Surgical approach to vesicourethral anastomotic stricture following radical prostatectomy.

INTRODUCTION: Vesicourethral anastomotic stricture following prostatectomy is uncommon but represents a challenge for reconstructive surgery and has a significant impact on quality of life. The aim of this study was to relate our experience in managing vesicourethral anastomotic strictures and present the treatment algorithm used in our institution. PATIENTS AND METHODS: We performed a descriptive, retrospective study in which we assessed the medical records of 45 patients with a diagnosis of vesicourethral anastomotic stricture following radical prostatectomy. The patients were treated in the same healthcare centre between January 2002 and March 2015. Six patients were excluded for meeting the exclusion criteria. The stricture was assessed using cystoscopy and urethrocystography. The patients with patent urethral lumens were initially treated with minimally invasive procedures. Open surgery was indicated for the presence of urethral lumen obliteration or when faced with failure of endoscopic treatment. Urinary continence following the prostatectomy was determinant in selecting the surgical approach (abdominal or perineal). RESULTS: Thirty-nine patients treated for vesicourethral anastomotic stricture were recorded. The mean age was 64.4 years, and the mean follow-up was 40.3 months. Thirty-three patients were initially treated endoscopically. Seventy-five percent progressed free of restenosis following 1 to 4 procedures. Twelve patients underwent open surgery, 6 initially due to obliterative stricture and 6 after endoscopic failure. All patients progressed favourable after a mean follow-up of 29.7 months. CONCLUSIONS: Endoscopic surgery is the initial treatment option for patients with vesicourethral anastomotic strictures with patent urethral lumens. Open reanastomosis is warranted when faced with recalcitrant or initially obliterative strictures and provides good results.

Tuberculosis: medico-legal aspects.

Tuberculosis is a diffusive infectious disease whose typical behaviour differentiates it from other infectious diseases spread by human-to-human transmission (flu, chicken pox, cholera, etc.) that follow a classic epidemic pattern. Indeed, in the presence of a known source of Koch bacilli that is capable of spreading the bacteria by air, not all exposed individuals inhale the bacteria, not all those who inhale them absorb them, not all those who absorb the bacteria are unable to eliminate them, not all who are able to eliminate them do so using delayed hypersensitivity, not all those who react with delayed hypersensitivity suffer lasting tissue damage (among other things, minor), not all who suffer tissue damage have anatomical sequelae, and not all those who have anatomical sequelae, however minimal, become carriers of bacilli in the latent period. The vast majority (90-95%) of the latter - which are in any case a portion, not the totality of those exposed - remain asymptomatic throughout their lives and never develop active tuberculosis. Based on these biological characteristics and the legal concepts of "epidemic" and "disease," it becomes highly problematic, if not impossible, to assert both that tuberculosis can cause events of sufficient magnitude to be associated with the crime of "epidemic," and that the mere diagnosis of a latent tuberculosis infection is sufficient to assume the presence of an illness legally prosecutable in criminal proceedings or a disability prosecutable in civil proceedings. Furthermore, clinically apparent tuberculosis is a temporarily-and in some cases permanently-disabling condition, and in certain work environments, even with the difficulties caused by the lack of available effective diagnostic tools and the insidious behaviour of the disease in the early stages, targeted monitoring to identify other persons who may become ill is appropriate.

Urgent lung transplantation national program: the Italian experience.

