Standard surgical treatment for benign prostatic hyperplasia is safe for patients over 75 years: analysis of 100 cases from a high-volume urologic center

OBJECTIVES: In this study, we aimed to determine the complications of standard surgical treatments among patients over 75 years in a high-volume urologic center. METHODS: We analyzed 100 consecutive patients older than 75 years who had undergone transurethral prostatic resection of the prostate or open prostatectomy for treatment of benign prostatic hyperplasia from January 2008 to March 2010. We analyzed patient age, prostate volume, prostate-specific antigen level, international prostatic symptom score, quality of life score, urinary retention, co-morbidities, surgical technique and satisfaction with treatment. RESULTS: Median age was 79 years. Forty-eight patients had undergone transurethral prostatic resection of the prostate, and 52 had undergone open prostatectomy. The median International Prostatic Symptom Score was 20, the median prostate volume was 83 g, 51% were using an indwelling bladder catheter, and the median prostatespecific antigen level was 5.0 ng/ml. The most common comorbidities were hypertension, diabetes and coronary disease. After a median follow-up period of 17 months, most patients were satisfied. Complications were present in 20% of cases. The most common urological complication was urethral stenosis, followed by bladder neck sclerosis, urinary fistula, late macroscopic hematuria and persistent urinary incontinence. The most common clinical complication was myocardial infarction, followed by acute renal failure requiring dialysis. Incidental carcinoma of the prostate was present in 6% of cases. One case had urothelial bladder cancer. CONCLUSIONS: Standard surgical treatments for benign prostatic hyperplasia are safe and satisfactory among the elderly. Complications are infrequent, and urethral stenosis is the most common. No clinical variable is associated with the occurrence of complications.

Cisto nasolabial bilateral como causa de obstrução nasal: relato de caso e revisão de literatura

INTRODUÇÃO: O cisto nasolabial é uma doença rara, normalmente unilateral, benigna, de origem embrionária, localizada em partes moles da região do sulco nasolabial e asa nasal. O diagnóstico é essencialmente clínico, levando em consideração a topografia do cisto, que geralmente é assintomático. OBJETIVO: Este artigo tem como objetivo principal à descrição de um caso incomum de cisto nasolabial bilateral com obstrução nasal, seu tratamento, aspectos anatomopatológicos e acompanhamento, além de revisão de literatura. RELATO DO CASO: Paciente do sexo feminino, parda, 24 anos de idade, apresentando abaulamento em região nasolabial e obstrução nasal. Exames físico e complementares compatíveis com cisto nasolabial. Indicado tratamento cirúrgico para exérese da lesão. CONSIDERAÇÕES FINAIS: O cisto nasolabial bilateral, apesar de raro, é uma possível causa de obstrução nasal, com boa resposta à terapia cirúrgica.

Community-acquired urinary tract infection: age and gender-dependent etiology

LO, Denise Swei et al. Community-acquired urinary tract infection: age and gender-dependent etiology. J. Bras. Nefrol. [online]. 2013, vol.35, n.2, pp. 93-98. ISSN 0101-2800. http://dx.doi.org/10.5935/0101-2800.20130016. INTRODUCTION: Choosing the antimicrobial agent for initial therapy of urinary tract infection (UTI) is usually empirical and should consider the prevalence of uropathogens in different age groups and gender. OBJECTIVE: To establish prevalence rates of uropathogens in community-acquired UTI in relation to age and gender. METHODS: Crosssectional study conducted in the emergency department (ED) of a general hospital, from January to December, 2010, in patients younger than 15 years old who had clinical suspicion of UTI and collected quantitative urine culture. UTI was defined as urine culture with growth of a single agent > 100.000 colony forming units (cfu)/mL in a midstream collection or > 50.000 cfu/mL in urethral catheterization. RESULTS: There were 63.464 visits to ED. 2577 urine cultures were obtained, of whom 291 were positive for UTI (prevalence = 11.3% of clinical suspicion and 0.46% of visits), 212 cases (72.8%) in females, median age = 2.6 years. The predominant uropathogen was E. coli (76.6%), followed by Proteus mirabilis (10.3%) and Staphylococcus saprophyticus (4.1%). Among infants < 3 months, prevalence rates of E. coli were significantly lower (50% vs 78.4%; OR = 0.276; p = 0.006). Higher prevalences of Staphylococcus saprophyticus occurred among patients > 10 years (24.4% vs 0.4%; OR = 79.265; p < 0.0001). Proteus mirabilis was significantly more prevalent in boys than girls (24.0% vs 5.2%; OR = 5.786; p < 0.001). CONCLUSIONS: E. coli was the most prevalent community-acquired uropathogen. Nevertheless, initial empiric antimicrobial treatment of UTI should consider the significant prevalence of other agents different from E. coli in infants < 3 months, the high prevalence of Staphylococcus saprophyticus in patients > 10 years and Proteus mirabilis in males.

