Circulating stem cell factor in patients with chronic idiopathic urticaria.

BACKGROUND: The nature of histamine-releasing factors involved in the pathogenesis of chronic idiopathic urticaria (CIU) is still controversial, since functional IgG autoantibodies specific for the high-affinity IgE receptor, Fc(epsilon)RI, can be detected in only 20% of patients showing a strong skin reactivity on the autologous serum skin test. The absence of systemic eosinophilia in CIU patients, along with the increase in mast cells in skin biopsy specimens, suggests a possible role for stem cell factor (SCF), the only cytokine/growth factor known to induce mediator release from human mast cells. OBJECTIVE: To investigate the possible role of SCF as a histamine-releasing factor in patients with CIU. METHODS: The SCF levels were measured in serum samples from 65 patients with CIU who scored strongly positive on the autologous serum skin test; of these patients, 32 had negative results and 33 had positive results on in vitro histamine release assay by a quantitative commercial sandwich immunoassay technique. Serum samples from 40 healthy subjects were used as controls. RESULTS: Serum SCF levels in all 65 CIU patients did not differ from those found in healthy controls. No difference in SCF levels was found between patients with positive and negative results on histamine release assay. CONCLUSIONS: An increase in serum SCF levels does not play a pathogenic role in CIU.     

Multiple lipomas linked to an RB1 gene mutation in a large pedigree with low penetrance retinoblastoma

Hereditary predisposition to lipomas is observed in familial multiple lipomatosis (OMIM 151900) and benign cervical lipomatosis (OMIM 151800) and can also be associated with mutations in the MEN1 and PTEN genes (OMIM 131100 and 153480, respectively). In addition, a recent report indicates that a few patients with hereditary retinoblastoma also have lipomas. Here we report on an extended family segregating a splice site mutation in the RB1 gene. Almost all adult carriers of this mutation had multiple lipomas while penetrance for retinoblastoma was incomplete. In an unrelated pedigree, which was reported previously, the identical mutation was only associated with low-penetrance retinoblastoma but not lipomas. Our data indicate that lipoma predisposition in hereditary retinoblastoma is not associated with specific RB1 gene mutations but is influenced by modifying factors linked to this gene.     

Assessment of CMV load in solid organ transplant recipients by pp65 antigenemia and real-time quantitative DNA PCR assay: correlation with pp67 RNA detection

After bone marrow (BM) or solid-organ (SO) transplantation viremic Cytomegalovirus (CMV) infection is observed frequently. Quantitative assay of CMV in blood helps the management of this clinical condition. In the present report, 83 samples from 39 solid organ recipients, three CMV assays were compared simultaneously for the first time: the Nuclisens CMV pp67 assay (nucleic acid sequence-based amplification, NASBA), an "in-house" quantitative real-time PCR assay (TaqMan) for CMV DNA, and pp65 antigenemia. The relation between CMV DNA and pp65 antigenemia, the quantitative assays, was evaluated on a larger group including 251 blood samples from 118 solid organ recipients. Real-time PCR provided the best results; > or =130 CMV DNA copies/2 x 10(5) peripheral blood leukocytes (PBLs) predicted > or =1 pp65 antigen positive (Ag+) cell/2 x 10(5) PBLs. By taking pp65 antigenemia as the "gold standard," the sensitivity of CMV DNA quantitation and of the pp67 RNA assay were 0.95 and 0.20, respectively, while the corresponding specificity values were 0.50 and 0.93. When real-time PCR was considered as the "gold standard," the sensitivity and specificity of the pp65 antigenemia were 0.65 and 0.91, respectively. Among the three tests examined, the sensitivity of the pp67 RNA assay was the lowest. On the other hand, the pp67 RNA assay was highly specific and effective in pinpointing high viremia patients. The present report, by providing predictive values for all three diagnostic profiles, DNA load, antigenemia, and pp67RNA, is a contribution for validation of real-time PCR as a new standard for quantitative assessment of CMV viremia in clinical settings.     

Early activation of gammadelta T lymphocytes in the elderly

T cell function is altered in vivo and in vitro in elderly compared with young subjects, and this alteration is believed to contribute to morbidity and mortality in man due to the greater incidence of infection, as well as autoimmunity and cancer in elderly. The majority of T cells express TCRalphabeta whereas TCRgammadelta is expressed on a minority of T cells. Moreover, it is known that gammadelta T lymphocytes display major histocompatibility complex (MHC)- unrestricted cytotoxicity that is reminiscent of natural killer (NK) activity. In view of earlier findings on both T cells and NK cells in the elderly, we hypothesised a different behaviour of gammadelta T lymphocytes from old subjects when compared with gammadelta T lymphocytes obtained from young people. Therefore, to gain further insight into mechanisms of immunosenescence in this little-studied population, we studied immunofluorescence analysis gammadelta T cells from the elderly. Our preliminary results show that the percentage of blood gammadelta T cells in lymphocytes from old subjects is decreased when compared with the young. Interestingly, these cells are more activated in the elderly than in young subjects; expression of CD69, an early activation marker, is increased in gammadelta T lymphocytes from old subjects after three hours of in vitro culture both with and without lipopolysaccharide stimulation. Thus, our findings, which need confirmation, strongly suggest that, in humans, gammadelta T cells are early responders when compared with alphabeta T cells. They may act as 'first aid' cells to replace the described deficit of the specific and aspecific immunity in elderly. In this view, the proinflammatory status, observable in the elderly, renders them ready to be stimulated by exogenous agents.     