INTRODUCTION: An urgent lung transplantation national program in Italy was developed over the past three years. Indispensable conditions that were included in the program were invasive respiratory support and/or extracorporeal vascular device (DECAP excluded). The aim of this study was to test the effectiveness of the program. MATERIALS AND METHODS: We analyzed urgent lung requests received between 2009 and 2011 taking into account primary pathology, request outcome, average waiting time, and organ origin. Taking as reference the same period of time, we also examined the ordinary waiting list, waiting list mortality, and number of transplantations performed and we have compared them with another three-year period prior to the activation of the program. RESULTS: The total number of urgent requests was 43. Primary pathologies with the highest incidence proportion were cystic fibrosis (40%) and idiopathic pulmonary fibrosis (26.6%). A total of 34 requests (79%) were successfully dealt with and 9 of them were suspended because of worsening conditions. The average waiting time was 17.9 days. During the same period of time 340 lung transplantations were performed and there were 499, 524, and 564 wait-listed patients in 2009, 2010, and 2011, respectively. The mortality rate was 21.3%. Over the previous three-year period 295 transplantations were performed and there were 457, 476, and 464 wait-listed patients in 2006, 2007, and 2008, respectively. Also the mortality rate was 25.3%. DISCUSSION: Urgent lung transplantations can provide patients in an imminent life-threatening situation with adequate care without affecting the mortality rate of patients on the ordinary waiting list.

Chiral recognition by the copper(II) complex of 6-deoxy-6-N-(2-methylaminopyridine)-beta-cyclodextrin.

A modified beta-cyclodextrin bearing a 2-aminomethylpyridine binding site for copper(II) (6-deoxy-6-[N-(2-methylamino)pyridine)]-beta-cyclodextrin, CDampy) was synthesized by C6-monofunctionalization. The acid-base properties of the new ligand in aqueous solution were investigated by potentiometry and calorimetry, and its conformations as a function of pH were studied by NMR and circular dichroism (c.d.). The formation of binary copper(II) complexes was studied by potentiometry, EPR, and c.d.. The copper(II) complex was used as chiral selector for the HPLC enantiomeric separation of underivatized aromatic amino acids. Enantioselectivity in the overall stability constants of the ternary complexes with D- or L-Trp was detected by potentiometry, whereas the complexes of the Ala enantiomers did not show and difference in stability. These results were consistent with a preferred cis coordination of the amino group of the ligand and of the amino acid in the ternary complexes ("cis effect"), which leads to the inclusion of the aromatic side chain of D-Trp, but not of that of L-Trp. In Trp-containing ternary complexes, the two enantiomers showed differences in the fluorescence lifetime distribution, consistent with only one conformer of D-Trp and two conformers of L-Trp, and the latter were found to be more accessible to fluorescence quenching by acrylamide and KI.

Suramin blocks the binding of interleukin-1 to its receptor and neutralizes IL-1 biological activities.

This report demonstrates the ability of the anti-cancer drug suramin to interfere with the binding of interleukin (IL)-1 to its receptor and to inhibit IL-1-induced biological activities. In a radioreceptor cell based assay, suramin inhibits the binding of IL-1 alpha to several murine cell lines expressing predominantly type I and type II IL-1 receptors. Affinity cross-linking experiments using IL-1 alpha and EL-4.6.1 cells confirms that suramin inhibits the binding of the ligand to the 80 kDa IL-1 type I receptor. In contrast, suramin fails to displace significantly prebound IL-1. In a cell-free system, suramin prevents the binding of IL-1 alpha and IL-1 beta to murine and human recombinant soluble type I IL-1 receptors. For example, the IC50 for suramin inhibiting IL-1 alpha and IL-1 beta binding to soluble human IL-1 receptor were 204 microM and 186 microM, respectively. The suramin analogues, NF-058 and NF-103 (which bear the same number of sulfate groups as suramin), are between three- and ten-fold less active than suramin in inhibiting IL-1 binding to EL-4.6.1 cells, and to recombinant soluble IL-1 receptor. Furthermore, in a dose-dependent manner suramin prevents several IL-1 mediated biological responses, including thymocyte proliferation, PGE-2 synthesis and IL-6 production. The inhibitory effect of the drug can be significantly reversed by the addition of excess cytokine. Taken together, the results indicate that suramin is a competitive IL-1 receptor antagonist. Because IL-1 participates in a broad range of immunological and inflammatory functions, the data suggest that suramin administration may influence important activities beyond those associated strictly with tumor inhibition.

Suramin interferes with interleukin-6 receptor binding in vitro and inhibits colon-26-mediated experimental cancer cachexia in vivo.

