Feasibility and safety of cangrelor in patients with suboptimal P2Y12 inhibition undergoing percutaneous coronary intervention: rationale of the Dutch Cangrelor Registry.

BACKGROUND: Despite the advances of potent oral P2Y12 inhibitors, their onset of action is delayed, which might have a negative impact on clinical outcome in patients undergoing percutaneous coronary intervention (PCI). Trials conducted in the United States of America have identified cangrelor as a potent and rapid-acting intravenous P2Y12 inhibitor, which has the potential of reducing ischemic events in these patients without an increase in the bleeding. As cangrelor is rarely used in The Netherlands, we conducted a nationwide registry to provide an insight into the use of cangrelor in the management of patients with suboptimal platelet inhibition undergoing (primary) PCI (the Dutch Cangrelor Registry). STUDY DESIGN: The Cangrelor Registry is a prospective, observational, multicenter, single-arm registry with cangrelor administered pre-PCI in: (1) P2Y12 naive patients with ad-hoc PCI, (2) patients with STEMI/NSTEMI with suboptimal P2Y12 inhibition including (3) stable resuscitated/defibrillated patients with out-of-hospital cardiac arrest (OHCA) due to acute ischemia and (4) STEMI/NSTEMI patients with a high thrombotic burden. Primary endpoint is 48 h Net Adverse Clinical Events (NACE), which is a composite endpoint of all-cause death, recurrent myocardial infarction (MI), target vessel revascularization (TVR), stroke, stent thrombosis (ST) and BARC 2-3-5 bleeding. The Dutch Cangrelor Registry will assess the feasibility and safety of cangrelor in patients with suboptimal P2Y12 inhibition undergoing (primary) PCI in the setting of acute coronary syndrome (ACS) and stable coronary artery disease (CAD) in the Netherlands.

IL-10 signaling in dendritic cells controls IL-1ß-mediated IFNγ secretion by human CD4+ T cells: relevance to inflammatory bowel disease.

Uncontrolled interferon γ (IFNγ)-mediated T-cell responses to commensal microbiota are a driver of inflammatory bowel disease (IBD). Interleukin-10 (IL-10) is crucial for controlling these T-cell responses, but the precise mechanism of inhibition remains unclear. A better understanding of how IL-10 exerts its suppressive function may allow identification of individuals with suboptimal IL-10 function among the heterogeneous population of IBD patients. Using cells from patients with an IL10RA deficiency or STAT3 mutations, we demonstrate that IL-10 signaling in monocyte-derived dendritic cells (moDCs), but not T cells, is essential for controlling IFNγ-secreting CD4+ T cells. Deficiency in IL-10 signaling dramatically increased IL-1ß release by moDCs. IL-1ß boosted IFNγ secretion by CD4+ T cells either directly or indirectly by stimulating moDCs to secrete IL-12. As predicted a signature of IL-10 dysfunction was observed in a subgroup of pediatric IBD patients having higher IL-1ß expression in activated immune cells and macroscopically affected intestinal tissue. In agreement, reduced IL10RA expression was detected in peripheral blood mononuclear cells and a subgroup of pediatric IBD patients exhibited diminished IL-10 responsiveness. Our data unveil an important mechanism by which IL-10 controls IFNγ-secreting CD4+ T cells in humans and identifies IL-1ß as a potential classifier for a subgroup of IBD patients.

Macrophage-mediated gliadin degradation and concomitant IL-27 production drive IL-10- and IFN-γ-secreting Tr1-like-cell differentiation in a murine model for gluten tolerance.

Celiac disease is caused by inflammatory T-cell responses against the insoluble dietary protein gliadin. We have shown that, in humanized mice, oral tolerance to deamidated chymotrypsin-digested gliadin (CT-TG2-gliadin) is driven by tolerogenic interferon (IFN)-γ- and interleukin (IL)-10-secreting type 1 regulatory T-like cells (Tr1-like cells) generated in the spleen but not in the mesenteric lymph nodes. We aimed to uncover the mechanisms underlying gliadin-specific Tr1-like-cell differentiation and hypothesized that proteolytic gliadin degradation by splenic macrophages is a decisive step in this process. In vivo depletion of macrophages caused reduced differentiation of splenic IFN-γ- and IL-10-producing Tr1-like cells after CT-TG2-gliadin but not gliadin peptide feed. Splenic macrophages, rather than dendritic cells, constitutively expressed increased mRNA levels of the endopeptidase Cathepsin D; macrophage depletion significantly reduced splenic Cathepsin D expression in vivo and Cathepsin D efficiently degraded recombinant γ-gliadin in vitro. In response to CT-TG2-gliadin uptake, macrophages enhanced the expression of Il27p28, a cytokine that favored differentiation of gliadin-specific Tr1-like cells in vitro, and was previously reported to increase Cathepsin D activity. Conversely, IL-27 neutralization in vivo inhibited splenic IFN-γ- and IL-10-secreting Tr1-like-cell differentiation after CT-TG2-gliadin feed. Our data infer that endopeptidase mediated gliadin degradation by macrophages and concomitant IL-27 production drive differentiation of splenic gliadin-specific Tr1-like cells.

