French mental health care system: Analysis of care utilisation patterns and the case for a stepped care approach.

CONTEXT: In France, spending on mental health and psychiatric care, in proportion to GDP, is close to the EU average. However, there are complaints that the French system is overwhelmed and potentially underfunded. OBJECTIVE: To describe the utilisation of psychiatric and mental health care in different settings to consider the appropriateness of care provision and resource allocation. METHODS: For the year 2018, several national databases on the use of all type of psychiatric care provision (full and part-time hospitalisations, private and public, public ambulatory care, private office-based psychiatrists) were cross-tabulated with diagnosis categories for different age groups and illness severity in order to assess the use of resources and evaluate the appropriateness of resource allocation. RESULTS: A sizable proportion of patients with mild and moderate mental disorders are treated in psychiatric care whilst there is insufficient continuity of care for patients with severe disorders, who are not adequately followed up after discharge from hospitals. This contributes to increase the rate of re-hospitalisations, the use of emergency departments, and longer stays in hospitals. CONCLUSION: The several components of the French mental health care system are used inappropriately, not only in geographical terms but also in terms of service use. We argue that strengthening the access to affordable psychotherapy and the implementation of a stepped-care approach could contribute to solve this issue.

The same or different psychiatrists for in- and out-patient treatment? A multi-country natural experiment.

AIMS: A core question in the debate about how to organise mental healthcare is whether in- and out-patient treatment should be provided by the same (personal continuity) or different psychiatrists (specialisation). The controversial debate drives costly organisational changes in several European countries, which have gone in opposing directions. The existing evidence is based on small and low-quality studies which tend to favour whatever the new experimental organisation is.We compared 1-year clinical outcomes of personal continuity and specialisation in routine care in a large scale study across five European countries. METHODS: This is a 1-year prospective natural experiment conducted in Belgium, England, Germany, Italy and Poland. In all these countries, both personal continuity and specialisation exist in routine care. Eligible patients were admitted for psychiatric in-patient treatment (18 years of age), and clinically diagnosed with a psychotic, mood or anxiety/somatisation disorder.Outcomes were assessed 1 year after the index admission. The primary outcome was re-hospitalisation and analysed for the full sample and subgroups defined by country, and different socio-demographic and clinical criteria. Secondary outcomes were total number of inpatient days, involuntary re-admissions, adverse events and patients' social situation. Outcomes were compared through mixed regression models in intention-to-treat analyses. The study is registered (ISRCTN40256812). RESULTS: We consecutively recruited 7302 patients; 6369 (87.2%) were followed-up. No statistically significant differences were found in re-hospitalisation, neither overall (adjusted percentages: 38.9% in personal continuity, 37.1% in specialisation; odds ratio = 1.08; confidence interval 0.94-1.25; p = 0.28) nor for any of the considered subgroups. There were no significant differences in any of the secondary outcomes. CONCLUSIONS: Whether the same or different psychiatrists provide in- and out-patient treatment appears to have no substantial impact on patient outcomes over a 1-year period. Initiatives to improve long-term outcomes of psychiatric patients may focus on aspects other than the organisation of personal continuity v. specialisation.

In-patient treatment in functional and sectorised care: patient satisfaction and length of stay.

BACKGROUND: Debate exists as to whether functional care, in which different psychiatrists are responsible for in- and out-patient care, leads to better in-patient treatment as compared with sectorised care, in which the same psychiatrist is responsible for care across settings. Aims To compare patient satisfaction with in-patient treatment and length of stay in functional and sectorised care. METHOD: Patients with an ICD-10 diagnosis of psychotic, affective or anxiety/somatoform disorders consecutively admitted to an adult acute psychiatric ward in 23 hospitals across 11 National Health Service trusts in England were recruited. Patient satisfaction with in-patient care and length of stay (LoS) were compared (trial registration ISRCTN40256812). RESULTS: In total, 2709 patients were included, of which 1612 received functional and 1097 sectorised care. Patient satisfaction was significantly higher in sectorised care (ß = 0.54, 95% CI 0.35-0.73, P<0.001). This difference remained significant when adjusting for locality and patient characteristics. LoS was 6.9 days shorter for patients in sectorised care (ß = -6.89, 95% CI -11.76 to -2.02, P<0.001), but this difference did not remain significant when adjusting for clustering by hospital (ß = -4.89, 95% CI -13.34 to 3.56, P = 0.26). CONCLUSIONS: This is the first robust evidence that patient satisfaction with in-patient treatment is higher in sectorised care, whereas findings for LoS are less conclusive. If patient satisfaction is seen as a key criterion, sectorised care seems preferable. Declarations of interest None.

