Search PubMed⌕ Search

Biomedical subjects

R Manthorpe

Publications and source records attributed to R Manthorpe.

At least 37 records · Page 2Linked to original sources
PubMed2000

Lower frequency of focal lip sialadenitis (focus score) in smoking patients. Can tobacco diminish the salivary gland involvement as judged by histological examination and anti-SSA/Ro and anti-SSB/La antibodies in Sjögren's syndrome?

OBJECTIVES: Prospectively collected computer database information was previously assessed on a cohort of 300 patients who fulfilled the Copenhagen classification criteria for primary Sjögren's syndrome. Analysis of the clinical data showed that patients who smoked had a decreased lower lip salivary gland focus score (p<0.05). The aim of this original report is to describe the tobacco habits in patients with primary Sjögren's syndrome or stomatitis sicca only and to determine if there is a correlation between smoking habits and focus score in lower lip biopsies as well as ciculating autoantibodies and IgG. METHODS: All living patients with primary Sjögren's syndrome or stomatitis sicca only, who were still in contact with the Sjögren's Syndrome Research Centre were asked to fill in a detailed questionnaire concerning present and past smoking habits, which was compared with smoking habits in a sex and age matched control group (n=3700) from the general population. In addition, the patients previous lower lip biopsies were blindly re-evaluated and divided by the presence of focus score (focus score = number of lymphocyte foci per 4 mm(2) glandular tissue) into those being normal (focus score </= 1) or abnormal (focus score > 1). Furthermore the cohort was divided into three groups; 10-45, 46-60 and >/= 61 years of age. Finally the focus score was related to the smoking habits. Seroimmunological (ANA; anti-SSA/Ro antibodies; anti-SSB/La antibodies; IgM-RF and IgG) samples were analysed routinely. RESULTS: The questionnaire was answered by 98% (n=355) of the cohort and the percentage of current smokers, former smokers and historical non-smokers at the time of lower lip biopsy was not statistically different from that of the control group. Cigarette smoking at the time of lower lip biopsy is associated with lower risk of abnormal focus score (p<0.001; odds ratio 0.29, 95%CI 0.16 to 0.50). The odds ratio for having focal sialadenitis (focus score > 1) compared with having a non-focal sialadenitis or normal biopsy (focus score </= 1) was decreased in all three age groups (10-45: odds ratio 0.27, 95%CI 0.11 to 0.71; 46-60: odds ratio 0.22, 95%CI 0. 08 to 0.59; and >/= 61: odds ratio 0.36, 95%CI 0.10 to 1.43) although there was only statistical significance in the two younger age groups. Moreover, among current smokers at the time of the lower lip biopsy there was a decreasing odds ratio for an abnormal lip focus score with increasing number of cigarettes smoked per week (p trend 0.00). In the group of former smokers, which included patients that had stopped smoking up to 30 years ago, the results were in between those of the smokers and the historical non-smokers (odds ratio 0.57, 95%CI 0.34 to 0.97, compared with never smokers). Present or past smoking did not correlate with the function of the salivary glands as judged by unstimulated whole sialometry, stimulated whole sialometry or salivary gland scintigraphy. Among former smokers, the median time lapse between the first symptom of primary Sjögren's syndrome and the performance of the lower lip biopsy was approximately half as long as the median time lapse between smoking cessation and biopsy (8 versus 15 years). Hence, symptoms of Sjögren's syndrome are unlikely to have had a significant influence on smoking habits at the time of the biopsy. Among the seroimmunological results only anti-SSA/Ro and anti-SSB/La antibodies reached statistical significance in a manner similar to the way smoking influenced the focus score in lower lip biopsies. On the other hand the level of significance was consistently more pronounced for the influence of smoking on the focus score than for the influence on anti-SSA/Ro and anti-SSB/La autoantibodies. CONCLUSION: This is believed to be the first report showing that cigarette smoking is negatively associated with focal sialadenitis-focus score >1-in lower lip biopsy in patients with primary Sjögren's syndrome. Furthermore, tobacco seems to decrea

Adult↗
PubMed1999

Sjögren's syndrome: lymphoma predisposition coupled with a reduced frequency of t(14;18) translocations in blood lymphocytes.

