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To report the results of a multicenter retrospective evaluation of the clinical outcomes of thermal ablation (TA) in a large series of autonomously functioning thyroid nodules (AFTN) with a follow-up protracted up to 3 years.Patients treated with single TA for an AFTN in Italy were included. Changes in nodule volume, TSH values, and ongoing anti-thyroid therapy were assessed at the 2-, 6-, 12-, 24-, and 36-month follow-up controls. Complications and need of any additional therapy after TA were also registered.A total of 361 patients (244 females, 117 males, median age 58 years, IQR 46-70 years) were included. Nodule volume was significantly reduced at all time points (p 0.001) (median volume reduction 58% at 6-month and 60% at 12-month). Serum TSH values increased significantly at all time points. After TA, anti-thyroid therapy was withdrawn in 32.5% of patients at 2 months, in 38.9% at 6 months, and in 41.3% at 12 months. A significant difference in the rate of patients who withdrawn medical therapy at 12 months was registered between small ( 10 mL) (74%), medium (49%), or large ( 30 mL) nodules (19%). A single major complication occurred (0.25%). Additional treatments were needed in 34/361 (9.4%) of cases including 4 (1.1%) surgical treatment.Image-guided thermal ablation offers a further safe and effective therapeutic option in patients with AFTN. Clinical outcomes are significantly more favorable in small than in large size AFTN.• Thermal ablations (TA) can be safely and effectively used in patients with autonomously functioning thyroid nodules (AFTN). • TA results in a clinically significant nodule volume reduction that is paralleled by TSH level normalization and anti-thyroid drug therapy discontinuation (after TA anti-thyroid therapy was withdrawn in 41.3% at 12 months). • Clinical outcomes after TA are more favorable in small nodules, and when a large amount of thyroid nodule tissue is ablated.

Background The International Agency for Research on Cancer (IARC) recently classified glyphosate, the most used herbicide worldwide, as a probable human carcinogen. We inquired into the association between occupational exposure to glyphosate and risk of lymphoma subtypes in a multicenter case-control study conducted in Italy. Methods The Italian Gene-Environment Interactions in Lymphoma Etiology (ItGxE) study took place in 2011–17 in six Italian centres. Overall, 867 incident lymphoma cases and 774 controls participated in the study. Based on detailed questionnaire information, occupational experts classified duration, confidence, frequency, and intensity of exposure to glyphosate for each study subject. Using unconditional regression analysis, we modelled risk of major lymphoma subtypes associated with exposure to glyphosate adjusted by age, gender, education, and study centre. Results Very few study subjects (2.2%) were classified as ever exposed to glyphosate. Risk of follicular lymphoma (FL) was elevated 7-fold in subjects classified as ever exposed to glyphosate with medium-high confidence, 4.5-fold in association with medium-high cumulative exposure level, 12-fold with medium-high exposure intensity, and 6-fold with exposure for 10 days or more per year. Significant upward trends were detected with all the exposure metrics, but duration. The overall p-value for an upward trend with four independent metrics was 1.88 × 10− 4. There was no association with risk of lymphoma (any subtype), Non Hodgkin Lymphoma, B-cell lymphoma, or the major lymphoma subtypes other than FL. Conclusions Our findings provide limited support to the IARC decision to classify glyphosate as Group 2A human carcinogen.

Benign thyroid nodules are a common clinical occurrence and usually do not require treatment unless symptomatic. During the last years, ultrasound-guided minimally invasive treatments (MIT) gained an increasing role in the management of nodules causing local symptoms. In February 2018, the Italian MIT Thyroid Group was founded to create a permanent cooperation between Italian and international physicians dedicated to clinical research and assistance on MIT for thyroid nodules. The group drafted this list of statements based on literature review and consensus opinion of interdisciplinary experts to facilitate the diffusion and the appropriate use of MIT of thyroid nodules in clinical practice. (#1) Predominantly cystic/cystic symptomatic nodules should first undergo US-guided aspiration; ethanol injection should be performed if relapsing (level of evidence [LoE]: ethanol is superior to simple aspiration = 2); (#2) In symptomatic cystic nodules, thermal ablation is an option when symptoms persist after ethanol ablation (LoE = 4); (#3) Double cytological benignity confirmation is needed before thermal ablation (LoE = 2); (#4) Single cytological sample is adequate in ultrasound low risk (EU-TIRADS ≤3) and in autonomously functioning nodules (LoE = 2); (#5) Thermal ablation may be proposed as first-line treatment for solid, symptomatic, nonfunctioning, benign nodules (LoE = 2); (#6) Thermal ablation may be used for dominant lesions in nonfunctioning multinodular goiter in patients refusing/not eligible for surgery (LoE = 5); (#7) Clinical and ultrasound follow-up is appropriate after thermal ablation (LoE = 2); (#8) Nodule re-treatment can be considered when symptoms relapse or partially resolve (LoE = 2); (#9) In case of nodule regrowth, a new cytological assessment is suggested before second ablation (LoE = 5); (#10) Thermal ablation is an option for autonomously functioning nodules in patients refusing/not eligible for radioiodine or surgery (LoE = 2); (#11) Small autonomously functioning nodules can be treated with thermal ablation when thyroid tissue sparing is a priority and ≥80% nodule volume ablation is expected (LoE = 3).

To compare technique efficacy and safety of laser ablation (LA) and radiofrequency ablation (RFA) in treatment of benign thyroid nodules.Institutional review board approval was obtained, and patients' consent was waived. 601 nodules were treated from May 2009 to December 2014 at eight centres, 449 (309 females, age 57 ± 14 years) with LA and 152 (107 females, age 57 ± 14 years) with RFA. A matched cohort composed of 138 patients from each group was selected after adjustment with propensity score matching. Factors influencing volume reduction at 6 and 12 months and complications were evaluated.No significant differences were observed in the baseline characteristics between groups after propensity score matching adjustment. Mean nodule reduction at 6 and 12 months was -67 ± 19% vs. -57 ± 21% (p 0.001) - 70 ± 19% vs. -62 ± 22% (p = 0.001) in LA group and in RFA group, respectively. Nodules with volume 30 mL had significantly higher percentage volume reduction at 6 and 12 months (-69 ± 19 vs. -50 ± 21, p = 0.001) and (-73 ± 18 vs. -54 ± 23 8, p = 0.001) in the LA group than in the RFA group, respectively. In both groups, operator's skills affected the results. Major complications occurred in 4 cases in each group (p = 0.116) Conclusions: LA and RFA showed nearly similar outcome but LA was slightly more effective than RFA in large nodules. Operator's skills could be crucial in determining the extent of nodule volume reduction regardless of the used technique.

To confirm the effectiveness of laser ablation on toxic nodules in a large population with three years of follow-up.Between 2009 and 2014, we treated 82 patients with hyperthyroidism related to the presence of a toxic nodular goitre. Patients were pre-treated pharmacologically with methimazole prior to single session of laser ablation (LA) and then followed up every 3 months with FT4 and TSH blood tests as well as ultrasound examination of the nodules treated.All patients responded to the treatment. The median nodule volume decreased from 12 ml (range 5-118 ml) to 5 ml (range 1.2-40 ml) after three years (p 0.001). The percentage of patients who discontinued methimazole therapy was reduced by increasing the initial volume of the toxic nodule. In nodules with a volume less than 5 ml, all patients were able to suspend methimazole; this percentage was reduced to 90.2% in nodules with a volume between 5 and 15 ml, 61.1% in those with volume 15-25 ml and only 28.5% in nodules larger than 25 ml. We had no major complications but only moderate pain and fever in the evening, a few hours after ablation therapy in 10% of treated patients.Single session of LA of toxic thyroid nodules is effective and safe, especially in nodules with a volume under 15 ml.

