Effect of oral calcium loading on intact PTH and calcitriol in idiopathic renal calcium stone formers and healthy controls

The calciuric response after an oral calcium load (l000 mg elemental calcium together with a standard breakfast) was studied in 13 healthy male controls and 21 recurrent idiopathic renal calcium stone formers, 12 with hypercalciuria (UCa×V>7.50 mmol/24 h) and nine with normocalciuria. In controls, serum 1,25(OH)2 vitamin D3 (calcitriol) remained unchanged 6 h after oral calcium load (50.6±5.1 versus 50.9±5.0 pg/ml), whereas it tended to increase in hypercalciuric (from 53.6±3.2 to 60.6±5.4 pg/ml, P=0.182) and fell in normocalciuric stone formers (from 45.9±2.6 to 38.1±3.3 pg/ml, P=0.011). The total amount of urinary calcium excreted after OCL was 2.50±0.20 mmol in controls, 2.27±0.27 mmol in normocalciuric and 3.62±0.32 mmol in hypercalciuric stone formers (P=0.005 versus controls and normocalciuric stone formers respectively); it positively correlated with serum calcitriol 6 h after calcium load (r=0.392, P=0.024). Maximum increase in urinary calcium excretion rate, δCa-Emax, was inversely related to intact PTH levels in the first 4 h after calcium load, i.e. more pronounced PTH suppression predicted a steeper increase in urinary calcium excretion rate. Twenty-four-hour urine calcium excretion rate was inversely related to the ratio of δ calcitriol/δPTHmax after calcium load (r=−0.653, P=0.0001), indicating that an abnormally up-regulated synthesis of calcitriol and consecutive relative PTH suppression induce hypercalciuria. Finally, late absorption of calcium as suggested by maximum urinary calcium excretion beyond 4 h after oral calcium load was as rare in hypercalciuric stone formers (2 of 12) as in controls (1 of 13) and did not occur in normocalciuric stone former

Interaction between rheumatoid arthritis and pregnancy: correlation of molecular data with clinical disease activity measures

Objective. The factors that induce remission of RA during pregnancy and the relapse occurring after delivery remain an enigma. In a previous study, we investigated gene-expression profiles of peripheral blood mononuclear cells (PBMC) in patients with RA and healthy women in late pregnancy and postpartum. Profiles of samples from both groups were similar in late pregnancy with elevated monocyte and decreased lymphocyte signatures. Postpartum, in RA PBMC the high level of monocyte transcripts persisted. Further increase was observed in adhesion, migration and signalling processes related to monocytes but also in lymphocytes despite similar clinical activity due to intensified drug treatment. This prompted us to investigate correlations between clinical parameters of disease activity and gene profiles. Methods. Transcriptome data were correlated with RADAI, CRP, monocyte and lymphocyte counts. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway annotations, monocytes and lymphocytes signatures were used as reference information. Results. Comparative analysis of PBMC expression profiles from RA patients during and after pregnancy with RADAI and CRP revealed a correlation of these disease activity parameters predominantly with monocyte transcripts. Genes related to cellular programs of adhesion, migration and response to infections were upregulated. Comparing clinically active and not-active RA patients postpartum revealed a cluster of 19 genes that could also identify active disease during pregnancy. Conclusion. The data suggest that an increase of the RADAI and an elevation of CRP is a consequence of molecular activation of monocytes. Furthermore, they indicate that molecular activation of T lymphocytes may remain clinically unrecognized postpartum. It is conceivable that a set of 19 genes may qualify as molecular disease activity marke

The CODE ambiguity-fixed clock and phase bias analysis products: generation, properties, and performance

