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1.
J Craniomaxillofac Surg ; 50(5): 400-405, 2022 May.
Article in English | MEDLINE | ID: mdl-35491325

ABSTRACT

The aim of this retrospective long-term study was to assess the influence of primary columella lengthening and presurgical nasoalveolar molding (NAM) on the skeletal development at the completion of growth in patients with bilateral cleft lip and palate (BCLP). Lateral cephalometric radiographs at the completion of growth of consecutively treated patients BCLP patients, operated by the same surgeon, who had undergone NAM were compared with a second group of BCLP patients who were not treated with NAM. The groups were matched for sex and age. Independent samples t tests were carried out. 23 Lateral cephalometric radiographs of BCLP patients (mean age 18.2 ± 1.3 years) who had undergone NAM were compared with a second group of 23 BCLP patients (mean age 18.4 ± 1.3 years) who were not treated with NAM. The only two significant differences were observed in Ans-Me/N-Me (control group = 0.6 ± 0.02; sample group = 0.57 ± 0.05; p = 0.019) and ILs^AnsPns (control group = 105.5 ± 7.9; sample group = 112.4 ± 8.6; p = 0.007). No other significant differences were observed in terms of facial skeletal development between the two groups. Presurgical NAM performed during infancy in BCLP patients does not seem to have negative effects on the skeletal development at the completion of craniofacial growth compared to the group of patients treated without NAM.


Subject(s)
Cleft Lip , Cleft Palate , Adolescent , Adult , Cleft Lip/diagnostic imaging , Cleft Lip/surgery , Cleft Palate/diagnostic imaging , Cleft Palate/surgery , Humans , Nasal Septum , Nasoalveolar Molding , Nose/diagnostic imaging , Nose/surgery , Retrospective Studies , Young Adult
2.
Proc Natl Acad Sci U S A ; 117(13): 7305-7316, 2020 03 31.
Article in English | MEDLINE | ID: mdl-32184325

ABSTRACT

Interleukin 10 (IL-10) is an antiinflammatory cytokine, but also promotes B cell responses and plays a pathogenic role in systemic lupus erythematosus (SLE). CD4+CCR6+IL-7R+T cells from human tonsils produced IL-10 following stimulation by naïve B cells, which promoted B cell immunoglobulin G (IgG) production. These tonsillar CCR6+B helper T cells were phenotypically distinct from follicular helper T (TFH) cells and lacked BCL6 expression. In peripheral blood, a CCR6+T cell population with similar characteristics was identified, which lacked Th17- and TFH-associated gene signatures and differentiation-associated surface markers. CD4+CCR6+T cells expressing IL-10, but not IL-17, were also detectable in the spleens of cytokine reporter mice. They provided help for IgG production in vivo, and expanded systemically in pristane-induced lupus-like disease. In SLE patients, CD4+CCR6+IL-7R+T cells were associated with the presence of pathogenic anti-dsDNA (double-stranded DNA) antibodies, and provided spontaneous help for autoantibody production ex vivo. Strikingly, IL-10-producing CCR6+T cells were highly abundant in lymph nodes of SLE patients, and colocalized with B cells at the margins of follicles. In conclusion, we identified a previously uncharacterized population of extrafollicular B helper T cells, which produced IL-10 and could play a prominent pathogenic role in SLE.


Subject(s)
B-Lymphocytes/immunology , Interleukin-10/immunology , Lupus Erythematosus, Systemic/immunology , Receptors, CCR6/immunology , T-Lymphocytes, Helper-Inducer/immunology , Adult , Animals , Antibody Formation , Child , Cytokines/immunology , Humans , Interleukin-10/biosynthesis , Interleukin-17/metabolism , Lupus Erythematosus, Systemic/metabolism , Mice , Mice, Inbred C57BL , Palatine Tonsil/cytology , Palatine Tonsil/immunology , Receptors, CCR6/biosynthesis , Th17 Cells/immunology
3.
Sci Rep ; 10(1): 3037, 2020 02 20.
Article in English | MEDLINE | ID: mdl-32080232

ABSTRACT

Allosteric modulation is involved in a plethora of diverse protein functions, which are fundamental for cells' life. This phenomenon can be thought as communication between two topographically distinct site of a protein structure. How this communication occurs is still matter of debate. Many different descriptions have been presented so far. Here we consider a specific case where any significant conformational change is involved upon allosteric modulator binding and the phenomenon is depicted as a vibrational energy diffusion process between distant protein regions. We applied this model, by employing computational tools, to the human muscarinic receptor M2, a transmembrane protein G-protein coupled receptor known to undergo allosteric modulation whose recently X-ray structure has been recently resolved both with and without the presence of a particular allosteric modulator. Our calculations, performed on these two receptor structures, suggest that for this case the allosteric modulator modifies the energy current between functionally relevant regions of the protein; this allows to identify the main residues responsible for this modulation. These results contribute to shed light on the molecular basis of allosteric modulation and may help design new allosteric ligands.