Even though hair analysis often seems to be the best choice for retrospective monitoring of cocaine intake, differentiating between incorporated cocaine and external contamination is widely debated. In this study we report results obtained in 90 hair samples from addicts. All samples were analyzed for cocaine, benzoylecgonine, norcocaine, cocaethylene, and tropococaine by gas chromatography‐mass spectrometry (GC‐MS) techniques coupled with direct immersion solid‐phase micro‐extraction. Cocaine concentrations were stratified into three classes of usage: light (0.5–3 ng/mg), moderate (3.1–10 ng/mg) and heavy (10.1–40 ng/mg). The Substance Abuse and Mental Health Services Administration cut‐off criteria for establishing active cocaine use were applied to the results. For all samples criteria were cocaine levels above 0.5 ng/mg (ranging from 1.63 to 39.29 ng/mg, mean 9.49 ng/mg), benzoylecgonine concentrations ≥ 0.05 ng/mg (ranging from 0.19 to 5.77 ng/mg, mean 1.40), and benzoylecgonine to cocaine % ratio ≥5% (from 6.43 to 26.09%). Norcocaine was present in 58.9% of samples (concentration range: 0.22–3.14 ng/mg) and was strongly predictive only of heavy cocaine use (sensitivity 100% for cocaine concentrations above 9.58 ng/mg). Twenty hair samples from moderate and heavy users tested positive for cocaethylene (concentration range: 0.22–1.98 ng/mg, mean 0.73 ng/mg). This study on hair samples with no chance of false positive cases highlights the very limited applications of testing minor cocaine metabolites for definitive proof of active cocaine consumption. © 2015 The Authors. Drug Testing and Analysis Published by John Wiley & Sons, Ltd.

Image-guided laser ablation therapy (LAT) of benign thyroid nodules demonstrated favorable results in randomized trials with fixed modalities of treatment. The aim of this retrospective multicenter study was to assess the effectiveness, tolerability, and complications of LAT in a large consecutive series of patients from centers using this technique in their routine clinical activity.Clinical records of 1534 consecutive laser-treated nodules in 1531 patients from eight Italian thyroid referral centers were assessed. Inclusion criteria were as follows: solid or mixed nodules with fluid component up to 40%; benign cytological findings; and normal thyroid function.LAT was performed with a fixed-power protocol, whereas the number of applicators and illumination times were different according to target size. From one to three illuminations with pullback technique and with a total energy delivery based on the nodule volume were performed during the same session. Patients were evaluated during LAT, within 30 days, and 12 months after the procedure.Total number of treatments was 1837; 1280 (83%) of nodules had a single LAT session. Mean nodule volume decreased from 27 ± 24 mL at baseline to 8 ± 8 mL 12 months after treatment (P.001). Mean nodule volume reduction was 72% ± 11% (range 48%-96%). This figure was significantly greater in mixed nodules (79% ± 7%; range 70%-92%) because they were drained immediately before laser illumination. Symptoms improved from 49% to 10% of cases (P.001) and evidence of cosmetic signs from 86% to 8% of cases (P.001). Seventeen complications (0.9%) were registered. Eight patients (0.5%) experienced transitory voice changes that completely resolved at the ear-nose-throat examination within 2-84 days. Nine minor complications (0.5%) were reported. No changes in thyroid function or autoimmunity were observed.Real practice confirmed LAT as a clinically effective, reproducible, and rapid outpatient procedure. Treatments were well tolerated and risk of major complications was very low.

Pregabalin, a GABA analogue, binds to the alpha 2 delta subunit of voltage-dependent calcium channels. It is recognised as efficacious in pathologies such as epilepsy, neuropathic pain, and anxiety disorders. Since pregabalin prescriptions have increased worldwide, reports of its abuse have been accumulating, mainly in patients with opioid abuse disorders. The present study investigated potential pregabalin abuse by means of hair analysis, a matrix that provides valuable retrospective information. Half of the pool of 280 susceptible patients had been occasional drug users and were being monitored for driving licence renewals. The other 140 patients had a history of opiate dependency and were monitored to assess compliance with methadone therapy. In view of determining pregabalin in hair samples, it was extracted in methanol, successfully derivatised to give the ethyl chloroformate derivative, and finally pregabalin was analysed by gas chromatography-tandem mass spectrometry. Selectivity, linearity, limit of detection, limit of quantification, recovery, intra- and inter-day precision, and accuracy of the quantification procedure were appraised. Pregabalin limits of detection and quantification were 30 pg/mg and 50 pg/mg, respectively. We found 10.7% of hair samples from methadone patients and 4.29% from occasional drug users were positive to pregabalin without medical prescription. The mean pregabalin concentration in hair was higher than in consumers with medical indications (1.45 ng/mg vs 0.74 ng/mg). These results suggest that pregabalin possesses a significant abuse potential particularly among individuals attending opiate dependence services and that pregabalin abuse is a serious emerging issue, which should be carefully monitored.

Background: The aim of the present trial on ultrasound (US)-guided laser ablation therapy (LAT) of solid thyroid nodules is to assess long-term clinical efficacy, side effects, and predictability of outcomes in different centers operating with the same procedure. Patients: Two hundred consecutive patients were randomly assigned to a single LAT session (group 1, 101 cases) or to follow-up (group 2, 99 cases) at four thyroid referral centers. Entry criteria were: solid thyroid nodule with volume of 6–17 mL, repeat benign cytological findings, normal thyroid function, no autoimmunity, and no thyroid gland treatment. Methods: Group 1: LAT was performed in a single session with two optical fibers, a 1064 nm Nd-YAG laser source, and an output power of 3 W. Volume and local symptom changes were evaluated 1, 6, 12, 24, and 36 months after LAT. Side effects and tolerability of treatment were registered. Group 2: Follow-up with no treatment. Results: One patient was lost to follow-up in each group. Group 1: Volume decrease after LAT was −49 ± 22%, −59 ± 22%, −60 ± 24%, and −57 ± 25% at 6, 12, 24, and 36 months, respectively (P < .001 vs baseline). LAT resulted in a nodule reduction of >50% in 67.3% of cases (P < .001). Local symptoms decreased from 38 to 8% of cases (P = .002) and cosmetic signs from 72 to 16% of cases (P = .001). Baseline size, presence of goiter (P = .55), or US findings (fluid component ≤ 20% [P = .84], halo [P = .46], vascularization [P = .98], and calcifications [P = .06]) were not predictive factors of a volume decrease > 50%. The procedure was well tolerated in most (92%) cases. No changes in thyroid function or autoimmunity were observed. In group 2, nodule volume increased at 36 months (25 ± 42%; P = .04). The efficacy and tolerability of the procedure were similar in different centers. Conclusions: A single LAT treatment of solid nodules results in significant and persistent volume reduction and local symptom improvement, in the absence of thyroid function changes.

