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Objective: To identify the role of the family's socio-economic and clinical characteristics on metabolic control in children and adolescents with type 1 diabetes., Methods: In this cross-sectional, multicentre study, 768 subjects with type 1 diabetes under 18 years of age were consecutively recruited from January 2008 to February 2009. Target condition was considered for HbA 1c values <7.5% (<58 mmol/mol). A multiple correspondence analysis (MCA) was performed to analyze the association between the socio-economic and clinical characteristics of the participants. A logistic regression analysis was performed to identify factors associated with the subjects metabolic control. In both analyses, the family's socio-economic status was represented, measured by the Hollingshead Four-Factor Index of Social Status (SES) or by parental years of education., Results: A total of 28.1% of subjects reached target HbA1c values. The MCA identified a strong association between at-target condition and several factors: high levels of SES or high levels of parental education, the use of the carbohydrate counting system, the use of insulin pumps, the use of the insulin delivery system over a short period of time, a normal body mass index. The logistic regression analysis showed that SES and the mother's years of education were significantly associated with the target condition [odds ratio (OR): 1.01, 95% confidence interval (CI): 1.01-1.03, p = 0.029; OR: 1.05, 95% CI: 1.01-1.10, p = 0.027, respectively)., Conclusions: Personal, clinical, and family characteristics were found to be associated with HbA 1c target. Their identification can be crucial in addressing strategies to optimize metabolic control and improve diabetes management., (© 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

This longitudinal population-based study analyses the frequency of diabetic ketoacidosis (DKA) at type 1 diabetes diagnosis in Italian children under 15 years of age, during 2004-2013. DKA was defined as absent (pH ≥ 7.30), mild/moderate (7.1 ≤ pH < 7.30) and severe (pH < 7.1). Two multiple logistic regression models were used to evaluate the time trend of DKA frequency considered as present versus absent and severe versus absent, adjusted for gender, age group and geographical area of residence at diagnosis. Overall, 9,040 cases were ascertained. DKA frequency was 40.3% (95%CI: 39.3-41.4%), with 29.1% and 11.2% for mild/moderate and severe DKA, respectively. Severe DKA increased significantly during the period (OR = 1.03, 95%CI: 1.003-1.05). Younger-age children and children living in Southern Italy compared to Central Italy were at significantly higher risk of DKA and severe DKA. Family history of type 1 diabetes and residence in Sardinia compared to Central Italy were significantly associated with a lower probability of DKA and severe DKA. The high frequency of ketoacidosis in Italy over time and high variability among age groups and geographical area of residence, strongly suggests a continuing need for nationwide healthcare strategies to increase awareness of early detection of diabetes.

Background: According to current guidelines, pancreatic cancer patients should be strictly selected for surgery, either palliative or resective., Methods: Population-based study, including all patients undergoing surgery for pancreatic cancer in Italy between 2010 and 2012. Hospitals were divided into five volume groups (quintiles), to search for differences among volume categories., Results: There were 544 hospitals performing 10 936 pancreatic cancer operations. The probability of undergoing palliative/explorative surgery was inversely related to volume, being 24.4% in very high-volume hospitals and 62.5% in very low-volume centres (adjusted OR 5.175). Contrarily, the resection rate in patients without metastases decreased from 86.9% to 46.1% (adjusted OR 7.429). As for resections, the mortality of non-resective surgery was inversely related to volume (p < 0.001). Surprisingly, mortality of non-resective surgery was higher than that for resections (8.2% vs. 6.7%; p < 0.01). Approximately 9% of all resections were performed on patients with distant metastases, irrespective of hospital volume group. The excess cost for the National Health System from surgery overuse was estimated at 12.5 million euro., Discussion: Discrepancies between guidelines on pancreatic cancer treatment and surgical practice were observed. An overuse of surgery was detected, with serious clinical and economic consequences., (Copyright © 2016 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.)

Osteoporosis represents a serious health problem worldwide associated with an increased risk of fractures and mortality. Nutrition should form part of bone disease prevention strategies, especially in the light of the population ageing and the diet effect on bone health. Thus the study aimed at verifying whether 1 year of oral supplementation with either extra virgin olive oil (VOO) enriched with vitamins D3, K1 and B6 (VitVOO) or VOO used as placebo (PlaVOO) is able to modify some bone turnover and oxidative stress markers. Bone mineral density (BMD) was assessed in 60 healthy post-menopausal women together with the bone vitamin K status by measuring undercarboxylated osteocalcine (ucOC) plasma levels, the ratio between ucOC and carboxylated osteocalcine (UCR) and the relations with oxidative stress markers. After 1 year (T 1), subjects taking VitVOO showed lower ucOC levels than those taking PlaVOO; the same trend was found for UCR. As far as BMD is concerned, a significant increase in T-score at T 1 in VitVOO subjects compared to PlaVOO was found. All oxidative stress markers as thiobarbituric acid reactive substances, lipid hydroperoxides and conjugated dienes showed a significant reduction after VitVOO supplementation, whilst plasma total antioxidant capacity values was significantly increased in VitVOO group compared to PlaVOO group at T 1. It might be suggested that the use of VitVOO in the diet of post-menopausal women could represent a proper tool for bone protection and a useful strategy against oxidative stress and related diseases, thus confirming the antioxidant role played by the added vitamins.

Unlabelled: Bisphosphonate treatment is used to prevent bone fractures. A controversial association of bisphosphonate use and risk of atrial fibrillation has been reported. In our study, current alendronate users were associated with a higher risk of atrial fibrillation as compared with those who had stopped bisphosphonate (BP) therapy for more than 1 year., Introduction: Bisphosphonates are widely used to prevent bone fractures. Controversial findings regarding the association between bisphosphonate use and the risk of atrial fibrillation (AF) have been reported. The aim of this study was to evaluate the risk of AF in association with BP exposure., Methods: We performed a nested case-control study using the databases of drug-dispensing and hospital discharge diagnoses from five Italian regions. The data cover a period ranging from July 1, 2003 to December 31, 2006. The study population comprised new users of bisphosphonates aged 55 years and older. Patients were followed from the first BP prescription until an occurrence of an AF diagnosis (index date, i.e., ID), cancer, death, or the end of the study period, whichever came first. For the risk estimation, any AF case was matched by age and sex to up to 10 controls from the same source population. A conditional logistic regression was performed to obtain the odds ratio with 95% confidence intervals (CI). The BP exposure was classified into current (<90 days prior to ID), recent (91-180), past (181-364), and distant past (≥365) use, with the latter category being used as a reference point. A subgroup analysis by individual BP was then carried out., Results: In comparison with distant past users of BP, current users of BP showed an almost twofold increased risk of AF: odds ratio (OR) = 1.78 and 95% CI = 1.46-2.16. Specifically, alendronate users were mostly associated with AF as compared with distant past use of BP (OR, 1.97; 95% CI, 1.59-2.43)., Conclusion: In our nested case-control study, current users of BP are associated with a higher risk of atrial fibrillation as compared with those who had stopped BP treatment for more than 1 year.

In Italy, ICD-9-CM is currently used for coding health conditions at hospital discharge, but ICD-10 is being introduced thanks to the IT-DRG Project. In this project, one needed component is a set of transcoding rules and associated tools for easing coders work in the transition. The present paper illustrates design and development of those transcoding rules, and their preliminary testing on a subset of Italian hospital discharge data.