Enzyme- and immunohistochemical study of a case of histiocytic necrotizing lymphadenitis

Summary A combined morphological, immunohistological, and enzyme histochemical analysis was performed on frozen and fixed lymph node tissue in a case of histiocytic necrotizing lymphadenitis (HNL) using conventional histology, a panel of monoclonal and polyclonal antibodies, and a series of common haematological enzyme reactions. Histology showed multiple paracortical necrotizing foci which, in a prominently necrobiotic background devoid of granulocytes, contained large numbers of foamy histiocytes and macrophages intermingled with cells resembling degenerating plasmacytoid T-cells. Most of the histiocytes were alpha₁-antichymotrypsin positive and foamy cells were also distinctly Leu-M1 positive. Strong granular acid phosphatase (AP) positivity was present in the cytoplasm of the macrophages and histiocytes. The cells with plasmacytoid features showed weaker and homogeneously diffuse AP staining. Alpha-naphthyl acetate esterase (ANAE) activity was much less striking than AP in the necrotizing foci and most of the ANAE negative cells corresponded to those with plasmacytoid features. No cells with B-cell lineage markers were present within the necrotizing foci; most of the occasional T-cells (Leu-1⁺, Leu-4⁺) present in the foci were Leu-2a⁺ (OKT8⁺) whereas OKT10⁺ lymphoid cells were abundant and appeared to correspond with the cells with plasmacytoid features. Our combined data confirm that the special type of necrosis found in HNL develops within foci of plasmacytoid T-cells undergoing regressive changes and apparently exhibiting distinct immunohistological and enzyme histochemical features.This study was supported in part by Grant n. 84.00525.44 from Consiglio Nazionale delle Ricerche Progetto Finalizzato Oncologia, Roma and by the Associazione Italiana per la Ricerca sul Cancro, Milano     

Functional evaluation of collagen fiber scaffolds for ACL reconstruction: cyclic loading in proteolytic enzyme solutions

The mechanical properties of anterior cruciate ligament (ACL) reconstruction scaffolds were evaluated after exposure to functional challenges in vitro: cyclic loading combined with various proteolytic enzymes. Scaffolds were prepared from collagen fibers that were uncrosslinked (UNXL), crosslinked with ultraviolet irradiation (UV), or 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDC; 10 or 25 mM). Structural properties of scaffolds were determined following 1-h exposure to saline, trypsin, or bacterial collagenase, with and without simultaneous cyclic tensile loading (0 to 50 g; 0.5 Hz) in vitro. The breaking load and stiffness of UNXL and UV crosslinked scaffolds were significantly reduced by exposure to either trypsin or collagenase. Cyclic loads interacted synergistically with enzymes, rendering UNXL scaffolds untestable and further decreasing the breaking load of UV crosslinked scaffolds by approximately 35%. In contrast, the breaking load and stiffness of EDC crosslinked scaffolds, which were greater than those of UNXL or UV crosslinked scaffolds, were virtually unaffected by the same load and enzyme treatments. These results suggest that EDC is more effective than UV for crosslinking and stabilizing load-bearing collagen fiber ACL reconstruction scaffolds. Application of cyclic loads and enzymes may lead to development of physiologically relevant in vitro test methods for load-bearing scaffolds.     

Postoperative Paenibacillus thiaminolyticus Wound Infection,Switzerland

Paenibacillus thiaminolyticus is a nonvirulent organism found in human and ruminant microbiota. However, P. thiaminolyticus can act as an opportunistic pathogen in humans. We describe a case of abdominal wall hematoma secondarily infected by P. thiaminolyticus. Our findings emphasize the risk for unusual Paenibacillus infections in otherwise healthy persons.     

Microsurgical versus endoscopic trans-sphenoidal approaches for clivus chordoma: a pooled and meta-analysis

Neurosurgical Review - Chordoma is a rare slow-growing neoplastic bone lesion. However, they show an invasive local growth and high recurrence rate, leading to an overall survival rate of 65% at 5...     

The role of multiparametric MRI in active surveillance for low-risk prostate cancer: The ROMAS randomized controlled trial

BackgroundWe aim to evaluate the impact of multiparametric magnetic resonance imaging and fusion-target biopsy for early reclassification of patients with low-risk Prostate Cancer in a randomized trial.Materials and methodsBetween 2015 and 2018, patients diagnosed with Prostate Cancer after random biopsy fulfilling PRIAS criteria were enrolled and centrally randomized (1:1 ratio) to study group or control group. Patients randomized to study group underwent multiparametric magnetic resonance imaging at 3 months from enrollment: patients with positive findings (PIRADS-v2>2) underwent fusion-target biopsy; patients with negative multiparametric magnetic resonance imaging or confirmed ISUP - Grade Group 1 at fusion-target biopsy were managed according to PRIAS schedule and 12-core random biopsy was performed at 12 months. Patients in control group underwent PRIAS protocol, including a confirmatory 12-core random biopsy at 12 months. Primary endpoint was a reduction of reclassification rate at 12-month random biopsy in study group at least 20% less than controls. Reclassification was defined as biopsy ISUP Grade Group 1 in >2 biopsy cores or disease upgrading.ResultsA total of 124 patients were randomized to study group (n = 62) or control group (n = 62). Around 21 of 62 patients (34%) in study group had a positive multiparametric magnetic resonance imaging, and underwent fusion-target biopsy, with 11 (17.7%) reclassifications. Considering the intention-to-treat population, reclassification rate at 12-month random biopsy was 6.5% for study group and 29% for control group, respectively (P < 0.001).ConclusionsThe early employment of multiparametric magnetic resonance imaging for active surveillance patients enrolled after random biopsy consents to significantly reduce reclassifications at 12-month random biopsy.