Sweat testing, an alternative matrix for establishing drug abuse, offers additional benefits to the more common biological samples. The authors developed a procedure using gas chromatography-mass spectrometry to test for Δ9-tetrahydrocannabinol, 11-nor-Δ9-tetrahydrocannabinol-9-carboxylic acid, cannabinol (CBN), and cannabidiol (CBD) in a sweat patch. The results were compared with urine and hair sample results.Urine, hair, and sweat samples were simultaneously collected from 12 patients who were involved, respectively, in forensic case and monitoring abuse. Selectivity, linearity, limit of detection (LOD), limit of quantification (LOQ), recovery, intraday and interday imprecision, and inaccuracy of the quantification procedure were validated. LODs in hair were 0.05 ng/mg for Δ9-tetrahydrocannabinol, CBN, and CBD, and 0.005 ng/mg for 11-nor-Δ9-tetrahydrocannabinol-9-carboxylic acid. The LOD for sweat was 0.30 ng/patch for all substances. The LOQ in hair was 0.1 ng/mg for Δ9-tetrahydrocannabinol, CBN, and CBD, and 0.01 ng/mg for 11-nor-Δ9-tetrahydrocannabinol-9-carboxylic acid. The LOQ was 0.4 ng/patch in sweat for each analyte. Cannabinoid in urine was determined by means of immunochemical screening (cutoff 11-nor-Δ-tetrahydrocannabinol-9-carboxylic acid 50 ng/mL).All subjects tested positive for 11-nor-Δ9-tetrahydrocannabinol-9-carboxylic acid and Δ9-tetrahydrocannabinol in urine and hair. In sweat samples, Δ9-tetrahydrocannabinol was found in all patches (0.4-2.0 ng/patch); 6 cases were positive for CBN (0.4-0.5 ng/patch) and 3 for CBD (0.4-0.6 ng/patch); 11-nor-Δ9-tetrahydrocannabinol-9-carboxylic acid was never detected in patches.Present sweat analysis results integrated the information from hair and urine and showed that sweat analysis is a suitable, noninvasive method for monitoring compliance with rehabilitation therapy and for detecting recent cumulative use of cannabinoids.

Objective. According to cross-sectional surveys, the prevalence of nontoxic nodular goiter appears to be higher in the adult population. Surgical intervention is indicated for the following: ( a) progressive goiter growth, ( b) compression of organs such as the trachea and esophagus, and ( c) significant aesthetic disfigurement. Ultrasound-guided laser photocoagulation for the treatment of benign thyroid nodules is a viable alternative to traditional surgery. However, studies that have appeared in literature since the introduction of ultrasound-guided laser photocoagulation for the treatment of benign thyroid nodules report contradictory data concerning the energy required for nodule ablation. The aim of the present trial was to evaluate retrospectively the efficacy of percutaneous laser thermal ablation in 2 groups of patients, one treated with low, and the other with high, total amount of energy. Design. Forty euthyroid patients were treated with 1 session of percutaneous laser photocoagulation treatment at low (median = 71 J/mL; 20 patients) and high (median = 578 J/mL; 20 patients) energy. The volume of the nodules was measured by the same investigator, blinded for treatment, using the ellipsoid formula before treatment, at 2, 4, 8, and 30 weeks, and every 6 months for 3 years thereafter. Results. Thyroid nodule ablation is effective over time only if a sufficient amount of energy (>400-500 J/mL for the nodular tissue to be treated) is given, although it incurs proportionate side effects. Conclusions. Percutaneous laser thermal ablation is a viable alternative to traditional surgery for the treatment of benign nodular thyroid disease only if a sufficient amount of energy is delivered.

This randomized controlled study was designed to test the efficacy and safety of percutaneous ultrasound (US)-guided laser photocoagulation (PLP) for treatment of subjects with compressive symptoms due to benign thyroid nodules and/or at high surgical risk. Twenty six subjects were randomized to the intervention (no. 13, age 68+/-3 yr, mean+/-SEM) or observation (no. 13, age 71+/-2 yr) groups. In the control group, the volume of nodules did not significantly change over the 30 week period of observation. In the intervention group, median nodule volume at baseline was 8.2 ml (range 2.8-26.9) and was not significantly different from that of the control group. Nodules decreased significantly (p0.0001) by 22% after 2 weeks (6.5 ml; range 2.4-16.7) and by 44% after 30 weeks (4.6 ml; range 0.69-14.2). Energy given was correlated (p0.05) with the reduction of thyroid nodule volume. All patients tolerated the treatment well and reported relief from compressive and cosmetic complaints (p0.05). At the time of enrolment 7/13 (54%) and 6/13 (46%) of patients in the intervention and control groups, respectively, had sub clinical hyperthyroidism. PLP normalized thyroid function at 6 and 30 weeks after treatment. In conclusion, PLP is a promising safe and effective procedure for treatment of benign thyroid nodules in patients at high surgical risk.

Latent autoimmune diabetes in adults (LADA) is identified by the presence of GAD65 autoantibodies in diabetic patients who do not require insulin treatment for at least six months after the diagnosis. Previous studies have shown that the risk for LADA, similarly to type 1 diabetes mellitus (T1DM), is increased in subjects carrying the HLA-DRB1*03-DQA1*0501-DQB1*0201 and/or HLA-DRB1*04-DQA1*0301-DQB1*0302 haplotypes. In the present study, we investigated the association between LADA and the CTLA-4 A/G polymorphism, another gene polymorphism associated with T1DM and other autoimmune diseases. The heterozygous A/G genotype was significantly more frequent among 80 LADA (69%) than among 85 healthy subjects of similar age and geographical provenience (47%) (OR = 2.47, corrected P= 0.023). Conversely, the homozygous A/A genotype was significantly less frequent in LADA subjects than in healthy controls (26% vs. 47%, OR = 0.4, corrected P= 0.028). The results of our study show that LADA is positively associated with the CTLA-4 A/G genotype, similarly to T1DM, thus providing further supporting evidence of the autoimmune origin of this form of diabetes mellitus of the adult.

It is well known that type 1 diabetes mellitus (T1DM) is a complex genetic disease resulting from the autoimmune destruction of pancreatic beta cells. Several genes have been associated with susceptibility and/or protection for T1DM, but the disease risk is mostly influenced by genes located in the class II region of the major histocompatibility complex. The attraction of leukocytes to tissues is essential for inflammation and the beginning of autoimmune reaction. The process is controlled by chemokines, which are chemotactic cytolines. Some studies have shown that CCR2-64I and CCR5-Delta 32 might be important for protection of susceptibility to some immunologically-mediated disorders. In the present study, we demonstrate the lack of association between CCR2-64I and CCR5-Delta 32 gene polymorphism and TIDM and we describe a new method for a simple and more precise genotyping of the CCR2 gene.