[Balloon pulmonary angioplasty for chronic thromboembolic pulmonary hypertension]. / Ballonpulmonalisangioplastiek voor chronische trombo-embolische pulmonale hypertensie.

Chronic thromboembolic pulmonary hypertension (CTEPH) is characterised by an elevated average blood pressure in the pulmonary artery (≥ 25 mmHg). This increase is secondary to fibrous organization of thromboembolic obstructions in the pulmonary arteries. CTEPH is associated with significant morbidity and mortality due to right-sided heart failure and ventilation-perfusion discrepancy. Therapy is aimed at normalising pulmonary artery pressure, and pulmonary endarterectomy is usually the treatment of first choice. When surgery is not possible because of peripheral disease localisation or comorbidity, percutaneous balloon pulmonary angioplasty (BPA) can be used. BPA is associated with improvements in functional status and haemodynamic profile. Initially procedural complications often occurred, but improvements in procedural technique have ensured that BPA is used increasingly worldwide. In this article, we discuss the history, procedural aspects and outcomes of BPA, and present our first experiences with BPA in a patient with CTEPH.

Increased production of interleukin-21, but not interleukin-17A, in the small intestine characterizes pediatric celiac disease.

Celiac disease (CD) is caused by inflammatory CD4(+) T-cell responses to dietary gluten. It is unclear whether interleukin (IL)-21 and IL-17A contribute to CD onset and lesion severity; therefore, we investigated IL-21 and IL-17A expression in biopsies from pediatric CD patients with different histopathological scores. High numbers of IL-21-producing cells were observed in pediatric CD lesions, even Marsh 1-2 lesions, whereas increased numbers of IL-17 secreting cells were not observed. Intraepithelial lymphocytes, CD4(+) T cells and also neutrophils secreted IL-21. Flow cytometry of lamina propria cells revealed a large population of IL-21- and interferon-γ (IFN-γ)-secreting CD3(+) T cells that did not secrete IL-17A. Adult CD patient biopsies also contained high numbers of IL-21-positive cells; however, enhanced numbers of IL-17-positive cells were observed in a small subgroup of patients with severe lesions. As duodenal tissue damage increases contact with microbe-associated molecular patterns, we hypothesized that microbial sensing by Toll-like receptors (TLRs) modulates T cell-derived cytokine secretion. Costimulation with TLR3 ligands during polyclonal T-cell activation significantly increased IL-21 secretion, whereas TLR2 ligands selectively enhanced IL-17A. These results demonstrate that an IL-17A-independent increase in IL-21 production by CD4(+) T cells is characteristic of pediatric CD. We hypothesize that incidental IL-17 secretion is caused by tissue damage rather than gluten-specific responses.

Hypoxia inducible factor-1-alpha (HIF-1alpha) is related to both angiogenesis and inflammation in rheumatoid arthritis.

OBJECTIVES: Despite the important role of the transcription factor HIF-1alpha in angiogenesis and inflammation, only a few studies on HIF-1alpha expression have been performed in RA patients. The aim of the present study was to identify the layer in synovial tissue of RA patients where HIF1a is expressed and to find out whether HIF-1alpha expression is related to both angiogenesis and inflammation in synovium from RA patients. METHODS: A reproducible staining method for HIF-1alpha was developed. HIF-1alpha -positive cells were quantified in synovial tissue from patients with RA. As control we used synovial tissue from patients with osteoarthritis (OA). The number of HIF-1alpha-positive cells was compared with the number of blood vessels present and was correlated with the amount of inflammation. The amount of inflammation was determined by counting inflammatory cells, by estimating the proliferation marker Ki67 in inflamed tissue, and by using a recently published synovitis score which gives an accurate estimate of the amount of inflammation present. RESULTS: HIF-1alpha was expressed weakly in the lining layer and strongly in the sublining layer in RA synovial tissue. In contrast, HIF-1alpha was only weakly expressed in OA synovial tissue. The number of HIF-1alpha -positive cells correlated strongly with the number of blood vessels in RA synovial tissue and with inflammatory endothelial cell infiltration (blood vessels), cell proliferation (Ki67) and the synovitis score. CONCLUSIONS: HIF-1alpha expression is strongest in the sub-lining layer of RA synovium and is related to both angiogenesis and inflammation in synovium from RA patients. These results thus suggest that HIF-1alpha could serve as an important new therapeutic target in RA, targeting both angiogenesis and inflammation.

