Linkage between rheumatoid arthritis susceptibility and the presence of HLA-DR4 and DR beta allelic third hypervariable region sequences in southern Chinese persons.

OBJECTIVE: To analyze HLA-DR and DQ associations with rheumatoid arthritis (RA) in patients from southern China. METHODS: In 66 patients and 45 controls, restriction fragment length polymorphism studies were performed using DRB, DQA, and DQB probes, and DRB allele-specific typing of polymerase chain reaction-amplified DRB DNA: RESULTS: The frequency of HLA-DR4 was significantly increased among RA patients (42.4% versus 17.8%). Increased frequencies of the DQA3 allele (77.8% versus 48.9%) and the DQB1*0302 allele (71.0% versus 46.3%), which are in linkage disequilibrium with DR4, were also found. Oligonucleotide typing showed that the amino acid sequence LLEQRRAA, spanning amino acid positions 67-74 of the DR beta molecule, was found in 19 of 49 patients and 5 of 32 controls. The main DR4 allelic subtypes found in the population were DRB1*0404 and DRB1*0405, both of which carried the sequence. There was no difference in subtype distribution between patients and controls. CONCLUSION: Chinese RA patients have an increased frequency of HLA-DR4 alleles which possess the same DRB third allelic hypervariable sequence shown to be associated with susceptibility in Caucasian RA patients.

Comparisons of spontaneous pain and tenderness in patients with primary fibromyalgia.

Pain was assessed in 47 patients with fibromyalgia in the University Rheumatology Clinic in Basle with the aid of three different techniques. First, a simple visual analog scale was used, later a body diagram on which patients could indicate pain separately in different regions of the body (pain score) and, finally, dolorimetric measurements at 56 typical PFS tender points. After four weeks of therapy, pain was again scored by patients using these techniques. The changes in assessment were compared with the aid of Spearman correlation. Data recorded with the aid of the body diagram correlated better with dolorimetric findings than did the results obtained from a simple visual analog scale. The severity of the disease can be more objectively assessed using these three techniques than it can using only the visual analog scale. In particular, the pain score and dolorimetry make possible a clear assessment of the value of therapeutic regimens.

[Rheumatic manifestations in HIV infection]. / Rheumatische Manifestationen bei HIV-Infektion.

The two main rheumatic manifestations of infection by human immunodeficiency virus (HIV) are arthropathies and autoimmune diseases. The pathogenesis of the rheumatic manifestations is currently undefined. Among the different mechanisms implicated, the severe immunosuppression and immunodysregulation, as well as recurrent infections are possible. A direct infection by HIV is another mechanism. The course of some rheumatic diseases may be altered by HIV-infection. Remission of rheumatoid arthritis during the course of HIV-infection is anecdotally reported in the literature, whereas patients with Reiter's syndrome seem to have a severe clinical course.

[Localized pressure pain in the diagnosis of generalized tendomyopathy (fibromyalgia)]. / Lokalisierte Druckschmerzen in der Diagnose der generalisierten Tendomyopathie (Fibromyalgie).

56 tender points were examined in 100 patients and 50 age- and sex-matched healthy volunteers using a dolorimeter. 24 of the 56 points were especially selected according to ability of discrimination, best possible distribution on the body, and easy localization. All 56 points as well as the 24 specially selected points were examined as to their sensitivity and specificity in the diagnosis of generalized tendomyopathy. The sensitivity and the specificity for both point-combinations were acceptable. The sensitivity and specificity of the 24 points were superior to the 56 points in the case of discrimination ability. A 100% sensitivity and specificity could not, however, be achieved. It remains to be considered if functional and vegetative symptoms must still be used to support the diagnosis of generalized tendomyopathy (fibromyalgia).

[Serum hyaluronic acid and aminoterminal procollagen III peptide in inflammatory and degenerative joint diseases]. / Serum-Hyaluronsäure und aminoterminales Prokollagen-III-Peptid bei entzündlichen und degenerativen Gelenkerkrankungen.

Serum levels of hyaluronic acid (HA) and the amino-terminal type III procollagen peptide (NP-III-P) were determined simultaneously by specific immunoassays in patients with rheumatoid arthritis (n = 41), osteoarthritis (n = 43), ankylosing spondylitis (n = 7), psoriatic arthritis (n = 6), and reactive arthritis (n = 6). Increased serum levels of both HA and NP-III-P, were found in rheumatoid arthritis and - although less pronounced - in osteoarthritis, differing significantly from age- and sex-matched controls (n = 77). Furthermore, patients suffering from active rheumatoid arthritis showed higher serum levels of both antigens than patients with inactive disease, and significant correlations were found in rheumatoid arthritis between acute phase plasma proteins, HA and NP-III-P, respectively. In contrast, determination of low molecular weight fractions of NP-III-P by Fab- assay proved not to be useful in regard to clinical application. No significant effects of anti-inflammatory treatment were evident in any of the parameters. In rheumatoid patients, the serum concentrations of HA were found to correlate positively with the serum reactivity of NP-III-P related antigens (r = 0.692) and with the excretion of urinary pyridinoline (r = 0.455). Thus, both parameters seem to reflect similar mechanisms of connective tissue activation and may be related to inflammatory activity in joint diseases.

