Dissertations / Theses on the topic 'Diagnosi clinica'

CLINICS IN THE LABORATORY An ethnography of uncertainty in prenatal diagnosis The research is an empirical investigation of scientific and medical uncertainty in the context of prenatal diagnosis. Combining sociology and anthropology of health with social studies of science and technology, its aim is to scrutinize the interaction between medicine and science in a clinical arena characterized by the fundamental role of scientific activity within the clinical laboratory. Modern medicine has evolved to a point where diagnostic judgements based on subjective evidence are progressively being supplanted by judgements based on objective evidence provided by laboratory procedures. Representing a typical example of geneticization of medicine, prenatal diagnosis is a pregnancy test based on devices and knowledge of genetics and, more specifically, cytogenetics. The hybrid character of prenatal diagnosis makes prenatal cytogenetic laboratories particularly uncertain and controversial. On the one hand, the role of laboratory data makes the scientific work critical in the process of decision-making. On the other hand, the scientific context of a cytogenetics laboratory is shaped and moulded by cultural, existential, juridical meanings, particular to clinical culture. Theoretically, this investigation draws upon the recent dialogue between two sociological disciplines illuminating their intersection and developing a new, innovative category in the sociology of medical science and technology. Uncertainty has been largely ignored or denied by medicine and science because of rationalist training and attitude. Social sciences’ scrutiny of work practices has demonstrated the distance between how these disciplines work in practice and the rhetoric of the official literature. Thus, the primary rationale of the methodological approach, which is inspired by qualitative analysis. In particular, the data came from ethnographic observations of the daily routines of physicians, biologists and technologists combined with informal and in-depth interviews of professionals as well as analysis of scientific documents such as articles, guidelines, protocols, and manuals The empirical analysis is structured in two main parts. First, a micro-social analysis is focused on laboratory procedures of manipulation and interpretation of biological samples. Uncertainty is a pervasive phenomenon which dominates the work practice of laboratory since it informs not only know-hows and professional identities, but also standardization programmes. Second, the analysis involves the articulation between the different social worlds which are part of the biomedial network. Comparing prenatal diagnosis to other biomedical platforms such as oncoematology, it demonstrates that uncertainty is embedded in the relationships between medical and scientific components. The suggestion is that the source, character, and amount of uncertainty is not merely technical, but it is negotiated and flexible. The social nature of uncertainty also means a more ambiguous definition of it. In fact, uncertainties are not merely a threat to practice, but they are also a resource which affords negotiation between identities of the different components of biomedical networks.<br>LA CLINICA NEL LABORATORIO Etnografia dell’incertezza nella diagnosi prenatale La ricerca prende le mosse dall’analisi empirica di un’area specifica della medicina, la diagnosi prenatale, caratterizzata dal ruolo fondamentale della componente scientifica di laboratorio, allo scopo di analizzare l’incertezza, un tema che accomuna sia gli studi sociali della salute che quelli della scienza e della tecnologia. Frutto della tendenza secolare, tipica della medicina moderna, ad inglobare saperi e strumenti aventi una genealogia scientifica, tale ambito medico rappresenta un caso esemplare di applicazione in campo sanitario di strumenti della scienza genetica e, più specificatamente, delle tecniche di analisi citogenetica. Il lavoro svolto dal laboratorio di citogenetica, una volta assunto un ruolo centrale in ambito sanitario, pur essendo fortemente caratterizzato dalla propria origine scientifica, risulta permeato e modellato da significati culturali e giuridici peculiari della medicina prenatale. Lo sforzo teorico è diretto a rielaborare prospettive analitiche su un argomento non certo nuovo, a partire dal dialogo tra due tradizioni sociologiche che, pur essendo state a lungo distanti, sembrano ora aver trovato diversi punti di contatto. Concepita dapprima in relazione ai processi decisionali medici, l’incertezza acquisisce successivamente una nuova centralità sociologica grazie allo studio empirico del lavoro scientifico, che dimostra il profondo iato tra la scienza che esiste in pratica e la scienza descritta nella letteratura. Da qui discende la scelta di un metodo ispirato a strumenti propri dell’indagine qualitativa, quali l’osservazione partecipante e l’intervista in profondità, orientati ad esplorare la dimensione lavorativa quotidiana nei diversi contesti medici e scientifici che compongono il network biomedico della diagnosi prenatale. Essendo rivolta unicamente al punto di vista dei professionisti, la ricerca si è svolta attraverso una graduale opera di avvicinamento alla prospettiva degli osservati, a partire dallo studio teorico della letteratura medico-scientifica di riferimento, dagli strumenti operativi quali le linee-guida e i protocolli, sino ad arrivare allo scambio di vedute in occasione della presentazione in un convegno scientifico di genetica. L’ibridizzazione tra medicina e scienza enfatizza un tratto comune alle pratiche di entrambi gli ambiti disciplinari, l’incertezza, studiata empiricamente da un duplice punto di vista. In primo luogo, si privilegia una prospettiva microsociale concentrata a ricostruire le strategie di addomesticamento dell’incertezza nella processazione e nell’interpretazione dei campioni biologici. Si intende così dimostrare come la pervasività dell’incertezza penetri in maniera costitutiva nel processo di soggettivazione professionale dei citogenetisti, nelle metodiche di analisi e, infine, nei programmi di standardizzazione. In secondo luogo, si allarga il campo di indagine all’articolazione delle diverse componenti che costituiscono tale piattaforma biomedica, comparandole con altre aree biomediche quali l’oncoematologia. Sia nelle relazioni tra i diversi elementi che compongono il laboratorio sia nelle relazioni tra i contesti medici e quelli scientifici, l’incertezza appare un fenomeno non esclusivamente di tipo tecnico, ma frutto di una percezione e di rappresentazioni che partecipano alla formazione tanto della cultura di un ambiente lavorativo quanto dello status professionale di chi vi lavora. L’incertezza risulta essere non solo un ostacolo, derivato dall’applicazione contestuale di regole generali, ma anche una risorsa di natura sociale, essenziale nell’articolare gli elementi eterogenei appartenenti ad una stessa rete.

An effective communication to children lead to a lower incidence of long-term psychopathological implications, such as lower levels of anxiety and distress, increases the child’s sense of control on the illness and furthers the expression of fears, suffers and anguishes. Moreover an effective diagnosis communication promotes the development of a trustful relationship between the physician and the child, a closer adherence to therapies and a consequently, and therefore bigger chance of healing, but also a higher quality of life and a lower incidence of relapses. Cancer can be defined as a “systemic” illness, that affect the all family; the psycological consequences of cancer diagnosis communication are similar for the ill child, parents and siblings, even when the child is a son of ill parents. In western medical culture a direct and clear communication of diagnosis, prognosis and treatment both to the child and the parents is considered to be a principle and above all a duty. However, it is well known from the literature that the communication process is strongly dependent from factors related to the cultural background, from the hospital environment and from the personal communicative style of each member of hospital staff. This manuscript describes three case studies which were performed and managed during a PhD. These research had the goal of investigate the topic of the diagnosis communication from different point of view, focusing on the ones from the parents of sick children, from the doctor and from parents affected by cancer. The aim of these studies was to identify the most common procedures used in different Italian hospitals and shed light on their effectiveness or disfunctions; the parents satisfaction was evaluated with reference to the diagnosis communication delivered to themselves and their children, both as parents of sick children and patients with children. Particular attention was given to physicians’ feelings and their communication skills as well as to the role of psychologists, the relationship with them and how these factors could influence the satisfaction level expressed.

BACKGROUND The exact incidence of cancer during gestation is yet to be determined but it is estimated that cancer occurs in 1 in 1000 pregnancies. The most common cancers in pregnancy are those with a peak incidence during the woman‘s reproductive period such as cancer of the breast and cervix, lymphoma, leukemia and melanoma. Cancer during pregnancy is a challenge about assistance and therapy, the aim of therapy in pregnancy is to give optimal treatment to the mother without harm to the fetus. After cancer diagnosis there are following problems such as the difficulty to stage it according usual criteria, the need to planner differentiated treatment, the need to delay or modify treatment in order to preserve the fetus, the risk of teratogenic effects of chemotherapy, the risk of fetal prematurity and so on. The aim of this study was to analyze the pregnancy outcome in a group of patients whit diagnosis of several malignancies during pregnancy. METHODS We retrospectively analyzed 34 patients who have been treated during pregnancy or after delivery because of several malignancies. Cancer was diagnosed at the moment of obstetric visit and all the patients were staged according to standard criteria pregnancy permitting. Serial visits were done by Oncologist and Obstetrician at the same time to take the relationship between pregnant state, cancer and therapeutic choices into account. Chemotherapy, when useful, was started in the second trimester. In all cases were done fetal monitoring and prematurity complications prophylaxis at viability age. Gestational age at delivery was established according to disease state and fetal risk of prematurity. Was avoided the neonatal spinal marrow aplasia attending two weeks from last chemotherapy course. Placental histology was studied in all cases about the presence of cancer cell or chemotherapy effect. RESULTS Surgery during pregnancy was performed in 27% of cases. Chemotherapy during pregnancy was given in 48% of cases. There were not cases of preeclampsia or stillbirth. 73% of patients delivered before 37 weeks of gestation, of them 42% delivered before 34 weeks of gestation in order to begin a therapy not indicated in pregnancy. The incidence of cesarean section was 73%. The incidence of neonates small for gestational age was 12%. There were not cases of congenital malformations. There were not cases of metastatic involvement of placenta. The neonatal outcome evaluated within 1 year from birth was good in all cases. The maternal mortality was 33% between 3-5 years after delivery. CONCLUSIONS Our data are in conformity with the Literature about the possibility to continue the pregnancy when cancer diagnosis. The possibility to receive in pregnancy chemotherapy in selected cases as standard of care is the assumption to have the same survival between the patients that interrupt the pregnancy and who not. According to advancement of perinatal care is possible to do delivery early, treating the patient with the therapy controindicated in pregnancy, without important complications after 32 weeks of gestation. All neonates had good outcome and follow-up, however the prematurity (69% advanced stage vs 25% early stage) was conditioned by cancer stage at the moment of diagnosis. In conclusion, the most important thing is to follow these patients into Specialized Hospital, taking care the cancer and the pregnancy at the same time.

La Realtà Aumentata è una tecnica di visualizzazione innovativa che, negli ultimi anni, ha subito un importante sviluppo grazie alla crescita tecnologica che caratterizza questo periodo; gli ambiti in cui ha trovato applicazione sono tra i più svariati, tra questi è possibile annoverare l’ambito educativo, militare, medico e molti altri. Lo scopo di questo elaborato è quello di mettere in risalto come l’ AR si sia sviluppata a partire dalle sue origini evidenziando gli strumenti, sia hardware che software, utilizzati per la sua implementazione e come questi si siano evoluti in risposta ad esigenze diverse degli utilizzatori dando particolare risalto al settore medico-sanitario che ha mostrato un interesse sempre più importante verso questa tecnologia. Verranno analizzate alcune tra le più innovative applicazioni di questa tecnica che hanno determinato una svolta nel trattamento dei pazienti mettendone in risalto le potenzialità sia in ambito diagnostico che terapeutico. Inoltre, sono stati identificati alcuni ambiti in cui la Realtà Aumentata non ha ancora trovato applicazione ma nei quali sarebbe in grado di garantire notevoli contributi alla pratica clinica favorendo il trattamento dei pazienti; nello specifico, data la sua alta diffusione nel mondo, verrà analizzata la patologia del rene policistico, verrà poi esaminato l’effetto dell’ AR sulla valutazione e il trattamento delle aritmie cardiache e infine, lo sviluppo più innovativo valutato riguarda la possibilità di realizzare un sistema di visualizzazione dinamica e tridimensionale per l’atrio; verrà analizzata l’implementazione del codice utilizzato per realizzare i modelli tridimensionali per ciascuna di queste applicazioni ed i risvolti clinici, sia sul paziente, sia sulla prassi clinica che la Realtà Aumentata permetterebbe di conseguire.

