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Biomedical subjects

R Manthorpe

Publications and source records attributed to R Manthorpe.

At least 91 records · Page 5Linked to original sources
PubMed1986

Patients with primary Sjögren's syndrome treated for two months with evening primrose oil.

Twenty-four female and 4 male patients, all fulfilling the Copenhagen criteria for primary Sjögren's syndrome (primary SS), were treated for 8 weeks with evening primrose oil (Efamol). Efamol is a seed oil which consists primarily of the n-6 essential fatty acids (EFA): cis-linoleic acid and gammalinolenic acid (GLA). The investigation was carried out as a randomized, double-blind, placebo-controlled, cross-over trial in order to determine whether long-term treatment of patients with primary SS with Efamol would improve the ocular and oral clinical status, and whether the levels of EFA in plasma and erythrocytes increase during Efamol treatment. The objective ocular status, evaluated by a combined ocular score, including the results from Schirmer-I test, break-up time and van Bijsterveld score, improved significantly during Efamol treatment when compared with Efamol start-values (p less than 0.05), but not when compared with placebo values (p less than 0.2). The GLA metabolite and prostaglandin-E1 (PGE1) precursor dihomogammalinolenic acid (20: 3n6, DGLA) increased both in plasma (p less than 0.001) and in erythrocytes (p less than 0.001) during treatment with Efamol. No correlations between objective ocular and oral status and DGLA values in plasma or erythrocytes were found.

Adult↗
PubMed1986

Erythrocyte complement C3b receptor (CR1) levels and immune complex-induced manifestations in patients with primary Sjögren's syndrome.

To assess the importance of low C3b receptor (CR1) numbers on erythrocytes for the development of clinical features in patients with primary Sjögren's syndrome (SS), two groups of patients were selected for investigation--one without (n = 13), and one with (n = 21) extraglandular, possibly immune complex-induced, clinical manifestations during the disease course. A preponderance (p less than 0.01) of low CR1 levels was found in patients with primary SS (mean 57%) as compared with normal controls (mean 70%), but the CR1 levels did not differ between the two groups of patients. The CR1 values did not correlate with the levels of circulating immune complexes and C3d. Although the preponderance of low CR1 levels is pathogenetically intriguing, it appears to be of little help in the clinical assessment of patients with primary SS.

Antigen-Antibody Complex↗
PubMed1986

Diagnostic significance of immunohistological skin examination in patients with primary Sjögren's syndrome and other chronic inflammatory connective tissue diseases.

Clinically unaffected skin from 57/84 (68%) patients with primary Sjögren's syndrome (primary SS) was found to contain intraepidermal in vivo deposits of IgG, using a direct immunofluorescence technique. Similar IgG deposits were found in only 4/26 (14%) patients with secondary SS, in 3/28 (11%) patients with rheumatoid arthritis without SS (RA), in 2/13 (15%) patients with systemic lupus erythematosus without SS (SLE), in 10/41 (24%) patients with other well-defined connective tissue disease (CTD) and in 2/65 (3%) of normal controls (p less than 0.001 for all groups compared to primary SS). Intraepidermal IgG deposits were found in 5/12 (42%) patients with incipient primary SS and in 6/15 (40%) patients with ill-defined CTD (NS). None of the patients with primary SS had immunoglobulin deposits in the dermo-epidermal junction zone, while this was observed in 12% of the patients with RA and in 20% of the patients with SLE. We conclude that the presence of intraepidermal IgG deposits is valuable in the differential diagnosis between primary SS and RA or SLE, even if RA and SLE are complicated with SS. Examination for intraepidermal IgG deposits should supplement the lupus band test.

Fluorescent Antibody Technique↗
PubMed1986

Characterization of intraepidermal IgG deposits in patients with primary Sjögren's syndrome.

In order to characterize the pathomechanisms behind intraepidermal in vivo deposits of IgG, which are found in 68% of patients with primary Sjögren's syndrome (primary SS), skin biopsies and serum from patients with epidermal IgG deposits were examined and compared to normal controls. Double-labelling experiments on skin biopsies, from 5 patients and 5 normal controls, showed that IgG deposits were predominantly located to surface membranes of OKT6 positive Langerhans cells. Only IgG1 and IgG3 were found deposited. Neither IgG2, IgG4, IgM, IgA, IgE, IgD, C1q, C3c, fibrinogen, albumin, beta-2 microglobulin nor C-reactive protein were found deposited in the epidermis of patients. Sera from 6 other patients with primary SS were examined for in vitro and in vivo binding of IgG to normal human epidermis. Using the athymic nude mouse/human skin model we were able to show that serum IgG from patients can be experimentally deposited in vivo in human skin transplants, but in vitro binding could not be demonstrated. The Fc-fragments of epidermal IgG were accessible to binding of anti-Fc-fragment antibodies and protein-A. We suggest that IgG-containing immune complexes constitute the intraepidermal IgG deposits seen in patients with primary SS, and that the binding possible is mediated by Fc-receptors of Langerhans cells and keratinocytes.

