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Activation of the immune system has been increasingly recognised to be associated with procoagulatory status in patients with inflammatory rheumatic disease. Changes in endothelial cell and platelet activation, blood flow, expression and activity of different coagulation factors, and impaired fibrinolysis serve as pathophysiological basis for enhanced risk of venous thromboembolism in inflammatory rheumatic diseases, such as rheumatoid arthritis (RA), connective tissue diseases and vasculitides. Recent studies identifying mechanisms for a functional role of coagulation factors beyond haemostasis have provided examples of interesting links between the coagulation system and innate immune activation. Furthermore, citrullinated fibrinogen is an important and early autoantigen in patients with RA carrying the HLA-DRβ1 shared epitope allele, which demonstrates an adaptive immune response to a coagulation factor in an inflammatory rheumatic disease. Additional studies have provided strong evidence that a multitude of different components of the haemostatic system (such as thrombin, fibrinogen, coagulation factor XIII and factors of the fibrinolytic system) are relevant mediators of inflammatory processes as well as of inflammatory control. Understanding the interactions between coagulation and the immune system in inflammatory rheumatic diseases will not only improve our knowledge of disease mechanisms, but could also permit the development of innovative therapeutic interventions. [ABSTRACT FROM AUTHOR]

Background. Radiologic evaluation of adults with febrile urinary tract infection (UTI) is frequently performed to exclude urological disorders. This study aims to develop a clinical rule predicting need for radiologic imaging. Methods. We conducted a prospective, observational study including consecutive adults with febrile UTI at 8 emergency departments (EDs) in the Netherlands. Outcomes of ultrasounds and computed tomographs of the urinary tract were classified as "urgent urological disorder" (pyonephrosis or abscess), "nonurgent urologic disorder," "normal," and "incidental nonurological findings." Urgent and nonurgent urologic disorders were classified as "clinically relevant radiologic findings." The data of 5 EDs were used as the derivation cohort, and 3 EDs served as the validation cohort. Results. Three hundred forty-six patients were included in the derivation cohort. Radiologic imaging was performed for 245 patients (71%). A prediction rule was derived, being the presence of a history of urolithiasis, a urine pH ⩾7.0, and/or renal insufficiency (estimated glomerular filtration rate, ⩽40 mL/min/1.73 m³). This rule predicts clinically relevant radiologic findings with a negative predictive value (NPV) of 93% and positive predictive value (PPV) of 24% and urgent urological disorders with an NPV of 99% and a PPV of 10%. In the validation cohort (n = 131), the NPV and PPV for clinically relevant radiologic findings were 89% and 20%, respectively; for urgent urological disorders, the values were 100% and 11%, respectively. Potential reduction of radiologic imaging by implementing the prediction rule was 40%. Conclusions. Radiologic imaging can selectively be applied in adults with febrile UTI without loss of clinically relevant information by using a simple clinical prediction rule. [ABSTRACT FROM AUTHOR]

We examined the role of fluorodeoxyglucose-positron emission tomography (FDG-PET) and the addition of involved field radiotherapy (IFRT) as potential modifiers of salvage therapy. From January 2000 to June 2007, 83 patients with chemosensitive relapsed or primary refractory diffuse large B-cell lymphoma (DLBCL) underwent FDG-PET scans following second-line chemotherapy before high-dose therapy with autologous stem cell rescue (HDT/ASCR). We evaluated the prognostic value of having a negative FDG-PET scan before HDT/ASCR and whether IFRT improved the outcomes. Median follow-up was 45 months, and the 3-year PFS, disease-specific survival (DSS) and OS were 72, 80 and 78%, respectively. Multivariate analysis revealed that a positive FDG-PET scan had worse PFS (hazard ratio=(HR) 3.4; P=0.014), DSS (HR=7.7; P=0.001) and OS (HR=5.4; P=0.001), and that patients not receiving IFRT had worse PFS (HR=2.7; P=0.03) and DSS (HR=2.8, P=0.059). Patients who received IFRT had better local control with fewer relapses within prior involved sites compared with those that did not receive IFRT (P=0.006). These outcomes confirm the important prognostic value of FDG-PET scans before undergoing HDT/ASCR. It also suggests that the role of IFRT should be evaluated further.Bone Marrow Transplantation (2009) 43, 941–948; doi:10.1038/bmt.2008.408; published online 12 January 2009 [ABSTRACT FROM AUTHOR]