Anaphylactic bronchospasm during general anesthesia is not related to asthma.

In the general population, a history of asthma (HA) is associated with a higher risk of mortality of anaphylactic shock (AS), but it is unknown whether this association remains valid for intra-operative AS. The goal of this retrospective study was to investigate whether a HA was associated with a higher risk of bronchospasm during intra-operative AS. We analyzed 106 patients (January 2009-December 2012) with intra-operative AS: 57% of them had a confirmed IgE-mediated reaction and 27% had a HA. On logistic regression, the only factor statistically associated with bronchospasm was a neuromuscular blocking drug, with both IgE- or non-IgE-mediated reactions. These results suggest that the mechanisms of bronchospasm in AS may be different from those of asthma and that, in the presence of bronchospasm during anesthesia, AS should be considered to be the most likely cause.

Users' and health professionals' values in relation to a psychiatric intervention: the case of psychiatric advance directives.

Although clinical and organisational benefits have been expected from Psychiatric Advance Directives (PADs), their take-up rates remain low and their evaluation disappointing. The endorsement of PADs by stakeholders is decisive for their use and understanding stakeholders' preferences for implementation is crucial. A Multinomial Discrete Choice analysis was carried out of options for designing, completing, and honouring PADs, with a view to enhancing user autonomy, therapeutic alliance, care coordination, and feasibility. Although autonomy underlies the whole process, the criteria determining options varied with the stage of the intervention. These criteria should be taken into account in future PAD intervention and evaluation processes.

Complementarity between microarray and immunoblot for the comparative evaluation of IgE repertoire of French and Italian cypress pollen allergic patients.

Cypress pollen represents the primary cause of respiratory allergies in Mediterranean areas. Patients allergic to Cupressus sempervirens pollen (Cups) (CPA) can be discriminated on the basis of the immunoglobulin E (IgE) binding to a basic 14 kDa protein (BP14) or to high-molecular-weight (HMW) glycoproteins only. Specific IgE repertoires of two differentially exposed CPA cohorts, French and Italian, were investigated using an IgE microarray system (some known major allergens from several allergenic sources) and individual IgE immunoblotting (IB) of whole Cups pollen extract separated by SDS-PAGE (all allergens from one allergenic source: cypress pollen). The prevalence of sensitization to BP14 was higher in French (37 %) than in Italian patients (17 %) and major differences were observed in IgE reactivities to lipid transfer proteins (LTPs). Thirty percent of the Italian CPA (4 % in the French group) had specific IgE against the Parietaria pollen LTP, independently of IB subgroups. Regarding peach LTP sensitization, all Pru p 3+ Italian CPA (10 %) were in the HMW+ subgroup, while Pru p 3+ French CPA (20 %) were all included in the BP14+ subgroup. BP14 sensitization is likely a marker of Cups exposure and is, in French CPA, significantly correlated to Pru p 3 sensitization. The IgE immunoblot and microarray are complementary tools that highlight differences in the subtle sensitization profile between groups of patients in comparative studies.

[Advanced directives in psychiatry: A review of the qualitative literature, a state-of-the-art and viewpoints]. / Les directives anticipées en psychiatrie : revue de la littérature qualitative, état des lieux et perspectives.