Background: In the last decade, perforator flaps have been introduced for the treatment of pressure ulcers as alternative to the more popular myocutaneous local flaps. We reviewed our single-team 11-year experience in order to define whether real advantages could be achieved., Methods: We analyzed 143 patients undergoing perforator flap surgery for a single late-stage pressure sore. All patients underwent the same protocol treatment. Data regarding associated pathologies, demographics, complications, healing, and hospitalization times were collected., Results: Ninety-three percent of 143 patients were white Caucasian, and 61% were men, with median age of 51 years. Of 143 stage 4 ulcers, 46.2% were ischial, 42.7% sacral, and 11.2% trochanteric. The most common diagnosis was traumatic paraplegia/tetraplegia (74.9%); no significant difference was found in diagnosis distribution and in ulcer location between recurrent and nonrecurrent patients. We performed 44 S-GAP, 78 I-GAP, 3 PFAP-am, and 18 PFAP-1 flaps. At 2 years' follow-up, the overall recurrence was 22.4% and new ulcer occurrence was 4.2%. Mean hospital stay was 16 days. The overall complication percentage was 22.4%, mostly due to suture-line dehiscence (14%) and distal flap necrosis (6.3%). PFAP flaps had a significant higher risk of developing recurrence than I-GAP flaps. The recurrence risk was significantly higher for subjects suffering from coronary artery disease., Conclusions: Late-stage pressure sore treatment with local perforator flaps can achieve reliable long-term outcomes in terms of recurrences and complications. When compared to previously published data, perforator flaps surgery decreased postoperative hospital stay (by an average of nearly 1 week), reoperations (5.6%), and occurrences.

Background: Outside the USA, Agency for Healthcare Research and Quality (AHRQ) prevention quality indicators (PQIs) have been used to compare the quality of primary care services only at a national or regional level. However, in several national health systems, primary care is not directly managed by the regions but is in charge of smaller territorial entities. We evaluated whether PQIs might be used to compare the performance of local providers such as Italian local health authorities (LHAs) and health districts., Methods: We analysed the hospital discharge abstracts of 44 LHAs (and 11 health districts) of five Italian regions (including ≈18 million residents) in 2008-10. Age-standardized PQI rates were computed following AHRQ specifications. Potential predictors were investigated using multilevel modelling., Results: We analysed 11 470 722 hospitalizations. The overall rates of preventable hospitalizations (composite PQI 90) were 1012, 889 and 988 (×100 000 inhabitants) in 2008, 2009 and 2010, respectively. Composite PQIs were able to differentiate LHAs and health districts and showed small variation in the performance ranking over years., Conclusion: Although further research is required, our findings support the use of composite PQIs to evaluate the performance of relatively small primary health care providers (50 000-60 000 enrollees) in countries with universal health care coverage. Achieving high precision may be crucial for a structured quality assessment system to align hospitalization rate indicators with measures of other contexts of care (cost, clinical management, satisfaction/experience) that are typically computed at a local level., (© The Author 2013. Published by Oxford University Press on behalf of the European Public Health Association.)

Aim: The purpose of this study was to determine the influence of the place of living on periodontal status of 62 Down's syndrome (DS) subjects resident at home (DSH) or in specialized institutes (DSI) in central-eastern Italy., Methods: The demographic characteristics of the subjects and the periodontal variables were evaluated according to their living conditions. Descriptive analyses were conducted by stratifying subjects into three age groups (0-13; 14-22; >23 years), using medians and 25th-75th percentiles to summarized data. Comparisons between DSH and DSI subjects were performed using Wilcoxon rank sum test. The effect of demographic and clinical variables on periodontal status was evaluated by means of quantile regression analysis., Results: No significant differences resulted between DSH and DSI patients, when compared for gender, age and mental retardation. No significant differences were found in the periodontal variables for the subjects with 0-13 years, while DSI subjects between 14 and 22 years of age presented higher levels of plaque index, probing depth, clinical attachment loss and a lower number of surviving teeth compared to DSH subjects. When DSI and DSH groups ≥ 23 years of age were compared, no differences were observed in the periodontal conditions except for PI and the number of surviving teeth. Age, body mass index and severe mental retardation were found to be significant predictors of periodontal conditions., Conclusions: Institutionalization has a negative effect on surviving teeth number of Down's syndrome subjects. Furthermore, the home care seems to produce benefits on the periodontal conditions of DSH 14-22 years of age., (© 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

The scarcity of human and structural resources for specialized gastroenterology care is a problem in many Western countries. Data regarding the resources for Italian Gastroenterology, so far lacking, have been thus searched and evaluated. Based on an agreement protocol between the Italian Association of Hospital Gastroenterologists and Endoscopists (AIGO) and the Ministry of Health, national data regarding all Institutions providing gastroenterological care were analysed. Hospital beds in Gastroenterology units are presented by region, regimen of stay and per million inhabitants as of January 2011. Association of Hospital Gastroenterologists and Endoscopists also performed a survey of gastroenterology units in all Italian regions regarding number of ordinary/day hospital beds and the number of staff gastroenterologists. The Ministry data showed a total of 174 Gastronterology Units in Italy, a total of 2062 hospital beds for the discipline, for a proportion of 34.2 beds per million inhabitants. The Association of Hospital Gastroenterologists and Endoscopists survey showed a total of 1425 gastroenterologists in Italy. These data should represent a key reference for appropriate planning of specialized care for digestive diseases., (Copyright © 2014 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

A multi-centre, observational, cross-sectional study was carried out to determine whether the health-related quality of life (HRQOL) of adolescents with type 1 diabetes is affected by different insulin treatment systems, and which features of HRQOL are impacted by the respective insulin treatment. The study regarded 577 adolescents, aged 10-17 years, with type 1 diabetes treated with continuous subcutaneous insulin infusion (CSII) (n = 306) or multiple daily injections (MDI) (n = 271). The Insulin Delivery System Rating Questionnaire was validated in Italian and was self-completed by the subjects during a routine visit to the centres. Subjects were compared following the domains of the questionnaire. Good HRQOL was seen in subjects treated with either MDI or CSII. Significant differences were not found in the domains for general diabetes, including diabetes worries, social burden and psychological well-being. Multiple quantile regression analysis showed that CSII confers significant advantages in terms of HRQOL with improvements in treatment satisfaction, perceived clinical efficacy and reduction in treatment interference with daily activities. This favourable impact was more evident in subjects reporting lower HRQOL scores, suggesting that CSII may be especially useful for individuals perceiving a poor HRQOL. Analysis of the domains indicated that CSII was associated with a higher HRQOL than MDI. Life-course HRQOL evaluation using a standardised questionnaire can ensure better chronic disease management. This is particularly important when providing individualised care for adolescents, as they become increasingly responsible for managing their diabetes.

In this study of drying water-based nanofluid droplets, we report the influence of surface functional groups and substrate surface energies on crack formation and dry-out shape. These two key parameters are investigated by allowing nanofluids with several functional groups grafted on polystyrene nanoparticle surfaces to dry on various substrates. These experiments result in a variety of regular crack patterns with identical nanoparticle diameter, material, concentration, and drying conditions. We demonstrate that, despite the various patterns observed, the crack spacing/deposit height ratio is constant for similar substrate surface energies and linearly increases with this parameter. Moreover, this study shows that the crack shape is strongly influenced by surface functional groups as a result of particle interactions (depending on the particle surface potentials) and compaction during solvent evaporation.

