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Biomedical subjects

A Fabbri

Publications and source records attributed to A Fabbri.

At least 37 records · Page 2Linked to original sources

Are subjects with erectile dysfunction aware of their condition? Results from a retrospective study based on an Italian free-call information service.

The aim of the study was to analyse the socio-demographic and epidemiological characteristics of the Italian male population affected by sexual disturbances. Men complaining of erectile dysfunction (ED) who called the Pfizer program "Man and Woman in Health" between April 18th 2001 and May 27th 2002 and asked for information about their medical condition, were interviewed by trained doctors using a computer-assisted questionnaire. 16007 out of 25018 calls were considered for statistical analysis. Mean age of callers was 48.8+/-14.2 yr, reporting ED in 83% of cases. In the majority of men ED was severe (58%) and lasting more than 3 yr (25%). Multivariate analysis revealed that diabetes, depression, prostate surgery, heart disease, neurological disorders, liver and renal diseases were all significant and independent contributors to the degree of erectile impairment adjusted for age (p<0.001). The principal concomitant medications were anti-hypertensive (23%), antidiabetic (9%) and cardiovascular agents (6%). Cigarette smoking was present in 24%. On directed questioning of the caller, anxiety and distress were perceived as the most frequent causes of ED (42%) across all age groups, followed by the presence of concomitant disease/s (26%) especially in aging men. Also, a large number of men (41 %) with severe ED waited for more than 3 yr before looking for medical referral. Interestingly, only 19% had ever tried any specific medication for ED. These data indicate that 5 yr after worldwide approval and release of sildenafil, ED is still largely undiagnosed and under-treated, possibly because it is still perceived as a condition mainly due to distress or advancing age and therefore not deserving medical referral. Effective prevention of ED commences with better awareness of the pathological causes by the population and modification of risk factors by the doctors.

Adult↗

A new polymorphism (Ser362Thr) of the L-myc gene is not associated with lung adenocarcinoma risk and prognosis.

The non-coding variation in the second intron of the L-myc gene, generating an EcoRI polymorphism, is associated with lung cancer risk and prognosis. We carried out sequence analysis of the L-myc gene in lung adenocarcinoma (ADCA) patients to identify functional polymorphisms and identified a new single nucleotide polymorphism (SNP) in the third exon of the gene causing a Ser362Thr conservative amino acid change in the C-terminus of the encoded protein. This polymorphism showed significant linkage disequilibrium with the L-myc EcoRI polymorphism located at 1751 bp distance. Genotyping of the Ser362Thr SNP in 220 Italian ADCA patients and in 230 general population controls revealed a similar low frequency (0.10-0.11) of the Thr allele in both groups. The multivariate odds ratio was 0.68 (95% confidence interval (CI) 0.38-1.22). In the ADCA patients, no significant association between the Ser/Thr polymorphism and survival was observed. Thus, the present results do not support candidacy of the L-myc Ser362Thr polymorphism for the functional polymorphism of the L-myc genomic region.

Adenocarcinoma↗

A combined HPLC-immunoenzymatic comprehensive screening for suspected drug poisoning in the emergency department.

OBJECTIVE: To review the results of a comprehensive drug screening as first line diagnostic tool in patients attending an emergency department for suspected drug poisoning. METHODS: A comprehensive drug screening was carried out in plasma or urine, or both, of 310 patients combining an HPLC multidrug profiling system and a fluorescence polarisation immunoassay. RESULTS: In 64.2% of cases the screening confirmed the diagnosis of drug poisoning, in 13.9% suspected drugs were measurable at non-toxic concentrations, and in 21.9% no drugs were found. The suspected drugs were fully confirmed in a minority of cases, (symptomatic patients: 28.2% compared with asymptomatic: 16.5%). Symptomatic patients were less likely to have at least one suspected drug (29.6% compared with 57.7%; p<0.001), and more likely to have at least one unsuspected drug found at analysis (17.4% compared with 3.1%; p = 0.005). In 5% of patients, asymptomatic when first observed, one or more unsuspected drugs were found. In 6 of 29 patients, with suspected poisoning of an unspecified drug, the screening identified the specific drug and excluded acute intoxication in the remaining cases. CONCLUSION: A rapid comprehensive drug screening adds to the diagnosis of patients with suspected drug poisoning, identifying unsuspected drugs in symptomatic patients and excluding drugs in asymptomatic subjects.