The renin–angiotensin system plays a major role in voiding dysfunction of ovariectomized rats

Aims: The renin–angiotensin system (RAS) plays a major role in cardiovascular diseases in postmenopausal women, but little is known about its importance to lower urinary tract symptoms. In this study we have used the model of ovariectomized (OVX) estrogen-deficient rats to investigate the role of RAS in functional and molecular alterations in the urethra and bladder. Main methods: Responses to contractile and relaxant agents in isolated urethra and bladder, as well as cystometry were evaluated in 4-month OVX Sprague–Dawley rats. Angiotensin-converting enzyme activity and Western blotting for AT1/AT2 receptors were examined. Key findings: Cystometric evaluations in OVX rats showed increases in basal pressure, capacity and micturition frequency, as well as decreased voiding pressure. Angiotensin II and phenylephrine produced greater urethral contractions in OVX compared with Sham group. Carbachol-induced bladder contractions were significantly reduced in OVX group. Relaxations of urethra and bladder to sodium nitroprusside and BAY 41-2272 were unaffected by OVX. Angiotensin-converting enzyme activity was 2.6-fold greater (p < 0.05) in urethral tissue of OVX group,whereas enzyme activity in plasma and bladder remained unchanged. Expressions of AT1 and AT2 receptors in the urethra were markedly higher in OVX group. In bladder, AT1 receptors were not detected, whereas AT2 receptor expression was unchanged between groups. 17β-Estradiol replacement (0.1 mg/kg, weekly) or losartan (30 mg/kg/day) largely attenuated most of the alterations seen in OVX group. Significance: Prolonged estrogen deprivation leads to voiding dysfunction and urethral hypercontractility that are associated with increased ACE activity and up-regulation of angiotensin AT1/AT2 receptor in the urethral tissue.

Renal papillary necrosis

In 1877, Dr. Nikolaus Friedreich (1825- 1882; student of Virchow who became Professor of Pathology at Heidelberg and who also described Friedreich’s ataxia) first described renal papillary necrosis (RPN) in patients with prostatic hypertrophy and secondary hydronephrosis. Thereafter in 1937, Froboese and Günther emphasized the association of this entity with diabetes mellitus. These authors also observed renal papillary necrosis in cases of urinary tract obstruction even in the absence of diabetes mellitus.

Effects of ischemia and reperfusion on subpopulations of rat enteric neurons expressing the P2X7 receptor