Sjögren's syndrome (SS) is a systemic autoimmune disorder with a strong tumor predisposition (a 44-fold elevated incidence of non-Hodgkin's lymphoma has been reported). By polymerase chain reaction analysis of t(14;18), a key lymphomagenic event in peripheral blood lymphocytes, we found a lower frequency in a subset of 12 SS patients positive for SS-A/SS-B autoantibodies than in 21 healthy subjects and 20 SS patients lacking these SS marker autoantibodies (P < 0.001). All 14 mutants sequenced displayed signs typical of V(D)J recombinase activity. This perplexing result of a low rate of t(14;18) in a population strongly predisposed to t(14;18)-associated tumor development may be explained by a constitutive deficiency in V(D)J recombinase leading to autoimmunity and increased lymphoproliferation.

Antibodies, Antinuclear↗
PubMed1999

Extrahepatic manifestations of chronic hepatitis C infection and the interrelationship between primary Sjögren's syndrome and hepatitis C in Swedish patients.

OBJECTIVE: To analyse the frequency of some extrahepatic manifestations of chronic hepatitis C virus (HCV) infection in northern European patients, including a postulated association between HCV and primary Sjögren's syndrome (SS). DESIGN: Cohort study. SETTING: Department of Medicine, Malmö University Hospital, Sweden. PATIENTS: Twenty-one patients with HCV infection and 53 with primary SS (according to the Copenhagen criteria). MAIN OUTCOME MEASURES: Cryoglobulins were analysed in all patients, while patients with primary SS were investigated with regard to markers of HCV infection, and HCV patients with objective tests of SS (Schirmer-1 test, break-up time, van Bijsterveld score, sialometry, labial salivary gland biopsy) and antibodies against nuclear antigens, smooth muscle (SMA) and mitochondria (AMA). HCV antigens in small salivary glands from lower lip biopsies were detected by immunohistochemical analysis. RESULTS: Only one of the SS patients had detectable cryoprecipitates, while another was HCV-positive. None of the 21 HCV patients had cryoprecipitates. A total of 14/21 (67%) patients with HCV infection had at least one abnormal objective test suggestive of xerostomia or keratoconjunctivitis sicca, while eight (38%) had objective evidence of both eye and salivary gland involvement. HCV antigens were not detected in affected glands. Only two patients had clinical symptoms of SS, and two fulfilled the Copenhagen criteria for SS. None of the HCV-positive patients had detectable antibodies against SS-A, SS-B, RNP, Jo-1, PCNA or Scl-70, and the frequency of ANA/SMA/AMA was low. CONCLUSIONS: While involvement of salivary and lacrimal glands was common in Swedish patients with HCV infection, cryoglobulinaemia was not observed. The pathogenetic mechanism responsible for glandular inflammation appears to be different from that in primary SS. HCV infection does not seem to be an aetiological factor for primary SS in this population. These observations suggest that viral, genetic or possibly environmental factors may be responsible for the reported high frequencies of systemic complications associated with chronic hepatitis C infection in southern Europe.

Adult↗
PubMed1998

Abnormal DNA damage-inducible protein in cells from Sjögren's syndrome patients.

Antinuclear antibodies are commonly found in patients with Sjögren's syndrome. It has been suggested that the development of antinuclear antibodies depends on the activation of the spliceosome and other transcription-related subcellular particles, some of which have recently been shown also to function in DNA-modifying processes, such as DNA repair and V(D)J recombination. These observations add weight to a previously proposed model for the aetiology of Sjögren's syndrome. This includes the abnormal processing of the T-cell receptor and immunoglobulin genes. To test this hypothesis further, the present study on DNA-modifying proteins in Sjögren's syndrome was initiated. Gel-shift experiments using protein extracted from UV-treated Sjögren cells provided evidence of high molecular weight DNA-binding protein in six out of 12 Sjögren patients studied (but not among seven healthy controls). Some Sjögren sera displayed antibodies to protein extracts from cells treated with psoralen plus UVA radiation. These results indicate an abnormal DNA damage-inducible response in Sjögren's syndrome. It may therefore be concluded that alterations in nuclear protein may play a role in the aetiology of Sjögren's syndrome.

Antibodies, Antinuclear↗
PubMed1998

Matrix metalloproteinase (MMP)-9 type IV collagenase/gelatinase implicated in the pathogenesis of Sjögren's syndrome.