Dopo che il progetto sul genoma umano è stato completato nell'aprile del 2003, il flusso continuo di nuovi database e dati di sequenziamento ha iniziato a trasformare il campo della genomica in scienza basata sui dati. La bioinformatica analizza i dati sperimentali grezzi con l'obiettivo di ottenere informazioni che descrivono le condizioni biologiche misurate, fornendo così un potente strumento per studiare specifici meccanismi molecolari e genetici. Questa conoscenza deve essere combinata con la genomica per decifrare le interrelazioni tra geni, elementi regolatori, vie metaboliche e interazioni proteiche. L'apprendimento profondo, conosciuto come Deep Learning, e’ una sottodisciplina dell'apprendimento automatico, è stato recentemente applicato al campo della genomica, portando a risultati notevoli. I due obiettivi principali di questo lavoro sono: lo sviluppo e le applicazioni di strumenti bioinformatici che consentano lo studio delle basi genetiche della leucemia linfoblastica acuta e l'uso di tecniche di apprendimento profondo per l'identificazione di piccoli elementi di RNA non codificanti del genoma umano. Questa tesi fornisce al lettore una panoramica completa della recente evoluzione della genomica come campo interdisciplinare di ricerca strettamente connesso con l'informatica e l'analisi dei dati.<br>After the completion of the human genome project in April 2003, the continuous flow of sequencing data and the development of new databases began to transform the field of genomics into data-driven science. Bioinformatics analyses raw experimental data with the aim to obtain information describing biological processes, thus providing a powerful tool to investigate specific molecular and genetic mechanisms. This domain knowledge in combination with genomics allows to decipher the interrelationships between genes, regulatory elements, metabolic pathways, and protein interactions. Deep learning, a subdiscipline of machine learning, has been recently applied to the field of genomics, leading to remarkable results. The two main objectives of this study were: the development and application of bioinformatic tools for the study of the genetic basis of acute lymphoblastic leukaemia, and the usage of deep learning techniques for the identification of small non-coding RNA elements in the human genome. This dissertation provides a comprehensive overview of the recent evolution of genomics as an interdisciplinary field of research strongly associated with computer science and data analysis.

Lo studio utilizza un disegno longitudinale a misure ripetute per la valutazione process-outcome di un rolling groups psicodinamico per pazienti con diagnosi di abuso di cocaina. La terapia condotta su 18 pazienti è stata effettuata all’interno del Centro Clinico Cocainomani dell’ASP di Brescia. Gli strumenti utilizzati sono: DAST-20, OQ-45, DSQ, CALPAS Group, GMLCS. Le analisi condotte attraverso il Multilevel Models evidenziano dei miglioramenti attendibili sia rispetto al sintomo che riguardo al funzionamento psicologico e all’assetto difensivo. La lunghezza della partecipazione alla terapia e la stabilità del gruppo influenzano l’esito. I pazienti che restano di più in trattamento sperimentano una maggiore qualità delle relazioni all’interno del gruppo. Diversamente l’alleanza dell’individuo è influenzata dalle modificazioni del legame del gruppo nel corso del tempo.

lo studio è stato effettuato su 7 pazienti tutti con segni e sintomi riconducibili a deiscenza del canale semicircolare superiore.Valutati con esami della funzionalità vestibolare(in particolare VEMPs) e tc scans ad alta risoluzione.Si è visto che ai VEMPs spessa il ruolo diagnostico principale.

Secondo un recente rapporto dell’Organizzazione Mondiale della Sanità un miliardo di persone, distribuite in tutto il mondo, vive con una malattia neurologica, con 50 milioni di casi di epilessia e 24 milioni di casi di demenza questi ultimi destinati ad aumentare fino a 114 milioni nel 2050, soprattutto per quanto riguarda la malattia di Alzheimer (AD) e la demenza vascolare (VD) che rappresentano le due forme principali, giustificando la prima il 50% e la seconda circa il 20% di tutte le cause di demenza. Nello scenario preoccupante di questa grossa diffusione si inserisce la difficoltà di una diagnosi precoce la quale avrebbe indubbi vantaggi per assicurare interventi tempestivi. Nella fase iniziale è difficile distinguere i sintomi della demenza da un normale invecchiamento, nonché distinguere AD,VD e depressione in quanti i sintomi iniziali sono molto simili. Gli attuali criteri per la diagnosi di AD e VD fanno riferimento ad alcune linee guida e seguono un iter diagnostico basato su test neuropsicologici e test di neuroimaging che però non sono sufficienti per una diagnosi precoce. Si cerca infatti di individuare marker diagnostici correlati al danno cerebrale che avviene in queste patologie, ossia la morte neuronale. Tra i possibili marker, sta suscitando particolare interesse il 24S-idrossicolestrolo, un ossisterolo, principale metabolita del colesterolo a livello del SNC che passando attraverso la barriera ematoencefalica si immette nella circolazione sistemica. Essendo il 24S-idrossicolesterolo di sola origine cerebrale, una sua variazione di concentrazione nel sangue di pazienti patologici rispetto ai normali riflette un’alterata omeostasi del colesterolo a livello del sistema nervoso centrale come conseguenza del danno neurologico. Scopo di questo lavoro è stato quindi quello di sviluppare e validare un metodo analitico in LC-MS/MS per il dosaggio del 24S-idrossi nel siero con successiva applicazione all’analisi di campioni controllo e patologici e precisamente di 20 pazienti affetti da Alzheimer ad insorgenza tardiva (LOAD), 20 pazienti affetti da VD e 20 pazienti con Mild Cognitive Impariment (MCI), uno stadio preclinico di demenza. I risultati mostrano una diminuzione significativa dei valori medi di 24S-idrossicolesterolo nei pazienti con AD e VD rispetto ai controlli, mentre un aumento nei pazienti con MCI. Una differenza poco significativa è stata evidenziata tra pazienti AD e LOAD.<br>According to a recent WHO report, there is 1 billion of people spread all over the world, living with a neurological diseases, in particular 50 million of cases of epilepsy and 24 cases of dementia, that will increase to 114 million within the 2050, especially for Alzheimer’s disease (AD) and vascular dementia (VD), the two main forms of dementia. Alzheimer’s disease represents 50% and vascular dementia 20% of all dementia cases. In the worrying scenario of this wide diffusion there is also a difficulty of early diagnosis that could have got clear advantages to ensure timely intervention. In the early stage is difficult to distinguish symptoms of dementia from a normal ageing as well to distinguish AD from VD and depression. The current standards for dementia diagnosis refer to some guidelines and follow a diagnostic procedure based on neuropsychological and neuroimaging tests that are however not sufficient for early diagnosis. Try to find diagnostic markers linked to brain damage that happens in this kind of pathologies, that is neuronal death. Between the possible markers, it is of great interest 24s-Hydroxycholesterol, oxysterol, the main cholesterol metabolites in the CNS that goes into systemic circulation through the haematoencephalic barrier. The simple variation of concentration of 24S- Hydroxycholesterol, produced only by the brain, in the blood of pathologic patients compared to healthy people entail an altered cholesterol homeostasis in CNS as a consequence of brain damage. The main purpose of this work is to develop and support an analytic method in LC-MS/MS for the serum 24S- Hydroxycholesterol dosage with following application to the analysis of control and pathologic samples (20 persons suffering from late beginning Alzheimer’s disease, 20 persons suffering from VD and 20 persons with MCI, a preclinical dementia stage). The results prove a significant fall in 24S- Hydroxycholesterol average values between people suffering from AD and VD compared to controls, and an increase between sufferers from MCI. A negligible difference has been picked out between AD and LOAD patients.

Footrot is a disease which has been known for approaching 200 years, and by the first half of the 18th century it was known to be infectious. The disease is characterised by lameness originating from severe pain in the foot, with important consequences on productivity and animal welfare. Despite substantial progresses have been made with regard to aetiology, pathogenesis and control strategies, footrot is still widespread in several sheep producing countries, including Italy. This is certainly true in the Author’ s experience as a sheep veterinary practitioner in Central Italy. The Introduction reviews current knowledge on footrot aetiology, epidemiology, pathogenesis, clinical signs, diagnostics and control strategies. Elements of infrared thermography and its use as a diagnostic tool in veterinary medicine, with particular reference to lameness are presented. Two studies, aimed at establishing circadian rhythms of the temperature by thermography of the interdigital space in healthy sheep and sheep affected by footrot, are presented in the experimental section. This was meant to be a preliminary contribution at establishing a “normal” temperature range of this area, ultimately aiming at being able to detect deviation from this range during inflammatory abnormalities of the foot for diagnostic purposes. In Study 1, 360 thermoghaphic images of the interdigital space and the rectal temperature were obtained from 10 healthy sheep every 3 hours during 24 hours observation period. In Study 2, 32 sheep affected by footrot were similarly sampled on day 0 and 14. Study 1 showed a statistically significant effect of time over the monitored temperatures, confirming how important it is to consider circadian rhythmicity of the superficial skin temperature whilst establishing a normal range.<br>La pedaina è una malattia nota da oltre 200 anni, la cui contaggiosità è riconosciuta dalla prima metà del 1800, caratterizzata da zoppia podale su base algica e forti ricadute sulla produttività ed il benessere animale. Nonostante i progressi compiuti sugli aspetti eziologici, patogenetici e sulle strategie di controllo della malattia, la stessa è ancora molto diffusa nei Paesi con popolazioni ovine di rilievo, inclusa l'Italia. Questa è certamente l’ esperienza professionale dell'Autore nel corso della pratica clinica veterinaria svolta in Italia centrale. La parte introduttiva fornisce una rassegna approfondita delle conoscenze attuali sulla pedaina, trattando elementi di eziologia, epidemiologia, patogenesi, segni clinici, diagnosi e metodi di controllo della malattia. Vengono quindi forniti elementi di termografia ad infrarossi e la sua applicazione in ambito diagnostico veterinario, specificamente nella diagnosi di zoppia. Nella parte sperimentale vengono descritti due studi volti alla determinazione tramite rilievo termografico di possibili ritmi circadiani della temperatura cutanea interdigitale del piede ovino sano ed affetto da pedaina virulenta tramite. Si vuole contribuire preliminarmente alla determinazione di un range di temperatura “normale” di questa area, così da poter poi rilevare a fini diagnostici eventuali variazioni del range in corso di patologie infiammatorie podali. Nello Studio 1 si sono ottenuti 360 termogrammi dello spazio interdigitale di 10 pecore sane, insieme alla temperatura rettale, ogni 3 ore nell’arco delle 24 ore. Nello Studio 2, si sono campionate 32 pecore affette da pedaina ottenendo 128 termogrammi ai giorno 0 e 14. Lo Studio 1 ha messo in evidenza un effetto statisticamente significativo del tempo sulla temperatura monitorata, confermando la necessità di considerare la ritmicità circadiana della temperatura superficiale cutanea ogni qualvolta se ne voglia determinare un range di normalità.