Subject(s)
Models, Molecular , Receptor, Muscarinic M2/metabolism , Allosteric Regulation , Allosteric Site , Crystallography, X-Ray , Humans
4.
J Phys Chem Lett ; 9(22): 6393-6398, 2018 Nov 15.
Article in English | MEDLINE | ID: mdl-30358398

ABSTRACT

The exchange of vibrational energy in proteins is crucial for their function. Here, we establish a connection between quantities related to it with geometry-based properties such as the proteins' residues coordination number. This relation is proven by molecular simulation in a neuro-pharmacologically relevant transmembrane receptor. The connection demonstrated here paves the way to studies of protein allostery and conformational changes based solely on protein structure.


Subject(s)
Receptor, Muscarinic M2/chemistry , Energy Transfer , Molecular Dynamics Simulation , Protein Conformation , Vibration
5.
Sci Total Environ ; 624: 1429-1442, 2018 May 15.
Article in English | MEDLINE | ID: mdl-29929254

ABSTRACT

Mountain ecosystems are sensitive and reliable indicators of climate change. Long-term studies may be extremely useful in assessing the responses of high-elevation ecosystems to climate change and other anthropogenic drivers from a broad ecological perspective. Mountain research sites within the LTER (Long-Term Ecological Research) network are representative of various types of ecosystems and span a wide bioclimatic and elevational range. Here, we present a synthesis and a review of the main results from ecological studies in mountain ecosystems at 20 LTER sites in Italy, Switzerland and Austria covering in most cases more than two decades of observations. We analyzed a set of key climate parameters, such as temperature and snow cover duration, in relation to vascular plant species composition, plant traits, abundance patterns, pedoclimate, nutrient dynamics in soils and water, phenology and composition of freshwater biota. The overall results highlight the rapid response of mountain ecosystems to climate change, with site-specific characteristics and rates. As temperatures increased, vegetation cover in alpine and subalpine summits increased as well. Years with limited snow cover duration caused an increase in soil temperature and microbial biomass during the growing season. Effects on freshwater ecosystems were also observed, in terms of increases in solutes, decreases in nitrates and changes in plankton phenology and benthos communities. This work highlights the importance of comparing and integrating long-term ecological data collected in different ecosystems for a more comprehensive overview of the ecological effects of climate change. Nevertheless, there is a need for (i) adopting co-located monitoring site networks to improve our ability to obtain sound results from cross-site analysis, (ii) carrying out further studies, in particular short-term analyses with fine spatial and temporal resolutions to improve our understanding of responses to extreme events, and (iii) increasing comparability and standardizing protocols across networks to distinguish local patterns from global patterns.

6.
Proc Natl Acad Sci U S A ; 115(4): E762-E771, 2018 01 23.
Article in English | MEDLINE | ID: mdl-29311338

ABSTRACT

Increasing evidence suggests that early neurodevelopmental defects in Huntington's disease (HD) patients could contribute to the later adult neurodegenerative phenotype. Here, by using HD-derived induced pluripotent stem cell lines, we report that early telencephalic induction and late neural identity are affected in cortical and striatal populations. We show that a large CAG expansion causes complete failure of the neuro-ectodermal acquisition, while cells carrying shorter CAGs repeats show gross abnormalities in neural rosette formation as well as disrupted cytoarchitecture in cortical organoids. Gene-expression analysis showed that control organoid overlapped with mature human fetal cortical areas, while HD organoids correlated with the immature ventricular zone/subventricular zone. We also report that defects in neuroectoderm and rosette formation could be rescued by molecular and pharmacological approaches leading to a recovery of striatal identity. These results show that mutant huntingtin precludes normal neuronal fate acquisition and highlights a possible connection between mutant huntingtin and abnormal neural development in HD.


