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In this study, 2-dimensional gas chromatography (GC × GC) was used to obtain a detailed fatty acid (FA) profile of sheep milk and to evaluate the effects of a rumen-protected conjugated linoleic acid (rpCLA) supply, breed, days in milk (DIM), sampling period, and number of lambs suckling on the FA profile. Twenty-four ewes, from 3 autochthonous breeds of the Veneto Alps (Brogna, Foza, and Lamon), were housed in 6 pens (2 pens/breed), according to DIM (38 ± 23 d) and body weight (61 ± 13 kg). The ewes and their offspring of 3 pens (1 pen/breed) were fed ad libitum a total mixed ration (control), and the other animals received the same diet supplemented with 12 g/d per ewe, plus 4 g/d for each lamb older than 30 d, of an rpCLA mixture. The study lasted 63 d. Two composite milk samples for each ewe were prepared during the first and second months of the trial. The pooled milk samples were analyzed in duplicate for FA profile by 2-dimensional gas chromatography, which allowed us to obtain a detailed FA profile of sheep milk, with 170 different FA detected, including many that were present in small concentrations. The milk relative proportions of individual FA, groups of FA, or FA indices were analyzed by PROC MIXED of SAS (SAS Institute Inc., Cary, NC), considering diet, breed, DIM, and sampling period as sources of variation. The random effect of animal was used to test diet, breed, and DIM, whereas the effects of period were tested on the residual. Breed had a small influence on milk FA profile, mainly on branched- and odd-chain FA. Within breed, animal repeatability for the relative proportions of milk FA was notable for almost all monounsaturated FA and for saturated FA with 14 to 19 carbon atoms, except C16:0, and less so for polyunsaturated FA. The inclusion of rpCLA (CLA cis-9,trans-11 and CLA trans-10,cis-12) increased the presence of the same CLA isomers in the milk as well as that of CLA trans-9,trans-11, and decreased the proportions of de novo-synthesized short-chain FA. From a cluster analysis based on the matrix of correlation coefficients among all FA relative proportions, 3 main FA groups were observed: the first included mainly odd- or branched-chain saturated FA, C18:0, C16:0 and CLA trans-10,cis-12; the second included monounsaturated FA or polyunsaturated FA with 16 to 20 carbons, CLA cis-9,trans-11, and CLA trans-9,trans-11; and the third included short- to medium-chain saturated FA, polyunsaturated FA with 2 to 5 double bonds, and 3 CLA isomers not affected by rpCLA addition (CLA trans-11,cis-13, CLA cis-9,cis-11, and CLA cis-10,cis-12)., (Copyright © 2015 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.)

The objectives of this study were to characterize the variation in curd firmness model parameters obtained from coagulating bovine milk samples, and to investigate the effects of the dairy system, season, individual farm, and factors related to individual cows (days in milk and parity). Individual milk samples (n = 1,264) were collected during the evening milking of 85 farms representing different environments and farming systems in the northeastern Italian Alps. The dairy herds were classified into 4 farming system categories: traditional system with tied animals (29 herds), modern dairy systems with traditional feeding based on hay and compound feed (30 herds), modern dairy system with total mixed ration (TMR) that included silage as a large proportion of the diet (9 herds), and modern dairy system with silage-free TMR (17 herds). Milk samples were analyzed for milk composition and coagulation properties, and parameters were modeled using curd firmness measures (CFt) collected every 15 s from a lacto-dynamographic analysis of 90 min. When compared with traditional milk coagulation properties (MCP), the curd firming measures showed greater variability and yielded a more accurate description of the milk coagulation process: the model converged for 93.1% of the milk samples, allowing estimation of 4 CFt parameters and 2 derived traits [maximum CF (CF(max)) and time from rennet addition to CF(max) (t(max))] for each sample. The milk samples whose CFt equations did not converge showed longer rennet coagulation times obtained from the model (RCT(eq)) and higher somatic cell score, and came from less-productive cows. Among the sources of variation tested for the CFt parameters, dairy herd system yielded the greatest differences for the contrast between the traditional farm and the 3 modern farms, with the latter showing earlier coagulation and greater instant syneresis rate constant (k(SR)). The use of TMR yielded a greater tmax because of a higher instant curd-firming rate constant (k(CF)). Season of sampling was found to be very important, yielding higher values during winter for all traits except k(CF) and k(SR). All CFt traits were affected by individual cow factors. For parity, milk produced by first-lactation cows showed higher k(CF) and k(SR), but delays in achieving CF(max). With respect to stage of lactation, RCT(eq) and potential asymptotic CF increased during the middle of lactation and stabilized thereafter, whereas the 2 instant rate constants presented the opposite pattern, with the lowest (k(CF)) and highest (k(SR)) values occurring in mid lactation. The new challenge offered by prolonging the test interval and individual modeling of milk technological properties allowed us to study the effects of parameters related to the environment and to individual cows. This novel strategy may be useful for investigating the genetic variability of these new coagulation traits., (Copyright © 2015 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.)