Background: Asymmetric dimethylarginine (ADMA), an endogenous nitric oxide (NO) formation inhibitor, has emerged as a promising biomarker of NO-associated endothelial dysfunction in cardiovascular diseases as well in chronic renal failure and pre-eclampsia but only recently this amino acid was associated also to the pathogenesis of some respiratory diseases, such asthma and cystic fibrosis. Although ADMA is an established marker of endothelial dysfunction in adults its biological relevance in the pediatric age is still unclear. Theoretically, due to its interference with nitric oxide (NO) production, ADMA might be involved in the pathogenesis of several disorders originating early in life. Interest has been specially focused on its potential role in neonatal lung biology, as NO is a critical regulator of lung morphogenesis and homeostasis. ADMA has been indicated as a mediator of the physiologically high pulmonary vascular resistance during fetal life, and implicated in the pathogenesis of persistent pulmonary hypertension of the newborn. Thus, there is considerable demand for a specific, sensitive and rapid method for ADMA and related metabolites for quantitative determination in biological fluids of adults with NO related disorders and preterm newborn involving in clinical study for diagnosis of cardiovascular and pulmonary diseases. The interest in potentially fundamental role of this metabolite, in basic and clinical research, led to the development of numerous analytical methods for the quantitative determination of ADMA and dimethylarginines in biological systems, notably plasma, serum and urine, but not, at the moment, in exhaled breath condensate (EBC), which is a potential rich source for countless biomarkers that can provide valuable information about respiratory as well as systemic diseases. EBC is obtained as breath exhaled from the lungs into a cooled collecting device, thereby condensing the vapor and aerosolized droplets emerging with the breath. Quantification of ADMA and related metabolites was made by several methods based on HPLC, coupled with fluorescence and mass spectrometric methods such as LC–MS/MS and GC–MS, capillary electrophoresis and ELISA. Moreover to apply the method in pediatric clinical research is very important to have a small volume of sample used for analysis, especially for plasma and serum. Objectives: The aim of this thesis was finalized to applied the method, created and validated in our laboratory, for simultaneous determination of arginine, ADMA, SDMA, NMMA, homo-arginine and citrulline in plasma samples of healthy adults and patients with different pathologies such as hyperglycemia, heart diseases and pre-eclampsia, and in plasma and serum of term and preterm newborns. To evaluate if ADMA is detectable in exhaled breath condensate of asthmatic and healthy children, we developed an alternative technique that can enhance our UPLC/MS/MS method in term of sensitivity using large injection volumes enriched online in a trap column that would compensate for the possible dilution effects in EBC samples. Methods: The method was characterized by simple and rapid preparation, short time analysis, accurate quantification on different biological matrices (plasma, serum and EBC) using stable isotope labeled internal standard and very low amount of sample by Ultrahigh-Performance Liquid Chromatography (UPLC) run coupled with electrospray ionization (ESI) in the positive mode tandem mass spectrometry detection. We measured circulating ADMA and related compounds concentrations in a group of very premature newborns at birth and during the first week of life. We enrolled different type of pathologic populations versus normal populations: adult control group was constituted of 36 healthy subject (18 males and 18 females, medium age 36.5 years) and 15 women in normal pregnancy (medium age of 32 years); and pathologic population was constituted of 15 women with pre-eclamptic pregnancy (medium age of 32 years), 20 subjects with heart diseases (10 males and 10 females, medium age of 75.5 years) and 30 hyperglycemic patients (16 males and 14 females, medium age 71 years). In pediatric field we enrolled a group of 31 extremely low birth weight (ELBW) newborns versus 30 term newborn to evaluate whether ADMA levels correlate with specific perinatal/neonatal risk factors or short-term outcome indicators; and EBC samples from a group of 29 children with asthma 5,8 to 16,3 years old and 62 healthy controls 5,1 to 15,4 years old. Results and conclusions: In healthy adults plasma and serum we did not found appreciable differences in concentration of ADMA and related metabolites, except for Arg and relative ratio versus ADMA, that appeared higher more than 60% in serum than in plasma. In adult subjects with heart diseases ADMA and SDMA values were respectively of 0.89±0.17µM and 0.72±0.26µM, significantly higher than normal controls (p<0.05); hyperglycemic subjects, instead have shown ADMA levels of 0.47±0.13µM significantly lower (p=0.002) than healthy subjects. There was any significant difference in SDMA concentrations between two studied populations. We observed that ADMA concentrations are significantly lower in pregnant pre-eclamptic women than in the control group at the time of delivery, but these data have some important limitation, owing to the small number of subjects enrolled and to the possible confounding effects of anti-hypertensive therapy in the pre-eclamptic group. In ELBW newborns ADMA, NMMA and SDMA concentrations remained stable from delivery to day 7 and were not dependent on gender, gestational age or birth weight. ADMA levels resulted significantly higher in infants born to mothers with histologic chorioamnionitis than in infants delivered for other maternal or fetal indications. We speculate that ADMA might be involved in the complex biological events associated with fetal exposure to chorioamnionitis. In this thesis, was also developed and validated a sensitive and selective method for the quantification of ADMA, arginine, SDMA, NMMA, citrulline, homo-arginine, tyrosine and nitrotyrosine simultaneously, in human EBC based on UPLC–MS/MS enrichment technology. Actually, do not exist in literature, any analytical method to detect ADMA and its related compounds in EBC human samples. The assay demonstrated excellent accuracy, precision, linearity and specificity for the intended clinical purpose and a good reproducibility of method of collection, demonstring that it is possible to measure ADMA in exhaled breath condensate. EBC ADMA values in asthmatic children (median value 2,17 [1,15-3,19] µmol/mL) were significantly higher than in healthy children (median value 1,1 [0,7-1,5] µmol/mL, p<0,001) and in the asthmatic group ADMA values were significantly correlated with inhaled corticosteroids dosage ICS (p=0,005; r=0,406). Conclusions: The UPLC-ESI/MS/MS method applied at adult populations with different NO-related endothelial dysfunctions, confirmed data from the literature. The fast run time, the feasibility of high sample throughput and the small amount of sample required make this method very suitable for routine analysis in the clinical setting. Preliminary data on neonatal and pediatric field, show that this method is a very good analytical tool for study dimethylarginines and their metabolism in healthy and disease conditions, it particularly suitable for future applications in the pediatric medicine. These data focus on ADMA as a biologically active molecule associated to exposure to antenatal inflammation, and we suggest its role deserves further investigation in larger clinical studies or appropriate experimental models. This was, also, the first study that demonstrates ADMA dosage feasibility in exhaled breath condensate, showing that ADMA is increased in asthma and has a possible role in asthmatic inflammation. Further studies will clarify the role of ADMA as a biomarker of asthmatic inflammation and a possible target for new pharmacological approaches.<br>Presupposti: L' ADMA, dimetilarginina asimmetrica, è un analogo metilato dell'aminoacido arginina. Essa viene prodotta all'interno delle cellule attraverso processi di metilazione di catene polipeptidiche e rilasciata in circolo dopo proteolisi. L'ADMA compete con l'arginina, precursore necessario per la sintesi dell'ossido nitrico, per il legame con l'enzima ossido nitrico sintetasi (NOS), inibendone così la sintesi. L’NO è il più potente vasodilatatore conosciuto, che svolge un ruolo chiave, agendo sul sistema endoteliale, nel mantenimento di una grande varietà  di meccanismi omeostatici del nostro organismo. E' noto da tempo che l'ADMA, per inibizione della produzione di NO, è coinvolta nella patogenesi delle principali disfunzioni indotte da stress ossidativo NO-dipendente a livello cardiovascolare, renale e recentemente anche nell'ambito delle malattie respiratorie come l'asma e la fibrosi cistica, in quanto contribuisce ad aggravare lo stato infiammatorio e l'iperreattività  delle vie aeree. Analizzando i dati riportati in letteratura, si è notato che non vi sono studi longitudinali sulle concentrazioni di ADMA in età neonatale, sia nei soggetti a termine che in quelli prematuri, né sono stati ad oggi dosati i livelli di ADMA nel condensato dell'aria espirata, che si ritiene essere un biofluido la cui composizione riflette quella del liquido di superficie delle vie aeree, oltre ad essere caratterizzato dalla non invasività  e la semplicità  nell'esecuzione della metodica di prelievo. Scopo dello studio: il presente lavoro ha avuto in primo luogo lo scopo di applicare il metodo UPLC-ESI-MS/MS messo a punto nel nostro laboratorio, su una popolazione di adulti sani al fine di verificare la validità  della metodica, confermando i dati esistenti in letteratura. Si è poi passati all'applicazione su soggetti adulti affetti da diverse patologie (iperglicemia, cardiopatie, preeclampsia) per verificarne l'applicabilità  in ambito clinico, ed infine è stata presa in considerazione la popolazione pediatrica, determinando in maniera longitudinale la concentrazione sierica di ADMA e delle altre arginine metilate (SDMA, NMMA) in un gruppo di neonati a termine in prima e terza giornata di vita e in un gruppo di neonati pretermine di peso neonatale estremamente basso (< 1000 g - ELBW) durante il primo mese di vita. Per quanto riguarda lo studio delle malattie respiratorie lo scopo è stato quello di valutare se l'ADMA è dosabile nel condensato dell'aria espirata in bambini affetti da asma in buon controllo, con o senza terapia, confrontati con un gruppo di bambini sani e verificare la riproducibilità della metodica di analisi dell'ADMA sull'EBC. Materiali e metodi: La determinazione quantitativa è stata effettuata attraverso una separazione cromatografica in UPLC e analisi dei campioni mediante uno spettrometro di massa a triplo quadrupolo. Le caratteristiche del metodo sono costituite dall'utilizzo di quantità  esigue di campione, elevata specificità  e sensibilità  strumentale. Per poter ricavare i valori di riferimento della popolazione adulta sono stati arruolati 36 soggetti sani (18 uomini e 18 donne di età  media pari a 36.5 anni) come gruppo di controllo rispetto a pazienti con infarto miocardico (20 soggetti di cui 10 uomini e 10 donne di età  media pari a 75.5 anni) e diabete di tipo II insulino resistente (30 soggetti di cui 16 uomini e 14 donne di età  media pari a 71 anni). Lo studio sulle donne in gravidanza ha previsto l'arruolamento di 15 donne affette da pre-eclampsia confrontate con 15 donne in gravidanza normale (età  media 32 anni per entrambi i gruppi). L'applicazione in ambito pediatrico ha infine coinvolto un gruppo di 31 neonati di peso estremamente basso alla nascita (ELBW <1000 grammi) rispetto al gruppo di controllo di 30 neonati sani a termine, e un gruppo di 29 bambini asmatici di età compresa tra 5,8 e 16,3 anni confrontati con i relativi controlli sani (62 bambini di età  compresa tra 5,1 e 15,4 anni), di cui è stato raccolto il condensato dell'aria espirata. Risultati: I valori dei diversi metaboliti ottenuti sui soggetti adulti sani hanno confermato i dati riportati in letteratura, mentre nei soggetti cardiopatici le concentrazioni di ADMA ed SDMA sono state rispettivamente pari a 0.89±0.17µM e 0.72±0.26µM , risultando entrambi significativamente più alti rispetto ai controlli sani (p<0.05), a differenza invece dei soggetti iperglicemici che hanno mostrato livelli significativamente inferiori (p=0.002) di ADMA (0.47±0.13µM) rispetto ai relativi controlli, ma nessuna differenza nelle concentrazioni di SDMA. Il confronto tra donne gravide sane e con pre-eclampsia, ha invece evidenziato che la concentrazione di ADMA al momento del ricovero è stata significativamente più bassa nelle gravide ipertese rispetto alle gravide normotese (p=0.006), contrariamente a quanto riportato in letteratura, mentre a 30 giorni di distanza dal parto la situazione si è invertita. Nel gruppo dei neonati a termine, l'ADMA in prima giornata è risultata estremamente elevata, all'incirca 2-3 volte maggiore rispetto agli adulti. La sua concentrazione è diminuita rapidamente, riducendosi già  del 25% in terza giornata di vita. Nei soggetti pretermine di peso estremamente basso il dosaggio di ADMA è risultato sensibilmente più basso rispetto ai neonati a termine senza variazioni nel tempo. Considerando insieme i due gruppi di neonati, è presente una correlazione significativa tra valori di ADMA in prima ed in terza giornata e l'età  gestazionale, nonché il peso neonatale. Lo studio condotto sull'EBC ha, infine dimostrato che è possibile misurare l'ADMA nel condensato con una buona riproducibilità  intrasoggetto a distanza di 24 ore. I valori di ADMA nei bambini asmatici (mediana 2,17 [1,15-3,19] µmol/mL) sono risultati significativamente più elevati rispetto a quelli dei bambini sani (mediana 1,1 [0,7-1,5] µmol/mL, p<0,001) evidenziando anche una significativa correlazione dei livelli di questo metabolita con il dosaggio dei farmaci corticosteroidei inalatori ICS (p=0,005; r=0,406) assunti dai soggetti asmatici. Conclusioni: Il metodo sviluppato in questo studio soddisfa i requisiti analitici di precisione, riproducibilità , specificità , sensibilità  e recupero analitico indispensabili per l'impiego in ambito clinico. Esso inoltre può essere facilmente automatizzabile e adatto per il suo impiego su larga scala consentendo l'applicazione in qualità  di metodo diagnostico nell'ambito delle patologie da stress ossidativo e disfunzione endoteliale e delle malattie cardiovascolari. L'uso di una quantità  esigua di campione, inoltre ne suggerisce l'impiego per lo studio delle diverse patologie del neonato come la sepsi, l'ipertensione polmonare e lo scompenso cardiaco. Infine, essendo questo il primo studio che dimostra la fattibilità  del dosaggio dell'ADMA e dei biomarker di stress ossidativo nel condensato dell'aria espirata, ottenendo risultati concordanti con lavori precedenti che dimostravano un aumento di ADMA nell'asma in altre matrici biologiche, ci sono i presupposti per estendere la casistica per confermare il suo possibile ruolo come biomarker nell'infiammazione asmatica e come possibile target di nuovi approcci farmacologici.