Patterns of diffusion through skin capillaries in patients with long-term diabetes.

We used intravital fluorescence videomicroscopy to study the pattern of transcapillary and interstitial diffusion in the nail folds of 13 patients with long-term diabetes and of 12 healthy controls. In both groups intravenously injected sodium fluorescein left the intravascular compartment. Its distribution in the pericapillary space and in the remote parts of the interstitial space was measured on single frames of the television tape by videodensitometers that are sensitive to intensities of fluorescent light. In the diabetics the dye passed both physiologic diffusion barriers--the capillary wall and the pericapillary space--in significantly increased amounts (P less than 0.01). The enhanced penetration of the tracer into the remote area caused an early homogeneous, milky blurring of the capillary image, whereas in the controls the pericapillary space remained clearly delineated for as long as 40 to 50 minutes after the appearance of the dye. The altered pattern of diffusion could be explained by increased permeability of the diffusion barriers, or, alternatively, by either changes of the mobility of the dye due to binding of the dye by intravascular or interstitial proteins or abnormal hemodynamics in the microvascular circulation. This technique provides a quantitative, noninvasive method of studying the natural history of diabetic microangiopathy.

Transcapillary and interstitial diffusion of Na-fluorescein in chronic venous insufficiency with white atrophy.

White atrophy (atrophie blanche) in the medial ankle region due to chronic venous insufficiency (stasis syndrome) was studied in 12 patients by fluorescence video microscopy [1,8]. After intravenous bolus injection of 1 ml of 20% Na-fluorescein the dynamic phenomena of transcapillary and interstitial diffusion of the dye were analyzed by a videodensitometer which has moved on single frames of the TV-recordings across white atrophy at different times after dye appearance. White atrophy is characterized by 3 main areas: 1) the avascular field sensu strictu, 2) the border region with enlarged and tortuous capillary loops, and 3) the more remote capillaries showing less altered morphology. The dye reached the ankle skin after 39.2 +/- 13.3 S and leaved rapidly the intravascular compartment. In the region of the border capillaries, the maximal fluorescent light intensity was reached after 5 min, in the centre of the avascular field only after 40 min. Initially, the densitometer curves show a 'valley' which is slowly filled up by the dye. At 40 min and later on the highest light intensities were measured in the central parts of the avascular field ('mountain'), where the clearance was just beginning. The slow diffusion of the small tracer into the avascular field explains that white atrophy is a predilection site for venous ulcer formation.

Fluorescence microlymphography.

Microneedles, 0.2 mm o.d., were connected to a microsyringe and mounted on a micromanipulator. Under microscopic control, 0.01 ml of a 25% solution of FITC-labeled dextran-40 or dextran-150 were injected into the subepidermis at the big toe near the nailfold or in the medial ankle region. Fluorescence intravital microscopy revealed a network of lymphatic microvessels. The comparison with recent anatomic studies reveals that the reticular network visualized by FITC-dextran corresponds to the network in the stratum papillare. In 20 healthy subjects lymphatic capillaries were detected in a restricted area on the lateral aspect of the big toe. In 10 patients with primary lymphedema, the dye expanded to almost the entire dorsal skin surface of the big toe. In two cases, enlarged and tortuous microvessels of pathologic shape were observed. Fluorescence microlymphography is a simple and nearly atraumatic approach for depicting the intravital anatomy of human skin lymphatic capillaries.

Dosage in low-dose heparin prophylaxis.

We investigated whether the dosage of heparin injected subcutaneously for the postoperative prophylaxis of thromboembolism influences efficacy. We considered prospective, controlled or comparative, randomized studies in which heparin was administered in a dosage of 5,000 U b.i.d. or t.i.d. subcutaneously. In major surgical procedures in general surgery, gynecology, urology and chest surgery, 2 x 5,000 and 3 x 5,000 U of heparin/day lower the frequency of postoperative deep venous thrombosis from about 30% to about one-fourth and one-third that amount, respectively. With regard to orthopedic/traumatic surgery, in a study of only 40 patients, 2 x 5,000 U/day reduced the incidence of thrombosis by one-half. The use of the higher dosage resulted in a decrease in DVT in 5 of 7 reports, but the other two authors measured no prophylactic effect at all. Proof that subcutaneous heparin prophylaxis is also able to reduce the number of fatal postoperative pulmonary emboli has been produced only in the case of the higher dosage. In our own group of patients there is no correlation between body weight and frequency of hemorrhagic complications. In our patients there is no relation between malignant tumor as the primary disease and the occurrence of hemorrhagic complications. There is no evidence that the lower dosage causes fewer hemorrhagic complications than the higher dosage.