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Purpose: To characterize patients with APS and to propose a new approach for their follow-up. Query ID="Q1" Text="Please check the given names and familynames." Methods: Monocentric observational retrospective study enrolling patients referred to the Outpatients clinic of the Units of Endocrinology, Diabetology, Gastroenterology, Rheumatology and Clinical Immunology of our Hospital for Autoimmune diseases. Results: Among 9852 patients, 1174 (11.9%) [869 (73.9%) female] were diagnosed with APS. In 254 subjects, the diagnosis was made at first clinical evaluation (Group 1), all the other patients were diagnosed with a mean latency of 11.3 ± 10.6 years (Group 2). Group 1 and 2 were comparable for age at diagnosis (35.7 ± 16.3 vs. 40.4 ± 16.6 yrs, p = .698), but different in male/female ratio (81/173 vs 226/696, p = .019). In Group 2, 50% of patients developed the syndrome within 8 years of follow-up. A significant difference was found after subdividing the first clinical manifestation into the different outpatient clinic to which they referred (8.7 ± 8.0 vs. 13.4 ± 11.6 vs. 19.8 ± 8.7 vs. 7.4 ± 8.1 for endocrine, diabetic, rheumatologic, and gastroenterological diseases, respectively, p < .001). Conclusions: We described a large series of patients affected by APS according to splitters and lumpers. We propose a flowchart tailored for each specialist outpatient clinic taking care of the patients. Finally, we recommend regular reproductive system assessment due to the non-negligible risk of developing premature ovarian failure.

Multiple forms of stigmatization are experienced by caregivers of children with autism among ethnic minority (EM) groups in various countries. Such forms of stigmatization can lead to delayed assessment and services for mental health among children and caregivers. This review identified the research literature on the types of stigmatization experienced by caregivers of children with autism with an EM background. A total of 19 studies published after 2010 (i.e., 12 from the USA, 2 from the UK, 1 from Canada, and 1 from New Zealand) of caregivers of 20 ethnicities were identified and reviewed, and their reporting qualities systematically also assessed. Four main themes: (1) self-stigma, (2) social stigma, (3) stigma towards EM parents of children on the autism spectrum, and (4) service utilization stigma, and nine sub-themes were identified. The discrimination experienced by caregivers were extracted, synthesized, and further discussed. While the reporting quality of the studies included is good, the depth of the understanding of this under-researched yet important phenomenon is very limited. The multiple forms of stigmatization experiences are complex, and it may be difficult to disentangle whether the causes of stigmatization were autism and/or EM related, and the types of stigmatization can vary enormously among different ethnic groups in different societies. More quantitative studies are needed to quantify the impacts of multiple forms of stigmatization on families of children with autism in EM groups so that more socially inclusive support for caregivers with an EM background in host countries can be developed.

The recent introduction of tile manufacturing systems based on double-pressing technology has aroused great interest, particularly in the porcelain tile field, which imitates natural products and requires a ceramic body [...]

Objectives: Pheochromocytomas are rare tumors which can present with heterogeneous secretion profiles, clinical manifestations, and radiologic appearance. Under a histopathological point of view, they can be characterized as more or less aggressive with the Pheochromocytoma of the Adrenal gland Scaled Score (PASS) and the Grading system for Adrenal Pheochromocytoma and Paraganglioma (GAPP) score. The aim of this study is to analyze the texture analysis characteristics of pheochromocytoma and identify whether the texture analysis can yield information aiding in the diagnosis and the characterization of those tumors. Methods: Radiological, biochemical, and histopathological data regarding 30 consecutive patients with histologically confirmed pheochromocytoma were analyzed. Images obtained in the unenhanced, late arterial, venous, and delayed phases were used for the texture analysis. Results: Urinary epinephrine and metanephrine levels showed a significant correlation (R2= 0.946; R2= 699) in the multivariate linear model with texture features, as well as Ki-67 (R2= 0.397), PASS score (R2= 0.182), GAPP score (R2= 0.705), and cellularity showed a significant correlation (R2= 0.389). The cluster analysis based on radiomic features resulted in 2 clusters, with significative differences in terms of systolic and diastolic blood pressure values at the time of diagnosis (p= 0.025), GAPP score (4 vs 6, p= 0.05), histological pattern (1–2, p= 0.039), and comedonecrosis (0% vs 50%, p= 0.013). Conclusion: In conclusion, our study provides the proof of concept for the use of texture analysis on contrast-enhanced CT images as a noninvasive, quantitative tool for helping in the characterization of the clinical, biochemical, and histopathological features of pheochromocytoma.

