Polymorphism in the LMP2 gene influences susceptibility to extraspinal disease in HLA-B27 positive individuals with ankylosing spondylitis.

OBJECTIVE--To investigate the potential influence of the HLA-linked LMP2 gene on disease susceptibility in HLA-B27 individuals with ankylosing spondylitis (AS). METHODS--A polymorphic CfoI restriction enzyme site in the coding region of the LMP2 gene was evaluated in genomic DNA samples from 193 white and 49 Chinese B27 individuals with well documented AS, 97 of whom had had acute anterior uveitis (AAU) and 97 peripheral arthritis; 42 samples from normal, white, B27 positive blood donors in whom AS was excluded were also evaluated. RESULTS--Analysis of B27 white AS individuals with AAU, peripheral arthritis, or both, revealed significant differences in genotypic distribution of this bi-allelic locus compared with B27 AS patients without extraspinal manifestations (p < 0.005) or B27 controls (p < 0.01). Furthermore, homozygosity for one LMP2 gene allele was significantly more prevalent in AS patients with AAU (71.3%) (p < 0.01) or peripheral arthritis (68.3%) (p < 0.02) than in B27 controls (45.2%). A similar genotypic distribution was noted in B27 Chinese AS individuals with extraspinal manifestations compared with those with axial disease alone. CONCLUSIONS--These findings support the involvement of the HLA linked LMP2 gene in the expression of disease in B27 individuals and represent a novel finding in rheumatic disease.     

Ankylosing spondylitis in North India: a clinical and immunogenetic study.

Fifty-one North Indian patients with ankylosing spondylitis (AS) are described with mean age of onset 21.2 years and male to female ratio of 16:1. AS began with peripheral arthritis in 47%, low back pain in 41%, acute anterior uveitis in 10%, and heel pain in 2% of the patients. 76% of 51 patients had one of the extra-axial features of AS: peripheral arthritis (61%), heel pain (24%), anterior uveitis (22%), urethritis (12%), kidney disease (10%), mucosal ulcerations (6%), aortic incompetence (4%), and apical pulmonary fibrosis (4%). A majority (71%) of the patients with peripheral arthritis had mono- or oligoarthritis affecting mainly the lower limb joints. Two patients had coexistent rheumatoid arthritis also. HLA-B27 antigen was detected in 48 (94%) of 51 patients compared with 7 (6%) of 118 controls (relative risk 254; Fisher's exact p = 3.49(-29]. On comparing patients with juvenile onset AS and patients with adult onset disease we found peripheral arthritis to be more frequent at the beginning and during the course of disease in the former.     

The LMP2 polymorphism is associated with susceptibility to acute anterior uveitis in HLA-B27 positive juvenile and adult Mexican subjects with ankylosing spondylitis

INTRODUCTION—An association between polymorphism of the HLA linked LMP2 locus and the development of acute anterior uveitis (AAU) has previously been described in B27 positive white subjects with ankylosing spondylitis (AS). This study evaluated LMP2 alleles in two HLA-B27 positive Mexican populations of patients with spondyloarthropathy known to have a different clinical spectrum of disease from white people.
PATIENTS AND METHODS—The study populations consisted of 90 AS patients from Guadalajara with predominantly adult onset disease and 80 AS patients from Mexico City with predominantly juvenile onset disease. LMP2-CfoI amplified fragment length polymorphisms were determined after polymerase chain reaction amplification and digestion with CfoI restriction enzyme.
RESULTS—There was an increased LMP2A allelic frequency in patients who had had AAU in both Guadalajara (31.8%) and Mexico City (33.3%) when compared with non-AAU patients (15.2% and 17.7% of Guadalajara and Mexico City populations, respectively). The odds ratio relating LMP2A allelic frequency and AAU for the combined population, stratified by age at onset of disease, was 2.51 (p=0.01). LMP2 alleles did not influence the age at onset of disease or the development of peripheral arthritis.
CONCLUSIONS—These data support the view that polymorphism at the LMP2 locus is associated with the development of AAU in B27 positive subjects with AS. The requirement for both the less common LMP2 allele and HLA-B27 is consistent with the low prevalence of AAU in Mexican patients with spondyloarthritis.