Providing sufficient amounts of outdoor air to occupants is a critical building function for supporting occupant health, well-being and productivity. In tropical climates, high ventilation rates require substantial amounts of energy to cool and dehumidify supply air. This study evaluates the energy consumption and associated cost for thermally conditioning outdoor air provided for building ventilation in tropical climates, considering Singapore as an example locale. We investigated the influence on energy consumption and cost of the following factors: outdoor air temperature and humidity, ventilation rate (L/s per person), indoor air temperature and humidity, air conditioning system coefficient of performance (COP), and cost of electricity. Results show that dehumidification of outdoor air accounts for more than 80% of the energy needed for building ventilation in Singapore's tropical climate. Improved system performance and/or a small increase in the indoor temperature set point would permit relatively large ventilation rates (such as 25 L/s per person) at modest or no cost increment. Overall, even in a thermally demanding tropical climate, the energy cost associated with increasing ventilation rate up to 25 L/s per person is less than 1% of the wages of an office worker in an advanced economy like Singapore's. This result implies that the benefits of increasing outdoor air ventilation rate up to 25 L/s per person--which is suggested to provide for productivity increases, lower sick building syndrome symptom prevalence, and reduced sick leave--can be much larger than the incremental cost of ventilation.

In this study GC×GC was used to study the effects of pasture, hay, concentrate (indoor), and indoor plus 8 g/day of a rumen-protected conjugated linoleic acid (indoor-CLA) diets on the detailed fatty acid (FA) profiles of six tissues (muscles, fatty tissues, and liver) collected from 36 lambs. This powerful technique allowed the quantification of 128 FAs, of which 21 SFAs, 16 MUFAs, 19 PUFAs were identified by reference standards. The diets had similar, but not identical, effects on FA profiles (g/100 g FA) in the various tissues, as both indoor diets reduced total PUFAs (from 8.91 ± 6.27 to 8.06 ± 5.97; p < 0.05) and n-3 PUFAs (from 2.70 ± 2.37 to 1.50 ± 1.69; p < 0.01) and increased n-6 PUFA (from 3.76 ± 2.46 to 4.58 ± 3.42; p < 0.01), branched (from 2.37 ± 2.05 to 3.23 ± 0.54; p < 0.01), odd-chain FAs (from 5.88 ± 5.33 to 7.07 ± 1.51; p < 0.01) compared to pasture. Indoor-CLA increased CLAc9,t11 (from 0.42 ± 0.13 to 0.53 ± 0.19; p < 0.01), CLAt10,c12 (from 0.07 ± 0.06 to 0.12 ± 0.22; p < 0.05), and CLAc11,t13 (from 0.02 ± 0.04 to 0.05 ± 0.04; p < 0.05) compared to indoor.

"Nostrano-cheeses" are traditional alpine cheeses made from raw cow's milk in Trentino-Alto Adige, Italy. This study identified lactic acid bacteria (LAB) developing during maturation of "Nostrano-cheeses" and evaluated their potential to produce γ-aminobutyric acid (GABA), an immunologically active compound and neurotransmitter. Cheese samples were collected on six cheese-making days, in three dairy factories located in different areas of Trentino and at different stages of cheese ripening (24 h, 15 days, and 1, 2, 3, 6, and 8 months). A total of 1,059 LAB isolates were screened using Random Amplified Polymorphic DNA-PCR (RAPD-PCR) and differentiated into 583 clusters. LAB strains from dominant clusters (n = 97) were genetically identified to species level by partial 16S rRNA gene sequencing. LAB species most frequently isolated were Lactobacillus paracasei, Streptococcus thermophilus, and Leuconostoc mesenteroides. The 97 dominant clusters were also characterized for their ability in producing GABA by high-performance liquid chromatography (HPLC). About 71% of the dominant bacteria clusters evolving during cheeses ripening were able to produce GABA. Most GABA producers were Lactobacillus paracasei but other GABA producing species included Lactococcus lactis, Lactobacillus plantarum, Lactobacillus rhamnosus, Pediococcus pentosaceus, and Streptococcus thermophilus. No Enterococcus faecalis or Sc. macedonicus isolates produced GABA. The isolate producing the highest amount of GABA (80.0±2.7 mg/kg) was a Sc. thermophilus.

The aim of this study was to test the modeling of curd-firming (CF) measures and to compare the sheep milk of 3 Alpine breeds supplemented with or without rumen-protected conjugated linoleic acid (rpCLA). Twenty-four ewes of the Brogna, Foza, and Lamon breeds were allotted to 6 pens (2 pens/breed) and fed a diet composed of corn grain, corn silage, dried sugar beet pulp, soybean meal, wheat bran, wheat straw, and a vitamin-mineral mixture. The rpCLA supplement (12 g/d per ewe plus 4 g/d for each lamb older than 30 d) was mixed into the diet of 1 pen per sheep breed (3 pens/treatment) to provide an average of 0.945 and 0.915 g/d per ewe of the cis-9,trans-11 C18:2 and trans-10,cis-12 C18:2 conjugated linoleic acid isomers, respectively. The trial started at 38 ± 23 d after parturition, and individual morning milk samples were collected on d 16, 23, 37, 44, and 59 of the trial. Milk samples were analyzed for composition, and duplicate samples were assessed for milk coagulation properties (MCP). A total of 180 CF measures for each sample (1 every 15s) were recorded. Model parameters were the rennet coagulation time, the asymptotic potential CF, the CF instant rate constant, the syneresis instant rate constant, the maximum CF achieved within 45 min (CFmax), and the time at achievement of CFmax. The data were analyzed using a hierarchical model that considered the fixed effects of breed, diet, lamb birth, and initial days in milk, which were tested on individual ewe (random) variance; the fixed effect of sampling day, which was tested on the within-ewe sample (random) variance; and the fixed effect of instrument or cuvette position (only for MCP), which was tested on the residual (replicates within samples) variance. The local Alpine sheep breeds displayed similar milk compositions, traditional MCP, and CF modeling parameters. Supplementation with rpCLA triggered changes in milk composition and worsened MCP (e.g., delayed rennet coagulation time, slower CF instant rate constant, and a doubling of syneresis instant rate constant), but did not influence potential CF. Overall, our results indicate that rpCLA supplementation reduced the actual maximum CF (CFmax) but did not modify the interval between rennet addition and CFmax or time to CFmax., (Copyright © 2014 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.)