Some type 2 diabetic subjects develop secondary failure to sulphonylurea treatment and require insulin therapy. To test the diagnostic sensitivity and specificity of epitopes of GAD65 autoantibodies (GAD65Ab) for insulin requirement, in patients with latent autoimmune diabetes of the adult, we studied 569 adult subjects with a clinical diagnosis of type 2 diabetes mellitus. All the patients had been initially treated with hypoglycemic agents and/or diet for at least 1 yr. The presence of GAD65Ab (61/569, 10.7%) depended on insulin therapy (P0.0001), low BMI (P0.0001), and low basal C-peptide (P = 0.01). The majority of GAD65Ab-positive subjects (47/61, 77%) had antibodies directed to both middle (GAD65-MAb) and COOH-terminal (GAD65-CAb) epitopes. However, GAD65-CAb were more frequent in insulin-treated subjects (92% of GAD65Ab+ individuals) than in subjects treated with hypoglycemic agents and/or diet (18.2% of GAD65Ab+ individuals), while the exclusive presence of GAD65-MAb was more frequent in subjects treated with hypoglycemic agents and/or diet (81.8% vs. 8%) (P0.0001). The presence of GAD65-CAb had a diagnostic specificity for insulin requirement as high as 99.4% (compared with 96.9% of GAD65Ab as measured in the traditional radiobinding assay) and identified a subgroup of patients with low BMI, low basal C-peptide values, and a need for insulin therapy. Subjects carrying only GAD65-MAb were phenotypically indistinguishable from GAD65Ab-negative patients. Patients positive for GAD65-M+CAb, but not those positive for GAD65-MAb only, showed an increased risk for thyroid autoimmunity, as revealed by the presence of thyroid peroxidase autoantibodies. Our study demonstrates that the use of epitope-specific antibody assays improves the diagnostic specificity of GAD65Ab, and that the presence of GAD65Ab binding to COOH-terminal epitopes is strongly associated with a need for insulin requirement.

The authors present the case of a 24-year-old girl who was sexually assaulted after administration of gamma-hydroxybutyrate (GHB) and morphine. She had been living in an international college for foreign students for about 1 year and often complained of a general unhealthy feeling in the morning. At the end of the college period she returned to Italy and received at home some video clips shot by a mobile phone camera. In these videos she was having sex with a boy she met when she was studying abroad. Toxicological analysis of her hair was done: the hair was 20-cm long. A 2/3-cm segmentation of all the length of the hair was performed. Morphine and GHB were detected in hair segments related to the period of time she was abroad. The analyses of hair segments were performed by gas chromatography/mass spectrometry (GC/MS) and the concentration of morphine and GHB were calculated. A higher value of GHB was found in the period associated with the possible criminal activity and was also associated with the presence of morphine in the same period.

The major histocompatibility complex class I chain-related MIC-A and MIC-B genes are located on chromosome 6 between the histocompatibility leucocyte antigen (HLA)-B and the B-associated transcript genes. The presence of 21-hydroxylase autoantibodies is a sensitive and specific marker of autoimmune Addison’s disease. We studied the polymorphism of exon 5 of the MIC-A gene, of intron 1 of the MIC-B gene, and of HLA-DRB1, -DQA1, and -DQB1 genes in 28 autoimmune (21-hydroxylase autoantibody positive) Addison’s disease patients and in 75 healthy subjects from central Italy. The MIC-A5.1 allele was significantly more frequent in Addison’s disease patients (79%) than in healthy subjects (36%) [odds ratio (OR) = 6.52, corrected P (Pc) = 0.0015], whereas MIC-A6 was significantly reduced in affected subjects (15% vs. 56%, OR = 0.13, Pc = 0.002). The A5.1/A5.1 genotype had an OR for autoimmune Addison’s disease as high as 18.0 and an absolute risk of 1 per 1131. In the presence of MIC-A5.1, MICB-CA-25 was significantly increased in Addison’s disease patients (25% vs. 4%, OR = 8.0, P = 0.0039, Pc = 0.047). The MICB-CA-17 allele was absent in Addison’s disease patients, but present in more than 25% healthy individuals (OR = 0.10, P = 0.0025, Pc = 0.03). Among HLA-DR and -DQ haplotypes, only DRB1*03-DQA1*0501-DQB1*0201 (DR3/DQ2) was significantly more frequent in Addison’s disease patients than in healthy subjects, but only in the presence of MIC-A5.1. The frequency of MIC-A5.1 was significantly increased in Addison’s disease patients only in the presence of HLA-DR3-DQ2. Our study demonstrates that susceptibility to autoimmune Addison’s disease is linked to the MIC-A microsatellite allele 5.1 and that both MIC-A5.1 and HLA-DR3/DQ2 are necessary to confer increased genetic risk for Addison’s disease.

Analysis of the MICA gene revealed a trinucleotide repeat (GCT) microsatellite polymorphism within the transmembrane region. So far, seven alleles of the exon 5 of the MICA gene, which consist of 4, 5, 6, 7, 9, and 10 repetitions of GCT or five repetitions of GCT with an additional nucleotide insertion (GGCT), have been identified. These alleles have been accordingly named A4, A5, A6, A7, A9, A10, and A5.1, and the sizes are, respectively, 179 bp, 182 bp, 186 bp, 189 bp, 194 bp, 197 bp, and 185 bp. We analyzed 1100 Italian subjects for MICA exon 5 microsatellite polymorphism. A new peak corresponding to 191-bp size was observed in one individual, and we confirmed the presence of new polymorphism in exon 5 by sequencing, which consisted of eight GCT repeats. We named this allele, as a current nomenclature, MICA8.

Purpose: The literature reports a wide range of percentages of ablation in the treatment of thyroid nodules. The aim of this nested case-control study was to evaluate whether the different morphological (well-defined vs. agglomerate) characteristics of nodules affect the success rate. Materials and methods: We selected 20 patients with a single and /or dominant well-defined nodule (group 1) and 20 with a nodular formation resulting from the fusion of multiple nodules (group 2). All the nodules were treated by the laser method receiving the same energy. Results: At 6 months, patients in group 1 showed a greater decrease in volume than those in group 2. These differences were more evident after 12 months. Conclusions: Our study demonstrates that the efficacy of laser treatment can be predicted by nodule morphology and contributes to explaining the wide differences in the percentages of ablation reported in literature.

This study assessed the variations in smoking habit in physicians in a General Hospital in Central Italy in 12 years. Data were collected from medical records of workers who underwent health surveillance in 1998-99 and in 2010-11. The prevalence of smokers was 26.3% (male 25.6%, female 27.6%) in 1998-99 and 19.2% (male 19.8%, female 18.5%) in 2010-11. As compared to 1998-99, the prevalence of smokers in 2010-11 was reduced in both sex and in all age classes. Despite the relevant reduction, the prevalence of smokers among physicians remains still high. Occupational physicians could play an important role against tobacco smoking, as they can provide a brief counseling to all smoking physicians during medical health surveillance at workplace and take part in worksite health promotion programmes.

Nodular thyroid disease is very frequent in iodine-deficient areas affecting at least 50% of the population. Percutaneous laser ablation (LA) represents an effective method and an alternative to conventional surgery. Since the first description of the LA methodology for thyroid nodules, various studies have suggested some modifications to increase the percentage of volume reduction of the nodules. One of these alternatives involves the injection of anesthetic in the pericapsular thyroid space with detachment of the capsule itself from the surrounding tissue. The aim of this study was to retrospectively evaluate whether using local anesthetic during LA is more effective in reducing volume size of treated nodules, and whether it causes fewer side effects than using no local anesthesia.A retrospective analysis was conducted on 100 LA procedures performed on 100 patients between January 2009 and December 2011. The patients were divided into two groups: Group A (n = 50) received Lidocaine around the capsule of the thyroid nodule and Group B (n = 50) did not receive any local anesthetic treatment. Before treatment, the median volume size of the nodules of the two groups was similar.The results of our study demonstrate that the injection of local anesthetic does not help reduce nodule volume and that side effects (fever and pain) increase about threefold in the early hours following LA treatment. Thus, we do not recommend local anesthesia before LA of thyroid nodules.