     

Characterization and outcome of uveitis in 350 patients with spondyloarthropathies

This retrospective study analyzed 350 patients with the diagnosis of spondyloarthropathies (SPA) (207 with ankylosing spondylitis (AS), 80 with undifferentiated spondyloarthropathies (USPA) and 63 with psoriatic arthritis (PsA)) attended at a tertiary referral hospital for a minimum period of 5 years. All the patients presented complete clinical (axial and peripheral involvement, heel enthesopathies, extra-articular manifestations) and radiologic (sacroiliac, lumbar, dorsal and cervical spine) evaluation. HLA-B27 and respective alleles were searched. These data were compared with the occurrence of uveitis during the follow-up of the SPA patients. Thirty AS patients (14.5%) presented 55 episodes of acute anterior uveitis; there was statistical association between uveitis and juvenile-onset AS (P = 0.0094) and achillean (P = 0.0003) and plantar (P = 0.0067) enthesopathies; one AS patient presented a single episode of posterior uveitis, associated to tuberculosis. Seven USPA patients (8.8%) presented 13 episodes of acute anterior uveitis; it was not observed statistical association with any variable; one patient presented a single episode of posterior uveitis, associated to toxoplasmosis. Five HLA-B27 positive PsA patients (8%) presented 13 episodes of acute anterior uveitis. All the 26 positive HLA-B27 SPA patients with anterior uveitis tested for the HLA-B27 alleles were HLA-B*2705. No patient presented ophthalmologic severe sequelae of the anterior uveitis. Concluding, anterior uveitis was associated to the juvenile onset of the disease and to the enthesophatic involvement of the lower limbs in AS patients. The HLA-B*2705 allele was predominant in the anterior uveitis patients, whilst posterior uveitis was rare and associated to infectious disease.     

HLA class I associations of ankylosing spondylitis in the white population in the United Kingdom.

OBJECTIVE: To investigate the HLA class I associations of ankylosing spondylitis (AS) in the white population, with particular reference to HLA-B27 subtypes. METHODS: HLA-B27 and -B60 typing was performed in 284 white patients with AS. Allele frequencies of HLA-B27 and HLA-B60 from 5926 white bone marrow donors were used for comparison. HLA-B27 subtyping was performed by single strand conformation polymorphism (SSCP) in all HLA-B27 positive AS patients, and 154 HLA-B27 positive ethnically matched blood donors. RESULTS: The strong association of HLA-B27 and AS was confirmed (odds ratio (OR) 171, 95% confidence interval (CI) 135 to 218; p < 10(-99)). The association of HLA-B60 with AS was confirmed in HLA-B27 positive cases (OR 3.6, 95% CI 2.1 to 6.3; p < 5 x 10(-5)), and a similar association was demonstrated in HLA-B27 negative AS (OR 3.5, 95% CI 1.1 to 11.4; p < 0.05). No significant difference was observed in the frequencies of HLA-B27 allelic subtypes in patients and controls (HLA-B*2702, three of 172 patients v five of 154 controls; HLA-B*2705, 169 of 172 patients v 147 of 154 controls; HLA-B*2708, none of 172 patients v two of 154 controls), and no novel HLA-B27 alleles were detected. CONCLUSION: HLA-B27 and -B60 are associated with susceptibility to AS, but differences in HLA-B27 subtype do not affect susceptibility to AS in this white population.     

Dutch patients with familial and sporadic ankylosing spondylitis do not differ in disease phenotype

OBJECTIVE: To assess potential differences in the phenotypic expression between familial and sporadic ankylosing spondylitis (AS). METHODS: Clinical data from the patient record forms were compared between 55 patients with AS from multicase families (i.e., families in which > or = 2 first-degree relatives have the disease) (familial AS) and 110 sex and age matched patients with AS who did not have a first-degree relative with the disease (sporadic AS). RESULTS: Between familial and sporadic AS no differences were found in age at disease onset, age at diagnosis, or prevalences of peripheral arthritis and acute anterior uveitis. CONCLUSION: Potential differences in genetic makeup are not reflected in differences in the phenotypic expression of familial and sporadic AS.     

