Did the first description of patients with polymyalgia rheumatica take place in Scotland or in Denmark?

The first description of polymyalgia rheumatica (PMR) is generally attributed to Dr. Bruce. In an 1888 article entitled Senile rheumatic gout, he described five male patients aged from 60 to 74 years whom he had visited at the Strathpeffer spa in Scotland. In 1945, Dr. Holst and Dr. Johansen reported on five female patients examined over several months at the Medical Department of Roskilde County Hospital in Denmark. These patients suffered from hip, upper arms, and neck pain associated with elevated ESR and constitutional manifestations such as low-grade fever or loss of weight. In the same year, Meulengracht, another Danish physician, reported on two patients with shoulder pain and stiffness associated with fever, weight loss, and an increased erythrocyte sedimentation rate. As in the five patients reported by Dr. Holst and Dr. Johansen, a prolonged recovery time was recorded. On reading and comparing these three accounts, we question whether it is correct to attribute the first description of PMR to Dr. Bruce and put forward shifting this accolade to the three Danish physicians.

A step-by-step guide to ileoanal J-pouch MRI interpretation.

BACKGROUND: Multidisciplinary management of patients with an ileoanal pouch requires dedicated imaging to identify structural problems of the pouch associated with dysfunction. The purpose of this study is to provide a framework for interpretation of magnetic resonance imaging (MRI) scan of the ileoanal pouch to enable surgeons and radiologists to work cohesively, optimise diagnosis and ultimately improve patient care. METHODS: We propose a protocol for structured MRI assessment of the ileal pouch, aiming to provide surgeons a systematic report of the anatomy, its variations and pouch complications. This guide consists of studying the characteristics of the bowel, mesentery and anal canal. RESULTS: The presented checklist is designed to systematically interpret and identify abnormalities of the ileoanal pouch on MRI. It focuses on the characteristics of the bowel (encompassing pre-pouch ileum, pouch and rectal cuff), mesentery and anal canal. The different elements of the checklist are presented in the associated supplementary video. CONCLUSIONS: A combination of clinical assessment, endoscopic evaluations and imaging is fundamental to achieving accurate diagnosis of ileoanal pouch surgery complications and pouch dysfunction.

Strictureplasty for Crohn's disease of the small bowel in the biologic era: long-term outcomes and risk factors for recurrence.

BACKGROUND: The number of indications for strictureplasty for Crohn's disease has been greatly reduced since the widespread use of biologics, although the risk of intestinal failure remains. The aim of the study was to analyze the outcomes of strictureplasty and to identify risk factors for site-specific recurrence in the era of biologics. METHODS: Consecutive patients treated with strictureplasty for Crohn's disease between 2002 and 2018 were retrospectively included. Univariate analysis was carried out. Risk factors for recurrence were identified through a multilevel logistic regression analysis. RESULTS: Two hundred sixty-six patients were included in the study ( 171 males, median age 39.5 years, range 18-76 years). The majority of the 718 strictures requiring surgery in these patients were located in the ileum (61%), treated with conventional strictureplasty (89.6%) and required an additional resection (73.7%). Median follow-up time and time to recurrence were 96 months and 62.5 months respectively. The site-specific recurrence rate was 12.2% at 5 years and 25.7% at 10 years. Smoking was associated with a higher risk of recurrence in patients with milder disease. The 10-year recurrence rate was significantly higher for strictureplasties performed in the terminal ileum (30.9%, p = 0.0019) as compared to the ileum (21.8%) and the jejunum (8.4%). Multilevel logistic regression analysis showed that postoperative exposure to biologics (OR 4.74, p 0.001), nonconventional strictureplasty (OR 3.57, p 0.008) and a strictureplasty performed on a previous anastomosis (OR 13.58, p 0.002) were associated with site-specific recurrence. CONCLUSIONS: Strictureplasty is associated with optimal long-term outcomes in the biologic era and should be performed when feasible, to reduce the risk of intestinal failure in Crohn's disease patients.

Clinical practice guidelines for patients with polymyalgia rheumatica: the need for an active involvement of all stakeholder is still unmet.

Not available.

The role of the general practitioner and the out-of-hospital public rheumatologist in the diagnosis and follow-up of patients with polymyalgia rheumatica.

