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Introduction Bone metastases are frequent in patients with cancer. Electrochemotherapy (ECT) is a minimally invasive treatment. Preclinical and clinical studies supported the use of ECT in patients with metastatic bone disease (MBD). The purposes of this multicentre study are to confirm the safety and efficacy of ECT, and to identify appropriate operating procedures in different MBD conditions. Materials and methods 102 patients were treated in 11 Centres and recorded in the REINBONE registry (a shared database protected by security passwords): clinical and radiological information, ECT session, adverse events, response, quality of life indicators and duration of follow-up were registered. Results 105 ECT sessions were performed (one ECT session in 99 patients, two ECT sessions in 3 patients). 24 patients (23.5%) received a programmed intramedullary nail after ECT, during the same surgical procedure. Mean follow-up was 5.9 ± 5.1 months (range 1.5–52). The response to treatment by RECIST criteria was 40.4% objective responses, 50.6% stable disease and 9% progressive disease. According to PERCIST criteria the response was: 31.4% OR; 51.7% SD, 16.9% PD with no significant differences between the 2 criteria. Diagnosis of breast cancer and ECOG values 0–1 were significantly associated to objective response. A significant decrease in pain intensity and significant better quality of life was observed after ECT session at follow-up. Conclusion The results are encouraging on pain and tumour local control. ECT proved to be an effective and safe treatment for MBD and it should be considered as an alternative treatment as well as in combination with radiation therapy.

There is a growing need for more systematic, robust, and comprehensive information on the value-add of climate services from both the demand and supply sides. There is a shortage of published value-add assessments that focus on the decision-making context, involve participatory or co-evaluation approaches, avoid over-simplification, and address both the quantitative (e.g., economic) and qualitative (e.g., social) values of climate services. The 12 case studies that formed the basis of the European Union-funded SECLI-FIRM project were co-designed by industrial and research partners in order to address these gaps while focusing on the use of tailored sub-seasonal and seasonal forecasts in the energy and water industries. For eight of these case studies, it was possible to apply quantitative economic valuation methods: econometric modelling was used in five case studies while three case studies used a cost/loss (relative economic value) analysis and avoided costs. The case studies illustrated the challenges in attempting to produce quantitative estimates of the economic value-add of these forecasts. At the same time, many of them highlighted how practical value for users—transcending the actual economic value—can be enhanced; for example, through the provision of climate services as an extension to their current use of weather forecasts and with the visualisation tailored towards the user.

Context. The Metis coronagraph on board Solar Orbiter offers a new view of coronal mass ejections (CMEs), observing them for the first time with simultaneous images acquired with a broad-band filter in the visible-light interval and with a narrow-band filter around the H I Ly-alpha line at 121.567 nm, the so-called Metis UV channel. Aims. We show the first Metis observations of a CME, obtained on 16 and 17 January 2021. The event was also observed by the EUI/FSI imager on board Solar Orbiter, as well as by other space-based coronagraphs, such as STEREO-A/COR2 and SOHO/LASCO/C2, whose images are combined here with Metis data. Methods. Different images are analysed here to reconstruct the 3D orientation of the expanding CME flux rope using the graduated cylindrical shell model. This also allows us to identify the possible location of the source region. Measurements of the CME kinematics allow us to quantify the expected Doppler dimming in the Ly-alpha channel. Results. Observations show that most CME features seen in the visible-light images are also seen in the Ly-alpha images, although some features in the latter channel appear more structured than their visible-light counterparts. We estimated the expansion velocity of this event to be below 140 km s(-1). Hence, these observations can be understood by assuming that Doppler dimming effects do not strongly reduce the Ly-alpha emission from the CME. These velocities are comparable with or smaller than the radial velocities inferred from the same data in a similar coronal structure on the east side of the Sun. Conclusions. The first observations by Metis of a CME demonstrate the capability of the instrument to provide valuable and novel information on the structure and dynamics of these coronal events. Considering also its diagnostics capabilities regarding the conditions of the ambient corona, Metis promises to significantly advance our knowledge of such phenomena.

In this work, we present an investigation of the wind in the solar corona that has been initiated by observations of the resonantly scattered ultraviolet emission of the coronal plasma obtained with UVCS-SOHO, designed to measure the wind outflow speed by applying Doppler dimming diagnostics. Metis on Solar Orbiter complements the UVCS spectroscopic observations that were performed during solar activity cycle 23 by simultaneously imaging the polarized visible light and the H I Lyman-alpha corona in order to obtain high spatial and temporal resolution maps of the outward velocity of the continuously expanding solar atmosphere. The Metis observations, taken on May 15, 2020, provide the first H I Lyman-alpha images of the extended corona and the first instantaneous map of the speed of the coronal plasma outflows during the minimum of solar activity and allow us to identify the layer where the slow wind flow is observed. The polarized visible light (580-640 nm) and the ultraviolet H I Ly alpha (121.6 nm) coronal emissions, obtained with the two Metis channels, were combined in order to measure the dimming of the UV emission relative to a static corona. This effect is caused by the outward motion of the coronal plasma along the direction of incidence of the chromospheric photons on the coronal neutral hydrogen. The plasma outflow velocity was then derived as a function of the measured Doppler dimming. The static corona UV emission was simulated on the basis of the plasma electron density inferred from the polarized visible light. This study leads to the identification, in the velocity maps of the solar corona, of the high-density layer about +/- 10 degrees wide, centered on the extension of a quiet equatorial streamer present at the east limb - the coronal origin of the heliospheric current sheet - where the slowest wind flows at about 160 +/- 18 km s(-1) from 4 R-circle dot to 6 R-circle dot. Beyond the boundaries of the high-density layer, the wind velocity rapidly increases, marking the transition between slow and fast wind in the corona.

