Increased risk of osteoporosis in postmenopausal women with type 2 diabetes mellitus: a three-year longitudinal study with phalangeal QUS measurements.

Type 2 diabetes mellitus (T2DM) is associated with a higher risk of fractures even in presence of normal or increased bone mineral density. The purpose of this three-year longitudinal study was to evaluate the risk of osteoporotic fractures by assessing the changes of Quantitative Ultrasound (QUS) parameters in a group of postmenopausal women with type 2 diabetes mellitus (T2DM) compared with non-diabetic controls. The measurements were taken on a group of 18 postmenopausal women affected by T2DM and 18 healthy age-matched controls, aged 55-70 years, referring to the Osteolab laboratory at the ISBEM Research Institute (Brindisi, Italy) between 2009 and 2013. Subjects had baseline and 3-year follow-up measurements with phalangeal QUS carried out by a DBM Sonic Bone Profiler 1200 (Igea®); medical history, current drug therapies and risk factors for fractures were recorded for each patient. The analyzed phalangeal QUS parameters were Amplitude-Dependent Speed of Sound (AD-SoS), Bone Transmission Time (BTT), Fast Wave Amplitude (FWA) and Signal Dynamic (SDy). At the baseline visit we found no statistically significant difference between T2DM and non-diabetic patients when looking at phalangeal QUS parameters. At the three-year follow-up visit, a significantly higher decrease of both BTT (P<0.001) and AD-SoS (P<0.001) parameters was found in the T2DM group. On the contrary, the decrease of FWA was significantly higher in non-diabetic controls (P<0.001). Our data confirm the ability of phalangeal QUS to detect differences in the risk of osteoporotic fractures in T2DM postmenopausal women compared to non-diabetic controls. The study suggests that T2DM women present a higher cortical porosity and increased trabecular bone density compared to non-diabetic controls, respectively shown by the higher decrease of both AD-SoS and BTT and the lower decrease of FWA.

The potential of accelerator-based techniques as an analytical tool for forensics: The case of coffee.

We discuss how different accelerator-based techniques can be employed synergistically as a powerful analytical tool for forensic studies of foodstuff. Brazilian and Jamaican coffees were chosen as a showcase due to its popularity and potential risk of adulteration and/or falsification. Comprehensive characterization of major and trace elements, age since production and compound contents were achieved using different techniques, including PIXE (Particle-Induced X-ray Emission), FTIR (Fourier Transform Infrared), and AMS-14C (Accelerator Mass Spectrometry - Radiocarbon Analysis). While PIXE provides information on the elements present in the samples, FTIR probes the types of compounds through their vibrational spectra. Finally, AMS-14C is capable of dating organic samples regarding their harvesting time. Five different laboratories from research institutions around the world took part in the experiments. The integration of the results obtained with different techniques provided multifaceted perspectives on the coffee under study, thus allowing a direct assessment of the material for forensic purposes such as authentication, determination of provenance, and combat counterfeiting.

Oral iron chelator deferasirox in the treatment of secondary hemochromatosis following bone marrow transplantation in a patient with severe aplastic anemia.

Iron overload sometimes complicates the clinical course of bone marrow transplantation and can cause damage to liver and heart function. A patient with post-transplantation secondary hemochromatosis was treated with deferasirox, which not only normalized ferritin levels, but also reduced hepatic iron to normal values as measured by biosusceptometry with a superconducting quantum interference device. Side effects were minimal. The use of deferasirox to reduce post-transplant iron burden merits evaluation in a larger patient population.

Plasma NT-proBNP levels and the risk of atrial fibrillation after major lung resection.

