RELATIONSHIP AMONG SYMPTOMS SCORE,PROSTATE VOLUME AND URINARY FLOW RATES IN 543 PATIENTS WITH AND WIHTOUT BPH

BACKGROUND. Studies on the relationship among symptom score, urinary flow rate, and prostate volume in men with lower urinary tract symptoms (LUTS) continue to be of great interest. METHODS. A total of 2,418 men, aged 30-86 years, agreed to participate in an interview and to complete a questionnaire regarding voiding patterns. All subjects answering positively to one or more of the questions were submitted to a diagnostic assessment, based on the algorithm outlined by the guidelines of the International Consultation on Benign Prostatic Hyperplasia (BPH). Five hundred forty-three out of the 2,418 participants (22.45%) were evaluated. At the end of the diagnostic evaluation, 400 men with LUTS but without concomitant conditions (except BPH) known to interfere with normal voiding were selected. Descriptive statistics were used to characterize age, symptom score (International Prostate Symptom Score), prostate volume, and urinary flow rate distribution in these patients. Correlations among the aforementioned parameters were evaluated by means of a multivariate, multiple linear regression and logistic regression model. RESULTS. As reported in other studies, only weak or modest correlations were found. Moreover, the 400 cases were classified according to four age decades. The decrease in peak and mean flow rate per decade of age was similar (0.5 and 0.4 ml/sec); the increase in prostate volume and in total symptom score per decade was 3.3 cc and 0.6, respectively. In patients less than 50 years old, most of the correlations were stronger than those observed in the entire population of 400 men (age and prostate volume, c.c. 0.2864; age and peak flow rate, c.c. -0.2689; age and mean flow rate, c.c. -0.3034). However, symptom score continued to be weakly correlated with age and prostate volume (c.c. 0.0498 and 0.1966, respectively). In the last part of the study, men were assigned to different treatment strategies. Patients who were assigned to surgical treatment had higher prostate volume and IPSS and lower urinary flow rate than those assigned to nonsurgical treatment. CONCLUSIONS. We believe that the reason for the weak statistical association frequently reported in the literature is mainly the urology clinic-based population from which the patient samples were drawn. Data emerging from this analysis support the hypothesis that age is one of the principal factors influencing the relationship among symptom score, urinary flow rate, and prostate volume. (C) 1998 Wiley-Liss, Inc

Analysis of viral nucleic acids in duodenal biopsies from adult patients with active celiac disease: in search for an etiological relationship

BACKGROUND AND AIM: Celiac Disease (CD) is a multisystemic chronic inflammatory autoimmune disease which develops in genetically predisposed subjects and it is triggered by the ingestion of gluten. After the interaction between HLA-DQ2/DQ8 and gluten-derived peptides, lymphocytes T CD4+ start a specific immune response which ends in a chronic inflammation and mucosal damage. CD pathogenesis is complex and not entirely understood, probably due to an alteration in the gastrointestinal immune system or to its aberrant regulation. Furthermore, many environmental and immune factors could be involved, particularly viral infections. The aim of the study was to observe possible relationships between CD and infections from HHV-6 A/B, EBV, CMV, adenovirus and rotavirus. MATERIAL AND METHODS: Thirty-nine adult patients (aged 18-65 yrs) have been enrolled: specifically, 24 duodenal biopsies from active CD patients and 15 biopsies from non-CD patients were analyzed. CD diagnosis has been performed by means of serological antibodies, histology of duodenal biopsies and duodenal biopsy organ culture. Viral nucleic acids were extracted from duodenal biopsies and then amplified using Real-Time PCR technique. RESULTS: HHV-6B was found in 62.5% of CD patients and in 73.3% of non-CD patients (p=0.13). EBV was found in 4.5% of CD patients and 6.7% of non-CD patients (p=0.35). Nucleic acids from HHV-6A, CMV, adenovirus and rotavirus were not detected in any group. HHV-6B viral load in CD patients was higher than in non-CD patients, but data were not statistically significant (p=0.54). CD patients with HHV-6B viral load >50000 copies/ml resulted to be younger and had lower anti-tTG antibody titers found at organ culture than patients with lower HHV-6B viral load (p>0.05). CONCLUSIONS: There seems to be no difference in viral load and/or in the detection of viruses between CD and non-CD patients. Thus, our data do not support the possible relationship between CD and viral infections, although a larger population is needed to confirm our study results