Neoplastic diseases are frequently associated with metabolic changes collectively known as cancer cachexia. The presence of cachexia complicates therapeutic intervention and is an important cause of death in cancer patients. At present there is no effective treatment for cachexia. Recently, the involvement of interleukin-6 (IL-6) in the wasting of colon-26 adenocarcinoma-bearing mice was demonstrated. The research presented here establishes an anticachectic role for the experimental drug suramin, since it partially blocks (up to 60%) the catabolic effects associated with the growth of this tumor in vivo. Suramin prevents the binding of IL-6 to its cell surface receptor subunits, as demonstrated by radioreceptor binding assay and affinity crosslinking experiments. Furthermore, the uptake of radioactive IL-6 by the liver is significantly reduced in suramin-treated mice. On the other hand, the drug is approximately 10-fold less potent in inhibiting the binding of tumor necrosis factor-alpha to indicator cell line in vitro and fails to block liver uptake of this cytokine in vivo. Collectively, these results suggest that suramin inhibits cancer-associated wasting, in part by interfering with the binding of IL-6 to its receptor. Whether suramin inhibits the action of other factors/cytokines that may also participate in colon-26-mediated cachexia is not yet known.

[A comparison between traditional mammography and digital with storage phosphors]. / Confronto tra mammografia tradizionale e digitale con fosfori a memoria.

Conventional and digital mammographic images obtained with storage phosphors were compared. The digital images were acquired with high-resolution 3rd-generation (HR III) screens and specifically adapted algorithms. The experience was made both on a phantom and in vivo. The phantom study was carried out by comparing conventional with digital radiographs acquired with: a) same kV (28) and same mAs; b) same kV (24) and same mAs; c) 28 kV with 30% mAs reduction, in digital images only. The results obtained upon counting the amount of recognizable details per image demonstrated slight loss of information in digital radiographs only when mAs was reduced by 30%. Two hundred patients were studied; they were divided into four groups according to the type of breast (medium inherent contrast or solid breast) and to exposure factors. After conventional mammography, an additional digital radiograph was performed using one of the three techniques previously employed on the phantom. Separately, 10 ductogalactographies and 10 magnification radiographs of microcalcifications were compared; the same exposure factors were used in these images too. The radiographs were viewed by three expert mammographic radiologists; contrast quality and spatial resolution were investigated and a score was given to each image on a 3-grade scale (insufficient, sufficient, good). The comparison of the mean values obtained showed higher contrast and better enhancement of nodular lesions on digital images, on which, however, the depiction of microcalcifications was worse than on conventional radiographs, especially with lower radiation doses, even though the number of detected microcalcifications was the same.

Direct association of interleukin-6 with a 130-kDa component of the interleukin-6 receptor system.

Affinity cross-linking of membrane bound 125I-interleukin-6 (IL-6) on several cell lines revealed a three-band pattern of IL-6-containing cross-linked complexes with molecular masses of 100, 120, and 150 kDa. To identify the membrane components that were associated with IL-6 in the three complexes, we employed the Denny-Jaffe reagent, a heterobifunctional, cleavable cross-linker that allows the transfer of 125I from the ligand to its receptor. Samples cross-linked with Denny-Jaffe reagent were analyzed by two-dimensional SDS-polyacrylamide gel electrophoresis in which the cross-linker was cleaved prior to the second dimension. This analysis revealed that IL-6 directly associates with a 130-kDa membrane protein thus allowing the formation of the 150-kDa complex. In addition, both the 100- and 120-kDa cross-linked complexes were shown to include an 80-kDa membrane glycoprotein associated with one and two IL-6 molecules, respectively.

[The computed tomographic diagnosis of malignant pleural mesothelioma. A multicenter study]. / Diagnosi con Tomografia Computerizzata del mesotelioma pleurico maligno. Studio multicentrico.