Epidemiology of spondyloarthritis in Brazil

During the period of 2006 to 2007, 28 university centers in Brazil used a standardized protocol of investigation to study the epidemiological, clinical and radiological variables of 1036 consecutive patients with the diagnosis of spondyloarthritis (SpA). Validated translated (Portuguese) versions of the Bath Ankylosing Spondylitis (AS) Disease Activity Index and the Bath AS Functional Index were applied. Patient diagnoses were predominantly AS (72.3%), followed by psoriatic arthritis (13.7%), undifferentiated SpA (6.3%), reactive arthritis (3.6%), juvenile SpA (3.1%) and arthritis related to inflammatory bowel disease (1.0%). There was a predominance of male (73.6%) and white (59.5%) patients. Pure axial disease was observed in 36.7% of the patients, whereas the mixed pattern (axial, peripheral and entheseal) was observed in 47.9%. The most common extra-articular involvement was anterior uveitis (20.2%). HLA-B27 was positive in 69.5% of the tested patients.     

Osteoarticular manifestations of pustulosis palmaris et plantaris and of psoriasis: two distinct entities.

OBJECTIVE: To test the hypothesis that pustulosis palmaris et plantaris and psoriatic arthritis (PsA) are two distinct diseases, and that the associated dermatoses are therefore also distinct diseases. METHODS: We prospectively performed clinical, radiological, biological, and bone scan investigations in 23 outpatients with pustolotic arthritis and 23 outpatients with PsA, matched by gender, age (+/- one year) and duration of arthritis (+/- two years). RESULTS: The anterior chest wall, especially the sternocostoclavicular joints, was more frequently involved in pustulotic arthritis than in PsA, both clinically (82% v 43%; p < 0.001) and radiologically (47% v 17%; p < 0.05). Sternocostoclavicular joints generally presented with erosive lesions in PsA, and with large ossifications in pustulotic arthritis. Peripheral joint involvement was mono- or oligoarticular, affecting proximal joints, in pustulotic arthritis (74% v 21%; p < 0.01), and polyarticular, involving small distal joints, in PsA (60% v 0%; p < 10(-4)), in which condition it was also more often erosive (43% v 8%; p < 0.01). The frequency of sacroiliitis and of spine involvement was similar in pustulotic arthritis and PsA. Biology and bone scan did not help distinguish between the two groups. CONCLUSIONS: Pustulotic arthritis and PsA are clinically and radiologically different, therefore pustulosis palmaris et plantaris and psoriasis are most probably distinct dermatological diseases.     

The outcome of ankylosing spondylitis: a study of 100 patients

The outcome was studied in 100 patients with adult-onset primary ankylosing spondylitis (AS). After a mean disease duration of 16 yr, 51.5% of the patients were employed in full-time work. Cessation of work occurred at a mean disease duration of 15.6 yr, and was significantly associated with female sex, low levels of education, acute anterior uveitis, 'bamboo spine' and the co-existence of non- rheumatic diseases. Functional outcome was studied by analysing activities of daily living, and revealed similar findings in males and females. Most of the loss of function occurred during the first 10 yr of disease, and correlated significantly with the occurrence of peripheral arthritis, spinal X-ray changes of AS and development of 'bamboo spine'. After > 20 yr of disease, > 80% of the patients still complained of daily pain and stiffness, and > 60% reported daily use of drugs.      

Ossification of the posterior longitudinal ligament in three geographically and genetically different populations of ankylosing spondylitis and other spondyloarthropathies