[1] We report on the first geochemical investigation of the Monticchio maar lakes (Mt. Vulture volcano, southern Italy) covering an annual cycle that aimed at understanding the characteristic features of the physical structures and dynamics of the two lakes. We provide the first detailed description of the lakes based on high-resolution conductivity-temperature-depth (CTD) profiles, chemical and isotopic (H and O) compositions of the water, and the amounts of dissolved gases (e.g., He, Ar, CH4, and CO2). The combined data set reveals that the two lakes, which are separated by less than 200 m, exhibit different dynamics: one is a meromictic lake, where the waters are rich in biogenic and mantle-derived gases, while the other is a monomictic lake, which exhibits complete turnover of the water in winter and the release of dissolved gases. Our data strongly suggest that the differences in the dynamics of the two lakes are due to different density profiles affected by dissolved solutes, mainly Fe, which is strongly enriched in the deep water of the meromictic lake. A conceptual model of water balance was constructed based on the correlation between the chemical composition of the water and the hydrogen isotopic signature. Gas-rich groundwaters that feed both of the lakes and evaporation processes subsequently modify the water chemistry of the lakes. Our data highlight that no further potential hazardous accumulation of lethal gases is expected at the Monticchio lakes. Nevertheless, geochemical monitoring is needed to prevent the possibility of vigorous gas releases that have previously occurred in historical time.

Calcific tendinitis of the rotator cuff is a benign pathology which usually heals spontaneously. The most important classification to better understand and treat this pathology was proposed by Uhthoff. In this classification, there are the pre-calcific, calcific and post-calcific stages. The calcific stage has three phases: formation, rest and resorption. The treatment of calcific tendinitis thus depends on the phase. Careful investigation of the patient’s history, X-ray analysis, and an objective examination lead to proper treatment for that phase. Therefore, it can vary from simple medical and physical therapy to needle aspiration with ultrasound, up to arthroscopic removal. However, when choosing the treatment, it is important to remember that the pathology is benign and tends to heal spontaneously, as demonstrated in many cases.

The Mediterranean Sea, rich in biodiversity and with a large number of endemic species, provides sustenance for millions of people living along its coasts. Due to its position it also represents the natural route between major oil production areas and oil consumers. Its preservation passes also through satellite technologies which are ever and ever playing an increasing role in environmental monitoring. Italy, recognizing its contribution, has decided to invest in this sector with the satellite Mission COSMO-SkyMed. Its frequent revisiting time, day and night and all weather acquisition capability, makes it an essential part together with aerial and naval component of the National Contingency Plan (United Nations Conference on Trade and Development, Review in Maritime Transport. Available at http://unctad.org/en/PublicationsLibrary/rmt2015_en.pdf) to contrast marine oil pollution.

The putative DNA encapsidation genes encoded by open reading frames (ORFs) 25, 26, 30, 34, 43, 45/42 and 54 were cloned from Varicella-zoster virus (VZV) strain Ellen. Sequencing revealed that the Ellen ORFs were highly conserved at the amino acid level when compared to those of nineteen previously published VZV isolates. Additionally, RT-PCR provided the first evidence that ORF45/42 was expressed as a spliced transcript in VZV-infected cells. All seven ORFs were expressed in vitro and full length products were identified using a C-terminal V5 epitope tag. The in vitro products of the putative VZV terminase subunits encoded by ORFs 30 and 45/42 proved useful in protein-protein interaction assays. Previous studies have reported the formation of a heterodimeric terminase complex involved in DNA encapsidation for both herpes simplex virus-type 1 (HSV-1) and human cytomegalovirus (HCMV). Here we report that the C-terminal portion of exon II of ORF45/42 (ORF42-C269) interacted in GST-pull down experiments with in vitro synthesized ORF30 and ORF45/42. The interactions were maintained in the presence of anionic detergents and in buffers of increasing ionic strength. Cells transiently transfected with epitope tagged ORF45/42 or ORF30 showed primarily cytoplasmic staining. In contrast, an antiserum directed to the N-terminal portion of ORF45 showed nearly exclusive nuclear localization of the ORF45/42 gene product in infected cells. An ORF30 specific antiserum detected an 87 kDa protein in both the cytoplasmic and nuclear fractions of VZV infected cells. The results were consistent with the localization and function of herpesviral terminase subunits. This is the first study aimed at the identification and characterization of the VZV DNA encapsidation gene products.

Une simulation informatique Monte Carlo a ete utilisee pour modeliser l'auto-association de copolymeres modeles comme les caseines. Dans un systeme a un composant, la caseine α s1 et la caseine β montrent une tendance lourde a former de grosses micelles avec, pour la caseine α s,1 , des micelles en forme de fleur ou de ver. La caseine α s2 forme des petites micelles dans un systeme a un composant, et a des difficultes a former des micelles mixtes dans des melanges de 2 ou 3 composants, ce qui est attribue a sa structure tetra-bloc (alternant des blocs hydrophobes et des blocs hydrophiles), ou un des blocs hydrophobes est attache aux deux extremites d'un bloc hydrophile, ce qui reduit son aptitude a s'auto-associer aves les autres blocs hydrophobes. L'ordre d'accroissement de la taille de la micelle depend du fait que l'association hydrophobe est autorisee ou non entre blocs sur la meme chaine. Quand elle est autorisee, les chaines tendent a se replier sur elles-memes, ce qui rend la micellisation plus difficile. L'ordre d'accroissement de la taille de la micelle est donc α s2 < β < α s1 . Dans le dernier cas, deux blocs hydrophobes aux extremites de la chaine α s1 sont capables de s'associer avec plus d'un noyau central hydrophobe de la micelle et agissent ainsi comme un pont entre deux micelles. Dans les systemes binaires, seuls les melanges caseine α s1 -caseine β montrent une preference forte a former des micelles quand les blocs hydrophobes des deux chaines sont meles relativement regulierement dans la partie centrale, avec un rapport 1:1 des deux chaines. Quand la caseine α s2 est presente dans les simulations binaires, elle a un role predominant dans la micellisation en limitant la croissance des micelles. Ceci est probablement du au second bloc hydrophobe des chaines α s2 qui ont une faible propension a s'associer avec les autres blocs hydrophobes et ainsi une faible capacite a propager la croissance de la micelle. Une situation similaire est observee dans les melanges a 3 caseines α s1 + α s2 + β a des taux de 1:1:1 et de 4:1:4.

