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Background. Cystic fibrosis (CF) is an autosomal recessive disease caused by mutations in the gene encoding the cystic fibrosis transmembrane conductance regulator (CFTR), responsible for chloride and sodium ion exchange across epithelial membranes. Dysfunctional CFTR induces the production of thick/viscous mucoid secretions in multiple organs, in particular the airways, where an augmented mucus viscosity is determined by the pathological increase in proteins, mucin and biological polymers. This process impairs muco-ciliary clearance, promoting chronic inflammation and bacterial infection leading to airway remodeling; these, in turn, can progress to respiratory failure, the most common cause of death for CF patients. Therefore, as sputum composition depends on lung condition, the determination of its properties represents a relevant parameter to indirectly monitoring lung disease. We previously (Abrami et al Magn Res Med, p.427, 2020; Abrami et al Magn Res Med, p. 2323, 2018;) employed Low Field Nuclear Magnetic Resonance (LF-NMR) to measure the spin-spin relaxation time (T2m) of the water hydrogens present in the CF sputum. These data showed that T2m measured in CF sputum indirectly correlated with circulating/local inflammation markers and a directly correlated with FEV1 (forced expiratory volume in the first second, i.e. the amount of air that is exhaled in the first second purposefully trying to breath out as much air as possible). Thus, the assessment of sputum by T2m, provides a useful tool for the indirect monitoring of lung disease in CF patients. Here, we explore the possibility of T2m to detect lung function improvements following treatment by the novel drug Kaftrio. This is a triple modulator (Tezacaftor/Ivacaftor/Elaxacaftor) able to improve CFTR protein function. Approved by E.M.A in 2020, Kaftrio has been shown to have beneficial effects not only in CF patients with mild-to-moderate disease but also in those with more severe pulmonary status. Methods. Sputum samples from 17 CF subjects, provided by Burlo Garofolo Hospital -Centro Regionale Fibrosi Cistic-, following a procedure approved by the Ethics Committee (prot n. 0005431/2020, CEUR-2019-Em-408), were collected (by voluntary expectoration) before and after Kaftrio administration (total samples 34). Sputum samples were studied by LF-NMR to determine T2m. The data obtained were related to lung function evaluated by FEV1. Results. In 58% of cases, Kaftrio administration improved both FEV1 and T2m, thus indicating a positive effect of the drug on lung function. In 25% of cases Kaftrio determined a reduction of both FEV1 and T2m, indicating no significant benefic effect on lung function. Finally, in only 17% of cases, Kaftrio treatment resulted in discordant variation of FEV1 and T2m, i.e. FEV1 increase and T2m decrease. This odd observation may be attributed to the fact that Kaftrio caused the dehydration of the mucus reducing its quantity (FEV1 increase) but worsening its nano-structure thus resulting in T2m decrease. Conclusions. Here we demonstrate that T2m can be effectively used to evaluate CF lung function following Kaftrio administration. Thus, besides being able to monitor lung disease exacerbation (our previous results) in CF patients, here we show that T2m can monitor lung function following drug therapy. Considering that T2m determination is very inexpensive does not require specialized personnel and it is not of any discomfort for the patient, it can become a valuable monitoring tool of lung function in CF diseases.

Background Real-world studies can provide information on those patients routinely excluded from clinical trials such as epilepsy patients with tumour aetiology. Perampanel (PER) is a once-daily oral anti-seizure medication for focal-onset seizures, with or without focal to bilateral tonic-clonic seizures, and generalised tonic-clonic seizures. This study evaluated PER’s effectiveness and safety when used in everyday clinical practice to treat epilepsy patients with tumour aetiology. Material and Methods Patients with epilepsy with tumour aetiology were identified from a pooled analysis of 44 prospective/retrospective/cross-sectional clinical practice studies. Retention was assessed after 3, 6 and 12 months of PER treatment. Effectiveness assessments comprised responder rate (≥50% seizure frequency reduction), seizure freedom rate (no seizures since at least the prior visit), and the proportions of patients with unchanged or worsening seizure frequency. Adverse events (AEs), psychiatric AEs, and AEs leading to discontinuation were also evaluated. Results Overall, 127 patients with focal-onset and/or generalised-onset seizures with tumour aetiology were identified (mean age, 46.6 years; 54.8% male; mean duration of epilepsy, 9.7 years). Seizure types at baseline were focal-onset only (97.6%), generalised-onset only (1.6%), and focal-onset and generalized-onset (0.8%). Mean (standard deviation) PER doses at baseline and last visit were 2.6 (1.4) and 5.8 (2.5) mg/day, respectively. At 3, 6 and 12 months, retention rates were 88.0%, 79.5% and 65.3%, respectively. Reasons for discontinuation included AEs (16.8%) and lack of efficacy (5.3%). Mean time under PER treatment was 11.0 months. At 12 months, 71.2% of patients were responders and 38.3% were seizure free; 11.9% and 3.4% of patients had unchanged and worsening seizure frequency, respectively. At the last visit (last observation carried forward), responder and seizure freedom rates were 66.9% and 34.2%, respectively, and the percentages of patients with unchanged or worsening seizure frequency were 15.3% and 6.8%, respectively. AEs were reported for 36.2% of patients, most frequently dizziness/vertigo (13.8%) and somnolence (9.5%). AEs led to discontinuation of 16.8% of patients over 12 months and 13.0% of patients experienced psychiatric AEs. Conclusion PER was effective and generally well tolerated when used to treat patients with epilepsy with tumour aetiology in clinical practice. Supported by Eisai