STUDY DESIGN—Cross sectional.
RESEARCH QUESTIONS—(a) Is any clinical variable of ankylosing spondylitis (AS) associated with the presence of ossification of the posterior longitudinal ligament (OPLL)? and (b) Is OPLL present in patients with AS from different geographical or genetic backgrounds?
METHODS—Three groups were assembled: (1) a prospective group of 103 consecutive AS patients from two community based rheumatology clinics from Guadalajara, who were evaluated using: a questionnaire with disease characteristic variables; clinical assessment by a neurologist; lateral radiographic views of the cervical spine and somatosensory evoked potentials (SSEP). (2) Fifty one spondyloarthropathies (SpA) patients from Mexico city whose cervical spine films were retrospectively reviewed. (3) Thirty nine AS patients from Edmonton, Canada whose cervical spine films were retrospectively reviewed and compared with 72 controls.
RESULTS—Group 1: 74% of the 103 patients were men and 86% were HLA-B27 positive. The mean age was 35 years, and mean (SD) disease duration 10 (8) years. OPLL was reported in 16 patients (15.5%; 95%C I 9, 22). OPLL was statistically associated with older age (p=0.001), longer disease duration (p=0.001), clinical myelopathy (p=0.03), worst functional index (p=0.042), restricted axial movement measurements (all p<0.001), radiological sacroiliitis (p<0.001 for linear association), osteitis pubis (p=0.009), hip involvement (p=0.006 for linear association), and abnormal SSEP (p=0.008). Group 2: 92% of 51 patients were men; the mean age was 30 years and the mean (SD) disease duration 11 (7) years. OPLL was reported in 15 (29%, 95%CI 17, 41) patients (nine AS, two psoriatic arthritis, three juvenile AS, and one Reiter's syndrome). Group 3: 95% of the 39 patients were men; the mean of age was 46 years and disease duration of 18 (10) years. OPLL was reported in nine (23%; 95%CI 10, 36) patients, including one with psoriatic arthritis, and two with Crohn's disease. OPLL was observed in two of the control group.
CONCLUSIONS—The prevalence of OPLL in AS and SpA is higher than previously recognised and seems to be associated with variables identifying more severe axial disease.

Keywords: ankylosing spondylitis; ossification of the posterior longitudinal ligament; psoriatic arthritis; Reiter's syndrome     

Alkaline phosphatase isoenzyme activities in rheumatoid arthritis: hepatobiliary enzyme dissociation and relation to disease activity.

OBJECTIVES--Hyperphosphatasaemia has been observed occasionally in patients with rheumatoid arthritis (RA), and it has been suggested that the serum alkaline phosphatase (ALP) level is related to the activity of the disease. Therefore, the relationship between serum ALP and RA was studied. METHODS--The serum activities of hepatobiliary enzymes (ALP isoenzymes, gamma-glutamyltranspeptidase (GTP), leucine aminopeptidase (LAP), aspartate aminotransferase (AST), and alanine aminotransferase (ALT)), immunoglobulins, RA haemagglutinin test (RAHA), C reactive protein (CRP), and erythrocyte sedimentation rate (ESR) were observed in 288 patients with rheumatoid arthritis. RESULTS--Serum biliary ALP (ALP1) activity was detected in 31.6% of the patients. In patients positive for ALP1 the respective values of total ALP (ALPt) (p < 0.001), liver ALP (ALP2) (p < 0.001), bone ALP (ALP3) (p < 0.05), gamma-GTP (p < 0.001), LAP (p < 0.001), immunoglobulins IgG (p < 0.01), IgA (p < 0.01), and IgM (p < 0.01), RAHA (p < 0.001), CRP (p < 0.001), ESR (p < 0.001), and articular index (p < 0.001) were significantly higher than in patients who did not have ALP1. Significant Spearman's rank correlations (rs) were demonstrated between serum ALP2 level and the respective values of ALPt (rs = 0.9128, p < 0.001), ALP1 (rs = 0.4443, p < 0.001), ALP3 (rs = 0.5898, p < 0.001), gamma-GTP (rs = 0.2903, p < 0.001), LAP (rs = 0.3093, p < 0.001), IgA (rs = 0.2299, p < 0.01), IgM (rs = 0.1773, p < 0.05), RAHA (rs = 0.2420, p < 0.01), CRP (rs = 0.3532, p < 0.001), ESR (rs = 0.4006, p < 0.001). the articular index (rs = 0.4006, p < 0.001). However, no significant difference or correlation was noted for either AST or ALT. In many patients who showed abnormal hyperphosphatasaemia, hepatobiliary enzyme dissociation was observed: levels of ALPt (in 12.8%), ALP1 (in 31.6%), ALP2 (18.8%), gamma-GTP (in 4.3%), and LAP (in 19.3%) were abnormally high, but both AST and ALT were within normal limits. CONCLUSION--These findings are considered to be characteristic of RA, and suggest the existence of latent or subclinical hepatobiliary involvement and an association between the expansion of hepatobiliary involvement and the mechanism of disease activation. Thus measurement of the serum levels of ALP and its isoenzymes in RA is considered to be important.     