Purpose: Patients submitted to curative surgery for non-functioning pancreatic neuroendocrine neoplasms (NF-PanNENs) exhibit a variable risk of disease relapse. Aims of this meta-analysis were to estimate the rate of disease recurrence and to investigate the risk factors for disease relapse in patients submitted to curative surgery for NF-PanNENs. Methods: Medline/Pubmed and Web of Science databases were searched for relevant studies. A meta-regression analysis was performed to investigate the source of recurrence rate heterogeneity. Pooled hazard ratios (HRs) and 95% confidence intervals (95% CI) were used to assess the effect of each possible prognostic factor on disease-free survival. Results: Fifteen studies, involving 2754 patients submitted to curative surgery for NF-PanNENs, were included. The pooled rate of disease recurrence was 21% (95% CI 15–26%). Study quality (Odds ratio, OR 0.94, P= 0.016) and G3-PanNENs rate (OR 2.18, P= 0.040) independently predicted the recurrence rate variability. Nodal metastases (HR 1.63, P< 0.001), tumor grade G2-G3 (G1 versus G2: HR 1.72, P< 0.001, G1 versus G3 HR 2.57, P< 0.001), microvascular (HR 1.25, P= 0.046) and perineural (HR 1.29, P= 0.019) invasion were identified as significant prognostic factors. T stage (T1-T2 versus T3-T4, P= 0.253) and status of resection margins (R0 versus R1, P= 0.173) did not show any significant relationship with NF-PanNENs recurrence. Conclusion: Disease relapse occurs in approximately one out of five patients submitted to curative surgery for NF-PanNENs. Nodal involvement, tumor grade, microvascular and perineural invasion are relevant prognostic factors, that should be taken into account for follow-up and for possible trials investigating adjuvant or neoadjuvant treatments.

Purpose: Several single-nucleotide polymorphisms in genes encoding for transporters have been associated with serum thyroid hormone concentrations with inconsistent results. The aim of this study was to assess the clinical significance of the rs17606253 in SLC16A10gene alone and in combination with the DIO2Thr92Ala variation in athyreotic patients. Methods: One-hundred patients submitted to total thyroidectomy and treated with levothyroxine were included. Pre- and post surgical serum TSH levels did not differ by more than ± 0.5 mIU/l. Results: Both patients carrying the wild-type allele or heterozygous for rs17606253 in SLC16A10gene had a significant reduction in FT3 post surgical levels (p= 0.01 and p< 0.0001, respectively) while Thr92Ala in DIO2gene was associated with reduced FT3 levels for heterozygous and rare homozygous patients (p< 0.0001 and p= 0.01, respectively). We identified two groups (“FT3 unchanged” and “FT3 reduced”) using a cutoff of at least 0.5 pg/ml as a significant variation between pre- and post surgical FT3 values. In this case, the rs17606253 was not statistically associated with reduced FT3 levels at genotype and allele levels. On the contrary, the Thr92Ala in DIO2gene was confirmed statistically associated with reduced FT3 levels after surgery with a p= 0.035 at genotype level and p= 0.014 at allele level. Conclusions: We confirmed the role of DIO2Thr92Ala polymorphism on T3 levels. On the contrary, SLC16A1rs17606253 polymorphism did not impair hormone levels in athyreotic patients treated with levothyroxine therapy.

Aims. The INTEGRAL mission provides a large data set for studying the hard X-ray properties of AGN and allows testing of the unified scheme for AGN.

Background:: Immune activation contributes to the persistent state of inflammation associated with metabolic dysfunction in obesity. The specific immune receptors that sense metabolic stress signals and trigger inflammation are nevertheless largely unknown, and little is known on inflammatory and immune gene regulation in obesity. Methods:: The study includes a cross-sectional and a longitudinal arm. Forty children and adolescents were enrolled: 22 obese subjects and 18 age-matched normal weight controls. Obese subjects participated in an 18-month therapeutic protocol, based on intensive lifestyle modification (dietary regimen, physical activity and behavioral interventions). Expression of genes involved in the inflammasome pathway, plasma concentration of the inflammasome-associated pro-inflammatory cytokines (interleukin (IL)-1ß and IL-18) and indexes of microbial translocation (lipopolysaccharide (LPS), soluble CD14 (sCD14) and intestinal fatty acid-binding protein) were analyzed at baseline in obese subjects compared with controls, and after 18 months in obese subjects. Results:: Cross-sectional analyses showed that the LPS-induced expression of genes involved in inflammasome (NLRP3, caspase 5 and NAIP), Nod-like receptors (NLRX1 and NOD1), downstream signaling (P2RX7, RAGE, RIPk2, TIRAP and BIRC2) and effector molecules (IFN-?, IL-12ß, IL-1ß, CCL2, CCL5, IL-6 and TNFa) was significantly increased in obese subjects at baseline as compared with normal weight controls. The baseline plasma concentration of inflammasome-related cytokines (IL-1ß and IL-18) and of microbial translocation markers (LPS and sCD14) was augmented in obese subjects as compared with controls as well. Longitudinal analyses indicated that intensive lifestyle modification resulted in a normalization of parameters in subjects with a significant reduction of BMI after 18 months. Conclusions:: In children and adolescents, obesity is characterized by the activation of the inflammasome and by an alteration of gut permeability. Successful lifestyle modification is effective in reducing inflammation, suggesting that inhibition of the inflammasome may be a potential therapeutic strategy in obesity.