The generation and use of GNSS analysis products that allowparticularly for the needs of single-receiver applicationsprecise point positioning with ambiguity resolution (PPP-AR) are becoming more and more popular. A general uncertainty concerns the question on how the necessary phase bias information should be provided to the PPP-AR user. Until now, each AR-enabling clock/bias representation method had its own practice to provide the necessary bias information. We have generalized the observable-specific signal bias (OSB) representation, as introduced in Villiger (J Geod 93:14871500, 2019) originally exclusively for pseudorange measurements, to carrier phase measurements. The existing common clock (CC) approach has been extended in a way that OSBs allowing for flexible signal and frequency handling between multiple GNSS become possible. Advantages of the proposed OSB-based PPP-AR approach are: GNSS biases can be provided in a consistent way for phase and code measurements and it is capable of multi-GNSS and suitable for standardization. This new, extended PPP-AR approach has been implemented by the Center for Orbit Determination in Europe (CODE). CODE clock products that adhere to the integer-cycle property have been submitted to the International GNSS Service (IGS) since mid of 2018 for three analysis lines: Rapid, Final, and MGEX (Multi-GNSS Extension). Ambiguity fixing is performed not only for GPS but also for Galileo. The integer-cycle property of between-satellite clock differences is of fundamental importance when comparing satellite clock estimates among various analysis lines, or at day boundaries. Both kinds of comparisons could be exploited at a very high level of consistency. Any retrieved comparison essentially indicated a standard deviation for between-satellite clocks from CODE of the order of 5 ps (1.5 mm in range). Finally, the integer-cycle property that may be recovered between the CODE Final clock and the accompanying bias product of consecutive daily sessions (using clock estimates additionally provided for the second midnight epoch) allows us to deduce GPS satellite clock and phase bias information that is consistent and continuous with respect to carrier phase observation data over two, three, or, in principle, yet more days. Phase-based clock densification from initially estimated integer-cycle-conform clock corrections at intervals of 300 s to 30 s (5 s in case of our Final clock product) is a matter of particular interest. Based on direct product comparisons and GRACE K-band ranging (KBR) data analysis, the quality of accordingly densified clock corrections could be confirmed to be on a level similar to that of of “anchor” (300s) clock corrections

A Randomized Prospective Study of Cefepime Plus Metronidazole with Imipenem-Cilastatin in the Treatment of Intra-abdominal Infections

Abstract : Background: : Presumptive antimicrobial therapy is an important aspect of the management of intra-abdominal infections. Together with surgery, antimicrobial combinations are still widely used to achieve the required spectrum of activity. The aim of this study was to evaluate the efficacy of parenteral cefepime + metronidazole vs imipenemcilastatin for the treatment of intra-abdominal infections in adult patients. Methods: : Patients with a clinically confirmed diagnosis of intra-abdominal infection were randomized to one of two treatment regimens: cefepime 2 g iv/12 h plus metronidazole 500 mg/8 h or imipenem-cilastatin 500 mg iv/6 h. The primary measure of clinical response was the decline of pre-treatment signs and symptoms of infection. The duration of follow-up was 30 days. Treatment failure was defined as either a lack of improvement or a worsening of pre-treatment signs and symptoms of infection. Surgical management of the infection was determined by the surgeon-in-charge. Results: : Of the 122 intended-to-treat patients included in the study, 60 patients (33 men) were randomized to cefepime + metronidazole and 61 (27 men) to imipenemcilastatin. Cefepime + metronidazole treatment was successful in 52 (87%) patients and imipenem-cilastatin in 44 (72%) patients (p = 0.004). Microbiological eradication was established in similar proportions in both groups (cefepime + metronidazole, 43; imipenem-cilastatin, 38). Conclusion: : Further studies are warranted to confirm the better results with the cefepime + metronidazole regimen for the treatment of intra-abdominal infection

In vivo imaging of murine endocrine islets of Langerhans with extended-focus optical coherence microscopy

Aims/hypothesis: Structural and functional imaging of the islets of Langerhans and the insulin-secreting beta cells represents a significant challenge and a long-lasting objective in diabetes research. In vivo microscopy offers a valuable insight into beta cell function but has severe limitations regarding sample labelling, imaging speed and depth, and was primarily performed on isolated islets lacking native innervations and vascularisation. This article introduces extended-focus optical coherence microscopy (xfOCM) to image murine pancreatic islets in their natural environment in situ, i.e. in vivo and in a label-free condition. Methods: Ex vivo measurements on excised pancreases were performed and validated by standard immunohistochemistry to investigate the structures that can be observed with xfOCM. The influence of streptozotocin on the signature of the islets was investigated in a second step. Finally, xfOCM was applied to make measurements of the murine pancreas in situ and in vivo. Results: xfOCM circumvents the fundamental physical limit that trades lateral resolution for depth of field, and achieves fast volumetric imaging with high resolution in all three dimensions. It allows label-free visualisation of pancreatic lobules, ducts, blood vessels and individual islets of Langerhans ex vivo and in vivo, and detects streptozotocin-induced islet destruction. Conclusions/interpretation: Our results demonstrate the potential value of xfOCM in high-resolution in vivo studies to assess islet structure and function in animal models of diabetes, aiming towards its use in longitudinal studies of diabetes progression and islet transplant

