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Biomedical subjects

R Manthorpe

Publications and source records attributed to R Manthorpe.

At least 163 records · Page 9Linked to original sources
PubMed1975

Glucocorticoid effect on repair processes in vascular connective tissue. Morphological examination and biochemical studies on collagen RNA and DNA in rabbit aorta.

Male rabbits were injured by a single mechanical dilatation of the aorta and then injected with prednisone 2 mg/kg saline for 14 days or starved. Morphological studies and biochemical measurements of the collagen metabolism, the content of alpha-amino nitrogen, RNA, DNA, water and fat, and the aorta to serum ratio of 125I-albumin were performed on the intima-media layer of the descending thoracic aorta. Prednisone inhibited the intimal thickening. In the media the infiltration by mononuclear cells, the proliferation and regeneration of the smooth muscle cells and the calcification were reduced. Prednisone caused a decrease in 0.45 M NaCl soluble collagen as well as in the dialysable and non-dialysable 14C-hydroxyproline fractions. The total amount of collagen, elastin and alpha-amino nitrogen was unchanged, whereas the 14C-proline incorporation in the non-dialysable protein fraction was inhibited to a greater extent than the 14C-hydroxyproline synthesis. The findings indicate that prednisone inhibits the biosynthesis of collagen, which is inhibited to a greater extent than the general protein synthesis. Prednisone increased the dialysable to non-dialysable 14C-hydroxyproline ratio consistent with a relative increase in the catabolism of newly synthesized collagen. The aortic content of RNA and DNA was reduced consistent with the inhibition of protein synthesis and cell proliferation. Finally prednisone decreased the aortic content of water when related to the wet weight and increased the aortic content of fat. The aorta to serum ratio of 125I-albumin was not influenced by prednisone. It is concluded that administration of glucocorticoid for 14 days exerts an inhibitory action on the histological reaction to injury as well as on the biosynthesis of collagen of the repair processes in vascular connective tissue. A comparison with the effects of prednisone on undamaged rabbit aorta (Manthorpe et al. 1974) demonstrates that the metabolism of collagen of vascular connective tissue during repair is more sensitive to the antianabolic effects of prednisone than collagen in the non-injured aorta. Starvation caused an increase of the aortic percentage of water but otherwise had no influence on the repair processes in the vascular connective tissue.

Animals↗
PubMedDate not supplied

Progress and regression within primary Sjögren's syndrome.

The purpose of this review is to give a modern view and an update of important areas in primary Sjögren's syndrome (SS), which may be the most common of the autoimmune systemic rheumatic diseases. Interest in aspects of primary SS including clinical manifestations, pathogenesis, aetiology, treatment, prognosis, etc has increased during the past three decades, the volume of scientific papers and the number of theses being the indicators. However, only a fraction of the money that is used for research into rheumatoid arthritis (RA) is used for SS, and the statement that SS is under-diagnosed, under-treated and under-researched will still be valid for several years to come. The topics that are focused on in this review are: (a) clinical areas with subsections on signs and symptoms, terminology, predictors for development of non-Hodgkin malignant lymphoma (NHML) and prognosis, (b) treatment, (c) the Danger model (aetiopathogenesis) and (d) pathology, including immunoglobulin G4 (IgG4)-positive cells.

Antibodies, Monoclonal↗
PubMedDate not supplied

Seroprevalence of Helicobacter pylori in primary Sjögren's syndrome.

OBJECTIVE: To study the seroprevalence of Helicobacter pylori (H. pylori) infection in patients with primary Sjögren's syndrome (SS), fulfilling the 1993 European classification criteria compared with three different control groups. METHODS: Serological tests investigating the presence of antibodies against H. pylori were performed by Enzyme Immuno Assay (EIA) and confirmed by immunoblot (IB). The samples were tested for antibodies against cytotoxin-associated-protein A (CagA). The three control groups included were: one simultaneously collected age-matched group of orthopaedic outpatients without rheumatological disease, a random primary care patient sample from the same geographic region and a group of age-matched blood donors. RESULTS: 45% of the SS patients (n = 164) were EIA-positive for H. pylori and 30% were positive in the confirming IB assay. 23% had antibodies to the CagA protein. We found a clear and statistically significant increase in seroprevalence with increasing age. These estimates were lower compared to the control group of orthopaedic patients but similar to those in the other two control groups, thus showing the importance of multiple control groups in case control studies. In the group of SS patients there were no significant associations between a positive EIA, IB or CagA for H. pylori and the presence of abnormal serum levels of autoantibodies (ANA, anti-SSA, anti-SSB, rheumatoid factor (RF)) or an abnormal lip biopsy. CONCLUSION: Swedish patients with primary SS do not have higher H. pylori seroprevalence rates than controls. Neither was H. pylori seropositivity associated with the presence of immunological markers of SS such as circulating autoantibodies or a lip biopsy with abnormal focus score.

Adolescent↗
PubMedDate not supplied

Autoimmune thyroiditis and primary Sjögren's syndrome: clinical and laboratory evidence of the coexistence of the two diseases.