The high prevalence of thyroid nodules in iodine-deficient areas is a practical problem because of the large number of patients requiring fine needle aspiration (FNA) to detect malignant nodules.To obtain an ultrasound (US) score for predicting malignant nodules and reduce the number of unnecessary and expensive FNA.All nodules observed from September 2001 to March 2006 were evaluated by US: echostructure, echogenicity, halo, microcalcifications and ratio between antero-posterior and transversal diameters (AP/TR). Two thousand six hundred and forty-two consecutive patients underwent US-guided FNA for a total of 3645 nodules.Logistic regression analysis showed a potent predictive role for solitary nodules and absence/ incomplete halo (p=0.000). A significant predictive role for microcalcifications and AP/TR ratio was also observed. A 10-point score was constructed using the standardized regression coefficient. Nodules with US scoreor=2.4, those between 2.5-5.4 andor=5.5 had a frequency of malignancy of 0.4, 1.1 and 5.6% (p0.001), respectively. Nodules withor=5.5 US score were characterized by a 66% sensitivity and a 76% specificity compared to the diagnostic values of single parameters which were either sensitive or specific.According to our data, we suggest FNA for nodules reaching a5.4 US score, whereas a clinical judgement should be used for the intermediate category nodules. When the score is lower than 2.5 we do not recommend FNA. The practical use of this US score can help reduce unnecessary and expensive FNA in iodine-deficient areas.

Passive smoking is one of the main risk factors for severe chronic diseases. Hospitals are appropriate settings for promoting tobacco smoking cessation and preventing passive smoking. Moreover, since 2003 Italian Law (no 3/2003) forbids smoking in enclosed workplaces. The smoking ban should be strictly observed in hospitals. This study assessed smoking ban observance and exposure to ETS in a group of paramedical personnel working in a General Hospital (n=1037). Each subject answered a self-administered questionnaire. The prevalence of smokers was 31.2% in females and 31.5% in males. 83% of non-smokers and 66.6% of smokers approved the smoking ban in the hospital but 39.6% of non-smokers and 17.4% of smokers stated it was not observed. Percentages of, respectively, 57.0% and 31.1% in 2004 had dropped in 2005 and in 2006, after Law no 3/2003 was implemented. More than 90% of paramedical personnel declared that workers usually smoked in the workplace. 11.1% of non-smokers reported they were often exposed to ETS and 50% sometimes. These result show the smoking ban was not fully observed in the Hospital, where many workers reported they were exposed to ETS. Occupational Physicians should encourage health workers to stop smoking by offering appropriate counselling.

Type 1 diabetes mellitus (T1DM) is a typical autoimmune disease and results from the destruction of insulin-producing beta cells of the pancreas. It develops in the presence of genetic susceptibility, even though more than 85% of patients with T1DM do not have a close relative with the disorder. The etiology of T1DM is complex, and both genetic and environmental factors play important roles. A permissive genetic background is required for the development of the islet autoimmune process. The strongest genetic association idengified is that with HLA class II genes located on the short arm of chromosome 6. It is well known that both HLA DRB1*04-DQA1*0301-DQB1*0302 (DR4-DQ8) and DRB1*03-DQA1*0501-DQB1*0201 (DR3-DQ2) are positively, and DRB1*15-DQA1*0102-DQB1*0602 is negatively, associated with T1DM. However, only a minority of the subjects carrying the high-risk haplotypes/genotypes develops the disease, which suggests that additional genes play a crucial role in conferring either protection or susceptibility to T1DM. Major histocompatibility complex (MHC) class I chain-related A (MICA) is located in a candidate susceptibility region and activates natural killer (NK) cells, T cells and gammadelta CD8 T cells by its receptor NKG2D. The polymorphism of the MICA gene is associated with T1DM in different populations as demonstrated in several papers published in the last 7 years.

Chemokines are chemotactic cytokines that orchestrate leukocyte trafficking in tissues, thus, playing an important role in regulation of immunological processes. The aim of this study was to investigate the association of human papillomavirus (HPV) infection and cervical cancer with two DNA polymorphisms of the chemokine receptors CCR5-delta32 and CCR2-64I. The study material consisted of 50 cervical intraepithelial neoplasia (CIN) cases and 50 of age and sampling-date matched controls, 100 invasive cervix cancer cases and 100 of their corresponding matched disease-free controls. Pyrosequencing was employed to genotype the CCR2-64I polymorphism. CCR5-delta32 was genotyped using standard PCR fragment length analysis. The frequencies of CCR2 and CCR5 genotypes from 150 patients and 150 healthy controls were representative of the general population according to the Hardy-Weinberg equilibrium analysis. Risk association was computed with conditional logistic regression analysis. HPV-positive individuals with the rare CCR5deelta32/delta32 genotype have a risk of 4.58 (CI = 0.40-52.64, p-value = 0.045) compare to HPV negative group. The delta-32 mutation on the CCR locus is imperceptibly associated with increased risk of HPV infection. In total, cervical neoplasia was not associated with genetic polymorphism of CCR2 and CCR5.

Summary Intracerebral hemorrhage (ICH) is associated with high mortality in patients on oral anticoagulant treatment. The normalization of hemostatic balance usually requires slow-acting or risky treatments, such as vitamin K, fresh frozen plasma or prothrombin complex concentrates, which have narrow therapeutic windows particularly in cardiopathic patients like those with mechanical heart valves. Recombinant activated factor VII (rFVIIa) seems useful in patients with normal or pathologic coagulation who have an ICH. We report of a patient on acenocumarol for mitro-aortic valve replacement, referred for headache and found at computerized tomography scanning to have a parietal hemorrhage with ventricular invasion. International normalized ratio was 3.22. The patient was treated with vitamin K and with a bolus of 80 μg/kg of rFVIIa, with correction of the international normalized ratio within 15 min. Sequential computerized tomographies showed progressive reduction of the hematoma and normalization of ventricular spaces and the patient fully recovered. No valvular dysfunctions or cardiac thrombi were found at sequential echocardiograms. Neurological examination at 3 months follow-up visit was completely normal. To our knowledge, this is the first report of the safe and successful use of rFVIIa to treat ICH in a patient on oral anticoagulants for prosthetic heart valves.

Because of its peculiar characteristics, hair analysis provides a way of obtaining information that cannot be acquired by other commonly used forensic medical analyses, such as blood or urine analysis. In the keratin matrix many xenobiotics are incorporated permanently, in contrast to the situation with blood or urine where they are generally only detectable for a few hours or days. Therefore hair analysis should be the method of choice in the clinical and forensic toxicology field when the assessment of repeated or chronic exposure to a drug is required, e.g. in the case of criminal responsibility, revocation/restoration of a driving licence or in workplace testing. Some factors that can affect the concentrations of drugs in hair, such as passive contamination, age, ethnicity and cosmetic treatment, must be considered. Analytical methodology is also very important: GC/MS/MS has proved to be a highly sensitive and specific technique for the detection of very low concentrations of such drugs in hair. In this study five cases of the application of hair analyses using this technique for the determination of abused drugs (opiates, cocaine, amphetamine, anabolic steroids) are described.

