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1.
J Endocrinol Invest ; 47(6): 1477-1485, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38112911

ABSTRACT

PURPOSE: MKNR3 is a paternally expressed gene whose mutations are the main cause of central precocious puberty (CPP). Protein circulating levels can be easily measured, as demonstrated in idiopathic CPP and healthy controls. No data are available for patients harboring an MKRN3 mutation. Our aim was to perform MKRN3 mutation screening and to investigate if circulating protein levels could be a screening tool to identify MKRN3 mutation in CPP patients. METHODS: We enrolled 140 CPP girls and performed MKRN3 mutation analysis. Patients were stratified into two groups: idiopathic CPP (iCPP) and MKRN3 mutation-related CPP (MKRN3-CPP). Clinical characteristics were collected. Serum MKRN3 values were measured by a commercially available ELISA assay kit in MKRN3-CPP and a subgroup of 15 iCPP patients. RESULTS: We identified 5 patients with MKRN3 mutations: one was a novel mutation (p.Gln352Arg) while the others were previously reported (p.Arg328Cys, p.Arg345Cys, p.Pro160Cysfs*14, p.Cys410Ter). There was a significant difference in circulating MKRN3 values in MKRN3-CPP compared to iCPP (p < 0.001). In MKRN3-CPP, the subject harboring Pro160Cysfs*14 presented undetectable levels. Subjects carrying the missense mutations p.Arg328Cys and p.Gln352Arg showed divergent circulating protein levels, respectively 40.56 pg/mL and undetectable. The patient with the non-sense mutation reported low but measurable MKRN3 levels (12.72 pg/mL). CONCLUSIONS: MKRN3 defect in patients with CPP cannot be predicted by MKRN3 circulating levels, although those patients presented lower protein levels than iCPP. Due to the great inter-individual variability of the assay and the lack of reference values, no precise cut-off can be identified to suspect MKRN3 defect.


Subject(s)
Mutation , Puberty, Precocious , Ubiquitin-Protein Ligases , Humans , Puberty, Precocious/genetics , Puberty, Precocious/blood , Puberty, Precocious/diagnosis , Female , Ubiquitin-Protein Ligases/genetics , Child , Ribonucleoproteins/genetics , Ribonucleoproteins/blood , Child, Preschool , DNA Mutational Analysis , Case-Control Studies , Biomarkers/blood
2.
ESMO Open ; 6(5): 100279, 2021 10.
Article in English | MEDLINE | ID: mdl-34607284

ABSTRACT

BACKGROUND: KRAS is mutated in ∼30% of non-small-cell lung cancer (NSCLC) but it has also been identified as one of the mechanisms underlying resistance to tyrosine kinase inhibitors (TKIs) in EGFR-positive NSCLC patients. Novel KRAS inhibitors targeting KRAS p.G12C mutation have been developed recently with promising results. The proportion of EGFR-positive NSCLC tumours harbouring the KRAS p.G12C mutation upon disease progression is completely unexplored. MATERIALS AND METHODS: Plasma samples from 512 EGFR-positive advanced NSCLC patients progressing on a first first-line treatment with a TKI were collected. The presence of KRAS p.G12C mutation was assessed by digital PCR. RESULTS: Overall, KRAS p.G12C mutation was detected in 1.17% of the samples (n = 6). In two of these cases, we could confirm that the KRAS p.G12C mutation was not present in the pre-treatment plasma samples, supporting its role as an acquired resistance mutation. According to our data, KRASG12C patients showed similar clinicopathological characteristics to those of the rest of the study cohort and no statistically significant associations between any clinical features and the presence of the mutation were found. However, two out of six KRASG12C tumours harboured less common EGFR driver mutations (p.G719X/p.L861Q). All KRASG12C patients tested negative for the presence of p.T790M resistance mutation. CONCLUSIONS: The KRAS p.G12C mutation is detected in 1% of EGFR-positive NSCLC patients who progress on a first line with a TKI. All KRASG12C patients were negative for the presence of the p.T790M mutation and they did not show any distinctive clinical feature.