Background: Recent evidence suggests that distinction of subsets of rheumatoid arthritis (RA) depending on anti-cyclic citrullinated peptide antibody (anti-CCP) status may be helpful in distinguishing distinct aetiopathologies and in predicting the course of disease. HLA-DRB1 shared epitope (SE) and peptidylarginine deiminase type 4 (PADI4) genotype, both of which have been implicated in anti-CCP generation, are assumed to be associated with RA. Objectives: To elucidate whether PADI4 affects the clinical characteristics of RA, and whether it would modulate the effect of anti-CCPs on clinical course. The combined effect of SE and PADI4 on autoantibody profile was also analysed. Methods: 373 patients with RA were studied. SE, padi4_94C>T, rheumatoid factor, anti-CCPs and antinuclear antibodies (ANAs) were determined. Disease severity was characterised by cumulative therapy intensity classified into ordinal categories (CTI-1 to CTI-3) and by Steinbrocker score. Results: CTI was significantly associated with disease duration, erosive disease, disease activity score (DAS) 28 and anti-CCPs. The association of anti-CCPs with CTI was considerably influenced by padi4_94C>T genotype (C/C: OR = 0.93, p = 0.92; C/T: OR = 2.92, p = 0.093; T/T: OR = 15.3, p = 0.002). Carriage of padi4_94T exhibited a significant trend towards higher Steinbrocker scores in univariate and multivariate analyses. An association of padi4_94C>T with ANAs was observed, with noteworthy differences depending on SE status (SE−: OR = 6.20, p<0.04; SE+: OR = 0.36, p = 0.02) and significant heterogeneity between the two SE strata (p = 0.006). Conclusions: PADI4 genotype in combination with anti-CCPs and SE modulates clinical and serological characteristics of RA. [ABSTRACT FROM PUBLISHER]

Primary hyperoxaluria is characterized by severe urolithiasis, nephrocalcinosis, and early renal failure. As treatment options are scarce, we aimed for a new therapeutic tool using colonic degradation of endogenous oxalate by Oxalobactor formigenes. Oxalobacter was orally administered for 4 weeks as frozen paste (IxOC-2) or as enteric-coated capsules (IxOC-3). Nine patients (five with normal renal function, one after liver–kidney transplantation, and three with renal failure) completed the IxOC-2 study. Seven patients (six with normal renal function and one after liver–kidney transplantation) completed the IxOC-3 study. Urinary oxalate or plasma oxalate in renal failure was determined at baseline, weekly during treatment and for a 2-week follow-up. The patients who showed >20% reduction both at the end of weeks 3 and 4 were considered as responders. Under IxOC-2, three out of five patients with normal renal function showed a 22–48% reduction of urinary oxalate. In addition, two renal failure patients experienced a significant reduction in plasma oxalate and amelioration of clinical symptoms. Under IxOC-3 treatment, four out of six patients with normal renal function responded with a reduction of urinary oxalate ranging from 38.5 to 92%. Although all subjects under IxOC-2 and 4 patients under IxOC-3 showed detectable levels of O. formigenes in stool during treatment, fecal recovery dropped directly at follow up, indicating only transient gastrointestinal-tract colonization. The preliminary data indicate that O. formigenes is safe, leads to a significant reduction of either urinary or plasma oxalate, and is a potential new treatment option for primary hyperoxaluria.Kidney International (2006) 70, 1305–1311. doi:10.1038/sj.ki.5001707; published online 19 July 2006 [ABSTRACT FROM AUTHOR]

Regular calculation of urinary crystallization risk indices in patients suffering from urolithiasis is a recommended measure for treatment adjustment. The more the patient experiences either extensive stone formation or an enhanced recurrence rate, the more important risk index calculations. In patients suffering from primary hyperoxaluria type 1 (PH1), both criteria are met. Different methods of risk determination are known. All strategies for measuring the calcium oxalate (CaOx) crystallization risk of a given urine principally determine this parameter from voided urine. This “bladder urine”, however, has possibly passed stone material located in the urinary tract and thus may be depleted in lithogenic components. This is commonly the case for patients with PH1, who mostly experience a massive stone burden or severe nephrocalcinosis. Hence, the question arises as to whether we can adequately determine the crystallization risk in the urine of stone-bearing PH1-patients or not. Based on model calculations, we show that the determination of CaOx formation risk in PH1-patients requires knowledge of the restrictions in risk index interpretation: risk indices calculated from urinalysis (e.g. EQUIL) still indicate, even after strong in vivo stone formation, an enhanced but in fact strongly underestimated risk value. However, the outcome “enhanced” masks the patient’s true risk situation. The BONN Risk Index (BRI), in contrast, discloses the process of extreme in vivo crystal formation. As determined, inter alia, from the urinary concentration of free ionized calcium ([Ca2+]), BRI approaches abnormally low values, as, in consequence of CaOx - formation, [Ca2+] tends to values close to zero. Thus, calculations of urinalysis-based risk indices alone are insufficient strategies for the quantification of a PH1 patient’s CaOx crystallization risk. [ABSTRACT FROM AUTHOR]