Subject(s)
Huntington Disease/physiopathology , Neurogenesis , Cell Line , Cell Polarity , Humans , Huntington Disease/genetics , Induced Pluripotent Stem Cells , Telencephalon/cytology
7.
Proc Natl Acad Sci U S A ; 114(48): 12797-12802, 2017 11 28.
Article in English | MEDLINE | ID: mdl-29133396

ABSTRACT

Follicular helper T cells (TFHs) are a key component of adaptive immune responses as they help antibody production by B cells. Differentiation and function of TFH cells are controlled by the master gene BCL6, but it is largely unclear how this transcription repressor specifies the TFH program. Here we asked whether BCL6 controlled helper function through down-regulation of specific microRNAs (miRNAs). We first assessed miRNA expression in TFH cells and defined a TFH-specific miRNA signature. We report that hsa-miR-31-5p (miR-31) is down-regulated in TFH; we showed that BCL6 suppresses miR-31 expression by binding to its promoter; and we demonstrated that miR-31 inhibits the expression of molecules that control T-helper function, such as CD40L and SAP. These findings identify a BCL6-initiated inhibitory circuit that stabilizes the follicular helper T cell program at least in part through the control of miRNA transcription. Although BCL6 controls TFH activity in human and mouse, the role of miR-31 is restricted to human TFH cell differentiation, reflecting a species specificity of the miR-31 action. Our findings highlight miR-31 as a possible target to modulate human T cell dependent antibody responses in the settings of infection, vaccination, or immune dysregulation.


Subject(s)
B-Lymphocytes/immunology , CD40 Ligand/genetics , MicroRNAs/genetics , Proto-Oncogene Proteins c-bcl-6/genetics , Signaling Lymphocytic Activation Molecule Associated Protein/genetics , T-Lymphocytes, Helper-Inducer/immunology , Adaptive Immunity , Animals , B-Lymphocytes/cytology , CD40 Ligand/immunology , Cell Differentiation , Gene Expression Profiling , Gene Expression Regulation , Gene Regulatory Networks , Germinal Center/cytology , Germinal Center/immunology , Humans , Mice , Mice, Inbred C57BL , MicroRNAs/immunology , Primary Cell Culture , Promoter Regions, Genetic , Protein Binding , Proto-Oncogene Proteins c-bcl-6/immunology , Signal Transduction , Signaling Lymphocytic Activation Molecule Associated Protein/immunology , Species Specificity , T-Lymphocytes, Helper-Inducer/cytology
8.
J Atr Fibrillation ; 8(6): 1379, 2016.
Article in English | MEDLINE | ID: mdl-27909497

ABSTRACT

The term tachycardiomyopathy refers to a specific form of tachycardia-related cardiomyopathy caused by supraventricular or ventricular tachyarrhytmias that are both associated with ventricular rates higher than 120 bpm. The arrhythmias which are most frequently associated with these forms of heart disease are atrial fibrillation and atrial flutter, particularly found in the elderly population. The most frequent clinical manifestation is heart failure. In this case we are reporting a clinical case of a patient that came to our attention because of an episode of heart failure associated with atrial fibrillation and atrial flutter. The patient had also prolonged and repetitive strips of rapid conduction with wide QRS morphology. We don't know if the cause is pre excitation or ectopia. We showed that those strips of tachycardia with wide QRS, particularly when they were associated with atrial flutter, were so fast and consistent to determine the left ventricular contractile dysfunction; we showed also that those strips of wide complex tachycardia were caused by pre-excitation through an accessory right posteroseptal pathway and supported by the reentry circuit of common atrial flutter. The block of conduction through the accessory pathway and the elimination of atrial arrhythmia allowed the regression of left ventricular contractile dysfunction. We believe that this case is interesting because it shows that there is a strict continuity between sophisticated electrophysiological mechanisms and clinical manifestation.