BACKGROUND: Intestinal ischemia followed by reperfusion (I/R) may occur following intestinal obstruction. In rats, I/R in the small intestine leads to structural changes accompanied by neuronal death. AIM: To analyze the impact of I/R injury on different neuronal populations in the myenteric plexus of rat ileum. METHODS: The ileal artery was occluded for 35 min and animals were euthanized 6, 24, and 72 h, and 1 week later. Immunohistochemistry was performed with antibodies against the P2X7 receptor as well as nitric oxide synthase (NOS), calbindin, calretinin, choline acetyltransferase (ChAT), or the pan-neuronal marker anti-HuC/D. RESULTS: Double immunolabeling demonstrated that 100% of NOS-, calbindin-, calretinin-, and ChAT-immunoreactive neurons in all groups expressed the P2X7 receptor. Following I/R, neuronal density decreased by 22.6% in P2X7 receptor-immunoreactive neurons, and decreased by 46.7, 38, 39.8, 21.7, and 20% in NOS-, calbindin-, calretinin-, ChAT-, and HuC/D-immunoreactive neurons, respectively, at 6, 24, and 72 h and 1 week following injury compared to the control and sham groups. We also observed a 14% increase in the neuronal cell body profile area of the NOS-immunoreactive neurons at 6 and 24 h post-I/R and a 14% increase in ChAT-immunoreactive neurons at 1 week following I/R. However, the average size of the calretinin-immunoreactive neurons was reduced by 12% at 6 h post-I/R and increased by 8% at 24 h post-I/R. CONCLUSIONS: This work demonstrates that I/R is associated with a significant loss of different subpopulations of neurons in the myenteric plexus accompanied by morphological changes, all of which may underlie conditions related to intestinal motility disorder

Metachronic malignant transformation of small bowel and rectal endometriosis in the same patient

[ES] Background: Malignant transformation of intestinal endometriosis is a rare event with an unknown rate of incidence. Metachronous progression of endometriosis to adenocarcinoma from two distant intestinal foci happening in the same patient has not been previously reported. Case presentation: We describe a case of metachronic transformation of ileal and rectal endometriosis into an adenocarcinoma occurring in a 45-year-old female without macroscopic pelvic involvement of her endometriosis. First, a right colectomy was performed due to intestinal obstruction by an ileal mass. Pathological examination revealed an ileal endometrioid adenocarcinoma and contiguous microscopic endometriotic foci. Twenty months later, a rectal mass was discovered. An endoscopic biopsy revealed an adenocarcinoma. En bloc anterior rectum resection, hysterectomy and bilateral salpingectomy were performed. A second endometrioid adenocarcinoma arising from a focus of endometriosis within the wall of the rectum was diagnosed. Conclusion: Intestinal endometriosis should be considered a premalignant condition in premenopausal women.

Importanza prognostica delle citochine e loro ruolo nell'immunomodulazione: risultati di studi sperimentali in vivo e in vitro

Citokines are proteins produced by several cell types and secreted in response to various stimuli. These molecules are able to modify the behaviour of other cells inducing activities like growth, differentiation and apoptosis. In the last years, veterinary scientists have investigated the role played by these factors; in fact, cytokines can act as intercellular communicative signals in immune response, cell damage repair and hematopoiesis. Up to date, various cytokines have been identified and in depth comprehension of their effects in physiology, pathology and therapy is an interesting field of research. This thesis aims to understand the role played by these mediators during natural or experimentally induced pathologies. In particular, it has been evaluated the genic and protein expressions of a large number of cytokines during several diseases and starting from different matrix. Considering the heterogeneity of materials used in experimentations, multiple methods and protocols of nucleic acids and proteins extractions have been standardized. Results on cytokines expression obtained from various in vitro and in vivo experimental studies have shown how important these mediators are in regulation and modulation of the host immune response also in veterinary medicine. In particular, the analysis of inflammatory and septic markers, like cytokines, has allowed a better understanding in the pathogenesis during horse Recurrent Airway Obstruction, foal sepsis, Bovine Viral Diarrhea Virus infection and dog Parvovirus infection and the effects of these agents on the host immune system. As experimentations with mice have shown, some pathologies of the respiratory and nervous system can be reduced or even erased by blocking cytokines inflammatory production. The in vitro cytokines expression evaluation in cells which are in vivo involved in the response to exogenous (like pathogens) or endogenous (as it happens during autoimmune diseases) inflammatory stimuli could represent a model for studying citokines effects during the host immune response. This has been analyzed using lymphocytes cultured with several St. aureus strains isolated from bovine mastitic milk and different colostrum products. In the first experiment different cytokines were expressed depending on enterotoxins produced, justifying a different behaviour of the microrganism in the mammal gland. In the second one, bone marrow cells derived incubated with murine lymphocytes with colostrum products have shown various cluster of differentiation expression , different proliferation and a modified cytokines profile. A better understanding of cytokine expression mechanisms will increase the know-how on immune response activated by several pathogen agents. In particular, blocking the cytokine production, the inhibition or catalyzation of the receptor binding mechanism and the modulation of signal transduction mechanism will represent a novel therapeutic strategy in veterinary medicine.