Unlabelled: The article examines which subjectively evaluated indoor environmental parameters and building features mostly affect occupants' satisfaction in mainly US office buildings. The study analyzed data from a web-based survey administered to 52,980 occupants in 351 office buildings over 10 years by the Center for the Built Environment. The survey uses 7-point ordered scale questions pertaining to satisfaction with indoor environmental parameters, workspace, and building features. The average building occupant was satisfied with his/her workspace and building. Proportional odds ordinal logistic regression shows that satisfaction with all 15 parameters listed in the survey contributed significantly to overall workspace satisfaction. The most important parameters were satisfaction with amount of space (odds ratio OR 1.57, 95% CI: 1.55-1.59), noise level (OR 1.27, 95% CI: 1.25-1.29), and visual privacy (OR 1.26, 95% CI: 1.24-1.28). Satisfaction with amount of space was ranked to be most important for workspace satisfaction, regardless of age group (below 30, 31-50 or over 50 years old), gender, type of office (single or shared offices, or cubicles), distance of workspace from a window (within 4.6 m or further), or satisfaction level with workspace (satisfied or dissatisfied). Satisfaction with amount of space was not related to the gross amount of space available per person., Practical Implications: To maximize workspace satisfaction, designer should invest in aspects that increase satisfaction with amount of space and storage, noise level, and visual privacy. Office workers will be most satisfied with their workspace and building when located close to a window in a private office. This may affect job satisfaction, work performance, and personal and company productivity., (© 2011 John Wiley & Sons A/S.)

Although no study has definitively shown that unfocused screening of skin cancer is effective, many campaigns have been organized with the aim of increasing awareness on melanoma risk factors. The objective of this study was to analyse the results of the Skin Cancer Screening Day in Italy during the period 2005-2007, to determine the priorities for melanoma control plans in a Mediterranean country. A total of 5002 patients were screened by dermatologists in 31 cities. Individuals who considered themselves to have many naevi and those with a family history of melanoma showed a higher number of common and atypical naevi. Ten melanomas, 20 basal cell carcinomas and two squamous cell carcinomas were histopathologically confirmed. Our observations provide the following suggestions for melanoma prevention strategies: (a) an unfocused campaign is suitable to inform the public about the importance of self-examination of the skin, but is not useful to identify a larger number of melanomas; and (b) melanoma screening campaigns should focus on a selected population, which meets rigorous risk criteria to maintain higher cost-effectiveness. The financial support to effective melanoma screening programmes could be increased, especially in southern populations where lower levels of self-surveillance and socioeconomic conditions represent risk factors for late identification of melanoma.

Aim: A total of 371 patients under stable warfarin therapy were retrospectively selected to develop a pharmacogenetic algorithm to identify the individual maintenance dose., Materials & Methods: The variables that were entered into the algorithm were: VKORC1, CYP2C9 and CYP4F2 polymorphisms, body surface area and age., Results: The percentage of cases whose predicted mean weekly warfarin dose was within 20% of the actual maintenance dose was 51.8% considering patients overall, and were 36.2, 66.2 and 55.4%, respectively, taking into account patients requiring low (≤25 mg/week), intermediate (25-45 mg/week) and high (≥45 mg/week) doses. The algorithm could correctly assign 73.8 and 63.2% of patients to the low- and high-dose regimens, respectively. We developed and validated a pharmacogenetic algorithm in a series of Italian patients, we then tested, in the same series of italian patients, the formulas of three published algorithms. These three algorithms were developed and validated by their authors in a series of patients different from our own. The performance of our algorithm in our patients series was slightly higher than that achieved when using the three other algorithms in our patients series., Conclusion: The high predictive accuracy of low and high warfarin requirements of our algorithm warrants its application in prospective studies for clinical validation.