Subject(s)
Carcinoma, Non-Small-Cell Lung , Lung Neoplasms , Carcinoma, Non-Small-Cell Lung/drug therapy , Carcinoma, Non-Small-Cell Lung/genetics , ErbB Receptors/genetics , Humans , Lung Neoplasms/drug therapy , Lung Neoplasms/genetics , Mutation , Protein Kinase Inhibitors/therapeutic use , Proto-Oncogene Proteins p21(ras)/genetics
4.
Ann Ig ; 28(5): 339-48, 2016.
Article in English | MEDLINE | ID: mdl-27627665

ABSTRACT

BACKGROUND: The Mediterranean diet (MD) is considered one of the healthiest dietary models, as it decreases the risk of chronic diseases and may modulate the organism's early response to environmental pollution. In recent decades, Mediterranean countries have been replacing their traditional diet with other less healthy eating habits, especially among children and teenagers. OBJECTIVE: The aim of this study was to evaluate the MD and the level of adherence to it in 6-8 year old Italian children, in relation to residence, lifestyle, and social and family contexts. METHODS: A questionnaire was administered to the children's parents in two seasons in 5 Italian towns. The diet section contained 116 questions investigating the frequency of consumption of different types of food. The Italian Mediterranean Index (IMI) was calculated according to the intake of 6 typical Mediterranean and 4 non-Mediterranean foods. On the basis of IMI score, MD adherence was classified as low (≤ 3 IMI score), medium (4-5) and high (≥ 6). Total energy load and diet composition in micro- and macronutrients were calculated from consumption frequency. RESULTS: Diet analysis was computed on 1164 subjects with two complete questionnaires. Body mass index, calculated for each subject, showed that 28.9% of the children were overweight, the figure varying slightly with area of residence. Our findings showed that 59.0% of the children had a low score for MD adherence. CONCLUSIONS: The results of this study showed that most Italian children did not follow the MD and socio-economic characteristics appeared not to be associated with type of diet.


Subject(s)
Diet, Mediterranean , Life Style , Overweight/epidemiology , Parents , Patient Compliance/statistics & numerical data , Adult , Body Mass Index , Child , Diet Surveys , Feeding Behavior , Female , Humans , Italy/epidemiology , Male , Pediatric Obesity/epidemiology , Poverty/statistics & numerical data , Risk Factors , Surveys and Questionnaires
5.
Clin Genet ; 90(5): 445-450, 2016 11.
Article in English | MEDLINE | ID: mdl-26940245

ABSTRACT

Primary autosomal recessive microcephaly (MCPH) is a developmental disorder characterized by prenatal onset of abnormal brain growth. MCPH occurs both alone and as part of a broad range of neurodevelopmental syndromes with or without cortical malformations and growth retardation. Here we report a consanguineous Moroccan family with two siblings affected by severe primary microcephaly, failure to thrive, congenital dermatitis and severe developmental delay. Brain magnetic resonance imaging showed lissencephaly of frontal lobes and periventricular heterotopia of the gray matter. We performed both Comparative Genomic Hybridization array and whole exome sequencing (WES) analyses of the kindred. No quantitative defects were detected. However, WES identified a new homozygous missense variation in the penultimate nucleotide of exon 23 of RTTN gene (c.2953A>G;pArg985Gly). cDNA sequencing revealed two abnormal spliced products, one lacking only exon 23 and the other lacking exons 22 and 23 (out-of-frame). RTTN is a protein involved in cilia structure and function. Homozygous mutations in RTTN gene have been described in bilateral diffuse isolated polymicrogyria and, more recently, in microcephalic primordial dwarfism (PD). We found a novel homozygous mutation in RTTN associated with microcephalic PD as well as complex brain malformations and congenital dermatitis, thus expanding the phenotypic spectrum of both RTTN-associated diseases and ciliary dysfunction.


