Alessandra Ferrarini

Ente Ospedaliero Cantonale, Bellinzona, Ticino, Switzerland

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Publications (29)247.8 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Trials with pulverized brand-name antihypertensive drugs suggest that, from the perspective of taste acceptability, crushed candesartan, chlortalidon, hydrochlorothiazide, lercanidipine and lisinopril should be preferred to pulverized amlodipine, atenolol, bisoprolol, enalapril, irbesartan, losartan, ramipril, telmisartan and valsartan. Brand-name antihypertensive drugs and the corresponding generic medicines have never been compared with respect to their taste acceptability. We therefore investigated among healthy health care workers the taste acceptability of a pulverized 1mg-test dose of the brand-name and two generics containing either the dihydropyridine calcium-channel blocker amlodipine (Norvasc(®), Amlodipin-Mepha(®) and Amlodipin Pfizer(®)) or the angiotensin receptor antagonist candesartan (Atacand(®), Cansartan-Mepha(®) and Pemzek(®)). For this purpose, a smiley-face scale depicting four degrees of pleasure was used. Between November and December 2013, the taste test was performed among 19 nurses (15 female and 4 male subjects) and 12 physicians (5 female and 7 male subjects) aged between 25 and 49 years. Pulverized brand-names and generics containing either amlodipine or candesartan did not differ with respect to their taste acceptability.
    International Journal of Pharmaceutics 04/2014; · 3.99 Impact Factor
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    ABSTRACT: Acute benign myalgia cruris is characterized by transient bilateral calf pain that leads to difficulty walking. A regional outbreak of influenza virus B-associated myalgia cruris was observed during the seasonal influenza outbreak observed in Switzerland from week 1 to 13 of 2013. We performed a prospective case finding among the Swiss-Italian pediatric emergency units and pediatricians. A review of the literature was also performed. The diagnosis of myalgia cruris was made in 49 Swiss-Italian children aged 3.0-14 years (♂:♀=1.7). Flu-like symptoms were resolving when bilateral calf pain began that remitted over ⩽7 days. The creatine kinase-level, assessed in 28 patients, was elevated in 25. Nose swabs were positive for influenza virus B in 13 out of 14 cases. The blood cell count, measured in 41 cases, disclosed leucopenia in 12 and thrombocytopenia in 3. The review of the literature found 10 outbreaks of ⩾10 cases of influenza virus B-associated myalgia cruris, which included a total of 203 patients with a mean age of 7.3 years and a ♂:♀ ratio of 2.0. In conclusion influenza virus B caused a large Swiss-Italian outbreak of myalgia cruris. Our outbreak and the literature indicate that influenza virus B-associated myalgia cruris affects preschool- and school-aged children, primarily boys.
    Neuromuscular Disorders 01/2014; · 3.46 Impact Factor
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    ABSTRACT: Frontonasal dysplasia (FND) is a genetically heterogeneous malformation spectrum with marked hypertelorism, broad nasal tip and bifid nose. Only a small number of genes have been associated with FND phenotypes until now, the first gene being EFNB1, related to craniofrontonasal syndrome (CFNS) with craniosynostosis in addition, and more recently the aristaless-like homeobox genes ALX3, ALX4, and ALX1, which have been related with distinct phenotypes named FND1, FND2, and FND3 respectively. We here report on a female patient presenting with severe FND features along with partial alopecia, hypogonadism and intellectual disability. While molecular investigations did not reveal mutations in any of the known genes, ALX4, ALX3, ALX1 and EFNB1, comparative genomic hybridization (array CGH) techniques showed a large heterozygous de novo deletion at 11p11.12p12, encompassing the ALX4 gene. Deletions in this region have been described in patients with Potocki-Shaffer syndrome (PSS), characterized by biparietal foramina, multiple exostoses, and intellectual disability. Although the patient reported herein manifests some overlapping features of FND and PPS, it is likely that the observed phenotype maybe due to a second unidentified mutation in the ALX4 gene. The phenotype will be discussed in view of the deleted region encompassing the ALX4 gene. © 2013 Wiley Periodicals, Inc.