Bone is the most challenging tissue for DNA extraction and purification. Expensive commercial kits and specific equipments are often used in forensic and anthropology laboratories towards that goal. We present here an integrated procedure that gives satisfactory results for DNA preparation from fresh, ancient or weathered bones. Extraction is performed under simple but efficient vacuum-controlled conditions that greatly limit the risks of cross-contaminations. The whole process has been designed to minimize the need for expensive equipment and chemicals, and to be compatible with any molecular biology laboratory. In addition, no toxic reagents are necessary and the procedure is straightforward. Combined with quantitative polymerase chain reaction (qPCR), this method allows species identification and sex determination from subcellular amount of DNA (1-5 pg). In addition, enough DNA is generally obtained for human DNA profiling if necessary. The whole procedure from bone treatment to the final qPCR results takes less than 48 hours. This procedure should allow any laboratory with standard molecular biology equipment and expertise to perform bone DNA characterization whenever necessary.

Summary: There is evidence that the use oral bisphosphonates can lead to osteronecrosis of the jaws (ONJ). Although the occurrence of ONJ appears rare among oral bisphosphonates (BPs) users, it is important to know that it exists and can be opportunely minimized., Introduction: The purpose of this study is to evaluate the association between BPs prescribed for the secondary prevention of osteoporotic fractures and the occurrence of ONJ., Methods: An Italian record linkage claims database with a target population of around 18 million individuals (6 million over 55 years of age) constituted the data source. We conducted a nested case-control study within a cohort of individuals aged 55+ years old, who were discharged from hospitals with a primary diagnosis of incident osteoporotic fracture. The date related to the discharge diagnosis of ONJ was the index date. Conditional logistic regression for matched data was fitted to estimate the odds ratio (OR) along with 95 % confidence intervals (95 % CI) for the likely association between use of BPs and the risk of ONJ., Results: Any one of the 61 ascertained cases of ONJ (incidence rate, 36.6 per 100,000 person-years) was matched to 20 controls for a total of 1120 controls. When the exposure to BPs was modeled according to recency (i.e., exposure time window prior to the index date) of use, the adjusted OR (95 % CI) for current users was 2.8 (1.3-5.9) against never users. The cumulative use of BPs has shown to increase the incidence of ONJ among patients with primary osteoporotic fractures, although not statistically significant risk has been observed., Conclusions: Although the risk of BP-related ONJ appears low in non-oncological indications, it is important to be aware that it exists and to know how it may be predicted and possibly minimized.

Aims: Several studies confirmed the growing rate of Type 1 diabetes mellitus in childhood coinciding with increasing diagnosis of viral infections. A study investigating the incidence of Type 1 diabetes during 1996-1997 showed a higher notification of viral infections in the Pavia District. The aim was to confirm these results., Methods: This study evaluated the relationship between new cases of Type 1 diabetes and those of measles, mumps and rubella in 1996-2001, analysing data of newly-diagnosed Type 1 diabetes children, aged 0-14 years and enrolled into the RIDI (Italian Insulin-dependent Diabetes Registry) during the same years. Measles, rubella and mumps rates were calculated using as denominator the estimated 'population at risk', represented by the number of 0- to 14 year-old subjects who did not undergo the MMR (measles, mumps and rubella) vaccination. In order to investigate the association between Type 1 diabetes incidence and measles, rubella and mumps respectively, Spearman's rank correlation was used., Results: The analysis of the whole Registries data did not at first show any statistical significance between age-standardized Type 1 diabetes incidence density and estimated rates of measles, mumps and rubella notifications. Excluding data from Sardinia Registry, a significant association was observed between Type 1 diabetes incidence and mumps (P = 0.034) and rubella (P = 0.014), respectively, while there was no statistical significance between the incidence of measles cases and diabetes rates (P = 0.269)., Conclusions: According to our findings, mumps and rubella viral infections are associated with the onset of Type 1 diabetes. The statistical significance observed after exclusion of the Sardinian data suggests that other environmental factors may operate over populations with different genetic susceptibility., (© 2011 The Authors. Diabetic Medicine © 2011 Diabetes UK.)

Down syndrome (DS) is a chromosomal abnormality (trisomy 21) associated with a complex phenotype. Oxidative stress is known to play a major role in this pathology both due to genetic and epigenetic factors, suggesting that oxidative imbalance contributes to the clinical manifestation of DS. In particular, the implications of oxidative DNA damage in Down syndrome has been linked with neurodegeneration. Here we report the results of a double blind controlled trial aimed at investigating the protective effect of Coenzyme Q(10) on DNA oxidation in this clinical setting using the single cell gel electrophoresis technique., (Copyright © 2009 Elsevier Inc. All rights reserved.)

Shift-work, particularly night-work, interferes with the physiological circadian rhythm and has the potential to induce psycho-physiological disturbances. A nurse population was investigated to establish whether shift-work can induce changes in a number of immune variables. Lymphocyte immunophenotype and proliferative response, NK cytotoxicity, cytokines and cortisol were determined in 68 shift-working and 28 daytime nurses at baseline and at 12 months. None of the variables studied differed significantly between shift and daytime workers, either at baseline or at 12 months, except IL-1β and TNF-α, which were significantly higher among daytime nurses at baseline, but not at follow-up. No effect of shift-work on immune variable and cortisol levels was seen at 12 months after adjustment for baseline values and job seniority. The specific work schedule as well as job type likely influenced our results, suggesting that rotational shift-work does not necessarily affect the immune system adversely. The immune changes reported by other studies in shift-workers should not be generalized.

Objective: To investigate age-period-cohort effects on the temporal trend of type 1 diabetes in children age 0-14 years in Italian registries., Research Design and Methods: This report is based on 5,180 incident cases in the period 1990-2003 from the Registry for Type 1 Diabetes Mellitus in Italy (RIDI). Multilevel (random intercept) Poisson regression models were used to model the effects of sex, age, calendar time, and birth cohorts on temporal trends, taking into account the registry-level variance component., Results: The incidence rate was 12.26 per 100,000 person-years and significantly higher in boys (13.13 [95% CI 12.66-13.62]) than in girls (11.35 [10.90-11.82]). Large geographical variations in incidence within Italy were evident; incidence was highest in Sardinia, intermediate in Central-Southern Italy, and high in Northern Italy, particularly in the Trento Province, where the incidence rate was 18.67 per 100,000 person-years. An increasing temporal trend was evident (2.94% per year [95% CI 2.22-3.67]). With respect to the calendar period 1990-1992, the incidence rates increased linearly by 15, 27, 35, and 40% in the following time periods (P for trend < 0.001). With respect to the 1987-1993 birth cohort, the incidence rate ratio increased approximately linearly from 0.63 (95% CI 0.54-0.73) in the 1975-1981 cohort to 1.38 (1.06-1.80) in the 1999-2003 cohort. The best model, however, included sex, age, and a linear time trend (drift)., Conclusions: Large geographical variations and an increasing temporal trend in diabetes incidence are evident among type 1 diabetic children in Italy. Age-period-cohort analysis shows that the variation over time has a linear component that cannot be ascribed to either the calendar period or the birth cohort.