The effects of low-protein (LP) diets and rumen-protected CLA on DMI, ADG, carcass traits, and health status of double-muscled Piemontese young bulls were investigated. Forty-eight bull calves (BW = 237 ± 24 kg) were divided in 4 groups and housed in 12 fully slatted pens. Bulls were fed 2 diets differing in CP density [high-protein (HP) diet: CP = 145 g/kg of DM; LP diet: CP = 108 g/kg of DM] and top-dressed with 80 g/d of rumen-protected CLA or 65 g/d of hydrogenated soybean oil. Orts were collected weekly and feed intake was estimated on a pen basis, with 3 replicated pens for each treatment. Each bull was weighed monthly and examined for alterations of the locomotion system by using the locomotion score as an index of lameness and by counting the number of swollen joints. Carcass quality traits were measured at slaughter, after a feeding period of 332 d. Compared with HP, LP reduced ADG only during the first 4 mo of the trial (1.30 vs. 1.53 kg/d, P = 0.003). However, because of compensatory growth, over the whole trial, no significant effects attributable to CP or to additive were found on final BW (668 kg), ADG (1.19 kg/d), DMI (8.50 or 86 g/d per kg of BW(0.75)), dressing percentage (67.3%), carcass conformation (5.2 points), and carcass fat covering (1.87 points). Feed efficiency was affected by a CP × additive interaction (P = 0.030), with CLA improving feed efficiency when added to the LP diets, whereas feed efficiency was reduced with the HP diets. The addition of both LP and CLA reduced the number of bulls presenting swollen joints (P = 0.001), and LP improved the locomotion score (P = 0.021) compared with HP. It was concluded that 10.8 g/kg of CP density in the diet is sufficient for double-muscled Piemontese bulls. The reduction in CP density from 145 to 108 g/kg of DM, in addition to reducing the feeding cost, allows a strong reduction in N consumption without negative consequences on growth performance and carcass traits.

Background: The combined evaluation of serum pepsinogens A (PGA) and C (PGC), gastrin-17 (G17) and anti-H. pylori antibodies (anti-H. pylori)(GastroPanel) has recently been proposed as a useful aid for investigating H. pylori-associated gastric mucosal inflammation. Our aim was to evaluate whether GastroPanel can correctly classify children who need or not endoscopy (EGD)., Methods: GastroPanel was performed in 554 consecutive children subjected to EGD., Results: PGC and anti-H. pylori were sensitive (82.5% and 73.1%) and specific (58.1% and 84.0%) indices of H. pylori infection. Antral H. pylori colonization density, inflammation and activity grades were correlated with PGC. PGC and G17 were significantly higher in children with celiac disease (14.9+/-0.88 microg/L and 5.6+/-0.79 pmol/L) than in controls (8.5+/-0.38 microg/L and 2.4+/-0.24 pmol/L). The best cut-offs to distinguish H. pylori infected children from controls were 7.45 microg/L for PGC, 4.2 pmol/L for G17, 18 U for anti-H. pylori and 25 microg/L for PGA. With these cut-offs, GastroPanel had a NPV of 89.6% and a PPV of 66.8%., Conclusions: A negative GastroPanel result in children with upper abdominal non alarm symptoms, should allow the paediatrician to reasonably rule out the presence of major gastro-duodenal diseases and therefore avoid EGD.

Background: AGA IgA II and AGA IgG II have recently been suggested as reliable tools for celiac disease (CD) diagnosis. We compared their utility for diagnosis and monitoring CD in children with that of tTG IgA, an established CD marker., Methods: We studied a cohort of 161 CD and 129 control children in whom CD was histologically confirmed or ruled out. We followed 37 children with CD on a gluten-free diet for 12-84 months. In fasting sera, we measured AGA IgA II, AGA IgG II, and tTG IgA using ELISAs., Results: The best sensitivity (92.5%), specificity (97.6%), positive predictive value (98%), and negative predictive value (91.2%) were obtained using tTG IgA. AGA IgG II correctly identified 3 of 3 children with CD with total IgA deficiency who had negative AGA IgA II and tTG IgA results. In children <2 years old without total IgA deficiency, AGA IgG II and tTG IgA performed equally well (sensitivity 96.4% and specificity 100%). AGA IgA II, AGA IgG II, and tTG IgA concentrations diminished significantly (P < 0.0001) after 1 year of a gluten-free diet, reaching values below the cutoff in 87%, 70%, and 51% of cases, respectively., Conclusions: The best available index for diagnosing CD in children was tTG IgA. In infants <2 years old, AGA IgG II performed as well as tTG IgA in cases without total IgA deficiency and allowed detection of CD when total IgA was <0.06 g/L. Gluten-free diet monitoring can be achieved using any of the studied serum markers.

Background & Aims: The Helicobacter pylori gene cagA and s1 or m1 forms of vacA are more common in disease-associated strains. Recently, forms of cagA encoding multiple type C EPIYA segments (which increase phosphorylation-dependent CagA activity) and a new type i1 "intermediate region" polymorphism in vacA (which confers toxicity) have been described. We assessed the association of new and established cagA and vacA polymorphisms with disease., Methods: We studied 203 H pylori-infected subjects (53 gastric cancer [GC], 52 peptic ulcer [PU], and 98 gastritis). vacA signal, mid and intermediate region polymorphisms, cagA presence, and EPIYA-C segment number were analyzed by polymerase chain reaction., Results: cagA-positive strains were significantly associated with GC and PU (P < .001 and P < .05). GC risk was further associated with the number of cagA EPIYA-C segments (odds ratio [OR] = 7.37, 95% confidence interval [CI] = 1.98-27.48 for 1 EPIYA-C segment; OR = 32.5, 95% CI = 8.41-125.58 for 2 or more EPIYA-C segments). Increasing number of EPIYA-C segments also increased the risk of intestinal metaplasia. Type s1 and i1 vacA alleles were also associated with GC and type i1 vacA with PU (OR = 2.58, 95% CI = 1.19-5.61), including a significant association with duodenal ulcer. In multivariate analysis, the associations of cagA EPIYA-C segment number with GC and intestinal metaplasia as well as vacA i1 type association with PU remained., Conclusions: We confirmed the associations of cagA and vacA polymorphisms with disease but now define their most important features. For cancer risk, among Western strains, the most important factor is the number of cagA EPIYA-C segment. For PU risk, it is the intermediate region type of vacA.