Fluorescent Antibody Technique↗
PubMed1986

Treatment of Sjögren's syndrome: an overview.

This review focus on the double-blind clinical investigations in patients with Sjögren's syndrome and describe the historical developments. It is divided into two passages--systemic and topically treatment.

Bromhexine↗
PubMed1986

Impaired indomethacin-boosting of the defective natural killer cell activity in patients with primary Sjögren's syndrome.

As it has been shown that the natural killer (NK) cell activity is depressed and the prostaglandin (PG) metabolism is disturbed in patients with primary Sjögren's syndrome (primary SS), we examined the in vitro effect of indomethacin on the NK cell activity. The NK cell activity against K 562 target cells was measured in 20 female patients with primary SS and in 18 female normal controls matched for age. Blood mononuclear cells were incubated with indomethacin (1 microgram/ml). Median baseline NK cell activity in primary SS was 15.4% (range 5.8-50.4) versus 24.7% (range 6.2-47.4) in the controls (p less than 0.05). After in vitro exposure to indomethacin median NK cell activity in the patients was 21.2% versus 34.9% in the controls (p less than 0.02). Indomethacin-enhanced NK cell activity was significantly higher than baseline NK cell activity in both patients (p less than 0.05) and controls (p less than 0.01), but the NK cell activity of the patients was significantly less enhanced than that of the controls (p less than 0.02). We conclude that the impaired indomethacin-boosting of NK cell activity in patients with primary SS probably reflects a decreased capacity of blood mononuclear cells to produce PG in vitro.

Humans↗
PubMed1986

Smell and nasal findings in patients with primary Sjögren's syndrome.

As part of a clinical trial of the effect of Efamol on primary Sjögren's Syndrome (SS), 36 patients were interviewed about nasal symptoms and examined for sense of smell and nasal mucociliary clearance. The sense of smell was examined by quantitative olfactometry using coffee as a stimulant while mucociliary clearance was evaluated by the saccharin test. The findings were compared with those of an age and sex matched control group. 39% of the patients complained of dryness of the nose and 44% of nasal crust formation whereas none of the healthy controls had such complaints. In contrast no differences in sense of smell (subjectively as well as objectively) and mucociliary clearance could be demonstrated. Neither was there any correlation between mucociliary clearance and crust formation or dryness of the nose. Also the mucociliary clearance was not correlated to the "break up time" of the tear-film determined by the ophthalmologist. The present findings indicate that examination of the sense of smell and nasal mucociliary clearance is of little diagnostic value in primary SS and cannot be used for monitoration of disease activity.

Cilia↗
PubMed1986

Platelets in blood and salivary glands of patients with primary Sjögren's syndrome.

Circulating platelets from 15 patients with primary Sjögren's syndrome (primary SS) and from 15 normal controls were enumerated and their aggregability determined. Blood platelet concentrations were within the normal range, except for two patients in whom they were slightly decreased. 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). Plasma and saliva from 17 patients with primary SS and from 11 normal controls were examined for the platelet-specific release product beta-thromboglobulin (beta-TG). P-beta-TG was increased in the patients, although not significantly (p greater than 0.05). In saliva beta-TG was detected in 5 patients (11-150 ng/ml), but not in any of the controls. There was no correlation between levels of beta-TG in plasma and saliva. Lower lip minor salivary glands from 17 patients under evaluation for SS were examined for platelet accumulation. Indirect immuno-peroxidase staining with the monoclonal mouse anti-human platelet glycoprotein Ib antibody, showed platelet accumulation intravascularly in the inflamed areas. The combined results are in accordance with the hypothesis that platelet activation occurs in the salivary glands of patients with primary SS.

Humans↗
PubMed1986

In vivo IgG deposits and reduced density of Langerhans cells in the surface epithelium of cervix uteri of patients with primary Sjögren's syndrome.

Intraepithelial IgG deposits have previously been demonstrated in epidermis and oral labial mucosal epithelium of patients with primary Sjögren's syndrome. IgG has been shown to be located to cell surface membranes predominantly of OKT6 positive Langerhans cells (LC), which moreover are decreased in number in epidermis of these patients. In biopsies of cervix uteri from 17 patients with primary Sjögren's syndrome and 21 controls, the mucosal membrane was examined with a direct immunofluorescence technique, for in vivo deposits of immunoglobulins, fibrinogen and C3c in the stratified squamous epithelium. Epithelial deposits of IgG, similar to that found in skin and oral labial mucosa, were demonstrated in 4/17 patients, but in none of the controls. No deposits of IgM, IgA, fibrinogen or C3c were found in the biopsies from either patients or controls. OKT6 positive mucosal LC were demonstrated with an indirect immunofluorescence technique, and enumerated in vertical sections. The density of epithelial LC was found to be decreased in patients (p less than 0.05) as compared to controls. No correlation was found between presence of IgG deposits and density of LC, in agreement with the findings in skin of these patients.