CT features are described and accuracy of the method is discussed in the diagnosis of malignant pleural mesothelioma. Ninety-eight patients suffering from pleural disease mimicking mesothelioma were examined by means of III-generation CT scanners; according to the final diagnosis, 37 patients suffered from malignant pleural mesothelioma, 27 from other malignant pleural diseases and 34 from various benign diseases. In all patients a series of CT signs was evaluated: pleural thickening patterns, lesion spread and possible associated characters. In the diagnosis of mesothelioma CT showed 72.5% sensitivity, 63.8% specificity, 68.3% diagnostic accuracy, 68.5% positive predictive value and 68.2% negative predictive value. Some significant CT patterns in distinguishing malignant from benign pleural disease were identified, while the characterization of malignant disease (mesothelioma versus other neoplastic conditions) proved to be unreliable.

Multichain structure of the IFN-alpha receptor on hematopoietic cells.

The structure of IFN-alpha receptor was studied by 1) developing antibodies against the receptor, and 2) screening a number of cell lines by affinity cross-linking to identify cells that express different IFN-alpha 2 receptor structures. We report that two different patterns of IFN-alpha 2 receptor are observed in human cells of hematopoietic origin. The predominant form of the IFN-alpha receptor is a multichain structure in which IFN-alpha 2 forms complexes of 110 and 130 kDa (alpha-subunit). A high Mr complex of 210 kDa results from the association of alpha-subunit and other receptor components. In contrast, another form of the receptor has been identified in the IFN-alpha-resistant U-937 cell line and in some cases of acute leukemia. This form of the IFN-alpha receptor is characterized by the presence of the alpha- subunit, and the absence of the 110- and 210-kDa bands. Also a novel 180-kDa complex and a more prominent 75-kDa band are observed. Functional studies performed in U-937 cells showed that this cell line is not only partially resistant to the antiproliferative and antiviral effects of IFN-alpha, but also fails to down-regulate the alpha-subunit of the IFN-alpha receptor upon IFN-alpha binding.

Effects of low-dose propofol administration on central respiratory drive, gas exchanges and respiratory pattern.

The effects of sedative-hypnotic doses of propofol on respiratory drive and pattern have not yet been extensively described. Repeated small boluses of propofol (0.6-0.3 mg.kg-1) were administered to ten ASA I patients undergoing carpal tunnel release using regional anaesthesia. Airway pressure, capnography and pneumotachography were continuously recorded. With respect to basal values, no significant variations of respiratory rate, minute volume, tidal volume, inspiratory and expiratory time, total expiratory cycle, Ti/Ttot, TV/Ti, P0.1, EtCO2 and blood gas analysis were observed. Low doses of propofol, to maintain conscious sedation of light sleep, have not been shown to cause respiratory depression.

[Radiologic study of the thorax using the digital method (FCR 101). Evaluation of various parameters as related to exposure]. / Studio radiologico del torace con metodica digitale (FCR 101). Valutazione di alcuni parametri in relazione alla esposizione.

A computed radiography system with solid state detectors (FCR 101) was employed to evaluate the quality of digital images, with optimal and progressively lowered doses, in the study of the chest. Routine chest radiographs of in patients with no pathologic conditions of the chest were studied. The patients were divided into 3 groups: each patient in group A underwent two radiographs, one at 100% and the other at 50% exposure; patients in group B were imaged with 100% and 25% doses, and those in group C received 50% and 25% exposure. Several parameters were employed for image evaluation, and a value was given to each of them (1 = good, 2 = sufficient, 3 = insufficient). Upon comparison of the average values obtained, we observed that the digital technique allowed a most accurate and well-defined representation of the examined parameters at 100% exposure dose and that a 50% reduction did not decrease the informative content in the least. A 25% reduction, however, determined a high degree of background noise and a subsequent, though slight, loss of information.

[Double-contrast enema. Study of the mucosal pattern and the organ profile with conventional and digital methods]. / Clisma a doppio contrasto. Studio del disegno mucoso e del profilo d'organo con le metodiche tradizionale e digitale.