9.
Haemophilia ; 22(4): 537-42, 2016 Jul.
Article in English | MEDLINE | ID: mdl-26988465

ABSTRACT

INTRODUCTION: Pharmacokinetic (PK) studies on recombinant FIX concentrate, Nonacog alpha, were conducted with different sampling time designs which gave rise to not complete and homogenous outcomes. In addition, patient's FIX genotype/PK relationship has never been investigated. AIM: Investigate how different sampling times may affect PK parameters and try to find a FIX genotype/PK relationship. PATIENTS AND METHODS: A cohort pharmacokinetic, Nonacog Alpha single-dose, open-label, non-comparative study was conducted in eight Comprehensive Care Haemophilia Centres in Italy. Seventeen previously treated moderate or severe haemophilia B patients were enrolled. Factors IX:C one-stage clotting assay, FIX genotype and PK analysis were centralized. RESULTS: The evaluation of PK outcomes showed a quite long half-life, smaller clearance and volume of distribution of Nonacog Alpha in comparison with the results from previously reported studies, where blood sampling was stopped too early. The relationship between PK outcomes and FIX genotype showed that small deletions displayed the higher clearance and shorter half-life, the nonsense mutations (the lower and the longer respectively), and missense mutations were in between. CONCLUSIONS: It is evident that area under the curve (AUC) and other PK parameters depend from the sampling time design. In order to have a complete evaluation of clotting factors in vivo decay, blood samples must be collected until the baseline factor concentration has been achieved again. Due to the relationship between FIX genotype and clearance, tailored prophylaxis of HB patients could be partially predicted by genotyping.


Subject(s)
Factor IX/genetics , Hemophilia B/genetics , Area Under Curve , Coagulants/pharmacokinetics , Coagulants/therapeutic use , Codon, Nonsense , Cohort Studies , Drug Administration Schedule , Factor IX/metabolism , Factor IX/therapeutic use , Genotype , Half-Life , Hemophilia B/drug therapy , Hemophilia B/pathology , Humans , Italy , Male , Mutation, Missense , ROC Curve , Recombinant Proteins/biosynthesis , Recombinant Proteins/pharmacokinetics , Recombinant Proteins/therapeutic use
10.
Phys Chem Chem Phys ; 18(8): 5702-6, 2016 Feb 17.
Article in English | MEDLINE | ID: mdl-26553504

ABSTRACT

We perform here enhanced sampling simulations of N-terminally acetylated human α-synuclein, an intrinsically disordered protein involved in Parkinson's disease. The calculations, consistent with experiments, suggest that the post-translational modification leads to the formation of a transient amphipathic α-helix. The latter, absent in the non-physiological form, alters protein dynamics at the N-terminal and intramolecular interactions.


Subject(s)
Molecular Dynamics Simulation , alpha-Synuclein/chemistry , alpha-Synuclein/metabolism , Acetylation , Circular Dichroism , Humans , Molecular Conformation , Parkinson Disease/physiopathology , Protein Processing, Post-Translational
11.
J Physiol Pharmacol ; 66(3): 441-7, 2015 Jun.
Article in English | MEDLINE | ID: mdl-26084226

ABSTRACT

Zeolites are microscopic minerals of volcanic origin, and the zeolite most commonly used in medicine is clinoptilolite. Over the years, clinoptilolite has been tested in several ways: as an antioxidant, as an adjuvant in anticancer therapy due to its ability to capture chemotoxins, as an antidiarrhoeal agent and as a chelating agent for heavy metals. The aim of this study was to evaluate the ability of clinoptilolite to absorb ethanol in vivo in healthy drinkers. We enrolled 12 healthy drinkers in this study. The study was conducted as follows: phase 1: consumption of a hydroalcoholic solution containing 25 g of ethanol; phase 2: use of a 16.25 mL medical device containing clinoptilolite (2.5 g of clinoptilolite within a single-dose sachet) + consumption of a hydroalcoholic solution containing 25 g of ethanol; phase 3: use of a 32.5 mL medical device (5 g of clinoptilolite within a single-dose sachet) + consumption of a hydroalcoholic solution containing 25 g of ethanol. At the time of blood sampling, alcohol ingestion was also measured using an Alcolmeter instrument, and the results showed that the two methods overlapped. Reductions of 43%, 35%, 41% and 34% in blood ethanol at 30, 60, 90 and 120 minutes, respectively, were observed after the consumption of 5 g of clinoptilolite + 25 g of ethanol in both males and females, whereas the consumption of 2.5 g of clinoptilolite did not result in a statistically significant reduction in blood ethanol. In particular, the blood ethanol reduction was more significant in males. Our study highlights and confirms the ability of clinoptilolite to decrease the absorption of ingested ethanol by reducing blood alcohol levels. This effect was statistically significant at a dose of 5 g.


