Use of statins is associated with an increased risk of rheumatoid arthritis.

OBJECTIVES: Statins offer significant cardiovascular benefits. Their use, however, influences immune regulation, which may potentially facilitate autoimmunity, eventually resulting in autoimmune diseases such as rheumatoid arthritis (RA).The authors studied whether statin use was associated with an increased risk of developing RA by conducting a case-control study using the Netherlands Information Network of General Practice database. METHODS: The authors identified 508 patients aged 40 years or older with a first-time diagnosis of RA in the period 2001-2006. Each RA case was matched to five controls for age, sex and index date, which was selected 1 year before the first diagnosis of RA. Odds ratios for the first-time diagnosis of RA were verified by a referral to a rheumatologist and/or at least one prescription of disease-modifying anti-rheumatic drugs and/or two prescriptions of corticosteroids after the date of first diagnosis. RESULTS: Cases were more often users of statins (15.9%) compared to controls (8.6%). After adjustment for cardiovascular risk factors and use of comedication, statin use was associated with an increased risk of incident RA (adjusted OR, 1.71 (95% CI 1.16 to 2.53); p=0.007). A consistent trend of increasing risk with increased cumulative duration, cumulative defined daily doses and number of prescriptions was not observed. However, a small trend between the potency of statin treatment and the risk of RA was found. CONCLUSIONS: Statin use seems to be associated with an increased risk of developing RA. Our findings should be replicated by additional studies.

The use of a two-way analysis of variance to compare the methods for the assay of anhydrous dibasic calcium phosphate in the European, Japanese and United States Pharmacopoeias.

Tri-PEC (IPEC-Americas, IPEC-Europe and JPEC) carried out a two-way analysis of variance (Round Robin testing) for the assay of Anhydrous Dibasic Calcium Phosphate (CaHPO4) at the request of the Pharmacopoeial Discussion Group (PDG). On the basis of the result obtained, the difference in the assay results for anhydrous CaHPO4 using the different methods of the 3 Pharmacopoeias was not significant, while the difference in the results for the 3 different batch samples tested by 3 different methods was significant (p < 0.05). On the basis of these results, the methods from the 3 Pharmacopoeias, did not give different results, and thus the methods themselves should be considered equivalent.

The safety of pharmaceutical excipients.

Excipients are essential ingredients of medicinal products. Approximately 1000 excipients are today in use in marketed pharmaceuticals. The safety issues regarding excipients can be classified into three categories: quality, toxicology and improper use. An overview of the current status, regulatory requirements and improvements is given.

Anti-sulphatide antibodies in peripheral neuropathy.

A study was carried out on 135 patients with chronic idiopathic neuropathy (63), neuropathy associated with monoclonal gammopathy (51, including eight with anti-MAG antibody activity) and the Guillain-Barré syndrome (GBS) (21). Serum IgM, IgG and IgA anti-sulphatide antibody titres were compared with titres in 304 patients with other neurological or immunological diseases and in 50 normal subjects. Titres were presented a) as the highest serum dilution at which reactivity could be detected, and b) in the linear region of the optical density curve. A substantial number of patients with neurological or immunological diseases had higher titres than normal subjects. Compared with normal and disease controls, five patients with neuropathy associated with IgMk monoclonal gammopathy had raised titres of IgM anti-sulphatide antibodies and one patient with GBS had raised IgM, IgG and IgA anti-sulphatide antibodies in the acute phase of the disease. Two patients had a predominantly axonal sensory neuropathy with presenting symptoms of painful paresthesiae and minimal neurological deficit. Three patients had a predominantly demyelinating sensorimotor neuropathy associated with anti-MAG antibody activity. The patient with GBS had extensive sensory loss and antibody titres returned to normal within three weeks. Raised titres of anti-sulphatide antibodies occurred in several types of neuropathy, but all had some degree of sensory impairment and associated immunological abnormality.

Anti-GM1 antibodies in patients with Guillain-Barré syndrome.

Anti-GM1 antibodies were measured in 22 patients with the Guillain-Barré syndrome (GBS) and compared with anti-GM1 antibody activity in patients with other neurological or immunological diseases and in normal subjects. Four out of 22 patients with GBS had raised IgM, IgG, or IgA anti-GM1 antibody activities. All four patients were tetraparetic with only minimal or no sensory deficit. Three of the patients had highly raised antibody activity and showed severe residual deficits, while of the remaining patients with GBS, only one remained severely affected. One patient had anti-GM1 antibodies specific for GM1, whereas the other three patients showed antibody activity with asialo-GM1 or GD1b. The presence of anti-GM1 antibodies may define a subgroup of patients with GBS who have a poor prognosis.

Complement activation and the production of inflammatory mediators during the treatment of severe sepsis in humans.