Type IV collagenases/gelatinases (matrix metalloproteinases MMP-2 and MMP-9) in labial salivary glands (LSG) and saliva in Sjögren's syndrome (SS) and healthy controls were studied. Zymograms and Western blots disclosed that SS saliva contained 92/82 kD MMP-9/type IV collagenase duplex. Specific activity measurement disclosed 53.1+/-9.8 U/mg protein MMP-9 in SS compared to 16.5+/-2.6 U/mg in healthy controls (p=0.01). MMP-2 did not differ between SS and controls. In SS salivary glands, MMP-2 and MMP-9 were also expressed, in addition to stromal fibroblasts and occasional infiltrating neutrophils, respectively, in acinar end piece cells. In addition, an effective proMMP-9 activator, human trypsin-2 (also known as tumor-associated trypsin-2 or TAT-2), was found in acinar end piece cells and in saliva. Interestingly, proteolytically processed MMP-9 was found in saliva (vide supra), and in vivo activated MMP-9 was significantly higher in SS than in controls (p=0.002). LSGs, particularly in SS, were characterized ultrastructurally by areas containing small cytoplasmic vesicles in the basal parts of the epithelial cells associated with areas of disordered and thickened basal lamina. Based on our results, we conclude here that SS saliva contains increased concentrations of MMP-9, which is of glandular origin in part. Pro MMP-9 is to a large extent proteolytically activated. This is probably mediated by the most potent pro MMP-9 activator found in vivo thus far, namely trypsin-2. Therefore, the MMP 9/trypsin-2 cascade may be responsible for the increased remodelling and/or structural destruction of the basement membrane scaffolding in salivary glands in SS. Due to the role of basal lamina as an important molecular sieve and extracellular matrix-cell signal, these pathological changes may contribute to the pathogenesis of the syndrome.

Blotting, Western↗
PubMed1998

Epidemiology of Sjögren's syndrome, especially its primary form.

During the last decades different sets of criteria have been used for defining primary Sjögren's syndrome. Using these criteria prevalence estimates have varied between 0.04%-4.8%. This hundred-fold distribution in estimated frequency is partly due to differences in age groups studied, classification criteria used and methods used for objective evaluation of lachrymal and salivary gland hypofunction. Another problem which makes comparison between studies difficult is that workshop recommendations for the various objective tests are very often not strictly followed. Population based studies tend to identify cases with less severe disease and higher prevalence rates. Furthermore, there seems to be little correlation between dryness symptoms reported by subjects and objective hypofunction of lachrymal and/or salivary glands. Possible explanations to these findings include selection bias towards more severe cases in clinical (university) studies and a low predictive value for some criteria in population studies.

Cross-Sectional Studies↗
PubMed1997

The effect of dynamic strength back exercise and/or a home training program in 57-year-old women with chronic low back pain. Results of a prospective randomized study with a 3-year follow-up period.

STUDY DESIGN: A prospective, randomized investigation. OBJECTIVES: To compare the effect of dynamic strength back muscle training with that of a home training program and to evaluate the long-term effect of the home training program in patients with chronic low back pain. SUMMARY OF BACKGROUND DATA: In a health survey of 57-year-old women, those with chronic low back pain were selected using the Nordic Questionnaire. Of 172 women with low back pain, 74 participated in the study. METHODS: The participants were randomly assigned to either dynamic strength back exercises at a fitness center and a home training program or to the home training program for the first 3 months, after which both groups continued to pursue the home training program. Follow-up observation was by examination at 3 and 12 months and by mailed questionnaire after 3 years. The primary effect variables were disability, sick-leave, and use of health care services. RESULTS: Both training groups manifested significant improvement at the 3- and 12-month follow-up examinations, yet the adherence rate was much better in the group assigned to the fitness center. Those who adhered to the training program for the first year manifested significant improvement according to the 3-year follow-up questionnaire. There was a significant reduction in the number of women on sick-leave and in use of health care services after 1 year, but not after 3 years. CONCLUSIONS: The home training program was as effective as the supervised dynamic strength muscle training program and yielded lasting improvement after at least 1 year of adherence. The adherence rate was much better, however, when the training was supervised at the start.

