Diagnostic and clinical value of anti-cyclic citrullinated peptide antibodies compared with rheumatoid factor isotypes in rheumatoid arthritis

OBJECTIVE: To assess the additional diagnostic and clinical value of the second test generation of anti-cyclic citrullinated peptide antibodies (CCP2) compared with rheumatoid factor isotypes (IgG-RF, IgA-RF, IgM-RF) in patients with rheumatoid arthritis. METHODS: This was a prospective study on 715 patients: rheumatoid arthritis (n = 295), degenerative or other inflammatory joint disease (n = 163), connective tissue disease or vasculitis (n = 103), and healthy controls (n = 154). Sera from each subject were tested for CCP2 and RF isotypes by enzyme linked immunosorbent assay (ELISA). Agreement with clinical indices such as disease activity, joint destruction, disease duration, and other laboratory tests was assessed. Sensitivity and specificity of the tests were evaluated taking the clinical diagnosis as the gold standard. RESULTS: Highest sensitivity was found for IgM-RF (66.4%) and CCP (64.4%). Highest specificity was achieved by CCP (97.1%) and IgG-RF (91.0%). In rheumatoid patients with high disease activity or severe joint damage, CCP was more often present (81.4% and 83.6%) than all RF isotypes. Of special diagnostic value was the detection of positive CCP in 34.5% of all patients with rheumatoid arthritis when all measured RF isotypes (IgG-RF, IgA-RF, and IgM-RF) were negative. CONCLUSIONS: As a screening method for rheumatoid arthritis the IgM-RF and the CCP assays are superior to other RF isotypes. Positivity in the highly specific CCP ELISA supports the diagnosis of rheumatoid arthritis. CCP proved to be a powerful diagnostic tool, especially in ambiguous cases or RF negative patients with rheumatoid arthritis.     

Assessment of vertical changes during maxillary expansion using quad helix or bonded rapid maxillary expander

Objective:To determine if there is a significantly different effect on vertical changes during phase I palatal expansion treatment using a quad helix and a bonded rapid maxillary expander in growing skeletal Class I and Class II patients.Materials and Methods:This retrospective study looked at 2 treatment groups, a quad helix group and a bonded rapid maxillary expander group, before treatment (T1) and at the completion of phase I treatment (T2). Each treatment group was compared to an untreated predicted growth model. Lateral cephalograms at T1 and T2 were traced and analyzed for changes in vertical dimension.Results:No differences were found between the treatment groups at T1, but significant differences at T2 were found for convexity, lower facial height, total facial height, facial axis, and Frankfort Mandibular Plane Angle (FMA) variables. A comparison of treatment groups at T2 to their respective untreated predicted growth models found a significant difference for the lower facial height variable in the quad helix group and for the upper first molar to palatal plane (U6-PP) variable in the bonded expander group.Conclusion:Overall, both the quad helix expander and the bonded rapid maxillary expander showed minimal vertical changes during palatal expansion treatment. The differences at T2 suggested that the quad helix expander had more control over skeletal vertical measurements. When comparing treatment results to untreated predicted growth values, the quad helix expander appeared to better maintain lower facial height and the bonded rapid maxillary expander appeared to better maintain the maxillary first molar vertical height.     

Two novel AIRE mutations in autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) among Indians

Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) is a rare recessive disorder resulting from mutations in the autoimmune regulator ( AIRE ) gene. There is no information on AIRE mutations in Indians. In a cross-sectional study, nine patients (eight families), from four referral hospitals in India, were studied for AIRE mutations by direct sequencing. We screened for new mutations in 150 controls by allele-specific PCR. The patients had 1–7 known components of APECED. Three patients had unusual manifestations: presentation with type 1 diabetes; chronic sinusitis and otitis media; and facial dysmorphism. All patients carried homozygous, probably recessive, AIRE mutations. Two unrelated patients from a small in-bred community (Vanika Vaisya) in south India carried an unreported missense mutation, p.V80G, in the N-terminal caspase recruitment domain. Another unique mutation, p.C302X, resulting in a truncated protein with deletion of both zinc-finger domains, was detected in a patient from Gujarat. Neither mutation was detected in controls. Other mutations, previously described in Caucasians, were: 13 base pair deletion (p.C322fsX372) in 4 (38%), and Finn-major (p.R257X) and p.R139X (Sardinian) mutation in one subject each. In conclusion, in this first series of APECED in Indians, we detected AIRE mutations previously reported in Caucasians, as well as unique mutations. Of these, p.V80G is possibly an ancestral mutation in an in-bred community.     

Untersuchungen über die Reduktion des Oxyhämoglobins, „Sauerstoffzehrung“, am lebenden Gewebe und ihre Abhängigkeit vom jeweiligen Zustand des Organismus

Zusammenfassung Bei 200 Arbeitern wurde die Zeit, die nach Abschnürung der Finger zur Reduktion des O₂Hb zu Hb benötigt wird (R.Z.) durch Spektroskopie des Blutes am Finger festgestellt. Dabei zeigte sich sowohl ohne wie mit vorausgeschickter Atempause, nach letzterer noch ausgesprochener, ein deutlicher Unterschied; am stärksten war die R.Z. bei schwerer Hitzearbeit verkürzt, während die Arbeiter mit Gifteinwirkung (CS₂, Cyan) dieselben Werte wie ausgeruhte Schwerarbeiter vor der Arbeit hatten, und zwar die Durchschnitts- und die extremen Werte bei den einzelnen Gruppen. Bei CO-Wirkung scheinen die Verhältnisse ähnlich zu liegen. Es wird in Analogie zu der akuten Cyanwirkung als Ursache der Verlängerung der R.Z. bei Giftwirkung eine Schädigung der Zellatmung angenommen. Im übrigen steigt das O₂-Bedürfnis mit der Arbeit und die Parallele der normalen Altersreaktion zur vorzeitigen Abnutzungsreaktion liegt nahe.     

