Dietary habits affect fatty acid composition of visceral adipose tissue in subjects with colorectal cancer or obesity.

PURPOSE: Aim of this study was to identify a possible relationship among dietary fatty acids (FA) intake, FA adipose tissue (AT) profile and cancer condition in lean vs obese subjects affected or not by colorectal cancer (CRC). Actually, inadequate dietary habits together with physical inactivity are primary determinants of obesity and cancer risk. Changes in lipid metabolism play a crucial role in different types of cancer and key enzymes involved in lipid-metabolic pathways, such as stearoyl-coA-desaturase 1 (SCD-1), are differentially expressed in normal and cancer tissues. METHODS: Food frequency questionnaires (FFQ) were analyzed by Winfood software. FA were assessed by gas-liquid chromatography in visceral AT samples. Estimated desaturase activities were calculated as precursor FA/product FA ratio. Desaturase gene expressions were evaluated by RT-qPCR. RESULTS: Lean and obese CRC subjects showed inadequate dietary habits. In particular, lean CRC subjects showed increase in the intake of saturated FA, specifically palmitic (p = 0.0042) and stearic acid (p = 0.0091), and a corresponding reduction of monounsaturated FA consumption, in particular oleic acid (p = 0.002) with respect to lean without CRC. Estimated SCD-1 activity in AT was increased in all the groups vs lean without CRC (pANOVA = 0.029). CONCLUSIONS: Unhealthy eating habits, characterizing obese and CRC subjects, may influence the visceral AT profile and contribute to the alteration of the metabolic pathways. The quality of the diet, other than the quantity, can have a main role in the establishment of inflammatory microenvironment and in metabolic changes favouring CRC.

The pre-mir-27a variant rs895819 may contribute to type 2 diabetes mellitus susceptibility in an Iranian cohort.

PURPOSE: The study was aimed at investigating the association between hsa-mir-27a polymorphism rs895819 (T/C) and type 2 diabetes mellitus (T2DM) susceptibility in a large Iranian cohort. METHODS: In this case-control study, the investigated population consisted of T2DM patients (n = 204) and sex- and age-matched controls (n = 209). We used the polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP) for genotyping. RESULTS: We observed significant differences between T2DM patients and controls for weight (p = 0.002), BMI (p < 0.001), systolic blood pressure (p < 0.001), diastolic blood pressure (p < 0.001), fasting plasma glucose (p < 0.001), triglyceride (p = 0.004) and LDL cholesterol (p = 0.051). Moreover, we found that genotype distributions were significantly different between groups (p < 0.05) and that the rs895819-C allele is more frequent in controls (p = 0.030, OR = 0.72, 95 % CI 0.53-0.97). CONCLUSION: Our study shows that rs895819 in hsa-mir-27a is associated with T2DM susceptibility and that the C allele conveyed a protective role against T2DM. Larger multicentric and specific functional studies will be necessary to obtain a deeper comprehension of the role of rs895819 and hsa-mir-27a and how they are involved in the development of diabetes.

Evaluating the association of common UBE2Z variants with coronary artery disease in an Iranian population.

Coronary artery disease (CAD) is the leading cause of cardiovascular mortality worldwide. Genome-wide association studies have discovered several variants associated with CAD. Notably, a recent study has identified UBE2Z rs46522 at 17q21.32 as a CAD-susceptibility variant in Europeans. However, association of this locus with CAD in non-Europeans has not been investigated. Herein, we evaluated the contribution of rs46522 and a variant in high linkage disequilibrium in UBE2Z 3'-UTR (rs1057897) to the CAD susceptibility by performing association study in an Iranian population. This study recruited 300 angiographically-confirmed CAD patients and 300 asymptomatic controls. Genotypes were determined by TaqMan genotyping assay. Multivariate logistic regression analysis revealed that rs46522 was associated with the susceptibility to CAD assuming codominant [TT vs. CC: 2.68 (1.36-5.31), P: 1.1717e-2], dominant [CT+TT vs. CC: 1.74 (1.12-2.69), P: 1.2675e-2], recessive [TT vs. CC+CT: 2.12 (1.13-3.98), P: 1.9369e-2] and log-additive [1.61 (1.17-2.21), P: 2.967e-3] models. However, no association was observed for rs1057897 under any genetic models. In conclusion, we provide the first evidence for association of rs46522 with the susceptibility to CAD in an Iranian population and discussed about regulatory potential and functional role of the studied variants to provide clues for its association with CAD and promote further research.