Elastic scattering measurements have been performed for the Li-6 + p system in inverse kinematics at the energies of 16, 20, 25 and 29 MeV. The heavy ejectile was detected by the large acceptance MAGNEX spectrometer at the Laboratori Nazionali del Sud (LNS) in Catania, in the angular range between similar to 2(0) and 12(0) in the laboratory system, giving us the possibility to span almost a full angular range in the center of mass system. Results will be presented and discussed for one of the energies.

Elastic-scattering measurements have been performed for the Li6+p system in inverse kinematics at the energies of 16, 20, 25, and 29 MeV. The heavy ejectile was detected by the large acceptance MAGNEX spectrometer at the Laboratori Nazionali del Sud in Catania, Italy. The results are considered in a Jeukenne-Lejeune-Mahaux and a continuum discretized coupled-channel calculation framework. © 2015 American Physical Society.

Dipalmitoylphosphatidylcholine vesicles were used as a biological membrane model to investigate the interaction and the permeation properties of trimethoprim and brodimoprim as a function of drug protonation. The drug-membrane interaction was studied by differential scanning calorimetry. Both drugs interacted with the hydrophilic phospholipid head groups when in a protonated form. An experiment on the permeation of the two drugs through dipalmitoylphosphatidylcholine biomembranes showed higher diffusion rate constants when the two drugs were in the uncharged form; lowering of the pH (formation of protonated species) caused a reduction of permeation. Drug uptake by human neutrophil cells was also investigated. Both drugs may accumulate within neutrophils; however, brodimoprim does so to a greater extent. This accumulation is probably due to a pH gradient driving force, which allows the two drugs to move easily from the extracellular medium (pH approximately 7.3) into the internal cell compartments (acid pH). Once protonated, both drugs are less able to permeate and can be trapped by the neutrophils. This investigation showed the importance of the physicochemical properties of brodimoprim and trimethoprim in determining drug accumulation and membrane permeation pathways.

The purpose of this study was the calculation of fracture risk in a prospective study on postmenopausal women by quantitative ultrasound (QUS) at the phalanges. A total of 2341 postmenopausal women were recruited in 5 centers in Italy during 2006 and 2007 for QUS measurement during a screening program for osteoporosis. Two ultrasound parameters were collected: amplitude-dependent speed of sound (AD-SoS) and ultrasound bone profile index (UBPI). Women were then recontacted in 2010 and were asked about fracture occurrence during the period since previous QUS measurement. Data about new fracture occurred in this period, site and cause of fracture were requested. Two thousand two hundred eleven women were successfully recontacted. Mean age of the recruited women was 60.9±10.0yr, mean age at menopause was 49.3±4.4yr, mean body mass index (BMI) was 26.5±4.6kg/m 2 . A total number of 108 new major osteoporotic fractures occurred during the 3-yr period, of which 23 are hip fractures, 51 are vertebral fractures. Relative risk (RR) per standard deviation (SD) decrease for major fractures was 1.77 (confidence interval [CI]: 1.59–1.97) for AD-SoS and 2.06 (CI: 1.78–2.37) for UBPI. When corrected for age, BMI, age at menopause, the RRs are still significant and equal to 1.44 (CI: 1.26–1.65) for AD-SoS and 1.67 (CI: 1.39–2.00) for UBPI. RR for vertebral fractures was 1.63 (CI: 1.41–1.88) for AD-SoS and 1.73 (CI: 1.44–2.08) for UBPI. RR for hip fractures was 1.92 (CI: 1.55–2.37) for AD-SoS and 2.68 (CI: 1.86–3.86) for UBPI. Ultrasound parameters AD-SoS and UBPI are able to significantly predict future major fractures in a prospective cohort of more than 2000 postmenopausal women.

In man the GH-releasing hexapeptide His-DTrp-Ala-Trp-DPhe-Lys-NH2 (GHRP-6) has been shown to be active even after oral administration. On the other hand, it has been shown that arginine (ARG) totally restores the reduced somatotropic responsiveness to GHRH observed in aging. Based on the foregoing, in this study we verified the GH-releasing activity of oral GHRP-6 (300 µg/kg) in normal aging and the possible enhancing effect of 8 g oral ARG on the GH-releasing effect of GHRP-6. Eight young (age 24–32 yr) and 8 elderly (age 66–85 yr) subjects were studied. In all the GH response to GHRH (1 µg/kg iv) was also studied. Both IGF-I levels and the GH response to iv GHRH were lower in elderly than in young subjects (mean±SE, IGF-I: 65.1±9.1 vs 142.9±9.4 µg/L, p

Bone impairment is a well-known complication in childhood acute lymphoblastic leukemia (ALL) survivors but less is known about bone dynamics during ALL therapy. We longitudinally assessed by Quantitative Ultrasound (QUS) skeletal modifications during this treatment.Forty-four newly diagnosed ALL children underwent bone measurement by QUS parameters BTT (Bone Transmission Time) and AD-SoS (Amplitude-Dependent Speed of Sound), mainly reliant on bone density and cortical thickness, respectively. Measurements were performed at diagnosis, and 6, 12, and 24 months thereafter. The occurrence of skeletal complications such as fractures, vertebral collapse, osteonecrosis, and osteopenia was related to measurement outcome.A rapid deterioration of bone properties measured by BTT and AD-SoS was evident in the first semester of therapy (p0.001). Subsequently, the next measurements were characterized by progressive uncoupling of the two QUS parameters (p0.001). These were both significantly reduced at the end of therapy (p0.001). Twelve subjects with in-treatment skeletal complications displayed an almost two-fold decrease of both parameters (p0.001). BTT decreasing more than 1 Standard Deviation (SD) over 6 months of therapy was able to predict skeletal complication occurrence (p0.001).This report represents the largest longitudinal cohort systematically submitted to bone condition assessment from the beginning to the end of therapy for childhood ALL. Bone deterioration occurs early and persists throughout therapy, consistent with bone properties uncoupling. This pattern possibly reflects an initial impairment of both mineral density and cortical thickness with a subsequent recovery of this latter. QUS permits an early detection of bone deterioration and related skeletal complications in childhood ALL.