Human p21Waf1protein is well known for being transcriptionally induced by p53 and activating the cell cycle checkpoint arrest in response to DNA breaks. Here we report that p21Waf1protein undergoes a bimodal regulation, being upregulated in response to low doses of DNA damage but rapidly and transiently degraded in response to high doses of DNA lesions. Responsible for this degradation is the checkpoint kinase Chk1, which phosphorylates p21Waf1on T145 and S146 residues and induces its proteasome-dependent proteolysis. The initial p21Waf1degradation is then counteracted by the ATM-Chk2 pathway, which promotes the p53-dependent accumulation of p21Waf1at any dose of damage. We also found that p21Waf1ablation favors the activation of an apoptotic program to eliminate otherwise irreparable cells. These findings support a model in which in human cells a balance between ATM-Chk2-p53 and the ATR-Chk1 pathways modulates p21Waf1protein levels in relation to cytostatic and cytotoxic doses of DNA damage.

The ability of levofloxacin, moxifloxacin, ciprofloxacin, amoxicillin/clavulanic acid and ceftriaxone to interfere on biofilm produced by Pseudomonas aeruginosa, Haemophilus influenzaeand Streptococcus pneumoniaeisolated from patients with chronic obstructive pulmonary disease was evaluated. The effects of antibiotics were evaluated on formation of biofilm (at 1/2, 1/4 and 1/8 X MIC) and on preformed biofilm (at epithelial lining fluid peak concentrations) by means of a spectrophotometric method. Levofloxacin was the most active compound followed by ciprofloxacin, moxifloxacin and amoxicillin/clavulanic acid and ceftriaxone. Levofloxacin may contribute to clear the reservoir of pathogens involved in chronic obstructive pulmonary disease, thus leading to decreased occurrence of acute exacerbations.

Crohn's Disease is an inflammatory bowel disease associated with a variety of systemic manifestations, including large and small airway involvement. The latter is most often a subclinical one, and requires expensive and invasive diagnostic approaches. Nitric Oxide (NO) can be detected non-invasively in the exhaled air (eNO) and be considered as a surrogate marker of airway inflammation. eNO tested at multiple expiratory flows can be used to distinguish the alveolar concentration of NO (CalvNO) from the total amount of fractional eNO (FeNO). The aim of our study is to compare FeNO and concentration of alveolar nitric oxide (CalvNO) levels and to assess their relationship with pulmonary involvement in Crohn's patients differing in clinical stage and therapeutic regimens versus a group of healthy subjects. Thirty Crohn's patients not showing clinical evidence of pulmonary diseases and 21 non-smoking, non-atopic healthy controls were enrolled. FeNO (14.9±10.2 ppb vs10.1±6.3 ppb, p=0.049) and CaIvNO (4.4±2.2 ppb vs2.6±1.9; p=0.006) values were found to be significantly higher in Crohn's patients than in healthy controls. Both FeNO and CaIvNO correlated positively with the Crohn's Disease Activity Index. In conclusion, our results for FeNO and CaIvNO confirm the presence of subclinical pulmonary involvement in Crohn's disease. eNO measurement may be of clinical value in the follow-up of Crohn's patients.

Rheumatoid arthritis (RA) is associated with enhanced atherosclerosis and impaired endothelial function early after the onset of the disease and cardiovascular (CV) disease represents one of the leading causes of morbidity and mortality. It is well known that disease modifying antirheumatic drugs (DMARDs) are able to improve the course of the disease and the quality of life of these patients, but little is known about the effects of DMARDs on CV risk and endothelial dysfunction. Our goal was to examine the effects of long-term therapy with DMARDs on endothelial function and disease activity in early RA (ERA). Twenty-five ERA patients (mean age 52 ± 14.6 years, disease duration 6.24 ± 4.10 months) without evidence of CV involvement were evaluated for disease activity score (DAS-28), 2D-echo derived coronary flow reserve (CFR), common carotid intima-media thickness (IMT) and plasma asymmetric dimethylarginine (ADMA) levels at baseline and after 18 months of treatment with DMARDs (10 patients with methotrexate and 10 with adalimumab). DMARDs significantly reduced DAS-28 (6.0 ± 0.8 vs. 2.0 ± 0.7; P< 0.0001) and improved CFR (2.4 ± 0.2 vs. 2.7 ± 0.5; P< 0.01). Common carotid IMT and plasma ADMA levels did not show significant changes. The present study shows that DMARDs, beyond the well known antiphlogistic effects, are able to improve coronary microcirculation without a direct effect on IMT and ADMA, clinical markers of atherosclerosis. Treatment strategies in ERA patients with high inflammatory activity must be monitored to identify beneficial effects on preclinical markers of vascular function.

