Inverse association between circulating APRIL levels and serological and clinical disease activity in patients with systemic lupus erythematosus

OBJECTIVE: To assess longitudinal expression of a proliferation-inducing ligand (APRIL) in patients with systemic lupus erythematosus (SLE) and its correlation with B lymphocyte stimulator (BLyS) expression, serum anti-dsDNA titres, and clinical disease activity. METHODS: Sixty eight patients with SLE were longitudinally followed up for a median of 369 days. At each visit the physician assessed disease activity by SLEDAI, and blood was collected for determination of serum APRIL and BLyS levels and of blood APRIL and BLyS mRNA levels. Fifteen normal control subjects underwent similar laboratory evaluation. RESULTS: Dysregulation of APRIL was not as great as that of BLyS. Changes in serum levels of APRIL and BLyS over time were usually discordant, whereas blood levels of APRIL and BLyS mRNA strongly paralleled each other. Serum APRIL levels modestly, but significantly, inversely correlated with serum anti-dsDNA titres in anti-dsDNA positive patients analysed in aggregate. Moreover, serum APRIL levels modestly, but significantly, inversely correlated with clinical disease activity in all patients analysed in aggregate. CONCLUSION: Serum levels of APRIL and BLyS are differentially regulated. APRIL may serve as a down modulator of serological and/or clinical autoimmunity in patients with SLE. This may have important ramifications for BLyS targeted treatment, and it remains to be determined whether agents which neutralise only BLyS will be preferable to agents which neutralise both BLyS and APRIL.     

Type 2 von Willebrand disease causing defective von Willebrand factor-dependent platelet function.

Type 2 von Willebrand disease causing defective von Willebrand factor-dependent platelet function comprises mainly subtypes 2A, 2B and 2M. The diagnosis of type 2 von Willebrand disease may be guided by the observation of a disproportionately low level of ristocetin cofactor activity or collagen-binding activity relative to the von Willebrand factor antigen level. The decreased platelet-dependent function is often associated with an absence of high molecular weight multimers (types 2A and 2B), but the high molecular weight multimers may also be present (type 2M and some type 2B), and supranormal multimers may exist (as in the Vicenza variant). Today, the identification of mutations in particular domains of the pre-provon Willebrand factor is helpful to classify these variants and to provide further insight into the structure-function relationship and the biosynthesis of von Willebrand factor. Thus, mutations in the D2 domain, involved in the multimerization process, are found in patients with type 2A, formerly named IIC von Willebrand disease. Mutations in the D3 domain characterize the Vicenza variant, or type IIE patients. Mutations in the A1 domain may modify the binding of von Willebrand factor multimers to platelets, either increasing (type 2B) or decreasing (types 2M and 2A/2M) the affinity of von Willebrand factor for platelets. In type 2A disease, molecular abnormalities identified in the A2 domain, which contains a specific proteolytic site, are associated with alterations in folding that impair the secretion of von Willebrand factor or increase its susceptibility to proteolysis. Finally, a mutation localized in the C terminus cysteine knot domain, which is crucial for the dimerization of von Willebrand factor subunit, has been identified in a rare subtype 2A, formerly named IID.     

Post‐operative behavioural management in bariatric surgery: a systematic review and meta‐analysis of randomized controlled trials

Recent research has provided evidence that bariatric surgery maximizes long‐term weight loss in patients with severe obesity. However, a substantial number of patients experience poor weight loss outcome and weight regain over time. Post‐operative behavioural management may facilitate long‐term weight control in bariatric surgery population. The objective of this systematic review and meta‐analysis was to determine the effects of post‐operative behavioural management on weight loss following bariatric surgery. Eligible articles were systematically searched in electronic databases. Among the 414 citations, five randomized controlled trials, two prospective and eight retrospective cohort trials analysing behavioural lifestyle interventions and support groups fulfilled the inclusion criteria. The main finding is that behavioural management had a positive effect on weight loss following surgery. In 13 studies, patients receiving behavioural management had greater weight loss than patients receiving usual care or no treatment. A meta‐analysis of five randomized controlled trials suggests greater weight loss in patients with behavioural lifestyle interventions compared with control groups. Post‐operative behavioural management has the potential to facilitate optimal weight loss following bariatric surgery, but conclusions were limited by the small and heterogeneous samples of studies. A more rigorous empirical evaluation on its clinical significance is warranted to improve effectiveness of bariatric surgery.     

Prävalenz chronischer Schmerzen in Deutschland

Background

There are no up to date data from representative samples of the general German population on the prevalence of debilitating pain and of pain diseases available.