AIM: Supraventricular tachyarrhythmias, most frequently atrial fibrillation (AF), occur in 8-30% of patients undergoing major pulmonary resection. The aim of this study was to characterize a biochemical marker in order to identify subjects at higher risk of postoperative AF. The authors tested the hypothesis that elevated preoperative plasma levels of N-terminal brain-type natriuretic peptide (NT-pro-BNP) may predict the occurrence of postoperative AF. METHODS: Fifty-five consecutive patients undergoing elective major thoracic surgery were selected. All patients had 12-lead electrocardiogram and transthoracic echocardiographic evaluation at entry. Plasma NT-pro BNP levels were determined both at baseline and at the first postoperative day. Patients were monitored thereafter to detect the occurrence of AF. For statistical analysis, an unpaired Student t test was used to compare continuous variables, chi(2) tests or Fischer exact tests were used for categorical variables, as needed. RESULTS: Eight (14.54%) of the 55 patients developed AF with a peak incidence on postoperative days 2 to 3. Baseline NT-pro-BNP was more than two fold higher in patients who developed AF (506.1+/-108.4 pg/mL versus 197.7+/-54.9 pg/mL; P=0.001). Other relevant clinical and diagnostic parameters were not different in the two groups. Patients with NT-pro-BNP level above the median (113.0 pg/mL) had 8-fold increase risk of postoperative AF. CONCLUSION: A preoperative elevated plasma NT-pro-BNP level was associated with the occurrence of AF in patient undergoing major thoracic surgery. Baseline NT-pro-BNP levels may be proposed as a biochemical marker to detect patients at higher risk of postoperative AF who could benefit from prophylactic therapeutic medication.

Characterization of a recurrent translocation t(2;3)(p15-22;q26) occurring in acute myeloid leukaemia.

Six patients with de novo acute myeloid leukemia (AML) and a t(2;3)(p15-21;q26-27) were identified among approximately 1000 cases enrolled in the GIMEMA trial. The t(2;3) was the sole anomaly in three patients, whereas in three cases monosomy 7, trisomy 15 and 22, and trisomy 14 represented additional aberrations. No cryptic chromosome deletions at 5q, 7q, 12p, and 20q were observed. One patient carried a FLT3 D835 mutation; FLT3 internal tandem duplication (ITD) was not detected in three patients tested. Characterization of the translocation breakpoints using a 3q26 BAC contig specific for the PRDM3 locus showed that the breakpoints were located 5' to EVIl as follows: within myelodysplatic syndrome (MDS) intron 1 (# 3), between MDS1 exons 2 and 3 in three patients (# 1, 2, 4) with a 170bp cryptic deletion distal to the breakpoint in one (# 2), and in a more centromeric position spanning from intron 2 to the 5' region of EVI1 (# 6, 5). A set of 2p16-21 BAC probes showed that the breakpoints on chromosome 2p were located within BCL11A in two separate regions (# 1, 4 and # 2-5), within the thyroid adenoma-associated (THADA) gene (# 6) or distal to the ZFP36L2 locus (# 3). Regulatory elements were present in proximity of these breakpoints. RACE PCR studies revealed a chimeric transcript in 1/6 patient analyzed, but no fusion protein. Quantitative PCR showed a 21-58-fold over-expression of the EVIl gene in all cases analyzed. The patients showed dysplasia of at least two myeloid cell lineages in all cases; they had a low-to-normal platelet count and displayed an immature CD34+ CD117+ immunophenotype. Despite intensive chemotherapy and a median age of 43 years (range 36-59), only two patients attained a short-lived response; one patient is alive with active disease at 12 months, five died at 4-14 months. We arrived at the following conclusions: (a) the t(2;3) is a recurrent translocation having an approximate 0.5% incidence in adult AML; (b) breakpoints involve the 5' region of EVIl at 3q26, and the BCL11A, the THADA gene or other regions at 2p16.1-21; (c) cryptic deletions distal to the 3q26 breakpoint may occur in some cases; (d) the juxtaposition of the 5' region of EVIl with regulatory elements normally located on chromosome 2 brings about EVI1 overexpression; (e) clinical outcome in these cases is severe.

Recent documents dating: an approach using radiocarbon techniques.

The possibility to develop an absolute technique, independent from the paper conservation conditions, to date recent paper documents (i.e. less than 50 years old) for forensics purposes is discussed. We suggest the possibility to use the curve representing the strong increase in the atmospheric radiocarbon concentration induced in the last 50 years by nuclear weapons tests as reference to date paper documents, with a resolution down to a few months. The results obtained in the analysis of two known age documents are presented together with a first order mathematical model developed in order to take into account the contributions of the different tree rings employed in the paper production.