Subject(s)
Carrier Proteins/genetics , Dermatitis/genetics , Growth Disorders/genetics , Microcephaly/genetics , Brain/diagnostic imaging , Brain/physiopathology , Cell Cycle Proteins , Comparative Genomic Hybridization , Consanguinity , Dermatitis/physiopathology , Exons/genetics , Female , Growth Disorders/diagnostic imaging , Growth Disorders/physiopathology , Homozygote , Humans , Infant , Magnetic Resonance Imaging , Male , Microcephaly/physiopathology , Mutation , Pedigree , Phenotype
6.
Ann Ig ; 27(4): 646-56, 2015.
Article in English | MEDLINE | ID: mdl-26241109

ABSTRACT

INTRODUCTION: The MAPEC-Life project aims to study the biological effects of early exposure to air pollutants on the oral mucosa cells of school-age children in five Italian cities. A questionnaire was created to evaluate the association between outdoor and indoor airborne pollutants, lifestyle, diet and biomarker effects. The feasibility and reliability of the questionnaire were evaluated. METHODS: A questionnaire was drawn up to be filled in by the parents of 6-8-year-old children. It consisted of 148 questions on the children's health, physical activity, environmental exposures and the frequency of food consumption at the main meals. First we conducted a questionnaire feasibility study involving 53 volunteer parents. We then performed a reliability study by administering the questionnaire to a further 156 parents and again one month later (test/retest method). The correlations between answers at the first and second administration of the questionnaire were evaluated using the Kappa statistic and Spearman's coefficient. RESULTS: After verifying the feasibility of the questionnaire, we conducted a reliability analysis on 132 completed questionnaires. The percentage of agreement between the first and the second responses given was over 70%, all K values being greater than 0.6. The analysis of calories and macronutrients also showed good agreement. CONCLUSIONS: The questionnaire drawn up for the study proved to be sufficiently reliable for gathering information about the factors of interest in our study of the relationship between air pollution and early biological effects in children.


Subject(s)
Air Pollution, Indoor , Diet , Environmental Exposure , Health Status , Motor Activity , Surveys and Questionnaires , Air Pollution, Indoor/adverse effects , Child , Environmental Exposure/adverse effects , Environmental Monitoring/methods , Feasibility Studies , Female , Health Surveys , Humans , Italy , Male , Parents , Reproducibility of Results
7.
Diabetes Obes Metab ; 17(7): 689-98, 2015 Jul.
Article in English | MEDLINE | ID: mdl-25846577

ABSTRACT

AIMS: To evaluate third-line thiazolidinedione (TZD) or glimepiride therapy in patients inadequately controlled on metformin + exenatide twice daily, and third-line exenatide twice daily in patients inadequately controlled on metformin + glimepiride. METHODS: In this randomized, open-label, multicentre trial, 144 patients with type 2 diabetes inadequately controlled [glycated haemoglobin (HbA1c) >9% (75 mmol/mol) after 3 months' treatment or >7% (53 mmol/mol) at two consecutive visits 3 months apart, after 6 months' treatment] on metformin + exenatide twice daily were re-randomized to add-on TZD or glimepiride, and 166 patients inadequately controlled on metformin + glimepiride received add-on exenatide twice daily. Changes in HbA1c, body mass index (BMI), lipids, hypoglycaemia and vital signs were evaluated. RESULTS: The median duration of triple therapy was ∼2 years. In patients inadequately controlled on metformin + exenatide twice daily, add-on TZD decreased HbA1c levels significantly better than add-on glimepiride: 130-week difference 0.48% [95% confidence interval (CI) 0.19-0.77] or 5.2 mmol/mol (95% CI 2.1-8.4; p = 0.001), but with significantly increased BMI and systolic blood pressure. The ratio of documented symptomatic (blood glucose ≤70 mg/dl [3.9 mmol/l]) hypoglycaemia rates for add-on glimepiride to add-on TZD was 8.48 (p < 0.0001). Add-on exenatide twice daily after metformin + glimepiride significantly reduced HbA1c levels: mean [standard deviation (s.d.)] change from baseline -0.35 (0.89)% [-3.8 (9.7) mmol/mol] and BMI: mean (s.d.) change from baseline -0.82 (1.9) kg/m(2) at 130 weeks, with a slightly increased rate of documented symptomatic hypoglycaemia from metformin + glimepiride (ratio 1.49). CONCLUSIONS: TZD, but not glimepiride, was an effective and well tolerated third-line therapy in patients without glycaemic control after long-term therapy with metformin + exenatide twice daily. Exenatide twice daily was an effective and well tolerated third-line therapy in patients inadequately controlled on metformin + glimepiride.