At present, the mechanism(s) underlying the reduced spontaneous and stimulated GH secretion in aging is still unclear. To obtain new information on this mechanism(s), the GH responses to both single and combined administration of GH-releasing hormone (GHRH; 1 microgram/kg iv) and arginine (ARG; 30 g infused over 30 min), a well known GH secretagogue probably acting via inhibition of hypothalamic somatostatin release, were studied in seven elderly normal subjects and seven young healthy subjects. Basal GH levels were similar in both groups, while insulin-like growth factor-I levels were lower in elderly subjects (76.7 +/- 9.2 vs. 258.3 +/- 29.2 micrograms/L; P = 0.01). In aged subjects GHRH induced a GH increase (area under the curve, 314.9 +/- 91.9 micrograms/L.h) which was lower (P = 0.01) than that in young subjects (709.1 +/- 114.4 micrograms/L.h). On the other hand, the ARG-induced GH increase in the elderly was not significantly different from that in young subjects (372.8 +/- 81.8 vs. 470.6 +/- 126.5 micrograms/L.h). ARG potentiated GH responsiveness to GHRH in both elderly (1787.1 +/- 226.0 micrograms/L.h; P = 0.0001 vs. GHRH alone) and young subjects (2113.0 +/- 444.3 micrograms/L.h; P = 0.001 vs. GHRH alone). The potentiating effect of ARG on the GHRH-induced GH response was greater in elderly than in young subjects (1013.0 +/- 553.5% vs. 237.9 +/- 79.1%; P = 0.0001); thus, the GH increase induced by combined administration of ARG and GHRH overlapped in two groups. In conclusion, these results show that, differently from the GHRH-induced GH increase, the somatotroph response to combined administration of ARG and GHRH does not vary with age. Our finding suggests that an increased somatostatinergic activity may underlie the reduced GH secretion in normal aging.

The 230-kbp murine cytomegalovirus (MCMV) genome is predicted to encode 182 open reading frames (orfs). One gene whose functional role is not known is encoded by the 762-bp m136 orf. Sequence analysis of rat cytomegalovirus (RCMV) strains Maastricht and English revealed homologous orfs, pr136, and ORF HJ4, respectively. Conservation of these orfs suggested that m136 and the RCMV homologs might play a role during virus replication. Expression of an epitope tagged form of m136 (m136-V5) yielded a polypeptide of 34 kDa that localized to the perinuclear region of transfected mouse 3T3 fibroblasts. Three independently generated MCMV m136 mutants were isolated and characterized. Mutations were introduced into the m136 orf by inserting either a beta-glucuronidase (m136-beta-gluc) or a guanosine phosphoribosyl transferase (m136-gpt) expression cassette into a unique BglII site, or by inserting a gpt cassette into a deleted region (Deltam136) of m136. No differences were observed in viral yield, plaque size, and plaque morphology between the parental strain and any of the m136 mutant viruses. In vivo analysis using a SCID mouse virulence model showed a consistently measurable attenuated phenotype for all three m136 mutants. The results showed that although the m136 gene was not essential for replication in vitro or in vivo, an intact m136 gene was necessary to yield wild type virulence during infection of the host.

Patients submitted to shoulder hemiarthroplasty for the treatment of fracture of the humeral head were analyzed. The study was conducted from 1991 to June 2001 using 2 different prosthetic models: the Neer cemented prosthesis and the Randelli cementless prosthesis. The authors were able to evaluate 93 cases out of 148 operated on. A review of data revealed the essential importance of reconstruction of the tuberosity and rehabilitation. It was also observed that the age of the patient and the severity of the fracture did not in any way influence results. X-ray examinations did not shed light on loosening phenomena in prosthetic implants. Erosion of the glenoid was observed only when two factors coexisted: incorrect position of the prosthesis and low mobility of the shoulder. The study allowed us to reveal numerous prognostic elements, both favorable and adverse, and to measure their importance and priority.

Patients submitted to oblique capsular shift were followed-up; this is a personal method used to treat recurrent anterior and anteroinferior dislocation of the shoulder. A total of 186 patients were followed-up. The results were good as there were no recurrences, recovery of shoulder movement was early and ample, and the Constant score was about 81.2.