Polymyalgia rheumatica (PMR) is a chronic inflammatory disease characterized by shoulder and pelvic girdle pain. Its onset peaks around the age of 75; the prevalence increases until the age of 90 and it is more frequent in females. Diagnosis is mostly performed on the basis of symptoms. An increase of serum inflammatory markers is indicative, but not essential, while therapy is mainly based on glucocorticoids. Since there is no universal agreement about diagnostic criteria for PMR, its detection is still difficult. There are discordant opinions about the fact that PMR can be recognised and managed by general practitioners (GPs), while patients with atypical features need to be referred to the rheumatologist. In the Italian setting, the absence of recent epidemiological studies is associated with the total lack of a research protocol in primary care, from which relevant information could be derived. The out-of-hospital public rheumatologist is a peculiar figure of the Italian National Health System, who takes care of outpatients. Although differences between the different Italian regional health services exist, this professional figure has proved to be effective in reducing delay and increasing accuracy in PMR diagnosis.

Nonergodic subdiffusion from Brownian motion in an inhomogeneous medium.

Nonergodicity observed in single-particle tracking experiments is usually modeled by transient trapping rather than spatial disorder. We introduce models of a particle diffusing in a medium consisting of regions with random sizes and random diffusivities. The particle is never trapped but rather performs continuous Brownian motion with the local diffusion constant. Under simple assumptions on the distribution of the sizes and diffusivities, we find that the mean squared displacement displays subdiffusion due to nonergodicity for both annealed and quenched disorder. The model is formulated as a walk continuous in both time and space, similar to the Lévy walk.

A new mechanism of NK cell cytotoxicity activation: the CD40-CD40 ligand interaction.

NK recognition is regulated by a delicate balance between positive signals initiating their effector functions, and inhibitory signals preventing them from proceeding to cytolysis. Knowledge of the molecules responsible for positive signaling in NK cells is currently limited. We demonstrate that IL-2-activated human NK cells can express CD40 ligand (CD40L) and that recognition of CD40 on target cells can provide an activation pathway for such human NK cells. CD40-transfected P815 cells were killed by NK cell lines expressing CD40L, clones and PBL-derived NK cells cultured for 18 h in the presence of IL-2, but not by CD40L-negative fresh NK cells. Cross-linking of CD40L on IL-2-activated NK cells induced redirected cytolysis of CD40-negative but Fc receptor-expressing P815 cells. The sensitivity of human TAP-deficient T2 cells could be blocked by anti-CD40 antibodies as well as by reconstitution of TAP/MHC class I expression, indicating that the CD40-dependent pathway for NK activation can be downregulated, at least in part, by MHC class I molecules on the target cells. NK cell recognition of CD40 may be important in immunoregulation as well as in immune responses against B cell malignancies.

A myeloma paraprotein with specificity for platelet glycoprotein IIIa in a patient with a fatal bleeding disorder.

Impaired platelet aggregation, normal shape change, and agglutination and normal ATP secretion and thromboxane synthesis in response to high concentrations of thrombin or arachidonic acid were found in a patient with multiple myeloma and hemorrhagic tendency. The purified IgG1 kappa or its F(ab1)2 fragments induced similar changes when added in vitro to platelet-rich plasma from normal subjects. In addition, the paraprotein inhibited adhesion to glass microbeads, fibrin clot retraction, and binding of radiolabeled fibrinogen or von Willebrand factor to platelets exposed to thrombin or arachidonic acid without affecting intraplatelet levels of cAMP. The radiolabeled para-protein bound to an average of 35,000 sites on normal platelets but it bound to less than 2,000 sites on the platelets from a patient with Glanzmann's thrombasthenia. Immunoprecipitation studies showed that the platelet antigen identified by the paraprotein was the glycoprotein IIIa. Furthermore, binding of radiolabeled prostaglandin E1 (PGE1) to resting platelets as well as binding of von Willebrand factor to platelets stimulated with ristocetin were entirely normal in the presence of patient's inhibitor. These studies indicate that bleeding occurring in dysproteinemia may be the result of a specific interaction of monoclonal paraproteins with platelets. In addition, our data support the concept that the interaction of fibrinogen and/or von Willebrand factor with the platelet glycoprotein IIb-IIIa complex is essential for effective hemostasis.