Background: The Th2 cytokine IL-4 might limit H. pylori associated gastric inflammation and favour H. pylori clearance. The aim of the study was to verify whether IL-4 -588C>T SNP, or two SNPs of the gene coding the alpha chain of IL-4 receptor (IL-4RA Ex5+14A>G, IL-4RA Ex11+828A>G) considered singly or as haplotypes, are correlated with H. pylori virulence genes or H. pylori associated diseases., Methods: We studied 144 patients with non-cardia gastric cancer (NCGC)(41/50 with present or past H. pylori infection), 75 with duodenal ulcer (DU)(66 H. pylori infected) and 171 with gastritis (CG)(107 H. pylori infected). cagA gene was present in 24/28 NCGC, 45/59 DU and 56/107 CG., Results: All SNPs were in Hardy-Weinberg equilibrium. IL-4RA haplotypes frequencies were estimated using Arlequin software. Neither the SNPs nor the IL-4RA haplotype correlated with disease diagnosis, H. pylori infection, degree of mucosal inflammation or intestinal metaplasia. IL-4 -588T allele (OR=3.69, 95% CI:1.34-10.16) and IL-4RA GA haplotype (p<0.05) enhanced the risk for cagA positive infections. IL-4RA GA haplotype correlated with IL-4 protein levels in H. pylori infected gastric mucosa., Conclusions: IL-4 and IL-4RA gene polymorphisms concur in selecting the H. pylori infecting strain, probably influencing the IL-4 signalling pathway.

Several bacterial and host-related factors concur in causing Helicobacter pylori eradication failure. We ascertained the role of bacterial virulence genes (cagA, vacA), clarithromycin resistance [Cla(R), 23S ribosomal RNA (rRNA) mutations], host polymorphism of CYP2C19 (polyphosphoinositide, PPI, metabolism) and of the cytokines IL-1B-31C>T, IL-1RN VNTR, IFN-gamma+874A>T, TNF-alpha-1031T>C, TNF-alpha-857C>T, TNF-alpha-376G>A, TNF-alpha-308G>A, TNF-alpha-238G>A, IL-10-1082A>G, IL-10-819C>T, IL-10-592C>A, IL-12A+6686G>A, IL-12B+15485A>C. Two groups of H. pylori-infected and H. pylori-treated patients were retrospectively identified: 45 not eradicated and 57 eradicated. Treatment failure was significantly correlated with Cla(R) (all resistant strains in non-eradicated patients); with TNF-alpha-238, IL10-819, IL10-592, IL-12B+15485 single nucleotide polymorphism (SNP); with IL10 ATA/ATA haplotype; and with antral inflammatory grade. On considering Cla(S)-infected patients only, logistic regression analysis (eradication = dependent; TNF-alpha-238, IL12B + 15485 genotypes, IL10 ATA/ATA as present or absent, antral gastritis grade = covariates) confirmed as significantly correlated with eradication antral gastritis grade only (Exp(B) = 6.48; 95% CI, 1.2-35.01). In conclusion, the bacterial determinant causing triple therapy failure is clarithromycin resistant, being virulence genes not involved. The host related factors that favor eradication are those linked to inflammation: a higher inflammatory infiltrate in the mucosa, possibly favored by genotypes able to down regulate the anti-inflammatory cytokine response, enhance the chance of eradication success.

This work focuses on the main DNA repair pathways, highlighting their role in gastrointestinal carcinogenesis and the role of mitochondrial DNA (mtDNA), mutations being described in several tumor types, including those of the gastrointestinal tract. The mismatch repair (MMR) system is inherently altered in patients with hereditary non-polyposis colorectal cancer, and plays a role in carcinogenesis in a subset of sporadic colorectal, gastric and esophageal cancers. Alterations in homologous recombination (HR) and non-homologous end-joining (NHEJ) also contribute to the development of pancreatic cancer. Gene polymorphisms of some X-ray cross-complementing (XRCCs), cofactor proteins involved in the base excision repair pathway, have been investigated in relation to gastric, colorectal and pancreatic cancer. Yet only one polymorphism, XRCC1 Arg194Trp, appears to be involved in smoking-related cancers and in early onset pancreatic cancer. Although evidence in the literature indicates that mtDNA somatic mutations play a role in gastric and colorectal carcinogenesis, no sound conclusions have yet been drawn regarding this issue in pancreatic cancer, although an mtDNA variant at 16519 is believed to worsen the outcome of pancreatic cancer patients, possibly because it is involved in altering cellular metabolism.