Subject(s)
Diabetes Mellitus, Type 2/drug therapy , Hypoglycemic Agents/administration & dosage , Metformin/administration & dosage , Peptides/administration & dosage , Sulfonylurea Compounds/administration & dosage , Thiazolidinediones/administration & dosage , Venoms/administration & dosage , Adult , Aged , Blood Glucose/analysis , Body Mass Index , Diabetes Mellitus, Type 2/blood , Drug Administration Schedule , Drug Therapy, Combination , Europe , Exenatide , Female , Glycated Hemoglobin/analysis , Humans , Hypoglycemia/chemically induced , Lipids/blood , Male , Middle Aged , Prospective Studies , Treatment Failure
8.
J Clin Endocrinol Metab ; 98(10): 4152-9, 2013 Oct.
Article in English | MEDLINE | ID: mdl-23884776

ABSTRACT

CONTEXT: ß-Cell function (BCF) declines over the course of type 2 diabetes, but little is known about BCF changes across glucose tolerance status (GTS) categories, and comparisons of direct vs surrogate measures. OBJECTIVE: To assess longitudinal changes in BCF across GTS. DESIGN: The Insulin Resistance Atherosclerosis Study is a multicenter, observational, epidemiologic study. SETTING: Four clinical centers in the US that could identify subjects likely to have impaired fasting glucose (IFG) or impaired glucose tolerance (IGT). PATIENTS: We compared longitudinal changes in BCF in 1052 subjects over 5 years. Subjects were categorized according to baseline GTS: normal glucose tolerance (NGT: n = 547), impaired fasting glucose or impaired glucose tolerance (IFG/IGT: n = 341), and newly diagnosed type 2 diabetes (n = 164). INTERVENTIONS: None. MAIN OUTCOME MEASURES: BCF was assessed from a frequently sampled iv glucose tolerance test (AIR, acute insulin response), and the homeostasis model assessment of BCF (HOMA B). RESULTS: NGT and IFG/IGT subjects increased their insulin secretion over time, whereas those with type 2 diabetes experienced either decline or little change in BCF. After adjustment for demographic variables and change in insulin resistance, change in HOMA B underestimated the magnitude of changes in BCF, as assessed by change in AIR. Relative to NGT, the 5-year change in insulin secretion in IFG/IGT and type 2 diabetes was 31% and 70% lower (by HOMA B) and 50% and 80% lower (by AIR). CONCLUSIONS: The decline in BCF over time in IFG/IGT and type 2 diabetes may be more pronounced than previously estimated; HOMA B may underestimate this decline significantly.


Subject(s)
Diabetes Mellitus, Type 2/physiopathology , Glucose Intolerance/physiopathology , Insulin Resistance/physiology , Insulin-Secreting Cells/physiology , Prediabetic State/physiopathology , Adult , Aged , Atherosclerosis/physiopathology , Blood Glucose , Fasting/physiology , Female , Glucose Tolerance Test , Humans , Longitudinal Studies , Male , Middle Aged
9.
HIV Med ; 14(8): 481-90, 2013 Sep.
Article in English | MEDLINE | ID: mdl-23560682

ABSTRACT

OBJECTIVES: The aim of the study was to investigate the incidence of AIDS-defining cancers (ADCs) and virus-related and non-virus-related non-AIDS-defining cancers (NADCs) in HIV-infected patients compared with the general population, and to assess the risk factors associated with these malignancies. METHODS: We performed a retrospective cohort study for the period from 1999 to 2009 of HIV-infected patients residing in the Local Health Authority of Brescia (northern Italy). Observed cancers in patients with HIV infection were compared with expected cancers in the population living in the same area using standardized incidence ratios (SIRs). Risk factors were assessed using Poisson regression analysis. RESULTS: A total of 5090 HIV-infected patients were included in the study, with 32 390 person-years of follow-up. We recorded 416 tumours in 390 HIV-infected patients. Two hundred of these (48.1%) were ADCs, 138 (33.2%) were non-virus-related NADCs and 78 (18.7%) were virus-related NADCs. An increased risk (SIR = 4.2) of cancers overall was found in HIV-infected patients. A large excess of ADCs (SIR = 31.0) and virus-related NADCs (SIR = 12.3) was observed in HIV-infected patients, while the excess risk for non-virus-related NADCs was small (SIR = 1.6). The highest SIRs were observed for Kaposi sarcoma among ADCs and for Hodgkin lymphoma among virus-related NADCs. Conversely, among non-virus-related NADCs, SIRs for a broad range of malignancies were close to unity. In multivariate analysis, increasing age and CD4 cell count < 50 cells/µL were the only factors independently associated with all cancers. CONCLUSIONS: Among HIV-infected people there was an excess of ADCs and also of NADCs, particularly those related to viral infections. Ageing and severe immunodeficiency were the strongest predictors.