Top-down approach from satellite to terrestrial rover application for environmental monitoring of landfills.

This paper describes a methodology to perform chemical analyses in landfill areas by integrating multisource geomatic data. We used a top-down approach to identify Environmental Point of Interest (EPI) based on very high-resolution satellite data (Pleiades and WorldView 2) and on in situ thermal and photogrammetric surveys. Change detection techniques and geostatistical analysis supported the chemical survey, undertaken using an accumulation chamber and an RIIA, an unmanned ground vehicle developed by CNR IIA, equipped with a multiparameter sensor platform for environmental monitoring. Such an approach improves site characterization, identifying the key environmental points of interest where it is necessary to perform detailed chemical analyses.

Cannabis through the looking glass: chemo- and enantio-selective separation of phytocannabinoids by enantioselective ultra high performance supercritical fluid chromatography.

By using the Inverted Chirality Columns Approach (ICCA) we have developed an enantioselective UHPSFC method to determine the enantiomeric excess (ee) of (-)-Δ9-THC in medicinal marijuana (Bedrocan®). The ee was high (99.73%), but the concentration of the (+)-enantiomer (0.135%) was not negligible, and it is worth a systematic evaluation of bioactivity.

Transient subdiffusion from an Ising environment.

We introduce a model in which a particle performs a continuous-time random walk (CTRW) coupled to an environment with Ising dynamics. The particle shows locally varying diffusivity determined by the geometrical properties of the underlying Ising environment, that is, the diffusivity depends on the size of the connected area of spins pointing in the same direction. The model shows anomalous diffusion when the Ising environment is at critical temperature. We show that any finite scale introduced by a temperature different from the critical one, or a finite size of the environment, cause subdiffusion only during a transient time. The characteristic time, at which the system returns to normal diffusion after the subdiffusive plateau depends on the limiting scale and on how close the temperature is to criticality. The system also displays apparent ergodicity breaking at intermediate time, while ergodicity breaking at longer time occurs only under the idealized infinite environment at the critical temperature.

Nonergodic subdiffusion from transient interactions with heterogeneous partners.

Spatiotemporal disorder has been recently associated to the occurrence of anomalous nonergodic diffusion of molecular components in biological systems, but the underlying microscopic mechanism is still unclear. We introduce a model in which a particle performs continuous Brownian motion with changes of diffusion coefficients induced by transient molecular interactions with diffusive binding partners. In spite of the exponential distribution of waiting times, the model shows subdiffusion and nonergodicity similar to the heavy-tailed continuous time random walk. The dependence of these properties on the density of binding partners is analyzed and discussed. Our work provides an experimentally testable microscopic model to investigate the nature of nonergodicity in disordered media.

Light-induced rotation of dye-doped liquid crystal droplets.

We investigate both theoretically and experimentally the rotational dynamics of micrometric droplets of dye-doped and pure liquid crystal induced by circularly and elliptically polarized laser light. The droplets are dispersed in water and trapped in the focus of the laser beam. Since the optical torque acting on the molecular director is known to be strongly enhanced in light-absorbing dye-doped materials, the question arises whether a similar enhancement takes place also for the overall optical torque acting on the whole droplets. We searched for such enhancement by measuring and comparing the rotation speed of dye-doped droplets induced by a laser beam having a wavelength either inside or outside the dye absorption band, and also comparing it with the rotation of pure liquid crystal droplets. No enhancement was found, confirming that photoinduced dye effects are only associated with an internal exchange of angular momentum between orientational and translational degrees of freedom of matter. Our result provides also direct experimental proof of the existence of a photoinduced stress tensor in the illuminated dye-doped liquid crystal. Finally, peculiar photoinduced dynamical effects are predicted to occur in droplets in which the molecular director is not rigidly locked to the flow, but so far they could not be observed.

Natural polysaccharide-based gels for dairy food preservation.

The innovative packaging systems described in the present work, based on natural gels, have been shown to increase the shelf life of the Mozzarella cheese, without adding any chemical substance and without thermal procedures. Physical, physicochemical, microbiological, analytical, and mechanical analyses were used to monitor the quality of the cheese as a function of storage type and storage time. In particular, microbiological analysis confirmed that the characteristics of the Mozzarella cheese stored at 4 degrees C in gel are maintained for more than 15 d, whereas samples stored in the mother solution lost important characteristics after 5 d. A penetration test (texture) confirmed that the Mozzarella cheese preserved in the gel maintained mechanical properties similar to those of the fresh product, even after storage for 30 d at 4 degrees C.

