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Biomedical subjects

R Manthorpe

Publications and source records attributed to R Manthorpe.

At least 73 records · Page 4Linked to original sources

Autoimmune antibodies and pregnancy outcome in women with false-positive syphilis test results. A retrospective controlled investigation of women from 5170 deliveries.

Nine pregnant women with false-positive syphilis test results, and 13 matched controls, were screened for autoimmune antibodies to ascertain whether any relationship might exist between their presence and the occurrence of obstetric problems. Investigations included assays for anti-cardiolipin antibodies (ACA), lupus anticoagulant (LAC), anti-nuclear antibodies (ANA) (including antibodies against extractable nuclear antigen), anti-smooth muscle antibodies, anti-mitochondrial antibodies, anti-DNA antibodies, IgM-RF and complement factors. We found no significant difference in the incidence of obstetric problems between the two groups. Except that significantly more women were positive for ACA in the group with false-positive syphilis tests than in the control group, there were no differences between the groups with regard to the antibodies tested for. There was only one case of SLE, a patient positive for LAC, and who had had several miscarriages and no pregnancy resulting in a live birth. Our findings suggest that it would be unwarranted to devote resources to routine screening for these antibodies in healthy women with a false-positive syphilis test result, though the presence of LAC could possibly be used as an indicator of the risk of spontaneous abortion due to SLE.

Antiphospholipid Syndrome↗

Clinical and immunological features of Sjögren's syndrome in patients with primary biliary cirrhosis with emphasis on focal sialadenitis.

Serological and pathological findings in 21 patients with primary Sjögren's syndrome (primary SS) were compared with those in 32 patients with primary biliary cirrhosis (PBC). In ELISA, anti-SS-B/La antibodies were detected in sera from 14 (67%) of the patients with primary SS, but only from 12 (38%) of those with PBC. With the Ouchterlony test, anti-SS-A/Ro antibodies were found in sera from 15 (71%) of the primary SS patients, but in no PBC patient. Of those PBC patients investigated prospectively with objective tests, four of 11 (36%) had keratoconjunctivitis sicca, and five of 15 (33%) had pathological sialometry results. In contrast, all PBC patients but one (i.e., 14 of 15 or 93%) showed evidence of focal sialadenitis. In immunochemical study of PBC patients, IgM immunoreactivity was found in the stroma, particularly adjacent to excretory ducts and acini in salivary glands (5 of 5), whereas no such IgM deposits were observed in patients with primary SS (3 of 3), nor in healthy controls (n = 20). We conclude that the frequency of anti-SS-A/Ro and anti-SS-B/La antibodies in serum is lower in PBC patients than in patients with primary SS. The incidence of focal sialadenitis is high in PBC, though only one third of the PBC patients studied here showed clinical evidence of glandular dysfunction. With immunochemical techniques, sialadenitis associated with PBC is distinguishable by its significant IgM reaction from sialadenitis in primary SS.

Aged↗

SS-B/La antigen purification, and ELISA detection of anti-SS-B/La antibodies in sera from patients with inflammatory connective tissue diseases.

SS-B/La antigen was purified by immunoadsorbent columns with immunoglobulin from a patient with primary Sjögren's syndrome. Monitoring of the purification was facilitated by the fused rocket-immunoelectrophoresis technique. Technical ELISA variables for the detection of serum antibodies against the SS-B/La antigen were evaluated, and a recommended procedure is described. Prospective investigation of anti-SS-B/La antibodies in 103 blood donors and 131 patients with chronic inflammatory connective tissue diseases, including 43 patients with primary Sjögren's syndrome was performed. Anti-SS-B/La antibody concentrations were above normal in 65% of the patients with primary Sjögren's syndrome (verified by the strictly objective Copenhagen criteria for keratoconjunctivitis sicca and xerostomia) and 9% of patients with other chronic connective tissue diseases. The predictive value for primary Sjögren's syndrome among patients with increased levels of the anti-SS-B/La antibodies attending a rheumatology clinic was 78%.

Antibodies, Antinuclear↗

Circulating IgM rheumatoid factors in patients with primary Sjögren's syndrome.