Use of Rheology and portable Low-Field NMR for the monitoring of lung functions in cystic fibrosis patients Gabriele Grassi5*, Michela Abrami1, Massimo Maschio2, Massimo Conese3, Marco Confalonieri4, Fabio Gerin1, Barbara Dapas5, Rossella Farra6, Alessandra Adrover7, Lucio Torelli6, Barbara Ruaro4, Mario Grassi1, 1 Department of Engineering and Architecture, University of Trieste, Via Valerio 6/A, I-34127 Trieste, Italy 2 Institute for Maternal and Child Health, IRCCS Burlo Garofolo, Via dell'Istria, 65, I-34137, Trieste, Italy 3 Department of Medical and Surgical Sciences, Foggia University, Ospedali Riuniti, Via L. Pinto, 1, I-71122 Foggia, Italy 4 Cattinara University Hospital, Pulmonology Department, Strada di Fiume 447, I-34149 Trieste, Italy 5 Department of Life Sciences, Cattinara University Hospital, Trieste University, Strada di Fiume 447, I-34149 Trieste, Italy 6 Clinical Department of Medical, Surgical and Health Sciences, Cattinara University Hospital, Trieste University, Strada di Fiume 447, I-34149 Trieste, Italy. 7 Department of Chemical Engineering, Materials and Environment, Sapienza University of Roma, Via Eudossiana 18, I-00184 Rome, Italy *Corresponding author: Gabriele Grassi Department of Life Sciences Cattinara University Hospital Trieste University Strada di Fiume 447, I-34149 Trieste, Italy e-mail: ggrassi@units.it “Declarations of interest: none”. Abstract Background. Cystic fibrosis (CF) is an autosomal recessive disease caused by mutations in the gene encoding of the cystic fibrosis transmembrane conductance regulator (CFTR) responsible for chloride and sodium ion exchange across epithelial membranes. Dysfunctional CFTR induces the production of thick/viscous mucoid secretions in multiple organs, in particular the airways, where an augmented mucus viscosity is determined by the pathological increase in proteins, mucin and biological polymers. This process impairs mucociliary clearance, promoting chronic inflammation and bacterial infection leading to airway remodeling, which, in turn, may progress to respiratory failure, the most common cause of death for CF patients. Therefore, as sputum is a rich and noninvasive source of biomarkers of inflammation/infection, the determination of mucus properties is a relevant parameter able to indirectly monitor lung disease. We previously (Abrami et al Magn Res Med, p.427, 2020; Abrami et al Magn Res Med, p. 2323, 2018;) employed Low Field Nuclear Magnetic Resonance (LF-NMR) to measure the spin-spin relaxation time (T2m) of the water hydrogens present in the CF sputum. These data showed that the T2m measured in CF sputum had an indirect correlation with circulating/local inflammation markers and a direct correlation with FEV1 (forced expiratory volume in the first second, i.e. the amount that is exhaled in the first second purposefully trying to breath out as much air as possible). Thus, the assessment of the physical properties of sputum by T2m, may well provide a useful tool for the indirect monitoring of lung disease in CF patients. Here the T2m significance in the monitoring of CF lung disease was further investigated by studying the correlation of T2m with: 1) sputum viscoelasticity, 2) mucociliary clearability index(MCI)/cough clearability index(CCI) and 3) sputum average mesh-size. Methods. Sputum samples from 25 consenting CF subjects were analyzed by rheology tests (elastic modulus G and zero shear viscosity 0) and Low Field Nuclear Magnetic resonance (T2m). MCI/CCI were calculated from the rheological parameters. The average mesh-size () of the sputum structure was then evaluated by rheology/LF-NMR, together with FEV1 for each patient. Results. There was an inverse correlation between G/ and T2m, indicating that a worsening of the lung condition (T2m-FEV1 drop) is paralleled by an increase in sputum viscoelasticity (G and 0) favoring mucus stasis/inflammation. A direct correlation was also observed between T2m and MCI/CCI, showing that T2m provides information as to airway mucus clearing. Moreover, there was a direct correlation between T2m and the average sputum mesh size ( Conclusions. We demonstrated a correlation between T2m and the sputum viscoelasticity/average mesh-size and with MCI/CCI, parameters related to airway mucus clearing. This correlation was assessed, for the first time, by a combined analysis based on rheology and LF-NMR. This novel approach provided information as to the macro- (viscosity, elasticity, average magnetic relaxation time) and micro-scale (mesh size distribution) characteristics of CF sputum. In conclusion, the present data strengthen the potential of our test to provide indirect monitoring of airway disease course in CF patients.