To evaluate the contribution of the MHC class I chain-related A (MICA) gene polymorphism to the genetic risk of systemic lupus erythematosus (SLE).HLA-DRB1-DQA1-DQB1 genotyping, MICA exon 5 microsatellite genotyping and HLA-B8 genotyping were performed in 48 Italian SLE patients and in 158 healthy control subjects.Of HLA class II haplotypes, only DRB1*03-DQA1*0501-DQB1*0201 (DR3-DQ2) was significantly more frequent among SLE patients than among healthy control subjects [odds ratio (OR) = 6.5, corrected P0.0026]. HLA-B8 was detected in 31% SLE patients and 13% healthy control subjects (OR = 3.0, P = 0.005). The allele-wise comparison between patients and controls showed that both MICA5 (OR = 2.5, corrected P0.0005) and MICA5.1 (OR = 2.4, corrected P0.0005) were positively and MICA9 (OR = 0.2, corrected P0.0005) was negatively associated with the disease. The MICA5/5.1 genotype was positively associated with SLE (OR = 28.9, corrected P0.0015) also in subjects negative for DR3-DQ2 (OR22.6, corrected P0.011). The simultaneous presence of DR3-DQ2 and MICA5.1 was detected in 15/48 (31%) SLE and in 10/158 (6%) healthy control subjects (OR = 6.7, corrected P0.011). The simultaneous combination of DR3-DQ2 and MICA5 was found in 10/48 (21%) SLE patients and in only 1/158 healthy control subjects (OR = 41.3, corrected P0.011). Logistic regression analysis showed the independent positive associations of MICA5 and MICA5.1 and negative association of MICA9 with the disease, and revealed that the interaction of the three major markers (DR3-DQ2, MICA5 and MICA5.1) was associated with increasing genetic risk, which was highest (OR30.3) in DR3-DQ2-positive subjects carrying the MICA5-5.1 genotype.Our study provides the first demonstration of the independent association of the MICA gene polymorphism with genetic risk of SLE.

The attraction of leukocytes to tissues is essential for inflammation and the initiation of the autoimmune reaction. The process is controlled by chemokines, which are chemotactic cytokines. We investigated whether human chemokine receptor gene polymorphisms, namely CCR5-Delta32 and CCR2-64I, are associated with susceptibility to autoimmune Addison's disease. Genotyping was performed in 56 patients and 127 healthy controls by a new method using pyrosequencing for CCR2-64I and by polymerase chain reaction and detecting gel for CCR5-Delta32. None of the CCR2 or CCR5 alleles was found to be associated, either positively or negatively, with disease risk. Our results indicate that the CCR2-64I and CCR5-Delta32 gene polymorphisms do not play a major role in conferring genetic risk for, and/or protection against, autoimmune Addison's disease.

Cholecystectomy is a common surgical procedure performed in patients with sickle cell disease (SCD). Postoperative complications, including acute painful vaso-occlusive crisis and acute chest syndrome, have been described frequently after either traditional or laparoscopic cholecystectomy (LC). It's still not clear if preoperative blood transfusion, hyperhydration, intraoperative body temperature conservation may reduce complications rate. The Authors reviewed the charts of seven patients with SCD operated on LC for symptomatic gallbladder lithiasis and describe their perioperative management. In 3 patients preoperative endoscopic removal of stones was achieved. Five patients with HB lower than 9 g/dl and/or HbS higher than 40% were transfused preoperatively and all the patients were hyperhydrated. Intraoperative monitoring was achieved for early recognition of ventilation to perfusion mismatch and acid-base balance or temperature modifications. The Authors reported only one case of postoperative lower extremities pain. This study suggests that LC is a safe procedure in SCD if appropriate monitoring and perioperative management are achieved.

The polymorphism of the major histocompatibility complex class I chain-related A gene is associated with type 1 diabetes mellitus. The major histocompatibility complex class I chain-related A gene 5 allele is significantly more frequent in Caucasian type 1 diabetes mellitus children than in healthy subjects, but no information is available on the association with adult-onset type 1 diabetes mellitus or with the so-called slowly progressive latent autoimmune diabetes of the adult in the same ethnic group. In this study we estimated the frequency of major histocompatibility complex class I chain- related A gene alleles and human leukocyte antigen-DRB1*03-DQA1*0501-DQB1*0201 and human leukocyte antigen-DRB1*04- DQA1*0301-DQB1*0302 in 195 type 1 diabetes mellitus subjects, in 80 latent autoimmune diabetes of the adult subjects, and in 158 healthy subjects from central Italy. Major histocompatibility complex class I chain-related A gene 5 was significantly associated with type 1 diabetes mellitus only in the 1-25 yr age group at diagnosis, and the odds ratio of the simultaneous presence of both major histocompatibility complex class I chain-related A gene 5 and human leukocyte antigen-DRB1*03- DQA1*0501-DQB1*0201 and/or human leukocyte antigen-DRB1*04-DQA1*0301-DQB1*0302 was as high as 54 and higher than 388 when compared with double negative individuals. Adult-onset type 1 diabetes mellitus (age at diagnosis,25 yr) and latent autoimmune diabetes of the adult were significantly associated with major histocompatibility complex class I chain-related A gene 5.1, which was not significantly increased among diabetic children. Only the combination of major histocompatibility complex class I chain-related A gene 5.1 and human leukocyte antigen-DRB1*03-DQA1*0501-DQB1*0201 and/or human leukocyte antigen-DRB1*04-DQA1*0301-DQB1*0302 conferred increased risk for adult-onset type 1 diabetes mellitus or for latent autoimmune diabetes of the adult. Our study provides demonstration of the existence of distinct genetic markers for childhood/young-onset type 1 diabetes mellitus and for adult-onset type 1 diabetes mellitus/latent autoimmune diabetes of the adult, namely major histocompatibility complex class I chain-related A gene 5 and major histocompatibility complex class I chain-related A gene 5.1, respectively.

Aims/hypothesis. A distinct family of MHC genes has been identified in the class III region and denominated MHC Class I chain-related genes (MIC). The MIC-A gene is located between the TNFA and the HLA-B genes. The aim of our study was to test the association of the polymorphism of the MIC-A gene with Type I (insulin-dependent) diabetes mellitus and evaluate the interaction between MIC-A and TNFA, HLA-B, HLA-DR and HLA-DQ gene polymorphism.¶Methods. Type I diabetic (n = 95) and healthy (n = 98) Italian subjects were typed for exon 5 of MIC-A and for HLA-DRB1, HLA-DQA1, HLA-DQB1 and TNFA alleles. All subjects were also typed for the presence of HLA-B8 or HLA-B15.¶Results. The frequency of MIC-A5 was increased in diabetic subjects (53 % vs 15 %) (OR = 6.1) (corrected p, p c < 0.0005). Among HLA class II haplotypes, both HLA-DRB1*03-DQA1*0501-DQB1*0201 (DR3-DQ2) and DRB1*04-DQA1*0301-DQB1*0302 (DR4-DQ8) (“at-risk class II haplotypes”) were positively associated with diabetes (OR = 6.7 and 6.0, respectively) (p c < 0.003). Also HLA-B8 was more frequent among Type I diabetic subjects than among healthy control subjects (OR = 2.8, p = 0.01). None of the TNFA alleles were statistically significantly associated with Type I diabetes. The MIC-A5 exon was negatively associated with age at clinical onset of diabetes (p = 0.012). Thus, 68 % diabetic subjects younger than 25 years and 29 % older than 25 years were carrying this allele. Both MIC-A5 and the at-risk class II haplotypes were independently associated with Type I diabetes and the combined association of the two markers had the highest relative risk (OR = 172). In subjects younger than 25 years, the OR of MIC-A5 was as high as 21.7 and was more than twofold that of at-risk class II haplotypes (OR = 9.5). The MIC-A5 exon was not in linkage disequilibrium with any of the HLA-class I, class II or TNFA alleles studied.¶Conclusions/interpretation. The MIC-A gene polymorphism is associated with genetic risk for Type I diabetes and the combination of MIC-A5 and at-risk class II haplotypes is now to be seen as the strongest genetic marker for this disease. [Diabetologia (2000) 43: 507–514]