Revisione critica dei risultati e nuovi algoritmi decisionali sulla chirurgia dell'OSAS

Obstructive sleep apnoea/hypopnoea syndrome (OSAHS) is the periodic reduction or cessation of airflow during sleep. The syndrome is associated whit loud snoring, disrupted sleep and observed apnoeas. Surgery aims to alleviate symptoms of daytime sleepiness, improve quality of life and reduce the signs of sleep apnoea recordered by polysomnography. Surgical intervention for snoring and OSAHS includes several procedures, each designed to increase the patency of the upper airway. Procedures addressing nasal obstruction include septoplasty, turbinectomy, and radiofrequency ablation (RF) of the turbinates. Surgical procedures to reduce soft palate redundancy include uvulopalatopharyngoplasty with or without tonsillectomy, uvulopalatal flap, laser-assisted uvulopalatoplasty, and RF of the soft palate. More significant, however, particularly in cases of severe OSA, is hypopharyngeal or retrolingual obstruction related to an enlarged tongue, or more commonly due to maxillomandibular deficiency. Surgeries in these cases are aimed at reducing the bulk of the tongue base or providing more space for the tongue in the oropharynx so as to limit posterior collapse during sleep. These procedures include tongue-base suspension, genioglossal advancement, hyoid suspension, lingualplasty, and maxillomandibular advancement. We reviewed 269 patients undergoing to osas surgery at the ENT Department of Forlì Hospital in the last decade. Surgery was considered a success if the postoperative apnea/hypopnea index (AHI) was less than 20/h. According to the results, we have developed surgical decisional algorithms with the aims to optimize the success of these procedures by identifying proper candidates for surgery and the most appropriate surgical techniques. Although not without risks and not as predictable as positive airway pressure therapy, surgery remains an important treatment option for patients with obstructive sleep apnea (OSA), particularly for those who have failed or cannot tolerate positive airway pressure therapy. Successful surgery depends on proper patient selection, proper procedure selection, and experience of the surgeon. The intended purpose of medical algorithms is to improve and standardize decisions made in the delivery of medical care, assist in standardizing selection and application of treatment regimens, to reduce potential introduction of errors. Nasal Continuous Positive Airway Pressure (nCPAP) is the recommended therapy for patients with moderate to severe OSAS. Unfortunately this treatment is not accepted by some patient, appears to be poorly tolerated in a not neglible number of subjects, and the compliance may be critical, especially in the long term if correctly evaluated with interview as well with CPAP smart cards analysis. Among the alternative options in Literature, surgery is a long time honoured solution. However until now no clear scientific evidence exists that surgery can be considered a really effective option in OSAHS management. We have design a randomized prospective study comparing MMA and a ventilatory device (Autotitrating Positive Airways Pressure – APAP) in order to understand the real effectiveness of surgery in the management of moderate to severe OSAS. Fifty consecutive previously full informed patients suffering from severe OSAHS were enrolled and randomised into a conservative (APAP) or surgical (MMA) arm. Demographic, biometric, PSG and ESS profiles of the two group were statistically not significantly different. One year after surgery or continuous APAP treatment both groups showed a remarkable improvement of mean AHI and ESS; the degree of improvement was not statistically different. Provided the relatively small sample of studied subjects and the relatively short time of follow up, MMA proved to be in our adult and severe OSAHS patients group a valuable alternative therapeutical tool with a success rate not inferior to APAP.