Acute Disease↗

Prospective validation of a proposal for diagnosis and management of patients attending the emergency department for mild head injury.

BACKGROUND: In mild head injury, predictors to select patients for computed tomography (CT) and/or to plan proper management are needed. The strength of evidence of published recommendations is insufficient for current use. We assessed the diagnostic accuracy and the clinical validity of the proposal of the Neurotraumatology Committee of the World Federation of Neurosurgical Societies on mild head injury from an emergency department perspective. METHODS: In a three year period, 5578 adolescent and adult subjects were prospectively recruited and managed according to the proposed protocol. Outcome measures were: (a) any post-traumatic lesion; (b) need for neurosurgical intervention; (c) unfavourable outcome (death, permanent vegetative state or severe disability) after six months. The predictive value of a model based on five variables (Glasgow coma score, clinical findings, risk factors, neurological deficits, and skull fracture) was tested by logistic regression analysis. FINDINGS: At first CT evaluation 327 patients (5.9%) had intracranial post-traumatic lesions. In 16 cases (0.3%) previously undiagnosed lesions were detected after re-evaluation within seven days. Neurosurgical intervention was needed in 71 patients (1.3%) and an unfavourable outcome occurred in 39 cases (0.7%). The area under the ROC curve of the variables in predicting post-traumatic lesions was 0.906 (0.009) (sensitivity 70.0%, specificity 94.1% at best cut off), neurosurgical intervention was 0.926 (0.016) (sensitivity 81.7%, specificity 94.1%), and unfavourable outcome was 0.953 (0.014) (sensitivity 88.1%, specificity 95.1%). INTERPRETATION: The variables prove highly accurate in the prediction of clinically meaningful outcomes, when applied to a consecutive set of patients with mild head injury in the clinical setting of a 1st level emergency department.

Adolescent↗

The Rac-activating toxin cytotoxic necrotizing factor 1 oversees NK cell-mediated activity by regulating the actin/microtubule interplay.

The cell cytoskeleton is widely acknowledged as a master for NK cell function. Specifically, actin filaments guide the NK cell binding to target cells, engendering the formation of the so-called immunological synapse, while microtubules direct the killer behavior. All these cytoskeleton-dependent activities are competently governed by the Rho GTPases, a family of regulatory molecules encompassing the three different subfamilies, Rho, Rac, and Cdc42. By using a Rac GTPase-activating bacterial protein toxin from Escherichia coli named cytotoxic necrotizing factor 1 (CNF1), we obtained results supporting the activation of Rac GTPase as a booster for effector cell-binding efficiency, recruitment ability, and, consequently, cytotoxicity. In particular, the augmented killer capacity of CNF1-treated NK cells was associated with the increased expression of certain cell adhesion or activation-associated molecules and the reshaping of the actin and microtubule networks. Importantly, CNF1 counteracted the activity exerted by toxins disrupting the cytoskeletal architecture. Hence, the activation of Rho GTPases, particularly Rac, induced by CNF1, appears to orchestrate a dynamic cross talk between microtubules and actin filaments, leading to a fruitful NK cell activity and polarization state. Our findings suggest that protein toxins might be viewed as modulators of NK cell cytotoxic activity and could possibly be regarded as useful pharmacological tools for certain Rho-linked immune diseases in the near future.

Actins↗

Dilated intercellular spaces as a marker of oesophageal damage: comparative results in gastro-oesophageal reflux disease with or without bile reflux.