    American Journal of Medical Genetics Part A 12/2013; · 2.30 Impact Factor
  • International Journal of Pharmaceutics 11/2013; 457(1):353-6. · 3.99 Impact Factor
  • Developmental Medicine & Child Neurology 11/2013; · 2.68 Impact Factor
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    ABSTRACT: Little information is available on ureteral or vesical involvement in Henoch-Schönlein syndrome. To determine the features of this condition we performed a formal analysis of peer-reviewed scientific literature on this topic. The US National Library of Medicine database was used as the data source. All articles published as full-length articles or letters were collected. Reports published in languages other than English, French, German, Italian or Spanish were not considered. We analyzed 32 reports describing 35 cases (24 male and 11 female subjects aged between 3.5 and 63, median 7.0 years) with ureteral (n = 30), vesical (n = 4), or both ureteral and vesical involvement (n = 1). The presentation included colicky abdominal pain, macroscopic hematuria (sometimes containing blood clots), urinary tract infection or urinary retention. The diagnosis of ureteral involvement was often fortuitous. Patients with vesical involvement were managed conservatively. However, the majority of those with ureteral involvement were managed surgically. Ureteral or vesical involvement is unusual and likely underappreciated in Henoch-Schönlein syndrome. Improved recognition and wider appreciation of this involvement can help to avoid associated morbidity. Management must be individualized for each patient. A multidisciplinary approach may be of value in planning medical treatment, surgical intervention, and follow-up.
    Pediatric Nephrology 09/2013; · 2.94 Impact Factor
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    ABSTRACT: There is growing concern about elevated blood pressure in children and adolescents, because of its association with the obesity epidemic. Moreover, cardiovascular function and blood pressure level are determined in childhood and track into adulthood. Primary hypertension in childhood is defined by persistent blood pressure values ≥ the 95th percentile and without a secondary cause. Preventable risk factors for elevated blood pressure in childhood are overweight, dietary habits, salt intake, sedentary lifestyle, poor sleep quality and passive smoking, whereas non-preventable risk factors include race, gender, genetic background, low birth weight, prematurity, and socioeconomic inequalities. Several different pathways are implicated in the development of primary hypertension, including obesity, insulin resistance, activation of the sympathetic nervous system, alterations in sodium homeostasis, renin-angiotensin system and altered vascular function. Prevention of adult cardiovascular disease should begin in childhood by regularly screening for high blood pressure, counseling for healthy lifestyle and avoiding preventable risk factors.
    Current Hypertension Reports 07/2013; · 3.90 Impact Factor
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    ABSTRACT: More and more data indicate the importance of palatability when selecting drugs for children. Since hypertension is uncommon in children, no child-friendly palatable formulations of these agents are currently available. As a consequence, in everyday practice available tablets are crushed and administered mixed with food or a sweet drink. We started investigating the issue of palatability of drugs among children in 2004 using smile-face scales. In the first trial we compared taste and smell acceptability of pulverized angiotensin receptor antagonists among nephropathic children and found that the score assigned to candesartan was significantly higher than that assigned to irbesartan, losartan, telmisartan and valsartan. In the second trial we compared the taste of pulverized amlodipine and lercanidipine among children and found that the score assigned to lercanidipine was significantly higher. Our third trial was performed using pulverized β-adrenoceptor blockers, angiotensin-converting enzyme inhibitors, calcium-channel antagonists and diuretics among medical officers and pediatricians. The palatability scores assigned to chlorthalidone, hydrochlorothiazide and lisinopril were significantly higher to those assigned to atenolol, bisoprolol, enalapril and ramipril. In conclusion pulverized amlodipine, atenolol, bisoprolol, enalapril, irbesartan, losartan, ramipril, telmisartan and valsartan are poor tasting. From the child's perspective, lercanidipine, candesartan, chlorthalidone, hydrochlorothiazide and lisinopril are preferable.
