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Biomedical subjects

R Manthorpe

Publications and source records attributed to R Manthorpe.

At least 55 records · Page 3Linked to original sources

Autoimmune liver disease in patients with primary Sjögren's syndrome.

Forty-five patients with primary Sjögren's syndrome were studied for evidence of autoimmune liver disease. Twenty-nine patients had normal liver function tests, normal IgM and a normal test for antimitochondrial antibodies and smooth muscle antibodies. Among the remaining 16 patients, abnormal liver function tests were found in 12 (27% of all patients); eight of these patients had biochemical cholestasis. Elevated plasma IgM (> 2 g/l) was observed in nine patients, three with normal liver function tests, while antimitochondrial antibodies were positive in six patients, one with normal liver function tests, and smooth muscle antibodies were found in three. Based on these findings and percutaneous liver biopsy, a diagnosis of primary biliary cirrhosis was established in four patients and autoimmune chronic active hepatitis in two. The present study showed that abnormal liver function tests in patients with primary Sjögren's syndrome are frequent and may indicate associated autoimmune liver disease. These data further emphasize the systemic nature of autoimmune disorders.

Adult↗

Salivary gland scintigraphy in subjects with and without symptoms of dry mouth and/or eyes, and in patients with primary Sjögren's syndrome.

The major salivary glands were examined with 99m-Tc-pertechnetate scintigraphy in randomly selected subjects with (n = 30) and without (n = 12) symptoms of dry mouth and/or eyes, and in patients with primary Sjögren's syndrome (1 degree SS, n = 17). The scans were quantitatively evaluated and compared to other objective tests used to diagnose 1 degree SS. As compared with those for asymptomatic subjects, most values for the scintigraphic variables were non-significantly lower for symptomatic subjects and the time-activity curves were slightly flatter for all major salivary glands. In patients with 1 degree SS most values for the scintigraphic variables were significantly lowered and the submandibular glands were the glands most affected, as reflected in a flat time-activity curve, while the parotid glands were mainly affected during stimulated secretion. The scintigraphic variables correlated with the self-rated dryness of mouth in symptomatic subjects and with the abnormality of sialometry results in patients with 1 degree SS. We conclude that salivary gland scintigraphy is a sensitive and valid method to measure salivary gland function and abnormalities.

Aged↗

Complement activation in patients with primary Sjögren's syndrome: an indicator of systemic disease.

Sixteen patients with primary Sjögren's syndrome, verified according to the Copenhagen criteria, were investigated for evidence of complement activation. Thirteen of the patients had intact functional activity of both the classical and alternative pathways, with normal concentrations of the complement proteins C1q, C1s, C3, C4 and the complement protein fragments C2a and C3d in the circulation. In contrast, three patients showed clear evidence of complement activation. Further investigation of these patients revealed manifestations of glomerulonephritis, vasculitis and primary biliary cirrhosis. Six months later, one patient developed a malignant non-Hodgkin lymphoma. We conclude that complement activation is generally not associated with primary Sjögren's syndrome. Evidence of complement activation in patients considered to have primary Sjögren's syndrome should raise the suspicion of concomitant systemic disease and/or extraglandular activity.

Aged↗

Association of dry eyes and dry mouth with anti-Ro/SS-A and anti-La/SS-B autoantibodies in normal adults.

OBJECTIVE: To evaluate the extent to which seemingly healthy, mature adults with mild symptoms of dry eyes or dry mouth share the immunologic features found in patients with Sjögren's syndrome. METHODS: Of 705 subjects in Malmö, Sweden (age range 52-72 years) who responded to a questionnaire, 35% reported some symptoms of dry eyes or mouth. A random subgroup of the symptomatic subjects (n = 77) and an age- and sex-matched control group from among the asymptomatic subjects (n = 32) were evaluated objectively by serologic testing and by various measures of exocrine gland function. RESULTS: The symptomatic subjects had relatively impaired exocrine gland function and elevated levels of anti-Ro and anti-La (1.54-2.88-fold increase compared with the asymptomatic subjects, 95% confidence interval [CI] 1.41, 4.03). The 2 autoantibodies correlated with each other (r = 0.64, 95% CI 0.49, 0.78) as well as with selected clinical measures of glandular function. CONCLUSION: The association between self-reported symptoms of dry eyes or dry mouth and anti-Ro and anti-La, found in more than one-third of mature adults in this study, suggests that the immune abnormalities and exocrine gland dysfunction found in Sjögren's syndrome affect a substantial proportion of the general population.