Rheumatoid arthritis (RA) is associated with enhanced atherosclerosis and impaired endothelial function early after the onset of the disease and cardiovascular (CV) disease represents one of the leading causes of morbidity and mortality. It is well known that disease modifying antirheumatic drugs (DMARDs) are able to improve the course of the disease and the quality of life of these patients, but little is known about the effects of DMARDs on CV risk and endothelial dysfunction. Our goal was to examine the effects of long‐term therapy with DMARDs on endothelial function and disease activity in early RA (ERA). Twenty‐five ERA patients (mean age 52 ± 14.6 years, disease duration 6.24 ± 4.10 months) without evidence of CV involvement were evaluated for disease activity score (DAS‐28), 2D‐echo derived coronary flow reserve (CFR), common carotid intima‐media thickness (IMT) and plasma asymmetric dimethylarginine (ADMA) levels at baseline and after 18 months of treatment with DMARDs (10 patients with methotrexate and 10 with adalimumab). DMARDs significantly reduced DAS‐28 (6.0 ± 0.8 vs. 2.0 ± 0.7; P< 0.0001) and improved CFR (2.4 ± 0.2 vs. 2.7 ± 0.5; P< 0.01). Common carotid IMT and plasma ADMA levels did not show significant changes. The present study shows that DMARDs, beyond the well known antiphlogistic effects, are able to improve coronary microcirculation without a direct effect on IMT and ADMA, clinical markers of atherosclerosis. Treatment strategies in ERA patients with high inflammatory activity must be monitored to identify beneficial effects on preclinical markers of vascular function.

Summary.: The objective of this study was to examine the in vivo effect of melatonin on rat mitochondrial liver respiration. Two experiments were performed: For experiment 1, adult male rats received melatonin in the drinking water (16 or 50 µg/ml) or vehicle during 45 days. For experiment 2, rats received melatonin in the drinking water (50 µg/ml) for 45 days, or the same amount for 30 days followed by a 15 day-withdrawal period. At sacrifice, a liver mitochondrial fraction was prepared and oxygen consumption was measured polarographically in the presence of excess concentration of DL-3-β-hydroxybutyrate or L-succinate. Melatonin treatment decreased Krebs’ cycle substrate-induced respiration significantly at both examined doses. The stimulation of mitochondrial respiration caused by excess concentration of substrate recovered after melatonin withdrawal. Basal state 4 respiration was not modified by melatonin. Melatonin, by curtailing overstimulation of cellular respiration caused by excess Krebs’ cycle substrates, can protect the mitochondria from oxidative damage.

Abstract: A convenient procedure for the synthesis of bis-quaternary ammonium salts from long-chain alkyldimethylamines and epichlorohydrin is studied. An improved preparation of bis-quaternary ammonium salts from N,N-dimethyloctylamine, N,N-dimethyldodecylamine or N,N-dimethyloleylamine, their amine hydrochlorides, and epichlorohydrin can be achieved by carrying out the reaction in an aqueous micellar medium. The amine hydrochlorides are used as functional surfactants to produce the self-micellization and solubilization of reactants. The formation of micelles is a necessary condition for a successful quaternization. Comparison of the quaternization performance in ethanol, ethanol/water mixtures, and aqueous micellar medium leads to the conclusion that this micellar-improved synthesis enables easier and cheaper access to bis-quaternary ammonium salts by avoiding the formation of the mono-quaternary ammonium salts as intermediates, and by using water as solvent under mild reaction conditions. Mechanistic aspects of the quaternization reaction in micellized medium are also suggested.

Aqueous micellar systems proved to be an excellent reaction medium for the selective synthesis of bis-quaternary ammonium salts 5a-c from epichlorohydrin 2 and long-chain alkyldimethylamines 1a-c, in the presence of the corresponding amine chlorohydrates 3a-c as functional surfactants. Unlike alcohol or alcohol-water mixtures as reaction medium, mono-quaternary ammonium salts 4a-c were formed, if any, in very small amounts under micellar conditions, allowing a more direct and rapid access to these quaternary ammonium gemini surfactants.

When patients complain of problems, physicians are used to look for some physical or physiological abnormality ruling out infections, inflammatory or cancer. Unfortunately, when we talk about functional disorders we usually cannot observe any defects and it is only possible for us to know of them through the words of our patients. Developing criteria and guidelines is not an easy process, in particular for functional gastrointestinal diseases, when no disease-based biological markers exist. It is difficult to define a medical disorder in the absence of a biological ‘gold standard’. The Rome II classification is based on the assumption that for each disorder there are symptom custers. Symptoms have in common disturbances in sensory and/or motor gastrointestinal function, which sometimes may overlap across anatomic regions. Nevertheless, several studies provide evidence for site-specific syndromes.

The aim of the study was to assess the quality of lung preservation offered by Euro-Collins solution (EC), Cold Modified Blood solution (CMB) and low potassium University of Wisconsin solution (UWLP).