Subject(s)
Ethanol/pharmacokinetics , Zeolites/administration & dosage , Zeolites/pharmacology , Adolescent , Adult , Alcohol Drinking , Dosage Forms , Drug Interactions , Ethanol/blood , Female , Humans , Male , Middle Aged , Pilot Projects , Sex Factors , Young Adult
12.
Obes Surg ; 25(12): 2344-51, 2015 Dec.
Article in English | MEDLINE | ID: mdl-25948283

ABSTRACT

BACKGROUND: We evaluated dietary intakes, body composition, micronutrient deficiency, and response to micronutrient supplementation in 47 patients before and for 6 months after laparoscopic sleeve gastrectomy (LSG). METHODS: Before, 3, and 6 months after LSG, we measured dietary intakes with food-frequency questionnaires, body composition with bioimpedance analysis (BIA) and bioelectrical vector analysis (BIVA), and plasma concentrations of iron, Zn, water-, and lipo-soluble vitamins. RESULTS: After LSG, energy intake significantly decreased and patients lost weight, fat mass, and free-fat mass. BIVA showed a substantial loss of soft tissue body cell mass (BCM) with no change in hydration. Before surgery, 15 % of patients were iron deficient, 30 % had low levels of zinc and/or water-soluble vitamins, and 32 % of vitamin 25(OH)-D3. We treated iron deficiency with ferrous sulfate, isolated folate deficiency with N5-methyiltetrahydrofolate-Ca-pentahydrate, and deficiencies in vitamin B1, B12, or Zn, with or without concomitant folate deficiency, with multivitamin. No supplementation was given to vitamin 25(OH)-D3 deficient patients. At first follow-up, 7 % of patients developed new deficiencies in iron, 7 % in folic acid (n = 3), and 36 % in water-soluble vitamins and/or zinc whereas no new deficit in vitamin 25(OH)-D3 occurred. At final follow-up, deficiencies were corrected in all patients treated with either iron or folate but only in 32 % of those receiving multivitamin. Vitamin 25(OH)-D3 deficiency was corrected in 73 % of patients even though these patients were not supplemented. CONCLUSION: LSG-induced weight loss is accompanied by a decrease in BCM with no body fluid alterations. Deficiencies in water-soluble vitamins and Zn respond poorly to multivitamin supplementation.


Subject(s)
Body Composition/physiology , Dietary Supplements , Micronutrients/administration & dosage , Obesity, Morbid/diet therapy , Obesity, Morbid/surgery , Adult , Avitaminosis/epidemiology , Avitaminosis/etiology , Avitaminosis/prevention & control , Female , Folic Acid/blood , Folic Acid Deficiency/etiology , Gastrectomy/adverse effects , Humans , Laparoscopy/adverse effects , Male , Micronutrients/pharmacology , Middle Aged , Nutrition Therapy , Obesity, Morbid/epidemiology , Obesity, Morbid/metabolism , Postoperative Complications/prevention & control , Postoperative Period , Retrospective Studies , Trace Elements/blood , Vitamins/blood , Young Adult
14.
J Intern Med ; 276(5): 454-69, 2014 Nov.
Article in English | MEDLINE | ID: mdl-25069756

ABSTRACT

BACKGROUND: High mobility group box 1 (HMGB1) is a small nuclear protein with two functions. In the nucleus, it helps to wrap DNA around nucleosomes. When secreted, it recruits inflammatory cells and induces cytokine production. Before HMGB1 is secreted from inflammatory cells, it relocates to the cytoplasm, which partially or totally depletes cell nuclei of HMGB1. We previously showed that cells lacking HMGB1 contain 20% fewer nucleosomes and 30% more RNA transcripts levels genome-wide. OBJECTIVE: We hypothesized that the depletion of nuclear HMGB1 plays a role in inflammation that can enhance or complement the role of extracellular HMGB1. METHODS: We analysed the transcriptional profile of wild-type and Hmgb1-/- mouse embryonic fibroblasts (MEFs) as a proxy for cells that have lost HMGB1 from their nuclei. We explored the transcriptome of wild-type and Hmgb1-/- macrophages differentiated in the presence of granulocyte-macrophage colony-stimulating factor, before and after exposure to LPS/IFN-γ. In the same cells, histones and nuclear HMGB1 were quantified. RESULTS: We found that Hmgb1-/- MEFs show a transcriptional profile associated with stress and inflammation responses. Moreover, wild-type macrophages that have secreted HMGB1 because of LPS/IFN-γ exposure rapidly reduce their histone content as much as cells that genetically lack HMGB1. Importantly, unstimulated Hmgb1-/- macrophages activate transcriptional pathways associated with cell migration and chemotaxis. CONCLUSIONS: We suggest that nucleosome loss is an early event that facilitates transcriptional responses of macrophages to inflammation, particularly chemotaxis. HMGB1's dual roles in the nucleus and in the extracellular space appear to be complementary.


