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Biomedical subjects

F Chiarelli

Publications and source records attributed to F Chiarelli.

At least 127 records · Page 7Linked to original sources

Evaluation of the components of insulin-like growth factor (IGF)-IGF binding protein (IGFBP) system in adolescents with type 1 diabetes and persistent microalbuminuria: relationship with increased urinary excretion of IGFBP-3 18 kD N-terminal fragment.

OBJECTIVE: IGFs and their binding proteins (IGFBPs) have an important role in controlling glucose homeostasis and there is evidence to support their involvement in complications related to type I diabetes. The aim of this study was to evaluate the components of the IGF-IGFBP system in adolescents with type 1 diabetes that had developed persistent microalbuminuria (MA). DESIGN AND PATIENTS: A cohort of 49 adolescents with type 1 diabetes were enrolled in the study. Patients were evaluated at baseline and 1 year later (follow-up). Twenty-six patients with persistent urinary albumin excretion (UAE) of more than 20 microg/min/1.73 m2 (21.6-109. 4 microg/min/1.73 m2) in three different nocturnal urinary collections within 6 months were considered to have MA (baseline mean: 41.9 +/- 22.3 microg/min/1.73 m2; follow-up: 55.9 +/- 24.8 microg/min/1.73 m2). Twenty-three patients with UAE of less than 20 microg/min/1.73 m2 were assigned to the group without MA (baseline mean: 8.6 +/- 3.7 microg/min/1.73 m2; follow-up: 11.8 +/- 4.2 microg/min/1.73 m2). Fasting serum levels of IGFBP-1, IGFBP-2, IGFBP-3, IGF-I and free-IGF-I were determined using appropriate immunoenzymatic, radioimmuno- or immunoradiometric assays. Overnight 12-h urinary collections were obtained and assessed for IGFBP-3 levels, determined by immunoradiometric assay. Urinary and circulating immunoreactive IGFBP-3 forms were determined by Western-immunoblotting (WIB) analysis using a specific polyclonal antibody and monoclonal antibodies directed against N-terminal and C-terminal epitopes of IGFBP-3. IGFBP-3 protease activity was determined using protease assay and by analysis of the intact over the fragmented immunoreactive forms of IGFBP-3 determined by WIB analysis. RESULTS: Patients with MA showed higher levels of urinary IGFBP-3 (649 +/- 440 ng/h/m2) than patients without MA (398 +/- 229 ng/h/m2; P < 0.05). Urinary levels of IGFBP-3 were directly correlated to UAE (P < 0.001). WIB analysis, using monoclonal antibodies directed against characterized N-terminal and C-terminal IGFBP-3 epitopes, determined that the immunoreactive form of IGFBP-3 found in urine from patients with diabetes was an N-terminal 18 kD fragment. Serum IGFBP-3 levels were lower in patients with MA (baseline: 3613 +/- 598 microg/l; one year follow-up: 3347 +/- 624 microg/l) compared with patients without MA (baseline: 4701 +/- 1484 microg/l; follow-up: 4177 +/- 703 microg/l; P < 0.001). In serum from patients with MA, intact IGFBP-3 was decreased, as indicated by WIB analysis. Conversely, IGFBP-3 proteolysis was increased in patients with MA (baseline: 131 +/- 21% of control; follow-up: 130 +/- 23% of control), compared to patients with normal UAE (baseline: 96 +/- 23% of control; follow-up: 96 +/- 14% of control; P < 0.001). Serum IGFBP-3 protease activity was directly correlated to urinary IGFBP-3 levels (P < 0.001). Serum IGFBP-1 levels were increased in patients with MA (baseline: 36 +/- 20 microg/l; follow-up: 36 +/- 17 microg/l) compared with patients without MA (baseline: 17 +/- 11 microg/l; follow-up: 18 +/- microg/l; P < 0.05). Serum IGFBP-2 levels were also persistently increased in patients with MA (baseline: 503 +/- 134 microg/l; follow-up: 484 +/- 166 microg/l) compared with patients without MA (baseline: 375 +/- 83 microg/l; follow-up: 390 +/- 85 microg/l; P < 0.05). On the other hand, free IGF-I levels were decreased in patients with MA (baseline: 2.3 +/- 1. 5 microg/l; follow-up: 2.5 +/- 1. (ABSTRACT TRUNCATED)

Adolescent↗

Centro-temporal spikes in non-epileptic children: a long-term follow up.