Subject(s)
HIV Infections/epidemiology , Lymphoma, AIDS-Related/epidemiology , Neoplasms/epidemiology , Acquired Immunodeficiency Syndrome/complications , Adult , Age Factors , Aged , CD4 Lymphocyte Count , Cohort Studies , Comorbidity , Female , Hodgkin Disease/epidemiology , Humans , Italy/epidemiology , Male , Middle Aged , Poisson Distribution , Regression Analysis , Retrospective Studies , Risk Factors , Sarcoma, Kaposi/epidemiology , Young Adult
10.
Diabetologia ; 56(1): 112-20, 2013 Jan.
Article in English | MEDLINE | ID: mdl-23052060

ABSTRACT

AIMS/HYPOTHESIS: Insulin clearance may decline as an early mechanism compensating for deteriorating insulin sensitivity. However, no previous studies have investigated the association between subclinical inflammation or impaired fibrinolysis and insulin clearance. We examined the association between plasminogen activator inhibitor (PAI)-1, C-reactive protein (CRP), TNF-α, leptin and fibrinogen and the progression of metabolic clearance rate of insulin (MCRI) over time. METHODS: We studied 784 non-diabetic white, Hispanic and African-American individuals in the Insulin Resistance Atherosclerosis Study (IRAS). Insulin sensitivity, acute insulin response and MCRI were determined from frequently sampled intravenous glucose tolerance tests at baseline and at 5-year follow-up. Inflammatory and fibrinolytic proteins were measured in fasting plasma at baseline. RESULTS: MCRI had declined significantly by 29% at the 5-year follow-up. We observed a significant association between higher plasma PAI-1 levels and the decline in MCRI in multivariable-adjusted regression models (ß = -0.045 [95% CI -0.081, -0.0091]). Higher plasma CRP and leptin levels were associated with a decline in MCRI in unadjusted models, but these associations were non-significant after adjusting for BMI and waist circumference (ß = -0.016 [95% CI -0.041, 0.0083] for CRP; ß = -0.044 [95% CI -0.10, 0.011] for leptin). A higher plasma TNF-α concentration was associated with a decline in MCRI in unadjusted (ß = -0.071 [95% CI -0.14, -0.00087]) but not in multivariable-adjusted (ß = -0.056 [95% CI -0.13, 0.017]) models. Plasma fibrinogen level was not associated with the change in MCRI. CONCLUSIONS/INTERPRETATION: We identified that higher plasma PAI-1 (but not CRP, TNF-α, leptin or fibrinogen) levels independently predicted the progressive decline of insulin clearance in the multiethnic cohort of the IRAS.


Subject(s)
Atherosclerosis/etiology , Hypoglycemic Agents/pharmacokinetics , Insulin Resistance , Insulin/pharmacokinetics , Overweight/physiopathology , Plasminogen Activator Inhibitor 1/blood , Prediabetic State/etiology , Atherosclerosis/epidemiology , Body Mass Index , Cohort Studies , Diabetic Angiopathies/blood , Diabetic Angiopathies/epidemiology , Diabetic Angiopathies/immunology , Diabetic Angiopathies/metabolism , Female , Fibrinogen/analysis , Follow-Up Studies , Humans , Hypoglycemic Agents/blood , Inflammation Mediators/blood , Insulin/blood , Leptin/blood , Male , Metabolic Clearance Rate , Middle Aged , Overweight/blood , Overweight/immunology , Overweight/metabolism , Prediabetic State/epidemiology , Prospective Studies , Risk Factors , United States/epidemiology
12.
Ann Ig ; 22(2): 165-75, 2010.
Article in Italian | MEDLINE | ID: mdl-20476656