Subject(s)
HMGB1 Protein/metabolism , Inflammation/metabolism , Macrophages/metabolism , Nucleosomes/metabolism , Animals , Cell Line , Cell Nucleus/physiology , Chemotaxis , Histones/genetics , Histones/metabolism , Inflammation/genetics , Lipopolysaccharides/pharmacology , Liver/cytology , Liver/embryology , Macrophages/cytology , Macrophages/drug effects , Transcription, Genetic
15.
Acta Chir Belg ; 114(2): 125-30, 2014.
Article in English | MEDLINE | ID: mdl-25073211

ABSTRACT

BACKGROUND: In this prospective non-randomized observational cohort study we evaluated: the feasibility and effectiveness of primary umbilical hernia repair with open tension-free and sutureless technique using a porcine small intestinal submucosa (Surgisis) prosthesis, the quality of the treatment in terms of reduction of postoperative discomfort and the complications at early and long-term follow-up. METHODS: Thirty-six consecutive patients, mean age 45.25 +/- 12.19 years, affected by primary umbilical uncomplicated hernia with a defect size < or = 3 cm, were treated in a day-surgery setting. A tailored flat Surgisis graft was used to ensure an overlap of at least 2 cm; in all patients the mesh was fixed by fibrin glue. Collected data included: visual analogic scale (VAS) pain scores at 24 hours, 72 hours, and 7, 15, and 30 days and number of analgesic medications after operation, complications rate, the quality of life measured by Short Form 36 health survey questionnaire (SF-36) before the operation and at long term follow-up. RESULTS: The mean follow-up time was 5.6 +/- 1.4 years. Postoperative pain was low: the mean visual analogic scale (VAS) scores were 2.8 at 24 h, 1.8 at 72 h, and 0.9, 0.3, and 0.04 at 7, 15, and 30 days, respectively. 77.8% of the patients (28/36) did not use any analgesic drugs. Seroma was reported in 13.8% of the patients (5/36); there were no hematomas, infection, chronic pain and no major complications or mortality (< or = 30 days). Recurrence rate was 2.8% (1/36). Patient satisfaction showed a significant improvement in all SF-36 domain scores (P < 0.001). CONCLUSIONS: The biologic mesh seems to be a safe and reliable device for repairing primary umbilical hernia with high patient comfort, even if not yet an alternative to synthetic mesh.


Subject(s)
Collagen/therapeutic use , Hernia, Umbilical/surgery , Herniorrhaphy/instrumentation , Pain, Postoperative/prevention & control , Surgical Mesh , Adult , Aged , Feasibility Studies , Female , Fibrin Tissue Adhesive , Follow-Up Studies , Humans , Male , Middle Aged , Prospective Studies , Secondary Prevention , Suture Techniques , Time Factors , Treatment Outcome
16.
Int J Surg ; 12 Suppl 1: S165-9, 2014.
Article in English | MEDLINE | ID: mdl-24866066

ABSTRACT

INTRODUCTION: Parathyroidectomy (PTx) is recommended in patients affected by secondary hyperparathyroidism (2HPT) of chronic kidney disease-mineral bone disorders (CKD-MBD), resistant to medical treatment. Analyzing total parathyroidectomy with muscular or subcutaneous autoimplantation (TPai) outcomes in hemodialysis (HD) 2HPT patients, and monitoring intact parathyroid hormone (iPTH) levels, we evaluated long-term functional results of subcutaneous parathyroid glandular tissue autoimplantation. METHODS: 40 HD 2HPT patients, resistant to medical treatment, and awaiting for renal transplantation, underwent total parathyroidectomy with subcutaneous autoimplantation of 9-12 fragments of not nodular hyperplasia parathyroid tissue in not dominant forearm. iPTH were analyzed 24 h, and 3-6-12-24 months after surgery. The 1.08-6.99 pmol/L range was taken as reference of normal iPTH level based on which eu- (1.08-6.99), hypo- (<1.08), aparathyroidism (0) and persistence or relapse (>6.99) of disease were determined. RESULTS: In every case PTai determined an extraordinary improvement of quality of life, associated with a notable reduction of iPTH serum level. Immediate normalization of iPTH was achieved in 50% of cases; hypoparathyroidism in 25% of cases and persistence of disease in 25% were observed. Long term follow-up showed a reduction of hypoparathyroidism and an increase of relapse rate up to 20%. Grafting resection was never performed. DISCUSSION: Subcutaneous autotrasplantation is a very simple and fast surgical technique. Nevertheless, similar success and recurrence rates were reported following muscular or subcutaneous grafting, as confirmed in our experience. CONCLUSIONS: Subcutaneous grafting was effective as muscular implantation, with comparable functional results, but avoiding its potential complications.