Incidence and Predictors of Left Ventricular (LV) Thrombus after ST-Elevation Myocardial Infarction (STEMI) in the Holy Capital of Saudi Arabia

BackgroundPatients with acute myocardial infarction (AMI) especially those with large MI (myocardial infarction) as identified by ST elevation in multiple contiguous ECG leads or anterior MI, may suffer significant myocardial damage leading to impaired wall motion and contractility which may lead to the formation of left ventricular thrombus (LVT) in the patient. This study was aimed to establish the incidence of LV thrombus and determine the predictors associated with the formation of LV thrombus in patients with AMI.MethodsThis retrospective study was held at the only cardiothoracic centre of Makkah, which provides tertiary level cardiac services. A total of 3084 consecutive patients with acute MI between 2016 and 2019 were identified and divided into two groups i.e. group I (with LVT) and group II (without LVT). The case notes, echocardiography data and cardiac catheterization lab records were reviewed to identify patients with LV thrombus. Regression analysis was employed to evaluate the predictors responsible for the formation of LV thrombus.ResultsThe overall incidence for LV thrombus was determined as 8.4% (n = 260/3084), while in the subpopulation of pilgrims, it was 8.2% (83/1001). Mean age for patients with and without LVT was 54 ± 11 years vs 56 ± 12 years (p < 0.003), respectively. There was no significant difference between the two groups with respect to gender, diabetes, hypertension, smoking, Arabic speaking or BMI>30. Coronary thrombus aspiration was utilized in 17% vs 12% (p < 0.023) patients with LVT and without LVT, respectively. It was observed that the patients with cardiac arrest tend to develop more LVT i.e. 8.5% vs 5.2% (p < 0.033). However, LV thrombus formation was significantly associated with anterior STEMI with incidence of LVT reaching 13.4% and low ejection fraction (all MI types) i-e. 32 ± 9% vs 42 ± 11%, with p < 0.000 for both independent predictors.ConclusionsLV thrombus is a relatively common occurrence in patients with acute MI, especially those with anterior STEMI and low ejection fraction<30%. Appropriate imaging studies are required for all acute MI patients in order to ascertain the presence or absence of LV thrombus as it has major influence on further management.     

Anterior chest wall involvement in seronegative arthritides

Summary Material from a 10-year retrospective study of 268 patients with seronegative arthritis was analyzed with regard to the frequency of radiographic anterior chest wall (ACW) joint or bone lesions. Changes of the sternoclavicular joint were found in 17% of patients with ankylosing spondylitis (AS), in 6–9% of patients with reactive and psoriatic arthritis, and in 48% of patients with arthritis associated with palmoplantar pustular (PPP) lesions. The manubriosternal joint (MSJ) was involved in 51–57% of patients with AS and PPP lesions as well as in 18–24% of patients with reactive and psoriatic arthritis. The presence of ACW involvement was significantly related in AS, reactive and PPP associated arthritis to the duration of the disease; in AS to advanced sacroiliitis, and involvement of the spine and root joints; in psoriatic and reactive arthritis to the presence of peripheral erosive polyarthritis; in reactive arthritis to sacroiliitis and spondylitis; and in psoriatic arthritis to root joint involvement.     

Prevalence of the spondyloarthritides in patients with uveitis

OBJECTIVE: To determine the prevalence of the spondyloarthritides in patients with uveitis and to establish criteria for certain subtypes of this group of diseases. METHODS: In a university-based prospective study, we examined 433 patients with different types of uveitis for signs of spondyloarthritides as defined by the classification criteria of the European Spondylarthropathy Study Group (ESSG). RESULTS: Forty-four of the 433 uveitis patients (36 with acute anterior uveitis and 8 with other types of uveitis) had spondyloarthritis according to the ESSG classification criteria. Nineteen of these 44 patients had ankylosing spondylitis (AS), 11 had undifferentiated spondyloarthritis, 9 reactive arthritis, and 5 psoriatic arthritis. CONCLUSION: Uveitis is associated not only with AS and reactive arthritis, but also with undifferentiated spondyloarthritis and psoriatic arthritis. The ESSG criteria are helpful in identifying these spondyloarthritides in uveitis patients.     

Clinical features and followup study of HLA-B27 positive patients presenting with peripheral arthritis

A comparison was made between HLA-B27 positive patients with peripheral arthritis and patients with ankylosing spondylitis (AS). The distribution of peripheral joint involvement in HLA-B27 positive seronegative arthritis was not the same as that in AS; significant differences were also noted in the sex ratio and incidence of uveitis. Followup of the patients with peripheral arthritis revealed that 25% had developed a further criterion for Reiter's syndrome, 45% had persistent seronegative arthritis and in 55% the arthritis had resolved.     