Development of Clinical Decision Support Systems based on Mathematical Models of Physiological Systems

In the last years of research, I focused my studies on different physiological problems. Together with my supervisors, I developed/improved different mathematical models in order to create valid tools useful for a better understanding of important clinical issues. The aim of all this work is to develop tools for learning and understanding cardiac and cerebrovascular physiology as well as pathology, generating research questions and developing clinical decision support systems useful for intensive care unit patients. I. ICP-model Designed for Medical Education We developed a comprehensive cerebral blood flow and intracranial pressure model to simulate and study the complex interactions in cerebrovascular dynamics caused by multiple simultaneous alterations, including normal and abnormal functional states of auto-regulation of the brain. Individual published equations (derived from prior animal and human studies) were implemented into a comprehensive simulation program. Included in the normal physiological modelling was: intracranial pressure, cerebral blood flow, blood pressure, and carbon dioxide (CO2) partial pressure. We also added external and pathological perturbations, such as head up position and intracranial haemorrhage. The model performed clinically realistically given inputs of published traumatized patients, and cases encountered by clinicians. The pulsatile nature of the output graphics was easy for clinicians to interpret. The manoeuvres simulated include changes of basic physiological inputs (e.g. blood pressure, central venous pressure, CO2 tension, head up position, and respiratory effects on vascular pressures) as well as pathological inputs (e.g. acute intracranial bleeding, and obstruction of cerebrospinal outflow). Based on the results, we believe the model would be useful to teach complex relationships of brain haemodynamics and study clinical research questions such as the optimal head-up position, the effects of intracranial haemorrhage on cerebral haemodynamics, as well as the best CO2 concentration to reach the optimal compromise between intracranial pressure and perfusion. We believe this model would be useful for both beginners and advanced learners. It could be used by practicing clinicians to model individual patients (entering the effects of needed clinical manipulations, and then running the model to test for optimal combinations of therapeutic manoeuvres). II. A Heterogeneous Cerebrovascular Mathematical Model Cerebrovascular pathologies are extremely complex, due to the multitude of factors acting simultaneously on cerebral haemodynamics. In this work, the mathematical model of cerebral haemodynamics and intracranial pressure dynamics, described in the point I, is extended to account for heterogeneity in cerebral blood flow. The model includes the Circle of Willis, six regional districts independently regulated by autoregulation and CO2 reactivity, distal cortical anastomoses, venous circulation, the cerebrospinal fluid circulation, and the intracranial pressure-volume relationship. Results agree with data in the literature and highlight the existence of a monotonic relationship between transient hyperemic response and the autoregulation gain. During unilateral internal carotid artery stenosis, local blood flow regulation is progressively lost in the ipsilateral territory with the presence of a steal phenomenon, while the anterior communicating artery plays the major role to redistribute the available blood flow. Conversely, distal collateral circulation plays a major role during unilateral occlusion of the middle cerebral artery. In conclusion, the model is able to reproduce several different pathological conditions