The prevalence of primary Sjögren's syndrome (primary SS) among patients with autoimmune thyroiditis (AT), and that of AT among patients with primary SS were studied prospectively. Of 63 patients with AT, one had precipitating antibodies against SS-A/Ro antigen together with objectively verified primary SS, and none had precipitating anti-SS-B/La antibodies; in contrast 17/63 (27%) had above normal values of anti-SS-B/La antibodies, as tested with ELISA. Of 19 AT patients tested objectively for xerostomia and keratoconjunctivitis sicca, six (32%) had keratoconjunctivitis sicca together with xerostomia and four (21%) had autoimmune sialadenitis. The prevalence of AT in patients with primary SS (n = 28) was 18%; of the 28 patients, 64% had an enlarged or abnormal thyroid gland on palpation and four of them (14%) had cytology verified AT. Ten (36%) had anti-thyroglobulin and/or antimicrosomal autoantibodies. Based upon the present investigation we conclude that the prevalence of primary SS is ten times higher among patients with AT, and that of AT is nine times higher among patients with primary SS, compared with the general population.

Adult↗
PubMedDate not supplied

Xerostomia.

This communication describes the etiology, frequency, and various symptoms involved in the phenomenon of dry mouth and also discusses in detail the objective tests generally used when evaluating patients for xerostomia as the oral component of Sjögren's syndrome. It is stressed here that no single test has a sufficiently high specificity and sensitivity and consequently we recommend that at least two tests should give abnormal results before the xerostomia diagnosis is accepted.

Biopsy↗
PubMedDate not supplied

Epidermal IgG deposits in patients with chronic inflammatory connective tissue diseases: diagnostic value and correlation to clinical and immunological parameters in patients with primary Sjögren's syndrome.

Thirty-seven patients with primary Sjögren's syndrome (Primary SS), 12 patients with incipient primary SS, 100 patients with other chronic inflammatory connective tissue diseases (CTD) and 20 healthy controls had a punch biopsy taken from clinically unaffected skin from the buttock. Direct immunofluorescence examinations revealed intraepidermal IgG deposits in 68% of patients with primary SS, in 42% of patients with incipient primary SS, in 13% of patients with rheumatoid arthritis (RA, n = 31), in 15% of patients with systemic lupus erythematosus (SLE, n = 13), in 24% of patients with other well-defined CTD (n = 41), in 40% of patients with ill-defined CTD (n = 15) and in 10% of healthy controls. Immunoglobulin deposits along the dermoepidermal junction zone (DEJ) were not found in any of the patients with primary SS, but were present in 16% of the patients with RA and in 23% of the patients with SLE. In the patients with primary SS, no correlation was found between intraepidermal IgG deposits and age, disease duration, extraglandular manifestations, P-IgG concentration, ANA, rheumatoid factors or circulating immune complexes. Examination for intraepidermal IgG deposits seems valuable in the differential diagnosis between primary SS and RA or SLE, and it could supplement the lupus band test.

Adult↗
PubMedDate not supplied

Jaccoud's syndrome. A nosographic entity associated with systemic lupus erythematosus.

Six Scandinavian cases of Jaccoud's syndrome, resulting from systemic lupus erythematosus (SLE) are described; 1 patient suffered from both SLE and rheumatoid arthritis (RA). Clinically, the patients showed hand deformities similar to those of RA with pronounced ulnar deviation and swan-neck configuration. Clinically, however, the hands in cases of Jaccoud's syndrome differ from those in RA because the deformities develop more slowly, without much pain, and hand function is well-preserved. Radiologically, subluxation develops in the metacarpophalangeal joints without the typical rheumatoid joint-associated osseous destruction. The presence of erosions and hooks are exceptional and, if present, they are not typical of RA. It is important that Jaccoud's syndrome be recognized and differentiated from RA because an incorrect diagnosis could lead to a choice of therapy inappropriate for patients with SLE.

Adult↗
PubMedDate not supplied

CD4+ T-lymphocytopenia without HIV infection: increased prevalence among patients with primary Sjögren's syndrome.

OBJECTIVE: Primary Sjögren's syndrome (1 degree SS) is an autoimmune disease, usually accompanied by manifest immune hyperactivity. In some cases the disease converts to malignant neoplasia. On the other hand, there are clinical similarities to HIV infection. Since the rare phenomenon of persistent depletion of CD4+ T-lymphocytes in peripheral blood without HIV infection was recently defined as idiopathic CD4+ T-lymphocytopenia (ICL), we have used the ICL criteria to investigate the prevalence of this phenomenon among 1 degree SS patients. METHODS: During the period 1988-94, 115 caucasian patients (10 males), mean age 57.8 (range 19-82) years, with 1 degree SS were prospectively studied. Lymphocyte subsets were investigated by means of monoclonal antibodies and flow cytometry. For the detection of HIV and HTLV antibodies, we used an enzyme immunoassay (for HIV-1 and HIV-2), Western blot techniques (HIV-1, HIV-2, HTLV-I and HTLV-II), and the polymerase chain reaction procedure (HIV-1, HTLV-I and HTLV-II). HIV antigens were tested for with the HIV-1 p-24 Ag test. RESULTS: Six patients with 1 degree SS fulfilled the criteria for ICL. While the clinical condition of 5 of those six patients remained stable, one patient developed malignant lymphoma three years after her disease was classified as a case of ICL. The prevalence of ICL among our 115 patients with 1 degree SS was 5.2%, which is significantly higher than the rates reported for any other patient or population group. We have estimated the relative risk of ICL in 1 degree SS patients to vary from 3.4 to 6,000 (P values of 0.0001-0.025). CONCLUSION: We suggest that subjects with ICL should be carefully examined for 1 degree SS and, if its presence is confirmed, that they should be followed with regard to the possible complications of this disease, including the development of malignant lymphoma.

Adult↗