1,721,006 research outputs found
Permanent Neonatal Diabetes Mellitus (PNDM) in a patient with R201H/KCNJ11 gene mutation: Unusual clinical course
No full textKCNJ11 gene encodes Kir6.2, subunit of the β-cell ATP-dependent K-channel
(made up of 4 Kir6.2 and 4 sulfonylurea receptor 1 subunits); its heterozygous
activating mutation is a frequent cause of PNDM. Our 20y old pt was
the only child born from healthy unrelated parents (BW 2.3Kg, L 48cm). High
plasma glucose (PG) (10-16.7mmol/l) and glycosuria (no ketonuria) appeared
at 2d of life reaching 33.3mmol/l at 12d. Despite the progressive PG increase
and low fasting C-peptide (Cp) (149pmol/l at 12d, nv 178-680), she showed
good health conditions and regular weight gain until 35d old. Insulin (Ins) (1
IU/Kg/d) was started at 37d of life, because of ketonuria and failure to thrive
(PG 32mmol/l). Ins/Kg/d, progressively reduced, was stopped at 2.5y because
of good metabolic control and frequent hypoglycaemic events. Cp decreased
from 149pmol/l (at 12d) to undetectable value (8.5m old) with a subsequent
increase (119pmol/l, at 20m). At diagnosis anti-Ins and anti-β-cell antibodies
(AA) were negative. OGTT at 2.9y: normal fasting PG (4.5mmol/l) and Ins
(47.3pmol/l), impaired GT (8.4mmol/l at 120‘), blunted Ins peak (87.5pmol/
l). HbA1c constantly <7%. At 4.1y and 7.5y: PG at 120‘ 7.2 and 11.7mmol/l,
respectively. At 8y, Ins therapy was restored (0.8 U/kg/d) having high HbA1c
values (10.2-11.5%) and anti-gliadin AA were detected; asymptomatic celiac
disease was confirmed by biopsy. At 19.7y, IVGTT showed low basal
(231pmol/l, nv 281-1317pmol/l) and peak (265pmol/l) Cp. A transition G->A
at position 602, with a His->Arg at codon 201 (R201H), was identified in the KCNJ11 gene (mutation absent in parents). Ins was progressively reduced and
stopped within 11d and glibenclamide (Gl) administered (increasing dose:
after 3m 0.39mg/Kg/d, no HbA1c increase). After 4w on Gl, Cp raised to
1158pmol/l. This mutation is the most frequent genetic defect associated with
PNDM: no one of 9 described pts currently older than 3y experienced honey
moon, 8/9 being constantly Ins-treated (1 adult pt on tolbutamide since childhood).
Our data indicate that this mutation can confer a broad range of clinical
presentation and prompts the KCNJ11 gene analysis in all cases of ND
TERAPIA CON MECASERMINA IN UN BAMBINO CON IPERINSULINISMO CONGENITO DA MUTAZIONE DI INS-R
No full textPRESENTAZIONE DEL CASO, STORIA CLINICA E SINTOMATOLOGIA
L’uso per fi ni terapeutici della Mecasermina, insulin-like growth factor 1 (IGF1) umano ricombinante trova indicazione nella terapia della bassa statura di bambini con un defi cit primitivo documentato di IGF-1.
Il Leprecaunismo, noto come S. di Donohue, è una rara patologia congenita caratterizzata da insulino-resistenza, severo defi cit accrescitivo intra-uterino e post-natale, fenotipie caratteristiche, alterazione del controllo dell’assetto glicemico, con iperinsulinismo e iperandrogenismo associato. L’outcome prognostico è segnato da morte entro il primo anno di vita in quasi tutti i pazienti descritti.
Descriviamo l’outcome di un bambino che attualmente ha 3,5 anni, nato a 35,4 settimane con un ritardo di crescita endouterino severo (peso alla nascita: 1149 gr; lunghezza: 38 cm; circonferenza cranica: 28 cm). Alla nascita presentava facies dismorfi ca caratteristica, con orecchie a basso impianto, attaccatura bassa dei capelli, ipertricosi, lipoatrofi a sottocutanea, ipotrofi a muscolare, macrogenitalismo. Dopo la nascita la crescita è stata estremamente stentata con iperglicemia (327 mg/dl) alternata a ipoglicemia (10 mg/dl) anche durante l’infusione endovenosa di glucosio, iperinsulinismo (1000 mcU/dl)ed elevato C peptide (43,41 ng/ml), ipertensione refrattaria alla terapia farmacologica (113/74 mmHg). La madre ha avuto molti aborti precedenti la nascita del piccolo e i genitori sono consanguinei.
Ha iniziato terapia con diazossido alla dose di 5mg/kg/die ed ACE inibitore alla dose do 0,02 mg/kg/die con una risposta parziale.
IPOTESI DIAGNOSTICHE
Nel sospetto di Iperinsulinismo congenito, è stato avviato lo stidio del gene del recettore per l’insulina (INS-R).