Goals of Work: The way to inform cancer patients varies widely among different countries. In most Mediterranean countries, the traditional approach has been of partial disclosure of the truth. The intent of our work was to find if the attitude in Italy has changed in recent years and if differences still exist among different geographical regions in our country. Both patients' and physicians' attitudes vary in Italy depending on geographical area. In the South, the focus is on traditional values and full involvement of patients' family, with limited communication to (and limited autonomy of) the patient. Such attitude is less pronounced in Central Italy, whereas the North is more oriented to open communication and full decisional autonomy of the patient., Materials and Methods: Approximately 600 consecutive patients in three different centres in Northern, Central and Southern Italy (respectively, Udine, Ancona and Catanzaro) were asked to answer a 26-item questionnaire on communication aspects to investigate the quality of the information given and potential differences between geographical areas., Results: Questionnaires were completed by 587 patients (median age 60 years, 57% women), mainly with gastrointestinal (32%) or breast cancer (30%). About 370 patients (63%) had active disease at time of interview. A high proportion of patients were correctly informed on diagnosis (86%) and therapy (84%). On the contrary, patients fully aware of their prognosis were only about 43%. Nevertheless, most patients (60%) stated they were completely satisfied with the information received. There were differences between geographical areas on various information aspects, with patients from Southern Italy being, in general, less informed., Conclusions: In Italy, the cultural attitude towards communication in oncology is changing on both the physician and the patient side. There are still significant geographical differences, but there is a general trend suggesting improved awareness about diagnosis and treatment, with the notable exception of prognosis.

Despite evidence that cardiac troponin I (cTnI) identifies patients with advanced heart failure (HF) at risk of death, data on heterogeneous HF populations are scarce. Our purpose was to verify and analyze the prognostic role of cTnI in acute HF patients admitted to the emergency department. This was an observational longitudinal prospective study carried out in an urban hospital. We studied 99 patients discharged from the department between March and December 2002 with a HF diagnosis and samples of cTnI. Patients with acute coronary syndromes, myocarditis or renal failure were excluded. The main outcome was death from any cause. The detection level of the cTnI assay was 0.05 ng/ml. cTnI was detected in 45.5% of HF patients. These patients had a higher NYHA class (P<0.001) at initial presentation and longer hospitalization (P=0.004) than cTnI-negative patients. Nineteen deaths occurred during the study: 17 for HF and 2 for acute coronary syndrome. Finally, detectable cTnI was associated with increased mortality risk (RR 4.7; 95% CI 1.3-17.1; P=0.021) also after adjustment for other adverse prognosis factors (age, NYHA class and presence of relapses). Our HF cTnI-positive patients had a worse clinical presentation and longer hospitalization. cTnI is a significant independent predictor of death and of longer hospitalization. It could be used for the early identification of HF patients at an increased risk of death in the long term, and of longer hospitalization. Thus, cTnI can aid decision-making and clinical management in the emergency department.

Neural tube defects (NTDs) have a complex and imperfectly understood etiology, in which both genetic and environmental factors might be involved. The aim of the study was to describe an excess of cases of NTDs in a small area in central Italy. Over a 2-wk period in autumn 2002, three diagnoses of anencephaly were made in a 2773-km(2) area. As a consequence of these events, information on known risk factors as well as data on environmental changes, or epidemics of infectious diseases, in 2002-2004, were collected. The NTD rate was estimated for 10,000 births (live and stillborn) in this area. The 95% confidence intervals of rates were estimated assuming Poisson distribution of cases. Six cases of NTD were observed, with an NTD prevalence rate of 18.5 per 10,000 births (95% CI 17.0, 20.12). No evidence of known risk factors was reported. During summer 2002, the local service for environmental surveillance observed that the threshold level of drinking-water bacterial contamination had been exceeded, which probably resulted in an adjustment in the amount of chlorine added. The major difficulty in making hypotheses regarding the causes of birth defects is linking environmental risk factors exposure to fetal outcome. The prompt gathering of data may be essential. Thus, we emphasize the need for the activation of a population-based congenital malformation registry in order to achieve a deeper understanding of these events etiology.

Aim: Bioelectrical impedance analysis (BIA) can monitor diabetics suffering from the frequently occurring state of hyperglycemia, as this can cause alterations in the water distribution in the body. The aim of the present study was to evaluate the relationship between the composition of the body and the diabetic disease during decompensation through the impedanciometric analysis in diabetic patients of type 1 and type 2 and to understand the possible alterations of water distribution., Methods: The study was carried out with 52 subjects (8 males, 44 females), average years 46.5; 15 of them were diabetic, 7 characterised by diabetes of type 1 and 8 by diabetes of type 2. All the patients recruited were in poor metabolic control (glycosylated hemoglobin [HbAlc] >6%). In order to avoid any errors during the evaluation ofa water distribution in the body, patients suffering from hypertension were excluded from the recruitment process. All patients underwent impedanciometry total body using the HUMAN IM SCAN apparatus multifrequency., Results: Through the application of BIA, our work has shown how diabetic patients have a lower quantity of extracellular water (ECW) and exchangeable potassium (Ke) in the body, as compared to non-diabetic patients. The causes of this could be the alteration of the plasmic osmolarity and the possible reduction of the mass of metabolically active cells. Further-more a relationship between fructosamine in the blood and Ke has been found and, alongside another, more significant, between HbA1c and Ke. According to the opinions of the authors, such results are worthy for further studies in order to obtain a greater accuracy in the evaluation of the amount of Ke and an alternative in estimation of metabolic control.

We conducted a psychological assessment during oncogenetic counseling for hereditary breast/ovarian cancer. Anxiety and depression were assessed with the HAD scale, and family functioning and satisfaction with FACES III. HAD was administered at baseline (t(1)), at risk communication (t(2)), at genetic test result communication, or at first surveillance in not tested subjects (t(3)); FACES III was administered at baseline only. We analysed a total of 185 questionnaires administered to the 37 subjects studied. Although not pathological, distress was significantly higher at t(2) and t(3) (p = 0.027 and p = 0.039, respectively). Health and marital status were significantly associated with distress. In a disease-free condition, anxiety was higher (p = 0.027) at t(2), and for single status, depression increased from t(1) to t(2) (p = 0.026). Families were perceived to be well functioning, and subjects were satisfied with their families. The data collected in this analysis could help to improve the quality of oncogenetic counselling in clinical practice.