Lung functionality assessment in cystic fibrosis (CF) patients is extremely relevant as most patients succumb to respiratory failure. Inflammatory markers (IMs) and respiratory functional tests, i.e. forced expiratory volume in the first second (FEV1), are used to test pulmonary functions/inflammation and to guide therapy. However, FEV1 has suboptimal reproducibility, and IMs detection is costly. Thus, aim of this work is to use rheology to assess lung functionality/inflammation recurring to the characterization CF patients sputum. Despite some known problems connected with the rheological characterization of inhomogeneous biological fluids, we found that there is a statistical linear correlation among the sputum elastic properties (G’ evaluated at different frequencies) and FEV1, while no correlation exists between the sputum viscous properties (G’’ evaluated at different frequency, and zero shear viscosity) and FEV1. In addition, we found a not linear correlation between sputum elastic properties and the average magnetic relaxation time of water hydrogens entrapped in the sputum. We believe that the potential impact of these rheological findings on health is considerable

Background: Patients with cystic fibrosis (CF) are at high risk of developing severe forms of viral respiratory infections. This study aimed at comparing symptoms and clinical course of SARS-CoV2 infection with other respiratory infections in patients with CF. Methods: We carried out a prospective multicentre cohort study within the Italian CF Society involving 32 CF centres following 6,597 patients. CF centres were contacted to collect baseline and follow-up data of all patients who had reported symptoms suggestive of COVID-19 or who had had contact with a positive/suspected case between the end of February and July 2020. Symptoms and clinical course of the infection were compared between patients who tested positive by molecular testing (cases) and those who tested negative (controls). Results: Thirty patients were reported from the centres, 16 of whom tested positive and 14 negative. Fever, cough, asthenia and dyspnea were the most frequently reported symptoms and their frequency were not significant different between groups. Eight cases (50%) were hospitalised but none required ICU admission. Two adults with a history of lung transplant required non-invasive ventilation;none required ICU admission. All patients fully recovered without short-term sequelae. Changes in FEV1 (percent of predicted) after recovery were not significantly different between groups (median, interquartile range: 3.0%, –1.5, 5.5 among cases and –3.0%, –8.5, 6.3 among controls, P = 0.48). Conclusions: Symptoms and clinical course of SARS-CoV-2 infection in our patients was not significantly different from other respiratory infections. The clinical course of COVID-19 was relatively favourable, however CF patients with severely impaired respiratory function and organ transplant may develop complications and a negative outcome. The study is ongoing, and we are recruiting patients during the second wave of the pandemic.

Summary What is already known about this subject Fasting triglycerides above 1.17 mmol/L have been shown to be useful to select obese children and adolescents who may present impaired glucose tolerance in a Canadian cohort. Fasting plasma glucose is associated with the risk to present impaired glucose tolerance in several cohorts of obese children and adolescents. What this study adds When applied to Italian cohorts of obese children and adolescents, the triglycerides cut-off of 1.17 mmol/L has similar validity as in the Canadian cohort to select patients who may present impaired glucose tolerance. Fasting plasma glucose and fasting triglycerides can be combined to obtain an accurate criterion to select obese children and adolescents who may present impaired glucose tolerance. Objectives We aimed to validate fasting triglycerides > 1.17 mmol L−1, a criterion recently proposed for selecting obese children at risk of impaired glucose tolerance (IGT), and to assess whether the accuracy of triglycerides (TG) can be improved by the use of other variables. Methods We studied an Italian cohort of 817 obese children and adolescents (8–18.4 years) who underwent clinical examination, fasting blood analysis and the oral glucose tolerance test (OGTT). The discriminative properties of TG > 1.17 mmol L−1 were assessed and compared with those observed in a Canadian cohort from which this criterion was derived: 71.4 [57.8–85.1]% sensitivity and 64.1 [57.7–70.4]% specificity. The possible contribution of other variables was evaluated by assessing the net reclassification improvement (NRI), i.e., the net increase in the percentage of subjects correctly classified. Results Thirty-nine children (4.7%) had IGT. The 1.17 mmol L−1 TG threshold showed 66.6 [51.8–81.4]% sensitivity and 68.2 [64.9–71.5]% specificity, thus successfully validated. Fasting plasma glucose (FPG) was independently associated with IGT (odds ratio = 3.86 [2.09–7.14], P 1.17 mmol L−1. Conclusions TG > 1.17 mmol L−1 is a useful criterion to detect roughly 66% of obese children with IGT through OGTT performed in about 33% of all obese children. However, the ‘TG≥1.13 mmol L−1 plus FPG≥4.44 mmol L−1’ criterion improved discrimination accuracy, leading to the possibility of detecting even more than 66% of obese children with IGT though limiting OGTT to just 25% of all obese children.

