Effect of treatment on the outcome of very early rheumatoid arthritis

OBJECTIVE: To evaluate the effect of treatment on the outcome of very early RA. METHODS: In a 3-year prospective study of 27 patients with very early RA (VERA) (symptoms <4 months before diagnosis) and 122 patients with early RA (symptoms between 4-24 months) the effect of active treatment on the clinical picture, functional capacity, and radiological progression was evaluated. RESULTS: Initially VERA patients had a more active clinical picture and worse functional capacity. Despite a higher number of DMARDs used in VERA patients, C-reactive protein and Ritchie index remained significantly higher in these patients (although significant improvement occurred). They also had a more rapidly progressive disease (higher Larsen score/month of symptoms) during pre-treatment period, the progression of which was retarded with early, active DMARD therapy. By the end of 3 years, the rate of progression ran parallel in both groups. CONCLUSION: Active treatment had an impact on the rate of radiological progression and clinical activity but not on the functional outcome in patients with initially active RA of short duration.     

HLA typing and seropositivity in finnish and in polish patients with rheumatoid arthritis and amyloidosis

Summary We determined HLA-A,-B,-C and-DR antigens in 83 patients with rheumatoid arthritis (RA) and reactive secondary amyloidosis (RSA), 60 in Finland and 23 in Poland, and compared the results with control RA patients and blood donors. There were no significant differences in the frequencies of HLA between the RA patients with and those without RSA in either Finland or Poland, and no significant differences between the Finnish and Polish patients with RSA. All the RSA patients from Finland and 70% of the RSA patients from Poland were seropositive. In the development of RSA, the prolonged period of inflammatory stimuli may play a more important role than genetic factors.     

Reactive arthritis after an outbreak of Yersinia pseudotuberculosis serotype O:3 infection

OBJECTIVE: To determine the occurrence and clinical characteristics of reactive arthritis (ReA) after an outbreak of Yersinia pseudotuberculosis serotype O:3 infection. METHODS: From 15 October to 6 November 1998, a widespread outbreak of Y pseudotuberculosis serotype O:3 occurred in Finland. A questionnaire on musculoskeletal symptoms was mailed to 38 patients with infection confirmed by culture. All patients who reported joint symptoms were interviewed by phone and their medical records of outpatient visits or hospital admission because of recent joint symptoms were reviewed. RESULTS: Thirty three of 38 (87%) patients returned the questionnaire. Reactive musculoskeletal symptoms were reported by 5/33 (15%): four patients (12%) fulfilled the criteria for ReA and one additional patient had reactive enthesopathy. The patients with ReA were adults (age range 40-47 years), whereas the patient with reactive enthesopathy was a 14 year old boy. In all patients with ReA, the arthritis was polyarticular. In addition to peripheral arthritis, other musculoskeletal symptoms included sacroiliitis (one patient), pain in Achilles tendon (one patient), and heel pain (two patients). HLA-B27 was positive in all the three patients tested. In three of four patients with ReA, the duration of acute arthritis was over six months. CONCLUSION: Y pseudotuberculosis serotype O:3 infection is frequently associated with ReA and the clinical picture is severe.     

False-negative serological HLA-B27 typing results may be due to altered antigenic epitopes and can be detected by polymerase chain reaction

Serological typing with the microlymphocytotoxicity test (MLCT) and flow cytometry (FC) using HLA-B27 antisera is commonly used for the determination of HLA-B27. However, in some patients tested more than once, negative results have turned out to be positive at following investigations. We retested by polymerase chain reaction (PCR) samples from 20 randomly selected patients with reactive arthritis or Reiter's syndrome who had now been followed for 20 yr. Ten of the patients were originally tested to be HLA-B27 positive and 10 HLA-B27 negative by the MLCT. All 10 serologically HLA-B27 positive individuals were also positive in the PCR. However, 2/10 patients interpreted as being HLA- B27 negative were positive by PCR. At this time, the same two patients were also positive in the routine MLCT and FC using four different monoclonal antibodies against HLA-B27. PCR is superior to serological techniques to determine HLA-B27 positivity unequivocally, since it is based on the detection of HLA-B27 gene sequences.      