Background: Treatment of celiac disease (CD) is based on the avoidance of gluten-containing food. However, it is not known whether trace amounts of gluten are harmful to treated patients., Objective: The objective was to establish the safety threshold of prolonged exposure to trace amounts of gluten (ie, contaminating gluten)., Design: This was a multicenter, double-blind, placebo-controlled, randomized trial in 49 adults with biopsy-proven CD who were being treated with a gluten-free diet (GFD) for > or =2 y. The background daily gluten intake was maintained at < 5 mg. After a baseline evaluation (t0), patients were assigned to ingest daily for 90 d a capsule containing 0, 10, or 50 mg gluten. Clinical, serologic, and histologic evaluations of the small intestine were performed at t0 and after the gluten microchallenge (t1)., Results: At t0, the median villous height/crypt depth (Vh/Cd) in the small-intestinal mucosa was significantly lower and the intraepithelial lymphocyte (IEL) count (x 100 enterocytes) significantly higher in the CD patients (Vh/Cd: 2.20; 95% CI: 2.11, 2.89; IEL: 27; 95% CI: 23, 34) than in 20 non-CD control subjects (Vh/Cd: 2.87; 95% CI: 2.50, 3.09; IEL: 22; 95% CI: 18, 24). One patient (challenged with 10 mg gluten) developed a clinical relapse. At t(1), the percentage change in Vh/Cd was 9% (95% CI: 3%, 15%) in the placebo group (n = 13), -1% (-18%, 68%) in the 10-mg group (n = 13), and -20% (-22%, -13%) in the 50-mg group (n = 13). No significant differences in the IEL count were found between the 3 groups., Conclusions: The ingestion of contaminating gluten should be kept lower than 50 mg/d in the treatment of CD.

The objective was to assess the knowledge about ischaemic stroke among selected groups of persons at high risk for stroke. Outpatients referred to 3 hospital ultrasound departments in the Marche Region (Italy) were asked to answer a questionnaire. Data were collected on: (1) demographic characteristics; (2) risk profile determined using Coppola et al.'s scoring system; (3) knowledge about symptoms, risk factors, part of the body injured and best referral option for stroke. Of the 352 respondents, around 52% were unable to report even one warning symptom of stroke, while 58.4% of participants at increased risk did not know any risk factors. Only 64.5% identified the brain as the part of the body injured by stroke. Only 59.4% considered the Emergency Department as the best referral option in the event of stroke. This study confirms poor knowledge about stroke in our study population, particularly in subjects with increased stroke risk.

Purpose: Evaluation of morphologic risk factors for posttraumatic epilepsy (PTE) by using brain magnetic resonance imaging (MRI) in serial assessments

Objective: The aim of this study was to evaluate patient and tumor characteristics in 102 patients with unknown primary tumors (UPT) prospectively treated with a combination of carboplatin, doxorubicin, and etoposide, to identify clinical variables predictive of response and survival., Patients and Methods: The association between clinical characteristics and outcome was evaluated by univariate and multivariate analysis: chi(2) test and logistic regression analysis were used to study variables predictive of response, and survival analysis, comparison of survival curves and Cox multiple regression analysis to study variables predictive of survival., Results: We obtained 26.5% objective responses (95% confidence interval: 18.2-36.1%) and a median survival of 9 months (95% confidence interval: 7-11 months). Several variables were associated with response to treatment and survival at univariate analysis. At multivariate analysis the number of tumor sites, bone/visceral involvement and epithelial tumor markers were significantly predictive of response; presence of pain, serum alkaline phosphatase, carboplatin AUC and response to treatment were significantly associated with survival., Conclusions: The identification of variables that can predict prognosis and response to treatment in patients with UPT may be useful to offer aggressive treatment to sensitive subsets of patients and provide therapeutic alternatives to those with a low probability of benefiting from standard treatment. In our patients the use of carboplatin AUC higher than 6 and response to treatment were the most important factors associated with prognosis, together with presence of pain and serum alkaline phosphatase. However, larger series and identification of new disease markers are necessary to better define predictive and prognostic variables in UPT patients.

Diabetic microangiopathy produces widespread small vessel impairment which particularly affects renal glomeruli functions. Microalbuminuria is the earliest marker of microangiopathic kidney disease and has also recently been recognised as a marker of macroangiopathic cardiovascular involvement. To determine correlations between daily microalbuminuria, local microangiopathic kidney damage, systemic macroangiopathic involvement and functional brain microcirculation, 70 Type 2 diabetic subjects who were diagnosed more than 5 years ago underwent carotid (to determine index of macro- and microangiopathy) and interlobar kidney artery color Doppler (to determine microangiopathic involvement), transcranial Doppler (to determine alterations in brain vasomotor reserve), and evaluation of daily albumin excretion rate. All the indices of microcirculatory involvement in the kidney, brain and small vessels downstream-from the carotid arteries were closely related (for all p<0.001) but never correlated with the macroangiopathy index. Daily microalbuminuria correlated with all the micro- (p<0.0001) and macroangiopathic (p<0.005) Doppler indices. These findings confirm that microangiopathy is the main cause of the diabetic increase in the albumin excretion rate and support the view that microalbuminuria can be considered a powerful biomarker of widespread macroangiopathy. Our results suggest microalbuminuria may also identify cerebrovascular diabetic involvement, as it predicts both macroangiopathic carotid alteration and microvascular brain impairment.

Objective: The Registry for Type 1 Diabetes Mellitus in Italy (RIDI) Study Group was established to coordinate the registries of type 1 diabetes in Italy. This report is based on 3,606 children younger than 15 years diagnosed with type 1 diabetes and prospectively registered during 1990-1999 by nine centers, covering >35% of the Italian population., Research Design and Methods: Registries were pooled in four geographic macro-areas: north, central, south, and insular. The completeness of registration was assessed by the capture-recapture method. Poisson regression analysis was used to evaluate temporal trend in incidence., Results: Large variations in incidence were confirmed not only between Sardegna and the mainland but also among peninsular areas. In Sardegna, there was an excess of boys (the boy-to-girl incidence ratio was 1.4). The overall incidence showed average increases of 3.6% (P <0.001) and 3.7% (P <0.001) per year in peninsular Italy and in Sardegna, respectively. Significant increases in incidence rates were found in boys aged 10-14 years (6.7%, 95% CI 0.5-13.3) and in girls aged 5-9 years (6.6%, 0.5-13.1) living in the southern area. The incidence rate also increased in boys aged 10-14 years (5.0%, 0.3-10) and in girls aged 0-4 years (4.9%, 0.8-9.1) living in Sardegna., Conclusions: Italy is a country with large geographical variations in incidence rates of type 1 diabetes. However, the rates are evenly increasing both in the mainland and Sardegna, suggesting that similar environmental factors are operating over populations that have different genetic backgrounds.

To investigate the effects of posaconazole (POS) and amphotericin B (AMB) combination therapy in cryptococcal infection, we established an experimental model of systemic cryptococcosis in CD1 mice by intravenous injection of three distinct clinical isolates of Cryptococcus neoformans. Therapy was started 24 h after the infection and continued for 10 consecutive days. POS was given at 3 and 10 mg/kg of body weight/day, while AMB was given at 0.3 mg/kg/day. Combination therapy consisted of POS given at a low (combo 3) or at a high (combo 10) dose plus AMB. Survival studies showed that combo 3 was significantly more effective than POS at 3 mg/kg for two isolates tested (P value, < or = 0.001), while combo 10 was significantly more effective than POS at 10 mg/kg for all three isolates (P values ranging from <0.001 to 0.005). However, neither combination regimen was more effective than AMB alone. For two isolates, combination therapy was significantly more effective than each single drug at reducing the fungal burden in the brain (P values ranging from 0.001 to 0.015) but not in the lungs. This study demonstrates that the major impact of POS and AMB combination therapy is on brain fungal burden rather than on survival.