BACKGROUND: The dilation of oesophageal intercellular spaces, clearly apparent in transmission electron microscopy images, is a marker of cellular damage induced by acid. AIM: To analyse the presence of dilated intercellular spaces and to quantify the scores in controls and in patients with gastro-oesophageal reflux disease or duodenal gastro-oesophageal reflux accompanied by erosive or non-erosive reflux disease. METHODS: Thirty-eight symptomatic patients with gastro-oesophageal reflux disease or duodenal gastro-oesophageal reflux and 12 asymptomatic controls, classified on the basis of pH-metry and bilimetry, underwent endoscopy. Six tissue biopsies were taken from the normal mucosa for light microscopy and transmission electron microscopy evaluation. Dilated intercellular spaces were measured on photomicrographs of the specimens (at least 100 transects were measured for each patient). RESULTS: Twenty-two patients with gastro-oesophageal reflux disease had normal macroscopic mucosa but, at histology, five patients with erosive gastro-oesophageal reflux disease had mild oesophagitis and one had moderate oesophagitis. Seven patients with duodenal gastro-oesophageal reflux had normal mucosa, whilst three with erosive duodenal gastro-oesophageal reflux had mild oesophagitis at histology. At transmission electron microscopy, all controls had dilated intercellular spaces of less than 1.69 microm. Each symptomatic patient had a mean dilated intercellular space value and a mean value of the maximum dilated intercellular space at least three or more times greater than that in controls (P < 0.001). No statistical differences were observed between erosive and non-erosive oesophagitis. CONCLUSIONS: The dilated intercellular space is an extremely sensitive marker of damage in gastro-oesophageal reflux disease, duodenal gastro-oesophageal reflux and non-erosive reflux disease, and serves as the most appropriate marker of damage evaluation in non-erosive reflux disease reported to date. A mean dilated intercellular space of 0.74 micro m provides a cut-off score for damage. No quantitative or qualitative differences in dilated intercellular space scores were found between pure and mixed acid reflux.

Adult↗

Experience with an elective vacuum assisted cardiopulmonary bypass in the surgical treatment of renal neoplasms extending into the right atrium.

PURPOSE: We evaluate the results of an elective cardiopulmonary bypass conceived to minimize the surgical risk related to its use with temporary circulatory arrest and deep hypothermia in the treatment of patients with renal tumor extending into the right atrium. MATERIALS AND METHODS: From July 1996 to December 2000, 19 patients with renal neoplasm and venous involvement were admitted to our department. Three patients 4, 57 and 58 years old with a right (2) and left (1) renal tumor extending into the right atrium underwent radical nephrectomy and tumor thrombus removal using a normothermic cardiopulmonary bypass. The bypass circuit was connected with a vacuum assisted venous drainage giving a negative pressure of 20 to 40 mm. Hg. Neither circulatory arrest nor hypothermia was used. Tumor thrombus was extracted through a longitudinal "cavotomy" and removed along with the kidney. RESULTS: Total cardiopulmonary bypass time was 14, 19 and 22 minutes, respectively. No intraoperative or postoperative complications due to surgical technique occurred. No significant bleeding was observed at the time of cavotomy and all neoplastic tissue was removed. Pathological examination documented renal cell carcinoma in 2 cases and Wilms tumor in 1. All the patients are alive 30, 42 and 15 months, respectively, after the operation. CONCLUSIONS: Normothermic cardiopulmonary bypass with vacuum assisted venous drainage makes circulatory arrest and hypothermia unnecessary and avoids the potential complications associated with these procedures. With respect to veno-venous shunts this technique guarantees complete surgical control of the thrombus and avoids the need for extensive dissection of the retrohepatic vena cava and Pringle maneuver.

Cardiopulmonary Bypass↗

Hijacking Rho GTPases by protein toxins and apoptosis: molecular strategies of pathogenic bacteria.

Certain bacterial toxins and type-III-translocated virulence factors have a peculiar property: they exert part of their actions by modulating Rho GTPases. These toxins target the actin cytoskeleton of host cells and reorganize it to their own advantage, either to facilitate macropinocytosis, which is required for invasive bacteria to enter cells, or to block pathogen sequestration by macrophages. In addition, by acting on Rho GTPases, bacteria may also interfere with the fate of host cells, favoring survival or death depending on their needs. Rho GTPases control the activation of NF-kappaB, which is involved in the expression of antiapoptotic proteins and mediates immunological responses as well. Here, we give a perspective on how NF-kappaB may participate in linking Rho-acting toxins and apoptosis.