A Budget Impact Model Of The Addition Of Telotristat Ethyl Treatment In Patients With Uncontrolled Carcinoid Syndrome

Sixteen pluriparous lactating buffaloes were divided in two groups homogeneous for parity, lactation stage, milk yield and weight. The diets assigned to two groups, based on maize silage (M group) and sorghum silage (S group), had the same energy-protein level (0.90 Milk FU/kg DM and 155 g/kg DM of crude protein). Five records of milk yield and quality during lactation were carried out. The physical-chemical characteristics (pH, fat, protein, lactose and urea), somatic cell count, coagulation properties and nutritional parameters (cholesterol, alfa tocopherol, 13 cis and trans retinol and 13 cis/trans retinol ratio) were analysed. Statistical analysis was performed using a factorial model. The average daily milk yield during experimental period was similar: 9.29 and 9.55 kg respectively in M and S groups. Fat and protein content were not different, while the urea content was significantly different varying from 39.13 mg/dl in M group to 45.55 mg/dl in S group. The coagulation properties, the estimated Mozzarella yield, somatic cell count and the nutritional parameters analysed were not different between the two groups. These results indicate that the sorghum silage diet utilised did not affect the milk yield and quality, then it could be adopted in lactating buffaloes.

The aim of this work was to evaluate a possible relationship among the size of preovulatory follicle (PF), the size and ultrasonographic appearance of the corresponding corpus luteum (CL) and the functionality of CL based on plasma progesterone (P4) concentration. Moreover, the relationship among PF size, the CL appearance and functionality, and the conception rate after artificial insemination (AI) was studied. Thirty adult buffaloes were used for this study. The animals were synchronized with PRID+PMSG+PGF2α and artificially inseminated. The ovaries were ultrasonografically examined every 12 h starting from 24 h before the AI until ovulation occurred, and then at day 7,14,21,28,35 to study the CL and to diagnose pregnancy. At the same time, blood sample were collected for P4 determination carried out by RIA. On the basis of echogenic appearance, the corpora lutea (CLs) were classified as belonging to: grade 1, greyish structure bounded by an indistinct border; grade 2: increasing darker grey structure more distinguishable from the ovarian stroma; grade 3: a well defined granular CL, dark grey in colour clearly separated from the stroma. Significative difference was found in the diameter of PF and in that of CL in relation to the CL echogenic appearance. Well defined granular CL, distinguishable from the ovarian stroma and dark grey in colour (grade 3) resulted to have a bigger diameter compared with CLs belonging to a grade 1 or 2, and resulted to derive from a larger PF. Positive correlation was found between plasma P4 concentration and CL diameter. The PF diameter was larger in buffaloes become pregnant after AI respect to the non-pregnant. The CL diameter, also, was significatively larger in the pregnant buffalo in confront to the non-pregnant since the first observation at day 7, while significative difference in P4 value was found starting from day 21 after AI.

Buffalo cows were submitted to three superovulatory treatments. T1 (n = 7): PRID for 10 days (d0-d9) plus decreasing doses of 500 IU FSH/LH (12 h-intervals d7‑d10); T2 (n = 8): PRID for 11 d (d0-d10) plus 2000 IU PMSG at d7; T3 (n = 9): PRID for 11 d plus 2000 IU PMSG at d7 and decreasing doses of 175 IU FSH/LH (12 h-intervals d10‑ d11). Overall plasma inhibin‑A (In-A) concentrations correlated with large follicles (LF, diameter >6mm, R=0.83, P10 mm at d12- 13 (T1=5.0+/-1.4, T2=1.2+/-0.9, T3=8.3+/-2.3). In-A concentrations significantly rised at d11-13 of T1 and T3. In-A seems a good indicator of the follicular development during superovulation in buffalo cows, while E2 is not. Furthermore T3 was followed by better ovarian follicular responses.