Methods

A cross-sectional survey of a representative sample of the German general population including persons ≥?14 years of age was conducted in 2012 based on face-to-face interviews using standardized questionnaires. Chronic pain was assessed by the widespread pain index (WPI), disability by the subscales physical functioning and role function of the European Organisation for Research and Treatment of Cancer (EORTC QLQ-C30) and psychological distress by the patient health questionnaire (PHQ-4). Chronic pain with associated physical and social impairments was defined by at least one pain site over 3 months in the WPI and at least one response of a moderate or severe impairment in both subscales of the EORTC 30 QLQ-C30. Chronic pain with associated physical, mental and social impairment (pain disease) required in addition a probable depressive and/or anxiety disorder in the PHQ-4.

Results

A total of 2,515 out of 4,480 (56.1 %) of contacted persons finished the study of which 32.9 % reported chronic pain, 5.4 % reported chronic pain with associated physical and social impairments and 2.3 % associated physical, mental and social impairments. No participants with local pain (only one pain site) but 24.0 % of participants with widespread pain (6–19 pain sites) met the criteria of a pain disease.

Conclusions

The reports of chronic pain in epidemiological studies do not necessarily imply a suffering (physical, psychological and social impairment) from pain.     

Dietary intake of antioxidant (pro)-vitamins, respiratory symptoms and pulmonary function: the MORGEN study

BACKGROUND—A study was undertaken toinvestigate the relationships between the intake of the antioxidant(pro)-vitamins C, E and β-carotene and the presence of respiratorysymptoms and lung function.
METHODS—Complete data were collected in across sectional study in a random sample of the Dutch population on6555 adults during 1994and 1995. Antioxidant intake was assessed by asemi-quantitative food frequency questionnaire and respiratory symptoms(cough, phlegm, productive cough, wheeze, shortness of breath) wereassessed by a self-administered questionnaire. Prevalence odds ratiosfor symptoms were calculated using logistic regression analysis. Linear regression analysis was used for forced expiratory volume in one second(FEV₁) and forced vital capacity (FVC). The results are presented as a comparison between the 90th and 10th percentiles ofantioxidant intake.
RESULTS—Vitamin C intake was not associatedwith most symptoms but was inversely related with cough. Subjects witha high intake of vitamin C had a 53 ml (95% CI 23 to 83) higherFEV₁ and 79 ml (95% CI 42 to 116) higher FVC than thosewith a low vitamin C intake. Vitamin E intake showed no associationwith most symptoms and lung function, but had a positive associationwith productive cough. The intake of β-carotene was not associatedwith most symptoms but had a positive association with wheeze. However,subjects with a high intake of β-carotene had a 60 ml (95% CI 31 to89) higher FEV₁ and 75 ml (95% CI 40 to 110) higher FVCthan those with a low intake of β-carotene.
CONCLUSIONS—The results of this studysuggest that a high intake of vitamin C or β-carotene is protectivefor FEV₁ and FVC compared with a low intake, but not forrespiratory symptoms.

     

Pharmacokinetics of loratadine in patients with renal insufficiency

The disposition of loratadine, a new orally active histamine H1 receptor antagonist and its primary metabolite descarboethoxyloratadine were characterized in adult volunteers with normal renal function (group I), patients with chronic renal failure, i.e., creatinine clearance less than 30 mL/min (group II), as well as chronic hemodialysis patients (group III). The effect of hemodialysis on the disposition of loratadine and descarboethoxyloratadine was also assessed. Subjects in groups I and II were given a single oral 40 mg dose of loratadine while the patients in Group III received two single 40 mg doses of loratadine (during an interdialytic period and just prior to hemodialysis). Loratadine was rapidly absorbed and the decline of plasma concentrations after attainment of the Cmax was biexponential in all subjects. No significant differences in t1/2 beta were observed between the three groups (8.7 +/- 5.9, 7.6 +/- 6.9, 8.6 +/- 1.6 hrs: in groups I, II, and III, respectively). The apparent total body clearance and apparent volume of distribution of loratadine also did not differ significantly among the three groups. No significant differences in the Cmax or tmax of the metabolite were observed. The metabolite AUC infinity 0 however was significantly greater in group II subjects: (212.4 +/- 37.8, 469.5 +/- 95.4, 325.2 +/- 114.6 ng.hr/mL; groups I, II, and III, respectively). No significant relationship was observed between the terminal elimination half-life of loratadine or descarboethoxyloratadine and creatinine clearance. Hemodialysis augmented endogenous clearance by less than 1%. The disposition of loratadine is not significantly altered in patients with severe renal insufficiency nor is hemodialysis an effective means of removing loratadine or descarboethoxyloratadine from the body.