Objectives: Anti-tissue transglutaminase antibody (anti-tTG) determination using second-generation (human antigen) enzyme-linked immunoassays (ELISAs) is a very accurate test to diagnose celiac disease (CD). In this study, we compared 2 second-generation ELISAs (Celikey tTG; Pharmacia Diagnostics GmbH & Co, Freiburg, Germany, and QuantaLite; Inova Diagnostics, San Diego, CA) and antiendomysial antibodies (EMAs) with a new indirect chemiluminescence immunoassay (LIAISON tTG; DiaSorin S.p.A., Saluggia, Italy) in diagnosing and monitoring CD in children., Patients and Methods: Antiendomysial antibodies, anti-tTGs and total immunoglobulin A were measured in the sera of 103 control children, 101 children with histologically proven CD and 31 CD children on gluten-free diet (GFD)., Results: Anti-tissue transglutaminase antibody mean levels were significantly higher in CD with respect to control or GFD children. The sensitivity value of EMAs, LIAISON tTG, Celikey tTG and QuantaLite in diagnosing CD was 97.7%, 97.0%, 94.1% and 98.0%, respectively, and the corresponding specificity values were 91.1%, 98.1%, 97.1% and 96.1%, respectively. The degree of mucosal destruction (Marsh criteria) was correlated with EMA semiquantification (P < 0.01) and with the circulating levels of anti-tTGs measured using LIAISON (P < 0.05) or QuantaLite (P < 0.01). Twenty-six CD children were followed up from 5 to 25 months after GFD. The circulating levels of anti-tTGs measured with any of the 3 assays significantly dropped after GFD., Conclusions: Anti-tissue transglutaminase antibody determination with second-generation ELISAs is as effective as EMAs for CD diagnosis. The novel chemiluminescent method described in the present paper for the detection of anti-tTGs in the diagnosis of CD had the highest sensitivity and specificity values. The anti-tTG test correlates with the degree of mucosal destruction and is suitable for verifying patient compliance to dietary treatment.

Purpose: To study the prognostic value for overall survival of baseline assessment of functional status, comorbidity, and quality of life (QoL) in elderly patients with advanced non-small-cell lung cancer treated with chemotherapy., Patients and Methods: Data from 566 patients enrolled onto the phase III randomized Multicenter Italian Lung Cancer in the Elderly Study (MILES) study were analyzed. Functional status was measured as activities of daily living (ADL) and instrumental ADL (IADL). The presence of comorbidity was assessed with a checklist of 33 items; items 29 and 30 of the European Organisation for Research and Treatment of Cancer (EORTC) core questionnaire QLQ-C30 (EORTC QLQ-C30) were used to estimate QoL. ADL was dichotomized as none versus one or more dependency. For IADL and QoL, three categories were defined using first and third quartiles as cut points. Comorbidity was summarized using the Charlson scale. Analysis was performed by Cox model, and stratified by treatment arm., Results: Better values of baseline QoL (P = .0003) and IADL (P = .04) were significantly associated with better prognosis, whereas ADL (P = .44) and Charlson score (P = .66) had no prognostic value. Performance status 2 (P = .006) and a higher number of metastatic sites (P = .02) also predicted shorter overall survival., Conclusions: Pretreatment global QoL and IADL scores, but not ADL and comorbidity, have significant prognostic value for survival of elderly patients with advanced non-small-cell lung cancer who were treated with chemotherapy. Using these scores in clinical practice might improve prognostic prediction for treatment planning.

Late capsular hematoma after the implantation of silicone breast prostheses for augmentation mammaplasty is an extremely rare complication. The case of a patient in whom two late intracapsular hematomas occurred two times after augmentation mammaplasty with textured silicone implants is reported. Magnetic resonance imaging clearly showed fluid accumulated within the capsule. No identifiable etiology could be demonstrated, although the breakdown of an eroded capsular artery is suspected, caused by friction between the rough surface of the textured prosthesis and the fibrous capsule. Two hematomas in a single patient have not been described previously in the literature.

A model to predict voluntary water intake (WI) of a pig fed a known diet in a known environment is described. The daily retentions of protein, lipid, water and ash were estimated over time using a published pig growth model. Food intakes were estimated using published methods. WI was estimated by adding the amounts required for digestion (WD), faecal excretion (Wfec), growth (WG), evaporation (WE), urinary excretion (WU) and by then subtracting the water arising from feed (WF), from nutrient oxidation (WO) and synthesis of body constituents (WS). WD was predicted assuming an absorption of water of 0.10, 0.16 and 0.07 kg/kg digestible carbohydrate, crude protein and lipid respectively. Wfec was estimated taking into account the water associated with the undigested protein (0.86 kg/kg), diethyl ether extract (-12.11 kg/kg), crude fibre (1.86 kg/kg), ash (-0.42 kg/kg) and N-free extract (4.4 kg/kg). The basal level of WE was estimated from the heat production of the pig fed ad libitum (MJ/d) as: 0.25 x (metabolizable energy - energy retained as protein and lipid) x 0.4, where 0.25 is the assumed proportion of the insensible heat loss at the comfort temperature and 0.4 is the water lost per MJ dissipated heat. WE in a hot environment was predicted by assuming that evaporation increased up to three times the basal level to offset the decreased sensible heat loss. To predict WU a water requirement for renal excretion of 2.05 and 3.40 kg/osmol excreted N as urea and minerals respectively was assumed. The urinary load of N and minerals was predicted from the intake of digestible nutrients and their retention. From the oxidation of 1 kg carbohydrate, protein, and fat it was assumed that 0.6, 0.42 and 1.07 kg water (WO) were released respectively. WS was predicted by assuming a release of 0.16, 0.07 and 0.57 kg water per kg retained protein, retained lipid coming from digestible lipid, and retained lipid coming from digestible carbohydrate respectively. The model is strongly rooted in a theoretical structure. When its predictions were compared with data from suitable experiments, the results were not significantly different. Both the pattern and the magnitude of responses of the model to changes in body weight, feed intake and environmental temperature are sensible and it allows a fuller prediction of voluntary water intake than the methods currently available.