The research moves from a postmodern paradigm and from the theoretical perspectives of Symbolic Interactionism (Mead, 1934; Blumer, 1969) and of Social Constructionism (Gergen, 1985; Berger e Luckmann, 1966). According to this theoretical framework, the different aspects related to identities and gender are considered plural and mutable processes of construction, historically and culturally situated and interconnected to the dimensions of the discourse and narratives, of doing and of the performance in every context of daily life (West e Zimmerman, 1987; Denzin, 2003; Salvini, 2011). There are three main objectives of the research and they concern the analysis of the discursive processes of construction of the identity related to the biographies and the narratives of gender transitions; the analysis of the discursive processes connected to the mental health professionals’ practices related to gender transitions, the diagnostic process and the psychological services, as well as possible attributions of sense on the interlocutors’ biographies by mental health professionals; and the reflection on the implications of such discursive processes and narratives in the psychological and psychiatric practices and in the processes of negotiation of meanings among professionals and people in transition, on the light of the complexity of the narratives and the exigencies of people. Narrative interviews (Hermanns, 2004) with 25 people in transition and episodic interviews (Flick, 2007) with 11 professional figures have been deployed. Both types of interviews allow to highlight points of view and personal theories used by the participants to give sense to the process of gender transition and the own experience, told and reconstructed in the dialogue. The methods for the analysis have included discourse analysis (Potter e Wheterell, 1987) and narrative analysis, in particular the version of dialogic-performative analysis (Riessman, 2008), through the identification of interpretive repertoires and self-positions. Narrative and discursive processes have been analyzed underlying the pragmatic and performative elements and the multivoiceness, mine included, as researcher in relation to the others. From the analysis of the interviews, different voices and discourses related to the own biography, as well as to the practices by the professionals, emerge. For the first objective, different narrative and discursive modalities underlie the impact and the pragmatic effect of some dimensions of meaning, such as those related to the ideal or reconstructed “normality”, to the “right-wrong body”, to the deterministic “nature”, to the interpersonal “recognition”, to “pathology” or “deviance” and finally, to the agency and the idiosyncraticity in the construction of the identity. For the second objective, it is possible to underlie the impact and the pragmatic effect of other dimensions of meaning, such as “gender dysphoria” as an ambiguous category, the “adaptation to reality” as an assumption in the transition, “subjectivity versus objectivity”, the “non-binary people” as a dilemma and finally, the “responsibility” and the “power” as critical and relevant aspects in the clinical practice. This research can contribute to highlight the narrative specificities and the exigencies of both groups, and in particular of the people in transition. This can be useful in order to inform and to offer further elements for the comprehension of trans experiences and life stories in the clinical field, problematizing the concept of diagnosis. Finally, the results can contribute to a reflexive knowledge of the clinical work for the gender transition, referring to the different modalities of signify both the diagnosis and the relationship and their pragmatic effects.<br>La ricerca muove da un paradigma epistemologico postmoderno e assume le prospettive dell’interazionismo simbolico (Mead, 1934; Blumer, 1969) e del costruzionismo sociale (Gergen, 1985; Berger e Luckmann, 1966) come cornici teoriche generali della ricerca. I diversi aspetti legati alle identità̀ e al genere sono letti come processi di costruzione plurali e mutevoli, storicamente e culturalmente collocati e legati alle dimensioni del discorso e delle narrazioni, del fare e della performatività in ogni contesto della vita quotidiana (West e Zimmerman, 1987; Denzin, 2003; Salvini, 2011). Tre sono gli obiettivi principali della ricerca e riguardano l’analisi dei processi discorsivi di costruzione dell’identità̀ legati ai percorsi di transizione di genere e alle biografie da parte delle persone in transito; l’analisi dei processi discorsivi legati alle pratiche dei/lle professionisti/e inerenti ai percorsi di transizione di genere, il processo diagnostico e i servizi psicologici, nonché́ possibili attribuzioni di senso sulle biografie degli interlocutori da parte dei/lle professionisti/e della salute mentale e infine, la riflessione sulle implicazioni di tali processi discorsivi nelle pratiche e nei processi di negoziazione di significati tra professionisti e persone in transito, alla luce della complessità̀ delle narrazioni ed esigenze di questi ultimi. Sono state condivise interviste narrative (Hermanns, 2004) con 25 persone in transito e interviste episodiche con 11 professionisti/e della salute mentale (Flick, 2007). Entrambe le forme di intervista consentono di mettere in luce i punti di vista soggettivi e le teorie personali usate dalle persone per dare senso ai diversi aspetti del proprio percorso e della propria esperienza, raccontati e ricostruiti nel dialogo. I metodi di analisi scelti in questa ricerca hanno compreso l’analisi del discorso (Potter e Wheterell, 1987) e l’analisi dialogico-performativa (Riessman, 2008), attraverso l’individuazione di repertori interpretativi e posizionamenti identitari. I processi narrativi e discorsivi sono stati analizzati mettendone in risalto gli aspetti pragmatici e performativi, sottolineandone la multivocalità̀, compresa la mia voce come ricercatrice in relazione. Dall’analisi delle interviste emerge come diverse siano le voci e i discorsi che le persone raccontano e che mettono in relazione alla propria biografia, così come alle pratiche da parte dei/lle professionisti/e. Per la prima linea di indagine, diverse modalità̀ narrative e discorsive emergenti mettono in luce la portata e gli effetti pragmatici di diverse dimensioni di senso, ad esempio, relative alla “normalità̀” ideale o ricostruita, “al corpo giusto-sbagliato”, alla “natura” determinante, al “riconoscimento” interpersonale, alla “malattia” o alla “devianza” e infine, alla scelta intenzionale e alla soggettività̀ nella costruzione della propria identità. Per la seconda linea di indagine si possono mettere in luce la portata e gli effetti pragmatici di altre dimensioni di senso, ad esempio, la “disforia” come categoria ambigua, “l’adattamento alla realtà̀” come presupposto della transizione, “soggettività̀ versus oggettività̀”, la “non binarietà̀ come dilemma” e infine, “la responsabilità̀ e il potere” come aspetti critici e rilevanti nella pratica operativa. Questa ricerca può̀ pertanto contribuire a mettere in luce le specificità̀ narrative e le esigenze di entrambi i gruppi, e in particolare delle persone in transito. Ciò̀ può̀ essere utile al fine di informare e offrire elementi ulteriori per la comprensione delle esperienze delle persone in transito nell’ambito clinico, problematizzando il costrutto della diagnosi. Infine, i risultati possono contribuire ad una comprensione riflessiva del lavoro clinico per la transizione di genere, in riferimento ai diversi modi di significare sia la diagnosi sia la relazione e ai loro effetti pragmatici.

“Naturally occurring cancers in pet dogs and humans share many features, including histological appearance, tumour genetics, molecular targets, biological behaviour and response to conventional therapies. Studying dogs with cancer is likely to provide a valuable perspective that is distinct from that generated by the study of human or rodent cancers alone. The value of this opportunity has been increasingly recognized in the field of cancer research for the identification of cancer-associated genes, the study of environmental risk factors, understanding tumour biology and progression, and, perhaps most importantly, the evaluation and development of novel cancer therapeutics”.(Paoloni and Khanna, 2008) In last years, the author has investigated some molecular features of cancer in dogs. The Thesis is articulated in two main sections. In section 1, the preliminary results of a research project aimed at investigating the role of somatic mutations of Ataxia-Telangiectasia mutated (ATM) gene in predisposing to cancer in boxer dogs, are presented. The canine boxer breed may be considered an unique opportunity to disclose the role of ATM somatic mutation since boxer dogs are known to be dramatically susceptible to cancer and since they may be considered a closed gene pool. Furthermore, dogs share with human the some environment. Overall, the abovementioned features could be considered extremely useful for our purposes. In the section 2, the results of our studies aimed at setting up accurate and sensitive molecular assays for diagnosing and assessing minimal residual disease in lymphoproliferative disorders of dogs, are presented. The results of those molecular assay may be directly translated in the field of Veterinary practice as well as the may be used to improve our objective evaluation of new investigational drugs effectiveness in canine cancer trials.

“Naturally occurring cancers in pet dogs and humans share many features, including histological appearance, tumour genetics, molecular targets, biological behaviour and response to conventional therapies. Studying dogs with cancer is likely to provide a valuable perspective that is distinct from that generated by the study of human or rodent cancers alone. The value of this opportunity has been increasingly recognized in the field of cancer research for the identification of cancer-associated genes, the study of environmental risk factors, understanding tumour biology and progression, and, perhaps most importantly, the evaluation and development of novel cancer therapeutics”.(Paoloni and Khanna, 2008) In last years, the author has investigated some molecular features of cancer in dogs. The Thesis is articulated in two main sections. In section 1, the preliminary results of a research project aimed at investigating the role of somatic mutations of Ataxia-Telangiectasia mutated (ATM) gene in predisposing to cancer in boxer dogs, are presented. The canine boxer breed may be considered an unique opportunity to disclose the role of ATM somatic mutation since boxer dogs are known to be dramatically susceptible to cancer and since they may be considered a closed gene pool. Furthermore, dogs share with human the some environment. Overall, the abovementioned features could be considered extremely useful for our purposes. In the section 2, the results of our studies aimed at setting up accurate and sensitive molecular assays for diagnosing and assessing minimal residual disease in lymphoproliferative disorders of dogs, are presented. The results of those molecular assay may be directly translated in the field of Veterinary practice as well as the may be used to improve our objective evaluation of new investigational drugs effectiveness in canine cancer trials.

Il carcinoma epatocellulare (HCC) rappresenta il tumore epatico primitivo più comune con una incidenza fino all’85%. È uno dei tumori più frequenti al mondo ed è noto per l’elevata letalità soprattutto in stadio avanzato. La diagnosi precoce attraverso la sorveglianza ecografica è necessaria per migliorare la sopravvivenza dei pazienti a rischio. Il mezzo di contrasto ecografico migliora la sensibilità e la specificità diagnostica dell’ecografia convenzionale. L’ecografia con mezzo di contrasto (contrast-enhanced ultrasound, CEUS) è pertanto considerata una metodica valida per la diagnosi di HCC a livello globale per la sua ottima specificità anche a fronte di una sensibilità subottimale. L’aspetto contrastografico delle lesioni focali epatiche ha portato un team di esperti allo sviluppo del sistema Liver Imaging Reporting and Data System (LI-RADS) con l’obiettivo di standardizzare la raccolta dati e la refertazione delle metodiche di imaging per la diagnosi di HCC. La CEUS è una metodica operatore-dipendente e le discordanze diagnostiche con gli imaging panoramici lasciano spazio a nuove tecniche (Dynamic Contrast Enhanced UltraSound, DCE-US) volte a migliorare l’accuratezza diagnostica della metodica e in particolare la sensibilità. Un software di quantificazione della perfusione tissutale potrebbe essere di aiuto nella pratica clinica per individuare il wash-out non visibile anche all’occhio dell’operatore più esperto. Il nostro studio ha due obiettivi: 1) validare il sistema CEUS LI-RADS nella diagnosi di carcinoma epatocellulare in pazienti ad alto rischio di HCC usando come gold-standard l’istologia quando disponibile oppure metodiche di imaging radiologico accettate da tutte le linee guida (tomografia computerizzata o risonanza magnetica con aspetto tipico) eseguite entro quattro settimane dalla CEUS; 2) valutare l’efficacia di un software di quantificazione della perfusione tissutale nel riscontro di wash-out per la diagnosi di HCC in CEUS.<br>Hepatocellular carcinoma (HCC) is the most common primary liver cancer with an incidence of up to 85%. It is one of the most frequent cancers in the world and is known for its high lethality, especially in the advanced stage. Early diagnosis through ultrasound surveillance is needed to improve survival of at-risk patients. The ultrasound contrast agent improves the sensitivity and diagnostic specificity of conventional ultrasound. Contrast-enhanced ultrasound (CEUS) is therefore considered a valid method for diagnosing HCC globally due to its excellent specificity even if its sensitivity is suboptimal. The aspect of focal hepatic lesions on CEUS led a team of experts to develop the Liver Imaging Reporting and Data System (LI-RADS) with the aim of standardizing data collection and reporting of imaging methods for the diagnosis of HCC. CEUS is an operator-dependent examination and the diagnostic discrepancies with panoramic imaging leave room for new techniques such as the Dynamic Contrast Enhanced UltraSound (DCE-US) aimed at improving the diagnostic accuracy and in particular the sensitivity of the echography. A tissue perfusion quantification software could be of help in clinical practice to identify the wash-out that is not visible even to the eye of the most experienced operator. Our study has two objectives: 1) to validate the CEUS LI-RADS system in the diagnosis of hepatocellular carcinoma in patients at high risk of HCC using histology as a gold standard when available or radiological imaging methods accepted by all guidelines (computed tomography or magnetic resonance imaging) performed within four weeks from CEUS; 2) evaluate the efficacy of a tissue perfusion quantification software in the detection of wash-out for the diagnosis of HCC in CEUS.