Do educational methods affect students' ability to remove artificial carious dentine? A randomised controlled trial.

This trial aimed to evaluate the influence of two educational methods on students' ability to remove artificial carious dentine. Traditional lecture and lecture plus a live demonstration of artificial carious tissue removal were compared in a blind two-parallel-group design. Twenty-six students were randomly divided into two groups, and their skills were evaluated according to the following criteria: time spent on the dentine excavation procedure (in min), students' perceived confidence in conducting the procedure (graded assessed on a scale from 0 to 10), and the outcome of artificial carious tissue removal, evaluated by measuring the residual dyed artificial carious dentine layer (in µm). Statistical analyses were carried out using a t-test to compare the students' confidence and time spent on the procedure, and a two-way ANOVA was used to compare residual artificial decayed dentine with educational methods and tooth region (incisal, medium, and cervical thirds) as factors. There were no differences between the methods regarding excavation time (P = 0.898) and students' confidence (P = 0.382). The residual artificial carious dentine results showed that the educational method (P < 0.001) and cavity region (P < 0.001) were statistically significant, as was their interaction (P = 0.040). The lecture plus live demonstration group presented the best results for artificial caries removal. Although there were no differences between the two groups for the cervical region, the best results for the lecture plus live demonstration group was in the other two-thirds of the tooth.

Depigmentation therapy in vitiligo universalis with cryotherapy and 4-hydroxyanisole.

Vitiligo is a disease characterized by the loss of melanocytes, resulting in progressive depigmentation of skin, and areas of normally pigmented skin can be of cosmetic concern. Several options have been tried to remove the pigment and make the skin a more even colour. We present an easy and effective therapeutic procedure based on single-session cryotherapy followed by topical 4-hydroxyanisole (4-HA).

Synthesis and characterization of polyethylenimine-based iron oxide composites as novel contrast agents for MRI.

OBJECT: Use of polyethylenimines (PEIs) of different molecular weight and selected carboxylated-PEI derivatives (PEI-COOH) in the synthesis and stabilization of iron oxide nanoparticles, to obtain possible multifunctional contrast agents. MATERIALS AND METHODS: Oxidation of Fe(II) at slightly elevated pH and temperature resulted in the formation of highly soluble and stable nanocomposites of iron oxides and polymer. Composites were characterized and studied by atomic force microscopy (AFM), transmission electron microscopy (TEM), X-ray diffractometry, AC and DC magnetometry, NMR relaxometry and magnetic resonance imaging (MRI). RESULTS: From AFM the dimensions of the aggregates were found to be in the ~150-250 nm size region; the mean diameter of the magnetic core of the compounds named PEI-25, PEI-500 and PEI-COOH60 resulted d approximately 20 +/- 5 nm for PEI-25, d approximately 9.5 +/- 1.0 nm for PEI-500 and d approximately 6.8 +/- 1.0 nm for PEI-COOH60. In PEI-COOH60 TEM and X-ray diffractometry revealed small assemblies of mineral magnetic cores with clear indications that the main constituents are maghemite and/or magnetite as confirmed by AC and DC SQUID magnetometry. For PEI-COOH60, the study of NMR-dispersion profiles revealed r (1) and r (2) relaxivities comparable to superparamagnetic iron-oxide commercial compounds in the whole investigated frequency range 7 < or = nu < or = 212 MHz. CONCLUSION: PEI-25 was studied as possible MRI contrast agent (CA) to map the cerebral blood volume (CBV) and cerebral blood flow (CBF) in an animal model obtaining promising results. The reported compounds may be further functionalized to afford novel multifunctional systems for biomedical applications.

A Randomized Double-blind Clinical Trial of Dentin Surface Treatments for Composite Restorations in Noncarious Cervical Lesions: A 36-month Evaluation.