Sepsis or septic shock is frequently associated with activation of the complement system, coagulation and fibrinolytic changes and the release of several cytokines. In this study we analyzed the relation of complement activation to the inflammatory mediators, hemodynamic and biochemical parameters and severity of illness and outcome in 20 consecutive patients with clinically defined sepsis. Levels of C3a and C3d were elevated in 90% of the patients (median levels 0.19 mg/l and 8.6 mg/l respectively) in comparison to 14% and 42%, respectively of 7 patients with non-septic shock. Levels of C4 were decreased in only 1 of the 20 septic patients. Levels of TNF and IL-6 were elevated in 94% and 100% of the patients, Levels of TNF and IL-6 were elevated in 94% and 100% of the patients, respectively (median levels 122 ng/l and 1300 U/ml) and were clearly interrelated (r = 0.67, p less than 0.01). C3a levels correlated with the APACHE II score (r = 0.57, p less than 0.05) and high C3a levels were associated with fatal outcome (p less than 0.05). C3a was also correlated inversely with mean arterial pressure (r = 0.50, p less than 0.01). Levels of complement C3a and C3d significantly correlated with levels of plasminogen activator inhibitor-1 (PAI) and correlated inversely with AT-III levels. We found no correlation between these complement products and leukocyte counts or lactate levels, nor was there a correlation between C3a or C3d and the cytokines TNF and IL-6. Levels of C3a and C3d did not decrease significantly during the first 24 h of treatment, in contrast to a clear decrease in IL-6 levels in all patients and a decrease in TNF in the surviving patients. TNF levels remained stable or increased in the non-survivors. We conclude that both the complement system and the cytokine system are involved in the pathogenesis of septic shock and may be involved in the development of some of the fatal complications like hypotension and disseminated intravascular coagulation.

TRA-1-60: a new serum marker in patients with germ-cell tumors.

TRA-1-60 is a monoclonal antibody (MAb) that recognizes a mucin-like antigenic determinant expressed on the surface of embryonal carcinoma (EC) progenitor cells. In order to determine whether this antigen is released into the serum of patients with a non-seminomatous germ-cell tumor (NSGCT), we developed a sensitive 2-step immunoenzymometric assay. Of 42 EC-positive NSGCT patients tested, 32 (76%) were found to release TRA-1-60-reactive antigen into their serum, in contrast to 1 positive finding in 10 EC-negative NSGCT patients. The marker was found in 67% (10/15) of the EC-positive patients who were negative for both AFP and HCG. Sera from seminoma patients did not contain elevated levels of the TRA-1-60 antigen. Therefore, we propose that the TRA-1-60 antigen is a useful additional serum marker for following the progress of NSGCT(EC+) patients.

[2 men with active syphilis infection and HIV-I infection]. / Twee mannen met actieve luesinfectie en HIV-I-infectie.

We report the case histories of two men who were living together and who were seropositive for human immune deficiency virus (HIV) and also had positive syphilis tests. Conceivably, reactivation of an earlier syphilis infection (which had been treated) had occurred after infection with HIV. It is therefore recommended to treat such patients according to the standard of treatment of neurosyphilis.

Quantitation of IgM, IgA and IgG rheumatoid factors by ELISA in rheumatoid arthritis and other rheumatic disorders.

We describe the evaluation of an enzyme-linked immunosorbent-assay (ELISA) for the measurement of IgM, IgA and IgG rheumatoid factor (RF). Results were obtained from sera of normal controls and patients with different rheumatic disorders in a cross-sectional study. Both human and rabbit IgG could be used as antigen in the assays. IgA-RF and IgG-RF were measured after pepsin digestion. The WHO reference preparation was used to standardise IgM-RF, but could not be used in the IgA- and IgG-RF assay, because neither IgA- nor IgG-RF could be detected in this standard serum. The ELISA for detection of RF is a highly sensitive and reproducible method and quantitation of results can be standardised. It yields good discriminative values for RA versus controls, in particular when more RF-isotypes are determined. In RA patients a correlation between IgM-, IgA- and IgG-RF concentrations does exist, although a wide variation was found in the ratio of these concentrations.

Isotherms in ion exchange as obtained from break-through curves. II. Simple isotherms.

Isotherms for ion exchange equilibria can be obtained from break-through curves. The present work is concerned with experimental results from resin analyte combinations without selectivity reversal.

Determination of phenol in the presence of resorcinol applying substitution with excess bromine water; structure of the bromination products.

Bromination with a large excess of bromine results in the formation of a tetrabromo product for phenol and a pentabromo derivative for resorcinol. It is possible to determine the active bromine in the tetrabromo product after its isolation by filtration. This can also be done in the presence of resorcinol as its pentabromo derivative does not precipitate. The method gives good results (96-97% +/- 1%) for quantities of 8 mg and higher of phenol in the presence of a maximum of 25 mg resorcinol. From the 1H- and 13C-NMR spectra of the bromination products it could be concluded that they have a quinoidal structure.

Reversed-phase ion-pair partion chromatography of biogenic catecholamines and their alpha-methyl homologues with tributylphosphate as stationary phase.

Ion-pair partition chromatography is applied to the separation of the biogenic catecholamines and their alpha-methyl homologues. A useful selectivity has been obtained using an adduct-forming organic stationary phase (tributylphosphate). The retention of the compounds can be regulated easily by means of the concentration of the counter-ion (the perchlorate ion) in the mobile phase. The selectivity for separation of amines from amino acids can be influenced by changing the pH of the aqueous phase. The phase system shows a good long-term stability and reproducibility with respect to the capacity ratios and the efficiency.