BACKGROUND: Advance Directives are written documents, which are used for people to notify their preference for a future situation when they are unable to give their consent. In psychiatry, psychiatric advance directives (PADs) can be used for patients with chronic psychotic disorders such as schizophrenia, or a bipolar disorder. PADs give the patient an opportunity to state wishes in advance about his/her treatment when he/she is in an acute state of illness. PADs were initially developed as a way for patients to defend themselves against the power of the psychiatrists, but are likely to become a useful tool in psychiatric care. PADs may contain information about medication, non pharmaceutical devices, and the name of a proxy decision maker. The main objective is to reduce the number of compulsory hospitalisations. OBJECTIVE: This article is a qualitative review which carries out a state-of-the-art on the use of PADs for people with chronic psychotic disorders and defines suggestions to include this intervention in the French psychiatric context. METHOD: We used the keywords psychiatric advance directives, crisis card, Ulysse directives, joint crisis plan (JCP) in the MEDLINE database to propose a qualitative review. We selected original clinical studies about the use of PADs for people with psychotic disorders. RESULTS: We included 36 articles. The qualitative analysis identified seven main themes: different types of PADs, effectiveness of PADs, practical use of PADs, patient's views, clinician's views, economical aspects, and legal aspects. The content of the PADs is consistent with psychiatric standard care in nearly all cases, regarding medical instructions, pre-emergency interventions, non-hospital alternatives and non-medical personal care. Patients use their PADs to describe prodromal symptoms of relapse and to suggest a treatment and a hospitalisation in advance. PADs are not used to refuse all treatments. Patients show a strong interest in creating a directive and a high level of satisfaction when using it. They feel they have more control over their mental health problem and are more respected and valued as a person. Thirty-six to fifty-three percent of clinicians had positive opinions regarding PADs. They valued the increase of the patient's autonomy and the prevention of relapse, but were concerned about difficulties for accessing the documents, and about the lack of training of the medical teams. Clinicians also feared the pressure of relatives or partners on treatment decisions. The qualitative analysis revealed the specific benefit of the JCP, a particular type of PADs negotiated with the medical team, on the reduction of the general number of admissions. We can identify practical problems such as the lack of accessibility to PADs in emergency situations, and the clinician's reluctance to use PADs. The only economical evaluation showed a non-significant decrease in total costs. DISCUSSION: PADs are used in a few countries, although their benefits in terms of patient's perceptions and compulsory admissions are promising. The JCP proposes a specific clinical approach based on therapeutic alliance. Its creation also involves the clinician, family members and a neutral mediator in a negotiated process. The JCP is likely to be the most efficient PAD model in reducing compulsory admissions. The use of the JCP appears to be relevant in the context of the new French legislation, establishing outpatient commitment orders and could be an effective way to improve the relationships with patients.

Clinical significance of anti-Ro52 (TRIM21) antibodies non-associated with anti-SSA 60kDa antibodies: results of a multicentric study.

Ro52 antigen has recently been identified as TRIM21 protein, but the clinical significance of anti-Ro52/TRIM21 antibodies remains controversial. The aim of this multicentric study was to investigate the significance of anti-Ro52 antibodies without anti-SSA/Ro60 antibodies in various connective diseases. Sera were selected by each laboratory using its own method (ELISA, immunodot or Luminex technology), and then performed with ANA Screen BioPlex™ reagent (BIO-RAD). Among the 247 screened sera, 155/247 (63%) were confirmed as anti-Ro52 positive and anti-SSA/Ro60 negative. These sera were analyzed for the detection of other antibodies in relation with clinical settings. Isolated anti-Ro52 antibodies were detected in 89/155 (57%) sera. For the remaining sera (66/155), the main antibodies associations were Sm/SmRNP or Chromatin (n=38; 57%), Jo1 (n=17; 26%) and CenpB (n=9; 14%). Clinical data from the 155 patients showed high prevalence in autoimmune diseases (73%) including myositis or dermatomyositis (n=30), lupus (n=23); Sjögren and/or sicca syndrome (n=27); CREST or Systemic sclerosis (n=11) and autoimmune hepatitis (n=11). We found that pulmonary manifestations were often associated with the presence of anti-Ro52 antibodies (n=34, 22%), in addition with anti-tRNA synthetases, anti-SRP or anti-Ku antibodies (18/34) or isolated in half of cases (16/34). Separate detection of anti-Ro52 antibodies might be useful in related antisynthetase syndrome diagnosis. The presence of anti-Ro52 antibodies should probably precede development of autoimmune disease and must induce sequential follow-up of positive patients, particularly in interstitial lung disease progression.

