Impact of red blood cell transfusions on intestinal barrier function in preterm infants.

OBJECTIVE: To determine the relationships of red blood cell (RBC) transfusion and enteral feeding to changes in intestinal permeability (IP) measured by the relative intestinal uptake of lactulose (La) and rhamnose (Rh) in preterm infants <33 wk gestation. DESIGN/METHODS: Infants 240-326wk gestation received La/Rh solution enterally on study days 1, 8 and 15.Urinary La/Rh ratio was measured by HPLC. Hematocrit preceding transfusion, total RBC transfusion volume, volume/kg, and feeding status during each study interval (birth-d1; d1-d8, and d8-d15) were determined. RESULTS: Of the seventeen (40.5%) subjects who received≥1 transfusion during the study period, 12 (70.6%) infants were <28 wk gestation and 5 (29.4%) infants were≥28 wk gestation, p < 0.0001. Lower pre-transfusion hematocrit was observed in intervals preceding high IP (La/Rh > 0.05) than in intervals preceding low IP (La/Rh≤0.05) measurements (33 vs 35.8, p = 0.1051). RBC transfusions occurred more frequently in intervals preceding high IP than in intervals preceding low IP (26.8%; vs 8.3%, p = 0.0275) with 5-fold higher total RBC volume and volume/kg in intervals preceding any time point with high IP. RBC transfusion during an interval was associated with a three-fold increased risk of high IP (aOR 2.7; 95% C.I 0.564-12.814; p = 0.2143). Exclusive breast milk exposure and post-menstrual age reduced the risk for high IP following RBC transfusion. CONCLUSIONS: Both RBC transfusion number and volume was associated with subsequent high IP measurements in preterm infants <33 weeks gestation and potentially may contribute to impairment of the preterm intestinal barrier.

Accuracy of FDG-PET-CT in the diagnostic work-up of vascular prosthetic graft infection.

OBJECTIVES: To investigate the diagnostic accuracy of fluoro-2-deoxy-d-glucose positron emission tomography (FDG-PET) compared with computed tomography (CT) scanning and added value of fused FDG-PET-CT in diagnosing vascular prosthetic graft infection. DESIGN: Prospective cohort study with retrospective analysis. MATERIALS: Twenty five patients with clinically suspected vascular prosthetic infection underwent CT and FDG-PET scanning. METHODS: Two nuclear medicine physicians assessed the FDG-PET scans; all CT scans were assessed by two radiologists. Fused FDG-PET/CT were judged by the radiologist and the nuclear medicine physician. The concordance between CT and FDG-PET and the inter-observer agreement between the different readers were investigated. RESULTS: Fifteen patients had a proven infection by culture. Single FDG-PET had the best results (sensitivity 93%, specificity 70%, positive predictive value 82% and negative predictive value 88%). For CT, these values were 56%, 57%, 60% and 58%, respectively. Fused CT and FDG-PET imaging also showed high sensitivity and specificity rates and high positive and negative values. Inter-observer agreement for FDG-PET analysis was excellent (kappa = 1.00) and moderate for CT and fused FDG-PET-CT analysis (0.63 and 0.66, respectively). CONCLUSION: FDG-PET scanning showed a better diagnostic accuracy than CT for the detection of vascular prosthetic infection. This study suggests that FDG-PET provides a useful tool in the work-up for diagnosis of vascular prosthetic graft infection.

Mode of action of abatacept in rheumatoid arthritis patients having failed tumour necrosis factor blockade: a histological, gene expression and dynamic magnetic resonance imaging pilot study.

OBJECTIVES: Abatacept is the only agent currently approved to treat rheumatoid arthritis (RA) that targets the co-stimulatory signal required for full T-cell activation. No studies have been conducted on its effect on the synovium, the primary site of pathology. The aim of this study was to determine the synovial effect of abatacept in patients with RA and an inadequate response to tumour necrosis factor alpha (TNFalpha) blocking therapy. METHODS: This first mechanistic study incorporated both dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI) and arthroscopy-acquired synovial biopsies before and 16 weeks after therapy, providing tissue for immunohistochemistry and quantitative real-time PCR analyses. RESULTS: Sixteen patients (13 women) were studied; all had previously failed TNFalpha-blocking therapy. Fifteen patients completed the study. Synovial biopsies showed a small reduction in cellular content, which was significant only for B cells. The quantitative PCR showed a reduction in expression for most inflammatory genes (Wald statistic of p<0.01 indicating a significant treatment effect), with particular reduction in IFNgamma of -52% (95% CI -73 to -15, p<0.05); this correlated well with MRI improvements. In addition, favourable changes in the osteoprotegerin and receptor activator of nuclear factor kappa B levels were noted. DCE-MRI showed a reduction of 15-40% in MRI parameters. CONCLUSION: These results indicate that abatacept reduces the inflammatory status of the synovium without disrupting cellular homeostasis. The reductions in gene expression influence bone positively and suggest a basis for the recently demonstrated radiological improvements that have been seen with abatacept treatment in patients with RA.