International audience; no abstract

What is already known about this subject Fasting triglycerides above 1.17 mmol/L have been shown to be useful to select obese children and adolescents who may present impaired glucose tolerance in a Canadian cohort. Fasting plasma glucose is associated with the risk to present impaired glucose tolerance in several cohorts of obese children and adolescents. What this study adds When applied to Italian cohorts of obese children and adolescents, the triglycerides cut-off of 1.17 mmol/L has similar validity as in the Canadian cohort to select patients who may present impaired glucose tolerance. Fasting plasma glucose and fasting triglycerides can be combined to obtain an accurate criterion to select obese children and adolescents who may present impaired glucose tolerance.We aimed to validate fasting triglycerides 1.17 mmol L(-1) , a criterion recently proposed for selecting obese children at risk of impaired glucose tolerance (IGT), and to assess whether the accuracy of triglycerides (TG) can be improved by the use of other variables.We studied an Italian cohort of 817 obese children and adolescents (8-18.4 years) who underwent clinical examination, fasting blood analysis and the oral glucose tolerance test (OGTT). The discriminative properties of TG 1.17 mmol L(-1) were assessed and compared with those observed in a Canadian cohort from which this criterion was derived: 71.4 [57.8-85.1]% sensitivity and 64.1 [57.7-70.4]% specificity. The possible contribution of other variables was evaluated by assessing the net reclassification improvement (NRI), i.e., the net increase in the percentage of subjects correctly classified.Thirty-nine children (4.7%) had IGT. The 1.17 mmol L(-1) TG threshold showed 66.6 [51.8-81.4]% sensitivity and 68.2 [64.9-71.5]% specificity, thus successfully validated. Fasting plasma glucose (FPG) was independently associated with IGT (odds ratio = 3.86 [2.09-7.14], P 0.001), besides TG. The bivariate criterion of TG ≥ 1.13 mmol L(-1) plus FPG ≥ 4.44 mmol L(-1) had a 69.2 [54.7-83.7]% sensitivity and a 78.2 [76.8-79.6]% specificity, thus displaying a 12.6% NRI (P 0.001) compared with TG1.17 mmol L(-1) .TG 1.17 mmol L(-1) is a useful criterion to detect roughly 66% of obese children with IGT through OGTT performed in about 33% of all obese children. However, the 'TG≥1.13 mmol L(-1) plus FPG≥4.44 mmol L(-1) ' criterion improved discrimination accuracy, leading to the possibility of detecting even more than 66% of obese children with IGT though limiting OGTT to just 25% of all obese children.

To investigate the relationship between postprandial nutrient balance, satiety and hormone changes induced by two different meals taken after a moderate intensity exercise bout. Ten prepubertal obese children participated in the study. The experiment was designed as a cross-over study for repeated measures. Each test period lasted five consecutive hours during which the children were under medical supervision. The effects of two isocaloric meals were compared after a moderate intensity exercise (4 multiples of resting metabolic rate, 30 min, cycling): a low-fat/high-carbohydrate meal (meal A) and a high-fat/low-carbohydrate meal (meal B). Pre and postprandial (3 h) substrate oxidation, biochemical parameters, gastrointestinal hormone concentrations and appetite were measured. The main results were: (i) higher fat balance (5.1±5.0 vs −5.0±6.6 g, P=0.001) and lower carbohydrate balance after meal B than A (−9.7±13.3 vs 11.3±18.3 g, P

Carbohydrate counting (CHC) in combination with nutritional education has been used to optimize the insulin dose in patients with type 1 diabetes (T1D). The aim of this study was to test the impact of CHC and nutritional education on changes in dietary habits, body composition and body fat distribution in children with T1D treated with insulin pumps (CSII). Twenty-five children with T1D and CSII were recruited and valuated at baseline and after 18 months of follow-up. They were trained in CHC and following standard nutrition education program (based on American Diabetes Association and International Society of Pediatric and Adolescent Diabetes guidelines); clinical, biochemical and nutritional variables were measured. In the total population, body composition, body fat distribution and biochemical variables did not change, at follow-up; HbA1c was significantly reduced (8.50 ± 0.77 vs 7.92 ± 0.74 %; p < 0.001) without changing insulin/kg/day requirement. In the sub-group of patients with a significant HbA1c reduction (ΔHbA1c ≥ 0.5 %, n = 12), the carbohydrate (CHO) intake was significantly higher at follow-up (53.0 ± 4.0 vs 57.6 ± 2.5 %; p < 0.01); on the contrary, fat (31.3 ± 3.6 vs 28.5 ± 1.6 %; p < 0.05) and protein intake (15.4 ± 1.8 vs 13.3 ± 1.6 %; p < 0.01) significantly decreased. Patients without a significant HbA1c reduction did not show any difference. CHC, in combination with nutritional education, does not affect dietary habits, body composition and body fat distribution in children with T1D treated with CSII. Moreover, the sub-group of subjects showing a significant improvement in glycometabolic control reported an increase in CHO intake and a reduction in fat and protein intake.

Granuloma annulare (GA) has rarely been reported in childhood, and its etiology still remains unclear. Its association with type 1 diabetes (T1D) and other chronic systemic diseases such as autoimmune thyroiditis (AT) or rheumatoid arthritis has been reported. There is no description in the literature of pediatric cases and the simultaneous association of GA and multiple autoimmune diseases in the same subject. We report the case of a 5-year-old girl who presented onset signs and symptoms of T1D. The diagnosis of T1D was confirmed by the presence of autoimmune T1D antibodies. Moreover, AT was also diagnosed by autoantibodies and positive ultrasound. One month later, coin-size erythematous lesions appeared initially on the trunk but soon spread over the body. Once dermatophytosis had been excluded, a skin biopsy confirmed a diagnosis of GA. Although a clear mechanism remains still unknown, clinicians must take into consideration an association of GA in patients with T1D or AT to avoid unnecessary medical investigations and/or inadequate pharmacological treatment.

