Zoledronic acid in patients with stage IIIA/B NSCLC: results of a randomized, phase III study.

BACKGROUND: Bone metastases are common in patients with advanced non-small-cell lung cancer (NSCLC) and can have devastating consequences. Preventing or delaying bone metastases may improve outcomes. PATIENTS AND METHODS: This study evaluated whether zoledronic acid (ZOL) delayed disease progression or recurrence in patients with controlled stage IIIA/B NSCLC after first-line therapy. Patients received vitamin D and calcium supplementation and were randomized to i.v. ZOL (every 3-4 weeks) or no treatment (control). The primary end point was progression-free survival (PFS). RESULTS: No significant intergroup differences were observed in PFS or overall survival (OS). Median PFS was 9.0 months with ZOL versus 11.3 months for control. Fifteen ZOL-treated (6.6%) and 19 control patients (9.0%) developed bone metastases. Estimated 1-year OS was 81.8% for each group. ZOL safety profile was consistent with previous clinical data, but with higher discontinuations versus control. Fifteen ZOL-treated (6.6%) and five control patients (2.3%) had renal adverse events. Two cases of osteonecrosis of the jaw were reported. CONCLUSIONS: ZOL did not significantly affect PFS or OS in stage IIIA/B NSCLC patients with controlled disease, with a trend toward worsening PFS in the longer-term follow-up. Few patients experienced bone metastases, possibly limiting the potential ZOL impact on disease course.

Meat quality traits and canonical discriminant analysis to identify the use of illicit growth promoters in Charolais bulls.

The administration of anabolic agents in farm animals to improve meat production has been prohibited in EU, due to the potential risks to human health. Meat quality was investigated to detect the effects of illegal administration of dexamethasone or prednisolone or 17ß-estradiol on Charolais bulls. Three groups of 6 bulls were treated and 12 bulls were the control. Meat quality parameters were measured on live animals, carcasses and on samples of Longissimus thoracis and multivariate statistical data analysis was applied. In Charolais bulls, these parameters were affected by growth promoter administration and the multivariate canonical discriminant analysis was able to distinguish between treated and untreated animals mainly due to three electronic nose's parameters, 24 h carcass temperature and drip loss. Therefore, meat quality control and the multivariate analysis could be useful as a first screening to address targeted controls on farms suspected of illicit use of growth promoters.

Canonical discriminant analysis and meat quality analysis as complementary tools to detect the illicit use of dexamethasone as a growth promoter in Friesian bulls.

A screening method based on meat quality parameters and production traits for detecting the effects of illegal administration of dexamethasone in Friesian bulls was assessed. Twenty finishing bulls were divided into an untreated control group (n=8) and two treatment groups receiving dexamethasone orally at dosages of 1.4 (n=6) or 0.7 (n=6)mg per head per day for 60 days. The animals were slaughtered 26days after cessation of treatment. Thirty-six parameters were measured on live animals, carcasses and samples of the longissimus thoracis muscle. The production traits were similar between groups, but there were significant differences in meat quality between treatment groups. The higher dosage of dexamethasone improved meat tenderness, while the lower dosage resulted in more saturated red meat, with increased meat cooking shrinkage and cooking loss. The use of a portable 'electronic nose' as a screening tool was not successful in discriminating between treated and untreated meat. These results indicate that a multivariable approach using canonical discriminant analysis may be a complementary tool to identify meat from animals illegally treated with dexamethasone, based on several parameters (meat flavour, cooking and thawing loss, tenderness, colour and live weight gain), which are part of the normal analysis of meat quality.

Fate of selected pathogens in spiked «SALAME NOSTRANO¼ produced without added nitrates following the application of NONIT™ technology.