Glutamic acid decarboxylase (GAD)65 autoantibodies (GAD65Ab) in type 2 diabetic subjects with secondary failure to sulphonylurea treatment identify the so-called latent autoimmune diabetes of the adult (LADA). The aim of our study was to estimate the risk for endocrine autoimmunity in type 2 diabetic subjects with GAD65Ab.We analysed serum samples from 600 adult subjects with a clinical diagnosis of type 2 diabetes mellitus for the presence and levels of GAD65Ab and antibodies directed against the islet autoantigen IA-2/ICA512 (IA-2/ICA512Ab). All the patients had been treated initially with hypoglycaemic agents and/or diet for at least 1 year. GAD65Ab+ subjects were studied for the presence of thyroid peroxidase autoantibodies (TPOAb), 21 hydroxylase autoantibodies (21OHAb) and frequency of HLA class II haplotypes.GAD65Ab were found in 67/600 (11%) and IA-2/ICA512Ab in 12/600 (2%) subjects (P0.0001). The presence of GAD65Ab, but not that of IA-2/ICA512Ab, was significantly associated with insulin therapy, low BMI (P0.0001) and low basal C-peptide (P0.01). Islet-cell antibodies (ICA) were detected in 43/67 (64%) GAD65Ab+ and in 10/12 (83%) IA-2/ICA512Ab + subjects. TPOAb occurred more frequently in GAD65Ab+ (16/67, 24%) than in GAD65Ab-subjects (9/174, 5%) (P0.0001). 21OHAb were detected only in GAD65Ab+ subjects (3/67, 4.5%) (P = 0.03 vs. GAD65Ab-subjects). None of the 21OHAb+ subjects had metabolic or clinical signs of adrenal dysfunction. HLA-DRB1*03-DQA1*0501-DQB1*0201 (DR3-DQ2) was significantly more frequent in GAD65Ab+ subjects than in healthy controls (OR = 5.42, corrected P0.0026). The presence of TPOAb was significantly associated with DR3-DQ2 (P = 0.024).Our study demonstrates that the presence of GAD65Ab identifies a subgroup of type 2 diabetic patients with high risk for thyroid and adrenal autoimmunity, and that both GAD65Ab and TPOAb are associated with the presence of HLA-DR3-DQ2, in these patients.

The aims of this study were (a) to assess blood cadmium (B-Cd) concentrations and to establish a tentative reference interval; (b) to identify significant determinants of B-Cd, in a population from Umbria, Central Italy, which was not occupationally exposed to cadmium (Cd). Four hundred and thirty-four healthy blood-donors volunteered to answer a questionnaire and provide a blood sample for B-Cd analysis, which was performed by graphite furnace atomic absorption spectrophotometry. Blood Cd concentrations ranged from non-detectable values, i.e. below 0.1 microgram/l up to 3.4 micrograms/l and were not normally distributed. The median values and the 95th percentiles were 0.7 and 2.0 micrograms/l, respectively. Concentrations of B-Cd were more than double in smokers than in non-smokers, median values being 1.1 micrograms/l and 0.5 microgram/l, respectively. In current smokers, B-Cd values correlated with the number of cigarettes smoked daily (rs = 0.40, P = 0.0001) and with the cumulative exposure to cigarette smoke (rs = 0.35, P = 0.0001). Concentrations of B-Cd correlated with age in the non-smokers, but not in the smokers and were significantly higher in women than in men only in the non-smokers. Both in smokers and non-smokers, B-Cd concentrations were similar in subjects living in urban or in rural areas. In the whole study population the lower and the upper tentative reference limit were0.1 and 2.2 micrograms/l, respectively, as computed by a non-parametric rank-based method. The upper limit was approximately double in smokers than in non-smokers (3.1 micrograms/l and 1.6 micrograms/l, respectively). Our results show that B-Cd concentrations in a general population from Umbria are in the range reported for general populations in Northern Italy and other European Countries. Smoking was the strongest determinant of B-Cd concentrations and age had a lesser effect.

Described is a method for the determination of orotic acid as its methyl ester in human urine. The method involves the use of solid-phase extraction to isolate pyrimidines from urine and derivatization with methanol and sulfuric acid, followed by isocratic high-performance liquid chromatography on a reversed-phase C18 column with UV absorbance detection. The assay is shown to be sufficiently sensitive for use in clinical investigations where elevated orotic acid excretion is suspected.

Insulin-dependent diabetes mellitus (IDDM) is an autoimmune disease that is characterized by the destruction of insulin-producing beta-cells in the pancreatic islets. A single administration of CFA prevents clinical hyperglycaemia in non-obese diabetic (NOD) mice. We have previously shown that CFA administration does not eliminate insulitis in the pancreas of the treated animals, but diverts the disease process from a destructive to a non-destructive pathway. We provide evidence that this phenomenon may be under cytokine control. Neutralizing monoclonal antibodies against IL-4 and IL-10 were injected, singularly or in combination, into CFA-treated NOD mice. Antibody treatment did not lead to the development of overt diabetes; however, a marked impairment of glucose tolerance was shown in about one half of the mice treated with a combination of the two antibodies at the end of the study. This functional abnormality correlated with the histological loss of pancreatic islet tissue. These studies suggest a role for IL-4 and IL-10 in CFA-induced protection from diabetes in the NOD mouse. They also suggest that, in this animal model, the nature of the autoimmune response to islet tissue (either destructive or non-destructive) may reflect the relative proportion of Th1- and Th2-type cytokines produced in the lesions.

We studied peripheral blood and apheresis samples from 39 consecutive normal donors who were parents or siblings of patients who received matched or mismatched bone marrow transplants using a combination of rhG-CSF-mobilized peripheral blood stem cells (PBSCs) and bone marrow (BM). BM was harvested from donors 1-7 days before starting rhG-CSF treatment: 12 micrograms/kg/day rhG-CSF was administered by continuous s.c. infusion for 4-7 days. Peripheral blood progenitor cells were harvested by leukapheresis using an automated continuous-flow blood cell separator, beginning on day 4 of rhG/CSF, for 1-4 consecutive days. Peak peripheral blood CD34+ cell and CFU-GM levels were reached simultaneously on day 5 or 6 of rhG-CSF administration. Median peak levels were 1.65% for CD34+ cells (range 0.34%-4.7%) and 142 CFU-GM/10(5) plated cells (range 16-700). The greatest numbers of CD34+ cells and CFU-GM, expressed per liter of blood volume processed, were harvested during the second and third leukapheresis: CD34+ cells 37.77 +/- 25.48 x 10(6) and CFU-GM 3.32 +/- 2.51 x 10(6) during the second leukapheresis, and CD34+ cells 37.01 +/- 16.33 x 10(6) and CFU-GM 3.82 +/- 4.36 x 10(6) during the third. The number of CD34+ cells and CFU-GM did not correlate with the sex, age, or body weight of the donors. This study indicates that this protocol for administration of rhG-CSF mobilizes large numbers of hematopoietic progenitor cells into the peripheral blood and that bone marrow harvesting before G-CSF administration does not impair stem cell mobilization.