characterized by heterogeneity in cerebrovascular haemodynamics and can not only explain generalized results in terms of physiological mechanisms involved, but also, by individualizing parameters, may represent a valuable tool to help with difficult clinical decisions. III. Effect of Cushing Response on Systemic Arterial Pressure. During cerebral hypoxic conditions, the sympathetic system causes an increase in arterial pressure (Cushing response), creating a link between the cerebral and the systemic circulation. This work investigates the complex relationships among cerebrovascular dynamics, intracranial pressure, Cushing response, and short-term systemic regulation, during plateau waves, by means of an original mathematical model. The model incorporates the pulsating heart, the pulmonary circulation and the systemic circulation, with an accurate description of the cerebral circulation and the intracranial pressure dynamics (same model as in the first paragraph). Various regulatory mechanisms are included: cerebral autoregulation, local blood flow control by oxygen (O2) and/or CO2 changes, sympathetic and vagal regulation of cardiovascular parameters by several reflex mechanisms (chemoreceptors, lung-stretch receptors, baroreceptors). The Cushing response has been described assuming a dramatic increase in sympathetic activity to vessels during a fall in brain O2 delivery. With this assumption, the model is able to simulate the cardiovascular effects experimentally observed when intracranial pressure is artificially elevated and maintained at constant level (arterial pressure increase and bradicardia). According to the model, these effects arise from the interaction between the Cushing response and the baroreflex response (secondary to arterial pressure increase). Then, patients with severe head injury have been simulated by reducing intracranial compliance and cerebrospinal fluid reabsorption. With these changes, oscillations with plateau waves developed. In these conditions, model results indicate that the Cushing response may have both positive effects, reducing the duration of the plateau phase via an increase in cerebral perfusion pressure, and negative effects, increasing the intracranial pressure plateau level, with a risk of greater compression of the cerebral vessels. This model may be of value to assist clinicians in finding the balance between clinical benefits of the Cushing response and its shortcomings. IV. Comprehensive Cardiopulmonary Simulation Model for the Analysis of Hypercapnic Respiratory Failure We developed a new comprehensive cardiopulmonary model that takes into account the mutual interactions between the cardiovascular and the respiratory systems along with their short-term regulatory mechanisms. The model includes the heart, systemic and pulmonary circulations, lung mechanics, gas exchange and transport equations, and cardio-ventilatory control. Results show good agreement with published patient data in case of normoxic and hyperoxic hypercapnia simulations. In particular, simulations predict a moderate increase in mean systemic arterial pressure and heart rate, with almost no change in cardiac output, paralleled by a relevant increase in minute ventilation, tidal volume and respiratory rate. The model can represent a valid tool for clinical practice and medical research, providing an alternative way to experience-based clinical decisions. In conclusion, models are not only capable of summarizing current knowledge, but also identifying missing knowledge. In the former case they can serve as training aids for teaching the operation of complex systems, especially if the model can be used to demonstrate the outcome of experiments. In the latter case they generate experiments to be performed to gather the missing data.