Background: The combination of paclitaxel (P) and carboplatin (C) is an effective treatment for advanced NSCLC. Gemcitabine (G) is an active new drug. We planned a phase I study to find the maximum tolerated dose (MTD) of the PCG combination. A phase II study was subsequently conducted to evaluate the activity and toxicity of PCG., Patients and Methods: Forty-five patients entered the study. Twenty-eight had stage IIIA-B disease, 17 stage IV. In the phase I study, with a fixed dose of C at AUC = 6 on day 1, P was escalated using increments of 25 mg/m2 starting from 175 mg/m2 on day 1 and G with increments of 200 mg/m2 starting from 800 mg/m2 on day 1 and 8., Results: Fourteen patients entered the phase I study. The MTD was reached at P 200 mg/m2, C AUC = 6 and G 1000 mg/m2. Neutropenic fever and grade 3 diarrhea were the dose limiting toxicities. Thirty-one patients were treated in the phase II study with P 175 mg/m2, C AUC = 6 and G 1000 mg/m2. Response rate was 57% (68% in stage III and 47% in stage IV). Myelosuppression was the main toxicity, with grade 3-4 leukopenia occurring in 35% of cases. Grade 3 anemia was observed in 24% of cases and grade 3-4 thrombocytopenia occurred in 34% of patients. Non-hematological toxicity was mild. Median survival and one-year actuarial survival were 20.5 months and 74% for stage III and 11.5 months and 47% for stage IV., Conclusions: PCG is a promising regimen for treating advanced NSCLC. A phase III study comparing PCG to paclitaxel plus carboplatin in advanced NSCLC is ongoing. On the other hand, we are planning to introduce the PCG regimen in the treatment of stage II-III patients in the setting of a multimodality treatment.

Dry matter degradability (DMD), gas production (GP), functional specific gravity (FSG), volume of gas associated (GA), water-holding capacity (WHC), and sedimentation measurements of orchard-grass (OG) and alfalfa (AA) hays (ground through a 8-mm screen) were studied before and after in vitro incubation with ruminal fluid for 2, 4, 8, 24, 48, and 72 h. The DMD was higher for AA than for OG (P < .001), but GP did not differ. The FSG of unfermented OG and AA was .59 and .73, respectively (P < .01). During fermentation, the FSG of OG increased more than did that of AA (from .93 to 1.39 for OG and from .97 to 1.27 for AA after 2 and 72 h, respectively), and GA decreased more rapidly (from .94 to -.04 mL/g DM and from .74 to .15 mL/g DM, respectively). The DMD was positively correlated with FSG (r = .83; P < .001) and, therefore, negatively with GA (r = -.72; P < .01). The WHC increased similarly in the two forages with fermentation time. Unfermented and fermented samples were incubated in sedimentation columns filled with distilled water for 19, 37, 75, 150, and 300 s. After 300 s of sedimentation time, the unfermented AA and OG samples tended to float (91.1 and 72.7% of DM, respectively). In contrast, fermented samples tended to sediment (90.7 and 90.9% of DM, respectively). There were only small effects of forage species and fermentation time on sedimentation tendency. Correlations between sedimentation measurements and DMD and FSG were not significant, with the only exception of DM recovered in the lower section of sedimentation columns after 75 s, which was particularly correlated with DMD (P < .01) and FSG (P < .05). The results suggest that degradation rate of fibrous particles is related to changes in FSG and GA and, therefore, could influence ruminal transit. However, FSG was unable to predict accurately the sedimentation behavior of samples.

Four primiparous Holstein cows were gradually introduced, according to a Latin square design, to four diets obtained from the factorial combination of two forage to concentrate ratios (70:30 and 50:50) and two concentrations of monensin sodium (0 and 300 mg/d per cow). Addition of monensin tended to depress feed intake and milk fat content without affecting milk production and without interactions with forage to concentrate ratios. Ruminal propionate percentage was increased more by the addition of monensin to the low forage diet than by the addition of monensin to the high forage diet. Serum urea and concentrations of nonesterified fatty acids tended to decrease when monensin was added to the high forage diet but did not change when monensin was added to the low forage diet. The results suggested that monensin had moderate positive effects on efficiency of milk production and might have an antiketogenic effect with high forage diets.