One hundred and sixty-five CKCS subjects, both healthy and affected by different stages of MMVD, were examined from November 2018 to June 2021 at the Veterinary Teaching Hospital in Lodi – University of Milan – Cardiology Section. Each dog was submitted to a clinical examination and echocardiographic, radiographic, and morphometric data were collected. Whole blood and plasma were collected for genetic analysis and biomarker (miRNA) evaluation. The objectives of this study were: 1) To describe breed-specific reference values for vertebral heart score (VHS), vertebral heart atrial size (VLAS), M-VLAS, and radiographic left atrial enlargement (RLAD) in healthy adults CKCS; 2) To conduct a genomic study on a population of Italian CKCS; 3) To characterize echocardiographic features of the mitral valve in this breed, focusing on dogs classified as American College of Veterinary Internal Medicine (ACVIM) B1, without clinical signs and without left atrial and ventricular enlargement; 4) To analyze the relationships and the prognostic value of morphometric variables in CKCS affected by MMVD; 5) To analyze the expression of miRNAs described in the literature as being involved in the pathophysiology of MMVD, and identified in dogs’ plasma. Results: 1) Healthy CKCS had a median VHS of 10.08 ± 0.56v, a VLAS, M-VLAS and RLAD respectively of 1.79 ± 0.3v, 2.23 ± 0.44v and 1.2 ± 0.34v; 2). The top 1% single-nucleotide polymorphisms (SNPs) of both Wright’s fixation index (FST) and cross-population extended haplotype homozygosity (XP-EHH) analyses localized 10 consensus genes on chromosomes 3-11-14-19; 3) Within class B1, older subjects showed significantly higher values of anterior mitral valve area (AMVA), width (AMVW), mitral valve annulus in diastole (MVAd) and systole (MVAs) and lower sphericity index (SI); 4) A more severe mitral regurgitant jet size and a thicker anterior mitral valve leaflet were observed in CKCS smaller than standard proposed by the Ente Nazionale della Cinofilia Italiana (ENCI) and with morphometric characteristics tending to brachycephalism; 5) miR-30b-5 was significantly higher in ACVIM B1 compared to healthy subjects (ACVIM class A) and the AUC was 0.79. According to the age of dogs, the expression of miR-30b-5p remained significantly higher in group B1&lt;3y (2.3 folds p=0.03), B1 3-7y (2.2 folds p=0.03), and B1&gt;7y (2.7 folds p=0.02) than in stage A. The AUCs were fair in discriminating group B1&lt;3y and A (AUC 0.78), and B1 3-7y and A (AUC 0.78), and good in discriminating group B1&gt;7y and A (AUC 0.82). Conclusions: 1) Findings supported previous studies recommending the use of breed-specific reference values for VHS, VLAS, M-VLAS and RLAD and provided background data for future radiographic evaluations of CKCS dogs with clinical signs of cardiac disease; 2) This genetic analysis expands the knowledge of the genetic basis of MMVD by identifying genes involved in the early onset of MMVD in CKCS; 3) This is the first study that describes measurements of the anterior mitral valve leaflet and the mitral valve annulus in the CKCS affected by MMVD at different stages. Differently aged B1 dogs have different clinical and echocardiographic patterns. Further investigations with a larger study population and an appropriate follow-up would highlight prognostic factors related to disease worsening within this heterogeneous ACVIM class; 4) The morphological study of CKCS showed that a more severe regurgitant jet size was observed in subjects with a shorter head and nose. Subjects with a smaller head stop angle had thicker anterior mitral valve leaflets. Dogs with cephalic morphology more similar to the King Charles spaniel breed, that is with a brachycephalic morphotype, showed a more severe regurgitant jet size and valvular characteristics related to worse forms of MMVD (thicker anterior mitral valve leaflet, greater mitral valve annulus and lower sphericity index); 5) miR-30b-5p increases in the plasma of asymptomatic CKCS and this can be considered a potentially promising biomarker even at an asymptomatic stage of disease, particularly at a young age.

Le terapie espressive sono considerate tecniche di intervento particolarmente efficaci da impiegare con bambini vittime di catastrofi naturali. In particolare diversi arti-terapeuti affermano che per bambini vittime di traumi, il disegno rappresenta una modalità preferenziale per esprimere emozioni poiché consente di rappresentare la complessità di vissuti , percezioni, pensieri e memorie di natura traumatica, attribuendo loro una forma e, quindi un senso. Nonostante questo l’efficacia dell’impiego dello strumento non è stata scientificamente dimostrata. Questa tesi presenta due studi, uno studio pilota e uno studio principale, finalizzati ad esplorare l’utilizzo del “test de trois dessins: avant, pendant et avenir” come strumento diagnostico e tecnica terapeutica da impiegare con bambini vittime di terremoti di Abruzzo, Haiti e Cile. Lo studio pilota è basato sull’analisi qualitativa di case-studies,mentre lo studio principale utilizza strumenti quantitativi e qualitativi. I risultati mostrano l’efficacia dello strumento nel rilevare la presenta del trauma psichico e nel favorire processi di elaborazione del trauma. Ricerche future sono necessarie per attuare una validazione dello strumento come tecnica diagnostiche e strumento terapeutico con bambini vittime di traumi.<br>Expressive therapies are considered one of the most effective intervention modality with children who have experienced traumatic events such as natural catastrophes. Particularly, several art therapists affirm that for trauma affected children, drawing is a preferential mode for expressing emotions, as it gives them the possibility of conveying the complexity of traumatic feelings, perceptions, thoughts and memories, by giving them a shape and, therefore, a sense. Notwithstanding these assumptions, the efficacy of art therapies with children exposed to natural disasters, has not been research proved. This thesis presents two studies, a pilot study and the main study, aimed at exploring the use of the “test de trois dessins: avant, pendant et avenir”, as a diagnostic tool and a therapeutic technique, with children victims of the earthquake in Italy, Haiti and Chilli. The pilot study is based on non-statistical qualitative observation of case studies, while the principal one employ of both qualitative and quantitative methodology. The results show the efficacy of the test in both pointing out the presence and the extent of the psychological trauma, and in enhancing the process of elaborating trauma. Further researches need to be done in order to validate the use of the “test de trois dessins: avanat, pendant et avenir” as a diagnostic and therapeutic tool with trauma affected children.

La meningite è un'infiammazione delle meningi, le membrane che rivestono il cervello e il midollo spinale. Di solito è causata da batteri o virus, ma può anche essere causato da farmaci o malattie (meningite di eziologia non infettiva). La meningite batterica è rara, ma di solito è grave e può essere pericolosa per la vita se non trattata immediatamente. La meningite virale (detta anche meningite asettica) è relativamente comune e molto meno grave. Rimane spesso non diagnosticata perché i suoi sintomi possono essere simili a quelli della comune influenza. Se tempestivamente diagnosticata, la meningite può essere trattata con successo. Quindi è riconoscere i segni di meningite, e se si sospetta che il bambino ha la malattia, richiedere assistenza medica immediatamente. Molti dei batteri e virus che causano la meningite sono abbastanza comuni e sono in genere associate ad altre patologie di routine. Batteri e virus che infettano la cute, l’apparato urinario, il tratto gastrointestinale o respiratorio possono diffondere per mezzo della circolazione sanguigna verso le meningi e causare il processo infettivo.In alcuni casi di meningite batterica, i batteri si diffondono nelle meningi a cvausa di un grave trauma alla testa o una grave infezione locale, come ad esempio una grave infezione all'orecchio (otite media) o infezione dei seni nasali (sinusite). Diversi tipi di batteri possono causare la meningite batterica. Nei neonati, le cause più comuni sono lo streptococco di gruppo B, Escherichia coli e Listeria monocytogenes. In bambini più grandi, Streptococcus pneumoniae (pneumococco) e Neisseria meningitidis (meningococco) sono più spesso le cause. Un altro batterio, Haemophilus influenzale tipo b (Hib), può anche causare la malattia, ma a causa di vaccinazioni infantili diffuse, questi casi sono diventati più rari. Allo stesso modo, molti virus possono causare la meningite virale, compresi gli enterovirus (come coxsackie, polio ed epatite A) e gli herpesvirus. I sintomi della meningite sono variabili e dipendono sia l'età del bambino / paziente adulto e la causa dell'infezione. Poiché la meningite sintomi simil-influenzali possono essere simili in entrambi i tipi di meningite, soprattutto nelle fasi iniziali, e batteriche possono essere molto gravi, è importante diagnosticare rapidamente l'infezione. La sua importanza deriva non solo dalla sua gravità, l'infezione progredisce rapidamente e può condurre alla morte, ma anche le conseguenze che può causare: danni e invalidità permanenti di vari tipi e livelli. E questo è il motivo per cui il solo sospetto di meningite in un sistema di allarme del paziente e causa una forte implicazione emotiva per tutti i professionisti sanitari coinvolti nel medico di emergenza chiamata solleva la necessità di un approccio metodologico basato sulla velocità, precisione e in particolare sulla scelta di sistemi che sono estremamente sensibili.<br>Meningitis is an inflammation of the meninges, the membranes that cover the brain and spinal cord. It is usually caused by bacteria or viruses, but it can also be caused by certain medications or illnesses (meningitis of non-infectious etiology). Bacterial meningitis is rare, but is usually serious and can be life-threatening if it's not treated right away. Viral meningitis (also called aseptic meningitis) is relatively common and far less serious. It often remains undiagnosed because its symptoms can be similar to those of the common flu. If promptly diagnosed, meningitis can be treated successfully. So it's important to get routine vaccinations, know the signs of meningitis, and if you suspect that your child has the illness, seek medical care right away. Many of the bacteria and viruses that cause meningitis are fairly common and are typically associated with other routine illnesses. Bacteria and viruses that infect the skin, urinary system, gastrointestinal or respiratory tract can spread by the bloodstream to the meninges through cerebrospinal fluid, the fluid that circulates in and around the spinal cord. In some cases of bacterial meningitis, the bacteria spread to the meninges from a severe head trauma or a severe local infection, such as a serious ear infection (otitis media) or nasal sinus infection (sinusitis). Many different types of bacteria can cause bacterial meningitis. In newborns, the most common causes are Group B streptococcus, Escherichia coli, and Listeria monocytogenes. In older kids, Streptococcus pneumoniae (pneumococcus) and Neisseria meningitidis (meningococcus) are more often the causes. Another bacteria, Haemophilus influenza type b (Hib), can also cause the illness but because of widespread childhood immunization, these cases are now rarer. Similarly, many different viruses can lead to viral meningitis, including enteroviruses (such as coxsackievirus, poliovirus, and hepatitis A) and the herpesvirus. The symptoms of meningitis vary and depend both on the age of the child/adult patient and on the cause of the infection. Because the flu-like symptoms can be similar in both types of meningitis, particularly in the early stages, and bacterial meningitis can be very serious, it's important to quickly diagnose an infection. Its importance stems not only from its gravity, the infection progresses rapidly and can lead to death, but also the consequences that can cause: damage and permanent disabilities of various types and levels. And this is the reason why the mere suspicion of meningitis in a patient cause alarm and strong emotional implications for all health professionals involved in emergency doctor called it raises the need for a methodological approach based on speed, accuracy and especially on the choice of systems that are highly sensitive.