OBJECTIVE:: This randomized, double-blind clinical trial aimed to evaluate the influence of different dentin surface treatments in noncarious cervical lesions (NCCLs). METHODS AND MATERIALS:: Twenty-nine patients participated in this study. One hundred sixty-five NCCLs were selected and randomly assigned to three groups: G0 (control group) with phosphoric acid etching for 15 seconds; G1: phosphoric acid etching for 30 seconds; and G2: ultrasound probe applied for 30 seconds on the dentin surface. Class V composite resin restorations were performed (Z350, 3M ESPE, St Paul, MN, USA). The restorations were evaluated at baseline and at six, 12, 24, and 36 months according to the World Dental Federation criteria. Survival curves were obtained using the Kaplan-Meier method and the log-rank test. Comparisons between groups and times were performed using the McNemar and Chi-square tests (α =0.05). RESULTS:: The presence of failures due to retention was statistically different among the groups ( p=0.012), and G0 and G2 showed better clinical performance than did G1. Sensitivity decreased over time in all groups. Marginal discoloration, postoperative sensitivity, and marginal adaptation were not different among the groups ( p>0.05). CONCLUSIONS:: The studied dentin surface treatments showed similar clinical performance to the conventional technique at 36 months in terms of marginal discoloration, marginal adaptation, and postoperative sensitivity. In contrast, increased acid-etching time resulted in a higher risk of failure due to retention over time in composite Class V restorations.

[Survey on sports practice and physical activity of primary school children living in the area of Bologna Local Health Unit in relation with some individual and environmental variables]. / Indagine sulla pratica sportiva e le abitudini motorie dei bambini della scuola primaria del territorio dell'Azienda USL di bologna in relazione ad alcune variabili individuali e ambientali.

A randomized stratified sample of 522 children attending the third class of primary schools within the area of Bologna Local Health Unit was analysed for physical activity and sports practice. Information about the children's habits and availability of facilities for physical and sports activities were collected by means of structured questionnaires completed by children (507 respondents), parents (491), reference teachers for physical education (26) and class teachers (46) during the school year 2006-07. At the same time, the children's heights and weights were measured in order to calculate BMI values. Regular sports activity is practised by 80.1% of children (males: 82.4%, females: 77.6%), with significant diferences between genders only in children with at least one non-Italian parent (M>F, p < 0.05); the practice of sports is influenced by the area of residence (metropolitan > plain and hills, p < 0.05) and nationality (Italians > non-Italians, p < 0.01). Children with at least one actively sports practising parent are involved more frequently in sports activities (p < 0.001). In free time, sedentary activities are prevalent for both sports-practising children and not. However children not involved in regular sports activities tend to practise outdoor physical activities with a frequency significantly higher than children involved in sports (17.3% vs 10.4% of respondents). The percentage of completely sedentary children, who stated that they practise neither sports nor physical activity in their free time, is 7.3% (metropolitan area: 4.5%, hills: 8.7%, plain: 10.6%). The prevalence of overweight is 24.4%, of obesity 9.7%, with a better distribution of BMI values in the metropolitan area where there is the highest occurrence of positive conditions and behaviours: availability of sports facilities, the highest prevalence of sports practice, and the lowest prevalence of completely sedentary children.

The aging population and Natural Occurring Retirement Communities (NORCs); local government, healthy aging, and healthy-NORCs.

BACKGROUND: The term Naturally Occurring Retirement Communities (NORCs) has been used since the 1980s. NORCs are defined as communities where people remain or move to when they retire. NORCs develop 'naturally', meaning that seniors tend to remain or move there when they retire, although the residences and physical environment were not constructed for a senior population. The term, Healthy-NORC, has been introduced and is associated with healthy aging. OBJECTIVES/METHODS: We describe how demographic trends will facilitate a dramatic growth in NORCs. Acknowledging the 'Determinants of Health' model, we suggest that some determinants impact people differently at different ages. We also suggest that more attention be focused on the impact of physical/social environments on health, and that some determinants of health are particularly relevant for seniors. We argue that NORCs exist on a spectrum, from NORC to H-NORC, and that health benefits for seniors increase as NORCs adopt additional characteristics associated with improved senior health. We also illustrate H-NORC research methods and policy options for local governments. RESULTS/CONCLUSION: Compared to the provision of additional medical and social services, H-NORCs represent a low-cost approach to facilitating healthy aging. Municipal governments can promote healthy aging and should pursue policies that will stimulate H-NORC development.