Anaphylactic death: A new forensic workflow for diagnosis

Anaphylaxis is a life-threatening or fatal clinical emergency characterized by rapid onset, and death may be sudden. The margin of certainty about the diagnosis of anaphylactic death is not well established. The application of immunohistochemical techniques combined with the evaluation of blood tryptase concentrations opened up a new field of investigation into anaphylactic death. The present study investigated eleven autopsy cases of anaphylactic death, carried out between 2005 and 2017, by the Departments of Forensic Pathology of the Universities of Foggia and Catania (Italy). An analysis of the medical records was carried out in all autopsies. Seven autopsies were carried out on males and four on females. Of the eleven cases, one showed a history of asthma, one of food ingestion, two of oral administration of medications, six did not refer any allergy history, and one subject was unknown. All cases (100%) showed pulmonary congestion and edema; 7/11 (64%) of the cases had pharyngeal/laryngeal edema and mucus plugging in the airway; only one case (9%) had a skin reaction that was found during external examination. Serum tryptase concentration was measured in ten cases, and the mean value was 133.5 µg/L ± 177.9. The immunohistochemical examination using an anti-tryptase antibody on samples from the lungs, pharynx/larynx, and skin site of medication injection showed that all cases (100%) were strongly immunopositive for anti-tryptase antibody staining on lung samples; three cases (30%) were strongly immunopositive for anti-tryptase antibody staining on pharyngeal/laryngeal samples; and eight cases (80%) were strongly immunopositive for anti-tryptase antibody staining on skin samples. We conclude that a typical clinical history, blood tryptase level >40 µg/L, and strongly positive anti-tryptase antibody staining in the immunohistochemical investigation may represent reliable parameters in the determination of anaphylactic death with the accuracy needed for forensic purposes

Role of Microenvironment in Glioma Invasion. What We Learned from In Vitro Models

The invasion properties of glioblastoma hamper a radical surgery and are responsible for its recurrence. Understanding the invasion mechanisms is thus critical to devise new therapeutic strategies. Therefore, the creation of in vitro models that enable these mechanisms to be studied represents a crucial step. Since in vitro models represent an over-simplification of the in vivo system, in these years it has been attempted to increase the level of complexity of in vitro assays to create models that could better mimic the behaviour of the cells in vivo. These levels of complexity involved: 1. The dimension of the system, moving from two-dimensional to three-dimensional models; 2. The use of microfluidic systems; 3. The use of mixed cultures of tumour cells and cells of the tumour micro-environment in order to mimic the complex cross-talk between tumour cells and their micro-environment; 4. And the source of cells used in an attempt to move from commercial lines to patient-based models. In this review, we will summarize the evidence obtained exploring these different levels of complexity and highlighting advantages and limitations of each system used

Recurrence of gastrointestinal and extra-intestinal symptoms in celiac patients affected by nickel allergic contact mucositis: when proper gluten-free diet is not enough

BACKGROUND AND AIM: Nickel (Ni) is a metal widely present in nature and the prevalence of Ni allergy is increasing. Allergic contact mucositis (MAC) induced by Ni-rich foods is often responsible for IBS-like disorders and it can be diagnosed by means of a Ni oral mucosa patch test (omPT). It has been observed that, after several months of correct gluten-free diet (GFD), many celiac disease (CD) patients show a recrudescence of gastrointestinal and extra-intestinal symptoms, although serological and histological remission has been achieved. This can be due to a Ni load induced by GFD: a greater consumption of Ni-rich foods (e.g. corn) would lead to a consequent intestinal sensitization to Ni in predisposed subjects. Our study aimed to assess the role played by Ni in the recurrence of symptoms in CD subjects after strict GFD. MATERIAL AND METHODS: Twenty celiac patients (all female, age 23-65 yrs) in serological and histological remission after at least 12 months of GFD have been consecutively included: they all were complaining recurrence gastrointestinal and extra-intestinal symptoms. Subjects with organic gastrointestinal pathologies were excluded. A symptom questionnaire (GSRS modified according to the Salerno Experts' Criteria) has been administered to all patients in 4 stages: T0 (during free diet - active CD); T1 (after 12 months of GFD - CD remission); T2 (during GFD - recurrence of symptoms); T3 (during GFD and after 3 months of low-Ni diet). Ni omPT was performed at T2. Statistical analysis was performed using Wilcoxon signed rank test. RESULTS: All 20 patients showed positive Ni omPT, with local and/or systemic alterations confirming Ni ACM diagnosis. The analysis obtained by comparing T2-T3 showed p-value <0.01 for: abdominal pain, bloating, swelling, increased number of evacuations, dermatitis, asthenia; p-value values <0.05 for: heartburn, acid regurgitation, borborygmus, flatulence, loose stools, urgent need for defecation, headache. The other variables were statistically not significant. CONCLUSIONS: Our data suggest that gastrointestinal and extra-intestinal symptoms observed in CD subjects after prolonged and correct GFD may be due to the necessary dietary change and an increased Ni intake. Specifically, these patients developed Ni MAC, diagnosed by specific Ni omPT. We also observed that regression of symptoms may occur after a proper low-Ni diet. We can conclude that GFD may lead to an increased consumption of Ni-rich foods and this could explain the recurrence of apparently gluten-dependent symptoms