The relevance of viral infections in allograft lesion development is still unclear, although some viruses such as HCMV, EBV, VZV, HHV6, HHV8, seem to have a particular role especially during the first months after transplantation, and the polyomavirus BK (BKV), JC (JCV) and the parvovirus B19, have been implicated in the occur of kidney injury after more time following transplant. In this study we investigated systemic and intrarenal viral infections in kidney transplant young recipients and we analysed the association of these data with the risk of acute rejection and chronic allograft injuries predictive of long-term dysfunction. The presence of DNA sequences of human herpesviruses, polyomaviruses, and parvovirus B19 was analysed in renal allograft biopsies performed at baseline, for acute renal dysfunction and for follow-up during the first two years post transplant. We evaluated le presence of viral sequences in 69 transplanted children and young adult who underwent kidney transplant from 2000 to 2006: donor age was less than 6 year in 15 cases. These results regarding the genomic viral presence in these patients were correlated with clinical data, viral DNAemia, renal function tests and allograft histology analysed at the same time points of the follow-up. Taken as a whole, viral DNA was detectable in 46% baseline biopsies and in 70% follow-up biopsies of kidney allografts, where it generally persisted. The most frequently detected viruses were B19 and HHV-6, already present in donor kidneys, and BKV and EBV, usually involving the allograft during follow-up. Among viruses, only the intrarenal persistence of B19 DNA and B19 DNAemia was associated with the development of chronic allograft injury: these kind of data were never demonstrated before in literature. Regarding HCMV DNAemia, it was considered a risk factor for acute rejection as already suggested in many works from the literature. So, we conclude that parvovirus B19 seems to electively target the kidney and its intrarenal persistence is associated with chronic kidney allograft injury. In the second part of this work, in order to identify new markers for a rapidly identification of viral infections occur early after transplantation and are often transmitted from the graft, we investigated whether EBV, HCMV, BKV, and parvovirus B19 genome sequences could be detected in kidney grafts, preservation and washing solutions before implantation, and whether they correlated with the occurrence of viral infections in the recipient. The investigation of different donor graft samples (i.e., biopsy, preservation and washing solutions) that we wholly named “Kidney Unit” (KU), increased the sensitivity of viral DNA testing, but also gave clues to the mechanism of viral transmission through the kidney graft while the different samples are enriched from different cells from the donor: resident kidney cells or circulated blood cells. Viral genome sequences were frequently detected in donor renal graft units, especially in preservation and washing solutions. Overall, viral DNA was detected in at least one type of sample, including biopsy, preservation and washing solutions, in 51/75 (68%) kidney grafts and B19 was the most frequently detected virus (47%). In agreement with their ability to establish latency in B lymphocytes and in monocytes progenitor cells, respectively, EBV and HCMV were probably carried by circulating blood cells, since viral DNA was generally detected in preservation and washing solutions, which are contaminated by blood cells, but not in kidney biopsies; whereas B19 DNA was often detected in kidney graft biopsies, besides in preservation and washing solutions, thus suggesting the virus probably infected resident kidney cells, which might be important sources of transmission to the recipient. BKV is supposed to have tropism for the kidney and to achieve latency in renal tubular epithelial cells; however, we detected BKV DNA only in one donor kidney biopsy, whereas viral DNA was generally detectable in the allograft during follow-up, where it persisted, as we previously demonstrated. The prevalence of EBV, HCMV, and BKV DNA was higher in preservation and washing solutions than in biopsies, indicating they were mainly carried by blood cells, whereas B19 was consistently detected in biopsies and solutions, suggesting virus was also present in resident kidney cells. Detection of viral DNA in kideny grafts was a significant risk factor for symptomatic infections in seronegative recipients in the early post-transplant period. In particular, EBV DNA-positive donor grafts were significantly associated with the risk of EBV infection in seronegative recipients, whereas the presence of B19 DNA in kidney grafts was a risk factor for B19 infection and/or DNAemia both in B19-seronegative and seropositive recipients. At variance, molecular testing for HCMV and BKV in donor graft had poor diagnostic utility. In conclusion, this study demonstrates that detection of viral nucleic acids in preservation and washing solutions of a solid organ, i.e., the kidney, before implantation could be a useful test to identify recipients with increased risk of infections, especially symptomatic infections, in the early post-transplant period. The sensitivity and specificity of the test depends on viral tropism for cells and tissues of the graft.<br>Il ruolo dell’infezione virale nell’insorgenza di lesioni nel rene trapiantato non è stato ancora del tutto precisato sebbene alcuni virus come HCMV, EBV, VZV, HHV6, HHV8, in una fase più precoce, e il poliomavirus BK (BKV) e JC (JCV) e al parvovirus B19, dopo più tempo dal trapianto, sembrano avere una precisa funzione nel determinare danni a carico del rene trapiantato. Infatti, tutti questi virus sono stati già descritti come importanti patogeni con tropismo renale. Nel presente studio sono state investigate le infezioni virali, intrarenali e sistemiche, in una casistica di bambini e giovani adulti che sono stati sottoposti a trapianto di rene dal 2000 al 2006. Più esattamente sono stati analizzati i dati della prevalenza delle sequenze genomiche virali intrarenali e delle infezioni sistemiche (DNAemia) in associazione con il rischio di insorgenza di rigetto acuto e/o di lesioni croniche del rene trapiantato. La presenza delle sequenze genomiche virali dei virus erpetici umani, dei poliomavirus e del parvovirus B19 è stata analizzata a livello della biopsie di rene eseguite al momento del trapianto, biopsie baseline, in presenza di disfunzioni renali acute e durante i primi due anni dal trapianto seguendo i tempi del protocollo di follow-up cioè a 6, 12 e 24 mesi post trapianto. Sono stati studiati 69 riceventi pediatrici, bambini e giovani adulti, con un’età media pari a 13 anni che avevano ricevuto il rene da donatore deceduto in 65 casi e in 4 casi da famigliare vivente: l’età dei donatori era inferiore a 6 anni in 15 casi. I risultati di questa prima parte dello studio, relativi alla prevalenza del DNA virale intrarenale sono stati correlati con i dati clinici, i dati di viremia (DNAemia), di funzionalità del rene trapiantato e con le valutazioni istologiche dello stesso momento del follow-up. Globalmente, il DNA virale è stato ritrovato nel 46% delle biopsie baseline e nel 70% delle biopsie di follow-up, dove generalmente persiste nelle biopsie successive. I virus più frequentemente identificati sono il parvovirus B19 e l’herpesvirus HHV6, già presenti a livello delle biopsie di rene del donatore. Mentre la presenza delle sequenze genomiche dei virus EBV e BKV è stata associata alla comparsa di lesioni acute nel rene trapiantato. Tra tutti i virus studiati e ritrovati a livello del rene del ricevente, soltanto il DNA del parvovirus B19 e le relativa DNAemia sono state associate con lo sviluppo di lesioni croniche del rene trapiantato: tale dato non era mai stato dimostrato in precedenti studi della letteratura. Per quanto riguarda il HCMV, la relativa DNAemia è stata considerata un fattore di rischio per la comparsa di episodi di rigetto acuto: dato, questo, già dimostrato e confermato con il nostro studio. Quindi è possibile concludere che il parvovirus B19 sembra preferire, in modo particolare, il rene come possibile bersaglio da infettare e la sua persistenza intrarenale è associata con la comparsa di lesioni croniche del rene trapiantato. Nella seconda parte del presente studio, con l’intento di identificare nuovi marcatori del rischio di infezione del ricevente trapiantato di rene, è stata valutata la presenza delle sequenze genomiche virali di EBV, HCMV, BKV, e del parvovirus B19 nel rene del donatore prima dell’impianto; più precisamente sono state analizzate le biopsie, le soluzioni di conservazione e di lavaggio dell’organo prima che questo venga trapiantato. È stato osservato poi se la presenza del DNA virale nell’unità rene (ovvero l’insieme dei diversi campioni derivati dal donatore: biopsia, soluzione di conservazione e di lavaggio) correlava con la comparsa dell’infezione virale nel ricevente. L’ indagine condotta a livello dei diversi campioni dell’unità rene del donatore, consente di aumentare la sensibilità del test molecolare, ma anche da maggiori indicazioni relative al meccanismo di trasmissione dell’infezione virale mediante il rene trapiantato dal momento che i diversi campioni dell’unità rene sono arricchiti di più frazioni cellulari del donatore: sono presenti sia le cellule residenti del rene a livello della biopsia, ma anche le cellule del sangue circolante soprattutto nel liquido di lavaggio. Le sequenze genomiche virali sono frequentemente identificate nell’unità rene del donatore, soprattutto nelle soluzioni di conservazione e di lavaggio. Globalmente, il DNA virale è stato identificato, in almeno un tipo di campione dell’unità rene, in 51 su 75 reni donati (68%) e il virus più ritrovato è il B19 (47%). In accordo con la loro capacità di definire uno stato di latenza dei linfociti B e nei monociti, il DNA dei virus EBV, nel primo caso, e HCMV nel secondo, sono stati identificati principalmente nelle soluzioni di lavaggio e di conservazione, poiché tali virus sono probabilmente veicolati dalle cellule del sangue periferico. Mentre, nel caso del parvovirus B19, il DNA virale è stato trovato spesso nelle biopsie del rene del donatore: questo suggerisce che il virus probabilmente infetta le cellule residenti del rene, le quali potrebbero essere un importante sorgente di trasmissione dell’infezione al ricevente. Il poliomavirus BK si pensa abbia un particolare tropismo per il rene e che vada in latenza nelle cellule epiteliali tubulari del rene: ciononostante nel presente studio il DNA di BKV è stato identificato solo in una biopsia di rene del donatore mentre è stato più volte ritrovato, anche in maniera persistente, nelle biopsie di follow-up. In generale, è stato possibile constatare che la presenza del DNA virale nel rene del ricevente è un importante fattore di rischio di infezione sistemica per il ricevente sieronegativo nel primo periodo successivo al trapianto. In particolare, la presenza del DNA di EBV nell’ unità rene donata comporta un più elevato rischio di infezione da EBV nel ricevente sieronegativo, mentre la persistenza di B19 nel rene del ricevente è un fattore di rischio di infezione e/o di DNAemia da B19 per il ricevente sia sieropositivo che sieronegativo. Al contrario questo tipo di indagine molecolare dell’unità rene del donatore, condotta per il HCMV e per BKV non mostra una valida utilità diagnostica. Concludendo, con questo studio è stato possibile dimostrare che l’identificazione di acidi nucleici virali a livello delle soluzioni di lavaggio e di conservazione del rene da trapiantare potrebbe essere un test molecolare particolarmente utile per riconoscere i riceventi con un maggior rischio di infezione, soprattutto sistemica. La sensibilità e la specificità di tale test molecolare dipende però dal tropismo del virus per le cellule o per il tessuto dell’organo da trapiantare.

Trata-se de um estudo observacional, descritivo e retrospectivo de 154 pacientes com diagnÃstico clÃnico e sorolÃgico de dengue internados em um hospital pÃblico terciÃrio, de referÃncia em doenÃas infecto-contagiosas, em Fortaleza-Ce, no perÃodo de janeiro a maio de 2008. O objetivo foi correlacionar exames laboratoriais, sintomas e sinais de alerta dentro da evoluÃÃo cronolÃgica da dengue, observando suas freqÃÃncias nas formas mais graves para que se possa ajudar nas tomadas de conduta terapÃuticas mais eficazes. A idade dos pacientes variou de 2 a 85 anos. A amostragem foi dividida em dois grupos: pacientes < 15 anos (n=66) e &#8805;15 anos (n=88). Na classificaÃÃo clÃnica, por se tratar de pacientes de um hospital terciÃrio, predominou a FHD (58,4%) seguido de DG (28,6%) e de DC (13%). Nos pacientes com DC foi observado alteraÃÃes laboratoriais importantes como plaquetopenia e elevaÃÃo nas transaminases, que motivaram suas internaÃÃes. As principais alteraÃÃes laboratoriais encontradas na FHD foram: plaquetopenia, hemoconcentraÃÃo, elevaÃÃo de transaminases. Resultados semelhantes foram observados no DG, no entanto hemoconcentraÃÃo nÃo foi detectada. Os sinais de alarme foram verificados com maior freqÃÃncia nas duas formas graves da dengue. Na DG, nos grupos <15 anos e &#8805;15 anos foram observados respectivamente manifestaÃÃes hemorrÃgicas: 55,55%, 69,23%; dor abdominal intensa e contÃnua: 72,22%, 65,38%; tontura postural: 11,11%, 23,08%; vÃmitos: 61,10%, 38,40%. Na FHD nas faixas etÃrias <15 anos e &#8805;15 anos apresentaram respectivamente manifestaÃÃes hemorrÃgicas: 52,27%, 65,22%; dor abdominal intensa e contÃnua: 97,73%, 71,74%; tontura postural: 9,09; 43,48; vÃmitos: 81,80%; 58,70%. Estes resultados dentro da evoluÃÃo cronolÃgica da doenÃa foram importantes, independente da forma clÃnica da dengue e da faixa etÃria. As alteraÃÃes laboratoriais foram na sua maioria a partir do 3 dia sendo mais evidentes no 5 dia e com restabelecimento dos valores atà o 11 dia. A detecÃÃo dos sinais de alerta em dengue dentro desta cronologia foi importante para a caracterizaÃÃo clÃnica de pacientes com FHD e DG. Portanto, esses resultados sÃo relevantes na avaliaÃÃo da doenÃa, pois estas alteraÃÃes e a detecÃÃo dos sinais de alerta dentro da evoluÃÃo cronolÃgica da doenÃa podem ser utilizados como sinalizadores para as formas mais graves e ajudar precocemente na tomada de conduta terapÃutica eficaz para o paciente.<br>This is an observational, descriptive and retrospective study of 154 patients who have been diagnosed clinically and serologically for dengue fever, interned in a tertiary public hospital in the city of Fortaleza of Cearà State, during the period of January â May, 2008, for the purpose of correlating the laboratory examinations, symptoms and alarming signs with the chronological evolution of the disease and to observe the frequencies of the more severe clinical forms of disease, so as to help adopt therapeutic conducts that are more effective. The patientsâ ages varied from two to 85 years. The study sample was divided in to two groups: patients < 15 years (n=66) and those &#8805;15 years (n=88). As the patients were all from a tertiary public hospital, the clinical classification of cases showed that hemorrhagic dengue fever (HDF) was predominant (58.4%), followed by severe dengue (SD â 28.6%) and classic dengue (CD - 13%). The CD patients showed alterations in the laboratory findings such as thrombocitopenia and rise of transaminases, which motivated their hospitalization. The principal laboratory alterations found in HDF patients were: thrombocytopenia, hemoconcentration and rise of transaminases. Similar alternations were found in SD patients, but hemoconcentration was not detected in them. The alarming signs were observed more frequently in the two severe forms of dengue. In the <15-years and &#8805;15-year groups, the respective clinical pictures were: hemorrhagic manifestations â 55, 55% and 69,23%; acute and continuous abdominal pain â 72,22% and 65,38%; and postural dizziness â 11,11% and 23,08%; vomiting â 61,10% and 38,40%. In the HDF patients, in the <15-years and &#8805;15-year subgroups, the respective hemorrhagic manifestations were: 52,27% and 65,22%; acute and continuous abdominal pain â 97,73% and 71,74%; and postural dizziness â 9,09% and 43,48%; vomiting â81,80% and 58,70%. Within the chronologic evolution of the disease, these results were important and were independent of the clinical form of the disease and the age group of the patients. In the majority of cases, the laboratory alterations were observed from the 3rd day onwards, being more evident on the 5th day and stabilizing to normal values by the 11th day. Within this chronology, the detection of alarming signs was important for the clinical characterization of HDF and SD cases in patients. These results appear to be relevant for the evaluation of the clinical disease, as the detection of the alarming signs within the chronologic evolution may be utilized as warning signals for the more severe forms of the disease, and hence could help in the early adoption of more efficient therapeutic strategies for the patients.