Oral glucose tolerance test unravels circulating miRNAs associated with insulin resistance in obese preschoolers.

BACKGROUND: Circulating microRNAs (miRNAs) may act as biomarkers of metabolic disturbances. OBJECTIVE: The aim of this study was to identify serum miRNAs signature of early insulin resistance in obese preschoolers. METHODS: Twelve obese children, aged 2-6 years, six insulin resistant (IR) and six controls were selected being age-matched, sex-matched and body mass index-matched. Profiling of 179 circulating miRNAs, known to be widely expressed in the bloodstream, was investigated by quantitative polymerase chain reaction at fasting and 120 min following a standard oral glucose tolerance test (OGTT). RESULTS: Twenty-one miRNAs were differentially regulated in IR obese preschoolers. miR-200c-3p, miR-190a and miR-95 were differently regulated both at fasting and 120 min after the OGTT. In controls, the fold changes of some miRNAs were correlated with Δglucose0-120 (miR-660, miR-26b-5p and miR-22-3p: p = 0.005 for all) and Δinsulin0-120 (miR-660 and miR-22-3p: p = 0.02 for both and miR-423-5p: p = 0.042). In IR patients, miR-1 fold changes were correlated with Δglucose0-120( r = -0.786; p = 0.036) and Δinsulin0-120( r = -0.821; p = 0.023). CONCLUSIONS: Our study identifies circulating miR-200c-3p, miR-190a and miR-95 as biomarkers of insulin resistance in obese preschoolers, being differentially regulated in IR patients both in fasting condition and after the OGTT. Expression of some circulating miRNAs seems reflecting glucose and insulin excursion following the OGTT differently in controls and IR obese preschoolers.

Intracerebral diffusion of paramagnetic cationic liposomes containing Gd(DTPA)2- followed by MRI spectroscopy: assessment of pattern diffusion and time steadiness of a non-viral vector model.

Cationic liposomes are generally considered as the non-viral counterparts of the more common viral vectors used in several gene therapy protocols, but their use as delivery vehicles is limited by their efficiency even if they display a lower toxicity. However, cationic liposomes are promising delivery systems in cell biology due to their ability to incorporate small molecules into their inner aqueous spheres and to deliver them into cells. Additionally, on the external surface they can bind therapeutic molecules such as nucleic acids, oligonucleotides, plasmids, etc. through electrostatic interactions. The aim of this work was to study the diffusion properties of such vehicles in vivo with a non-invasive technique and to monitor their tissue migration in order to collect information to be further used in gene therapy procedures. For this purpose, cationic liposomes containing the paramagnetic contrast agent Gd(DTPA)2- (Gd(III)-diethylenetriamine-N,N,N',N",N"-pentaacetic acid) were investigated because of their extended paramagnetic persistency in vivo, compared to the use of the contrast agent alone, and they were used to monitor the diffusion of such vehicles in an animal model (rat model). In particular, these vectors were injected into the rat brain through a stereotactic frame in a preformed cavity mimicking the lesion which had originated after surgical removal of the primary tumor. For the purpose of comparison, the same injection procedure was also applied to a control series of animals without a preformed brain lesion. Pattern diffusion and steadiness of the reported paramagnetic cationic liposomes were studied by means of Magnetic Resonance Imaging (MRI) which allowed us to monitor their diffusion and assess their intracerebral time availability up to 24 hours.

Gemcitabine and cisplatin versus mitomycin, ifosfamide, and cisplatin in advanced non-small-cell lung cancer: A randomized phase III study of the Italian Lung Cancer Project.