Background and OBJECTIVE: Results from a relatively small case-control study recently showed that niflumic acid increases the risk of serious mucocutaneous reactions in children. As a consequence, the Italian Ministry of Health sent a "Dear Doctor" letter in June 2001 to warn pediatricians about the alleged adverse effects. The objective of this study was to estimate and compare the incidence of mild and severe mucocutaneous reactions among children using niflumic acid, other nonsteroidal antiinflammatory drugs (NSAIDs), or nonopioid analgesics. DESIGN: Retrospective cohort study. SETTING: Italy is one of the few countries in which a specific primary care system is devoted to children up to 14 years of age: every child is registered at birth and receives free medical care from 1 of the approximately 6000 family pediatricians working for the National Health Service. This study was conducted with the Pedianet network of Italian family pediatricians who use computerized electronic patient records for routine care; 185 pediatricians participated in the study. The patient records comprise information on demographics, diagnoses, symptoms, prescriptions, referrals, laboratory examinations, and hospitalizations. PARTICIPANTS: Children aged 0 to 14 years and registered with 1 of the collaborating pediatricians between January 1, 1998, and May 31, 2001. MAIN OUTCOME MEASURES: The incidence rate of severe (hospitalized or referred) and mild mucocutaneous reactions (exanthema, disseminated or localized pruritus, urticaria, angioedema, fixed eruption, dermatitis, erythema multiforme, vesicles, bullae, pustules, toxic epidermal necrolysis, purpura, and vasculitis) was estimated during use of niflumic acid, other NSAIDs, or nonopioid analgesics. For each episode of drug use, the following covariates were assessed: age, gender, region, year, indication for study drug, use of antibiotics, antimycotic agents, glucocorticoids, and other NSAIDs. Multivariate Poisson regression analysis was used to estimate the adjusted relative risk of mucocutaneous disorders during use of niflumic acid compared with use of other NSAIDs or use of acetaminophen alone. RESULTS: The population included 193727 children, 45351 of whom received at least 1 of the study drugs. The most frequently prescribed drugs were niflumic acid, acetaminophen, and propionic acid derivatives (ketoprofen and flurbiprofen). Users of niflumic acid (n = 32150) were younger and slightly more often had otitis media or upper respiratory tract infections as an indication compared with the other NSAIDs. During use of the various study drugs we identified 1451 mild mucocutaneous events and 42 severe reactions. The incidence rates of severe and mild mucocutaneous reactions after the administration of any study drug were 10.3 per 100000 exposure person-days and 3.7 per 1000 exposure person-days, respectively. Both incidence rates decreased strongly with increasing age. In comparison with other NSAIDs, the adjusted relative risks of niflumic acid were 0.5 (95% confidence interval: 0.23-1.27) for severe and 0.9 (95% confidence interval: 0.79-1.11) for mild mucocutaneous reactions. The use of acetaminophen as a reference category instead of other NSAIDs, restriction of the children to those who received NSAIDs for respiratory tract infections, or restriction to those who did not use antibiotics never revealed an increased risk of serious or mild mucocutaneous reactions during use of niflumic acid. CONCLUSIONS: In comparison with other NSAIDs or acetaminophen, niflumic acid is not associated with an increased risk of severe or mild mucocutaneous reactions in children. This was true for the different age groups and various types of mucocutaneous reactions, was independent of the concomitant use of antibiotics, and was not sensitive to changes in our assumptions regarding exposure and outcomes

Prosthetic repair for abdominal wall hernia currently represents the gold standard. However, it is still difficult to identify the correct indication for prosthetic implant in borderline cases. The authors propose evaluating whether a prosthetic implant is absolutely contraindicated in potentially infected operating fields through the review of literature and personal experience.The authors performed ten prosthetic hernia repairs in potentially contaminated areas, with a preliminary preparation of the retromuscular-preperitoneal space hosting the prosthesis implant, and subsequent performance of the major operation.There were neither major nor minor complications with a 21-month follow-up (mean period).It is certain that both in noncomplicated inguinal hernia and in abdominal wall hernia repairs, the use of antibiotics can significantly reduce the number of infections. It is very important to underline that the success of the described procedure can be guaranteed only by an accurate preparation of the preperitoneal space: perfect haemostasis, temporary closure of the space with the insertion of iodine gauzes and suturing the edges, local antibiotic treatment, washing of the cavity, and accurate drainage.Prosthetic repair is the gold standard for inguinal, incisional, and all abdominal wall hernias and should be used, with the method described, even in potentially contaminated areas. The use of a prosthesis has to be avoided in clearly infected cases.

The surgical approach for the treatment of abdominal incisional hernias is a difficult problem. Only the use of prosthetic materials can provide a solution, yet their use in case of abundant loss of peritoneum can involve complications due to direct contact between the mesh and the intestine. The use of prosthetic materials in reconstruction of the abdominal wall highlights two closely connected problems: the kind of mesh to be used and the best implant site The prosthesis should be positioned only in the pre-peritoneal space or in the retromuscular prefascial plane. We report our experience with a surgical technique in which the peritoneum is integrated with an absorbable prosthesis and the nonabsorbable prosthesis is positioned in the neo-preperitoneal plane. From January 1992 to January 2000 65 patients underwent surgery for large incisional hernias. The follow-up period ranged from 6 to 60 months. There were 15 (23.1%) early complications (seromas, hematomas and infections) and 2 (3.1%) late complications: a fistula between the skin and the prosthesis and a subacute infection of the abdominal wall. No recurrence was noted. In patients with abundant loss of substance there is no real pre-peritoneal space; therefore a new one must be created to restore the mechanical and functional structure of the peritoneum. The prosthetic Vicryl® mesh permits good tissue repair with almost no involvement of the intestinal loop. Follow-up studies confirm the efficacy of this method.

The authors present a case of bilateral adrenal pheochromocytoma that occurred at their observation and surgically treated with a bilateral adrenalectomy. The authors review the literature in order to discuss the diagnostic and therapeutic option to treat these cases. They stress the importance of preoperative abdominal TC an MIBG scintigraphy and the importance of pre and intraoperative assessment to exclude extra adrenal localization of pheochromocytoma.

The authors compare the efficacy of epidural morphine analgesia with continuous intercostal extrapleural block using bupivacaine 0.5% after thoracotomy. They affirm that antalgic treatment in thoracotomised patients is the most important factor in preventing the onset of major complications that may negatively influence the results of surgery. The efficacy of the analgesic techniques examined was evaluated using El-Baz's visual analogic scale of pain, through the analysis of spirometric values and on the incidence of postoperative complications. The authors demonstrate that the extrapleural continuous nerve block is a reliable method of post-thoracotomic analgesia.