Lagrange-Singularitäten

In dieser Arbeit wird eine Deformationstheorie fürLagrange-Singularitäten entwickelt. Wir definieren einen Komplex von Moduln mit nicht-linearem Differential, densogenannten Lagrange-de Rham-Komplex, dessen ersteKohomologie isomorph zum Raum der infinitesimalenLagrange-Deformationen ist. Wir beschreiben die Beziehung diesesKomplexes zur Theorie der Moduln über dem Ring vonDifferentieloperatoren. Informationen zur Obstruktionstheorie vonLagrange-Deformationen werden aus derzweiten Kohomologie des Lagrange-de Rham-Komplexes gewonnen.Wir zeigen, dass unter einer geometrischen Bedingung an dieSingularität ie Kohomologie von des Lagrange-deRham-Komplexes ausendlich dimensionalen Vektorräumen besteht. Desweiteren wirdeine Methode zur effektiven Berechnung dieser Kohomologie fürquasi-homogene Lagrange-Flächensingularitäten entwickelt. UnterZuhilfenahme von Computeralgebra wird diese Methode für konkreteBeispiele angewendet.

Immunohistochemical and Molecular Prognostic/Predictive Markers in Neoplastic Diseases

Traditional morphological examinations are not anymore sufficient for a complete evaluation of tumoral tissue and the use of neoplastic markers is of utmost importance. Neoplastic markers can be classified in: diagnostic, prognostic and predictive markers. Three markers were analyzed. 1) Insulin-like growth factor binding protein 2 (IGFBP2) was immunohistochemically examined in prostatic tissues: 40 radical prostatectomies from hormonally untreated patients with their preoperative biopsies, 10 radical prostatectomies from patients under complete androgen ablation before surgery and 10 simple prostatectomies from patients with bladder outlet obstruction. Results were compared with α-methylacyl-CoA racemase (AMACR). IGFBP2 was expressed in the cytoplasm of untreated adenocarcinomas and, to a lesser extent, in HG-PIN; the expression was markedly lower in patients after complete androgen ablation. AMACR was similarly expressed in both adenocarcinoma and HG-PIN, the level being similar in both lesions; the expression was slightly lower in patients after complete androgen ablation. IGFBP2 may be used a diagnostic marker of prostatic adenocarcinomas. 2) Heparan surface proteoglycan immunohistochemical expression was examined in 150 oral squamous cell carcinomas. Follow up information was available in 93 patients (range: 6-34 months, mean: 19±7). After surgery, chemotherapy was performed in 8 patients and radiotherapy in 61 patients. Multivariate and univariate overall survival analyses showed that high expression of syndecan-1 (SYN-1) was associated with a poor prognosis. In patients treated with radiotherapy, such association was higher. SYN-1 is a prognostic marker in oral squamous cell carcinomas; it may also represent a predictive factor for responsiveness to radiotherapy. 3) EGFR was studied in 33 pulmonary adenocarcinomas with traditional DNA sequencing methods and with two mutation-specific antibodies. Overall, the two antibodies had 61.1% sensitivity and 100% specificity in detecting EGFR mutations. EGFR mutation-specific antibodies may represent a predictive marker to identify patients candidate to tyrosine kinase inhibitors therapy.

Applicazioni cliniche e sperimentali dell’ecografia toracica in pneumologia: la diagnostica precoce delle patologie pleuropolmonari

Lung ultrasound use is increasing in respiratory medicine thanks to its development in the latest years. Actually it allows to study diseases of the chest wall (traumas, infections, neoplasms), diaphragm (paralysis, ipokinesis), pleura (effusions, pneumothorax, thickenings, neoplasms) and lung parenchyma (consolidations, interstitial syndromes, peripheral lesions). One of the most useful application of chest ultrasound is the evaluation of effusions. However, no standardized approach for ultrasound-guided thoracenthesis is available. Our study showed that our usual ultrasonographic landmark (“V-point”) could be a standard site to perform thoracenthesis: in 45 thoracenthesis no pneumothorax occurred, drainage was always successful at first attempt. Values of maximum thickness at V-point and drained fluid volume showed a significative correlation. Proteins concentration of ultrasound patterns of effusions (anechoic, ipoechoic, moving echoic spots, dense moving spots, hyperechoic) were compared to those of the macroscopic features of fluids showing connection between light-yellow fluid and echoic moving spots pattern and between ipoechoic/dense moving spots and cloudy-yellow/serum-haematic fluids. These observations suggest that ultrasound could predict chemical-physical features of effusions. Lung ultrasound provides useful information about many disease of the lung, but actually there is not useful in obstructive bronchial diseases. Analysing diaphragmatic kinetics using M-mode through transhepatic scan we described a similarity between diaphragm excursion during an expiratory forced maneuver and the volume/time curve of spirometry. This allowed us to identify the M-mode Index of Obstruction (MIO), an ultrasound-analogue of FEV1/VC. We observed MIO values of normal subjects (9) and obstructed patients (9) comparing the two groups. FEV1/VC and MIO showed a significant correlation suggesting that MIO may be affected by airways obstruction; MIO values were significatively different between normal and obstructed so that it could identify an obstructive syndrome. The data show that it is possible to suspect the presence of obstructive syndrome of the airways using ultrasonography of the diaphragm.

Biomarkers in chronic obstructive pulmonary diseases. Clinical and functional correlations.