Aged↗

Salivary gland involvement in autoimmune thyroiditis, with special reference to the degree of association with Sjögren's syndrome.

From a total of 63 patients with autoimmune thyroiditis, 19 cases were further investigated to determine the degree of concomitant morphologic and functional salivary gland changes. For comparison, 21 of a total of 28 cases of primary Sjögren's syndrome were also examined. Of the 19 cases of autoimmune thyroiditis, 11 showed various degrees of salivary gland involvement on the basis of an analysis of lower lip salivary gland biopsy specimens, scintigraphy of the parotid, and unstimulated whole sialometry. Six of these cases fulfilled the criteria of primary Sjögren's syndrome. A remarkably high proportion of dark-staining acini was observed in the lower lip biopsy specimens of our patients with thyroiditis (8 of 19, 42%) and less among our patients with primary Sjögren's syndrome (5 of 21, 24%). We conclude that significant involvement of salivary glands may occur in cases of autoimmune thyroiditis, which indicates that common mechanisms may frequently be operative in the development of thyroid and salivary gland immune disease.

Adult↗

Effect of education, occupation and some lifestyle factors on common rheumatic complaints in a Swedish group aged 50-70 years.

The relation between common rheumatic diseases such as osteoarthrosis, arthralgia without definite signs of osteoarthrosis, subacromial shoulder pain, different forms of tendinitis, low back pain and neck pain, and the level of formal education, occupational workload and some lifestyle factors were examined in 502 of 900 randomly selected subjects aged 50-70 years. The group with rheumatic complaints had a higher proportion of subjects with a lower level of formal education (less than or equal to eight years) by bivariate analysis. In multivariate analysis, the major risk factors were: a self rated heavy workload (odds ratio (OR) 6.4), sleep disturbance (OR 3.6), and advanced age (OR 2.0 per five year increase) for osteoarthrosis; a self rated heavy workload for subacromial shoulder pain (OR 5.4) and low back pain (OR 4.8); and a self rated heavy workload (OR 8.0) and female sex (OR 4.8) for neck pain. A self rated heavy workload was strongly correlated with a low level of formal education. A heavy workload (i.e. previous or present principal occupation) could only be confirmed in the groups with neck pain and low back pain on the basis of available occupational classification data. Neck pain was thus associated with occupations entailing repetitive tasks and awkward posture with respect to the neck, shoulders, and back. Low back pain was associated with occupations entailing awkward posture with respect to the neck, shoulders, and back, and occupations entailing exposure to vibration and heavy manual work. It is concluded that, in a cross sectional sample of an elderly population, a low level of formal education and self rated heavy physical work are associated with the occurrence of adult rheumatic complaints, though the self rated heavy workload could only be verified in the groups with neck pain and low back pain. There correlations between heavy work and low back pain, and especially neck pain, suggest that successful prevention would mean a substantial economic gain to the community. Whether the level of education is a marker of risk factors other than a heavy occupational workload needs further evaluation.

Age Factors↗

Primary Sjögren's syndrome in patients with multiple sclerosis.

The relationship between multiple sclerosis (MS) and primary Sjögren's syndrome (PSS) is ambiguous; it was suggested that some patients diagnosed with MS may instead have PSS. In a recent epidemiologic study, the prevalence of PSS was 2.7% in southern Sweden. We randomly selected 30 patients with definite MS from our patient population and investigated them for evidence of PSS according to the Copenhagen criteria. One patient had clinical symptoms compatible with PSS and also fulfilled the Copenhagen criteria. In addition, five patients had keratoconjunctivitis sicca, one had xerostomia, and three had histopathologic evidence of sialadenitis in the lower lip salivary glands. However, one of these findings alone is not sufficient to support the diagnosis of PSS. We conclude that MS and PSS may coexist in the same individual, but PSS is not more common among MS patients than expected in the general population.