The intestinal microflora regulates cytokine production positively in spleen-derived macrophages but negatively in bone marrow-derived macrophages.

Besides its role as a barrier against potential pathogens, intestinal flora is presumed to protect the host by priming the immunological defense mechanisms. In this respect, the influence of intestinal flora on macrophage precursors was examined, and its modulating effect was compared on LPS-induced cytokine production by macrophages derived from bone marrow and spleen precursors (BMDM and SDM respectively). The regulation of IL-1, IL-6, TNF-alpha and IL-12 production in macrophages from germ-free and from three groups of flora-associated mice, conventional, conventionalized and E. coli-mono-associated mice, was investigated. The whole flora inhibited IL-1, TNF-alpha and IL-12 secretion by BMDM, whereas it had a stimulatory effect on IL-12 secretion by SDM. Implantation of E. coli alone enhanced cytokine secretion by BMDM but had a more limited effect than whole flora on SDM, enhancing only TNF-alpha and IL-12 secretion. Study of expression of mRNA showed a correlation with protein secretion for IL-6 but not for TNF-alpha and IL-1. IL-12 enhancement in BMDM seemed to be dependent on regulation of p35 mRNA expression while it was correlated to increased p40 mRNA expression in SDM. The results demonstrated that intestinal flora modulated bone marrow and spleen macrophage cytokine production in a differential manner and suggested a role for bacteria other than E. coli among the whole flora. The contrasting effects exerted by the intestinal flora on bone marrow and spleen precursors are an interesting observation in view of the different functions of these organs in immunity. The finding that intestinal flora enhanced IL-12 production in spleen is also potentially important since this cytokine is implicated in the determination of the relative levels of Th1 and Th2 responses and plays a pivotal role in host defense against intracellular microorganisms.

Systemic lupus erythematosus-associated catastrophic antiphospholipid syndrome occurring after typhoid fever: a possible role of Salmonella lipopolysaccharide in the occurrence of diffuse vasculopathy-coagulopathy.

We report a case of well-documented typhoid fever in a 30-year-old woman with inactive systemic lupus erythematosus with asymptomatic lupus anticoagulant and high-titer anticardiolipin antibody (aCL). Despite prompt eradication of the Salmonella typhi obtained with appropriate antibiotic therapy, multiple organ system dysfunction occurred. The central nervous system was involved, with ischemic infarcts in the occipital lobes. High-dose corticosteroid therapy failed to improve the neurologic manifestations, which responded to repeated plasmapheresis. A sharp fall in aCL and anti-beta2-glycoprotein I antibody titers was recorded before the start of plasmapheresis. At the same time, IgM and IgG antibodies to Salmonella group O:9 lipopolysaccharide became detectable; the IgM antibodies disappeared within 4 months, whereas the IgG antibodies remained detectable during the next 13 months. Despite treatment with high-dose corticosteroids and cyclophosphamide, rapidly progressive glomerulonephritis developed, leading to chronic renal failure. There is convincing evidence of a link between the S. typhi infection and the ensuing catastrophic syndrome in this patient, probably precipitated by bacterial antigens.

Anti-Sa antibody is an accurate diagnostic and prognostic marker in adult rheumatoid arthritis.