Back↗
PubMed1997

Contact allergy to gold and gold therapy in patients with rheumatoid arthritis.

Patients with rheumatoid arthritis were investigated for contact allergy to gold in connection with treatment with gold preparations. There were 57 patients with rheumatoid arthritis previously treated with gold, with or without cutaneous side-effects, as well as 20 patients intended for such treatment; all were exposed to patch and intradermal tests with gold sodium thiosulfate, gold sodium thiomalate and auranofin. Contact allergy to gold was demonstrated in 8 out of 77 patients (10.4%). In the retrospective material, gold allergy was found in 1.8%, in the prospective material in 35.0%. Contact allergy to gold is very frequent among patients with rheumatoid arthritis before gold therapy. In order to avoid early hypersensitivity reactions skin tests should be carried out before gold therapy is instituted.

Adolescent↗
PubMed1997

Disturbances of autonomic nervous function in primary Sjögren's syndrome.

Autonomic nervous function was evaluated by deep breathing [expiration/inspiration (E/I) ratio] and tilt table tests [acceleration (AI) and brake indices (BI)] in 19 patients with primary Sjögren's syndrome (pSS) and in 56 age matched controls. The E/I-ratio and systolic blood pressure (at rest, 1, and 8 min after tilt) were found to be significantly reduced (p < 0.001, p < 0.05, p < 0.01, p < 0.01 respectively) in patients with pSS whereas neither AI, BI nor diastolic blood pressure did differ significantly between patients and controls (NS). The van Bijsterveld's score correlated negatively with the AI (r = -0.77, p< 0.001) as well as the BI (r = -0.60, p < 0.01). No correlations were found between the 3 autonomic nerve function parameters (E/I-ratio, AI, BI) and unstimulated whole sialometry or salivary gland scintigraphy. We conclude that autonomic disturbances, mainly affecting the parasympathetic nerves are associated with pSS.

Adolescent↗
PubMed1997

Disturbances of autonomic nervous function in primary Sjögren's syndrome.

Autonomic nervous function was evaluated by deep breathing [expiration/inspiration (E/I) ratio] and tilt table tests [acceleration (AI) and brake indices (BI)] in 19 patients with primary Sjögren's syndrome (pSS) and in 56 age matched controls. The E/I-ratio and systolic blood pressure (at rest, 1, and 8 min after tilt) were found to be significantly reduced (p < 0.001, p < 0.05, p < 0.01, p < 0.01 respectively) in patients with pSS whereas neither AI, BI nor diastolic blood pressure did differ significantly between patients and controls (NS). The van Bijsterveld's score correlated negatively with the AI (r = -0.77, p < 0.001) as well as the BI (r = -0.60, p < 0.01). No correlations were found between the 3 autonomic nerve function parameters (E/I-ratio, AI, BI) and unstimulated whole sialometry or salivary gland scintigraphy. We conclude that autonomic disturbances, mainly affecting the parasympathetic nerves are associated with pSS.

Adolescent↗
PubMed1996

Assessment of the European classification criteria for Sjögren's syndrome in a series of clinically defined cases: results of a prospective multicentre study. The European Study Group on Diagnostic Criteria for Sjögren's Syndrome.

OBJECTIVE: To assess the recently proposed preliminary criteria for the classification of Sjögren's syndrome (SS) in a multicentre European study of a new series of clinically defined cases. METHODS: The criteria included six items: I = ocular symptoms; II = oral symptoms; III = evidence of keratoconjunctivitis sicca; IV = focal sialoadenitis by minor salivary gland biopsy; V = instrumental evidence of salivary gland involvement; VI = presence of autoantibodies. Each centre was asked to provide five patients with primary SS, five with secondary SS, five with connective tissue diseases (CTD) but without SS, and five controls (patients with ocular or oral features that may simulate SS). The preliminary six item classification criteria set was applied to both the SS patients and the non-SS controls, and the performance of the criteria in terms of sensitivity and specificity was tested. RESULTS: The criteria set was tested on a total of 278 cases (157 SS patients and 121 non-SS controls) collected from 16 centres in 10 countries. At least four of the six items in the criteria set (limiting item VI to the presence of Ro(SS-A) or La(SS-B) antibodies) were present in 79 of 81 patients initially classified as having primary SS (sensitivity 97.5%), but in only seven of 121 non-SS controls (specificity 94.2%). When the presence of item I or II plus any two of items III-V of the criteria set was considered as indicative of secondary SS, 97.3% (71 of 73) of the patients initially defined as having this disorder and 91.8% (45 of 49) of the control patients with CTD without SS were correctly classified. CONCLUSION: This prospective study confirmed the high validity and reliability of the classification criteria for SS recently proposed by the European Community Study Group.