    International Journal of Pharmaceutics 07/2013; · 3.99 Impact Factor
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    ABSTRACT: Aims: In symptomatic fever management, there is often a gap between everyday clinical practice and current evidence. We were interested to see whether the 3 linguistic regions of Switzerland differ in the management of fever. Methods: A close-ended questionnaire, sent to 900 Swiss pediatricians, was answered by 322 pediatricians. 214 respondents were active in the German-speaking, 78 in the French-Speaking and 30 in the Italian-speaking region. Results: Pediatricians from the French- and Italian-speaking regions identify a lower temperature threshold for initiating a treatment and more frequently reduce it for children with a history of febrile seizures. A reduced general appearance leads more frequently to a lower threshold for a treatment in the German-speaking than in the French- and Italian-speaking areas. Among 1.5 and 5 year-old children the preference for the rectal route is more pronounced in the German- than in the French-speaking region. French-speaking respondents more frequently prescribe ibuprofen and an alternating regimen with 2 drugs than German-speaking respondents. Finally, the stated occurrence of exaggerated fear of fever was higher in the German- and Italian-speaking regions. Conclusions: Switzerland offers the opportunity to compare 3 different regions with respect to management of febrile children. This inquiry shows regional differences in symptomatic fever management and in the perceived frequency of exaggerated fear of fever. The gap between available evidence and clinical practice is more pronounced in the French- and in the Italian-speaking regions than in the German-speaking region. © 2012 The Authors. British Journal of Clinical Pharmacology © 2012 The British Pharmacological Society.
    British Journal of Clinical Pharmacology 04/2012; · 3.69 Impact Factor
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    ABSTRACT: Both obesity and being underweight have been associated with increased mortality. Underweight, defined as a body mass index (BMI) ≤ 18.5 kg per m(2) in adults and ≤ -2 standard deviations from the mean in children, is the main sign of a series of heterogeneous clinical conditions including failure to thrive, feeding and eating disorder and/or anorexia nervosa. In contrast to obesity, few genetic variants underlying these clinical conditions have been reported. We previously showed that hemizygosity of a ∼600-kilobase (kb) region on the short arm of chromosome 16 causes a highly penetrant form of obesity that is often associated with hyperphagia and intellectual disabilities. Here we show that the corresponding reciprocal duplication is associated with being underweight. We identified 138 duplication carriers (including 132 novel cases and 108 unrelated carriers) from individuals clinically referred for developmental or intellectual disabilities (DD/ID) or psychiatric disorders, or recruited from population-based cohorts. These carriers show significantly reduced postnatal weight and BMI. Half of the boys younger than five years are underweight with a probable diagnosis of failure to thrive, whereas adult duplication carriers have an 8.3-fold increased risk of being clinically underweight. We observe a trend towards increased severity in males, as well as a depletion of male carriers among non-medically ascertained cases. These features are associated with an unusually high frequency of selective and restrictive eating behaviours and a significant reduction in head circumference. Each of the observed phenotypes is the converse of one reported in carriers of deletions at this locus. The phenotypes correlate with changes in transcript levels for genes mapping within the duplication but not in flanking regions. The reciprocal impact of these 16p11.2 copy-number variants indicates that severe obesity and being underweight could have mirror aetiologies, possibly through contrasting effects on energy balance.
    Nature 08/2011; 478(7367):97-102. · 38.60 Impact Factor
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    ABSTRACT: We report a 26-year-old female patient who was diagnosed within 4 years with chest sarcoma, lung adenocarcinoma, and breast cancer. While her family history was unremarkable, DNA sequencing of TP53 revealed a germline de novo non-sense mutation in exon 6 p.Arg213X. One year later, she further developed a contralateral ductal carcinoma in situ, and 18 months later a jaw osteosarcoma. This case illustrates the therapeutic pitfalls in the care of a young cancer patient with TP53 de novo germline mutations and the complications related to her first-line therapy. Suggestion is made to use the less stringent Chompret criteria for germline TP53 mutation screening. Our observation underlines the possibly negative effect of radiotherapy in generating second tumors in patients with a TP53 mutation. We also present a review of six previously reported cases, comparing their cancer phenotypes with those generally produced by TP53 mutations.