Five human rhabdomyosarcoma cell lines were used to investigate the surface expression of HER/erbB receptors, particularly of HER-2, HER-3 and HER-4, by flow cytometry. HER-2 was expressed in 3/5 rhabdomyosarcoma cell lines. HER-3 was expressed in all rhabdomyosarcoma cell lines. None of the rhabdomyosarcoma cell lines investigated showed HER-4 surface expression. To study the biological activity of HER/erbB receptors in rhabdomyosarcomas, cells were cultured in the presence of glial growth factor 2 (GGF-2), a specific ligand of HER-3 that is able to stimulate myogenesis in normal myoblasts. In 3 of 3 human rhabdomyosarcoma cell lines positive for both HER-2 and HER-3 receptors, the treatment with GGF-2 induced a significant increase in myogenic differentiation. Int. J. Cancer 87:29–36, 2000. © 2000 Wiley-Liss, Inc.

The aim was to investigate the regional and systemic haemodynamic consequences of bolus injection of fluids with different physical properties in the course of routine aortography. Iopamidol was compared with an equiosmolar solution of mannitol and with a 0.9 N saline solution. Continuous blood flow and Pulsatility Index (PI), as an index of regional vascular resistance, were measured by Doppler technique. Finger arterial pressure and heart rate were monitored at the time and for 3 min following each intraaortic bolus injections. The patients who underwent routine aortography were grouped according to the site of the flow measurements: common femoral artery, common carotid artery and brachial artery. Flow changes induced by the bolus infusion were evident for all the fluids but only at the femoral artery level. After an immediate (3 +/- 2 s) and brief (2 +/- 2 s) but marked reduction of flow and in-phase increase of PI following the bolus, further haemodynamic changes were observed only in the femoral artery, with a peak at 35 +/- 10 s and returning to baseline values after 70 +/- 15 s, in terms of both increased mean blood velocity and decreased PI. Saline and mannitol induced overall blood velocity alterations of 54% and 80%, respectively, and PI reductions of 44% and 57% compared with those induced by iopamidol. In the other vascular areas there was only a 17 +/- 2% increase of the physiological early diastolic backflow at the brachial artery level. Blood pressure decreased and heart rate increased in phase with the flow changes of the femoral artery. In conclusion: (1) a dramatic rheodynamic perturbation at the site of injection induces a vasodilating stimulus; (2) the haemodynamic response following injection results in marked vasodilation of only the tributary vascular bed; (3) flow steal may occur from other beds towards the lower limb vascular beds owing to vascular impedance imbalance; (4) a reduction of systemic arterial pressure is induced in phase with the regional vascular events and a reflex increase of the heart rate; and (5) the physical properties of the injected fluids influence the intensity of the perturbation, although the decisive triggering factor is the counterflowing bolus per se.

AbstractThe aim of this study was to hormonally induce lactation in prepubertal, nulliparous, and male goats both transgenic and non‐transgenic. Analysis of milk quality, recombinant protein expression levels, total amount of recombinant protein produced, and the affect on long‐term reproductive capability was assessed. Fifty‐one goats (Saanen, Alpine, and Toggenburg), male and non‐pregnant females, 2‐31 months of age, either non‐transgenic or transgenic were evaluated with a total of 10 transgenes (constructs) represented. Animals were given estradiol (0.25 mg/kg, IM) and progesterone (0.75 mg/kg, IM) on days 1, 3, 5, 7, 9, 11 and 13, while prednisilone (0.4 mg/kg, IM) was administered on days 14‐16 with mammary massage occurring daily from day 5 onward. Forty of 51 animals, (36 of 38 females and 4 of 13 males) produced milk with total volumes in the 30‐day experiment, ranging from 20 μl to 530 mls per day, or approximately 500 ul to 6.8 liters total. Milk composition was analyzed for various parameters (total protein, fat content, total solids and somatic cell count) with no significant differences found between induced and natural milk. Expression levels of recombinant proteins from transgenic animals that were analyzed during the induced lactation, and subsequently during normal lactations, were found to have no significant differences. Total amount of recombinant protein produced was evaluated at different expression levels with no statistical significance seen. While over 90% of the females placed in the regimen became pregnant, there was a correlation between increased age at time of induction and an increase in number of breedings, or reproductive cycles needed to establish a pregnancy after induction. For males, 100% placed in the regimen settled females after hormonal induction of lactation. Semen quality was evaluated prior to, during, and after hormonal treatments. Semen volume and sperm number did not differ; however, for a small percentage of males, there was a decrease in sperm and post thaw motility after hormonal treatments. These levels returned to normal within 4‐5 weeks. Subsequent natural lactations showed total milk volumes within breed standards. These findings indicate that hormonal induction of lactation in the caprine species is a viable alternative to pregnancy for initiating lactation and milk production, does not adversely impact reproductive performance long‐term, and can benefit the early assessment of recombinant proteins produced in a transgenic founder program.