OBJECTIVE: This study was undertaken in order to determine the natural evolution of centro-temporal spikes (CTS) in a healthy paediatric population. METHODOLOGY: Forty children and adolescents (mean age +/- SD: 9.9 +/- 4.1 years) with non-epileptic disturbances (tics, headache, pavor nocturnus, vertigo, etc), who showed CTS during routine EEG recordings were studied. No patient suffered from seizures. A clinical and electroencephalographic follow-up of at least 5.5 years was carried out in all subjects. RESULTS: At the follow-up examination, 33 of the 40 cases (82.5%) had no CTS or other epileptic discharges in awake and sleep EEGs, while six subjects continued to show CTS discharges in sleep EEG. Among those subjects who showed persistence of CTS in sleep EEG, rolandic epilepsy developed in two cases, while all other subjects continued to be seizure free. CONCLUSIONS: This study demonstrates that CTS can be present in non-epileptic children and adolescents; in the majority of subjects this EEG abnormality disappears spontaneously and only a small percentage of subjects who have persistence of this pattern develops rolandic epilepsy.

Action Potentials↗

Hypoglycaemia in children with type 1 diabetes mellitus.

Hypoglycaemia is a frequent acute complication of IDDM and is usually defined as a blood glucose level below 3.0 mmol/l. Hypoglycaemia stimulates several neuroendocrine responses, such as secretion of glucagon, adrenaline, growth hormone and cortisol, which are generally increased during this phenomenon. The true prevalence of hypoglycaemia is not known. Studies of the epidemiology of severe hypoglycaemia give prevalences ranging from 2.7 to 85.7 episodes per 100 patients per year. The major risk factor for severe hypoglycaemia is hypoglycaemia unawareness, which occurs particularly in patients with type 1 diabetes of long duration and in those with a history of frequent episodes of hypoglycaemia. The first step in the management of hypoglycaemia is to check blood glucose and to treat hypoglycaemia on the basis of symptoms. Hypoglycaemia requires urgent treatment with a fast-acting carbohydrate or, if severe, with parenteral glucagon or intravenous glucose. Prevention measures should be instituted to prevent subsequent episodes, particularly in younger children with hypoglycaemic seizures or when seizures are recurrent.

Adolescent↗

Prevention of microvascular complications in diabetic children and adolescents.

Diabetes mellitus causes profound alterations in many body tissues. Microvascular diabetic complications include diabetic neuropathy, nephropathy and retinopathy. Nephropathy first becomes manifest with hyperfiltration and microalbuminuria. These functional changes evolve over several years to a stage of marked deterioration of renal function. The possible preventive measures are metabolic control, reduction of dietary protein intake and use of ACE-inhibitors. Metabolic control is also important for the prevention of diabetic retinopathy. In fact, patients with HbA1c higher than 10% have an increased risk of progression of retinopathy. Moreover, an accelerated progression of retinopathy has been observed in patients with systemic hypertension following the onset of microalbuminuria. It has been demonstrated that diabetic neuropathy can also be present during childhood; therefore, it is possible to detect electrophysiological abnormalities in children and adolescents with IDDM. Glycaemic and blood pressure control are, so far, the main means for possible prevention or modification of the natural history of diabetic microvascular complications. Tight glycaemic control may have beneficial effects for diabetic neuropathy. In addition, other preventive measures, such as aldose reductase inhibitors, gangliosides, neurotrophic vitamins, etc., have been studied in the last years. However, no conclusive results have been obtained so far.

Adolescent↗

The role of nutrition in prevention of complications in insulin-dependent diabetes mellitus.

Nutrition management is an integral part of overall diabetic treatment that includes insulin, physical activity, emotional support and guidance. The aim of the present study was to evaluate a dietary approach in line with the recommended dietary allowances in terms of protein, total and saturated fat, carbohydrates as well as fibre and polyunsaturated fatty acid. A correct dietary approach may help to prevent and to reduce to a minimum any risk of hyperglycaemia, hypoglycaemia and important long-term complications such as obesity, hyperlipidaemia and hypertension, and at the same time normal growth development.

Adolescent↗

Insulin resistance in short children with intrauterine growth retardation.

Scientific evidence is accumulating for an association between intrauterine growth retardation (IUGR) and an increased risk of developing adult degenerative diseases, such as essential hypertension, non-insulin-dependent diabetes mellitus and ischaemic heart disease. A possible underlying mechanism for these conditions is insulin resistance. In this paper, mechanisms and methods of measurement of insulin resistance are briefly reviewed, and recent studies on the evaluation of insulin resistance in short children with IUGR are summarized. In our experience, short prepubertal children with IUGR show consistent insulin resistance, which becomes particularly evident during pubertal development.

Adolescent↗

Increased systemic oxidative stress after elective endarterectomy: relation to vascular healing and remodeling.