Asthma and chronic obstructive pulmonary disease (COPD) are two distinct lung diseases with distinctive clinical and inflammatory features. A proportion of asthmatic patients experience a fixed airflow obstruction that persists despite optimal pharmacologic treatment for reasons that are still largely unknown. We found that patients with asthma and COPD sharing a similar fixed airflow obstruction have an increased lung function decline and frequency of exacerbations. Nevertheless, the decline in lung function is associated with specific features of the underlying inflammation. Airway inflammation increases during asthma exacerbation and disease severity. Less is known about the correlations between symptoms and airway inflammation in COPD patients. We found that there is no correlation between symptoms and lung function in COPD patients. Nevertheless symptoms changes are associated with specific inflammatory changes: cough is associated with an increase of sputum neutrophils in COPD, dyspnoea is associated with an increase of eosinophils. The mechanisms of this correlation remain unknown. Neutrophils inflammation is associated with bacterial colonization in stable COPD. Is not known whether inhaled corticosteroids might facilitate bacterial colonization in COPD patients. We found that the use of inhaled corticosteroids in COPD patients is associated with an increase of airway bacterial load and with an increase of airway pathogen detection. Bacterial and viral infections are the main causes of COPD and asthma exacerbations. Impaired innate immune responses to rhinovirus infections have been described in adult patients with atopic asthma. Whether this impaired immune condition is present early in life and whether is modulated by a concomitant atopic condition is currently unknown. We found that deficient innate immune responses to rhinovirus infection are already present early in life in atopic patients without asthma and in asthmatic subjects. These findings generalize the scenario of increased susceptibility to viral infections to other Th2 oriented conditions.

La terapia combinata di cellule mesenchimali stromali e aceinibitori riduce la fibrosi renale in un modello animale di ostruzione ureterale unilaterale

Le cellule mesenchimali stromali (MSC) sono cellule multipotenti e numerosi studi hanno mostrato i loro effetti benefici nel danno renale acuto ma non sono ancora stati dimostrati potenziali effetti nella malattia renale cronica. L'ostruzione ureterale unilaterale (UUO) è un modello di fibrosi interstiziale nel quale l'attivazione di molecole vasoattive, citochine profibrotiche e infiammatorie gioca un ruolo patogenetico nello sviluppo dell'apoptosi e atrofia tubulare. Il sistema renina-angiotensina (RAS) gioca un ruolo chiave nello sviluppo della fibrosi renale e i farmaci che hanno come target l'angiotensina II, principale mediatore del RAS, sono attualmente la terapia più efficace nel ridurre la progressione della malattia renale cronica. E' noto che gli ACE-inibitori (ACEi) inducono un aumento compensatorio della renina plasmatica per la mancaza del feedback negativo sulla sua produzione. Tuttavia, la renina (R) promuove il danno renale non solo stimolando la produzione di ANGII, ma anche up-regolando geni profibrotici attraverso l'attivazione del recettore renina/prorenina. Lo scopo dello studio è stato indagare se l'infusione di MSC riduceva il danno renalein un modello animale di UUO e comparare gli eventuali effetti protettivi di ACEi e MSC in UUO. Abbiamo studiato 5 gruppi di ratti. A: sham operati. B: ratti sottoposti a UUO che ricevevano soluzione salina. C: ratti sottoposti a UUO che ricevavano MSC 3X106 nella vena della coda al giorno 0. D:ratti sottoposti a UUO che ricevevano lisinopril dal g 1 al g 21. E: ratti sottoposti a UUO che ricevevano MSC 3X106 nella vena della coda al giorno 0 e lisinopril dal g 1 al g 21. I ratti sono stati sacrificati al giorno 7 e 21. I risultati dello studio mostrano che MSC in UUO prevengono l'aumento della renina, riducono la generazione di ANGII e che in terapia combinata con ACEi riducono ulteriormente l'ANGII, determinando una sinergia nel miglioramento della fibrosi renale.