Does the use of tumour necrosis factor antagonist therapy in poor prognosis, undifferentiated arthritis prevent progression to rheumatoid arthritis?

OBJECTIVES: To evaluate the ability of tumour necrosis factor (TNF) antagonist therapy to produce remission and prevent progression to rheumatoid arthritis (RA) in patients with poor prognosis undifferentiated inflammatory arthritis (UA). METHODS: Patients with UA of <12 months' duration and having relapsed after a single parenteral corticosteroid injection were recruited into a double-blind, placebo-controlled trial of infliximab or placebo monotherapy administered at weeks 0, 2, 6 and 14. Methotrexate was added at week 14 if no clinical response (raised C-reactive protein (CRP) and clinical synovitis) was achieved. Standard outcomes were collected at baseline, infusion visits and weeks 26 and 52. The primary outcome was clinical remission at week 26. RESULTS: 17 patients were randomised (10 infliximab, 7 placebo) all with poor prognostic features. At week 14, the infliximab group had greater improvements in CRP and Health Assessment Questionnaire (HAQ) but by week 26 there was just a trend favouring infliximab for early morning stiffness, tender joint score, swollen joint score and HAQ; there was no significant difference in 28 joint count Disease Activity Score between the two groups. Furthermore, only three patients were in clinical remission (two infliximab, one placebo). By week 52, 100% patients in the infliximab group and 71% (5/7) patients in the placebo group had developed RA. CONCLUSIONS: In poor prognosis UA, a short course of TNF antagonist therapy provided modest short-term relief but did not prevent the development of RA. Patients with UA with a poor prognosis relapsing after corticosteroid have a high risk of evolving to RA and are suitable candidates for interventional treatment.

Can remission be maintained with or without further drug therapy in rheumatoid arthritis?

Remission is now the accepted goal of management in rheumatoid arthritis (RA). This article highlights the controversies surrounding the definition of remission and reviews the potential of current treatment options to achieve remission. Defining "true" remission can be difficult based on current criteria, which do not consider structural and physical function. Nonetheless, considerable advances in recent years have made the concept of remission a realistic goal. In early RA, substantial and largely irreversible radiographic damage is seen in 60% of patients within the first 2 years of diagnosis. Early therapeutic intervention would ideally lead to reduction in long-term disability in RA and likelihood of inducing and maintaining remission.Long-term maintenance therapy with disease-modifying antirheumatic drugs (DMARDs) has been shown to be effective in preventing flares of disease. Stopping therapy for short periods does not necessarily lead to flares, but the effect on long-term radiographic damage and potential to achieve similar levels of disease control following reinstatement of therapy is not established. Early use of tumour necrosis factor (TNF)-antagonist therapy (e.g. infliximab) has been shown to lead to significant improvement in disease activity measures (clinical and radiologic outcomes) when compared to monotherapy or combination DMARD and corticosteroid therapies. Response was shown to be sustained in 70% of patients receiving TNF-blocking therapy 1 year after stopping treatment. This suggests the significant role of TNF-blocking therapy in enabling sustainable remission without need for long-term administrations, which has important implications for favourable health economics. At present, little published evidence exists on the effects of withdrawal of TNF-blocking therapy in patients with established RA in remission. In conclusion, evidence indicates that remission is a realistic goal, but more evidence is required to establish optimal treatment strategies and define criteria for remission that include imaging and immunological as well as clinical assessment of the disease state.

Preliminary phytochemical screening of four common plants of family caesalpiniaceae.

Preliminary phytochemical screening of Bauhinia variegata, Cassia fistula, Cassia tora and Tamarindus indica did not reveal alkaloids and unbound anthraquinones while glycosides as well as flavonoids were present in all the four species of the family caesalpiniaceae. Cardiac glycosides were absent only in C. tora and saponins were present only in T. indica, B. variegata and T. indica were devoid of bound anthraquinones while bound anthraquinones were present in C. fistula and C. tora. Paper chromatography revealed 6 spots in solvent system I, and 5 spots in solvent system 2, showing different Rf values. The per cent yield of crude glycosides was 3.18 in B. variegata, 4.03 in C. fistula, 4.45 in C. tora and 4.14 in T. indica.