The importance of circulating rheumatoid factors (RF) in primary Sjögren's syndrome (primary SS) was evaluated retrospectively by examining medical case records of 80 consecutive patients. Increased levels of IgM RF, determined by the Waaler test, the latex fixation test and/or the ELISA test, were found in 47 patients (59%). Follow-up examination of the 41 patients in whom more than one (mean 4.9 (2-12)) RF determination over at least a two-year period (mean 5.6 (2-13) was present, showed that 12/41 patients (29%) were permanently RF-negative, 7/41 (17%) exhibited both positive and negative RF values and 22/41 (54%) were permanently RF positive. Variations in IgM RF levels were unrelated to disease duration. Except for involvement of joints, extraglandular manifestations were more common in patients with increased levels of RF. This finding, however, was only significant within the group of more rarely occurring extraglandular manifestations (serositis, interstitial nephritis, cutaneous vasculitis, lymphoproliferative disorders and intermittent fever) (p less than 0.01). IgM RF levels were likewise positively correlated (p less than 0.001) to positivity of IgG antinuclear antibodies as well as to the plasma concentrations of immunoglobulins.

Adult↗

The hypereosinophilic syndrome. Report of a case with successful medical treatment following cardiac biopsy.

Together with pronounced blood eosinophilia an endomyocardial biopsy is the method of choice in diagnosing and assessing the severity of the systemic disorder hypereosinophilic syndrome (HES). Eosinophilia is not uncommon in several connective tissue diseases which may share clinical manifestations with HES. We report a case of HES, investigated and followed up with cardiac biopsies. A missing right radial artery pulsation gave rise to several differential diagnostic considerations.

Biopsy↗

Circulating IgG from patients with primary Sjögren's syndrome deposited in the epidermis of normal human skin transplanted to athymic nude mice.

Sera from 7 patients with primary Sjögren's syndrome and from two control persons were administered intraperitoneally to athymic nude mice transplanted with normal human skin. Seven days after transfer of serum from 5 of the patients, intra-epidermal IgG1 and IgG3 deposits were demonstrated in the skin grafts by immunofluorescence. The deposits closely resembled in vivo deposits found in the skin of these patients. No correlation was found between the presence of epidermal deposits and levels of IgG1 and IgG3 in serum. No IgG deposits were found in skin grafts on animals given control serum, and neither could human IgG be detected in mouse skin adjacent to the grafts. Epidermal deposits of human-IgM, -IgA, -fibrinogen, -C3c and mouse-Ig were not demonstrated in biopsies from grafts or mouse skin. The results support the hypothesis that epidermal in vivo deposits of IgG in patients with primary Sjögren's syndrome are the result of Fc-receptor-mediated binding to epidermal cells.

Adult↗

Complement C3b receptors on erythrocytes, circulating immune complexes, and complement C3 split products in patients with primary Sjögren's syndrome.

Twenty-one patients with primary Sjögren's syndrome (SS) and 22 age- and sex-matched healthy controls were examined for levels of C3b receptors (CR1) on erythrocytes (by an enzyme-linked immunosorbent assay), levels of circulating immune complexes (IC) (by a polyethylene glycol precipitation complement consumption method), and C3 split products, C3d and C3c (by intermediate gel rocket immunoelectrophoresis). CR1 varied within a wide range (20-124%), and a preponderance of low numbers was found among patients with primary SS (P less than 0.05). The levels of circulating IC and C3d were elevated in primary SS patients (P less than 0.01) and were mutually correlated (P less than 0.01; tau = 0.5), but levels of circulating IC and C3d did not correlate with CR1 values. C3c concentrations were the same in patients and controls. It is possible that the CR1 level serves as a predictor for the development of IC-induced manifestations, and the C3d concentration serves as an objective parameter for disease activity in primary SS.

Adult↗

Behçet's disease (a severe case from Greenland).

Behçet's syndrome has to our knowledge not been described hitherto in Greenland Eskimos. A life-threatening case of Behçet's syndrome is described in a 22-year-old female Eskimo. Ulceration and scar formation in the oral and hypopharyngeal cavity were the main clinical manifestations. Treatment with broad-spectrum antibiotics and high-dose prednisone appeared effective.

Adult↗

Platelet function in patients with primary Sjögren's syndrome.