Peptidylarginine deiminase, the arginine to citrulline converting enzyme, is frequently recognized by sera of patients with rheumatoid arthritis, systemic lupus erythematosus and primary Sjögren syndrome

OBJECTIVE: Antibodies to citrulline-containing epitopes of filaggrin are highly specific for rheumatoid arthritis (RA). We studied whether the enzyme peptidylarginine deiminase (PAD), responsible for the post-translational modification of peptide-bound arginine residues to citrulline, constitutes an antigen for patients with RA. METHODS: IgG antibodies to PAD were measured by enzyme-linked immunosorbent assay (ELISA) in sera from patients with RA, systemic lupus erythematosus (SLE), primary Sj?gren syndrome (pSS), multiple sclerosis (MS) and healthy controls. RESULTS: Compared to healthy controls, raised levels of IgG antibodies to PAD were found in 50 of 57 recent-onset RA patients (88%) and in 40 (70%) of the same 57 patients 3 years later (p<0.0001 for both comparisons). Eleven of 51 (22%) patients with RA of long duration, 19/43 (44%) patients with SLE and 16/19 (84%) patients with pSS, but none of 20 patients with MS, had elevated anti-PAD levels. CONCLUSION: The arginine-citrulline converting enzyme PAD was recognized as a new antigen against which patients with inflammatory rheumatic diseases frequently show IgG class antibodies.     

Fibre in beverages can enhance perceived satiety

Background  A high intake of dietary fibre has been suggested to support the regulation of energy intake and satiety, which could contribute favourably to the increasing obesity problem. Aim of the study  To investigate the effects of three fibres differing in chemical and physical properties on perceived satiety and hunger-related attributes. Methods  A total of 19 healthy volunteers, age 18–30, mean BMI 23.2 kg/m² participated in the study. Measurement of food and satiety-related perceptions with ten attributes was performed by using 10-unit graphic intensity scales during a 120 min period after the ingestion the sample. The attributes evaluated were satiety, hunger (unipolar and bipolar scale), appetite, fullness, desire to eat something/sweet/savoury/the sample food and thirst. The sample foods used were a beverage without fibre, a guar gum beverage, a wheat bran beverage, an oat β-glucan beverage and wheat bread was used as the control. The fibre content of the samples was 0 g (beverage without fibre), 2.4 g (wheat bread), 7.8 g (guar gum) or 10.5 g (wheat bran and oat β-glucan beverage) per 400 g/1,000 kJ portion. Results  The area under curve (AUC) for perceived satiety was higher (169 vs. 83 cm min; t test P = 0.026) and the desire to eat was lower (AUC −179 vs. −83 cm min; t test P = 0.008) for the guar gum beverage as compared to the beverage without fibre. Also the beverage with oat β-glucan increased fullness and showed a trend of increasing perceived satiety and decreasing the desire to eat more than the beverage without fibre. Conclusions  Our results support the idea that dietary fibre in beverages can enhance their perceived satiety and decrease the desire to eat more than a beverage without fibre.     

Age at Onset of Type 1 Diabetes in Parents and Recurrence Risk in Offspring

OBJECTIVE

Our aim was to study the recurrence risk of type 1 diabetes in the offspring of parents with adult-onset (15–39 years) type 1 diabetes and to evaluate the transmission of diabetes within a continuum of parental age at onset of diabetes from childhood to adulthood.

RESEARCH DESIGN AND METHODS

Diabetes status of all offspring (n = 9,636) in two Finnish cohorts of parents with type 1 diabetes was defined until the end of year 2007. Cumulative incidences of type 1 diabetes among the offspring were estimated, and several factors contributing to the risk were assessed.

RESULTS

During 137,455 person-years, a total of 413 offspring were diagnosed with type 1 diabetes. The cumulative incidence by 20 years was 4.0% (95% CI 3.1–4.8) for the offspring of parents with adult-onset diabetes. The risk was equal according to the sex of the parents. The cumulative incidence decreased in parallel with the increase in age at onset of diabetes in the fathers. In the offspring of diabetic mothers, the risk was equal regardless of the age at onset of diabetes. However, the reduced risk in the maternal offspring was most pronounced in the daughters of the mothers with a diagnosis age <10 years.