High-resolution accelerator-based mass spectrometry: precision, accuracy and background.

Radiocarbon accelerator mass spectrometry (AMS) is a high-sensitivity analysis technique which is nowadays widely used in many research fields such as archaeology, geology, environmental and earth sciences. We report on the features of the new high throughput accelerator mass spectrometer at the University of Lecce, Italy. The experimental apparatus is described and its general characteristics are reported in terms of measurement precision, accuracy and achievable background.

"Real world" outcome of lenalidomide plus dexamethasone in the setting of recurrent and refractory multiple myeloma: extended follow-up of a retrospective multicenter study by the "rete ematologica pugliese".

This current retrospective multicenter analysis represents, to our knowledge, the first Italian study evaluating the efficacy and toxicity profile of "lenalidomide plus dexamethasone" as salvage therapy in patients with recurrent-refractory MM in the real life contest. Our study included patients who are usually excluded from clinical trials because of unfavorable baseline characteristics. Median OS was significantly longer in patients receiving "lenalidomide plus dexamethasone" for more than 12 months compared with those who had received "lenalidomide plus dexamethasone" for a shorter interval (P<0.0001). Median OS was not affected by best response achieved (P 0.4) and age (P 0.3). Quality of response did not correlate with number of previous lines of therapy (P 0.77) and age. Higher ORRs were recorded in the patients group with relapsed MM compared to those with refractory disease, but this difference was not statistically significant (P 0.38).

Analysis of clonal antigen receptor gene rearrangements in T-cells involved with Kaposi's sarcoma.

Kaposi's sarcoma (KS) is a multifocal neoplasm of unknown origin. All forms of KS are composed of spindle-shaped cells with elongated nuclei and sheets of endothelial-like cells. The proliferation of spindle cells is accompanied by the presence of an inflammatory infiltrate composed predominantly of T-cells. It has been suggested that this infiltrate might consist of a virally stimulated clonal population of T-lymphocytes which can produce growth factors initiating and substaining the proliferation of spindle-shaped cells. In this study we analyzed for clonal T-cell receptor gama gene rearrangements the T-cell populations present in the cutaneous infiltrate of seven cases of classical Kaposi's sarcoma using a polymerase chain reaction-based approach. Our data demonstrate the lack of a significant clonal population of T-cells in the cutaneous infiltrates of KS. This finding is indicative of a reactive polyclonal response of T-cells to the spindle-shaped cells and supports the contention that spindle-shaped cells are pathogenetically the central cell type in the disease. Our data also indicate that the anti-KS T-cell response, being polyclonal in nature, does not result from clonal expansion of T-cells targeting tumor-associated antigenic peptides.

Cardiomyopathies: focus on cardiovascular magnetic resonance.

Cardiomyopathies (CMPs) are a group of often inherited diseases characterised by abnormalities and associated dysfunction of heart muscle. In the past decade, cardiovascular magnetic resonance (CMR) has emerged as a powerful tool in their assessment, providing data that are complementary to other aspects of clinical evaluation. Key advantages of CMR are three-dimensional visualisation of the heart and its relationship to thoracic structures; gold-standard quantification of cardiac volumes and function, which can safely be repeated over time (no ionising radiation is involved); and tissue characterisation to detect focal scar and fatty infiltration. This paper reviews the role of CMR in the clinical assessment of patients with CMPs.

Recombinant human insulin-like growth factor-1: a new cardiovascular disease treatment option?