Platelet function tests were performed in 15 patients with primary Sjögren's syndrome (SS) and in 15 normal controls. Platelet counts were within the normal range in all except two patients in whom they were only slightly decreased. P-beta-thromboglobulin was increased in several patients compared to controls, although not significantly (p less than 0.1). Platelet aggregation was enhanced in patients when measured upon stimulation with epinephrine (p less than 0.05), ADP (p less than 0.01) and collagen (p less than 0.01). No correlation was found between enhanced platelet activity and sex, age, duration of disease, extraglandular manifestations, positive ANA test, elevated P-IgG or P-immune complexes. Enhanced platelet activity in patients with primary SS is a new observation. Future studies are needed to elucidate the pathogenetic background.

Adenosine Diphosphate↗

Immunoglobulin deposits in labial mucosal epithelium of patients suspected of Sjögren's syndrome.

Lower lip biopsies from twenty-three consecutive patients under evaluation for Sjögren's syndrome, and from six normal controls, were investigated for deposits of immunoglobulins, fibrinogen and C3, using a direct immunofluorescence technique. Deposits of both IgG and IgA were demonstrated in the mucosal epithelium in three of six patients with primary Sjögren's syndrome. Similar IgG deposits were found in two of three patients with xerostomia and in one of three patients with Sjögren's syndrome secondary to rheumatoid arthritis. Immunoglobulins were located in close relation to cell surfaces in the basal and suprabasal layers of the epithelium. Double labelling experiments indicated a partial topographic concordance between the immunoglobulin deposits and OKT6 positive Langerhans cells in the epithelium. No deposits of immunoglobulins, fibrinogen or C3 were found in the remaining eleven patients and six normal controls. We conclude that deposits of IgG and IgA in the labial mucosal epithelium seem to be a characteristic finding in patients with primary Sjögren's syndrome as well as in patients with xerostomia. The diagnostic value of this new observation needs to be clarified in future studies.

Adult↗

Epidermal Langerhans cells in patients with primary Sjögren's syndrome.

IgG-binding to the surface of Langerhans cells (LC) is a feature of primary Sjögren's syndrome and might be associated with qualitative and quantitative defects in LC. Fifteen patients with primary Sjögren's syndrome and 15 healthy controls had a punch biopsy performed from clinically unaffected skin. LC were enumerated in epidermal sheets by an immunoperoxidase technique, as well as demonstrated by immunofluorescence in vertical sections, which were furthermore examined for in vivo deposits of immunoglobulins, fibrinogen and C3. A significant (P less than 0.05) reduction in number of LC, measured on epidermal sheets, was found in patients as compared with controls. Examination of vertical sections did not reveal abnormalities in morphology or localisation of epidermal LC. Intraepidermal IgG deposits were demonstrated in 7/15 patients. In vivo deposits were not found in any of the controls. The density of epidermal LC was not correlated to the presence of intraepidermal IgG deposits.

Adult↗

Auranofin versus penicillamine in rheumatoid arthritis. One-year results from a prospective clinical investigation.

Forty patients with definite or classical active rheumatoid arthritis were stratified by the minimization procedure to auranofin (6 mg/day) or penicillamine (go slow and low regime). This investigation is a prospective planned 3 year patient and 'doctor-open' as well as 'doctor-blind' clinical trial. This article describes the results after 12 months. Both drugs decreased disease activity and improved the functional capacity in a similar way. Two patients in the auranofin group and 5 in the penicillamine group stopped treatment due to major side effects. Four other patients in the auranofin group left treatment: 2 due to death from unrelated cause and 2 according to the Helsinki II Declaration. After one year a further patient in the auranofin group and 2 in the penicillamine group stopped treatment due to lack of clinical effect. Side effects due to auranofin were statistically more frequent distal in the gastrointestinal tract (loose stools/diarrhoea) than with penicillamine. In contrast, penicillamine produced significantly more side effects in the oral cavity (mainly taste disturbances) than auranofin. Other side effects were about equal in the two groups, but 2 cases of severe proteinuria and one with obstructive lung disease were observed in the penicillamine group. Only 3 patients did not complain of any untoward effect during the 12-month period. We conclude that on the basis of this one year investigation it is an open question whether one should select auranofin or penicillamine for the treatment of clinical active rheumatoid arthritis.

Acute Disease↗