This review draws the recent state of the art in metabolic diagnosis and metaphylaxis of stone disease. It is the basis for the consensus approval with the other medical societies and institutions in Germany involved in the guideline process of the new “Urolithiasis Guideline”. The German Working Committee on Stone Disease reviewed critically the current literature in the field of urolithiasis—including the existing German and EAU-Guidelines as well as the Conference Book of the First International Consultation on Stone Disease. As far as possible the references were rated according to the EBM criteria. On this basis the expert group discussed all pathways and statements regarding the management of stone disease. The present review coincides with the consented guideline draft of the German Working Committee on Stone Disease. Occurrence of stone disease in the western world increases seriously. Modern lifestyle, dietary habits and overweight—problems of the affluent societies—emerge to be the important promoters of the “stone-boom” in the new millennium. This even affects children, whose stone prevalence is otherwise significantly less than that of adults. Criteria for the high risk group of stone formers were clearly defined. A diagnostic standard is formulated for the basic and the elaborate metabolic evaluation of a stone patient. Approximately 75% of all stone patients could anticipate stone recurrence with elementary reorientation of their lifestyle and dietary habits, summarized as general metaphylaxis. About 25% of the stone formers require additional pharmacological intervention to normalize their individual biochemical risk, precisely compiled for each stone type as specific metaphylaxis. [ABSTRACT FROM AUTHOR]

Protein Z (PZ) is a vitamin K–dependent plasma protein that serves as a cofactor for the inactivation of factor Xa. A number of investigators found low PZ levels in patients with haemorrhagic as well as thromboembolic diseases, although there is no clear evidence of a pathogenic link between PZ deficiency and these clinical disorders. Nevertheless, low PZ levels have been found in association with early fetal losses, especially those occurring before the 15th week of gestation and in patients with detectable antiphospholipid and anti–PZ antibodies. The current diagnostic relevance and therapeutic consequences of these parameters will be discussed. [ABSTRACT FROM AUTHOR]

A novel human leukocyte antigen B (HLA-B) allele, B*4440, is described. The allele was identified in an adult stem cell donor of Caucasian origin. HLA-B*4440 most closely matches to B*4403 differing by a substitution of three nucleotides at codon 44, 45, and 50. Thus, low-resolution HLA typing using sequence-specific oligonucleotide hybridization or amplification using sequence-specific primers gave inconclusive results. DNA sequencing confirmed a variation of codons 44 and 45 (AGG AAG→AGA GAG) and codon 50 (CCA→CCG), resulting in an amino acid substitution Lys→Glu at codon 45. [ABSTRACT FROM AUTHOR]

Presents a letter to the editor focusing on the diagnosis of a 49-year-old woman suffering from sclerotic plaques on her legs.

Investigations have been carried out on rats to obtain information about the selenium-containing proteins present in the microsomal fraction and especially in the endoplasmatic reticulum (ER) of the kidney. For the determination of the selenium levels instrumental neutron activation analysis via 75Se was used. After labeling of rats in vivo with 75Se-selenite and separation of the proteins in the renal homogenate and cell compartments by electrophoretic methods, the 75Se-containing proteins were detected by autoradiography. In this way, six selenium-containing proteins with molecular masses of 15, 16, 20, 23-25, 40-42 and 58-60 were found in the endoplasmatic reticulum. All of those were characterized as selenocysteine-containing selenoproteins. [ABSTRACT FROM AUTHOR]

The recovery of gait, gross motor proficiency, and hand function was examined in 23 children (13 males, 10 females; age 4 years 7 months to 15 years 10 months) with traumatic brain injury (TBI) over five months of in patient rehabilitation. We used gait analysis, the Gross Motor Function Measure, the Developmental Hand Function Test, and the Purdue Pegboard test. Brain injury had been severe (initial Glasgow Coma Scale GCS <8) in 17 children and moderate (GCS 8-10) in six children. Compared with healthy control children of the same age and sex, repeated gait analyses in ambulatory children with brain injury showed significant reductions of velocity, stride length and cadence, and impaired balance. Spatiotemporal gait variables were correlated with Gross Motor Function Measure scores. Hand function tests revealed deficits in fine motor skills, speed, and coordination. Degree of impairment increased with trauma severity. Despite significant improvements, differences in gait velocity, stride length, and hand function of children with brain injuries and controls were still present about 8 months after TBI. Hand motor skills improved less than gait. Young age at injury was not associated with better recovery. [ABSTRACT FROM AUTHOR]

Background and Objectives In the present article, we report on two patients with acute haemolytic transfusion reactions (AHTRs), and whom we were unable to transfuse, owing to alloantibodies that in vitro did not seem to be clinically significant. Materials and Methods The patients were a 67-year-old male and a 64-year-old female, both of whom developed antibodies to red blood cells (RBCs) after repeat blood transfusions. Serological analyses were carried out using standard techniques. Results Both patients developed an AHTR of the intravascular type following blood transfusions. Serological re-examination revealed weakly reactive alloantibodies with anti-JMH specificity in one patient, and with unclear specificity in the second. Rechallenging the patients with 15–30 ml of packed RBCs caused AHTRs, and blood transfusion became impossible in both cases. Conclusion Weak alloantibodies that in vitro do not seem to be clinically significant may cause severe AHTRs. [ABSTRACT FROM AUTHOR]