OBJECTIVES: To evaluate in various groups of patients with chronic joint disease the sensitivity and specificity of anti-Sa antibody, recently described in sera from adults with rheumatoid arthritis (RA); and to determine the prognostic significance of anti-Sa in initial sera from patients with long standing RA with or without severe joint destruction. METHODS: Serum samples from 489 patients were included. Of these, 154 were collected from patients with RA attending 2 rheumatology units. Controls were 335 patients with a variety of inflammatory joint diseases other than RA. IgG anti-Sa was detected using an immunoblotting method with purified Sa antigen from human placenta extracts. All patients were tested for the following antibodies: rheumatoid factor (RF), anti-keratin antibody (AKA), antiperinuclear factor (APF), and anti-RA 33. HLA class II DRB alleles were also determined. RESULTS: Anti-Sa was detected in 39.8% of RA sera overall, 46.7% of sera from the long standing RA group, and 23.5% of sera from the recent onset RA group (p<0.01). In patients with long standing RA, statistically significant associations were found between the presence of anti-Sa and the following variables: RF (p<0.0001), AKA (p<0.0001), APF (p<0.00001), and HLA DRB1*04 or 01 (p<0.01). In contrast, no association was found with anti-RA33. Anti-Sa was positive in 11 adult controls (7.8%) and in 26 pediatric patients with juvenile chronic arthritis (22%). The specificity of anti-Sa for RA was 92.1% in adults with well characterized rheumatic diseases and 85.9% in adults and children together. Among patients with long standing RA, those with destructive disease were more likely to test positive for anti-Sa (66.6%) than those with nondestructive disease (22.2%) (p<0.0001). Comparisons with other serologic markers for RA demonstrated that anti-Sa was sensitive (68.4%) and was also the test with the highest specificity (79%), positive predictive value (75%), and negative predictive value (71%) for discriminating between patients who do and those that do not develop late severe radiographic damage. CONCLUSION: Immunoblot-detected IgG anti-Sa is a sensitive serologic marker for RA patients with severe radiographic damage.

Comparison of the prognostic value of C-reactive protein and troponin I in patients with unstable angina pectoris.

This study assessed the prognostic value of cardiac troponin I (cTnI) and C-reactive protein (CRP) in unstable angina, and specifically in patients with angiographically proven coronary artery disease. These biochemical parameters, which are related to myocardial injury or to systemic inflammation, may help in short-term risk stratification of unstable angina. We prospectively studied 195 patients with unstable angina, 100 of whom had angiographically proven coronary artery disease (with normal creatine kinase [CK] and CK-MB mass). Serum concentrations of cTnI (N < 0.4 ng/ml) and CRP (N < 3 mg/L) were measured at admission, 12, and 24 hours later. The rate of in-hospital major adverse cardiac events (death, myocardial infarction, or emergency revascularization) was higher in patients with increased cTnI within the first 24 hours, regardless of the results of coronary angiography (23% vs 7%; p < 0.001). Conversely, events occurred at similar rates in patients with or without increased CRP. In patients with angiographic evidence of coronary artery disease, multivariate analysis showed that increased cTnI within 24 hours of admission (35 patients) was an independent predictor of major adverse cardiac events (odds ratio 6.7, range 1.7 to 27.3), but not cTnI levels at admission and CRP at 0, 12, and 24 hours. Thus, both in unselected patients with unstable angina and in patients with angiographically proven coronary artery disease, increased cTnI within 24 hours of admission, but not CRP, is a predictor of in-hospital clinical outcome. We also found a temporal link between cTnI increase and late elevation of CRP, suggesting that systemic inflammation may partially be a consequence of myocardial injury.

Influence of intestinal microflora on murine bone marrow and spleen macrophage precursors.

To investigate the adjuvant effect of intestinal flora on macrophage-colony-stimulating factor-responsive macrophage progenitors from spleen and bone marrow, we compared progenitor numbers and phenotypic characteristics of in vitro matured macrophages in germ-free and flora-associated mice (conventional, Escherichia coli-monoassociated and conventionalized mice). The data obtained show that the flora affected differentially bone marrow and spleen progenitors. It increased the numbers of progenitors in the spleen but not in the bone marrow. It did not modify the expression of F4/80, Mac-1 and major histocompatibility complex (MHC) class II on bone-marrow-derived macrophages (BMDM), while it clearly up-regulated MHC class II expression on spleen-derived macrophages (SDM). This effect was more pronounced in flora-associated ex germ-free mice than in conventional mice and it was greatly enhanced in the absence of M-CSF. In vitro stimulation by lipopolysaccharide had no effect on marker expression of BMDM, while it decreased F4/80 and enhanced MHC class II molecules on SDM from germ-free and flora-associated mice. However, the expression of MHC class II remained lower in germ-free mice. Enhancement of MHC class II molecule expression on SDM may contribute to the protective role of flora, because successful immune responses are dependent on the expression of these molecules.