    Familial Cancer 06/2011; 10(2):187-92. · 1.94 Impact Factor
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    ABSTRACT: Both obesity and being underweight have been associated with increased mortality. Underweight, defined as a body mass index (BMI) </= 18.5 kg per m(2) in adults and </= -2 standard deviations from the mean in children, is the main sign of a series of heterogeneous clinical conditions including failure to thrive, feeding and eating disorder and/or anorexia nervosa. In contrast to obesity, few genetic variants underlying these clinical conditions have been reported. We previously showed that hemizygosity of a approximately 600-kilobase (kb) region on the short arm of chromosome 16 causes a highly penetrant form of obesity that is often associated with hyperphagia and intellectual disabilities. Here we show that the corresponding reciprocal duplication is associated with being underweight. We identified 138 duplication carriers (including 132 novel cases and 108 unrelated carriers) from individuals clinically referred for developmental or intellectual disabilities (DD/ID) or psychiatric disorders, or recruited from population-based cohorts. These carriers show significantly reduced postnatal weight and BMI. Half of the boys younger than five years are underweight with a probable diagnosis of failure to thrive, whereas adult duplication carriers have an 8.3-fold increased risk of being clinically underweight. We observe a trend towards increased severity in males, as well as a depletion of male carriers among non-medically ascertained cases. These features are associated with an unusually high frequency of selective and restrictive eating behaviours and a significant reduction in head circumference. Each of the observed phenotypes is the converse of one reported in carriers of deletions at this locus. The phenotypes correlate with changes in transcript levels for genes mapping within the duplication but not in flanking regions. The reciprocal impact of these 16p11.2 copy-number variants indicates that severe obesity and being underweight could have mirror aetiologies, possibly through contrasting effects on energy balance.
    Nature. 01/2011; 478(7367):97-102.
  • [Show abstract] [Hide abstract]
    ABSTRACT: Both obesity and being underweight have been associated with increased mortality. Underweight, defined as a body mass index (BMI) </= 18.5 kg per m(2) in adults and </= -2 standard deviations from the mean in children, is the main sign of a series of heterogeneous clinical conditions including failure to thrive, feeding and eating disorder and/or anorexia nervosa. In contrast to obesity, few genetic variants underlying these clinical conditions have been reported. We previously showed that hemizygosity of a approximately 600-kilobase (kb) region on the short arm of chromosome 16 causes a highly penetrant form of obesity that is often associated with hyperphagia and intellectual disabilities. Here we show that the corresponding reciprocal duplication is associated with being underweight. We identified 138 duplication carriers (including 132 novel cases and 108 unrelated carriers) from individuals clinically referred for developmental or intellectual disabilities (DD/ID) or psychiatric disorders, or recruited from population-based cohorts. These carriers show significantly reduced postnatal weight and BMI. Half of the boys younger than five years are underweight with a probable diagnosis of failure to thrive, whereas adult duplication carriers have an 8.3-fold increased risk of being clinically underweight. We observe a trend towards increased severity in males, as well as a depletion of male carriers among non-medically ascertained cases. These features are associated with an unusually high frequency of selective and restrictive eating behaviours and a significant reduction in head circumference. Each of the observed phenotypes is the converse of one reported in carriers of deletions at this locus. The phenotypes correlate with changes in transcript levels for genes mapping within the duplication but not in flanking regions. The reciprocal impact of these 16p11.2 copy-number variants indicates that severe obesity and being underweight could have mirror aetiologies, possibly through contrasting effects on energy balance.