A solid state digital system (FCR 101) was employed in our comparative evaluation of the image quality of conventional versus digital techniques in the study of colon by means of double-contrast enema. Sixty patients were examined with a single AP view, using digital radiography with 100% radiation dose and progressive 50% and 75% reductions; the radiographs thus obtained were then compared with the corresponding conventional ones. The examined parameters were organ profile and mucosal pattern. Each digital and conventional radiograph was evaluated by 2 independent radiologists and a value was given to each parameter i.e., 1 = good, 2 = sufficient, 3 = insufficient. Upon comparison of the average values obtained for digital and conventional radiographs in optimal conditions and with a dose reduced by 50%, the digital technique was seen to give a more detailed and accurate representation of both low-contrast mucosal pattern and of organ profile. With the dose reduced by 75%, a slight increase was observed in background noise which caused a slight loss in image definition, but this did not reduce image readability with respect to conventional radiographs. To conclude, the digital method with a 50% exposure reduction is to be preferred in the examination of the colon, especially in pediatric radiology; furthermore, since this technique allows better detailing at lower contrast, it is to be preferred in the study of the pathologic conditions affecting mainly/only the mucosal pattern--e.g., cancer, ulcerative colitis, Crohn's disease, and so on. An exposure dose reduced by 75% may be used for following lesions previously diagnosed and when a less detailed depiction of the mucosal pattern is enough.

IL-6 and tumor necrosis factor-alpha. Autocrine and paracrine cytokines involved in B cell function.

IL-6 and TNF-alpha are synthesized and secreted by normal tonsillar B cells after stimulation with the polyclonal B cell activator Staphylococcus aureus Cowan strain 1 (SAC) and IL-2 as well as spontaneously by in vivo activated B cells from patients with hypergammaglobulinemia. Using specific neutralizing antibodies, both factors were shown to be involved in autocrine and/or paracrine regulation of B cell differentiation. IgG induced by SAC/IL-2 stimulation was reduced 73% with an anti-IL-6 antibody and 40% with an anti-TNF-alpha antibody. Similar effects of these antibodies were observed on the spontaneous in vitro IgG production by lymphoblastic B cells from six patients with hypergammaglobulinemia. Kinetic studies with SAC/IL-2-activated B cells revealed that the anti-TNF-alpha antibody must be present at the beginning of the culture to exert an effect on Ig production, whereas the anti-IL-6 antibody reduced Ig production even if added as late as day 3. This sequential action of TNF-alpha and IL-6 on B cell differentiation was reflected by different kinetics of release of these two cytokines into the supernatant of SAC/IL-2 activated B cells; TNF-alpha peaked at 24 h and IL-6 at 96 h after stimulation. In addition, it was shown that IL-6 production by in vitro-activated B cells was partially blocked by an anti-TNF-alpha antibody suggesting that TNF-alpha regulates IL-6 production in normal B cells via an autocrine pathway. We also investigated the effects of TGF-beta on TNF-alpha and IL-6 production by normal B cells. Although TGF-beta inhibited Ig production by in vitro-activated and in vivo-activated B cells, it did not inhibit the release of these cytokines from normal B cells. Furthermore, TGF-beta did not inhibit the induction of nuclear factor-IL-6 nor the expression of IL-6R on activated B cells. Thus, although the biologic effects of anti-IL-6 and TGF-beta on B cell Ig production are similar, their mechanisms of actions appear to be distinct.

Characterization of three monoclonal antibodies that recognize the interferon alpha 2 receptor.

The interferon system plays an important role in the control of viral infections and cell proliferation. These effects are mediated through the interaction of interferons with specific cell surface receptors. We report here the development of monoclonal antibodies against one of the subunits of the interferon alpha receptor. These antibodies detect a 110-kDa protein in surface-labeled cells and in Western blots, and 130- and 210-kDa bands after crosslinking to iodinated interferon alpha 2. No other subunits are disulfide-linked to the 130-kDa subunit or are coprecipitated by these antibodies. Analysis by two-dimensional gel electrophoresis revealed that the pI of this subunit is 3.5-5.0. We suggest that the protein recognized by these monoclonal antibodies be named the alpha subunit of the interferon alpha receptor.