IL-12 induces IFN-gamma expression and secretion in mouse peritoneal macrophages.

We previously reported that resting mouse peritoneal macrophages (PM) constitutively express low levels of IFN-gamma, whose production is consistently enhanced by exogenous IFN-gamma. In this study, we investigated the effects of IL-12 on the replication of vesicular stomatitis virus and on IFN-gamma gene expression in mouse PM. The addition of IL-12 to freshly explanted PM resulted in the persistence of an antiviral state to vesicular stomatitis virus, while control PM progressively became permissive for virus replication after 3 to 4 days in culture. The IL-12-induced antiviral state was inhibited by Abs to IFN-gamma, suggesting that endogenous IFN-gamma was largely responsible for this antiviral response. Moreover, IL-12 induced a consistent secretion of IFN-gamma, especially in cultured PM. The IL-1 2-induced antiviral state and IFN-gamma production were observed using PM from various strains of mice, including LPS-defective C3H/HeJ, NK-deficient bg/bg, DBA/2, Swiss (CD1), and Swiss nude mice treated or not with anti-asialo GM1 Abs. A 4-h treatment with IL-12 was sufficient to induce a marked accumulation of IFN-gamma mRNA, which was greater in cultured PM than in freshly harvested cells. Lastly, immunofluorescence studies in IL-12-stimulated macrophages clearly showed an enhancement of immunoreactive IFN-gamma compared with basal levels in cells exhibiting a macrophage (i.e., F4/80-positive) phenotype. Together, these findings demonstrate that IL-12 can directly stimulate mouse PM to produce IFN-gamma. We suggest that IL-12-induced IFN-gamma production by macrophages can play some role in the generation of the antiviral and immunoregulatory effects of IL-12.

Anticentromere antibodies in rheumatologic practice are not consistently associated with scleroderma.

Anticentromere antibodies identified by indirect immunofluorescence are a valuable aid to the diagnosis and prognosis of patients with systemic sclerosis since they are associated in 50% to 80% of cases with limited cutaneous systemic sclerosis, a pattern usually associated with a good prognosis. We studied clinical presentations in rheumatology patients with anticentromere antibodies by indirect immunofluoresence and by ELISA and/or Western blot, but without scleroderma or Raynaud's phenomenon. Eight of 34 (23.5%) rheumatology clinic patients with centromere antibodies met these criteria, seven women and one man, with a median symptom duration of six years (range 1-20 years). Four had Sjögren's syndrome, one had isolated xerostomia, one systemic lupus erythematosus, one seronegative symmetric polyarthritis and one primary biliary cirrhosis with arthralgia. The mean anticentromere antibody titer in these eight patients was similar to that in the patients who had at least Raynaud's phenomenon. Given the low incidence of scleroderma, these data illustrate the poor predictive value of anticentromere antibodies for the diagnosis of scleroderma in rheumatology clinic patients.

Diagnostic value of anti-RA33 antibody, antikeratin antibody, antiperinuclear factor and antinuclear antibody in early rheumatoid arthritis: comparison with rheumatoid factor.

The goal of this prospective longitudinal study was to determine the serological profile of early rheumatoid arthritis (RA), and to test whether antikeratin antibody (AKA), antiperinuclear factor (APF), anti-RA33 antibody and antinuclear antibodies (ANA) had an additional diagnostic value when prescribed after rheumatoid factor (RF)-detecting methods. Sixty-nine patients with early polyarthritis suggestive of RA, seen between 1991 and 1993, were included. Five autoantibodies (i.e. RF, AKA, APF, RA33, ANA) were looked for at regular intervals. After 24 months follow-up, patients were classified as having RA (n = 49), unclassified polyarthritis (UP; n = 15) or other rheumatic diseases. Among patients with early RA, the sensitivity of these markers was 40.8% for RF, 36.7% for AKA, 28.6% for APF and 28.6% for anti-RA33. Among RF-negative RA patients, 51.7% were positive for AKA, APF, anti-RA33 antibodies and/or ANA. Positivity of the three recent markers usually persisted throughout follow-up, whereas RF was lost by 58% of patients with early, RF-positive, treated RA. Using multivariate analysis, only latex, RF test and AKA or APF had an independent and statistically significant diagnostic value for early RA. Our data suggest that RF and AKA (or APF) should be concomitantly determined for diagnosis in patients with suspected early RA.