PURPOSE: To compare gemcitabine and cisplatin (GC) with mitomycin, ifosfamide, and cisplatin (MIC) chemotherapy in patients with stage IIIB (limited to T4 for pleural effusion and N3 for supraclavicular lymph nodes) or stage IV non-small-cell lung cancer (NSCLC). The end points were the evaluation of quality of life (QoL), response rates, survival, and toxicity. PATIENTS AND METHODS: Three hundred seven patients were randomized to receive either gemcitabine 1,000 mg/m(2) on days 1, 8, and 15 plus cisplatin 100 mg/m(2) on day 2, every 28 days, or mitomycin 6 mg/m(2), ifosfamide 3,000 mg/m(2), and mesna on day 1 plus cisplatin 100 mg/m(2) on day 2, every 28 days. The whole-blood cell count was repeated on day 1 in both arms and weekly in the GC arm before each gemcitabine administration. RESULTS: No major differences in changes in QoL were observed between the two treatment arms. The objective response rate was 38% in the GC arm compared with 26% in the MIC arm (P =.029). The median survival time was 8.6 months in the GC arm and 9.6 months in the MIC arm (P =.877, log-rank test). Grade 3 and 4 thrombocytopenia was significantly worse in the GC arm (64% v 28%, P <.001), whereas grade 3 and 4 alopecia was reported more commonly in the MIC arm (39% v 12%, P <. 001). CONCLUSION: We report an increased response rate without changes in QoL and a similar overall survival, time to progression, and time to treatment failure for the GC when compared with the MIC regimen in the treatment of advanced NSCLC.

Using cost-effectiveness league tables to compare interventions to prevent sexual transmission of HIV.

Cost-effectiveness information is needed to help public health decision makers choose between competing HIV prevention programs. One way to organize this information is in a 'league table' that lists cost-effectiveness ratios for different interventions and which facilitates comparisons across interventions. Herein we propose a common outcome measure for use in HIV prevention league tables and present a preliminary league table of interventions to reduce sexual transmission of HIV in the US. Fifteen studies encompassing 29 intervention for different population groups are included in the table. Approximately half of the interventions are cost-saving (i.e. save society money, in the long run), and three-quarters are cost-effective by conventional standards. We discuss the utility of such a table for informing the HIV prevention resource allocation process and delineate some of the difficulties associated with the league table approach, especially as applied to HIV prevention cost-effectiveness analysis.

Cost-threshold analyses of the National AIDS Demonstration Research HIV prevention interventions.

OBJECTIVE: The goal of the multisite National AIDS Demonstration Research (NADR) program was to reduce the sexual and drug injection-related HIV risks of out-of-treatment injection drug users and their sex partners. Previous analyses have established that the NADR interventions were effective at changing participants' risky behaviors. This study was to determine whether the NADR program also was cost-effective. METHODS: Data from eight NADR study sites were included in the analysis. A mathematical model was used to translate reported sexual and injection-related behavior changes into an estimate of the number of infections prevented by the NADR interventions and then to calculate the corresponding savings in averted HIV/AIDS medical care costs and quality-adjusted years of life, assuming United States values for these parameters. Because cost data were not collected in the original NADR evaluation, the savings in averted medical care costs were compared with the cost of implementing a similar intervention program for injection drug users. RESULTS: The eight NADR interventions prevented approximately 129 infections among 6629 participants and their partners. Overall, the NADR program would be cost saving (i.e. provide net economic savings) if it cost less than US$2107 per person and would be cost-effective if it cost less than US$10,264 per person. Both of these estimates are considerably larger than the US$273 per person cost of the comparison intervention. There was substantial cross-site variability. CONCLUSIONS: The results of this analysis strongly suggest that the NADR interventions were cost-saving overall and were, at the very least, cost-effective at all eight sites. In the United States and other developed counties, investments in HIV-prevention interventions such as these have the potential to save substantial economic resources by averting HIV-related medical care expenses among injection drug users.

Porcine von Willebrand factor binding to human platelet GPIb induces transmembrane calcium influx.