ABSTRACT

A random sample of 1,495 high school student of 9th and 13th grade in Brescia, North Italy, were interviewed about their alcohol consumption, knowledge and attitudes using an anonymous self-administered questionnaire. The percentages of students who usually consumed alcoholic beverage, were 39.7% and 30.3% in males and females, respectively, in 9th grade students and were 51.4% and 23.8% in males and females, respectively, in 13th grade students. The frequency of drunkenness during the month previous the interview was, among 9th graders: 6.9% males and 8.7% females; among 13th graders: 20.7% males and 13.3% females. The following variables were positively associated with alcohol consumption: 1) regular smoking; 2) peer alcohol drinking (best friend and partner); 3) parents' alcohol consumption. When comparing the present survey with a previously carried out in 1989, similar results were found as regards alcohol consumption; on the contrary higher prevalence of drunkenness was found in the 2008 survey, that in the 1989 one.


Subject(s)
Alcohol Drinking/epidemiology , Adolescent , Female , Humans , Italy/epidemiology , Male , Surveys and Questionnaires
13.
Int J Immunopathol Pharmacol ; 21(3): 751-6, 2008.
Article in English | MEDLINE | ID: mdl-18831914

ABSTRACT

Cryptococcus neoformans infections are typically associated with T-cell deficiencies, including acquired immunodeficiency syndrome (AIDS). Although highly active antiretroviral therapy (HAART) has strongly reduced AIDS-related opportunistic infections, the restoration and reactivation of CD4+ cells can induce an immune reconstitution inflammatory syndrome (IRIS), consisting in a deregulated inflammatory response to latent infectious pathogens and/or to their residual antigens. Cryptococcal lymphadenitis has occasionally been documented in IRIS. Here we report a case of histology- and culture-negative cryptococcal lymphadenitis associated with IRIS in an adult AIDS patient with a history of disseminated cryptococcosis, after the start of fully adherent HAART. Appropriate diagnosis was established on nested-PCR and sequence analysis of the interspacer region 2 of C. neoformans ribosomal DNA, and detection of slow-growing blastospores in enrichment cultures of fine-needle lymph node aspirate. Review of recent literature and our case findings suggest that IRIS-associated cryptococcal lymphadenitis is more likely the flare up of a latent infection rather than an immunopathological response to residual antigen of unviable cryptococci.


Subject(s)
AIDS-Related Opportunistic Infections/etiology , Cryptococcosis/etiology , HIV Seropositivity/complications , Inflammation/complications , Lymphadenitis/etiology , Adult , Humans , Male , Syndrome
14.
Opt Express ; 16(16): 12334-41, 2008 Aug 04.
Article in English | MEDLINE | ID: mdl-18679510

ABSTRACT

We report on a single-end diode-pumped waveguide laser providing output power in excess of 20 mW with 17% slope efficiency in robust single longitudinal and transverse mode operation at 1533.5 nm. The active medium was an Er:Yb-doped waveguide only 9-mm long fabricated by Ag-Na ion-exchange in a phosphate glass. The overall cavity length including butt-coupled fiber-Bragg-grating mirrors was <60 mm. We also report on high power waveguide lasers providing more than 160 mW output power and 46% slope efficiency in multimode operation. Feasibility of high power single mode waveguide lasers based on ion-exchange technology in phosphate glasses is also experimentally investigated by using a 50-mm long active waveguide specially designed for efficient single-end pumping.


Subject(s)
Lasers , Lenses , Refractometry/instrumentation , Equipment Design , Equipment Failure Analysis , Ions
15.
Opt Lett ; 32(8): 903-5, 2007 Apr 15.
Article in English | MEDLINE | ID: mdl-17375148

ABSTRACT

Optical burst amplification in a gain-stabilized amplifier may generate complex gain dynamics with nonlinear behavior. This phenomenon is thoroughly investigated by using a theoretical model and dedicated experiments. Design guidelines for optimized devices avoiding optical burst transmission impairments are proposed.