This study evaluated the effect of a novel formulation for starter culture associated with specific ripening conditions (NoNit™ technology) vs. a commercial¼ starter on the fate of selected pathogens and hygiene indicators during the fermentation and ripening of experimentally spiked salame nostrano (Italian dry sausage). Selected strains of Staphylococcus aureus 27R, Escherichia coli CSH26 K 12, Listeria innocua ATCC 33090 and Salmonella Derby 27 were inoculated into salami batter and challenged with two formulations of starter cultures (a commercial formulation and the NoNit™ formulation, consisting of Lactococcus lactis ssp. lactis, strain 340; L. lactis ssp. lactis, strain 16; Lactobacillus casei ssp. casei, strain 208 and Enterococcus faecium strain 614) with ripening at a low temperature. The proposed technology (NoNit™) performed better than the commercial formulation and limited the growth of spiked Escherichia coli, Staphylococcus aureus (including the production of enterotoxin), Salmonella Derby and Listeria innocua, yet maintained the basic product appearance and texture.

Meat cooking shrinkage: Measurement of a new meat quality parameter.

A parameter, meat cooking shrinkage (MCS), has been introduced based on investigations carried out on meat shrinkage caused by heat during cooking. MCS is the difference between the raw and cooked areas of the meat sample, expressed as a percentage of the raw area. The method uses a disk of meat (10mm thick and 55mm wide) measured before and after cooking in a hot air oven at 165°C for 10min, the meat having reached an internal temperature of 70°C. Video image analysis was used to measure the meat sample area. The proposed MCS protocol permits us to measure cooking loss and to reduce cost and variability, moreover it could be improved to obtain color and marbling measurements by developing the image analysis software. Analysing two or more parameters on the same sample, the correlations among them should improve analysis efficacy. A detailed description of the measurement protocol of MCS is reported as well as its application to beef and pork.

Performances and meat quality of two Italian pig breeds fed diets for commercial hybrids.

The effects of specific diets for commercial hybrids were investigated on 6 Casertana and 11 Mora Romagnola, two endangered Italian pig breeds. Average daily gain (ADG), feed conversion index (FCI), dressing percentage and meat and fat quality of animals bred under similar environmental and nutritional conditions were compared to define their optimal slaughtering weight. Animals were fed the same diets assuming that requirements of Mora Romagnola and Casertana did not differ, and changed every 30kg of weight gain. ADG and FCI were calculated every 15 days. Weight gains, divided into 5 groups based on live weight (LW) of animals (⩽60kg, 60160kg), showed higher values for Casertana than Mora Romagnola, particularly from 121 to 160kg LW (687g/d). Average FCI from 50 to 160kg LW was similar in both breeds (4.2). After 403 days of trial, animals were slaughtered at about 195kg LW. Carcass measurements showed that Casertana had higher dressing percentage and lean cuts than Mora Romagnola. Both breeds showed extraordinary high ultimate pH values of M. longissimus thoracis (5.96 and 6.15 for Casertana and Mora Romagnola, respectively) M. semimembranosus (6.37 and 6.30), showing an incomplete post mortem glycolysis. Colour of M. longissimus thoracis did not differ between breeds and was particularly dark. Chemical analysis of Casertana meat showed lower percentage of water and fat; the total amount of fatty acids (SFA, MUFA and PUFA) and the SFA/UFA ratio did not show significant differences between breeds. Results showed that from a growth point of view the optimal slaughtering weight of Casertana and Mora Romagnola should not exceed 160kg LW. Both breeds had an uncommon reactivity to stress probably due to interactions of genetic, nutritional and management factors.

Neonatal rhabdomyolysis as a presentation of muscular dystrophy.

We report a unique presentation of X-linked recessive dystrophy as neonatal rhabdomyolysis. There was induration of the proximal musculature in an otherwise well neonate and striking CK elevation, without myoglobinuria. Muscle biopsy at age 1 year showed dystrophic alterations, and X chromosome analysis showed a deletion within or adjacent to the Duchenne/Becker locus.

Determination of disodium clodronate in human plasma and urine using gas-chromatography-nitrogen-phosphorous detections: validation and application in pharmacokinetic study.