Background Environmental lead exposure is a possible causative factor for increased blood pressure and hypertension, but large studies at low-level exposure are scarce, and results inconsistent. Objective We aimed to examine the effects of environmental exposure to lead in a large population-based sample. Methods We assessed associations between blood lead and systolic/diastolic blood pressure and hypertension in 4452 individuals (46–67 years) living in Malmo, Sweden, in 1991–1994. Blood pressure was measured using a mercury sphygmomanometer after 10 min supine rest. Hypertension was defined as high systolic (≥140 mmHg) or diastolic (≥90 mmHg) blood pressure and/or current use of antihypertensive medication. Blood lead was calculated from lead in erythrocytes and haematocrit. Multivariable associations between blood lead and blood pressure or hypertension were assessed by linear and logistic regression. Two-thirds of the cohort was re-examined 16 years later. Results At baseline, mean blood pressure was 141/87 mmHg, 16% used antihypertensive medication, 63% had hypertension, and mean blood lead was 28 µg/L. Blood lead in the fourth quartile was associated with significantly higher systolic and diastolic blood pressure (point estimates: 1–2 mmHg) and increased prevalence of hypertension (odds ratio: 1.3, 95% confidence interval: 1.1–1.5) versus the other quartiles after adjustment for sex, age, smoking, alcohol, waist circumference, and education. Associations were also significant with blood lead as a continuous variable. Blood lead at baseline, having a half-life of about one month, was not associated with antihypertensive treatment at the 16-year follow-up. Conclusions Low-level lead exposure increases blood pressure and may increase the risk of hypertension.

We carried out a survey on blood lead levels in children living in three different communities in Umbria, Italy: Corciano, a small community (12,500 inhabitants), free of lead-using factories and with light traffic; Perugia, a medium-sized city (146,500 inhabitants); Deruta, a small community (7500 inhabitants) whose economy is based mainly on the production of artistic pottery, mostly in small home-operated factories. The study sample was made up of 539 children (275 boys and 264 girls); 156 of them attended nursery school (aged 3-6) and 383 primary school (aged 6-11). The mean blood lead level was significantly higher in Deruta than in Corciano (9.7 vs 8.3 micrograms/dl); Deruta children whose parents were occupationally exposed to lead had significantly higher blood lead levels than children of lead-unexposed parents (10.7 vs 9.0 micrograms/dl). The mean blood lead level was higher in Perugia than in Corciano children. On the average boys had higher blood lead levels than girls in all of the groups. We conclude that blood lead levels were low in the groups of children studied. Nevertheless children of ceramic workers and children living in a medium-sized city had greater lead absorption than children living in the control area.

This study assessed the smoking habit in 7,159 apprentices (females: 53.3%) in central Italy. In the period 1996-2006, each apprentice underwent a compulsory health examination to assess fitness for work carried out by specialists in Occupational Medicine. Demographic data and information on schooling, smoking habit, alcohol and coffee intake were collected by a questionnaire. Overall, 51.9% of apprentices were smokers. Smokers were fewer among female apprentices than among the males (48.3% vs 55.9%; chi-square test, p0.001). No decrease in the prevalence of smokers was evident during the study period. Low educational level, and daily intake of alcohol and coffee significantly increased the risk of being a smoker. Finding a high percentage of smokers among Italian apprentices with a low educational level who are employed in jobs for which few qualifications are required indicates the need for work-place activities against tobacco smoking habit. Specialists in Occupational Medicine who perform regular health surveillance of workers could play a role in the anti-smoking campaign by integrating their routine work with brief counselling sessions aimed at preventing smoking in young workers and helping smokers to stop and by collaborating in work-place health promotion programmes.

Naphthalene, the most volatile polycyclic aromatic hydrocarbon (PAH), was recently classified as possible human carcinogen by International Agencies for Research on Cancer Humans may be exposed to naphthalene from a wide variety of sources, including occupation, environment, personal habits. We assessed urinary excretion of 1-naphthol (1-NAF), biomarker of naphthalene exposure, in non-occupationally exposed subjects.Urinary 1-NAF, 1-hydroxypyrene (1-OHP), biomarker of exposure to pyrene and cotinine, biomarker of smoking habits, were measured in 104 adults (53 men, 51 women).1-NAF concentrations overlapped in males and females (median: men 0.35 Microg/g creat; women: 0.46 microg/g creat). Median concentration of 1-NAF was 6-fold higher in smokers compared to nonsmokers (respectively, 7.7 microg/g creatinine vs 1.3 microg/g creatinine). Between smokers, urinary cotinine was positively correlated to 1-naphthol (rho: 0.69; p0.01) and 1-OHP (rho: 0.53; p0.01). Higher 1-OHP concentrations were found in smokers (median: smokers 0.16 microg/g creatinine, not-smokers 0.05 microg/g creatinine;).In our study population, we found that 1-NAF excretion is much higher as compared to 1-OHP excretion. This is due to the ubiquitous presence of naphthalene in the environment. Smoking considerably increase the exposure to naftalene.

It may be advantageous to use sweat, rather than blood or urine, to monitor individuals' drug exposure for the purposes of drug treatment programs, employment initiatives, and forensic investigations. Forty-eight patients receiving methadone at the Public Service for the Treatment of Drug Dependence of Perugia (Italy) were monitored for 14 days by the analysis of methadone and cocaine present in two sweat patches, each worn for 7 days. The results were compared to those from the analysis of urine samples collected at the beginning of the study and after 7 days, as well as those from the analysis of hair collected on the fourteenth day. Sweat patch analysis was positive for methadone and its metabolite EDDP in 100% of patients. Some individuals were positive for cocaine in urine, sweat, and hair while others were positive for cocaine in only one of those samples. Results suggest analysis of a sweat patch indicates an individual's drug use or drug washout for the previous week, and provides an alternative to blood or urine analyses.

Patients who undergo transplantation with haploidentical “three-loci” mismatched T-cell-depleted bone marrow (BM) are at high risk for graft failure. To overcome the host-versus-graft barrier, we increased the size of the graft inoculum, which has been shown to be a major factor in controlling both immune rejection and stem cell competition in murine models. Seventeen patients (mean age, 23.2 years; range, 6 to 51 years) with end-stage chemoresistant leukemia were received transplants of a combination of BM with recombinant human granulocyte colony- stimulating factor-mobilized peripheral blood progenitor cells from HLA- haploidentical “three-loci” incompatible family members. The average concentration of colony-forming unit-granulocyte-macrophage in the final inoculum was sevenfold to 10-fold greater than that found in BM alone. The sole graft-versus-host disease (GVHD) prophylaxis consisted of T-cell depletion of the graft by the soybean agglutination and E- rosetting technique. The conditioning regimen included total body irradiation in a single fraction at a fast dose rate, antithymocyte globulin, cyclophosphamide and thiotepa to provide both immunosuppression and myeloablation. One patient rejected the graft and the other 16 had early and sustained full donor-type engraftment. One patient who received a much greater quantity of T lymphocytes than any other patient died from grade IV acute GVHD. There were no other cases of GVHD > or = grade II. Nine patients died from transplant-related toxicity, 2 relapsed, and 6 patients are alive and event-free at a median follow-up of 230 days (range, 100 to 485 days). Our results show that a highly immunosuppressive and myeloablative conditioning followed by transplantation of a large number of stem cells depleted of T lymphocytes by soybean agglutination and E-rosetting technique has made transplantation of three HLA-antigen disparate grafts possible, with only rare cases of GVHD.