The Insulin-like growth factor-1 (IGF-1) system is dynamic and complex, involving many binding proteins, binding-protein-related proteases, and receptors. It has emerged in time as a powerful defence to life processes of many cytotypes, tissues and systems. Mainly in body metabolism, diabetes and cardiovascular system, but also in brain and kidney, IGF-1 plays a key role in maintaining homeostasis, increasing progenitor cell potential, and improving physiologic performance both in rest and stress conditions. Its vasculoprotective and insulin sensitizing ability exerts a protective role on flow-metabolism coupling and organs function. Therapeutical human use of recombinant human IGF-1 (rhIGF-1) has been widely applied only in Laron syndrome, while being verified in many randomized controlled trials to improve glycemic control in type 1 and type 2 diabetes, and proposed in neurological disease such as amyotrophic lateral sclerosis, multiple sclerosis and Alzheimer disease. Sparse evidence exists moreover about rhIGF-1 use in insulin resistance, burns, catabolic and post-surgery states, acute and chronic renal failure, amyotrophic lateral and multiple sclerosis, brain injury, and immunoincompetence. Along with these data, results are available on cardiovascular benefit of administration of other growth factors, such as erythropoietin and vascular endothelial growth factor, or on cardiovascular side effects of growth factor antagonists such as trastuzumab in cancer therapy. We intended therefore to summarize in this review available human and animals evidence about rhIGF-1 effects on different systems with insights on rhIGF-1 cardiovascular effects. In view of its ability to improve flow-metabolism coupling, IGF-1 could indeed represent a new cardiovascular disease treatment option for many cardiac disorders such as ischemic heart disease and heart failure.

Moderate and severe plaque psoriasis: cost-of-illness study in Italy.

Psoriasis is a chronic inflammatory, immune-mediated skin disorder that affects 1.5-1.8 million people in Italy. The most common form of the disease is chronic plaque psoriasis, affecting about 90% of psoriasis patients, with about 20%-30% of them suffering from a moderate or severe condition. Little information is available about the economic impact of psoriasis in European countries. The primary objective of this study was to perform a cost-of-illness analysis of patients with moderate and severe plaque psoriasis in Italy. Therefore, direct, indirect costs, and intangible costs (quality of life - QoL) were assessed. In this national, multicenter, prospective, 3-month cost-of-illness study of moderate and severe plaque psoriasis, direct and indirect costs were assessed from the patient, third-party payer (National Health Service, NHS), and societal perspectives. From November 2003 to October 2004 consecutive patients were enrolled over a 1-year period, in order to minimize seasonal fluctuations in disease severity. 150 patients enrolled in 6 investigational sites in Italy, completed the study, and were eligible to be analyzed according to the study protocol. Intangible costs (QoL) were measured using SF36 and DLQI questionnaires. The mean total cost for psoriasis (average Psoriasis Area Severity Index [PASI] score 21.4), including direct and indirect items, was euro8,371.61 per patient per year. The mean cost for patients with moderate disease (PASI 20) was euro11,434.40 per year. Disease heavily affected QoL measured using SF36, and the impairment was greater in patients affected by a more severe form of disease. Moderate and severe plaque psoriasis is associated with extremely high costs, which are related to disease severity. Data from this study show that the more severe plaque psoriasis, the higher the direct and indirect costs for its management. Direct costs are higher than indirect costs; hospitalization represents the most significant item, accounting for 30% of the total expenses. QoL in moderate and severe plaque psoriasis is low compared with the population at large, confirming the high impact of plaque psoriasis on QoL. The relatively high average annual costs per patient point to the need for a more efficient and long-term control of psoriasis.

A protective role of a cholesteryl ester transfer protein gene variant towards ischaemic stroke in Sardinians.

OBJECTIVES: Cholesteryl ester transfer protein (CETP) plays a key role in the metabolism of high-density lipoprotein (HDL), a strong, inverse, independent risk factor for cardiovascular disease. We sought to investigate the relationship between a common variant of CETP gene, the Taq1 B polymorphism, that has been previously associated with CETP blood concentrations, and the risk of ischaemic stroke in a genetically homogenous population from the Sardinia island, Italy. This population has been previously shown to be a highly conservative sample. DESIGN: A total of 215 cases of ischaemic stroke and 236 controls were selected and characterized for the CETP Taq1 B polymorphism. Allele and genotype frequencies were compared amongst cases and controls. RESULTS: Age, hypertension and hypercholesterolaemia were independent risk factors for stroke in this cohort. We found that presence of the CETP Taq1 B2 allele was associated with a significantly decreased risk of ischaemic stroke when assuming a recessive mode of inheritance (OR 0.55, 95% CI = 0.34-0.90, P = 0.017). This result was confirmed by multivariate analysis, after adjustment for age, presence of hypertension and hypercholesterolaemia (OR 0.53, 95% CI = 0.32-0.88, P = 0.014). By performing separate analysis for gender we found that the effect was present in females but not in males, with a significant sex-CETP gene variant interaction for both recessive (P = 0.005) and additive (P = 0.029) modes of inheritance. CONCLUSIONS: Our data suggest that the Taq1 B2 allelic variant of the CETP gene may be associated, as a protective factor, with occurrence of ischaemic stroke. Further studies are needed to further elucidate the clinical implications of our finding.