An effective Australian-Chinese peer education program on HIV/AIDS/STDs for university students in China

<正> IntroductionCurrently,there are at least 850,000 peo-ple living with human immuno-deficiency virus(HIV) and acquired immuno-deficiency syn-drome (AIDS) in China.Among them 16-29years old account for about 65%.Accordingto the Chinese health authorities,if the pre-ventive measures are not effective,the figurecould reach as many as 10 million by the year2010.Since there are currently no cure or     

C5a receptors are detectable on mast cells in normal human skin and in psoriatic plaques but not in weal and flare reactions or in urticaria pigmentosa by immunohistochemistry

The expression of the receptor for the anaphylatoxin C5a on mast cells was studied with three monoclonal antibodies directed to the N-terminal domain of the C5a receptor. Human skin was investigated by immunohistology applied to sequential 2 μm sections of acrylate-embedded tissues. All anti-C5a receptor antibodies stained c-kit ⁺ or tryptase ⁺ cells which were metachromatic after toluidine blue staining in normal human skin. The binding of anti-C5a receptor antibodies was inhibitable by a peptide representing the first 31 amino acids of the C5a receptor. A similar expression of C5a receptors was found on mast cells in chronic psoriatic plaques. However, C5a receptors were not detectable on mast cells in weal and flare reactions or in lesional skin of urticaria pigmentosa. These findings suggest that (1) anti-C5a receptor antibodies directed to the N-terminal domain of the receptor are suitable tools for the identification of mast cells in acrylate-embedded sections of human skin, (2) mast cell activation in weal and flare reactions results in C5a receptor downregulation or receptor blockade and (3) mast cells in urticaria pigmentosa lack a typical marker of normal human skin mast cells. Received: 29 November 1995     

Virilizing hepatoblastoma—Significance of alpha-1-fetoprotein and human chorionic gonadotropin as tumor markers in diagnosis and follow-up

Hepatoblastoma was diagnosed in a 12 month old boy presenting with hepatomegaly and isosexual precocious puberty. Preoperative levels of both alpha-l-fetoprotein (AFP) and human chorionic gonadotropin (HCG) were highly elevated. The tumor was removed by hepatic trisegmentectomy. Tumor tissue contained high concentrations of AFP and HCG. On combination chemotherapy with cyclophosphamide (CYC), vincristine (VCR), adriamycin (ADR) and 5-fluoruracil (5-FU) HCG dropped over a period of 9 months to normal values. In contrast, AFP was undetectable following surgery. One year after initiation of therapy there is no clinical or radiological evidence of recurrence of the malignancy but the observation period is too short to draw any conclusions on the effect of therapy and the final outcome.     

C3a activates the respiratory burst in human polymorphonuclear neutrophilic leukocytes via pertussis toxin-sensitive G-proteins

In contrast to C5a, which represents a well-established potent activator of the respiratory burst in polymorphonuclear neutrophilic granulocytes (PMN), the functional role of C3a in the activation of PMN is, so far, poorly understood. Herein, the potential role of human C3a in the activation of the respiratory burst in human PMN was investigated. The release of reactive oxygen species (ROS) of PMN from healthy donors was measured by lucigenin-dependent chemiluminescence. C3a dose-dependently induced the production of ROS in human PMN in the range between 10 ng/mL and 1,000 ng/mL, whereas C3a-desArg was inactive. Flow cytometric measurement of H2O2 by dihydrorhodamine-123 labeling of anti-CD16-stained PMN showed that predominantly neutrophilic PMN are responsible for the C3a-induced activation of the respiratory burst. To exclude that C3a stimulation was caused by contamination with C5a, the specificity of C3a-induced activation of PMN was shown using monoclonal antibodies (MoAbs). Accordingly, the effect of C3a was completely abolished in the presence of Fab fragments of a blocking anti-C3a MoAb. In addition, blockade of the C5a receptor by the anti-C5a receptor (anti-C5aR) MoAb, S5/1, totally inhibited the C5a-induced production of ROS, whereas the C3a response in the presence of the anti-C5aR MoAb was unaffected. The specificity of the response was further confirmed by homologous desensitization after restimulation with C3a. In contrast, no cross-desensitization was observed upon stimulation with C5a. The C3a-induced ROS production by PMN was inhibited by pertussis toxin, indicating the involvement of guanine nucleotide-binding proteins (Gi proteins) in the signal transduction process initiated by C3a. In addition, stimulation of PMN by C3a resulted in a transient increase in the cytosolic free calcium concentration ([Ca2+]i) in a dose-dependent manner. In contrast to C3a- induced ROS production, C3a did not induce a chemotactic response in PMN, indicating functional qualitative differences as compared with C5a. In summary, these results show that C3a is a potent activator of the respiratory burst in human PMN. Therefore, these findings point to a novel role of C3a in the pathogenesis of inflammatory diseases associated with increased C3a levels and PMN activation.