Antibodies, Antinuclear↗

Fatty acid composition of adipose tissue and serum micronutrients in relation to common rheumatic complaints in Swedish adults 50-70 years old.

Biochemical markers of nutritional status, such as adipose tissue fatty acid composition and circulating levels of micronutrients, may reflect dietary habits, but may also be related to inflammatory activity. We examined the relationship between common rheumatic complaints such as osteo-arthrosis, arthralgia, tendinitis, low-back pain, and neck pain, and the composition of adipose tissue fatty acids, serum concentrations of retinol, ascorbic acid, alpha-tocopherol and selenium in 502, out of 900 randomly selected individuals 50-70 years old. Compared with control subjects the rheumatic group as a whole (p less than 0.01) as well as subgroups like those with arthralgia (p less than 0.01), subacromial shoulder pain (p less than 0.03), and low-back pain (p less than 0.05), had decreased proportions of adipose tissue arachidonic acid. The abnormalities correlated with the duration of the symptom-free period preceding adipose tissue sampling and could not be explained by the evaluation of possible confounding factors. Regarding other fatty acids and micronutrients there were no differences between symptomatic subjects and controls. One explanation for the low proportion of adipose tissue arachidonic acid may be increased eicosanoid production.

Adipose Tissue↗

Correlation of fatty acid composition of adipose tissue lipids and serum phosphatidylcholine and serum concentrations of micronutrients with disease duration in rheumatoid arthritis.

To establish the concentrations of micronutrients in serum, fatty acid composition in serum phosphatidylcholine and in adipose tissue, and their correlation with inflammation and disease duration in rheumatoid arthritis (RA), 21 consecutive patients with recently diagnosed disease (mean duration eight months), 21 patients with longstanding disease (mean duration 15 years), and 57 controls were examined. In the patients with RA low concentrations of the essential fatty acids, linoleic acid (18:2) and linolenic (18:3) acid, and high concentrations of total saturated fatty acids, both in serum phosphatidylcholine and in adipose tissue, were found, abnormalities that increased with disease duration. The proportion of 18:2 in serum phosphatidylcholine correlated inversely with such acute phase proteins as orosomucoid and C reactive protein. It is proposed that the decreases in essential fatty acids are related to increased activity in the desaturase/elongation enzymes, increased production of eicosanoids, or metabolic changes secondary to cytokine mediated inflammatory reaction. When the micronutrients were studied it was found that serum concentrations of selenium were lower in patients than in controls, but not those of ascorbic acid, alpha-tocopherol, retinol, folic acid, or cobalamine. Ascorbic acid concentrations tended to be lower in RA, however, and correlated inversely with those of haptoglobin, orosomucoid, and C reactive protein, indicating a relation between the ascorbic acid concentration and the degree of inflammation.

Acute-Phase Proteins↗

Rose bengal score--a possible key parameter when evaluating disease level and progression in primary Sjögren's syndrome.

The rose bengal score is one of the most commonly used tests for evaluation of ocular surface epithelial damage. The test is used in most Sjögren's syndrome criteria. We examined 24 female and four male patients with primary Sjögren's syndrome (primary SS) in order to evaluate possible correlation between the various tests for keratoconjuncivitis sicca (KCS), and for possible correlations to xerostomia and p-IgG levels. Among the KCS tests a high rose bengal score appeared to be the key parameter, being correlated to low break-up time (P less than 0.01), low tear lysozyme (P less than 0.01), appearance of snake-like chromatin in conjunctival imprints (P less than 0.05), low sialometry (P greater than 0.01) and high p-IgG (P less than 0.01). We followed another group of patients with primary SS (30 females and four males) for a mean period of 53 (range 27-76) months. The patients were divided according to their initial response to systemic treatment with bromhexine. KCS parametres and p-IgG were measured repeatedly during the observation period. Patients responding to and continuously treated with bromhexine (2/3 of patients) improved significantly (P less than 0.05) in rose bengal score, but had increasing levels of p-IgG. Non-responders kept their low tear-production rate and had also increasing p-IgG levels. However, when subdivided according to p-IgG level, the group of patients with relatively low p-IgG improved in rose begal score, whereas the high p-IgG-group increased in rose bengal score. The rose bengal score appears to be a useful key parameter when evaluating disease level and progression.