Functional ability, social support, and depression in rheumatoid arthritis.

OBJECTIVE: First, to investigate the patterns of functional ability, depressive feelings, and social support in early stage rheumatoid arthritis (RA) patients. Second, to demonstrate the stress buffering effect of social support. Social support is thought to reduce the impact of chronic stress on psychological well-being; for patients without social support the impact of functional ability on depressive feelings will be stronger. METHODS: In 4 waves with an intervening period of 1 year, longitudinal data was collected of 264 Dutch RA patients, of which 65% was female. At T1, the mean age of these patients was 53 years, while their mean disease duration was 22 months. In an interview at the patients' homes, data was collected on functional ability, social support en psychological well-being. The buffering effect of social support was examined by testing the significance of the (computed) stressor by social support interaction term in a regression analysis on depressive feelings. RESULTS: Although large differences between subjects existed, the mean scores on functional ability, social support, and depressive feelings barely changed from year to year. Patients who deteriorated in functional ability during one year had the best chances to improve next year, and visa versa. Furthermore, the stress by support interaction terms had no significant effect on depressive feelings in a regression analysis. CONCLUSIONS: This study demonstrated clearly the fluctuating pattern of RA in the first years after onset. The patients' level of depressive feelings was linearly related to the level of functional ability. Like many other studies, also this study could not provide evidence for the stress buffering effect of social support.

Serum matrix metalloproteinase 3 levels in comparison to C-reactive protein in periods with and without progression of radiological damage in patients with early rheumatoid arthritis.

OBJECTIVE: To evaluate serum matrix metalloproteinase 3 (MMP-3) levels in comparison to C-reactive protein (CRP) in periods with and without progression of radiological damage in patients with early rheumatoid arthritis (RA). METHODS: Thirty-two patients with RA and radiological progression (> or = 5 points according to the Sharp/van der Heijde method) during 6 months followed by a 6-month period without radiological progression (< or = 1 point) were selected from a prospective follow-up study of early RA patients. Serum MMP-3 levels, CRP, the erythrocyte sedimentation rate (ESR), disease activity index (DAS), swollen joint count (SJC), tender joint count (TJC), and Ritchie articular index (RAI) were measured monthly and results were transformed into mean values for the 6-month periods. RESULTS: During the period with radiological progression the mean serum MMP-3 correlated significantly with the mean CRP (r = 0.68, p < 0.001), ESR (r = 0.54, p = 0.001) and swollen joint count (r = 0.48, p = 0.006). In the period without radiological progression the mean serum MMP-3 only correlated with the mean CRP (r = 0.44, p = 0.012). Individual changes--expressed in percentages (%)--between the two periods showed a decrease in both the mean serum MMP-3 and CRP in 19 and an increase in 3 patients, in parallel with other markers of disease activity in these patients (69% of cases). The individual change (%) in mean serum MMP-3 or CRP did not correlate with the difference in radiological progression between the two periods. CONCLUSIONS: Serum MMP-3 and CRP are closely related and there seems to be no difference between serum MMP-3 and CRP with regard to the monitoring of the progression of radiological damage.

Estimating genetic differences in natural resistance in Rhön and Merinoland sheep following experimental Haemonchus contortus infection.