From 1985 through 1993, 113 patients affected with T1N0 glottic cancer were treated with irradiation alone at the Radiotherapy Department of Umberto I Hospital in Mestre, Italy. An anterior oblique beam of 12 MV X-rays (LINAC) or gamma-rays of a Cobalt unit were used. Dose distribution was always studied on CT scans and with a Theraplan V05-B, Theratronics. Patients age ranged 40-92 years (mean: 64.7 years) and they were mostly males. The dose was always 60 Gy/30 fractions referred to the 90% isodose. The dose to the target volume ranged 90-105%, with a mean of 99%. The follow-up ranged 26 to 98 months; the median and the mean are 38 and 40 months, respectively. Six patients had local relapses and were all operated on: cordectomy was performed in 3 of them and laryngectomy in the other 3. Radiation therapy yielded 94.7% disease control; the lesion was ultimately controlled in 100% of patients after surgical salvage. Fifteen patients died, all of them of non-neoplastic disease. The authors compared this technique with those most frequently used, i.e., wedged opposed lateral fields and wedged anterior oblique beams, and observed that it allows minimal volumes to be irradiated with maximal doses and yields results. Wedged beams are not necessary with this technique. The authors consider irradiation the treatment of choice for early glottic cancer and believe that surgery, with the conservative approach if feasible, should be limited to relapses.

The coplanar polycentric multiple 180 degrees single arc and narrow beams technique (PMA) allows high radiation doses to be delivered to the target, with similar dose distribution to that of brachytherapy. Since 1990, more than 100 patients have been treated: 80 had NSCLC, 12 had epidermoid head and neck (oral cavity and oropharynx) cancers, 8 brain tumors, 4 esophageal cancers and, sporadically, other patients had many other kinds of tumors, e.g., Hodgkin's and non-Hodgkin's lymphomas and sarcomas. X photons of a 12-MV Linac have always been used. NSCLC patients are assessable for local control, toxicity and survival, while the other patients only for local control and/or toxicity. As for 31 stage I-II lung cancer patients, CR has been observed in 82.8% of them and PR in 13.8%; the response was always assessed with chest radiography, CT, FBS, cytology and/or histology. The overall actuarial survival rate is 71% at 40 months, the disease-free survival rate is 75% and the local progression-free survival rate is 94%. As for 49 stage-III patients, CR has been observed in 40% of them and PR in 56%. The overall disease-free survival is 10% at 28 months (median survival: 14.37 +/- 0.6 months). The disease-free survival rate is 23%. The local progression-free survival rate is similar to the overall survival rate, which seems to prove the very high metastatic spread of this disease in advanced stages. Twelve head and neck cancer patients have been treated, 5 of them in stage II and 7 in stage IV. CR has been observed in all the patients in lower stages (100%), in 4/7 patients in stage IV (57%) and in 4/5 patients (80%) in the T4N0 subgroup. The response of brain tumors treated with the PMA technique is difficult to assess because radiographic, CT and MR images are difficult to correlate with patients clinical status. The patients in our series are still alive, with a medium follow-up of 7 months (range: 2-16 months). A longer follow-up is necessary before any other considerations on the effectiveness of this method can be made. This technique was used on the patients who were not eligible for the other techniques with high doses delivered to the tumor, because of its volume and/or shape. Four esophageal cancers were treated with palliative intent, because of absolute dysphagia, in alternative to HDR brachytherapy. All these patients have obtained symptom remission.(ABSTRACT TRUNCATED AT 400 WORDS)

From January 1984 to December 1992, twenty-eight patients affected with breast carcinoma in situ were treated with surgery (8 with radical mastectomy, 20 with quadrantectomy) at Umberto I Hospital in Mestre, Italy. The patients with multicentric lesions and treated with quadrantectomy received also radiation therapy. The dose was 50 Gy/25 fractions with 60Co and a boost of 10 Gy to the tumor bed. The mean age of our patients was 55 years (range: 34-74 years). Histology diagnosed lobular carcinoma in situ in 7 cases, intraductal carcinoma in 19 cases and comedocarcinoma in 2 cases. The median and the mean follow-up are 37 and 42 months (range: 24-128), respectively. The eight-year local control and the cause-specific survival rates are 100%. No local relapses have been observed. One patient died, of another neoplastic disease, free from breast disease. We believe that the conservative approach in breast carcinoma in situ, according to literature results and to our personal experience, should be more frequently preferred to radical surgery even in the patients with multicentric lesions.

A severe case of myiasis is reported in an Italian technician working in a forest yard in Illubabor (Ethiopia). The patient returned to Italy with fever, malaise and scattered skin lesions: these were papular at first, and later developed into furuncle-like, intensely burning boils which spread all over the body. Neutrophilic leukocytosis was present associated with increased IgA. From the lesions, 150 larvae were recovered and identified as Cordylobia rodhaini Gedoelst (Diptera, Calliphoridae), a myiasis agent adapted to various thin-skinned mammals in African forests, rarely observed in man. This is the first case recorded in Ethiopia and represents the most massive invasion by Cordylobia spp. published so far. The 3rd stage larva is described with some morphological details not reported by previous authors.

An unusual syndrome of lichen planus, characterized by ulcerations confined to the feet, permanent loss of toenails and a cicatricial alopecia of the scalp is reported, related to a 71 years old woman. Only eleven cases identical of this have been described as yet. Skin grafting to the ulcerous surfaces has been the treatment of choice, because offers the opportunity for a lasting therapeutic response.