The aim of this study was to assess the activity and toxicity of a platinum-based treatment on a group of patients with unknown primary tumours (UPTs). Patients with a diagnosis of UPT underwent a standard diagnostic procedure. Treatment was started within 2 weeks from diagnosis and consisted of carboplatin 400 mg m(-2) day 1, doxorubicin 50 mg m(-2) day 1, etoposide 100 mg m(-2) days 1-3, every 21 days. Response was evaluated after three courses and treatment continued in case of objective response (OR) or symptom control. A total of 102 patients were eligible. The median age was 59 years, sex male/female 54/48, histology was mainly adenocarcinoma or poorly differentiated carcinoma. Nodes, bone, liver and lung were the most frequently involved sites. In all, 79 patients received at least three courses of treatment; 26 patients received six courses or more. Six complete responses and 21 partial responses were observed, for a total of 27 of 102 ORs or 26.5% (95% confidence interval 18.2-36.1%). The median survival was 9 months and median progression-free survival was 4 months. Toxicity was moderate to severe, with 57.8% of patients experiencing grade III-IV haematological toxicity, mainly leucopenia. The regimen employed has shown activity in tumours of unknown primary site, but was associated with significant toxicity. Such toxicity may be considered unjustified, given the large proportion of patients with tumours not likely to respond. Efforts should therefore be addressed to identify predictors of response to chemotherapy, thus limiting aggressive treatment to those patients who could benefit from it.

The C(-344)T promoter polymorphism of the human aldosterone synthase (CYP11B2) gene has been associated with hypertension and cardiac hypertrophy, but there were contrasting data. We analysed the genotype/phenotype associations between this polymorphism and cardiovascular variables in a young adult population, where interactions among genes, gene-environment, and acquired ageing-related organ damage are reduced. Anthropometric measurements, blood pressure, heart rate, left ventricular variables (by echocardiography), and carotid artery wall intimal-media thickness (by high-resolution sonography and digitalized morphometry) were taken in 420 white Caucasian students (mean age 23.5 years, s.d. 2.5 years). CYP11B2 alleles were detected by genomic polymerase chain reaction followed by digestion. Taking into account the three possible models of inheritance, we found no differences in the considered variables, except for an independent effect of the C(-344) allele on SBP in males (TT 125.6 (1.6), TC 128.4 (1.2) and CC 130.5 (2.2), mmHg, media (ES), P=0.03), and on interventricular septum thickness in diastole in females (CC 6.98 (0.12) vs TT 6.87 (0.09) and TC 6.87 (0.07), mmHg, P<0.01), in the codominant model. In conclusion, the CYP11B2 C(-344)T polymorphism appears to have a slight role in the cardiovascular phenotype of young healthy adults, even if these genotype/phenotype relationships might change with ageing.

Background/aims: The mucosa of the ileal pouch after restorative proctocolectomy develops relevant adaptative changes but the real mechanisms and the evolution over time of these alterations are still unclear. The aims of the present work were to study the distribution of the mucosal changes at different levels in the reservoir and to evaluate the evolution of these alterations over a long follow-up period., Methodology: The severity of chronic and acute inflammation, villous atrophy, colonic-type mucins production and proliferative index were evaluated in the bioptical specimens from 46 patients (30 males, 16 females, mean age 38 years) with functioning pouch. We compared the histology of the upper pouch mucosa with the lower one. Then we divided the 46 patients into Group A-24 patients with a median follow-up of 11 years (range 9-16); Group B-22 patients with a median follow-up of 4 years (range 2-8), comparing the results from the two groups. Finally we performed a prospective evaluation in the 24 patients who were controlled in 3 subsequent follow-ups (1993-1994, 1996-97, 1999-2000)., Results: At the topographic evaluation only the acute inflammation was significantly more pronounced in the lower pouch area (p = 0.031). All the morphological changes showed a trend of greater severity in the group A patients, in particular villous atrophy (p = 0.005) and colonic-like mucins secretion (p = 0.006). At the prospective evaluation, the chronic inflammation showed a significant progressive worsening over time (p = 0.011)., Conclusions: Our experience showed that the transformation of the mucosa represents an "organ" response to the luminal environment and may progress over time.

Background: The objective of the study was to identify the parameter(s) of cardiopulmonary exercise testing (CPET) that can detect exercise-induced myocardial ischaemia (EIMI), and to determine its diagnostic accuracy for identifying patients with coronary artery disease (CAD)., Methods and Results: We prospectively studied 202 consecutive patients (173 men, 29 women, mean age 55.7+/-10.8 years) with documented CAD. All patients underwent an incremental exercise stress testing (ECG-St) with breath-by-breath gas exchange analysis, followed by a 2-day stress/rest gated SPECT myocardial scintigraphy (GSMS) as the gold standard for ischaemia detection. ROC analysis selected a two-variable model-O(2)pulse flattening duration, calculated from the onset of myocardial ischaemia to peak exercise, and deltaVO(2)/deltawork rate slope-to predict EIMI by CPET. GSMS identified 140 patients with reversible myocardial defects, with a Summed Difference Score (SDS) of 9.7+/-2.8, and excluded EIMI in 62 (SDS 1.3+/-1.6). ECG-St had low sensitivity (46%) and specificity (66%) to diagnose EIMI as compared with CPET (87% and 74%, respectively)., Conclusions: The addition of gas exchange analysis improves the diagnostic accuracy of standard ECG stress testing in identifying EIMI. A two-variable model based on O(2)pulse flattening duration and deltaVO(2)/deltawork rate slope had the highest predictive ability to identify EIMI.

As stated in the St. Vincent Declaration, the reduction of the number of lower extremity amputations (LEA) is one of the major targets in diabetes care. Little information on the prevalence of this complication is available in Italy at present. The aim of this study was to evaluate the impact of diabetes on LEA in a region of central Italy. The regional database of hospital discharge records was used to identify all the cases of non-traumatic LEA (Nt-LEA) that had occurred in 1997 and 1998. Diagnosis of diabetes and the type of surgical intervention were defined on the basis of the medical records. Amputations were categorised as minor or major according to the level of the surgical procedure. The duration of hospitalisation was used to analyse the impact of diabetes on the health care system. Prevalence of diabetes in people who underwent Nt-LEA was 55.9% and it was similar in patients who underwent minor or major amputation (58.7 and 55.0%, respectively). No difference between diabetic and non-diabetic patients was observed as regards sex, level of amputation and duration of hospitalisation. Age was the only predictor of diabetes in amputees. The lack of specific protocols for diabetes foot care or a non-homogeneous application of these protocols in the health care service could account for a similar prevalence of diabetes among patients who underwent minor or major amputation.

Material recovered from 374 fingerprints left by eleven laboratory workers on three different substrates (glass, wood, metal) at a standard pressure time of 30 s, with and without preliminary handwashing, was submitted to morphological, quantitative, and type analysis. Morphological and agarose-gel electrophoresis analysis showed that a non-negligible amount of epidermal corneal cells presented apoptotic alterations. The quantity of DNA recovered from fingerprints ranged between 0.04 to 0.2 ng, and in a significant number of experiments no DNA was detected. Handwashing reduced the amount of DNA recovered from fingerprints. The "shedder status" of the donor was a very important factor, causing inter-individual variations in the amount of DNA left by fingerprints. Spurious alleles from laboratory-based and secondary transfer contamination, stutters, and other artifacts described when analyzing low-copy-number DNA and capable of affecting correct profiles were observed.