Obesity is a complex public health issue. Recent data indicate the increasing prevalence and severity of obesity in children. Severe obesity is a real chronic condition for the difficulties of long-term clinical treatment, the high drop-out rate, the large burden of health and psychological problems and the high probability of persistence in adulthood. A staged approach for weight management is recommended. The establishment of permanent healthy lifestyle habits aimed at healthy eating, increasing physical activity and reducing sedentary behavior is the first outcome, because of the long-term health benefits of these behaviors. Improvement in medical conditions is also an important sign of long-term health benefits. Rapid weight loss is not pursued, for the implications on growth ad pubertal development and the risk of inducing eating disorders. Children and adolescents with severe obesity should be referred to a pediatric weight management center that has access to a multidisciplinary team with expertise in childhood obesity. This article provides pediatricians a comprehensive and evidence based update on treatment recommendations of severe obesity in children and adolescents.

The technology of maize without plough land possible to apply in USA and other countries with advanced agriculture, only by atrazine and simazine herbicides synthesis by J. Geigy Company from Switzerland Phillips and Young (1973) said in their book that in USA is practicing no-tillage system on millions acres. After recently dates published by Derpsh (2001) in USA no-tillage is practice on 21,120,000 ha, in Brazil on 14,330,000 ha, in Argentina 10,500,000 ha etc. The chernozem soil in Romania is very properly for no-tillage system. First experiments with no-tillage system have been since 1965 at maize, and at soybean since 2002 until 2005, obtaining remarkable results concerning maize and soybean yields. At genetically modified soybean crop the economic efficiency is very big because fuel consumption was 75 l/ha at classic system and only 21 l/ha at no-tillage system. The expenses with mechanical working were 217 Euro/ha at classic system and only 45 Euro/ha at no-tillage system.

The aim of this work was to determine the effect of intensive feeding (IF group) or pasture system (PS group) on the onset of puberty and on the ovarian size in buffaloes. The trial was carried out on 26 prepubertal 8-months old buffalo heifers weighing a mean of 134 kg (n =13 per group). The heifers were weighed monthly and, starting from the 13th month of age, blood samples were collected every 10 days to determine the concentration of plasma progesterone by RIA. Heifers were considered to have achieved puberty and cyclic ovarian activity when plasma progesterone levels exceeded 1 ng/ml for two samples with a lower intermediate value. After two cycles, the heifers were naturally mated. Transrectal ultrasonography was performed every twenty days to follow changes in size of ovaries and in follicles number. Significantly higher (P

Saulsbury et al emphasize the diagnostic challenge of periodic fevers in pediatrics by describing a case of PFAPA (Periodic Fever, Aphthous stomatitis, Pharyngitis, and Cervical Adenopathy) that was eventually diagnosed as TNFa Receptor-Associated Period Fever (TRAPS). PFAPA is a syndrome and not a specific disease and—as pointed out previously—some symptoms, for instance aphthous stomatitis, may not be present. Moreover, other symptoms are very common, for example abdominal pain, which is present in 60% of all cases. The importance of these symptoms warrants in many children the evaluation of different diagnoses, including other periodic fevers (hyper-IgD syndrome [HIDS], TRAPS) and even Crohn’s disease. We recently described three cases of HIDS in which the disease onset was characterized by a PFAPA-like symptomatology and by severe abdominal complaints.

Central Nervous System involvement in Monoclonal gammopathies of undetermined significance has seldomly been reported and in all the cases a demyelinating disease was found. We report the case of a young man who had been suffering for five years of progressive cerebellar syndrome. MRI showed marked cerebellar vermis atrophy. An IgG lambda monoclonal gammopathy was revealed in the serum. Cerebrospinal fluid examination showed oligoclonal bands and elevated Link-Index. Serologic research for HBV, HCV, HIV, Lues, Rubella, Measles was negative, as also genetic analysis for SCA1, SCA2, SCA3, SCA7 and Friederich's ataxia. Nerve conduction studies were normal. Plasmatic vit.E was low, but treatment with high doses of tocopherol was ineffective. i.v. immunoglobulins and steroids obtained only transient clinical benefits. In conclusion, we hypothesize a pathogenetic role of the IgG in this cerebellar atrophy.

Patients with cerebral neoplasms often report pain or other kinds of symptoms which, even though not directly connected to the disease itself, can cause complications in the approach to therapy and worsen the quality of life of the patients. The therapies aimed at controlling these kinds of disturbances are referred to as supportive therapies as they do not cure the underlying disease. However, these therapies should not be underestimated, because, by controlling these disturbances, they are able not only to greatly improve the quality of life of the neuro-oncologic patients but also increase their survival. Based on this hypothesis, we will discuss and examine the drugs more frequently used for supportive therapy in neuro-oncologic patients. We assert, in fact, that the desire to offer neuro-oncologic patients better assistance guarantees not only adequate specialized input from the health operators involved, concerning the quality of life and the uniqueness of the 'person-patient', but also the ability to be able to listen to the patients, understand their choices and allow them to express their priorities.