[Duodenopancreatectomy with conservation of the pylorus]. / Duodenopancreasectomia con conservazione del piloro.

The authors report on their initial experience with pylorus-preserving pancreatoduodenectomy. In the last three years 11 patients with neoplastic disease of the pancreatic head and ampullary region underwent the above mentioned procedure. The surgical technique carefully preserved the blood supply and innervation to the antro-pyloric region and duodenum was transected 2 cm distal to the pylorus. Postoperative mortality was 9%. Postoperative nasogastric suction was required for eight days (median). Long term results are quite good with a satisfactory restoration of intestinal function and a weight gain of 95% of pre-illness weight. At the present time preserving the pylorus appears an usefull modification of Whipple procedure.

In vitro modulation of human monocytes functions by RU 41740 (Biostim).

The in vitro effects of RU 41740, a mixture of two glycoproteins extracted from K. pneumoniae and possessing immunomodulatory activity, on human monocyte's cytotoxic activity, migratory capacity and monokine production were investigated. Exposure to RU 41740 in nanogram concentrations was associated with rapid increases in IL-1 and TNF production and marked augmentation in the monocytes' killing of TNF-sensitive targets, whereas killing of TNF-insensitive targets required longer exposures to microgram concentrations of this drug. Using otherwise effective treatment conditions, RU 41740 did not directly affect monocyte's spontaneous and FMLP-induced migration. The possible role of mononuclear cells stimulation and increased production of effector and regulatory monokines in the immunomodulatory activity of this product is addressed.

Modulation by suramin of NK and monocytic cell-mediated cytotoxicity in human and murine cells.

The in vitro effects of suramin, a compound recently tested in AIDS treatment, were investigated on human and murine NK and monocyte macrophage cytotoxicity and monocyte migratory ability. In a short-term, TNF-dependent assay, pre-exposure (4-18 h) to 100-400 micrograms/ml suramin was associated with a markedly increased cytotoxicity by human monocytes and murine-elicited peritoneal macrophages, paralleled by a greater cytotoxic capacity in the supernates of these effectors. Preincubation with the same pharmacological suramin concentrations also resulted in enhanced spontaneous and directed migration in monocytic cells. Suramin-preincubated human PBL and murine splenocytes were unchanged in their basal NK cytotoxicity but exhibited a deficient response to IFN. Pre- and post-incubations with suramin resulted in increased macrophagic cytotoxicity for TNF-insensitive targets. Conversely, postincubation of effectors with the drug at 100-400 micrograms/ml was associated with profound decreases in both NK and TNF-mediated macrophagic cytotoxicities, and prior exposure to suramin of macrophagic supernates resulted in reduced cytotoxic activity. The mechanisms involved in the complex modulatory activity of suramin for monocyte macrophages and NK cells and the possible therapeutic implications of these findings are discussed.

Stimulation of natural host defence mechanisms in rodents by nesosteine.

The effect of Nesosteine, a novel mucolytic agent, on natural host resistance mechanisms was investigated in different organs of mice and rats. Single or repeated administrations of nesosteine by the i.v. or oral route (per os) were associated with significant increases in lung and spleen NK-mediated cytotoxicity, and in alveolar and peritoneal macrophages direct cytotoxicity. In both species the dose-response curve was bell-shaped, and optimal activity on both parameters seen at 1 mg/kg i.v. x 1, 100 mg/kg per os x 1 or 20 mg/kg per os x 5. Increases of at least 100% in lung NK and alveolar macrophages cytotoxicity were found in mice 48 h after single oral dosing at 100 mg/kg. The possible importance of Nesosteine immunostimulatory capacity in the activity of this compound in chronic hypersecretive bronchopulmonary disorders is discussed.