Porcine von Willebrand factor (P-vWF) binds to human platelet glycoprotein (GP) Ib and, upon stirring (1500 rpm/min) at 37 degrees C, induces, in a dose-dependent manner, a transmembrane flux of Ca2+ ions and platelet aggregation with an increase in their intracellular concentration. The inhibition of P-vWF binding to GP Ib, obtained with anti GP Ib monoclonal antibody (LJ-Ib1), inhibits the increase of intracellular Ca2+ concentration ([Ca2+]i) and platelet aggregation. This effect is not observed with LJ-Ib10, an anti GP Ib monoclonal antibody which does not inhibit the vWF binding to GP Ib. An anti GP IIb-IIIa monoclonal antibody (LJ-CP8) shown to inhibit the binding of both vWF and fibrinogen to the GP IIb-IIIa complex, had only a slight effect on the [Ca2+]i rise elicited by the addition of P-vWF. No inhibition was also observed with a different anti GP IIb-IIIa monoclonal antibody (LJ-P5), shown to block the binding of vWF and not that of fibrinogen to the GP IIb-IIIa complex. PGE1, apyrase and indomethacin show a minimal effect on [Ca2+]i rise, while EGTA completely blocks it. The GP Ib occupancy by recombinant vWF fragment rvWF445-733 completely inhibits the increase of [Ca2+]i and large aggregates formation. Our results suggest that, in analogy to what is seen with human vWF under high shear stress, the binding of P-vWF to platelet GP Ib, at low shear stress and through the formation of aggregates of an appropriate size, induces a transmembrane flux of Ca2+, independently from platelet cyclooxygenase metabolism, perhaps through a receptor dependent calcium channel. The increase in [Ca2+]i may act as an intracellular message and cause the activation of the GP IIb-IIIa complex.

Phase-II randomized study of pre-operative IL-2 administration in operable NSCLC.

Lymphocytopenia is a prognostic factor for shorter survival in advanced lung cancer and it is likely related to an interleukin-2 (IL-2) deficiency occurring during cancer progression. Major surgery itself for cancer is known to induce lymphocytopenia in the postoperative period. Postoperative lymphocyte decrease in colorectal cancer can be prevented by preoperative administration of recombinant human (rhIL-2), indicating that it is possible to drive appropriately important host defence agents during critical events, such as major surgery. The aim of this study is to verify if recombinant human interleukin-2 (rhIL-2) administered preoperatively is able to prevent the lymphocyte decrease occurring after radical surgery in operable lung cancer. This phase II study included 40 patients with operable NSCLC screened as stage II or IIIA, randomized to receive rhIL-2, 9000000 IU subcutaneously twice daily for 3 days before surgery (treated group, 20 patients) or not (control group, 20 patients). At baseline, there were no significant differences in total lymphocyte number and lymphocyte subsets (T-cell, T-helper, CD8+, natural killer, CD4/CD8 ratio) between groups. Postoperatively the control group showed a decrease in total lymphocyte count, T-lymphocyte count, T-helper cell number and CD4/CD8 ratio, significant at the 14th postoperative day relative to baseline values. In contrast, in the rhIL-2 treated group, at the 3rd and at the 14th postoperative days, a significant increase was observed over both baseline and control group values of total lymphocyte count, T-cells and T-helper cells. NK cell number increased significantly only over the control group. CD4/CD8 ratio was increased at the 14th postoperative day significantly over both baseline and control values. At pathological staging after surgery, four patients in the rhIL-2 group and four in the control group resulted in stage pIIIB; one patient in the rhIL-2 group resulted in stage IV (contralateral metastasis). Indeed, 15/20 rhIL-2 treated patients and 16/20 control patients were radically operated. After a 24-month follow-up, 12/20 rhIL-2 treated patients were alive and 8/15 radically operated were disease-free; 8/20 control patients were alive and 4/16 radically operated were disease-free. Toxicity was mild to moderate and easy manageable; treatment was suspended in one patient due to skin rash with hypotension grade II. The preoperative administration of rhIL-2 is feasible and prevents lymphocyte decrease occurring postoperatively after surgery for lung cancer. Further studies are required to assess the impact on survival.

Secondary HIV transmission rates in a mixed-gender sample.