16.
Diabetologia ; 50(2): 259-67, 2007 Feb.
Article in English | MEDLINE | ID: mdl-17160407

ABSTRACT

AIMS/HYPOTHESIS: The aim of this 52-week, open-label, non-inferiority trial was to compare the safety and efficacy of exenatide (an incretin mimetic) with that of biphasic insulin aspart. MATERIALS AND METHODS: Patients on metformin and a sulfonylurea were randomised to exenatide (n = 253; 5 microg twice daily for 4 weeks, 10 microg thereafter) or biphasic insulin aspart (n = 248; twice-daily doses titrated for optimal glucose control), while continuing with metformin and sulfonylurea treatment. RESULTS: Glycaemic control achieved with exenatide was non-inferior to that achieved with biphasic insulin aspart (mean+/-SEM, HbA(1c) change: exenatide -1.04 +/- 0.07%, biphasic insulin aspart -0.89 +/- 0.06%; difference -0.15 [95% CI -0.32 to 0.01]%). Exenatide-treated patients lost weight, while patients treated with biphasic insulin aspart gained weight [between-group difference -5.4 (95% CI -5.9 to -5.0) kg]. Both treatments reduced fasting serum glucose (exenatide -1.8 +/- 0.2 mmol/l, p < 0.001; biphasic insulin aspart -1.7 +/- 0.2 mmol/l, p < 0.001). Greater reductions in postprandial glucose excursions following morning (p < 0.001), midday (p = 0.002) and evening meals (p < 0.001) were observed with exenatide. The withdrawal rate was 21.3% (54/253) for exenatide and 10.1% (25/248) for biphasic insulin aspart. Nausea (33% incidence, 3.5% discontinuation) was the most common adverse event observed with exenatide. CONCLUSIONS/INTERPRETATION: Exenatide treatment resulted in HbA(1c) reduction similar to biphasic insulin aspart and provided better postprandial glycaemic control, making it a potential alternative for the treatment of type 2 diabetes. Treatment with biphasic insulin aspart was associated with weight gain and lower risk of adverse gastrointestinal events. Although the availability of glucose-lowering agents associated with weight reduction may be considered a therapeutic advance, the long-term implications of progressive weight reduction observed with exenatide have yet to be defined.


Subject(s)
Diabetes Mellitus, Type 2/drug therapy , Hypoglycemic Agents/therapeutic use , Insulin/therapeutic use , Metformin/therapeutic use , Peptides/therapeutic use , Venoms/therapeutic use , Blood Glucose/drug effects , Blood Glucose/metabolism , Blood Pressure , Drug Therapy, Combination , Exenatide , Female , Glycated Hemoglobin/metabolism , Humans , Lipids/blood , Male , Middle Aged , Sulfonylurea Compounds/therapeutic use
17.
Opt Express ; 15(6): 3190-4, 2007 Mar 19.
Article in English | MEDLINE | ID: mdl-19532557

ABSTRACT

A compact and efficient single longitudinal mode laser based on a femtosecond laser written waveguide is demonstrated. A maximum output power exceeding 50 mW was measured in single longitudinal and transverse mode operation, with 21% slope efficiency. The active waveguide was fabricated on erbium-ytterbium-doped phosphate glass by direct writing with femtosecond laser pulses from a diode-pumped cavity-dumped oscillator.

18.
Eur J Clin Invest ; 36(8): 536-43, 2006 Aug.
Article in English | MEDLINE | ID: mdl-16893375

ABSTRACT

BACKGROUND: Staphylococcus aureus expresses a variety of adhesins involved in the colonization of host tissues. This study aimed to evaluate the role of staphylococcal surface proteins in the aetiology of infective endocarditis (IE) and the host immune response to infection. MATERIALS AND METHOD: The ELISA assays were used to assess the adherence of S. aureus isolates recovered from the blood cultures of 19 patients with IE (16 were drug abusers) to subendothelial matrix proteins. Anti-adhesin antibody titre was measured incubating surface-coated bacterial antigens with patients' IgG. S. aureus effects on platelet aggregation were evaluated with an aggregometer. RESULTS: Staphylococcus aureus isolates, from the patients with IE, exhibited a high expression of several surface components recognizing extracellular matrix proteins: clumping factors A and B (ClfA and ClfB) and fibronectin-binding proteins (FnbpA and FnbpB), whereas only four strains expressed the collagen-binding protein CNA. Bacteria also interacted with platelets both in the absence or presence of fibronectin or fibrinogen and some strongly supported platelet aggregation. Almost all patients presented significantly higher antibody reactivity to ClfA, ClfB, FnbpA, CNA and MAP (MHC class II analogous protein) than in sera from healthy individuals. On the contrary, the reactivity to CNA was remarkable only in three patients. The IgG preparations weakly inhibited the binding of bacteria to fibronectin, whereas they exhibited considerable blocking activity on staphylococcal attachment to fibrinogen or collagen. CONCLUSION: Adhesins ClfA, ClfB and FnbpA are produced in vivo and appear important factors both in valve colonization and in promoting host immune responses.