Between January 1989 and December 1994 we accomplished 130 CT-guided transthoracic fine needle aspirations (FNA) in 120 patients. Ten patients underwent a second FNA because of the negativity and doubts of the first. Diagnosis was targeted in 114 (95%) patients and 89% showed cytological evidence of malignancy. FNA-CT guided is reliable in the diagnosis of lung cancer, but less accurate in excluding diagnosis of malignancy. In our experience FNA had an accuracy with regard to lung cancer, of 92%. Sensitivity and specificity were respectively 93.8% and 100%. There were 6 false negative and 9 very negative. All patients should have bronchoscopy rather than FNA as the initial diagnostic procedure and perform it only in the absence of endobronchial lesions and malignant cells obtained with cytologic sputum or fiber bronchoscopy. In our experience 91 patients have lung cancer and thoracotomy was performed in 21% with confirm of diagnosis. FNA offers several advantages over other diagnostic procedures used in the evaluation of patients with intra-thoracic nodules and masses. The uses of small needles (20-22 gauge) and CT-guide has practically eliminated the risk of major haemorrhage. Deep and superficial lesions of the lung may be approached safely with FNA-CT guided and complications are no fatalities. Pneumothorax occurred in our experience in 5 cases and no occurred a chest drainage.

An observed case of carcinoid tumor of the large-bowel in a 68-year-old woman leads to an analysis of the clinical-diagnostic and therapeutic aspects of this rare gastrointestinal tumour. Carcinoid tumour represents 0.8-1.5% of malignant digestive tumours, in 6% of cases it is localized in large-bowel and in 2-3% in cecal-bowel. In our experience there is no specific symptoms and diagnosis was based on postoperative histopathologic analysis. Right hemicolectomy with lymphadenectomy performed and the operative specimen included a 7 cm diameter tumour, which had narrowed the lumen by 80% and infiltrated ileocecal valve. Carcinoid tumour presents considerable problems of diagnosis because symptoms are aspecific. Diagnosis is possible only in patients with high urinary levels of 5-HIAA, in presence of carcinoid syndrome and by endoscopic biopsy when tumour infiltrated gastrointestinal mucosa. False negative cases are frequent in small carcinoids (2 cm) because the tumour tissues are covered by integral mucosa. C.T., ultrasonography and angiography play a primary role in the diagnosis of this tumour but octreotide scintigraphy is very important for tumour and metastases localization in consequence of its ability to demonstrate somatostatin receptor positive tumours. Radical surgery is the only treatment in very little carcinoids to prevent metastases risk. Determinant risk factors are: primary size, localization, serosal penetration. In patients with any of these risk factors, resection with regional lymphadenectomy is recommended. Other prognostic factors include histologic differentiation, the presence of macroscopic residual disease after initial surgery and level of 5-HIAA in urine. We think that neither adjuvant chemotherapy, or radiotherapy may play a significant role in this neoplasm. Many authors report considerable unsuccessful with this treatment and it is used mainly for palliation. At present, the medical treatment of inoperable gastrointestinal carcinoid consist in association with interferon alpha and octreotide. During this treatment the size of the tumour is stable: reduction of symptoms and 5-HIAA urinary levels are noted.

Three patients with pleuropericardial cysts are reported. The authors accoding to what exists in literature confirm the congenital origin of this relatively rare pathology. It is benign and rapresents 6-19% of all mediastinal neoplasms. This lesion is more common in adults and prefer IV-VI decade of life. Usually this cyst constitute a casual radiological report because most of these tumours are asymptomatic. In our experience only one case was characterized by dyspnea. The authors, besides, consider CT of great help in diagnosis of pleuropericadial cyst in view of its high specificity. Thoracoscopy, result very important to diagnosis and exeresis of this neoplasm when doubts no persist as to the true nature of the lesion. Surgical treatment of pleuropericadial cyst is the only therapy. In our experience thoracotomy was preferred with excellent results and no postoperative complications or recurrences.

Pirenzepine, a muscarinic antagonist probably acting via stimulation of hypothalamic somatostatin release, abolishes the growth hormone releasing hormone (GHRH)-stimulated growth hormone (GH) rise in normal subjects but only blunts it in patients with anorexia nervosa (AN). This finding suggested the existence in AN of an alteration of cholinergic system and/or somatostatinergic tone. To further investigate these mechanisms, in 11 AN women patients (age 18.8 ± 0.9 years; BMI 13.4 ± 0.4 we studied the GH response alone (1 μg/Kg IV as a bolus at 0 min) and combined with pyridostigmine (PD, 120 mg orally, 60 min before GHRH administration), a cholinesterase inhibitor, or arginine (ARG 30 g infused over 30 min starting at 0 min), two compounds probably acting via inhibition of hypothalamic somatostatin (SS) release. The GH response to GHRH preceded by a previous (120 min before) neurohormone administration also was studied. All these tests also were performed in 20 normal age-matched women (age22.0 ± 1.8 yrs; BMI 20.1 ± 2.4). Basal serum GH levels were higher in AN patients than in normal volunteers (NV) (10.3 ± 3.4 versus 2.8 ± 0.3 μg / L ; p 0.001), whereas plasma IGF-1 levels were lower in AN patients than in NV (43.3 ± 10.6 versus 172.4 ± 13.9 μg / L ; p 0.00001). In AN patients, GHRH administration induced a GH rise higher, though not significantly, than that in NV [Δ area under the curve (AUC) 11173.6 ± 167.6 versus 834.6 ± 188.1 μg / L / h ). The GH response to the second of two consecutive GHRH boluses was lower (p 0.01) than that of the first one either in AN patients or in NV (67.6 ± 27.4 and 53.1 ± 25.7 μg / L / h , respectively). PD administration failed to modify the GHRH-induced GH rise in AN patients (1370.4 ± 228.4 versus 1268.8 ± 205.8 μg / L / h ), but enhanced it in NV 2285.4 ±234.6 versus 1070.1 ± 159.4 μ / L / h ; p 0.01). The GH response to PD + GHRH in AN patients was lower (p 0.01) than that in NV, ARG administration enhanced the GHRH-induced GH rise either in AN patients (3843.0 ± 659.7 μg / L / h ; p 0.02 versus GHRH alone) or in NV (3346.6 ± 424.1 μ / L / h ; p 0.01 versus GHRH alone), the two responses being similar. Our results demonstrate that, although ARG fails to modify the GHRH-induced GH response in NV, in AN the GH response to GHRH is inhibited by a previous neurohormone administration. These findings indicate the existence in AN of somatotroph refractiries to cholinergic influence but not to metabolic fuels such as arginine, whereas the negative GH-autofeed-back mechanism is preserved. Somewhat specific alterations of the somatostatin-mediated cholinergic influence or, alternatively, different actions for PD and ARG may be hypothesized.