[Musculoskeletal puncture, injection and infiltration: swiss rheumatologists' point of view]

Arthrocentesis, injection and infiltration of joints and soft tissues belong to the basic procedures in rheumatology. The indications and the practical performance are based on experience and tradition. Nowadays, a crucial reappraisal and adaption of indications and technical aspects appear important in the light of new evidence and technical developments. The main indications for puncture remain the search of an infectious arthritis and reduction of intra-articular pressure due to effusion. Good indications for the injection of glucocorticoids are inflammation in sterile joints and activated osteoarthritis. The local infiltration with corticosteroids in mechanically induced enthesopathies at the lateral epicondyle of the humerus or at the plantar fascia have to be questioned in the light of recent publications which show that this common practice is associated with a poorer outcome than without injection

Management von Obstipation im palliativen Setting : Vorschläge für die Umsetzung durch das interprofessionelle Team

Einleitung: Die Palliative Care hat sich zu einem umfassenden Ansatz für die Behandlung von komplexen Symptomen im Spektrum lebenslimitierender Krankheiten entwickelt. Obwohl Obstipation ein häufiges Symptom bei Palliativ-Patient:innen darstellt, scheint bei Health Professionals ein mangelndes Bewusstsein für das Management von Obstipation vorzuliegen. Das Management der Obstipation ist ein multimodaler Ansatz, welcher deren Prävention sowie Behandlung durch Medikation, Flüssigkeits- und Nahrungsaufnahme, Mobilität und Behandlung von obstipationsbedingtem Schmerz beinhaltet (siehe Abb. 1).1 Ziel dieses Managements ist die Wiederherstellung einer aus Patient:innen-Sicht angenehmen Stuhlgewohnheit und die Linderung von Schmerzen, die im Zusammenhang mit Obstipation auftreten können. Fragestellung: Wie kann das interprofessionelle Team das Management von Obstipation im palliativen Setting unterstützen? Methode: In den Datenbanken PubMed und CINAHL Complete wurde eine systematisierte Literaturrecherche durchgeführt. Fünf Studien wurden eingeschlossen. Ergebnisse: Obstipation im palliativen Setting ist aufgrund der veränderten Lebensverhältnisse als ein Langzeitsymptom zu betrachten. Es werden die Interventionen Darm-Massage, Bewegung / Ballaststoffe / Flüssigkeit sowie medikamentöse Interventionen vorgestellt (siehe Tab. 1). Diskussion: Die Interventions-Wahl kann durch fehlende vorherige Durchführung eines geeigneten Assessments sowie Fachwissens-Lücken erschwert sein. Health Professionals sollen Obstipation als interprofessionelle Thematik angehen, wobei auch nicht-medikamentöse Interventionen zum Einsatz kommen sollen. Bedürfnisse und Gewohnheiten der Betroffenen müssen im Management berücksichtigt werden. Schlussfolgerung: Das Symptom Obstipation soll im palliativen Setting im Fokus der Aufmerksamkeit des ganzen interprofessionellen Teams stehen

Fibromatosis of the Plantar Fascia: Diagnosis and Indications For Surgical Treatment

Plantar fibromatosis is a rare, benign lesion involving the plantar aponeurosis. Eleven patients (13 feet) underwent 24 operations, including local excision, wide excision, or complete plantar fasciectomy. Clinical results were evaluated retrospectively. There were no differences among the subgroups in postoperative complications. Two primary fasciectomies did not recur. Three of six revised fasciectomies, seven of nine wide excisions, and six of seven local excisions recurred. Our results indicate that recurrence of plantar fibromatosis after surgical resection can be reduced by aggressive initial surgical resection