Subject(s)
Antibodies, Bacterial/biosynthesis , Endocarditis, Bacterial/immunology , Staphylococcal Infections/immunology , Adhesins, Bacterial/immunology , Adult , Bacterial Adhesion/immunology , Endocarditis, Bacterial/microbiology , Enzyme-Linked Immunosorbent Assay/methods , Extracellular Matrix Proteins/immunology , Female , Humans , Immunoglobulin G/immunology , Male , Middle Aged , Platelet Adhesiveness/immunology , Platelet Aggregation/immunology , Staphylococcal Infections/complications
19.
Int J STD AIDS ; 16(7): 515-7, 2005 Jul.
Article in English | MEDLINE | ID: mdl-16004637

ABSTRACT

Extra-intestinal cryptosporidiosis, especially of the biliary and respiratory tract, is likely in the course of an intestinal involvement, whereas it is rare without such a localization. We report a case of pulmonary cryptosporidiosis without apparent intestinal involvement in an AIDS patient, with favourable outcome after antimicrobial combination therapy with paromomycin plus azithromycin. The successful response to antimicrobial treatment was subsequently maintained by effective highly active antiretroviral therapy (HAART). We suggest that respiratory cryptosporidiosis should be investigated in HIV-infected patients with pulmonary symptoms and low CD4 cell count, and, if detected, treatment should include HAART plus the combination of paromomycin and azithromycin.


Subject(s)
AIDS-Related Opportunistic Infections/drug therapy , Azithromycin/therapeutic use , Cryptosporidiosis/drug therapy , Cryptosporidium parvum/drug effects , Lung Diseases, Parasitic/drug therapy , Paromomycin/therapeutic use , AIDS-Related Opportunistic Infections/parasitology , Animals , Antiretroviral Therapy, Highly Active , Cryptosporidiosis/parasitology , Drug Therapy, Combination , HIV Infections/complications , HIV Infections/drug therapy , Humans , Lung Diseases, Parasitic/parasitology , Male , Middle Aged , Treatment Outcome
20.
Clin Microbiol Infect ; 10(4): 332-4, 2004 Apr.
Article in English | MEDLINE | ID: mdl-15059123

ABSTRACT

The BDProbeTec MTB assay for direct detection of Mycobacterium tuberculosis was evaluated in comparison with the AMTD-II assay on 94 samples from different patients with clinical suspicion of tuberculosis. Using a combination of culture on Lowenstein-Jensen medium (with or without preculture in BACTEC 9000) and clinical diagnosis as the standard, BDProbeTec MTB showed high sensitivity and specificity (96.1% and 100%, respectively), similar to AMTD-II (96.1% and 97.1%, respectively), with significantly higher sensitivity than the Ziehl-Neelsen stain for acid-fast bacilli (73%, p < 0.05).


Subject(s)
Mycobacterium tuberculosis/isolation & purification , Nucleic Acid Amplification Techniques/methods , Tuberculosis, Pulmonary/diagnosis , Tuberculosis/diagnosis , Culture Media , DNA Transposable Elements/genetics , DNA, Ribosomal/genetics , Humans , Mycobacterium tuberculosis/genetics , Mycobacterium tuberculosis/growth & development , RNA, Ribosomal, 16S/genetics , Reagent Kits, Diagnostic , Sensitivity and Specificity , Tuberculosis/microbiology , Tuberculosis, Pulmonary/microbiology
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