Acute otitis media (AOM) is an infection frequently found in children, but tends to be less frequent with age and its frequency in adults is only about 1%. The etiology of AOM in children is prevalently bacterial; numerous studies have shown the most common etiological agents. But the etiology in adults has not been well studied. The authors examined 40 cases of AOM in adults, the pathologic material was obtained by needle aspiration; in 32 samples there was bacterial growth. In the majority of the cases (94%) the bacteria isolated were the same as those found in children: S. pneumoniae, H. influenzae and B. catarrhalis; much rarer were S. pyogenes and S. aureus. On the potential beta-lactamase producing strains, this activity was measured. From our findings we believe that there is the necessity to have a rational antibiotic therapy (due to the difficulty in obtaining pathologic material) with active drugs for the probable etiological agents of AOM.

An observed case of leiomyosarcoma of the stomach in a 67 year old man leads to an analysis of the diagnostic, clinical and therapeutical aspects of this myoid tumour in the digestive tract representing 50-60% of cases. Symptoms are aspecific and gastric bleeding is the most common sign (50%). leiomyosarcoma always presents considerable problems of diagnosis and represents the most important among the various examined diagnostic investigations but it is maintained that surgery many times plays a primary role in the diagnosis of this tumour. The accuracy of gastrofiberoscopic biopsy is limited by frequent false-negative cases. False negative cases are obtained because the tumour tissues are usually covered by gastric mucosa and so the biopsy with standard forceps is too small and too superficial. The ultrasonographic finding of a gastric leiomyosarcoma is variegated, in fact it can be hyperechoic or hypoechoic. Frequently we can see echo-free spaces due to liquefactive necrosis and in such a case, an echogenic rim is demonstrable. According to our experience ultrasonography is very important in post-operative follow-up. The TC study can be considered superior to the other diagnostic investigations, in fact with it, detailed characteristics and location of the tumour, invasivity, metastatic dissemination, are recognized. It is still controversial the criterium concerning the diagnosis of malignant smooth muscle tumour of the gastrointestinal tract. We believe that number of mitoses (having five or more mitotic figures x 10 high-power fields), cellularity, pleomorphism, atypicality, together with macroscopic aspects (size, bleeding, ulcerations, necrosis, invasivity) are the most reliable indicators of malignancy.(ABSTRACT TRUNCATED AT 250 WORDS)

Out of a series of 1563 consecutive patients submitted to thoracotomy for lung cancer between 1980 and 1990, 278 patients underwent a resection for a non small cell lung cancer (NSCLC) with mediastinal node metastases (N2). Selection of cases for surgery was carried out using CT from 1983 and mediastinoscopy for the patients with mediastinal lymph nodes larger than 1.5 cm from 1985: all patients with positive mediastinoscopy were excluded from thoracotomy, but 10 cases underwent a resection after neoadjuvant radio-chemotherapy. The surgical procedures were pneumonectomy (106), lobectomy (146) and atypical resection (8) with ipsilateral mediastinal lymphadenectomy. Resection was complete in 236 patients (84.8%) and incomplete in 42 patients (15.2%). Postoperative mortality was 3.2%. Almost all patients received radiotherapy after surgery. Actuarial 5-year survival was 13.7% for the entire group and 18.5% for the patients who underwent curative resection; no patients survived 5 years after palliative resection (p0.05). There were no differences with regard to prognosis according to the histology of the tumors and to surgical procedures. A better prognosis is associated with: completeness of resection, involvement of only one level, low T classification. Five-year survival rate of patients with metastases only in upper mediastinum was 25%; on the contrary 5-year survival rate of patients with metastases in the lymph nodes of the lower mediastinum was only 8% (p0.05). In our opinion better results among the patients with metastases in the upper mediastinum depends on the selection obtained with mediastinoscopy.(ABSTRACT TRUNCATED AT 250 WORDS)