Expression and ATRA-driven modulation of adhesion molecules in acute promyelocytic leukemia.

On fresh leukemic cells taken from 30 patients with acute promyelocytic leukemia (APL) the membrane expression of a series of adhesion molecules including beta 2 integrins (CD11a/LFA-1, CD11b/Mac-1), selectin ligands (CD15/Le(x), CD15s/sLex) and tyrosine-phosphatase isoforms (CD45RA, CD45R0) was analyzed. The expression of these molecules was also studied in nine of these patients following the APL cells' culture with and without all-trans retinoic acid (ATRA). The fresh APL promyelocytes expressed CD45RA and CD15s on their surface, while CD11a, CD11b, CD15, and CD45R0 were constantly absent. In vitro treatment with ATRA consistently increased the expression of CD15, CD11b, and CD45R0 on leukemic promyelocytes; these changes were paralleled by a decrease of CD45RA display. The expression of sialylated antigen CD15s was fully independent from CD15 suggesting a differential enzymatic regulation within this selectin ligand system. ATRA was, however, incapable of promoting the up-regulation of CD11a in APL. As a result, asynchronous phenotype (CD11a-, CD11b+, CD15+, CD15s+/-, CD45RA-, CD45R0+) was generated that is normally undetectable on maturing myeloid cells. In order to provide a further control a case of acute agranulocytosis was also investigated, in which > 75% bone marrow cells were arrested at the promyelocyte stage; these bone marrow cells showed a surface phenotype identical to non-leukemic promyelocytes (CD11a+, CD11b+, CD15+, CD45R0+, CD45RA-) with a spontaneous ability to differentiate in vivo towards the more mature stages of myeloid differentiation. We therefore suggest that in fresh and ATRA-induced APL cells distinct, regular phenotypic changes are identifiable that are probably associated with t(15;17) and not seen in normal and activated bone marrow.

Expression and ATRA-driven modulation of adhesion molecules in acute promyelocytic leukemia.

On fresh leukemic cells taken from 30 patients with acute promyelocytic leukemia (APL) the membrane expression of a series of adhesion molecules including beta 2 integrins (CD11a/LFA-1, CD11b/Mac-1), selectin ligands (CD15/Le(x), CD15s/Le(x)) and tyrosine-phosphatase isoforms (CD45RA, CD45R0) was analyzed. The expression of these molecules was also studied in nine of these patients following the APL cells' culture with and without all-trans retinoic acid (ATRA). The fresh APL promyelocytes expressed CD45RA and CD15s on their surface, while CD11a, CD11b, CD15, and CD45R0 were constantly absent. In vitro treatment with ATRA consistently increased the expression of CD15, CD11b, and CD45R0 on leukemic promyelocytes; these changes were paralleled by a decrease of CD45RA display. The expression of sialylated antigen CD15s was fully independent from CD15 suggesting a differential enzymatic regulation within this selectin ligand system. ATRA was, however, incapable of promoting the up-regulation of CD11a in APL. As a result, asynchronous phenotype (CD11a-, CD11b+, CD15+, CD15s+/-, CD45RA-, CD45R0+) was generated that is normally undetectable on maturing myeloid cells. In order to provide a further control a case of acute agranulocytosis was also investigated, in which > 75% bone marrow cells were arrested at the promyelocyte stage; these bone marrow cells showed a surface phenotype identical to non-leukemic promyelocytes (CD11a+, CD11b+, CD15+, CD45R0+, CD45RA-) with a spontaneous ability to differentiate in vivo towards the more mature stages of myeloid differentiation. We therefore suggest that in fresh and ATRA-induced APL cells distinct, regular phenotypic changes are identifiable that are probably associated with t(15;17) and not seen in normal and activated bone marrow.

JURL-MK1 (c-kit(high)/CD30-/CD40-) and JURL-MK2 (c-kit(low)/CD30+/CD40+) cell lines: 'two-sided' model for investigating leukemic megakaryocytopoiesis.