Genetic parameters of natural resistance were estimated in Rhön and Merinoland (German Merino) sheep following experimental infection with Haemonchus contortus. A total of 133 Rhön and 244 Merinoland lambs descending from 5 and 6 rams, respectively, were evaluated. Each helminth-naive lamb was orally infected with 5000 infective third-stage larvae (L(3)) of the nematode H. contortus at 12 weeks of age. Faecal egg counts (FEC) and haematocrit values were measured in all lambs at 16 and 20 weeks of age. Seventy-nine Merinoland and 29 Rhön male lambs were slaughtered immediately after the second sampling and worms were collected. Mean worm burden was calculated and the length of adults worms from an aliquot was measured.FEC of Rhön sheep was higher compared with Merinoland sheep (P<0.01). H. contortus L(3)-larvae specific antibody (IgL) level was higher in Rhön sheep (P<0.05). However, no differences in haematocrit, worm burden and IgG antibody values could be found between the breeds. Heritabilities for log FEC (+/-S.E.) were 0.0 and 0.07 (+/-0.07) for the first sample in Rhön and Merinoland sheep, respectively. Values for the second sample were higher in both breeds (Rhön 0.35+/-0.14, P<0.05; Merinoland 0.17+/-0.07, P<0.05). Corresponding heritabilities for haematocrit were higher in Merinoland (0.56+/-0.20 and 0.51+/-0.27) compared with Rhön (0.29+/-0.12 and 0.08+/-0.13). Heritabilities for worm burden were high in Rhön (0.54+/-0.2) and low in Merinoland (0.06+/-0.14 and 0.11+/-0.15). Estimated values for IgL were between 0.13 (+/-0.11) for the first sample in both breeds and 0.30 (+/-0.18) for the second sample in Rhön sheep. Corresponding heritabilities for IgG were not different from 0.0 in both breeds (P>0.05). Positive phenotypic correlations were estimated for IgG and IgL values in both breeds (P<0.01). IgG was significantly (P<0.05) and positively correlated with worm burden in male Merinoland and IgL with worm burden in male Rhön sheep.

Protection studies with recombinant excretory/secretory proteins of Haemonchus contortus.

The efficacy of two recombinant proteins of Haemonchus contortus was studied in both adult sheep and young lambs. These 15 and 24 kDa excretory/secretory proteins were given combined, either supplemented or not with a glycan-rich insect cell extract. In 9-month-old sheep (trial 1), faecal egg output and worm burden were reduced by 49% and 55%, respectively, after vaccination with rec15/24, and by 46% and 65% after vaccination with rec15/24 and glycan extract. No reduction in egg output or number of worms was found in young lambs using the above recombinant proteins plus glycan-rich extract (trial 2). When trial 1 was repeated (trial 3), the protection could not be reproduced, possibly due to differences in batches of recombinant proteins. In all sheep, independent of their age, rec15/24-specific immunoglobulin (Ig)G1 and IgA titres were present, but 9-month-old protected sheep had significantly higher IgA titres than the lambs. Addition of glycans resulted in lower rec15/24-specific IgG1 and IgA in 9-month-old sheep after challenge. This did not affect the level of protection. A significant negative correlation was found between IgA and worm numbers in protected sheep immunized with rec15/24 supplemented with glycans. Total IgE and rec15/24 specific IgE titres were low. The number of eosinophils, mast cells, sheep mast cell protease (SMCP)+ cells and IgA+ cells did not differ between the protected and unprotected sheep, but the lambs had significantly fewer mast cells independent of their immunization.

Age-related protective immunity after vaccination with Haemonchus contortus excretory/secretory proteins.

Protection against an experimental challenge infection by immunization with excretory/secretory products (ES) from Haemonchus contortus, containing predominantly proteins of 15 and 24 kDa, depends on the age of the sheep. Vaccinated sheep 9 and 6 months of age had reduced final worm burdens of 82 and 77, respectively. No reduction in worm burden was found in 3-month-old lambs. Nine-month-old sheep had significantly higher ES-specific serum immunoglobulin (Ig)G1 and IgA during immunizations and after challenge infection than 3-month-old lambs. There was no correlation within the 9-month-old sheep between ES-specific IgA or IgG1 levels and protection, measured as worm burden. However, when the different age groups were combined, negative correlations between percentage protection and ES-specific IgA and IgG1 levels after challenge were found. At the end of the experiment, peripheral blood eosinophils and mast cell counts in abomasal tissue were also significantly higher in the vaccinated and challenged 9-month-old sheep than in the vaccinated and challenged 3-month-old or than in the 9-month-old sheep with challenge, but without vaccination. The responses measured in young lambs were similar to the responses in sheep, but the height of these responses was in general of a lower magnitude.

Serum matrix metalloproteinase 3 in early rheumatoid arthritis is correlated with disease activity and radiological progression.