We present a specific method for the determination of disodium clodronate in human plasma and urine using a gas-chromatographic system with nitrogen phosphorus detector (NPD). The compound was extracted from plasma and urine samples by an anion-exchange resin and derivatizated with bistrimethylsilyltrifluoroacetamide (BSTFA). Sodium bromobisphosphonate was used as internal standard. The calibration curves were linear in both plasma and urine, with a regression coefficient r > 0.9975 in plasma and r > 0.9977 in urine. The limit of quantitation was 0.3 microg/ml in plasma and 0.5 microg/ml in urine. The method was validated by intra-day assays at three concentration levels. During the study we carried out inter-day assays to confirm the feasibility of the method. The precision in plasma at 0.5, 15, and 45 microg/ml was 12.4, 0.2, and 6.5% (n = 40), respectively; in urine at 0.8, 8, and 40 microg/ml it was 8.6, 6.4, and 9.3% (n = 40), respectively. The method was accurate and reproducible, and was successfully applied to determine the pharmacokinetic parameters of clodronate in healthy volunteers after intravenous infusion and intramuscular injection of 200 mg of the compound. The Cmax after intravenous infusion and intramuscular injection was 16.1 and 12.8 microg/ml, respectively. AUC(0-48 h) after infusion administration and intramuscular injection was 44.2 +/- 18.0 and 47.5 +/- 12.4 h microg/ml, respectively. The elimination half-life in both administrations was 6.31 +/- 2.7 h.

Effect of poloxamer 407 on the adherence of Pseudomonas aeruginosa to corneal epithelial cells.

The effect of poloxamer 407 on Pseudomonas aeruginosa adherence to cultured epithelial cells from rabbit corneas was investigated. Three methods of bacterial quantification were used to assess P. aeruginosa adherence: scanning electron microscopy (SEM) counts, radioactivity counts, and viable bacteria counts. Confluent monolayers of rabbit corneal epithelial cells were incubated in agitation for 30 min at room temperature with H3-labeled or nonradiolabeled P. aeruginosa (10(10) bacteria/ml) in a solution of poloxamer 407 [2% or 4% in phosphate-buffered saline (PBS)] or PBS as control. Cell monolayers were washed to remove nonadherent bacteria and fixed with 2.5% glutaraldehyde and processed for SEM or processed for radioactivity counting or for culture on agar plates. The results showed that both solutions of poloxamer 407 inhibited approximately 75% of the bacterial adherence to epithelial cells (p < 0.05). Similar percentages of bacterial inhibition were obtained using the three methods of bacterial quantification. The use of an antiadherent agent such as poloxamer 407 in eye drops could possibly be a prophylactic approach to P. aeruginosa keratitis.

Effect of hybrid peptides of cecropin A and melittin in an experimental model of bacterial keratitis.

Synthetic peptides, ranging from 12 to 18 residues, containing partial sequences from natural cecropin A and melittin were tested for activity in an experimental pseudomonas keratitis model in rabbits. In separate experiments, two Pseudomonas aeruginosa strains: (a) a clinical isolated strain, and (b) an American Type Culture Collection (ATCC) strain, were inoculated into the stroma of one cornea of each rabbit. Peptides were topically applied at 0.1% in phosphate-buffered saline (PBS) and compared with PBS alone and 0.3% gentamicin eye drops. Clinical evaluation, based on the McDonald-Shadduck scale, was performed during a > 48-h period after the bacterial inoculation. The peptide-treated animals showed significantly lower (p < 0.05) inflammatory signs and lower anterior-segment bacterial damage compared with PBS-treated animals, after the first 6 h. The antiinflammatory/antimicrobial activity was non significantly differnt (p > 0.05) from that in animals treated with gentamicin. We conclude that peptides keeping the sequence KWKLFKK from cecropin A and at least the sequence VLKVL from melittin show promise as novel agents in topical ocular therapy of bacterial keratitis.

Circadian variations in the affinities of NAD kinase and NADP phosphatase for their substrates, NAD+ and NADP+, in dividing and nondividing cells of the achlorophyllous ZC mutant of Euglena gracilis Klebs (strain Z).