Two novel cell lines (JURL-MK1 and JURL-MK2) have been established from the peripheral blood of a patient in the blastic phase of chronic myelogenous leukemia. The cells grow in a single cell suspension with doubling times of 48 h (JURL-MK1) and 72 h (JURL-MK2). Cytogenetic analysis has shown that JURL-MK1 is hypodiploid whereas JURL-MK2 is near triploid and that both cell lines retain t(9;22). Moreover, JURL-MK1 and JURL-MK2 have a bcr/abl-fused gene with the same junction found in the patient's fresh cells, and both cell lines express the b3/a2 type of hybrid bcr/abl mRNA. The morphology and immunophenotype of these cell lines are reminiscent of megakaryoblasts. In both lines, a limited but consistent percentage of cells expresses gpIIbIIIa (CD41a), gpIIIa (CD61) and CD36, with no expression of gplb (CD42b), glycophorin A, hemoglobin and CD34. Both cell lines are clearly positive for CD33, CD43, CD45RO and CD63, while CD13, CD44, CD54, CD30 and CD40 are specific features of JURL-MK2. Among cytokine receptors, CD117/SCF-R is strongly displayed by a large fraction of JURL-MK1 cells but is hardly detectable on about 20% JURL-MK2 cells. Both cell lines are clearly positive for CD25/IL2R alpha, while a marked expression of CD116/GM-CSF-R and CDw123/IL3R alpha is restricted to JURL-MK2. Induction of cell differentiation in vitro has demonstrated that TPA is able to modulate the JURL-MK1 phenotype, causing an increased expression of platelet-associated antigens. The JURL-MK2 phenotype is easily modulated by both TPA and DMSO, which cause an increased expression of CD41a and CD117 accompanied by a decreased expression of CD30. Proliferation studies demonstrated that JURL-MK1 cell growth is enhanced by stem cell factor, while JURL-MK2 proliferation is unaffected by this cytokine. JURL-MK1 and JURL-MK2 are two novel cell lines with divergent biological features, representing a 'two-sided' model for investigating new aspects of megakaryocytopoiesis.

Common human leukocyte antigen alleles in pemphigus vulgaris and pemphigus foliaceus Italian patients.

Pemphigus refers to a group of autoimmune blistering skin diseases, mainly identified as pemphigus vulgaris and pemphigus foliaceus, both characterized by the presence of autoantibodies against keratinocyte adhesion molecules, leading to loss of cell-cell adhesion with consequent blister formation. Pemphigus vulgaris is reported to be associated with human leukocyte antigen DR4 and/or DR6 whereas no data are available on pemphigus foliaceus, except for the endemic Brazilian form (fogo selvagem), which is reported to be associated with DR1 and DR4. We here report human leukocyte antigen molecular typing on a total of 87 patients, 61 with pemphigus vulgaris and 26 with pemphigus foliaceus, versus 128 healthy matched controls. Generic typing showed an increase of DRB1*04 and DRB1*14 and a decrease of DRB1*07 in both pemphigus vulgaris and pemphigus foliaceus patients. Molecular subtyping of DR4+ and DR14+ subjects showed a highly significant association between the DRB1*1401 and both pemphigus vulgaris (p < 0.0001) and pemphigus foliaceus patients (p < 0.0001) together with a significant increase of the linked DQB1*0503 (pemphigus vulgaris p < 0.0001; pemphigus foliaceus p < 0.0001). Moreover, whereas the association between DRB1*0402 and pemphigus vulgaris (p < 0.0001) has been confirmed, no significant association between a specific allele of the DR4 group and pemphigus foliaceus, has been found. Therefore, at least in Italian patients, pemphigus vulgaris and pemphigus foliaceus share DRB1*1401 and DQB1*0503, as susceptible human leukocyte antigen alleles, whereas DRB1*0402 is only found associated with pemphigus vulgaris. The observation that both diseases, pemphigus vulgaris and pemphigus foliaceus, carry the same susceptible human leukocyte antigen alleles has been interpreted as a common genetic background predisposing to pemphigus as, like in other autoimmune disorders, it is not sufficient to explain the onset of the disease on the basis of the sole aforementioned alleles. Other linked genes and/or environmental factors should play a facilitating role in the outbreak of pemphigus, either pemphigus vulgaris or pemphigus foliaceus.