Objective: We used induction chemotherapy in a prospective, single-institution clinical trial intended to achieve resectability in patients with centrally located, unresectable T4 non-small cell lung cancer. Other types of IIIB disease were excluded. Methods: Between January 1990 and April 1996, we enrolled 57 patients with histologically confirmed non-small cell lung cancer. Eligibility criteria for T4 were clinical (superior vena cava syndrome, 9 patients), vocal cord paralysis (6 patients), dysphagia from esophageal involvement (1 patient), radiologic (computed tomography and magnetic resonance evidence of infiltration, 10 patients), bronchoscopic (tracheal infiltration, 11 patients), and thoracoscopic (histologically proven mediastinal infiltration, 20 patients). After 3 cycles of cisplatin (120 mg/m^2), vinblastine (4 mg/m^2), and mitomycin (2 mg/m^2), patients were reevaluated. Results: Forty-two patients (73%; 36 men, 6 women; age range, 42-75 years; mean, 58 years) responded to therapy and underwent thoracotomy; 11 patients did not respond, and 4 patients had major toxicity. Thirty-six patients (63% of the entire group) had complete resection. We performed 4 exploratory thoracotomies, 6 pneumonectomies, 32 lobectomies (20 procedures were associated with reconstruction of hilar-mediastinal structures). Overall, 4 patients had no histologic evidence of disease. We had 2 bronchopleural fistulas with 1 death and 5 other major complications. Overall survival at 1 and 4 years is 61.4% and 19.5%, respectively. Forty-two patients (73%) underwent exploratory operation, with a 4-year survival of 25.9%; 36 patients (63%) had complete resection, with a 4-year survival of 30.5%. Conclusions: Induction chemotherapy is effective for downstaging and surgical reconversion of centrally located T4 non-small cell lung cancer. Survival is promising, especially in patients whose disease becomes resectable. (J Thorac Cardiovasc Surg 1999;117:225-33)

Thymectomy is considered an effective therapeutic option for patients with myasthenia gravis (MG). We reviewed our 27-year experience with surgical treatment of MG with respect to long-term results and factors affecting outcome.

Surgical treatment of bullous emphysema has received renewed attention because of recent advances in minimally invasive techniques. We describe our experience in the thoracoscopic management of patients with bullous emphysema over the last 5 years.

There are several types of immunological tests available for the diagnosis and management of Helicobacter pylori infection. Most commercially available serological kits use the enzyme linked immunosorbent assay (ELISA) test format. Originally the kits used crude antigen preparations although many of the newer kits use a more purified antigen preparation, with often increased specificity but lower sensitivity. Near patient test kits are based either on latex agglutination or immunochromatography. Generally they have low sensitivities compared with laboratory tests. Western blotting, ELISA, and recombinant immunoblot assays (RIBA) have also been developed into commercially available kits and can be used to indicate the presence of specific virulence markers. An antigen detection kit has been developed for the detection of Helicobacter pylori in faeces. Immunological reagents have also been combined with other diagnostic modalities to develop immunohistochemical stains and DNA immunoassays. Helicobacter pylori is now recognised as the cause of gastritis and most cases of peptic ulcer disease (PUD); its long term carriage increases the risk of gastric adenocarcinoma sixfold and it is designated as a class I carcinogen. H pylori has also been implicated as a cause of gastric mucosa associated lymphoid tissue lymphomas. Its relation to non-ulcer dyspepsia remains controversial. Additionally, long term carriage of the organism may be associated with short stature in young girls and, in the general population, as a possible risk factor for the development of vasospastic disorders and possibly skin immunopathology such as urticaria. With the recognition of H pylori as an important human pathogen, it has become one of the growing number of organisms to have its complete genome sequence mapped. Serology is an important method of determining colonisation status and can be used for diagnosis, as a screening procedure, or to follow the efficacy of eradication regimens. Most serological assays are in the ELISA format although some are based on the latex agglutination reaction. These latter are used principally as near patient assays. Most assays detect IgG in serum although some detect serum IgA. More recently developed assays detect IgA in saliva and the production of affinity purified antibodies has led to the development of an antigen detection assay for faecal specimens. Serological reagents have also been used in immunocytochemistry and to speed up the detection of amplified products of the polymerase chain reaction (PCR)-DNA immunoassays.

The concurrent use of smoking and oral contraceptives affects the hemostatic balance, thereby inducing a thrombophilic state. In order to clarify the effects of this association on the hemostatic system, the possible changes in the markers of activation of coagulation (thrombin-antithrombin III complexes and prothrombin fragment F12) were evaluated in 35 women given a third-generation oral contraceptive for 6 months; 13 of these women (37.1) were mild or moderate smokers.No differences were found in basal levels of the coagulation and fibrinolytic parameters between smokers and non-smokers. During oral contraceptive administration, both F12 fragment and thrombin-antithrombin III complex concentrations significantly increased both in smokers and in non-smokers (p< 0.01). Fibrinogen plasma levels increased in both groups (p< 0.01). Antithrombin III activity was reduced in both groups during treatment, but the difference was significant only in smokers (p< 0.05)Although the sample size of smokers was too small to draw definitive conclusions, present results appeared to confirm previous data about the effect of the concurrent use of smoking and oral contraceptives on antithrombin III levels, but did not demonstrate any additional effect of moderate smoking on the activation of the clotting system induced by this oral contraceptive preparation.