Animals↗

Comprehensive drug screening in decision making of patients attending the emergency department for suspected drug overdose.

OBJECTIVES: This study aimed to evaluate the usefulness of a comprehensive drug screening method as a first line diagnostic tool on clinical decision making in patients attending an emergency department for suspected drug overdose in terms of agreement between physicians on patients' disposal. METHODS: Five emergency physicians retrospectively evaluated the records of 142 adult patients, admitted to the emergency department of a community hospital for suspected drug overdose. They were asked for an expert opinion on patients' disposal at the end of the observation period, based on paired records, with/without the results of a comprehensive drug screening. RESULTS: In the absence of the drug screening, a very poor agreement (kappa statistics) was observed between physicians. When the drug screening was available, the interobserver agreement for decision on patients' disposal increased to the fair to good range (global agreement: from 0.238 (0.019) to 0.461 (0.020) (mean(SE)); p<0.001). The agreement also increased when admission to an intensive care unit, to a general ward, and discharge from hospital were separately analysed. The availability of drug screening would have saved 21.7% of hospital admissions and 53.3% of high dependency and/or intensive care unit admissions. CONCLUSION: Comprehensive drug screening adds to decision making for patients attending an emergency department for suspected drug overdose, improving agreement among physicians on patients' disposal and potentially saving hospital resources.

Adult↗

Pathology of erection.

Erectile dysfunction (ED) is defined as the inability to achieve and maintain a penile erection which is adequate for satisfactory sexual intercourse. It is a significant male health problem affecting approximately 150 million men worldwide. This value is expected to more than double by the year 2025. The incidence of ED increases sharply with age since it is a common cross-cultural denominator, affecting 19 to 64% of men aged 40 to 80 years, both in developing and industrialized countries. Epidemiological studies may underestimate the true dimensions of the problem because of the embarrassment or stigma that is associated with ED. Men with ED may experience diminished self-image and self-esteem, anxiety and fears of rejection, and even depression as psychogenic factors. Pathologic conditions which are commonly encountered in the ageing male (diabetes, hypertension, atherosclerosis, cardiovascular disease, etc) as well as chronic diseases (arthritis, renal and hepatic failure, pulmonary disease) represent a frequent cause of organic ED and are often treated with medications that can interfere with sexual function at central and/or peripheral level. In addition, incorrect lifestyle--i.e. obesity, cigarette smoking, alcohol or drug abuse--may all contribute to the onset of ED. Finally, trauma or surgery affecting either the nervous system or interfering with the blood supply to the penis are associated with increased incidence of ED.

Disease↗

Non-invasive vascular imaging for erectile dysfunction.

In the era of orally active agents the clinical context of the diagnosis and treatment of erectile dysfunction (ED) has radically changed. There is a general trend oriented towards choosing invasive diagnostic testing and surgical treatment solutions. Along this view, penile pharmacotesting (PPT) may represent an inexpensive and easy diagnostic procedure to be performed in the office setting. However, this procedure provides no direct vascular imaging, has a high percentage of false diagnoses and its accuracy for subsequent treatment decisions remains quite limited. Hence, home testing with orally active agents may provide better information for the patient's goals. In the diagnostic work-up of ED, the combination of PPT plus colour-duplex Doppler ultrasonography (CDDU) has gained more credit because of a higher diagnostic accuracy than PPT alone, so that it should be always performed when possible. It represents an accurate mean to predict cavernous artery inflow and venous leakage when compared to more invasive diagnostic techniques; in fact it allows the measurement of the resistive index when maximal response to vasodilator challenge has occurred. In conclusion, we recommend CDDU to all ED patients with a significant risk of cardiovascular disease, as well as in the presence of penile plaques whereas a frequent involvement of neuro-anatomical structures occurs. Other vascular testing--i.e. natural penile tumescence, cavernosometry/graphy, angiography are reserved to selected patients in whom CDDU alone has provided inconsistent information.