Adult↗
PubMed1986

The effect of bromhexine on the kidney lesions in NZB-NZW-F1 mice.

The NZB-NZW-F1 mice develop a clinical picture resembling SLE and an exocrinopathy resembling Sjögren's syndrome. Three groups of hybrids were treated from their 20th week of age for 10, 17 and 20 weeks (groups 1, 2, 3) with Bromhexine in two different concentrations--6 & 60 mg/kg and placebo. NMRJ mice treated with placebo acted as healthy controls. After the treatment the kidneys were examined by light microscopy. The kidneys exhibited lupus-like lesions. Animals treated with 60 mg/kg Bromhexine for 17 weeks had a significantly lower degree of changes than had the other hybrids.

Animals↗
PubMed1986

Editorial comments to the four sets of criteria for Sjögren's syndrome.

The four most frequently used criteria for definition of Sjögren's syndrome--the Copenhagen, the Japanese, the Greek and the Californian criteria--are critically evaluated. The article focuses on the similarities and the dissimilarities as well as the advantages and the disadvantages between the various sets of criteria.

Humans↗
PubMed1986

Comparing diagnostic criteria for the salivary component of Sjögren's syndrome.

Sjögren's syndrome (SS) is defined by the presence of at least two out of three clinical features: keratoconjunctivitis sicca (KCS), xerostomia and another connective tissue disease (CTD). Various criteria have been used to diagnose the oral component of SS (xerostomia) including the presence of at least two out of the following three: lowered unstimulated whole saliva secretion rate, abnormal salivary scintigraphy and sialadenitis in a labial salivary gland biopsy (LSG) ("Copenhagen criteria"), or the solitary criterion of a focus score (FS) value greater than 1 in a LSG biopsy. We compared the application of these two diagnostic criteria on 52 patients suspected of having SS, and evaluated the interexaminer variation of LSG biopsy FS determination. Compared to the Copenhagen criteria, using FS as the only criterion for the oral component of SS would change the diagnosis in 7 (adding 3 and deleting 4 diagnoses of SS) of 52 patients suspected of having the disease. The FS value may be affected by the size of biopsy and interpretation of pathological changes. The overall interexaminer agreement on FS was 90%.

Humans↗
PubMed1986

Interleukin 2 augmentation of the defective natural killer cell activity in patients with primary Sjögren's syndrome.

Natural Killer (NK) cell activity against K562 target cells was measured in 21 female patients with primary Sjögren's syndrome (primary SS) and in 20 female normal controls matched for age. The in vitro effect of alpha-interferon (IF) and interleukin 2 (IL-2) on NK cell activity was examined and the percentage of large granular lymphocytes (LGL) in blood was measured. Median baseline NK cell activity in primary SS was 15.4% versus 24.4% in the controls (P less than 0.05). Median IF-enhanced NK cell activity in the SS group was 35.5% versus 49.6% in the controls (P less than 0.02). IL-2-enhanced NK cell activity was 35.5% versus 37.6% in the controls (n.s.) The proportion of LGL did not differ in the two groups. Median LGL/lymphocytes was 4.0% in the primary SS patients versus 4.5% in the controls (n.s.). We conclude that the defective NK cell activity in patients with primary SS is functional, as the number of LGL is normal. Further the NK cell activity off SS was restored by IL-2.

Adult↗
PubMed1986

Antibodies against SS-B/La and SS-A/Ro antigens in patients with primary Sjögren's syndrome.

An enzyme-linked immunosorbent assay for detection of serum antibodies against SS-B/La is described, and the frequency of anti-SS-B/La antibodies in 103 blood donors is tested. 67% of patients with primary Sjögren's syndrome (n = 21), verified by at least two abnormal tests for xerostomia as well as keratoconjunctivitis sicca (the Copenhagen criteria), were found to have IgG anti-SS-B antibodies, and 71% had anti-SS-A/Ro precipitating antibodies, when tested by Ouchterlony immunodiffusion. All patients with anti-SS-B/La antibodies had anti-SS-A/Ro antibodies. Anti-SS-A/Ro and -SS-B/La antibodies correlated with the presence of rheumatoid factor, antinuclear antibodies and hypergammaglobulinemia. The clinical manifestations of pseudolymphoma, Raynaud's phenomenon, fatigue and arthralgia, were more frequent in patients with anti-SS-B/La and/or -SS-A/Ro antibodies.

Antibodies, Antinuclear↗