Garnet and plagioclase pairs from fourteen selected samples, from garnet to sillimanite zones, collected along a NS traverse throughout the metamorphic basement of NE Sardinia, have been analyzed by microprobe.

We present a single case study of avoidance conditioning in a seriously amnesic patient with bilateral ischemic lesions of the brain. A four-path maze was used for conditioning. The procedure consisted in an aversive stimulus that the patient received every time he traced one of the four maze-paths connected to an electric shock generator with a stylus. Using a single case experimental design A-B-A, we found that the patient learned to avoid the path connected to the electric shock, although he never showed awareness of this. Our study confirms once again that conditioning is one of the residual learning capabilities in amnesic patients. Different neural systems are probably involved in conditioning processes.

Sudoite, the di-trioctahedral chlorite with ideal composition (Mg2Al)(Al2)(Si3Al)O10(OH)8 is a widespread rock-forming mineral in meta-siltstones and psammites of the Verrucano sequence of the Northern Apennines. Sub-ellipsoidal aggregates, probably derived from muscovite clasts, consisting of sudoite, pyrophyllite and muscovite, are common; sudoite may also occur as thin blades in the rock matrix. The co-existence of sudoite, Ferich chloritoid and pyrophyllite, reported here for the first time, has been observed in specimens from the M. Argentario and Monticiano-Roccastrada areas. This three-phase assemblage, diagnostic of a specific metamorphic facies, may be a tool for detailed zonation of low-grade terranes.

Patients undergoing pulmonary resections often present postoperative air leaks of varying magnitude and duration; this complication is more frequent with incomplete or absent interlobar fissures. Small leaks close spontaneously within 5-7 days; larger leaks may persist longer and could be associated with increased morbidity and prolonged hospitalization. We evaluated the role of different techniques to complete interlobar fissures before pulmonary lobectomy to prevent postoperative air leaks and reduce hospital stay and costs.

The applications of ultrasonography (US) in oncology have rapidly increased during the past few years. Technical improvements, development of new technologies, easy availability, and non-invasiveness are some of the reasons for the rapid diffusion of US. Nowadays a large number of malignancies, both superficial and deep-seated, can be examined by US. In order to give an overview of the present role of US in oncology it is necessary to discuss many different topics including tissue characterization, diagnostic role, staging, follow-up and future developments.

Plasma values of atrial natriuretic factor (ANF) were evaluated in 31 women with pregnancy-induced hypertension (PIH) and 31 normal pregnant women at the same age of gestation. In 27 women with PIH and 27 normal pregnant women forearm venous tone (FVT) was evaluated by Strain Gauge Plethysmography. Forearm vascular resistance (FVR) was measured as the ratio of mean blood pressure (MBP) to forearm blood flow. In addition Cardiac Index (CI) by means of transthoracic electrical bioimpedance and total peripheral vascular resistance (TPR) (with the Frank Equation) were also measured. In comparison with the normal pregnant women, the women with PIH had similar values of hematocrit (as an index of plasma volume) and significantly higher levels of FVR and TPR, while ANF plasma values did not differ significantly. Subdividing the women with PIH in relation to the presence of proteinuria (20.3 g/l), those with proteinuria, in addition to significantly higher levels of FVR and TPR, had significantly higher levels of FVT than normal pregnant women, while ANF plasma values were higher even though the difference was only near the level of significance. Hypertensive women with proteinuria also had higher values of FVT than hypertensive women without proteinuria. By means of multiple regression ANF did not show any significant correlations with hematocrit or sodium excretion. Hypertension with proteinuria seems to represent a more severe form of the disease in which, in addition to the probable influence of other factors such as the renin-angiotensin and prostaglandin systems, a greater increase in peripheral sympathetic tone than in hypertension alone appears to be present, causing a reduction in venous compliance in addition to the elevation in FVR and TPR, with increase in central blood volume and atrial stretch. This may explain the higher ANF plasma levels in these patients in comparison with normal pregnant women, even though the absence of a significant correlation of ANF with hematocrit and the fact that ANF increase was only near the level of significance may suggest a change in the relation between ANF secretion and atrial volume receptors in pregnancy either normal or complicated by hypertension. ANF does not seem to play an important role in water and sodium excretion in PIH probably because of the presence of very high plasma levels of hormones such as aldosterone, progesterone and oestriol which, together with renal prostaglandins, seem to be involved in diuresis and natriuresis in pregnancy.

