a large outbreak occurred in the general intensive care unit of the Ospedale di Circolo in Varese (Italy), caused by Pseudomonas aeruginosa producing the PER-1 extendedspectrum ␤-lactamase. A total of 108 clinical isolates of P. aeruginosa resistant to broad-spectrum cephalosporins were recovered from 18 patients. Epidemic isolates were characterized by synergy between clavulanic acid and ceftazidime, cefepime, and aztreonam. Isoelectric focusing of crude bacterial extracts detected two nitrocefin-positive bands with pI values of 8.0 and 5.3. PCR amplification and characterization of the amplicons by restriction analysis and direct sequencing indicated that the epidemic isolates carried a bla PER-1 determinant. The outbreak was of clonal origin as shown by pulsed-field gel electrophoresis analysis. This technique also indicated that the epidemic strain was not related to three other PER-1-positive isolates obtained at the same hospital in 1997. Typing by enterobacterial repetitive intergenic consensus-PCR showed that minor genetic variations occurred during the outbreak. The epidemic strain was characterized by a multiple-drug-resistance phenotype that remained unchanged over the outbreak, including extended-spectrum cephalosporins, monobactams, aminoglycosides, and fluoroquinolones. Isolation of infected patients and appropriate carbapenem therapy were successful in ending the outbreak. Our report indicates that the bla PER-1 resistance determinant may become an emerging therapeutic problem in Europe.

Our purpose was to determine the prevalence and features of metabolic syndrome (MS) in a series of long-term hematopoietic stem cell transplantation (HSCT) survivors. We assessed the clinical, metabolic and endocrinological data, and plasma TNF, leptin, resistin and adiponectin levels relating to 85 HSCT recipients. MS was diagnosed on the basis of the National Cholesterol Education Program-Adult Treatment Panel III criteria. Its prevalence was compared with that observed in an Italian population, and its relationship with the clinical and laboratory parameters was assessed univariately and multivariately. Twenty-nine HSCT recipients had MS instead of the 12.8 expected (P<0.0001), with hypertriglyceridemia being the most common feature. Univariate analysis indicated that high insulin and leptin levels, low-adiponectin levels and hypogonadism were significantly related to a diagnosis of MS; multivariate analysis indicated plasma leptin, insulin resistance, age and hypogonadism. We conclude that HSCT recipients are at increased risk of a form of MS that has particular clinical features. Plasma leptin levels are independently related to MS, thus suggesting that leptin resistance may play a role as a pathogenetic clue, as in other conditions in which MS occurs as a secondary phenomenon. MS deserves consideration as a life-threatening complication in patients who are probably cured of their underlying disease.

Background:The risk of thyroid carcinoma in patients with Graves disease has been particularly emphasized when nodules coexist with thyroid hyperplasia; a surgical approach has been suggested.

The natural history of beta thalassemia major (TM) has significantly changed during the last 2 decades. At present TM patients survive over their thirties and forties, but they have considerable morbidity. Bone demineralization is an important cause of morbidity in older patients; the etiology is multifactorial and partially unknown. We examined cross-sectionally 111 adult TM patients (66 females and 45 males, 32.6 ± 6 years), regularly transfused, properly chelated and replaced for endocrine defects. Bone demineralization was detected in 92.7% of patients, with different severity according to gender and site: osteopenia was the prominent finding at the femur, osteoporosis at lumbar spine (p<0.001), more evident in males. The femoral site was more influenced by biochemical and clinical factors; despite adequate replacement, femoral T-score was lower in the hypogonadic than in the eugonadic group (p =0.047). A significant correlation was found between bone mass and body mass index (BMI), alkaline phosphatase (ALP) and pre-transfusional Hb levels. Multivariate analysis indicated as significant regressors ALP, BMI and hypoparathyroidism (T-score: p=0.005, 0.035, 0.002; Z-score: 002, 0.009, 0.003, respectively) at femur, only ALP at lumbar spine (p= 0.008 and 0.045 for T and Z scores, respectively). Statistical significance was reached more frequently by T-score, while Zscore demonstrated to have a lower sensitivity. Despite best care facilities, bone demineralization in thalassemic patients remains a challenge; further exploration of the relationships between bone loss and endocrine, biochemical and hematologic variables is warranted to find effective measures to reduce bone pain and fracture risk.Response to Reviewers: We are grateful for the useful suggestions of the reviewers. We have revised our paper following their recommendations.Reviewers' comments: 1) In the Discussion session they comment that "....the correlation between alkaline phosphatase and bone mineralization indicates a prevalent role of reduced deposition over increased reabsorption, as reported by other Authors, at variance with others. We could not confirm the same relationship with osteocalcin, another marker of osteoblastic activity.".First of all the authors have not measured any of the markers of bone resorption. I believe that it is important for the paper and for the the discussion to include at least NTX or CTX measurements. I hope that they have available serum for such measurement. I suggest that CTX is more sensitive than NTX in the serum.-In the original paper, we did not include any marker of bone resorption because we had only partial data (different markers, incomplete series). It seems now evident that the importance of these indices to our work has been understated. In effect, we had available serum of most patients, so we decided to measure CTX following the useful suggestion of the reviewer; we recognize that this adjunct increases the scientific interest of our results. As pointed out in the revised paper (page 8, l...