OBJECTIVE: To analyze the clinical significance of serial measurements of serum matrix metalloproteinase 3 (MMP-3) levels in relation to markers of disease activity and radiological progression in early rheumatoid arthritis (RA). METHODS: In a 3 year prospective study of 33 patients with early RA (symptoms < 1 year at entry) monthly measurements of serum MMP-3 were transformed into time integrated values for 6 month periods for comparison with other markers of disease activity like swollen joint count (SJC), tender joint count (TJC), Ritchie articular index (RAI), the disease activity score (DAS), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and radiological progression, scored according to Sharp's method, in which erosions and joint space narrowing are scored separately and combined to a total Sharp score. RESULTS: Significant correlations were found between serum MMP-3 and SJC, ESR, and CRP during all periods and between 6 and 30 months with the DAS. There were no correlations between serum MMP-3 and TJC or the RAI. During the first 12 months serum MMP-3 was correlated only with the item joint space narrowing of the Sharp score. After 12 months of followup it was also correlated with the total Sharp score and after 18 months it was correlated with all 3 items of the Sharp score. There was a wide interindividual variation in the relation between serum MMP-3 and radiological progression but intraindividually this relation seemed to be rather constant. CONCLUSION: Time integrated values of serum MMP-3 are correlated with time integrated values of other markers of disease activity such as joint swelling, ESR, CRP, and the DAS. Of the radiological scores, as outcome measures, especially joint space narrowing correlated closely with cumulative serum MMP-3.

No increased mortality in patients with rheumatoid arthritis: up to 10 years of follow up from disease onset.

OBJECTIVE: To investigate mortality, functional capacity, and prognostic factors for mortality in an inception cohort of patients with recently diagnosed RA followed up for up to 10 years. METHODS: The observed mortality of this inception cohort with recently diagnosed RA, was analysed in relation to the expected mortality, calculated with the aid of life tables of the general population of the Netherlands (matched for age and sex). Functional capacity was measured by the Health Assessment Questionnaire. Prognostic factors for mortality were analysed multivariately by the Cox proportional hazards model. RESULTS: Between January 1985 and April 1997, 622 patients entered the study, and were included in the analysis of mortality. The death rate in the first 10 years of the disease was not significantly different from that of the general population. Fifty five patients from the study group died (16% up to 10 years of follow up). The most commonly reported causes of death were of cardiovascular and respiratory origin. The other causes of death could be classified into cancer, sepsis, amyloidosis, leukaemia, renal insufficiency of unknown cause, perforation of the oesophagus, probably related to the treatment with non-steroidal anti-inflammatory drugs, and pancytopenia during aurothioglucose treatment. Functional capacity improved significantly during the first six years compared with the value at start. Statistically significant predictors for death were age at the start and male sex. CONCLUSIONS: In contrast with earlier studies performed, no excess mortality in the first 10 years of an inception cohort of patients with RA was seen. In addition, the functional capacity was relatively constant during the first six years after an initial improvement from baseline. Age at start and male sex were the only statistically significant predictors for death.

The prognostic value of anti-cyclic citrullinated peptide antibody in patients with recent-onset rheumatoid arthritis.

OBJECTIVE: To study the predictive value of anticyclic citrullinated peptide antibody (anti-CCP) in patients with recent-onset rheumatoid arthritis (RA). METHODS: Outcome in terms of physical disability (Health Assessment Questionnaire) and radiologic damage (modified Sharp method) over 3-year and 6-year periods was determined in an inception cohort of 273 RA patients who had had disease symptoms for <1 year at study entry. Anti-CCP titers were determined at baseline and considered positive as recently described. Their prognostic value was studied by means of multiple regression analysis, in which anti-CCP positivity, sex, age at study entry, IgM rheumatoid factor (IgM-RF) status, Disease Activity Score (DAS), HLA-DR4 status, and (in a separate group of patients) shared epitope status were used as independent variables, and radiologic damage and functional disability as dependent variables. RESULTS: Patients with anti-CCP had developed significantly more severe radiologic damage after 6 years of followup. In multiple regression analysis, radiologic damage after 6 years followup was significantly predicted by IgM-RF status, radiologic score at entry, and anti-CCP status. Functional disability was significantly predicted by sex, age at entry, IgM-RF status, and DAS. CONCLUSION: Our data show that in almost 70% of RA patients, anti-CCP antibody is present at the early stages of disease. Anti-CCP-positive patients developed significantly more severe radiologic damage than patients who were anti-CCP negative, although in multiple regression analysis the additional predictive value was rather moderate.

Disease associated time consumption in early rheumatoid arthritis.