Prevalence of ossification of posterior longitudinal ligament in patients with ankylosing spondylitis

OBJECTIVE: To determine the prevalence of ossification of the posterior longitudinal ligament (OPLL) in patients with ankylosing spondylitis (AS). METHODS: A cross-sectional radiological examination was performed in patients diagnosed with AS. A bone and joint radiologist screened and confirmed the cervical radiographs of these patients. A review of the medical records was also conducted to investigate the relationship between the clinical manifestations and the actual expression of OPLL in patients with AS. RESULTS: Among 544 patients with AS, 470 (86.4%) were men and 96.1% were HLA-B27-positive. The mean age was 34.3 +/- 9.3 years and mean disease duration was 12.4 +/- 7.2 years. After reviewing the cervical radiographs, OPLL was found in 19 patients (3.5%; 95% CI 1.9, 5.0). The mean age of these 19 patients was 39.9 +/- 10.7 years, and the male to female ratio was 18:1. Interestingly, a statistically significant number of patients who expressed OPLL were older (p = 0.007). However, we were unable to determine whether OPLL was significantly associated with AS disease duration, peripheral arthritis, anterior uveitis/iritis, HLA-B27, anterior atlantoaxial subluxation, diffuse idiopathic skeletal hyperostosis, or other paraspinal ligament disorders. CONCLUSION: Our study showed that the frequency of OPLL in Korean patients with AS was 3.5%, which was considerably lower than previously reported values (15.5% in 103 Mexican AS). We were able to determine that OPLL in AS was associated with older age.     

LMP2 polymorphism is associated with extraspinal disease in HLA-B27 negative Caucasian and Mexican Mestizo patients with ankylosing spondylitis

OBJECTIVE: To determine the effects of HLA Class II genes, particularly LMP2 and previously implicated Class I genes, on susceptibility and disease expression in HLA-B27 negative ankylosing spondylitis (AS). METHODS: Patients included 41 HLA-B27 negative Caucasians from a total AS population of 546 and 17 HLA-B27 negative Mexican Mestizo. Controls included 4352 random HLA-B27 negative Caucasians. LMP2 genotype assignments were made on all patients and 282 random Caucasian controls by polymerase chain reaction-restriction fragment length polymorphism with the Cfo I restriction enzyme while HLA typing was performed on patients and controls using microcytotoxicity assays for Class I, and sequence specific probe-PCR for HLA-B60, B39, B38, and DR. RESULTS: The LMP2BB genotype was significantly decreased in Caucasian AS patients without extraspinal (ES) disease (25%) compared to AS patients with ES (64.7%) (p = 0.01) and random Caucasian controls (53.9%) (p = 0.007), even when those with colitis and psoriasis were excluded from analysis (ES+ 55.6% versus ES- 22.2%). This finding remained significant after stratification by HLA-DR. Similar trends were noted in the Mexican population. A potential role for HLA-DR8 and DR2 in susceptibility to disease was observed in Caucasian patients, although this observation requires confirmation. We could not confirm reported associations with HLA-B60 or B39. Peripheral arthritis was significantly more commonly observed in those who had had acute anterior uveitis (AAU) (75%) than in those who had not developed AAU (27.3%) (p = 0.04). CONCLUSION: HLA Class II encoded genes may have effects on disease susceptibility and/or phenotype in HLA-B27 negative individuals similar to those noted in HLA-B27 positive AS. Eccentric and axial phenotypes of disease may be immunogenetically determined.     

Relationships between defecographic findings,rectal emptying,and colonic transit time in constipated patients.