We describe herein the case of a 57 year old man who, over the last five years, has presented ataxic and spastic gait on the right side, a reduction in fine motor movement of the fingers mainly on the right side, superficial right side brachiocrural hypoesthesia and a marked dysarthria associated with internuclear ophthalmoplegia. The neurological picture, after an initial progressive worsening which lasted some months, remained relatively stable over the years. Repeated magnetic resonance imaging (MRI) of the brain and spinal cord documented the presence of demyelinating plaques spread in the white matter of the periventricular region and the semioval centres, and a right side paramedian plaque at the C4-C5 level, none of which were in the active phase. Oligoclonal bands were revealed in the cerebrospinal fluid (CSF). Monoclonal IgM/lambda gammopathy with anti-myelin and anti-nucleo reactivity, found with serum immunofixation, were confirmed several times in successive annual controls, not associated to myeloproliferative pathology. The lack of progression in the clinical picture would seem to contradict the diagnosis of late Multiple Sclerosis. The presence of antibody activity against the myelin might support the hypothesis of a pathogenetic role of the immunoglobulins at the onset of the demyelinating disease in this patient. However, in the end, there is the possibility of casual association with a poorly functioning immune system connected to age.

Diabetic foot is a complication of diabetes mellitus occurring in 15% of patients that is of specific surgical interest. Over the past few years, preventive measures and the use of new therapeutic resources has reduced the number of patients undergoing demolitive surgery. The authors present a concise but at the same time sufficiently detailed picture of modern knowledge of the physiopathology, clinical aspects and current therapeutic guidelines for diabetic foot. In particular, they analyse the validity of various forms of complementary treatment to surgery, including techniques to stimulate tissue repair processes, hyperbaric oxygen therapy and laser therapy, and they underline the importance of using a multidisciplinary approach to this pathology. To this end, they review all the articles on the subject reported on Medline from 1992 to June 1998, presenting and commenting on the most significant results.

The effect of lamotrigine (LTG) as add-on therapy on electroencephalogram (EEG) background activity was studied in 11 patients with refractory partial seizures with or without secondary generalization. The computerized EEG study was performed at rest with eyes closed (EC), during blocking reaction (BR), fixation (FIX), and mental arithmetic (MA) tasks. EEG spectral values were analyzed statistically using three-way ANOVA. The neuropsychological evaluation included a battery of six tests. Epileptic patients before LTG therapy, compared with control subjects, displayed at rest condition EEG changes consisting of higher delta and theta relative power coupled with lower alpha and beta power. During performance of attentive (BR) and cognitive (FIX) tasks, a decrease in alpha reactivity associated with a decrease of beta 1 and beta 2 power was found. The addition of LTG to previous therapy induced changes, although subtle, consisting of an increase in both alpha reactivity and beta power to attentive task. Neuropsychological evaluation did not evidence any impairment of cognitive functions. During LTG therapy, a decrease in seizure frequency occurred in 9 of the 11 patients whereas no changes were observed in the remaining 2. On the basis of these neurophysiologic and neuropsychological findings, LTG as add-on therapy does not seem to produce adverse side effects on mental activity; moreover, EEG data indicate a slight improvement in attentional processes.

Several studies have demonstrated substantial risk reduction by risk factor modification in patients with established coronary artery disease. The number of studies investigating the implementation of risk factor intervention in clinical practice, however, is limited. We have, therefore, recorded drug use and cardiovascular risk factors in all 148 patients who had undergone percutaneous coronary angioplasty (PTCA) in 1989 at the University Hospital, Zurich, on hospital admission, after 6 months and 5 years later. Most patients had antithrombotic treatment with little change over time (78%, 87% and 83% on admission, after 6 months and after 5 years respectively, p = 0.27). The use of beta-blockers decreased moderately after 5 years (73%, 81% and 61% respectively, p0.01). Calcium channel blockers were used frequently without significant change in the follow-up period (56%, 50% and 46%, p = 0.25). Five years after PTCA, 91% of patients with a history of hypertension were on antihypertensive drugs. The use of lipid-lowering drugs increased markedly (5%, 16% and 33% respectively, p0.01). However, only a small proportion of patients qualifying for lipid-lowering drugs according to Swiss guidelines were treated. The proportion of current smokers decreased from 26% on hospital admission in 1989 to 12% in 1994. We conclude that in our study population secondary prevention was generally satisfactorily implemented. However, better monitoring and treatment of increased lipid levels is mandatory.