There is evidence that GH secretion is reduced in normal elderly subjects as well as in patients with Alzheimer''s disease (AD). To clarify the mechanisms underlying this GH hyposecretory state in 14 elderly subjects (age 65–75 years) and 15 AD patients (age 61–78 years), we studied the effects of both pyridostigmine (PD, 120 mg orally), a cholinesterase inhibitor, and arginine (ARG, 0.5 g/kg i.v.), two substances likely acting via inhibition of hypothalamic somatostatin, on GH response to GHRH (1 (µg/kg i.v.). The GH response to PD alone was also studied. Twenty-two young healthy volunteers were studied as control group. Basal GH levels were similar in young, elderly and AD subjects (0.7 ± 0.2, 0.8 ± 0.2 and 0.9 ± 0.2 µg/1). IGF-I levels were lower (p < 0.005) in elderly (73.9 ± 8.2 µg/1) and in AD subjects (108.0 ± 5.9 µg/l) than in young subjects (288.7 ± 22.1 µg/l); however, they were higher (p < 0.01) in AD patients than in the elderly subjects. The PD-induced GH release did not significantly differ in young, elderly and AD subjects while the GH responses to GHRH in the elderly (AUC: 297.9 ± 49.2 µg/l/h) and in AD subjects (437.6 ± 93.5 µg/l/h) were lower (p < 0.01) than in young subjects (658.6 ± 100.1 µg/l/h). PD potentiated the GH response to GHRH both in elderly and in AD subjects (901.7 ± 222.4 and 1,070.3 ± 207.2 µg/l/h, p < 0.005) but these responses were lower (p < 0.0001) than those recorded in young subjects (2,041.1 ± 245.6 µg/l/h). ARG potentiated the GHRH-induced GH rise both in elderly and in AD subjects (1,545.2 ± 246.0 and 1,659.3 ± 196.8 µg/l/h,p < 0.001) but in this case, the GH response to GHRH + ARG overlapped with that in young subjects (2,140.2 ± 229.5 µg/l/h). In contrast to young subjects, in elderly and in AD subjects, the potentiating effect of ARG on GHRH-induced GH rise was higher (p < 0.01) than that of PD. These results show that testing neural controls of GH secretion with different neuroactive substances does not allow to differentiate normal aging from AD. In both groups, somatotroph responsiveness to GHRH is potentiated by the enhancement of the cholinergic activity but much more by ARG, which is compatible with the presence of a cholinergic impairments.

It is widely accepted that growth hormone (GH) secretion undergoes an age-related decrease in both animals and humans (Dieguez et al. 1988 Muller and Nistico 1989). Twenty-four-hour integrated GH concentrations have been shown to be lower in older versus younger subjects (Zadik et al. 1985). More recently, the study of the 24-h GH profile with frequent sampling techniques demonstrated that both day-time and night-time mean pulse amplitude and duration but not pulse frequency are reduced in aged humans (Vermeulen 1987; Van Coervorden et al. 1991). On the contrary, other authors (Iranmanesh et al. 1991) found significant reductions in GH secretory burst frequency and half-life but not in GH secretory burst half duration, amplitude or mass. Interestingly, though both slow wave sleep and nocturnal GH secretion are drastically reduced in the elderly, the small GH rises during sleep are nevertheless temporally related to slow wave stages (Van Coervorden et al. 1991).

Having observed 6 cases of benign tumours deriving from nerve sheaths, one of which was of exceptional size (19 x 11 x 10 cm), with an endothoracic localization over the past 5 years, the Authors analyse the etiopathogenetic problems, anatomo-clinical symptoms and the possible methods of treating these endothoracic tumours. Neurinomas represent between 60 and 70% of mediastinal neurogenic tumours which account for 20% of all cancers of the mediastinum. Their typical localization is the posterior mediastinum, along the paravertebral grooves, and the dimensions of these tumours vary between 3 and 8 cm, although on rare occasions they reach 15 cm. In all cases except that of the giant neurinoma, surgery took the form of straightforward enucleation. Follow-up has not revealed recidivation in any of the cases operated.

Galanin (GAL), a 29 amino acid neuropeptide, is known to increase both basal and growth hormone-releasing hormone (GHRH)-induced growth hormone (GH) secretion while not significantly increasing prolactin (PRL) secretion in man. GAL is also endowed with an inhibiting effect on glucose-stimulated insulin release in animals, but not in man. We studied the effect of GAL (80 pmol/kg/min infused over 60 minutes) on the arginine- (ARG, 30 g infused over 30 minutes) stimulated GH, PRL, insulin, and C-peptide secretion in eight healthy volunteers (age, 20 to 30 years). GAL induced an increase of GH (GAL v saline, area under curve [AUC], mean +/- SEM: 316.5 +/- 73.9 v 93.2 +/- 20.9 micrograms/L/h, P less than .05), but failed to modify both PRL and insulin secretion. GAL enhanced the ARG-induced stimulation of both GH (1,634.1 +/- 293.1 v 566.9 +/- 144.0 micrograms/L/h, P less than .02) and PRL secretion (1,541.9 +/- 248.8 v 1,023.8 +/- 158.7 micrograms/L/h, P less than .02). On the contrary, GAL blunted the ARG-stimulated insulin (816.3 +/- 87.7 v 1,322.7 +/- 240.9 mU/L/h, P less than .05), as well as C-peptide secretion (105.1 +/- 9.8 v 132.8 +/- 17.3 micrograms/L/h, P less than .02). ARG administration induced a transient increase of glucose levels (P less than .01 v baseline) followed by a significant decrease (P less than .05 v baseline). This latter effect was prevented by the coadministration of GAL. In conclusion, these results show that in man GAL potentiates the GH response to ARG, suggesting that these drugs act at the hypothalamic level, at least in part, via different mechanisms.(ABSTRACT TRUNCATED AT 250 WORDS)

The paper reports a case of intrathoracic hemangiopericytoma localised in mediastinum which was brought to the authors attention and treated surgically. Having analysed the tumour's macro- and microscopic histological and biological features and the most suitable methods of diagnosis, the authors stress that, in line with international literature, radical surgery extended to the surrounding tissues is the elective surgical treatment for hemangiopericytoma in a mediastinal site.

The authors take the opportunity of 11 cases of pulmonary hamartomas observed during the last 10 years, to specify the clinical and diagnostic problems and the therapeutic possibilities of this rare pulmonary neoplasm. The hamartochondroma is found mainly in the male sex, between the age of the fifth and sixth decades of life; the size of the neoplasm varies from 2 to 4 cm, rarely exceeding 10 cm. In 8 cases the operation was the simple enucleation of the hamartochondroma or its removal by atypical resection: in only one case, become of the conspicuous dimensions of the neoplasm, was it necessary to perform a typical lobectomy. The follow-up did not demonstrate any relapse, or the appearance of carcinoma of the lung in any of the cases under observation and surgically treated.