We have previously shown that NAD kinase and NADP phosphatase activities display circadian rhythms, in the soluble (SN) and membrane-bound (P) fractions of crude extracts of the achlorophyllous ZC mutant of the phytoflagellate Euglena gracilis (which displays circadian rhythmicity of cell division). We determined if changes in the affinity of NADP phosphatase and NAD kinase for their substrates, NADP+ and NAD+, were occurring by calculating the ratios 100(velocity found in Km conditions/velocity found in saturating conditions). The rationale was that if the affinity remained unchanged according to circadian time (CT), these values should always equal 50, independently of any changes in enzyme quantity; values greater than 50 should indicate increases in enzyme affinity, and values less than 50 decreases in affinity. Our results indicated that these values calculated for NADP phosphatase exhibited a complex pattern of rhythmicity, while those for NAD kinase displayed circadian variations strongly correlated with the rhythms in enzyme activity. The curves showed troughs at CT 00-04 both in dividing and nondividing cells and peaks at CT 18-20 or at CT 08-14 in cells sampled, respectively, from a dividing or a stationary culture. Such variations are indicative of changes in the kinetic properties of the enzyme, which may reflect modifications in its affinity either for effectors (such as Ca2(+)-calmodulin) or for its substrate, NAD+. This may be due to (i) the expression of different isoenzymes at different CTs; (ii) different posttranslational modifications of the enzyme; or (iii) concentrations of effectors varying in a circadian manner.

[Evaluation of malnutrition risk in adult hospital patients]. / Valutazione del rischio di malnutrizione in pazienti adulti ospedalizzati.

BACKGROUND: The aim of the study was to evaluate the validity and reliability of a risk of malnutrition screening tool (MST) proposed by Ferguson et al. for adult hospital patients. METHODS: The study included 207 consecutive patients admitted to a Hospital (118 males, 89 females, aged 61+/-16 years) including internal medicine (89), lung (60) and surgical (58) patients. The MST, consisting of three questions regarding appetite and recent unintentional weight loss, was applied to each patients. Peripheral lymphocytes and serum albumin considered as predictor of nutritional status were also evaluated. RESULTS: Forty-two patients (20% of overall population) resulted malnourished at admission and nutrition support was rapidly established. Of the remaining, 141 (85%), according to the score of MST were not at risk of malnutrition, while 24 (15%) were classified at risk. Peripheral lymphocytes and serum albumin were unable to discriminate the risk in well-nourished patients. CONCLUSIONS: The proposed MST is confirmed as strongly predictor of nutritional status. It is a simple, quick, reliable, valid tool and can be carried out nursing staff. Its routine application will consistently identify patients at risk of malnutrition so that nutrition care can be promptly started.

[Carcinoma of the gastric stump]. / Il carcinoma del monocone gastrico.

After having emphasized that carcinoma of the gastric stump represents a "major" risk in patients undergoing gastric resection, the authors describe the physiopathology of the new anatomical and functional status of the gastroenteric apparatus and underline the probable etiopathogenetic stages attributable to carcinogenesis. They then describe the treatment of this neoplasia with a marked aggressive character and conclude with the affirmation that the surgeon's efforts must be focused on the correct execution of gastroresection and the follow-up of gastro-resected patients in order to allow the early identification of precancerous conditions and therefore the commencement rational oncological prophylaxis.

[Use of monofilament prosthesis in inguinal hernia treatment: cost-benefit ratio]. / L'impiego delle protesi in monofilamento nella terapia dell'ernia inguinale: rapporto costo-beneficio.