The relations between defecographic findings, rectal emptying, and colonic transit time were analysed in 80 constipated patients (median age 49 years, range 22-87). Patients were classified into three clinically defined groups (slow transit, outlet obstruction, and a mixed group). Rectal evacuation was evaluation was evaluated by computer-based area calculation. There were no differences in defecographic findings except that evacuation was less efficient in the slow transit group compared with the mixed group (p < 0.01) and with the outlet obstruction group (P < 0.05). Transit time was prolonged in the slow transit and mixed groups compared with the outlet group (p < 0.001). Prominent impression of the puborectalis muscle during straining and the size of a rectocoele correlated with rectal emptying (p < 0.01). Perineal descent, anorectal angles, enterocoele, or intussusception were not significantly related to emptying. Prominent impression of the puborectalis muscle (p < 0.05) and impaired rectal emptying (p < 0.05) were more frequent in patients with prolonged transit time (six or more days). There was no significant correlation between transit time and rectal evacuation in the total study population. There was, however, an inverse relation between these variables (r = 0.40, p < 0.02) when all patients who claimed infrequent defecation (two or fewer/week) were analysed separately. These results did not confirm a direct relation between rectal evacuation and colonic transit time in constipated patients overall. The results are consistent with the suggestion that impaired colonic function may develop secondary to outlet obstruction in some patients.     

Intra-articular triamcinolone hexacetonide in knee osteoarthritis: factors influencing the clinical response.

OBJECTIVE--To assess the efficacy of a single intra-articular injection of triamcinolone hexacetonide (THA) in knee osteoarthritis (OA) and examine factors which may relate to treatment efficacy. METHODS--Eighty four patients with clinical and radiographic evidence of knee OA were recruited and randomly allocated to receive either THA (20 mg in 1 ml) or placebo (0.9% normal saline, 1 ml). Follow up assessments evaluated the following outcome variables: patient opinion of overall change in the treated knee, visual analogue pain score (VAS), distance walked in one minute (WD), and Health Assessment Questionnaire modified for lower limb function (HAQ). RESULTS--Seventy eight percent of THA and 49% of placebo treated patients reported overall improvement at week 1 (p < 0.05). At week 6, improvement was reported in 57% and 55% of patient groups, respectively. VAS improved in both groups at week 1 (THA, p < 0.001; placebo, p < 0.05) and week 6 (both p < 0.01). Improvement in VAS was significantly greater among THA treated patients at week 1 only (p < 0.01). Subgroup analysis of THA treated patients revealed greater improvement in VAS among patients with clinical evidence of an effusion (p < 0.05), and those who had synovial fluid successfully aspirated at the time of injection (p < 0.01). WD improved in THA treated patients at week 1 (p < 0.001), and in both groups at week 6 (THA, p < 0.001; placebo, p < 0.01). Improvements in HAQ were seen in THA patients only at weeks 1 and 6 (p < 0.05). Regression analysis did not identify any additional clinical, radiographic, or synovial fluid characteristics which influenced the response. CONCLUSIONS--THA provided short term pain relief in knee OA. Increased benefit was associated with both clinical evidence of joint effusion and successful aspiration of synovial fluid at the time of injection.     

Interleukin 1 beta, hand and foot bone mineral content and the development of joint erosions in rheumatoid arthritis.

OBJECTIVE--To assess the relationship between plasma levels of the cytokine interleukin-1 beta (IL-1 beta) and the progression of rheumatoid arthritis (RA). METHODS--Two subgroups of patients, one with persistently raised ESR (>/= 50 mm/hour, n = 16, group A) and one with persistently low ESR (</= 28 mm/hour), n = 18, group I) were chosen to represent stable extremes of inflammatory activity from a prospective study of 106 patients with active RA studied over one year in a single centre. The change from baseline in hand, foot and calcaneal bone mineral content measured by single photon absorptiometry and radiographic score of joint damage was measured over 12 months, together with plasma IL-1 beta and erythrocyte sedimentation rate. RESULTS--Significant progression of joint damage occurred in both subgroups over one year (p < 0.0001, paired t test) though progression was significantly less in the subgroup with low ESR (p < 0.05, ANOVA). Hand and foot bone mineral content decreased by almost 10% in the subgroup with raised ESR (p < 0.005, paired t test). Stepwise linear regression analysis revealed significant independent relationships between radiographic progression over one year and plasma IL-1 beta and ESR (multiple R 0.674, F = 11.64, p < 0.0002). No such relationships were observed for changes in bone mineral content parameters. CONCLUSIONS--Plasma IL-1 beta levels correlate weakly with progression of joint damage though not with loss of peripheral bone density in RA. A significant reduction in peripheral bone mineral content occurs over one year in patients with active RA with persistently raised ESR.