    Nature 01/2011; 478(7367):97-102. · 38.60 Impact Factor
  • Source
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    ABSTRACT: Obesity has become a major worldwide challenge to public health, owing to an interaction between the Western 'obesogenic' environment and a strong genetic contribution. Recent extensive genome-wide association studies (GWASs) have identified numerous single nucleotide polymorphisms associated with obesity, but these loci together account for only a small fraction of the known heritable component. Thus, the 'common disease, common variant' hypothesis is increasingly coming under challenge. Here we report a highly penetrant form of obesity, initially observed in 31 subjects who were heterozygous for deletions of at least 593 kilobases at 16p11.2 and whose ascertainment included cognitive deficits. Nineteen similar deletions were identified from GWAS data in 16,053 individuals from eight European cohorts. These deletions were absent from healthy non-obese controls and accounted for 0.7% of our morbid obesity cases (body mass index (BMI) >or= 40 kg m(-2) or BMI standard deviation score >or= 4; P = 6.4 x 10(-8), odds ratio 43.0), demonstrating the potential importance in common disease of rare variants with strong effects. This highlights a promising strategy for identifying missing heritability in obesity and other complex traits: cohorts with extreme phenotypes are likely to be enriched for rare variants, thereby improving power for their discovery. Subsequent analysis of the loci so identified may well reveal additional rare variants that further contribute to the missing heritability, as recently reported for SIM1 (ref. 3). The most productive approach may therefore be to combine the 'power of the extreme' in small, well-phenotyped cohorts, with targeted follow-up in case-control and population cohorts.
    Nature 02/2010; 463(7281):671-5. · 38.60 Impact Factor
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    ABSTRACT: Structural genomic abnormalities play a key role in the pathogenesis of human disorders and represent one of the first causes of mental impairment, complex syndromes and tumors. In order to detect these chromosomal abnormalities, many methodologies have been developed with limits. The new ARRAY based Comparative Genomic Hybridization (ARRAY CGH) is a revolutionary approach which allows to characterize very small genetic abnormalities undetectable by the standard approaches and in the absence of any associated clinical information. The aim of this article is to describe why the application of a new array CGH methodology is necessary in the etiological search for genetic diseases, what the limits of the standard approaches are and to whom arrayCGH analyses can be applied in a pediatric environment. Examples of our practice will be presented.
    Revue médicale suisse 02/2010; 6(237):390-2, 394-6.
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    [Show abstract] [Hide abstract]
    ABSTRACT: Obesity has become a major worldwide challenge to public health, owing to an interaction between the Western 'obesogenic' environment and a strong genetic contribution. Recent extensive genome-wide association studies (GWASs) have identified numerous single nucleotide polymorphisms associated with obesity, but these loci together account for only a small fraction of the known heritable component. Thus, the 'common disease, common variant' hypothesis is increasingly coming under challenge. Here we report a highly penetrant form of obesity, initially observed in 31 subjects who were heterozygous for deletions of at least 593 kilobases at 16p11.2 and whose ascertainment included cognitive deficits. Nineteen similar deletions were identified from GWAS data in 16,053 individuals from eight European cohorts. These deletions were absent from healthy non-obese controls and accounted for 0.7% of our morbid obesity cases (body mass index (BMI) >or= 40 kg m(-2) or BMI standard deviation score >or= 4; P = 6.4 x 10(-8), odds ratio 43.0), demonstrating the potential importance in common disease of rare variants with strong effects. This highlights a promising strategy for identifying missing heritability in obesity and other complex traits: cohorts with extreme phenotypes are likely to be enriched for rare variants, thereby improving power for their discovery. Subsequent analysis of the loci so identified may well reveal additional rare variants that further contribute to the missing heritability, as recently reported for SIM1 (ref. 3). The most productive approach may therefore be to combine the 'power of the extreme' in small, well-phenotyped cohorts, with targeted follow-up in case-control and population cohorts.