Erectile Dysfunction↗

[Cutaneous angiosarcoma arising after radiotherapy treatment of a breast carcinoma. Description of a case and review of the literature].

Cutaneous angiosarcomas occurring as a complication of radiation therapy for breast cancer are rare. To the best of our knowledge 37 cases have been reported in English literature during the last two decades. We describe a case of angiosarcoma arising in the skin of a breast previously irradiated for breast carcinoma. The patient, a 74-year-old woman, had been treated with conservative surgery and radiotherapy for a pT1N0 infiltrating ductal carcinoma of the left breast in 1993. Nine years later a skin lesion, which was interpreted as a recurrence, arose in the same site. A biopsy obtained from the lesion, and initially considered to be negative for cancer, showed istological features consistent with those of the atypical vascular lesion. Seven months later the same lesion transformed in a 5 x 3 reddish mass which at histological examination was diagnosed as an high grad post-irradiation angiosarcoma of the skin of the breast. Data on previously reported post iradiation angiosarcoma of the breast are reviewed; further consideration on differential diagnosis between those lesions and atypical vascular lesions are presented.

Aged↗

Dynamic testing in the evaluation of male gonadal function.

The maturation and physiologic functions of male sexual apparatus are under the control of the hypothalamic-pituitary-gonadal (HPG) axis. The determination of gonadotropins and testosterone as secretory products of pituitary and gonads, respectively, represents the first step in the evaluation of male sexual function and the diagnosis of disorders in male reproductive axis. However, there are several clinical situations that require a dynamic evaluation of this system and the measurement of basal gonadotropins and testosterone must be combined with specific dynamic tests. These mainly consist in GnRH stimulation, which evaluates the endocrine reserve capacity of the pituitary, and human chorionic gonadotropin (hCG) stimulation, which is used in the assessment of Leydig cells activity. The paper illustrates the technical aspects, the normal/pathological responses and the role of these two tests in assessing the male HPG axis in respect to different clinical diagnostic queries.

Adolescent↗

Epithelial cells challenged with a Rac-activating E. coli cytotoxin acquire features of professional phagocytes.

Activation of Rho, Rac and Cdc42 GTPases by an Escherichia coli cytotoxin (CNF1) has been reported to induce a phagocytic-like activity by epithelial cells in terms of a ruffle-driven capture and ingestion of large material. More recently, it has been reported that treatment with CNF1 induces superoxide anion release by these cells following a phagocytic stimulus. We herein show that in epithelial cells both transfection with the dominant form of Rac (RacV12) and treatment with the Rac-activating epidermal growth factor (EGF) may increase the secretion of superoxide anions on challenge with latex beads. Moreover, exposure to CNF1 induces a significant augmentation of acidic vesicles where the internalized particles were detectable. Our results indicate that (i) Rac is a pivotal GTPase for inducing in epithelial cells superoxide anion generation and (ii) the internalized material travels trough acidic compartments in CNF1-treated epithelial cells. Altogether this suggests a novel role for epithelial cells that, following Rac activation, might share with professional phagocytes the task of eliminating unwanted pathogens.

Bacterial Toxins↗

Epithelial cells and expression of the phagocytic marker CD68: scavenging of apoptotic bodies following Rho activation.

Macropinocytosis is a ruffling-driven process which drives the ingestion of large particles by both macrophages and epithelial cells. In this context, we have previously described a Rho-activating bacterial toxin from E. coli, the cytotoxic necrotizing factor 1 (CNF1), which allows epithelial cells to macropinocytose not only latex beads and bacteria, but also apoptotic cells in a fashion similar to that of professional phagocytes. We herein report that (i) epithelial cells express the typical phagocytic marker CD68, (ii) Rho activation by CNF1 varies the intracellular localization of CD68, which appears to be co-distributed, as in macrophages, with the homologous lysosomal protein Lamp-1. Together with the capability of digesting apoptotic cells following their internalization, our findings indicate that Rho-activated epithelial cells behave in most respects as professional phagocytes.

Acute-Phase Proteins↗