Antibodies to cardiolipin and beta 2 glycoprotein I in patients with polymyalgia rheumatica and giant cell arteritis.

IgG antibodies to cardiolipin and beta 2-glycoprotein I were looked for using an enzyme-linked immunosorbent assay (ELISA) in 19 patients with giant cell arteritis (meeting 1990 American College of Rheumatology criteria), including 16 with concomitant polymyalgia rheumatica (meeting Bird's criteria) and in three patients with isolated polymyalgia rheumatica. IgG anti-cardiolipin antibodies were demonstrated in eight patients (36%) and IgG anti-beta 2-glycoprotein I antibodies in two patients (9%) including one without anti-cardiolipin antibodies. Titers of anti-cardiolipin antibodies ranged from 27 to 190 units of IgG antiphospholipid antibodies (UGPL) (mean 71 UGPL). Of the eight patients with anti-cardiolipin antibodies, two had giant cell arteritis without polymyalgia rheumatica and six had polymyalgia rheumatica with clinical (n = 2) or histologic (n = 4) evidence of giant cell arteritis. None of the three patients with polymyalgia rheumatica but no giant cell arteritis had anti-cardiolipin or anti-beta 2 glycoprotein I antibodies. The VDRL was negative in the 14 patients who had this test. Tests for lupus anticoagulant were performed routinely, always with negative results. Among giant cell arteritis patients, those who tested positive for anticardiolipin antibody had significantly higher values for the erythrocyte sedimentation rate (p < 0.006) and for serum C-reactive protein (p < 0.03) and fibrinogen values (p = 0.05), and a trend toward higher platelet counts, as compared to those who tested negative for anticardiolipin antibody. The mean daily prednisone dose at the time of sampling was significantly lower in giant cell arteritis patients with anti-cardiolipin antibodies (p < 0.05); this difference may account for the apparent correlation between anti-cardiolipin antibodies and laboratory markers for inflammation. These data, as well as findings from serial measurements, suggest that anti-cardiolipin antibodies are present early in the course of giant cell arteritis and disappear within a few weeks of initiation of corticosteroid therapy in a dose of more than 25 mg prednisone per day. In this study, only one patient without anticardiolipin antibodies developed a cerebrovascular accident. Positive tests for anti-cardiolipin antibody or anti-beta 2 glycoprotein I antibody in a patient with polymyalgia rheumatica suggest a diagnosis of concomitant giant cell arteritis, which is usually symptomatic.

The influence of E. coli implantation in axenic mice on cytokine production by peritoneal and bone marrow-derived macrophages.

To assess the involvement of bacterial microflora in the development of host defenses, we compared in vitro LPS-induced cytokine production by macrophages in germ-free and E. coli monoxenic mice. E. coli implantation significantly increased IL-1 and IL-6 and, to a lesser extent, TNF activities of peritoneal and bone marrow-derived macrophages. These results suggest that exposure to microflora primes macrophages for an enhanced cytokine production, which may contribute to the activation of the antiinfectious defense. The priming was not restricted to peritoneal macrophages but was associated with a more general effect of the flora since the enhanced response of bone marrow-derived macrophages indicates an effect on macrophage precursors. Furthermore, a higher ability of peritoneal macrophages to produce IL-1 in axenic and monoxenic mice was observed as compared to bone marrow-derived macrophages. In contrast, bone marrow-derived macrophages demonstrated a higher ability to produce IL-6 and TNF but only 3 weeks after bacterial administration.