Information about the sexual behaviour of HIV-infected individuals is needed to predict the course of the sexually transmitted HIV epidemic in the US. The present study provides model-based estimates of the secondary transmission rate (i.e. the number of infections expected among the sex partners of already infected individuals) for a sample of HIV-positive persons in Atlanta. A mathematical model was used to estimate the secondary transmission rate of HIV infection for a sample of HIV-positive men and women in Atlanta, based on their self-reported sexual behaviour, extrapolated over a 15-year horizon. Separate rates were calculated for different transmission routes, including: from women to men-who-have-sex-with women (MSW) and from men-who-have-sex-with-men (MSM) to other MSM. Sensitivity analyses were conducted to assess the impact of different parametric and modelling assumptions. Restricted to the sub-sample that reported transmission risk behaviours, the mean number of secondary infections was 0.14 for transmission from women to MSW; 0.31 for transmission from MSW to women; and 0.84 for MSM to MSM transmission. Bisexual men were at especially high transmission risk, with 1.59 and 0.54 secondary infections expected among their male and female partners, respectively. The main analysis indicates that, in this sample, each current infection will lead to fewer than one future infection for all groups other than bisexual men, which suggests that the epidemic is contracting in this community, although this analysis cannot rule out the possibility of a growing epidemic among MSM. This method can be used to identify groups at high risk for HIV transmission and thereby to better target HIV prevention resources.

Efficacy and toxicity of vinorelbine-carboplatin combination in the treatment of advanced adenocarcinoma or large-cell carcinoma of the lung.

AIMS AND BACKGROUND: The aim of the study was to assess the activity and toxicity of the vinorelbine-carboplatin combination in advanced adenocarcinoma or large-cell carcinoma of the lung. The new vinca derivative, vinorelbine, shows promising activity when combined with cisplatin, but toxicity of the combination is substantial. METHODS: Accordingly, we substituted carboplatin for cisplatin in the combination in order to improve the therapeutic index. From March 1992 to March 1994, 55 untreated patients with undifferentiated unresectable or metastatic adenocarcinoma or large-cell carcinoma of the lung were recruited. The treatment consisted of a course of carboplatin (300 mg/m2) and vinorelbine (25 mg/m2) repeated every 4 weeks. The only grade 3 toxicity observed was 16 cases of grade 3 vomiting and 2 cases of grade 3 stomatitis. RESULTS: The positive response rate was 40% (partial response, 22 patients). In conclusion, the vinorelbine-carboplatin combination may be regarded as an active, safe regimen for the palliative treatment of advanced adenocarcinoma or large-cell carcinoma of the lung.

[The use of monoclonal antibodies that recognize the neural cell adhesion molecule (NCAM) in the diagnosis of bone marrow localization of small cell lung cancer]. / L'uso di anticorpi monoclonali che riconoscono la neural cell adhesion molecule (NCAM) nella diagnosi delle localizzazioni midollari di microcitoma polmonare.

We have used immunocytochemistry to identify tumor cells in bone-marrow aspirates of 40 untreated patients with small cell lung cancer and we compared the results with conventional histomorphology. The monoclonal antibodies (MAbs) used were NCC-LU-243 and NCC-LU-246 (both cluster 1). For each MAb 76 slides were evaluated. Sixty bone-marrow biopsies were also obtained from these patients. The positivity rate between the 2 MAbs was not statistically different (46% for NCC-LU-246 and 43% for NCC-LU-243). Bone-marrow biopsies detected tumor localization in 8/60 specimens (13%), significantly less than immunocytochemistry with anti-NCAM MAbs (p = 0.003). Moreover, bone-marrow aspirates were positive for cluster 1 antigen in 6/16 patients with limited disease at diagnosis. The results confirm that NCC-LU-243 and NCC-LU-246 have equivalent ability to identify bone-marrow involvement; immunocytochemistry appears to be better suited for this purpose than conventional bone-marrow biopsy; a non-negligible proportion of patients with "limited disease" might be understaged; the clinical value of detecting bone marrow involvement by immunocytochemistry is still unclear.

Probabilistic cost-effectiveness analysis of HIV prevention. Comparing a Bayesian approach with traditional deterministic sensitivity analysis.

In cost-effectiveness analysis, the incremental cost-effectiveness ratio is used to measure economic efficiency of a new intervention, relative to an existing one. However, costs and effects are seldom known with certainty. Uncertainty arises from two main sources: uncertainty regarding correct values of intervention-related parameters and uncertainty associated with sampling variation. Recently, attention has focused on Bayesian techniques for quantifying uncertainty. We computed the Bayesian-based 95% credible interval estimates of the incremental cost-effectiveness ratio of several related HIV prevention interventions and compared these results with univariate sensitivity analyses. The conclusions were comparable, even though the probabilistic technique provided additional information.