Objectives: The incidence of non-small cell lung cancer (NSCLC) is increasing among the elderly. We studied the toxicity and efficacy of a weekly schedule of gemcitabine and cisplatin in elderly patients with advanced NSCLC., Methods: Patients aged 70 years or above with advanced NSCLC were treated in a phase II prospective trial with gemcitabine 1,000 mg/m(2) and cisplatin 35 mg/m(2) on days 1, 8 and 15 every 28 days., Results: Forty-eight patients with a median age of 74 years (range 70-78) participated in the study. We observed 14 cases with partial response, 14 with stable disease and 16 with progressive disease, whilst 4 patients were not evaluable. By intention-to-treat analysis, partial response rate was 31.8% whilst progressive disease was 33.3%. Median survival was 9 months; 1-year survival probability was 34.4% and median time to progression was 4 months. Grade III-IV leukopenia was observed in 5/48 patients (10.4%), 20/48 patients (41.7%) had grade III-IV thrombocytopenia and 7/48 patients (14.6%) had grade III-IV anemia. One patient experienced grade III emesis and 2 patients had grade III-IV fatigue., Conclusions: At this dose and schedule the combination of gemcitabine and cisplatin appears to be an active and well-tolerated regimen for elderly patients with advanced NSCLC., (Copyright 2003 S. Karger AG, Basel)

We investigated the in vitro effects of therapeutical concentrations of S 21403 (a succinic acid derivative also known as KAD 1229 and mitiglinide) on insulin and glucagon secretion during a metabolic stimulus (glucose rising from 5 to 8.33 mM) or at a stable 2.22 mM glucose using the isolated perfused rat pancreas model, and we compared them with the patterns of repaglinide and glibenclamide. Control perfusions were also performed. During 8.33 mM glucose, insulin release peaked to 339.12+/-22.87 microU/ml in controls. S 21403 enhanced insulin release (first peak 413.02+/-14.90 microU/ml; P<0.03 vs. controls, P=ns vs. repaglinide, P<0.005 vs. glibenclamide). Repaglinide increased glucose-induced first peak secretion to 409.33+/-20.05 microU/ml within the eighth minute (P<0.05 vs. controls, P<0.01 vs. glibenclamide). Glibenclamide did not affect the first phase of glucose-induced insulin release (peak of 338.41+/-29.79 microU/ml) but potentiated and delayed the second phase. No drug affected glucagon release. In conclusion, S 21403 induces a faster, more physiological pattern of insulin release than the other drugs we tested.

Objectives and Design: Angiotensinogen (AGT) gene variants influence angiotensinogen plasma levels in children and young adults. The angiotensinogen promoter (-6)A variant facilitates gene transcription in human tissues and it has been associated with high blood pressure in older adults. A young adult population can be used as a model to study genotype/phenotype associations between AGT (-6) variants and cardiovascular variables., Methods and Results: Anthropometric measurements, blood pressure and heart rate were taken in 422 white Caucasian students (mean age 23.5 years, SD 2.5 years). Family history for hypertension, physical activity and smoking history were evaluated. Left ventricular variables were measured by echocardiography. Carotid artery wall intimal-media thickness (IMT) was measured by high resolution sonography and digitalized morphometry. The AGT G(-6)A alleles were evaluated by mutagenically separated polymerase chain reaction controlled by direct sequencing. No significant associations were found between angiotensinogen genotype and blood pressure, cardiac variables [except for deceleration time in females which increased with the number of (-6)A alleles] and IMT. Allele frequencies were similar between the first and third tertile of blood pressure and left ventricular mass, and were also similar between negative or positive family history for hypertension (the last group having significantly higher systolic blood pressure in males, P = 0.04 and diastolic blood pressure in females, P < 0.01). Moreover, no relevant interaction on the cardiovascular variables was found between AGT genotype and body mass index., Conclusions: The angiotensinogen G(-6)A variants do not affect cardiovascular parameters in young adults, but an effect of this polymorphism on cardiovascular phenotype (and hypertension) in older adults cannot be excluded. Additional factors, associated with ageing, should be present to unleash the supposed unfavourable potential of the (-6)A angiotensinogen variant.

Objective: The aim of the study was to use the physiological and operative severity score for the enumeration of mortality and morbidity (POSSUM) to assess the performance of our thoracic surgery unit during two successive periods of activity., Methods: From 1992 through 1997, 801 candidates for thoracic procedures at our institution were considered for the study. After validation of the logistic regression model, including the POSSUM score, observed and POSSUM-predicted morbidities were compared within two groups of patients divided by year of operation (group 1: 1992-1994, n=362; group 2: 1995-1997, n=439) by means of the z-test for the comparison of a proportion with an expected value., Results: The POSSUM-predicted morbidity was significantly lower than the observed one in the first period of activity of our unit (19.6 vs. 24.3%, respectively; z-test for the comparison of a proportion with an expected value, 2.25; P=0.01), whereas no difference was found in the second period (20.5 vs. 19.1%, respectively; z-test for the comparison of a proportion with an expected value, -0.71; P=0.76)., Conclusions: The result suggests a worse-than-expected performance of our unit in the first period of activity, showing that POSSUM can be reliably applied as an instrument of internal comparative audit in a thoracic surgery unit.

A checkerboard methodology, based on standardized methods proposed by the National Committee for Clinical Laboratory Standards for broth microdilution antifungal susceptibility testing, was applied to study the in vitro interactions of flucytosine (FC) and posaconazole (SCH 56592) (FC-SCH) against 15 isolates of Cryptococcus neoformans. Synergy, defined as a fractional inhibitory concentration (FIC) index of <0.50, was observed for 33% of the isolates tested. When synergy was not achieved, there was still a decrease in the MIC of one or both drugs when they were used in combination. Antagonism, defined as a FIC of >4.0, was not observed. The in vitro efficacy of combined therapy was confirmed by quantitative determination of the CFU of C. neoformans 486, an isolate against which the FC-SCH association yielded a synergistic interaction. To investigate the potential beneficial effects of this combination therapy in vivo, we established two experimental murine models of cryptococcosis by intracranial or intravenous injection of cells of C. neoformans 486. At 1 day postinfection, the mice were randomized into different treatment groups. One group each received each drug alone, and one group received the drugs in combination. While combination therapy was not found to be significantly more effective than each single drug in terms of survival, tissue burden experiments confirmed the potentiation of antifungal activity with the combination. Our study demonstrates that SCH and FC combined are significantly more active than either drug alone against C. neoformans in vitro as well in vivo. These findings suggest that this therapeutic approach could be useful in the treatment of cryptococcal infections.