Adult↗

Polyclonal B-cell activation is related to exocrine manifestations of primary Sjögren's syndrome.

Twenty-four female and four male patients with primary Sjögren's syndrome were examined in order to evaluate possible correlations between the exocrine disease manifestations and polyclonal B-cell activation parameters. All patients were examined three times over a 4-month period and none of them received any systemic medical treatment. Van Bijsterveld scores were negatively correlated to unstimulated whole salivary flow rate (sialometry) values (P less than 0.01) and break-up times (BUT) (P less than 0.01), while unrelated to Schirmer-1 values. Unstimulated sialometry values were, in addition, positively correlated to Schirmer-1 values (P less than 0.01), while BUT were unrelated to Schirmer-1 and unstimulated sialometry values. P-IgG levels were positively correlated to van Bijsterveld scores (P less than 0.01) and negatively correlated to break-up times (P less than 0.05), while unrelated to unstimulated sialometry and Schirmer-1 values. P-IgG levels were furthermore positively correlated to levels of P-IgM (P less than 0.05), P-IgA (P less than 0.05), serum IgM-RF (P less than 0.001) and serum ANA (P less than 0.01). Levels of P-IgM-RF were positively correlated to van Bijsterveld scores (P less than 0.01), but to none of the other exocrine manifestations. We conclude that the plasma levels of B-cell products seem to correlate positively with the degree of ocular involvement in patients with primary Sjögren's syndrome, indicating a relationship between the immunoinflammatory processes and the mucosal damage.

Adult↗

Dry eyes or mouth--an epidemiological study in Swedish adults, with special reference to primary Sjögren's syndrome.

The prevalence of dry eyes or dry mouth, and of primary Sjögren's syndrome (primary SS) according to the Copenhagen criteria were established in 705 randomly selected subjects, aged 52-72 years who answered a simple questionnaire, and of whom 247 (35%) reported symptoms. A subgroup with symptoms (n = 77) and a matched asymptomatic control group (n = 32) were examined with the Schimer-1 test (S1t), tear film break-up time (BUT), van Bijsterveld score (vB), unstimulated whole sialometry (Sialo) and, in about 40% of them labial salivary gland (LSG) biopsy and salivary gland scintigraphy. Apart from four cases of keratoconjunctivitis sicca (KCS) among controls, cases of KCS (15), xerostomia (12), autoimmune sialoadenitis (6) and primary SS (6) were exclusively confined to the symtomatic group. The calculated frequencies (with 95% confidence intervals) for the whole population were 14.9 (7.3-22.6)% for KCS, 5.5(3.0-7.9)% for xerostomia and 2.7 (1.0-4.5)% for autoimmune sialoadenitis and primary SS. The serum levels of ANA and RF were similar in the two groups, though those of anti-SS-B/La antibodies were higher in the group with symptoms (P less than 0.01).

Aged↗

The commonest rheumatic complaints of over six weeks' duration in a twelve-month period in a defined Swedish population. Prevalences and relationships.

In 900 randomly selected individuals, 50-70 years old, we examined the prevalence over the preceding 12-month period of rheumatic complaints of more than 6 weeks' duration. We found them to represent a major health problem, with an overall prevalence of 37.8%, the predominant diagnoses being subacromial shoulder pain (6.7%), neck pain (6.5%), low back pain (6.3%), osteo-arthrosis (8.5%), and arthralgia (4.9%). With a prevalence of 1.0%, primary fibromyalgia was as common as rheumatoid arthritis (0.7%) and other chronic arthritides (1.1%). The prevalences of the different diagnoses were higher among participants whose data were obtained from personal investigation by a physician than among non-participants where data were obtained by interview, letter, and scrutiny of case records. The odds ratio from incurring more than one rheumatic disease was higher for subacromial shoulder pain and lowest for arthralgia and osteo-arthrosis.

Aged↗