There is limited evidence reporting the epidemiology of forefoot neuroma (FFN) in the general population of the United Kingdom (UK). Consequently, estimated incidence or prevalence are not known although the condition is considered common in the National Health Service (NHS) and private health care sectors. Therefore, there is a need to determine the extent of this condition to inform appropriate healthcare provision. Furthermore, it is thought that an accurate and timely diagnosis would improve the patient experience and use of pathways through the NHS. A specific set of symptoms, associated with FFN, has been consistently documented in the literature. Despite this, the optimal method for FFN diagnosis is challenging and anecdotally highly variable between clinicians; currently no reliable or valid clinical diagnostic protocol exists for the diagnosis of symptomatic FFN in podiatric practice. Therefore, there is a need to develop a clinical diagnostic protocol and to determine its reliability and validity. It was anticipated that accurate diagnosis will inform more targeted service planning and promote effective clinical decision making on the management options available to address participant reported symptoms. Three sequential studies were designed and delivered within a local NHS podiatry service line. In study one, the clinical pathways were reviewed and the numerical values of individuals accessing the local podiatry service for a forefoot assessment were defined. Study two developed a clinical assessment protocol (FNCAP) with agreed expert consensus for the diagnosis of FFN. Through study three, the content validity and reliability of FNCAP for the diagnosis of FFN was established. The findings of this thesis validate the estimated regional incidence and prevalence rates of symptomatic persons registered to the podiatry service line. However, records provided little insight into the diagnostic methods used to identify FFN from other forefoot pathology. This led to the development of a clinical diagnostic protocol from expert consensus for FFN. Through the Delphi study, six themes related to the clinical diagnosis of FFN: location of pain, non weight-bearing sensation, weight-bearing sensation, observations, clinical tests and imaging were identified. The themes were integrated such that 21 recommendations were identified and refined to form a clinical diagnostic protocol for FFN. The diagnostic test study indicated that there is content validity for the items that form FNCAP. The intra-rater reliability tests for the FNCAP revealed a 'moderate' threshold of agreement value. The sensitivity (100%) and specificity (95.6%) scores for FNCAP were high and indicated the FNCAP could be useful for diagnosing FFN in most cases. Feasibility testing of the FNCAP has indicated some usefulness in diagnosing FFN but further investigations are required to determine the FNCAP applicability in clinical practice.

Contrary to the long-held assumptions, borderline personality disorder (BPD) is now considered a treatable disorder. Timely assessment has been recognised as one of the key treatment enablers and basic assessment standards have been stipulated by the UK’s National Institute for Health and Clinical Excellence (NICE). The current study was the first to have specifically investigated the quality of the diagnostic process in light of the government recommendations. Interpretative phenomenological analysis was used to analyse semi-structured interviews with eight adult female service users about their lived experiences with the original diagnostic disclosure of BPD. Five master themes and several subthemes featured in the majority of the participants’ experience: a) answer with a question mark; b) if only…; c) BPD like a star sign; d) star signs are not enough; it’s what happens afterwards!; e) being at the mercy of the system. Most participants’ experiences suggested that the original diagnostic process was largely negative and did not follow the national guidelines. Nevertheless, a minority of positive views also emerged. The findings are discussed with reference to the existing literature, whilst also detailing the study’s limitations, clinical and research implications.

Bradyarrhythmias are common clinical findings consisting of physiologic and pathologic conditions (sinus node dysfunction and atrioventricular [AV] conduction disturbances). Bradyarrhythmias can be benign, requiring no treatment; however, acute unstable bradycardia can lead to cardiac arrest. In patients with confirmed or suspected bradycardia, a thorough history and physical examination should include possible causes of sinoatrial node dysfunction or AV block. Management of bradycardia is based on the severity of symptoms, the underlying causes, presence of potentially reversible causes, presence of adverse signs, and risk of progression to asystole. Pharmacologic therapy and/or pacing are used to manage unstable or symptomatic bradyarrhythmias.

Inherited disorders of platelet function are a rare and heterogeneous group of diseases usually characterised by a mild to moderate bleeding tendency. Typical bleeding symptoms are easy bruising, epistaxis, menorrhagia as well as mucocutaneous and perioperative bleeding. The performance of platelet function diagnostics in children is hampered by age-dependent restriction of blood sample size, poor venous access, and the lack of reproducible test reference ranges for children of different age groups. Platelet function testing is limited to specialised centres, because platelet function test procedures are complicated and time-consuming, which most likely results in a relevant number of undiagnosed and incorrectly classified children with clinically relevant platelet function defects. Evaluation of bleeding history and bleeding symptoms is essential for a rational step-bystep approach to diagnosis. Platelet function diagnostics should be preceded by the exclusion of thrombocytopenia, von Willebrand disease, and secondary haemostasis defects. Light transmission aggregometry is still considered the standard for the assessment of platelet function. Every effort should be made to classify the specific platelet function defect in the patient, because this is essential for accurate treatment and counselling<br>Angeborene Thrombozytenfunktionsstörungen stellen eine seltene und heterogene Gruppe von Erkrankungen dar, welche meist durch eine leichte bis mittelschwere Blutungsneigung auffallen. Typische Blutungssymptome sind Hämatomneigung, Epistaxis, Menorrhagien sowie Schleimhaut- und perioperative Blutungen. Die Durchführung der Thrombozytenfunktionsdiagnostik bei Kindern wird erschwert durch die altersabhängig begrenzte Blutprobenmenge, schwierige Venenverhältnisse und das Fehlen von Referenzbereichen für Kinder unterschiedlichen Alters. Aufgrund der meist komplizierten und zeitaufwendigen Tests ist die Thrombozytendiagnostik auf spezialisierte Zentren begrenzt. Mit hoher Wahrscheinlichkeit wird eine relevante Anzahl von Kindern mit nichtdiagnostizierten bzw. unkorrekt klassifizierten, klinisch relevanten Thrombozytopathien übersehen. Die Erhebung der Blutungsanamnese und die Bewertung der Blutungssymptome sind erforderlich für eine stufenweise erfolgreiche Gerinnungsdiagnostik. Vor Durchführung einer Thrombozytenfunktionsdiagnostik sollten das Vorliegen einer Thrombozytopenie, einer von-Willebrand-Erkrankung und sekundärer Gerinnungsstörungen ausgeschlossen werden. Die Lichttransmissionsaggregometrie gilt noch immer als Standardmethode für die Beurteilung der Thrombozytenfunktion. Nach Möglichkeit sollte stets versucht werden, den vorliegenden spezifischen Thrombozytenfunktionsdefekt zu klassifizieren, da dies für eine adäquate Behandlung und eine gezielte genetische Beratung notwendig ist<br>Dieser Beitrag ist mit Zustimmung des Rechteinhabers aufgrund einer (DFG-geförderten) Allianz- bzw. Nationallizenz frei zugänglich

Objectives: MRI is of great clinical utility for the guidance of special diagnostic and therapeutic interventions. The majority of such procedures are performed iteratively (\"in-and-out\") in standard, closed-bore MRI systems with control imaging inside the bore and needle adjustments outside the bore. The fundamental limitations of such an approach have led to the development of various assistance techniques, from simple guidance tools to advanced navigation systems. The purpose of this work was to thoroughly assess the targeting accuracy, workflow and usability of a clinical add-on navigation solution on 240 simulated biopsies by different medical operators. Methods: Navigation relied on a virtual 3D MRI scene with real-time overlay of the optically tracked biopsy needle. Smart reference markers on a freely adjustable arm ensured proper registration. Twenty-four operators – attending (AR) and resident radiologists (RR) as well as medical students (MS) – performed well-controlled biopsies of 10 embedded model targets (mean diameter: 8.5 mm, insertion depths: 17-76 mm). Targeting accuracy, procedure times and 13 Likert scores on system performance were determined (strong agreement: 5.0). Results: Differences in diagnostic success rates (AR: 93%, RR: 88%, MS: 81%) were not significant. In contrast, between-group differences in biopsy times (AR: 4:15, RR: 4:40, MS: 5:06 min: sec) differed significantly (p<0.01). Mean overall rating was 4.2. The average operator would use the system again (4.8) and stated that the outcome justifies the extra effort (4.4). Lowest agreement was reported for the robustness against external perturbations (2.8). Conclusions: The described combination of optical tracking technology with an automatic MRI registration appears to be sufficiently accurate for instrument guidance in a standard (closed-bore) MRI environment. High targeting accuracy and usability was demonstrated on a relatively large number of procedures and operators. Between groups with different expertise there were significant differences in experimental procedure times but not in the number of successful biopsies.

This study examined the clinical utility of the recently released National Institute of Mental Health's (NIMH) research domain criteria (RDoC) by replicating and extending earlier work by using a demographically novel sample. Information retrieval and natural language processing of archival clinical records was used to achieve two main objectives: (1) estimate how well the RDoC domains match language used by clinicians by creating domain scores and (2) examine the differences between the DSM's and RDoC's ability to predict treatment outcome using these domain scores and DSM diagnoses. The social systems RDoC category was found to be the strongest predictor of treatment outcome across all diagnostic measures.

This study investigates the clinical problem-solving among Western-trained and traditionally trained acupuncturists. Fifty-six subjects with varying clinical experience were divided into four groups: physicians without acupuncture training (control), physician-acupuncturists, non-licensed physician-acupuncturists, and traditionally trained acupuncturists. Three clinical cases (two routine and one non-routine), were given to the subjects to provide diagnostic and treatment plans. The data were quantitatively and qualitatively analyzed. Subjects' diagnostic and treatment plans were evaluated against reference models for Western medicine and traditional Chinese medicine (TCM).<br>The results indicate that acupuncturists were influenced by their initial medical training. Physician-acupuncturists and non-licensed physician-acupuncturists' practices were greatly influenced by the training in Western medicine, regardless of their exposure to traditional Chinese medicine. The traditionally trained practitioners outperformed the other groups of subjects in the non-routine case. Accuracy in diagnoses and treatments for the non-routine case was also positively related to the length of clinical experience. The findings support theories of expertise that experts use forward reasoning when coping with familiar cases, and backward reasoning when encountering difficult cases.

A computer-aided Clinical Decision Support System (CDSS) for diagnosis and treatment often plays a vital role and brings essential benefits for clinicians. Such a CDSS could function as an expert for a less experienced clinician or as a second option/opinion of an experienced clinician to their decision making task. Nevertheless, it has been a real challenge to design and develop such a functional system where accuracy of the system performance is an important issue. This research work focuses on development of intelligent CDSS based on a multimodal approach for diagnosis, classification and treatment in medical domains i.e. stress and post-operative pain management domains. Several Artificial Intelligence (AI) techniques such as Case-Based Reasoning (CBR), textual Information Retrieval (IR), Rule-Based Reasoning (RBR), Fuzzy Logic and clustering approaches have been investigated in this thesis work. Patient’s data i.e. their stress and pain related information are collected from complex data sources for instance, finger temperature measurements through sensor signals, pain measurements using a Numerical Visual Analogue Scale (NVAS), patient’s information from text and multiple choice questionnaires. The proposed approach considers multimedia data management to be able to use them in CDSSs for both the domains. The functionalities and performance of the systems have been evaluated based on close collaboration with experts and clinicians of the domains. In stress management, 68 measurements from 46 subjects and 1572 patients’ cases out of ≈4000 in post-operative pain have been used to design, develop and validate the systems. In the stress management domain, besides the 68 measurement cases, three trainees and one senior clinician also have been involved in order to conduct the experimental work. The result from the evaluation shows that the system reaches a level of performance close to the expert and better than the senior and trainee clinicians. Thus, the proposed CDSS could be used as an expert for a less experienced clinician (i.e. trainee) or as a second option/opinion for an experienced clinician (i.e. senior) to their decision making process in stress management. In post-operative pain treatment, the CDSS retrieves and presents most similar cases (e.g. both rare and regular) with their outcomes to assist physicians. Moreover, an automatic approach is presented in order to identify rare cases and 18% of cases from the whole cases library i.e. 276 out of 1572 are identified as rare cases by the approach. Again, among the rare cases (i.e. 276), around 57.25% of the cases are classified as ‘unusually bad’ i.e. the average pain outcome value is greater or equal to 5 on the NVAS scale 0 to 10. Identification of rear cases is an important part of the PAIN OUT project and can be used to improve the quality of individual pain treatment.