    Nature 01/2010; 463:671-675. · 38.60 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Obesity has become a major worldwide challenge to public health, owing to an interaction between the Western `obesogenic' environment and a strong genetic contribution. Recent extensive genome-wide association studies (GWASs) have identified numerous single nucleotide polymorphisms associated with obesity, but these loci together account for only a small fraction of the known heritable component. Thus, the `common disease, common variant' hypothesis is increasingly coming under challenge. Here we report a highly penetrant form of obesity, initially observed in 31 subjects who were heterozygous for deletions of at least 593 kilobases at 16p11.2 and whose ascertainment included cognitive deficits. Nineteen similar deletions were identified from GWAS data in 16,053 individuals from eight European cohorts. These deletions were absent from healthy non-obese controls and accounted for 0.7% of our morbid obesity cases (body mass index (BMI)>=40kgm-2 or BMI standard deviation score>=4 P = 6.4×10-8, odds ratio 43.0), demonstrating the potential importance in common disease of rare variants with strong effects. This highlights a promising strategy for identifying missing heritability in obesity and other complex traits: cohorts with extreme phenotypes are likely to be enriched for rare variants, thereby improving power for their discovery. Subsequent analysis of the loci so identified may well reveal additional rare variants that further contribute to the missing heritability, as recently reported for SIM1 (ref. 3). The most productive approach may therefore be to combine the `power of the extreme' in small, well-phenotyped cohorts, with targeted follow-up in case-control and population cohorts.
    Nature 01/2010; 463(7281):671-5. · 38.60 Impact Factor
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    ABSTRACT: We report on two familial cases from a non-consanguineous marriage, presenting multiple intestinal and choanal atresia. Massive hydramnios and dilatation of the bowel were observed at 29 weeks of gestation during routine ultrasound scan of a healthy mother. The fetal karyotype was normal and cystic fibrosis screening was negative. Regular scans were performed throughout the pregnancy. The child was born at 34 weeks gestation. Choanal atresia was diagnosed at birth and abdominal investigations showed multiple atresia interesting both the small bowel and the colon. Further interventions were necessary because of recurrent obstructions. During the following pregnancy, a dilatation of the fetal intestinal tract was detected by ultrasonography at 27 weeks of gestation. Pregnancy was interrupted. Post-mortem examination of the fetus confirmed the stenosis of long segments of the small intestine associated with areas of colonic atresia. In both cases, histology and distribution were consistent with those reported in hereditary multiple intestinal atresia (HMIA). An association between multiple intestinal and choanal atresia has never been reported. We suggest it could correspond to a new autosomal recessive entity for which cytogenetic investigations and high-resolution array CGH revealed no visible anomalies.
    American Journal of Medical Genetics Part A 12/2009; 149A(12):2661-5. · 2.30 Impact Factor
  • Pediatrics in Review 12/2009; 30(12):479-85. · 0.82 Impact Factor
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    ABSTRACT: Interstitial deletions of 7q11.23 cause Williams-Beuren syndrome, one of the best characterized microdeletion syndromes. The clinical phenotype associated with the reciprocal duplication however is not well defined, though speech delay is often mentioned. We present 14 new 7q11.23 patients with the reciprocal duplication of the Williams-Beuren syndrome critical region, nine familial and five de novo. These were identified by either array-based MLPA or by array-CGH/oligonucleotide analysis in a series of patients with idiopathic mental retardation with an estimated population frequency of 1:13,000-1:20,000. Variable speech delay is a constant finding in our patient group, confirming previous reports. Cognitive abilities range from normal to moderate mental retardation. The association with autism is present in five patients and in one father who also carries the duplication. There is an increased incidence of hypotonia and congenital anomalies: heart defects (PDA), diaphragmatic hernia, cryptorchidism and non-specific brain abnormalities on MRI. Specific dysmorphic features were noted in our patients, including a short philtrum, thin lips and straight eyebrows. Our patient collection demonstrates that the 7q11.23 microduplication not only causes language delay, but is also associated with congenital anomalies and a recognizable face.
    European journal of medical genetics 03/2009; 52(2-3):94-100. · 1.57 Impact Factor

Publication Stats

426 Citations
247.80 Total Impact Points

Institutions

  • 2013–2014
    • Ente Ospedaliero Cantonale
      Bellinzona, Ticino, Switzerland
  • 2009–2011
    • University Hospital of Lausanne
      • Service de génétique médicale
      Lausanne, VD, Switzerland
    • University of Lausanne
      Lausanne, Vaud, Switzerland
  • 2007
    • Universität Bern
      Berna, Bern, Switzerland