INDAGINI DI I E II LIVELLO
Lo studio del gene dell’INS-R ha dimostrato una mutazione in omozigosi: c.3289C>T (CAG->TAG) p.Gln1097Stop (Q1097X).
DIAGNOSI ED EVENTUALE TERAPIA
Il defi cit accrescitivo ponderale e lineare e l’ipotrofi a muscolare si sono accentuate col trascorrere dei mesi epertanto è stata iniziata terapia con mecasermina (0,04 mg/kg bis in die). Non sono stati segnalati eventi avversi.
La dose del farmaco è stata progressivamente aumentata con incremento della crescita e della forza muscolare. La rarità del caso clinico e la terapia off-label somministrata con buona risposta anche in termini auxologici, identificano nella mecasermina una prospettiva terapeutica in una sindrome con una prognosi estremamente severa
Efficacy of Mecasermin Treatment and Long-Term Survival in a Child with Leprechaunism
No full textHomozygous mutation of Insulin receptor (INS-R) gene cause an extremely rare disease called Leprechaunism, and induce intrauterine
growth restriction with poor postnatal growth, hyperinsulinemia, postprandial hyperglycaemia, pre-prandial hypoglycaemia,
typical facies, lack of subcutaneous fat, thick skin, hypertrichosis, macrogenitosomia in males.
The survival is severely compromised in these patients. Treatment with diazoxide could ameliorate glycaemic control, however
these patients are signed by a high precocious lethality into the first 1-2 years of life. Anecdotical cases are described with a longer survival.
We describe the clinical case of a child with Leprechaunism, born from consanguineous parents, who had a homozygous mutation of the INS-R gene: c.3289 C>T (CAG->TAG) p.Gln 10975 stop (Q1097X). He was treated with diazoxide (5 mg/kg/day) and captopril (0.04 mg/kg/day), with a reduction of hyperglycaemia and hypertension.
However, the stop in ponderal and linear growth induced to try the off-label treatment with mecasermin (0.04 mg/kg bid). The dose was progressively increased to 0.06 mg/kg/bid. After 2 years of treatment with mecasermin, the child increased the weight to 5.9 kg, length to 65 cm, head circumference to 41 cm. His neuromotor development is significantly improved. He performed an encephalic MRI which showed non-specific alterations of the white matter subcortical and periventricular, possible evolution of neonatal prolonged hypoglycaemic events.
The peculiar outcome of our patient is linked to the long-term survival and the clinical improvement by mecasermin
MECASERMIN TREATMENT OF A CHILD WITH CONGENITAL HYPERINSULINISM LINKED TO INS-R MUTATION
No full textObjectives: Mecasermin is recombinant human insulin-like growth factor 1 (IGF1) which is approved for the treatment of short stature in children with documented primary IGF1 deficiency.
Leprechaunism, also known as Donohue syndrome, is a severe disease, secondary to a severe congenital insulin resistance, with prenatal and neonatal growth retardation, typical dysmorphic features, glycaemic dysregulation characterized by hyperinsulinemia and hyperandrogenism.
These patients have a poor prognosis with death in the first year of life.
Methods: We describe the case of a 3.5 years child, born at 35,4 weeks, with severe fetal growth restriction (weight 1149 gr; length: 38 cm; cranial circumference: 28 cm), typical facial features with low implant ears, low implant hairs, hypertrichosis, hypertrophic external genitalia, postnatal growth failure, and severe hyperglycaemia (327 mg/dl) alternated with hypoglycaemia (10 mg/dl) also during i.v. infusion of glucose; significant hyperinsulinism (1000 mcU/dl) with elevated C peptide levels (43,41 ng/ml), persistent hypertension (113/74 mmHg). He has consanguineous parents (cousins) and the mother underwent abortions before the baby was born.
Results: A treatment with diazoxide (5 mg/kg/day) was tried with limited efficacy. He was treated with ACE-inhibitor (Captopril) at the dose of 0,02 mg/kg/day with a low response. The Captopril dose was increased at 0,04 mg/kg/day with a regulation of the blood pressure (76/54 mmHg). The genetic study of INS-R was showed a homozygote mutation in the insulin receptor (INS-R) gene.
The mutation reported was c.3289C>T (CAG->TAG) p.Gln1097Stop (Q1097X). For the growth delay and the hypotrophic muscular masses he started a off-label treatment with mecasermin at increasing doses. He had no adverse events linked to the treatment. Otherwise, he improved growth and muscular strength.
Conclusions: The singular case is of relieve for the rarity of the disease and for the good response to the treatment with mecasermin, the real opportunity for these children with a severe disease otherwise with a poor prognosis
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variations on the Author
Full text link“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Appropriate Similarity Measures for Author Cocitation Analysis
Full text linkWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
Dispelling the Myths Behind First-author Citation Counts
Full text linkWe conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued
use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation
counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more
sophisticated methods
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