The diagnosis of Parkinson’s disease (PD) follows the UK Brain Bank Criteria, which demands bradykinesia and one additional symptom, i.e. rigidity, resting tremor or postural instability. The latter is not a useful sign for the early diagnosis of PD, because it does not appear before Hoehn and Yahr stage 3. Early symptoms of PD which precede the onset of motor symptoms are hyposmia, REM sleep behavioral disorder, constipation, and depression. In addition, an increasing number of patients whose PD is related to a genetic defect are being described. Thus, genetic testing may eventually develop into a tool to identify at-risk patients. The clinical diagnosis of PD can be supported by levodopa or apomorphine tests. Imaging studies such as cranial CT or MRI are helpful to distinguish idiopathic PD from atypical or secondary PD. SPECT and PET methods are valuable to distinguish PD tremor from essential tremor if this is clinically not possible. Using all of these methods, we may soon be able to make a premotor diagnosis of PD, which will raise the question whether early treatment is possible and ethically and clinically advisable<br>Dieser Beitrag ist mit Zustimmung des Rechteinhabers aufgrund einer (DFG-geförderten) Allianz- bzw. Nationallizenz frei zugänglich

Forming a medical diagnosis is a complicated reasoning process undertaken by physicians. Although there has been much research focusing on clinical reasoning approaches, there is limited empirical evidence in relation to causal attribution in medical diagnosis. The research on which this thesis is based explored and examined the social process of medical diagnosis and provides an explanation of the clinical reasoning and causal attribution used by physicians. The research was undertaken in an Emergency Department within an acute hospital, the data were collected using mixed method approach including one to one semi-structured interviews with individual physicians; observation of their medical assessments of patients and secondary data analysis of the subsequent recorded medical notes. The study involved 202 patients and 26 physicians. The analysis of the physicians’ semi-structured interviews, shows how physicians describe the diagnostic step process and how they blend their clinical reasoning skills and professional judgment with evidence-based medicine. Physicians apply prior learning of taught biomedical and pathophysiological knowledge to question patients using pattern recognition of common signs and symptoms of disease. These findings are portrayed through taped narratives of the physician/patient interaction during the medical diagnostic process, which shows how physicians control the medical encounter. The analysis/interpretation of documentary evidence (recorded medical notes) provides an insight into the way in which physicians used the information gathered during the diagnostic step process. By using SPSS it was possible to cluster the cases (individual patients) into groups. This stage-ordered classification procedure demonstrated commonality amongst individual cases whilst highlighting the uniqueness of any cases. A pattern emerged of two groups of cases: Group 1 - comprised of patients with the presenting complaints of chest pain, shortness of breath, collapse, abdominal pain, per rectal bleed, nausea, vascular and neurological problems and Group 2 - comprised of patients presenting with trauma, mechanical falls, miscarriage/gynaecological problems, allergies/rashes and dental problems. Findings show that the clinical reasoning approaches used varied according to the complexity of the patient’s presenting complaint. The recorded medical notes for the patients in Group 1, were comprehensive and demonstrated a combined approach of hypothetic-deductive and probabilistic reasoning which enabled the physicians to deal with the degree of uncertainty that is inherent in medicine. The recorded process in the medical notes was shortened for the majority of patients in Group 2, and here the clinical reasoning approach used was found to deterministic. It is acknowledged, that this is not always the case. By using crisp set QCA it was possible to explore causal conditions consistent with Group 1. Further analysis led to examination of the link of causal conditions presented in the medical notes with the individual impression/working diagnosis made by physicians.

The diagnosis of Parkinson’s disease (PD) follows the UK Brain Bank Criteria, which demands bradykinesia and one additional symptom, i.e. rigidity, resting tremor or postural instability. The latter is not a useful sign for the early diagnosis of PD, because it does not appear before Hoehn and Yahr stage 3. Early symptoms of PD which precede the onset of motor symptoms are hyposmia, REM sleep behavioral disorder, constipation, and depression. In addition, an increasing number of patients whose PD is related to a genetic defect are being described. Thus, genetic testing may eventually develop into a tool to identify at-risk patients. The clinical diagnosis of PD can be supported by levodopa or apomorphine tests. Imaging studies such as cranial CT or MRI are helpful to distinguish idiopathic PD from atypical or secondary PD. SPECT and PET methods are valuable to distinguish PD tremor from essential tremor if this is clinically not possible. Using all of these methods, we may soon be able to make a premotor diagnosis of PD, which will raise the question whether early treatment is possible and ethically and clinically advisable.<br>Dieser Beitrag ist mit Zustimmung des Rechteinhabers aufgrund einer (DFG-geförderten) Allianz- bzw. Nationallizenz frei zugänglich.

<p>Tularemia is a zoonosis caused by the small, fastidious, gram-negative rod Francisella tularensis that appears over almost the entire Northern Hemisphere. In Sweden, tularemia has appeared mainly in restricted areas in northern parts of central Sweden.</p><p> The disease can be transmitted through several routes: direct contact with infected animals, by vectors, through contaminated food or water or through inhalation of aerosolized bacteria. Distinct clinical forms of the disease are seen, depending on the route of transmission. During the last years, tularemia has emerged in new areas in central Sweden, south of the endemic area. The emergence of tularemia in the County of Örebro prompted the investigations presented in this thesis.</p><p> We performed a case-control study, using a mailed questionnaire, to identify risk factors for acquiring tularemia in Sweden (Paper I). After multivariate analysis, mosquito bites and cat ownership could be associated with tularemia in all studied areas while farming appeared as a risk factor only in endemic areas.</p><p> In Paper II, we evaluated a PCR analysis, targeting the tul4 gene, used on samples from primary lesions in patients with ulceroglandular tularemia. The method performed well, with a sensitivity of 78% and a specifi city of 96%. The clinical characteristics of tularemia in an emergent area in Sweden were studied Paper III), using case fi les and a questionnaire. Of 278 cases of tularemia reported during the years 2000 to 2004, 234 had been in contact with a doctor from the Department of Infectious Diseases at Örebro University Hospital, and were thus included. The ulceroglandular form of the disease was seen in 89% of the cases, with the primary lesion, in most cases, on the lower leg. An overwhelming majority of cases occurred during late summer and early autumn, further supporting transmission by mosquitoes. Erythemas overlying the affected lymph node areas were seen in 19% of patients with forms of tularemia affecting peripheral lymph nodes. Late skin manifestations, of various appearances, were seen in 30% of the cases, predominantly in women. A raised awareness of tularemia among physicians in the county during the course of the outbreak was found, as documented by the development of shorter doctor’s delay and less prescription of antibiotics inappropriate in tularemia.</p><p> Finally, we developed a simplifi ed whole-blood lymphocyte stimulation test, as a diagnostic tool in tularemia (Paper IV). The level of IFN-γ, as a proxy for lymphocyte proliferation, was measured after 24-h stimulation. Additionally, a tularemia ELISA with ultra-purifi ed LPS as the antigen was evaluated, showing a high sensitivity. The lymphocyte stimulation test, when performed on consecutive samples from subjects with ongoing tularemia was able to detect the disease earlier in the course of the disease than both the new ELISA and the tube agglutination test. Furthermore, all tularemia cases became positive in the lymphocyte stimulation test within 12 days of disease. In conclusion, this thesis describes risk factors for acquiring tularemia as well as the clinical characteristics of the disease in Sweden. Additionally, a Francisella PCR analysis and a tularemia ELISA based on highly purifi ed LPS is evaluated, and a simplified lymphocyte stimulation test, for early confirmation of the disease, is developed.</p><p>Henrik Eliasson, Department of Infectious Diseases,</p><p>Örebro University Hospital, SE-701 85 Örebro, Sweden,</p><p>henrik.eliasson@orebroll.se</p>

Increasing migratory processes and growing cultural diversity require to rethink usual patient approaches: how can a health professional diagnose and treat properly a patient if only relying on its own meaning of health and illness, without knowing other attitudes towards medical practices? The question becomes even more complex when the Other is encountered to understand and deal with psychological and existential suffering. This difficulty can be recognized in the confusion of both professional and patient as they attempt to answer questions not always shared or translatable. Migrants’ presence in care services and Law courts not only give us information about ourselves and our ways of taking care but it imposes a challenge, both epistemological and practical. It forces us to think back our models of well-being, etiology and treatment of suffering, because they are always incomplete and partial. The research aims to investigate – through three different studies and three different methods: questionnaire, interviews, ethnography - psychological assessment encounter between clinical mental health/forensic professional and migrant patient, focusing on practices, lived experienced, perceived difficulties, use of assessment instruments and diagnosis. This research tries to propose a theoretical reflection on these issues, integrating ethno- psychiatric and phenomenological perspective.<br>L'aumento dei processi migratori e la crescente diversità culturale impongono un ripensamento delle usuali modalità di approccio al paziente straniero. Come può un medico fare una diagnosi e trattare adeguatamente un paziente basandosi unicamente sul proprio significato di salute e malattia, senza conoscere altre modalità di pensare e utilizzare le pratiche mediche? La domanda diventa ancora più complessa e articolata quando l’incontro con l'Altro avviene per comprendere e curare la sofferenza psichica ed esistenziale. Una difficoltà – quella dell’incontro – che si esprime nella confusione vissuta dal professionista e dal paziente mentre tentano di rispondere a domande non sempre condivise o traducibili. La presenza dei migranti nei servizi di cura e nei tribunali non solo ci fornisce informazioni su noi stessi e sui nostri modi di curare, ma impone una sfida, sia epistemologica che pratica. Ci costringe a riconsiderare i nostri modelli di benessere, eziologia e trattamento della sofferenza, poiché sempre incompleti e parziali. La ricerca si propone di indagare – in tre differenti studi - l'incontro di valutazione diagnostica tra professionista della salute mentale – che lavora in ambito clinico e giuridico - e paziente/cliente migrante, focalizzando l’attenzione su pratiche, esperienze vissute, difficoltà percepite, uso di strumenti di valutazione e diagnosi. Tale ricerca si propone di offrire una riflessione teorica su tali tematiche, a partire da una integrazione tra la prospettiva etno-psichiatrica e quella fenomenologica.

Inherited disorders of platelet function are a rare and heterogeneous group of diseases usually characterised by a mild to moderate bleeding tendency. Typical bleeding symptoms are easy bruising, epistaxis, menorrhagia as well as mucocutaneous and perioperative bleeding. The performance of platelet function diagnostics in children is hampered by age-dependent restriction of blood sample size, poor venous access, and the lack of reproducible test reference ranges for children of different age groups. Platelet function testing is limited to specialised centres, because platelet function test procedures are complicated and time-consuming, which most likely results in a relevant number of undiagnosed and incorrectly classified children with clinically relevant platelet function defects. Evaluation of bleeding history and bleeding symptoms is essential for a rational step-bystep approach to diagnosis. Platelet function diagnostics should be preceded by the exclusion of thrombocytopenia, von Willebrand disease, and secondary haemostasis defects. Light transmission aggregometry is still considered the standard for the assessment of platelet function. Every effort should be made to classify the specific platelet function defect in the patient, because this is essential for accurate treatment and counselling.<br>Angeborene Thrombozytenfunktionsstörungen stellen eine seltene und heterogene Gruppe von Erkrankungen dar, welche meist durch eine leichte bis mittelschwere Blutungsneigung auffallen. Typische Blutungssymptome sind Hämatomneigung, Epistaxis, Menorrhagien sowie Schleimhaut- und perioperative Blutungen. Die Durchführung der Thrombozytenfunktionsdiagnostik bei Kindern wird erschwert durch die altersabhängig begrenzte Blutprobenmenge, schwierige Venenverhältnisse und das Fehlen von Referenzbereichen für Kinder unterschiedlichen Alters. Aufgrund der meist komplizierten und zeitaufwendigen Tests ist die Thrombozytendiagnostik auf spezialisierte Zentren begrenzt. Mit hoher Wahrscheinlichkeit wird eine relevante Anzahl von Kindern mit nichtdiagnostizierten bzw. unkorrekt klassifizierten, klinisch relevanten Thrombozytopathien übersehen. Die Erhebung der Blutungsanamnese und die Bewertung der Blutungssymptome sind erforderlich für eine stufenweise erfolgreiche Gerinnungsdiagnostik. Vor Durchführung einer Thrombozytenfunktionsdiagnostik sollten das Vorliegen einer Thrombozytopenie, einer von-Willebrand-Erkrankung und sekundärer Gerinnungsstörungen ausgeschlossen werden. Die Lichttransmissionsaggregometrie gilt noch immer als Standardmethode für die Beurteilung der Thrombozytenfunktion. Nach Möglichkeit sollte stets versucht werden, den vorliegenden spezifischen Thrombozytenfunktionsdefekt zu klassifizieren, da dies für eine adäquate Behandlung und eine gezielte genetische Beratung notwendig ist.<br>Dieser Beitrag ist mit Zustimmung des Rechteinhabers aufgrund einer (DFG-geförderten) Allianz- bzw. Nationallizenz frei zugänglich.