The interaction of amphotericin B (AmB) and azole antifungal agents in the treatment of fungal infections is still a controversial issue. A checkerboard titration broth microdilution-based method that adhered to the recommendations of the National Committee for Clinical Laboratory Standards was applied to study the in vitro interactions of AmB with fluconazole (FLC), itraconazole (ITC), and the new investigational triazole SCH 56592 (SCH) against 15 clinical isolates of Cryptococcus neoformans. Synergy, defined as a fractional inhibitory concentration (FIC) index of < or =0.50, was observed for 7% of the isolates in studies of the interactions of both FLC-AmB and ITC-AmB and for 33% of the isolates in studies of the SCH-AmB interactions; additivism (FICs, >0.50 to 1.0) was observed for 67, 73, and 53% of the isolates in studies of the FLC-AmB, ITC-AmB, and SCH-AmB interactions, respectively; indifference (FICs, >1.0 to < or =2.0) was observed for 26, 20, and 14% of the isolates in studies of the FLC-AmB, ITC-AmB, and SCH-AmB interactions, respectively. Antagonism (FIC >2.0) was not observed. When synergy was not achieved, there was still a decrease, although not as dramatic, in the MIC of one or both drugs when they were used in combination. To investigate the effects of FLC-AmB combination therapy in vivo, we established an experimental model of systemic cryptococcosis in BALB/c mice by intravenous injection of cells of C. neoformans 2337, a clinical isolate belonging to serotype D against which the combination of FLC and AmB yielded an additive interaction in vitro. Both survival and tissue burden studies showed that combination therapy was more effective than FLC alone and that combination therapy was at least as effective as AmB given as a single drug. On the other hand, when cells of C. neoformans 2337 were grown in FLC-containing medium, a pronounced increase in resistance to subsequent exposures to AmB was observed. In particular, killing experiments conducted with nonreplicating cells showed that preexposure to FLC abolished the fungicidal activity of the polyene. However, this apparent antagonism was not observed in vivo. Rather, when the two drugs were used sequentially for the treatment of systemic murine cryptococcosis, a reciprocal potentiation was often observed. Our study shows that (i) the combination of triazoles and AmB is significantly more active than either drug alone against C. neoformans in vitro and (ii) the concomitant or sequential use of FLC and AmB for the treatment of systemic murine cryptococcosis results in a positive interaction.

Obesity is often associated with type 2 (non insulin-dependent) diabetes. A growing body of evidence support the hypothesis that these two diseases share a common pathogenesis. Nevertheless, experience derived from clinical observation on type 2 diabetic patients indicates that reduction of body weight is not always accompanied by an improvement in metabolic control and that a good metabolic control is often obtained without influencing body composition. Aim of the present study was to evaluate the relationship between body mass and glycemic control in a type 2 diabetic population by a 3 years observational study. A cohort of 562 subjects was studied. At entry more than 80% of patients were overweight or obese according to the body mass index (BMI) scale and this proportion was not significantly reduced at the end of the follow-up. At entry all patients had a glycosylated hemoglobin (HbA1c) value above 8.1% whereas at the end of follow-up more than 2/3 of patients were in good metabolic control. No relationship was observed between modification of body mass and metabolic control. These data confirm the high frequency of obesity among type 2 diabetic individuals but they suggest that impaired glucose metabolism and alteration of body weight have different pathogenesis.

Aims: To assess the effects and safety of increasing sulphonylurea dosages or adding metformin in poorly controlled elderly Type 2 diabetic patients., Methods: A 18-month multicentre clinical study was performed on sulphonylurea-treated diabetic patients over 70 years of age with well-preserved renal function, steady fasting blood glucose > or = 200 mg/dl and HbA1c > or = 9%. Patients were randomly assigned to sulphonylurea increased up to its maximum dosage (1st group) or to addition of metformin (2nd group). Glycaemic control, lipid pattern, haemostatic status and safety were monitored during run-in, at baseline and at scheduled intervals for 18 months. Results refer to 85 patients in the 1st group and 89 patients in the 2nd with complete data., Results: Similar improvements in glycaemic levels were observed with both treatments within the first month and a similar decrease in HbA1c within the third month. No further changes occurred in glycaemic control. In the 1st group, fasting glucose (mmol/l, mean +/- SE) decreased from 14.21 +/- 0.49 to 9.88 +/- 0.21, average day-long glucose from 14.87 +/- 0.27 to 10.69 +/- 0.19 and HbAt1c(%) from 10.32 +/- 0.13 to 8.66 +/- 0.13. In the 2nd treatment group fasting glucose decreased from 14.59 +/- 0.61 to 9.05 +/- 37.28, average day-long glucose from 15.09 +/- 0.29 to 10.32 +/- 0.21 and HbA1c from 10.33 +/- 0.13 to 8.77+/-0.12 (for all P<0.0005). In this 2nd group, a decrease in LDL-cholesterol (P < 0.05) and an increase in HDL-cholesterol levels (P < 0.02) were also observed. In the 1st group, anthrombin III activity increased significantly (P<0.01). In the 2nd group, significant reductions in markers of platelet function (FP4 and betaTG, P < 0.01), thrombin generation (FPA, F1 + 2 and D-D, P<0.01), and fibrinolysis inhibition (PAI-1 activity, PAI-1 antigen, P< 0.001) were observed. Increases in some fibrinolytic activation markers (t-PA activity, and AT-III activity, P<0.01) occurred. Fasting lactate concentrations were unchanged in the metformin-treated group. No serious adverse effects were observed in either group., Conclusions: These results suggest that either high sulphonylurea dosages or a therapy combining lower sulphonylurea dosages with metformin are effective and safe in an aged but healthy population. Metformin provides additional benefits counteracting several cardiovascular risk factors but must be administered with caution, bearing in mind the general contra-indications for the drug but not age alone.

Objective: To assess the prognostic value of the APACHE II score and the American Society of Anesthesiologists (ASA) classification system in preoperative evaluation of patients., Design: Prospective study., Setting: University hospital, Italy., Subjects: 187 consecutive patients undergoing elective or emergency major general surgical operations., Interventions: Patients were evaluated preoperatively using both indices., Main Outcome Measures: Morbidity and mortality within 30 days., Results: Logistic regression and ROC curve analyses showed that the APACHE II score predicted morbidity and mortality well; it was superior to the ASA system in predicting outcome (area under the curve 0.894 for the APACHE II index, 0.777 for the ASA system; p < 0.001). The APACHE II score without its age points (area 0.888) had the same prognostic value as the complete score (area 0.894; p = 0.55)., Conclusions: The APACHE II score may help clinicians to evaluate preoperatively the risk of postoperative morbidity and death after major general surgical operations. Age does not seem to have a specific weight.

Aims/hypothesis: To evaluate the relation between the incidence of childhood Type I (insulin-dependent) diabetes mellitus and the degree of urbanization in the central-southern part of Italy., Methods: The incidence was determined in two areas: area A encompasses 3 regions of central-eastern Italy (Marche, Abruzzo, Umbria), whereas area B encompasses one southern region (Campania). During 1990-1995, 706 children aged 14 or under with insulin-dependent diabetes mellitus of recent onset were registered. The completeness of the case ascertainment in the registries analysed separately for each region was high, ranging from 96.3 % to 99%., Results: The age-standardized incidence was higher in area A (9.6 per 100000 person per year; 95 % confidence interval: 8.5-10.8) than in area B (5.4 per 100000 person per year; 95% confidence interval: 4.9-6.0). In both areas the standardized incidence ratios increased with the degree of urbanization (chi-squared for trend: area A= 140, p < 0.0001; area B = 79, p < 0.0001). The highest standardized incidence ratios were in the most urban communities., Conclusion/interpretation: This study showed a statistically significant difference in incidence of childhood insulin-dependent diabetes mellitus among different areas of the continental peninsula of Italy. People living in the rural communities appear to have a lower risk.