OBJECTIVE: To quantify the disease associated time consumption of normal activities of daily living and of treatment and monitoring activities in a cohort of patients with early rheumatoid arthritis (RA) with followup of at least 6 years. Comparison was made with a group of patients with asthma and chronic obstructive pulmonary disease (COPD). METHODS: A prospective and retrospective inventory was carried out, by interview and record investigation, of RA related and RA unrelated items covering the period from the start of the disease. Interviews were also performed in a group of patients with asthma and COPD. RESULTS: For patients with RA there was a mean disease associated time consumption of at least 1.9 h/day during the first 6 years of the disease. The time consumption was mainly due to extra time needed for activities of daily living and daily disease related activities. Patients with the greatest progression of radiographic damage, with the most severe disability, and with the greatest cumulative disease activity had the greatest time consumption. For patients with asthma and COPD the consumption of time was comparable. CONCLUSION: RA is a time consuming disease. Recognition of the disease associated time consumption will have implications for work (dis)ability assessments in patients with chronic diseases such as RA.

Can we see enough? A comparative study of film-screen vs digital radiographs in small lesions in rheumatoid arthritis.

The aim of this study was to evaluate the performance of digital radiography in the detection of early very small erosions and joint space narrowing in the hands and feet in rheumatoid arthritis. Fifty-three sets of film-screen and digital radiographs of the same hands and feet with very small and sometimes questionable lesions (possible erosions and cysts) were scored independently two times by four investigators. The percentage of lesions found in exactly the same position for each investigator was calculated. Intra-observer agreement between first and second reading in film-screen radiography was 64-76 % (mean 67 %), and in digital radiographs 60-71 % (mean 64 %). Agreement between film-screen and digital radiographs ranged from 54 to 64 % (mean 58 %) in the first reading and from 56 to 66 % (mean 62 %) in the second reading. Overall agreement between both techniques between first and second reading ranged between 62 and 73 % (mean 65 %). Digital radiography of the hands and feet can be used in patients suspected of rheumatoid arthritis and in follow-up of those patients, because small and early erosions can be seen equally well with the digital technique as compared with the conventional film-screen technique.

Serum levels of matrix metalloproteinase-3 in relation to the development of radiological damage in patients with early rheumatoid arthritis.

OBJECTIVE: To evaluate the significance of serum matrix metalloproteinase-3 (MMP-3) levels in relation to the development of radiological damage (X-ray damage) in early rheumatoid arthritis (RA). METHODS: Serum MMP-3 levels were measured in 46 healthy controls (CTRL), 19 osteoarthritis (OA) and 78 RA patients with joint symptoms for <1 yr at presentation (T0): 48 patients without and 30 with X-ray damage at T0. Serum MMP-3, measured by ELISA, and X-ray damage, scored according to Sharp's method, were assessed at 0, 6, 12 and 24 months. RESULTS: MMP-3 levels in CTRL and OA were low or undetectable with no differences between the groups (P=0.19). Levels in RA were higher than in CTRL (P<0.01). Initial MMP-3 levels in patients with X-ray damage at T0 (n=30) were higher than the levels in patients without any X-ray damage during follow-up (n=19) (P<0.01), but were not different from those in patients who developed X-ray damage during the study (n=29) (P=0.11). In the patients without X-ray damage at T0, there was a significant correlation between MMP-3 at T0 and the total X-ray damage after 6 months (r=0.34, P=0.02) and 12 months (r=0.32, P=0.03). This correlation was almost exclusively determined by joint space narrowing in the Sharp score. CONCLUSION: The serum MMP-3 level seems to be an indicator for the development of radiological damage in patients with early RA and appears to be particularly indicative of cartilage degradation.

Transient osteoporosis of the hip: presentation of (a)typical cases and a review of the literature.

Transient osteoporosis of the hip (TOH) is a rare disorder affecting primarily middle-aged men and women during the last trimester of pregnancy. The disease is characterized by pain in the involved joint with temporary osteopenia apparent on radiology without joint space narrowing or destruction, in the absence of other recognizable causes of synovitis or osteoporosis. Within a few months the pain as well as radiological abnormalities disappear spontaneously with complete resolution. In this paper the literature is reviewed, with particular focus on the topic of the role of magnetic resonance imaging (MRI) in the diagnostic procedure. Two patients with TOH, a father and daughter, are described. Such a familial appearance has not been reported before. Based on HLA-typing, the existence of an HLA-associated genetic predisposition nevertheless seems unlikely.