BACKGROUND: The authors aimed to demonstrate the real advantages in terms of cost and patient comfort of inguinal hernia surgery using monofilament prostheses. METHODS: A retrospective survey was carried out on two groups of patients: the first group, consisting of 1032 patients who underwent inguinal hernia surgery under general anesthetic between 1985 and 1995 at the Institute of General Surgery at the University Polyclinic of Messina, included cases of both emergency and elective surgery that did not use monofilament prosthesis. The second group, consisting of 348 patients operated under local anesthesia between 1996 and 1999 at the IV Division of General Surgery at the University Polyclinic of Messina, included cases of both emergency and elective surgery using tension-free techniques and polypropylene mesh. The numbers of recidivations and complications were compared, together with the relative costs of the methods used in both groups. CONCLUSIONS: In the light of these experimental results, it is clear that the use of biocompatible alloplastic materials in monofilament considerably reduces the risks of recidivation, without no significant increase in the number of dehiscences, infections or postoperative complications. Moreover, there was a striking reduction in costs linked not only to the shorter hospitalisation of patients and the reduced use of painkillers, but also a fall in the number of future hospital admissions owing to recidivation.

[Breast cancer today]. / Il carcinoma della mammella, oggi.

Authors, after a short dissertation about evolution, trough out the years, of the diagnosis and the therapy of the mammary carcinoma, specify the leading role of primary prevention. Self palpation and the mammography reduce of about 30% the mortality. Modern pharmacology and radiotherapy allow a surgical preservative approach, produce better esthetic and functional results. Preservative therapy (QUART) also warrants a good quality of life, and allows the excellent control of primary disease.

Intracerebroventricular administration of human umbilical cord blood cells delays disease progression in two murine models of motor neuron degeneration.

The lack of effective drug therapies for motor neuron diseases (MND), and in general for all the neurodegenerative disorders, has increased the interest toward the potential use of stem cells. Among the cell therapy approaches so far tested in MND animal models, systemic injection of human cord blood mononuclear cells (HuCB-MNCs) has proven to reproducibly increase, although modestly, the life span of SOD1G93A mice, a model of familial amyotrophic lateral sclerosis (ALS), even if only few transplanted cells were found in the damaged areas. In attempt to improve the potential efficacy of these cells in the central nervous system, we examined the effect and distribution of Hoechst 33258-labeled HuCB-MNCs after a single bilateral intracerberoventricular injection in two models of motor neuron degeneration, the transgenic SOD1G93A and wobbler mice. HuCB-MNCs significantly ameliorated symptoms progression in both mouse models and prolonged survival in SOD1G93A mice. They were localized in the lateral ventricles, even 4 months after administration. However, HuCB-MNCs were not found in the spinal cord ventral horns. This evidence strengthens the hypothesis that the beneficial role of transplanted cells is not due to cell replacement but is rather associated with the production and release of circulating protective factors that may act both at the central and/or peripheral levels. In particular, we show that HuCB-MNCs release a series of cytokines and chemokines with antiinflammatory properties that could be responsible of the functional improvement of mouse models of motor neuron degenerative disorders.

Phase III study in stage IV non-small-cell lung cancer patients treated with two courses of cisplatin/gemcitabine followed by a randomization to three additional courses of the same combination or gemcitabine alone.

BACKGROUND: This randomised phase III study investigated if in responsive and stable disease (SD) stage IV patients after two courses of cisplatin and gemcitabine, single-agent gemcitabine (experimental arm) was not inferior in terms of overall survival (OS) to cisplatin-gemcitabine (standard arm). PATIENTS AND METHODS: Noninferiority was defined as an increase in the hazard of death (HR) < or = 1.33 in the experimental arm. From January 2001 to February 2004, 340 patients were registered and 250 were randomised. Cisplatin was administered on day 1 at 75 mg/m2 and Gemcitabine on days 1 and 8 at 1250 mg/m2 every 3 weeks. RESULTS: Response rate after two courses was 29%. The 1-year progression-free survival was 13% in both arms. One-year survival was 52% in the standard and 42% in the experimental arm for an HR of 1.21 [90% confidence interval (CI) 0.97-1.51]. Postprogression survival was in favour of the standard arm (HR 1.30, 95% CI 0.99-1.70, P = 0.051). Grades 3-4 toxicity favoured in the experimental arm. CONCLUSION: In responsive and SD patients with stage IV non-small-cell lung cancer it was not possible to demonstrate that three courses of gemcitabine alone are not inferior, in terms of OS, to the standard approach of three courses of cisplatin-gemcitabine.