Antibodies to HTLV-III and the lymphadenopathy syndrome in multitransfused beta-thalassemia patients.

Antibodies to HTLV-III have been investigated in 118 multitransfused beta-thalassemia patients. Thirteen patients (11.01%) were found to be positive; 3 of these 13 showed clinical and immunological signs of the lymphadenopathy syndrome. A retrospective study carried out on 65 sera has shown that at least 6 patients were negative 3 years before the present investigation. This is the first extensive study on HTLV-III infection in multitransfused beta-thalassemics. It suggests that these patients are at risk for the acquired immune deficiency syndrome and related diseases.

A variant of ProMACE-CytaBOM chemotherapy for non-Hodgkin's lymphoma with threefold higher drug dose size but identical cumulative dose intensity. A pilot study of the Italian lymphoma study group (GISL).

BACKGROUND AND OBJECTIVE: The positive results of high-dose chemotherapy followed by rescue with bone marrow progenitor cell transplantation are generally ascribed to the high dose size (DS) of the drugs given. However, a concomitant marked increase in dose intensity (DI) is always involved. With the aim of comparing the role of DS and DI in non-Hodgkin's lymphomas, a variant of Fisher's ProMACE-CytaBOM regimen was designed in which the projected cumulative drug DIs remained the same as in the original schedule but the DSs were tripled. DESIGN AND METHODS: Dosages in mg/m(2), route and days of administration were the following: cyclophosphamide 1,950 i.v. on days 1, 64; methotrexate 360 i.v. days 15, 78; vincristine 1.4 iv days 15, 78, 43, 106; etoposide 360 i.v. days 29, 92; epirubicin 120 i.v. days 29, 92; bleomycin 15 i.v. days 43, 106; cytarabine 900 i.v. days 50, 113. Thirty-six outpatients with intermediate- and high-grade non-Hodgkin's lymphomas entered the pilot study; 29 were untreated and 7 had relapse disease. Clinical stage was I in 1 patient, II in 7, III in 5 and IV in 23; 10 had B symptoms; the IPI score was 0-2 in 29 cases and > or =3 in the remaining 7. RESULTS: Of the 29 previously untreated patients, 16 achieved complete remission, 8 partial remission, 4 developed progressive disease and 1 was withdrawn early from the study because of acute viral hepatitis; subsequently 4 relapsed and 3 died (2 of disease progression, 1 of causes unrelated to the disease). In the pre-treated group 3 patients obtained complete remission, 2 partial remission and in 1 patient the disease progressed; 3 of these pre-treated patients died (1 of progressive disease, 1 of a new relapse, 1 of myocardial infarction during therapy). With a 20-month median follow-up, the 30-month overall and relapse-free survival were 0.58 and 0.70, respectively. G-CSF was administered to all but 2 patients, with median delivery throughout the whole regimen of 8, 400 microg per patient. Actual cumulative DI was 0.82+/-0.11. Grade 3-4 hematologic toxicity consisted of anemia in 3 cases, of leukopenia in 8 and of thrombocytopenia in 2; the same grade of non-hematologic toxicity involved the liver in 2 cases, the heart in 1 (the above mentioned death), the digestive mucosa in 2 and the peripheral nerves in 1 patient. INTERPRETATION AND CONCLUSIONS: The iso-DI sequential variant of the ProMACE-CytaBOM regimen can be considered feasibile, relatively non-toxic, and can be given on an out-patient basis. Limited use of G-CSF is required (about 3 vials after each drug administration). Thus, a randomized trial with the original ProMACE-CytaBOM regimen can be designed.