Background CRC is the second leading cause of cancer death in Canada. Bevacizumab, a recombinant humanised monoclonal antibody that selectively binds to human vascular endothelial growth factor, is approved and funded for first line mCRC use in Canada. A substudy has also confirmed its effectiveness in KRAS wild-type patients. Recent evidence has also shown clinical benefit from anti-epidermal growth factor treatments panitumumab and cetuximab in these patients. Objective: We assessed cost-effectiveness of fluoropyrimidine-based chemotherapy (FBC) alone and in combination with bevacizumab, panitumumab or cetuximab for first line treatment of KRAS wild-type mCRC patients. Methods Cost-effectiveness to the Canadian health care system was estimated using separately reported trial survival and adverse event results for each comparator. We used a Markov model calibrated to progression-free/overall survival, and calculated quality-adjusted life years (QALYs). Health-state resource utilization was derived from published data and Canadian oncologist input. Health state utilities and unit prices were obtained from published literature and standard Canadian sources. Results Results per patient over a lifetime horizon, to a maximum 10 years with 5% discounting are presented below. Comparators are ordered by total cost, and the incremental cost-effectiveness ratio (ICER) of each is determined against the previous non-dominated therapy. Comparator Total Cost Total QALYs Δ Cost Δ QALYs ICER FBC $39,061 1.354 - - - Bevacizumab + FBC $104,054 1.848 $64,993 0.494 $131,631 Panitumumab + FBC $151,776 1.806 $47,722 -0.041 Dominated Cetuximab + FBC $161,596 1.865 $57,542 0.017 $3,327,501 Conclusion For first line treatment of KRAS wild-type mCRC in Canada, bevacizumab + FBC is associated with substantially lower costs than panitumumab + FBC or cetuximab + FBC. All three biologics may be associated with similar QALYs, although; this conclusion was based on the limitation of modelling life expectancy from separate trials. Given these findings, bevacizumab seems likely to offer the best value for money for this patient population. Disclosure D. Lawrence: Donna Lawrence is an employee of OptumInsight under contract with Roche. M. Maschio: Michael Maschio is an employee of OptumInsight under contract with Roche. S. Yunger: Simon Yunger is employee of Roche Canada. N. Aucoin: Dr. Aucoin has participated in advisory boards with Roche and Amgen. M. Weinstein: Dr. Weinstein is a consultant to OptumInsight for research under contract with Roche. All other authors have declared no conflicts of interest.

It is well known that deferoxamine (DFO) treatment in thalassemia major can produce ocular toxicity. In one experience, Visual evoked potentials (VEPS) to pattern reversal were formed to be altered in 4 out of 10 patients under conventional treatment with DFO, before supplementary high-dose i.v. deferoxamine. In all 4 cases the alterations consisted of bilaterally delayed P100 latency, always obtained by stimulation with high spatial frequency (15' checks) and associated in three cases with low spatial frequency (55'). Computerized EEG (cEEG) studies showed a generalized increase of slowing activity. All patients underwent high-dose DFO treatment.At the control performed at the end of treatment in all 4 cases with previous VEP alterations, a further delay in P100 latency was observed bilaterally while two of the six patients, without previous involvement, showed delayed responses when using checks of 15'. The EEG slowing activity was not modified. Three weeks after terminating i.v. DFO therapy, the patients were still under subcutaneous treatment (50 mg/kg/day); a more evident VEP recovery towards the initial values was observed in those patients without initial alterations. No significant changes were found between electrophysiological parameters and serum ferritin levels.Our results indicate that high-dose DFO therapy in patients with iron overload induces reversible visual impairment without significant changes in brain electrical activity. The employment of VEP in intensive chelation programs in thalassemia major is discussed.

We evaluated anti-HBs titers 2 months after vaccination with recombinant hepatitis surface antigen (rDNA-HBsAg) in 43 maintenance hemodialysis patients (MHP). Of these, 34 had not undergone hepatitis B virus vaccination previously (NV-MHP) and 9 had shown negative response to vaccination with plasma-derived HBsAg (HEVAC Pasteur; V-MHP). 120 healthy workers from the same hospital undergoing rDNA-HBsAg immunization were used as controls. All low responders (LR) (anti-HBs less than 100 mIU/ml) and nonresponders (NR; anti-HBs less than 10 mIU/ml) were given a booster dose 3 months after the last dose of vaccine. Seroconversion rates were lower in NV-MHP (52.9%) than in controls (98.4%). V-MHP showed higher seroconversion rates (88.9%) than NV-MHP. In each group, the number of responders (R; anti-HBs greater than or equal to 100 mIU/ml), LR and NR was as follows: controls 101, 17, 2; NV-MHP 6, 12, 16; V-MHP 8, 0, 1. After booster dose, 17/17 controls LR and no NV-MHP LR showed a rise in anti-HBs titers over 100 mIU/ml. Six months after the last dose of vaccine or the booster dose, anti-HBs titer fell under 10 mIU/ml in 4/12 MHP LR and under 100 mIU/ml in 6/14 MHP R. To achieve high seroconversion rates and to avoid the decline of anti-HBs to nonprotective titers in MHP, a booster injection should be made at different dates after the first vaccination.

The possible use of the human umbelical vein as a vascular transplant, following appropriate chemico-physical treatment is discussed. The properties of this new prosthesis have been studied on the basis, first, of physical and dynamic tests and, thereafter, following experimental intervention on 12 dogs in which a segment of the abdominal aorta was replaced. The animals were angiographed at varying times from the operation, up to a maximum of 8 months, and finally sacrificed for thorough histological study using various techniques.