Subject(s)
Hyperparathyroidism, Secondary/surgery , Parathyroid Glands/transplantation , Parathyroidectomy , Adult , Aged , Biomarkers/blood , Female , Follow-Up Studies , Humans , Male , Middle Aged , Parathyroid Glands/surgery , Parathyroid Hormone/blood , Parathyroidectomy/methods , Quality of Life , Retrospective Studies , Treatment Outcome
17.
Haemophilia ; 20(1): 106-13, 2014 Jan.
Article in English | MEDLINE | ID: mdl-24112640

ABSTRACT

Factor XI (FXI) deficiency is a rare inherited bleeding disorder invariably caused by mutations in the FXI gene. The disorder is rather frequent in Ashkenazi Jews, in whom around 98% of the abnormal alleles is represented by Glu117X and Phe283Leu mutations. A wide heterogeneity of causative mutations has been previously reported in a few FXI deficient patients from Italy. In this article, we enlarge the knowledge on the genetic background of FXI deficiency in Italy. Over 4 years, 22 index cases, eight with severe deficiency and 14 with partial deficiency, have been evaluated. A total of 21 different mutations in 30 disease-associated alleles were identified, 10 of which were novel. Among them, a novel Asp556Gly dysfunctional mutation was also identified. Glu117X was also detected, as previously reported from other patients in Italy, while again Phe283Leu was not identified. A total of 34 heterozygous relatives were also identified. Bleeding tendency was present in very few cases, being inconsistently related to the severity of FXI deficiency in plasma. In conclusion, at variance with other populations, no single major founder effect is present in Italian patients with FXI deficiency.


Subject(s)
Factor XI Deficiency/genetics , Factor XI/genetics , Alternative Splicing , Amino Acid Sequence , Amino Acid Substitution , Factor XI/chemistry , Factor XI Deficiency/blood , Factor XI Deficiency/diagnosis , Female , Genetic Heterogeneity , Genotype , Humans , Italy , Male , Models, Molecular , Molecular Sequence Data , Mutation , Mutation, Missense , Open Reading Frames , Protein Conformation , Protein Stability , Sequence Alignment , White People/genetics
18.
Scand J Surg ; 102(2): 129-35, 2013.
Article in English | MEDLINE | ID: mdl-23820690

ABSTRACT

BACKGROUND AND AIMS: While in the past, thoracotomy represented the traditional surgical approach for the treatment of epiphrenic diverticula, actually mini-invasive approach seems to be the preferred treatment as many series have been published in the recent years. This article describes the authors' experience with the laparoscopic approach for performing diverticulectomy, myotomy, and Nissen-Rossetti fundoplication. MATERIAL AND METHODS: From 1994 to 2010, 21 patients (10 men and 11 women), mean age 58.5 years (range 45-74 years), with symptomatic epiphrenic diverticulum underwent laparoscopic diverticulectomy, myotomy and Nissen-Rossetti fundoplication. RESULTS: The mean operative time was 135 min (range = 105-190 min). Mean hospital stay was 14.2 days (range = 7-25 days). In 5 patients (23.8%), a partial suture staple line leak was observed. Conservative treatment achieved leak resolution in all the cases. One patient (4.8%) died of a myocardial infarction in the postoperative period. After a mean clinical follow-up period of 78 months (range = 6-192 months), excellent or good outcome was referred with no dysphagia in 16 patients (80%) and only mild occasional dysphagia in 4 patients (20%). CONCLUSIONS: Surgical treatment of epiphrenic diverticula remains a challenging procedure also by mini-invasive approach, with major morbidity and mortality rates. For this reason, indications must be restricted only to selected and symptomatic patients in specialized centers.