CONCLUSIONS

Type 1 diabetes transmission ratio distortion is strongly related to the sex and age at onset of diabetes in the diabetic parents.Type 1 diabetes can occur at any age, although it is predominantly seen in children and young adults. Therefore, the majority of studies have been conducted in children aged <15 years. The recurrence risk in the offspring ranges from 3 to 6% depending on the study design, follow-up time, and the population where the study was conducted (1–3). Little is known about the recurrence risk in first-degree relatives of subjects diagnosed with type 1 diabetes, aged >15 years. The incidence of type 1 diabetes is much lower in young adults than in children (4–6). Consequently, the risk of family members may also be different among the diabetic subjects affected after childhood.Sex-related factors seem to be involved in the transmission of diabetes from one generation to the next (7). By 20 years of age, 5–8% of the offspring of diabetic men and only 2–5% of the offspring of diabetic women have been found to be affected (1–3,8). We have previously shown that the recurrence risk of diabetes in the offspring of parents diagnosed between 0–17 years of age was higher the younger the father was when diagnosed with type 1 diabetes. This pattern was not present in the offspring of the mothers (8). However, it is not known whether the sex-related factors play a role in the transmission of diabetes in adult-onset type 1 diabetes. We have now enlarged our study to also include the offspring of parents diagnosed with diabetes between 15 and 39 years of age. This gives us an opportunity to determine the risk in the offspring of parents with a broad age span at diagnosis and to elucidate whether there are differences in the risk between the offspring of diabetic mothers and fathers.     

Visual fields at school-age in children treated with vigabatrin in infancy

Purpose:   The use of vigabatrin (VGB) as an antiepileptic drug (AED) has been limited by evidence showing that it causes vigabatrin-attributed visual field loss (VAVFL) in at least 20–40% of patients exposed at school age or later. VGB is an effective drug for infantile spasms, but there are no reports on later visual field testing after such treatment. Our aim was to investigate the risk of VAVFL in school-age children who had received VGB in infancy.
Methods:   Visual fields of 16 children treated with VGB for infantile spasms were examined by Goldmann kinetic perimetry at age 6–12 years. Normal fields were defined as the temporal meridian extending to more than 70°, and mild VAVFL between 50 and 70°. Abnormal findings were always confirmed by repeating the test. Exposure data were collected from hospital charts.
Results:   Vigabatrin was started at a mean age of 7.6 (range, 3.2–20.3) months. The mean duration of therapy was 21.0 (9.3–29.8) months and cumulative dose 655 g (209–1,109 g). Eight children were never treated with other AEDs, five received only adrenocorticotropic hormone (ACTH) in addition to VGB, and three children had been treated with other AEDs. Fifteen children had normal visual fields. Mild VAVFL was observed in one child (6%) who had been treated with VGB for 19 months and who received a cumulative dose of 572 g.
Conclusions:   The risk of VAVFL may be lower in children who are treated with VGB in infancy compared to patients who receive VGB at a later age.     

Transoesophageal echocardiography should be considered in patients with ischaemic stroke or transient ischaemic attack

BACKGROUND AND PURPOSE: In this present study, we tried to find out if there is a subgroup of patients that should not undergo transoesophageal echocardiography (TEE) after an ischaemic stroke or transient ischaemic attack (TIA). METHODS: A total of 441 consecutive unselected patients with ischaemic stroke or TIA suitable for anticoagulation were examined with TEE in the acute phase. The patients were divided into five subcategories according to their rhythm, age and the findings in carotid sonography, and into two groups according to the presence of clinical risk factors for ischaemic stroke or TIA. RESULTS: From the 441 studied patients, 60 (14%) had chronic or paroxysmal atrial fibrillation (AF) and 381 (86%) were in sinus rhythm (SR). Of the patients in SR, 46 (12%) were below 50 years old. The carotid sonography was conducted in 240 patients above 50 years old and in SR, and <50% internal carotid artery (ICA) stenosis was found in 194 (81%) patients and > or =50% ICA in 46 (19%) patients. Potential cardiac sources of embolism were found in patients both with AF or in SR (70% versus 46%), both below and above 50-year-old patients in SR (37% versus 47%), both in over 50-year-old patients in SR with <50% ICA stenosis and > or =50% ICA stenosis (41% versus 61%) and in patients in SR either without or with clinical risk factors for ischaemic stroke or TIA (43% versus 51%). On the basis of the TEE study, oral anticoagulation was started in 36 (9%) patients in SR. CONCLUSION: These results support TEE in patients with ischaemic stroke or TIA who are candidates for receiving oral anticoagulation.