Objective: The aim of this study was to ascertain the safety and efficacy of bronchial sleeve resection and reconstruction of the pulmonary artery in patients who had undergone induction chemotherapy for lung cancer.Methods: Between January 1991 and July 1996, we operated on 68 patients who had received three cycles of cisplatin-based induction chemotherapy. In 27 of these cases, we performed a lobectomy (n = 25) or bilobectomy (n = 2) associated with reconstruction of the bronchus, the pulmonary artery, or both. In only five additional patients, pneumonectomy had to be carried out. Before chemotherapy, 14 patients were in stage IIIA and 13 were in stage IIIB. All patients in stage IIIB had T4 disease; no N3 cases were included. At thoracotomy, one patient had no evidence of tumor, six were in stage I, 13 were in stage II, six were in stage IIIA, and one was in stage IIIB. Sixteen patients had epidermoid carcinoma and 11 had adenocarcinoma.Results: Sixteen patients underwent bronchial sleeve resection; 11 had various types of pulmonary artery reconstruction, associated with the bronchial sleeve in eight cases. In 26 patients, resection was radical with histologically negative margins. Neither bronchial complications nor deaths occurred. One patient had empyema and two had wound infections. Mean chest tube duration was 6 days. After a postoperative follow-up of 4 to 69 months (mean 25 months), 14 patients are alive and free of disease, one is alive with disease, and 12 have died. There were no local recurrences. The 1- and 4-year survival rates are 78% and 39%, respectively. Conclusions: Although it is technically demanding, lobectomy associated with bronchovascular reconstruction is feasible, with good immediate and long-term results, after induction chemotherapy. (J Thorac Cardiovasc Surg 1997;114:830-7)

We conducted computed tomographic examinations of the chest in 171 patients with lung cancer whose disease was subsequently surgically staged; routine mediastinal exploration was undertaken in all patients undergoing thoracotomy (151), and in 20 patients only anterior mediastinotomy or mediastinoscopy was performed. We have considered three groups of patients: In Group I (including all 171 patients) mediastinal lymph nodes were evaluated for metastatic involvement; nodes were considered diseased when >1 cm. Sensitivity, specificity, and accuracy were 95%, 83%, and 89%. Among these 171 patients, 34 (Group II) had a central tumor otherwise considered operable, which was shown on plain roentgengrams to be in contact with the mediastinum; infiltration of hilar and mediastinal vessels and of mediastinal tissues was investigated preoperatively with computed tomography and then ascertained at thoracotomy. Sensitivity, specificity, and accuracy were 68%, 72% and 70%. Twenty-seven patients (Group III) had a peripheral tumor abutting the pleural surface and suspected to invade the parietal pleura and chest wall; patients with evident bone infiltration were excluded. Sensitivity, specificity, and accuracy of computed tomography were 50%, 90%, and 65%.

Studies were performed on the mechanical activity of iso- and antiperistaltic colon segments used to replace the esophagus. Transplants were challenged with a semiliquid bolus and/or a 0.1 N HCl solution, considered as common stimuli for an in situ esophagus, and the mechanical activity was investigated by means of synchronized manometric and cinefluorographic recordings. Basal activity of the interposed colon was limited to occasional monophasic waves of the segmenting type; the acid solution and the semiliquid bolus constantly elicited a peristaltic motor response transporting the contents to the gastric fundus or, in antiperistaltic colon, from the distal to the proximal part.

Chlorite-muscovite porphyroblasts occur in the low-grade metapelites from Nurra (NW Sardinia). Although actually heterogeneous and built up by two different intermixed minerals, the porphyroblasts strongly simulate optical homogeneity and produce microprobe analyses that are typical for metamorphic vermiculite. Transmission and scanning electron microscopy, combined with analytical facilities, leads to a deeper characterization of the porphyroblasts, that actually consist of a random association of chlorite and muscovite.

Twenty-six patients with a clinical diagnosis of spondylodiscitis were examined with non-contrast and contrast-enhanced MRI in order to define the contribution of gadolinium-DTPA (Gd-DTPA) and different pulse sequences, including a fat suppression sequence (SPIR). Spin echo (SE) T1-weighted images before and after Gd-DTPA injection and SE T2-weighted images were obtained in all patients. Twelve patients were also examined using the SPIR sequence following Gd-DTPA injection. Signal intensity and morphological features of the disc and vertebral lesions were then evaluated. The SE T1-weighted sequence with Gd-DTPA was very effective in showing the pathological changes at the level of the disc as an area of low signal intensity surrounded by a peripheral rim of enhancement in 24 of 26 cases (92%). This feature was not visible on non-enhanced images. As regards contiguous vertebral lesions this sequence was less informative, since in 8 of 26 cases (31%) the vertebral lesions became isointense and therefore not detectable. In 12 cases there was extension into the surrounding structures (spinal canal and/or paravertebral tissues). An enhanced SE T1-weighted sequence provided good anatomical definition of the extension of the infection in the spinal canal in all cases with this type of involvement (7 of 12). Regarding the 7 cases with paravertebral extension, no extension was visible in 1 case due to the reduced contrast with the surrounding fat following Gd-DTPA injection. The enhanced SPIR sequence was very effective, particularly in detecting the lesions in the vertebral bodies, avoiding the limitation of the enhanced SE T1-weighted sequence. The SPIR sequence was also effective in showing the extension within the spinal canal and the paravertebral fat. On the basis of our results the combination of a SE T1-weighted sequence without contrast and SPIR sequence with Gd-DTPA seems to be the best approach in cases of spondylodiscitis.