Adult↗
PubMed1996

Sudden onset unilateral renomegaly as an initial manifestation of primary Sjögren's syndrome in a teenage girl.

An 18-year old girl suddenly developed left-sided abdominal pain with otherwise normal clinical and urine examination. Ultrasound and computed tomography demonstrated a left renomegaly with uniformly normal structure without hydronephrosis, abnormal renal venous flow or ruptured extrauterine pregnancy. Renal biopsy showed lymphocytic interstitial nephritis, compatible with exocrine gland focus score abnormalities, consistent with those found in patients with Sjögren's syndrome. The renomegaly started to diminish after 10 days and the kidney reached normal size after 2 months. All objective tests for keratoconjunctivitis sicca and xerostomia were abnormal, although daily persistent dry eyes and dry mouth symptoms were absent. Serological tests showed high levels of anti-nuclear antibodies, anti-SS-A and anti-SS-B antibodies. Thus the patient fulfils the classification criteria for primary Sjögren's syndrome. The suddenly developed unilateral renomegaly may be an early clinical manifestation of this disease.

Adolescent↗
PubMed1995

Sjögren's syndrome.

The review describes the historical development and nomenclature of Sjögren's syndrome--primary and secondary. The strengths and weaknesses as well as similarities and dissimilarities for establishing the diagnosis of keratoconjunctivitis sicca and xerostomia used among the five most commonly classification criteria sets are focused upon in text and table. Validation of the different sets of criteria are performed. Primary and secondary disease activity markers and outcome measures as well as future research plans for improving diagnosis are dealt with.

Humans↗
PubMed1995

A comparative study of tenidap, a cytokine-modulating anti-rheumatic drug, and diclofenac in rheumatoid arthritis: a 24-week analysis of a 1-year clinical trial.

Tenidap is a novel anti-rheumatic drug that combines cytokine modulation with cyclo-oxygenase inhibition. This 24-week, multicentre, double-blind, randomized study compared the clinical efficacy, biochemical effects and safety of tenidap 120 mg/day (once daily) with diclofenac 150 mg/day (50 mg t.i.d) in the treatment of 384 patients with active rheumatoid arthritis. After 24 weeks, improvement with tenidap was significantly greater than with diclofenac for all five primary efficacy parameters, two of the four secondary efficacy parameters and 11 of the 13 Arthritis Impact Measurement Scales assessments. The superior efficacy of tenidap was apparent after 4 weeks of treatment with further improvements observed by 24 weeks. The probability of discontinuation due to lack of efficacy was significantly greater in the diclofenac group. Tenidap but not diclofenac was associated with significant, rapid and sustained reductions in C-reactive protein and serum amyloid A levels and with a significant reduction in plasma interleukin-6. The nature and frequency of side-effects were similar in the two groups as was the discontinuation rate for treatment-related safety reasons. Tenidap was associated with an equal incidence of elevated transaminases, but a higher incidence of mild (> or = 500 mg/24 h < 1500 mg/24 h) non-progressive, proteinuria of proximal tubular origin compared with diclofenac.

Acute-Phase Proteins↗
PubMed1994

A reduced level of multiple mutation in a shuttle vector passaged in Sjögren's syndrome cells.

Sjögren's syndrome is a systemic disorder with unknown etiology, displaying many signs of autoimmunity. Although the basic mechanism of this disease is unknown, a defect in somatic mutagenesis of antibody genes has been suggested. Using a shuttle vector plasmid, we here show that the number of vectors with multiple base changes in a marker gene was reduced in B cell lines from two patients with Sjögren's syndrome (8% in both), as compared with values reported for cell lines from normal human donors (16-27%). This finding suggests that a reduction of the rate of somatic mutagenesis may influence the development of symptoms in Sjögren patients.

B-Lymphocytes↗