Human Adipose-Derived Stem Cells in Madelung's Disease: Morphological and Functional Characterization

Madelung Disease (MD) is a syndrome characterized by the accumulation of aberrant symmetric adipose tissue deposits. The etiology of this disease is yet to be elucidated, even though the presence of comorbidities, either genetic or environmental, has been reported. For this reason, establishing an in vitro model for MD is considered crucial to get insights into its physiopathology. We previously established a protocol for isolation and culture of stem cells from diseased tissues. Therefore, we isolated human adipose-derived stem cells (ASC) from MD patients and compared these cells with those isolated from healthy subjects in terms of surface phenotype, growth kinetic, adipogenic differentiation potential, and molecular alterations. Moreover, we evaluated the ability of the MD-ASC secretome to affect healthy ASC. The results reported a difference in the growth kinetic and surface markers of MD-ASC compared to healthy ASC but not in adipogenic differentiation. The most commonly described mitochondrial mutations were not observed. Still, MD-ASC secretome was able to shift the healthy ASC phenotype to an MD phenotype. This work provides evidence of the possibility of exploiting a patient-based in vitro model for better understanding MD pathophysiology, possibly favoring the development of novel target therapies

Effect of bone proteins on human prostate cancer cell lines in vitro

BACKGROUND Despite the high incidence and serious consequences of skeletal metastasis in prostate cancer patients, the mechanisms involved in establishing secondary lesions in bone are not well-understood. In this study, the role of the mineralized bone matrix in the process of skeletal metastasis was evaluated. METHODS Attachment, migration, and proliferation responses of human prostate cancer cells to a crude bone protein extract (CBE) were studied. LNCaP and DU145 cells were utilized in 24-hr attachment assays. Boyden chamber chemotactic assays and cell proliferation assays utilized DU145 cells. RESULTS CBE and fibronectin (FN) promoted attachment of DU145 cells, whereas only FN facilitated attachment of LNCaP cells. CBE-mediated adhesion of DU145 cells was reduced by 94% with cycloheximide, by 98% with RGD peptides, and by 94% with an antibody to ΑvΒ3. Although DU145 cells migrated toward FN, CBE did not promote migration of DU145 cells. DU145 cells grown in the presence of CBE-containing media demonstrated a significant reduction in cell number by day 4. The antiproliferative effect of CBE was not due to cell toxicity. CONCLUSIONS In conclusion, results from this study indicate that mineralized bone proteins promote the attachment of DU145 cells in vitro and suggest that bone proteins may play a key role in vivo during the development of metastatic prostate lesions in bone. Prostate 36:14–22, 1998. © 1998 Wiley-Liss, Inc.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/34753/1/3_ftp.pd

Systemic T Cells Immunosuppression of Glioma Stem Cell-Derived Exosomes Is Mediated by Monocytic Myeloid-Derived Suppressor Cells

A major contributing factor to glioma development and progression is its ability to evade the immune system. Nano-meter sized vesicles, exosomes, secreted by glioma-stem cells (GSC) can act as mediators of intercellular communication to promote tumor immune escape. Here, we investigated the immunomodulatory properties of GCS-derived exosomes on different peripheral immune cell populations. Healthy donor peripheral blood mononuclear cells (PBMCs) stimulated with anti-CD3, anti-CD28 and IL-2, were treated with GSC-derived exosomes. Phenotypic characterization, cell proliferation, Th1/Th2 cytokine secretion and intracellular cytokine production were analysed by distinguishing among effector T cells, regulatory T cells and monocytes. In unfractionated PBMCs, GSC-derived exosomes inhibited T cell activation (CD25 and CD69 expression), proliferation and Th1 cytokine production, and did not affect cell viability or regulatory T-cell suppression ability. Furthermore, exosomes were able to enhance proliferation of purified CD4+ T cells. In PBMCs culture, glioma-derived exosomes directly promoted IL-10 and arginase-1 production and downregulation of HLA-DR by unstimulated CD14+ monocytic cells, that displayed an immunophenotype resembling that of monocytic myeloid-derived suppressor cells (Mo-MDSCs). Importantly, the removal of CD14+ monocytic cell fraction from PBMCs restored T-cell proliferation. The same results were observed with exosomes purified from plasma of glioblastoma patients. Our results indicate that glioma-derived exosomes suppress T-cell immune response by acting on monocyte maturation rather than on direct interaction with T cells. Selective targeting of Mo-MDSC to treat glioma should be considered with regard to how immune cells allow the acquirement of effector functions and therefore counteracting tumor progression