Subject(s)
Diverticulum, Esophageal/surgery , Esophageal Sphincter, Lower/surgery , Fundoplication/methods , Laparoscopy/methods , Aged , Female , Follow-Up Studies , Humans , Length of Stay , Male , Middle Aged , Operative Time , Surgical Stapling , Thoracotomy , Treatment Outcome
19.
G Chir ; 34(3): 82-5, 2013 Mar.
Article in English | MEDLINE | ID: mdl-23578412

ABSTRACT

Extra Ovarian Primary Peritoneal Carcinoma (EOPPC) is a rare type of adenocarcinoma of the pelvic and abdominal peritoneum. The objective examination and the histological aspect of the neoplasia virtually overlaps with that of ovarian carcinoma. The reported case is that of a 72 year-old patient who had undergone a total hysterectomy with bilateral annessiectomy surgery 20 years earlier subsequently to a diagnosis for uterine leiomyomatosis. The patient came to our attention presenting recurring abdominal pain, constipation, weight loss, severe asthenia and fever. Her blood test results showed hypochromic microcytic anemia and a remarkable increase CA125 marker levels. Instrumental diagnostics with Ultrasound (US) and CT scans indicated the presence of a single peritoneal mass (10-12 cm diameter) close to the great epiploon. The patient was operated through a midline abdominal incision and the mass was removed with the great omentum. No primary tumor was found anywhere else in the abdomen and in the pelvis. The operation lasted approximately 50 minutes. The post-operative course was normal and the patient was discharged four days later. The histological exam of the neoplasia, supported by immunohistochemical analysis, showed a significant positivity for CA 125, vimentin and cytocheratin, presence of psammoma bodies, and cytoarchitectural pattern resembling that of a serous ovarian carcinoma even in absence of primitiveness, leading to a final diagnosis of EOPPC. The patient later underwent six cycles of chemotherapy with paclitaxel (135 mg/m²/24 hr) in association with cisplatin (75mg/m²). At the fourth year follow-up no sign of relapse was observed.


Subject(s)
Carcinoma/diagnosis , Hysterectomy , Ovariectomy , Peritoneal Neoplasms/diagnosis , Aged , Female , Humans
20.
Int J Colorectal Dis ; 28(6): 783-93, 2013 Jun.
Article in English | MEDLINE | ID: mdl-22983757

ABSTRACT

PURPOSE: The purpose of this study was to examine short-term outcomes of rehabilitation treatment in patients with or without previous stapled transanal resection (STARR) for rectal outlet obstruction by using a novel rehabilitation score system (Brusciano score). METHODS: This is a retrospective cohort study conducted at a single tertiary referral institution including all patients with chronic functional constipation admitted to the outpatient unit from 2004 to 2009. RESULTS: Among 330 consecutive patients, 247 (74.8 %) (204 females and 43 males) showing a significantly higher rehabilitation score (mean of 15.7 ± 1.8; range, 7-25) than healthy controls (mean, 3.2 ± 1.2; range 2-6) (p < .0001) were selected for rehabilitation. Of the 247 patients evaluated, group A (no previous surgery) consisted of 170 patients (53 males; mean age, 44.8 ± 12.9 years; range, 19-80) of which 38 presented mixed constipation, whereas group B (previous surgery) consisted of 77 patients (18 males; mean age, 47.0 ± 11.2 years; range, 22-81). The Brusciano score, Agachan-Wexner score and quality of life improved in both groups of patients after treatment. Better improvements of Brusciano and Agachan-Wexner scores were observed in patients with previous STARR (group B). CONCLUSIONS: The rehabilitation score system employed in this study seems to be a useful tool in selecting and assessing the outcome of patients who might benefit from rehabilitation treatment. Constipation and quality of life were significantly improved by the rehabilitation treatment. Further studies are needed to clarify either the impact of rehabilitation treatment on long-term outcome of patients treated for rectal outlet obstruction or its role in those who develop problems over time.


Subject(s)
Digestive System Surgical Procedures/rehabilitation , Intestinal Obstruction/rehabilitation , Intestinal Obstruction/surgery , Rectal Diseases/rehabilitation , Rectal Diseases/surgery , Rectum/surgery , Surgical Stapling/rehabilitation , Adolescent , Adult , Aged , Aged, 80 and over , Case-Control Studies , Constipation/diagnostic imaging , Constipation/etiology , Defecography , Digestive System Surgical Procedures/adverse effects , Female , Humans , Intestinal Obstruction/physiopathology , Male , Manometry , Middle Aged , Rectal Diseases/physiopathology , Rectum/diagnostic imaging , Rectum/physiopathology , Surgical Stapling/adverse effects , Time Factors , Treatment Outcome , Young Adult
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