraction, -28 and -47%, TXA(2) formation, -37 and -75.4%, respectively, with concomitant increase in PGI(2). 2NTX-99 (20-40 microM) inhibited U46619-induced aggregation in rabbit platelet-rich plasma (PRP) (-74 +/- 6.7 and -96 +/- 2.4%, respectively) and inhibited collagen-induced aggregation in human PRP (-48.2 +/- 10 and -79.2 +/- 6%), whereas ozagrel was ineffective. In human embryonic kidney 293 cells transfected with the TXA(2) receptor isophorm alpha receptor, 2NTX-99 did not compete with the ligand, [(3)H]SQ29,548 ([(3)H][1S-[1alpha,2beta(5Z),3beta,4alpha]]-7-[3-[[2-(phenylamino)-carbonyl]hydrazino]methyl]-7-oxabicyclo[2,2,1]-hept-2-yl]-5-heptanoic acid), or prevent inositol phosphate accumulation. After oral administration (50-250 mg/kg), 2NTX-99 inhibited TXA(2) production in rat clotting blood (-71 and -91%); at 250 mg/kg, an area under the curve, 0 to 16 h, of 149.5 h/microg/ml and a t(1/2) of 6 h were calculated, with a C(max) value of 31.8 +/- 8.2 microg/ml. An excellent correlation between plasma concentrations and TXA(2) inhibition occurs. 2NTX-99 controls platelet function and vessel wall interaction by multifactorial mechanisms and possesses therapeutic potential.