It has been reported that systemic and local redox state may have an important role in the functional and organic changes characterizing the process of vascular response to injury. Carotid endarterectomy to remove atherosclerotic plaque is followed by a long lasting healing and remodeling process that can be carefully followed over time with noninvasive ultrasonography. Plasma vitamin C concentration and native LDL (n-LDL) content in lipid peroxides, vitamin E, beta-carotene, and lycopene as well as LDL susceptibility to peroxidation were assessed in 45 patients undergoing elective endarterectomy for internal carotid stenosis, at baseline, 24 hours, 3 and 15 days, and 1 month after surgery. Serial duplex scans were performed in all patients postoperatively and 3, 6, and 12 months. The changes in far wall thickness (FW) and % renarrowing from postoperatively to 12 months were used as remodeling indices. Plasma antioxidant vitamins and lag-phase showed a sharp and significant decrease during the first 24-hours after surgery remaining unchanged until the third day, whereas, an opposite trend was evidenced for n-LDL content in lipid peroxides and serum ceruloplasmin. After the third day all the parameters returned progressively to baseline within one month from endarterectomy. Interestingly, the n-LDL lipid peroxide content, the serum ceruloplasmin and the plasma vitamin C concentration, measured at 24 and 3 days from surgery, were significantly associated to the change in % renarrowing from postoperatively to 12 months. The higher the LDL content in lipid peroxides, the higher the serum level of ceruloplasmin, the lower the plasma content in vitamin C and the higher the % of vessel renarrowing. In conclusion, carotid endarterectomy with atherosclerotic plaque removal is associated with an acute and prolonged increase in systemic oxidative stress that influences vascular healing and late luminal loss.

Aged↗

Epilepsy with myoclonic absences with early onset: a follow-up study.

We studied six children (four girls and two boys) suffering from cryptogenic myoclonic absence seizures with early onset. The age at onset of the seizures ranged between 6 and 27.8 months (mean age +/- SD: 18.5+/-12.4 months). The neurologic evaluation was normal in all patients at the first hospital admission. After the diagnosis, we followed up all children for at least 5 years. At the end of follow-up, two of these patients (a girl and a boy) showed severe mental retardation, a high number (from one to three per day) of seizures, and persistent pathologic electroencephalograms. The other patients showed normal electroencephalograms: all of them were seizure free and without mental retardation. The two patients with mental retardation have been treated with polytherapy. In all other children we used valproate alone successfully. Our data suggest that myoclonic absence seizures with early onset can have a good long-term prognosis. Valproate is a useful anticonvulsant drug in these patients. Mental retardation is present only in patients with poor seizure control.

Anticonvulsants↗

Effectiveness of a prevention program for diabetic ketoacidosis in children. An 8-year study in schools and private practices.

OBJECTIVE: To shorten the period of carbohydrate intolerance preceding the diagnosis of IDDM in children. RESEARCH DESIGN AND METHODS: The incidence of diabetic ketoacidosis (DKA) was studied in newly diagnosed diabetic children aged 6-14 years, in the area of Parma, Italy, 8 years after an information program on DKA was introduced to teachers, students, parents, and pediatricians. Information was provided by displaying a poster with a few practical messages in 177 primary and secondary public schools. The pediatricians working in the same area were given equipment for the measurement of both glycosuria and blood glucose levels, as well as cards listing guidelines for the early diagnosis of diabetes, to be given to patients. A toll-free number was also provided. Clinical and laboratory features of 24 young diabetic patients diagnosed in the Parma area (group 1) were compared with those of 30 patients coming from two nearby areas in which no campaign for the prevention of DKA had been carried out (group 2). RESULTS: From 1 January 1991 to 31 December 1997, DKA was diagnosed in 3 children from group 1 (12.5%) and in 25 children from group 2 (83.0%) (chi 2 = 26.8; P = 0.0001). The three cases of DKA in group 1 were observed in 1991 (n = 1) and in 1992 (n = 2). No patients from the Parma area who had DKA were admitted to our unit after 1992. The duration of symptoms before diagnosis was 5.0 +/- 6.0 and 28.0 +/- 10.0 days (P < 0.0001), in groups 1 and 2, respectively, Metabolic derangements were less severe in patients of group 1 than in those of group 2. Hospitalization for the treatment of overt diabetes and for the teaching of self-management of the disease lasted 5.4 +/- 1.2 days in group 1 and 13.3 +/- 2.4 days in group 2 (P = 0.002). The total cost of the 8-year campaign was $23,470. CONCLUSIONS: The prevention program for DKA in diabetic children aged 6-14 years, carried out in the Parma area during the last 8 years, was successful. Thanks to this program, cumulative frequency of DKA in new-onset IDDM decreased from 78% during 1987-1991 to 12.5% during 1991-1997. None of the newly diagnosed diabetic children aged 6-14 years and from the Parma area were ever admitted to the hospital for DKA after 1992.

Adolescent↗

Increased Na+/Li+ countertransport activity may help to identify type 1 diabetic adolescents and young adults at risk for developing persistent microalbuminuria.

OBJECTIVE: To evaluate whether erythrocyte sodium-lithium countertransport (Na+/Li+ CT) activity may identify adolescents and young adults with childhood-onset of type 1 diabetes to be at greater risk to develop persistent microalbuminuria and incipient diabetic nephropathy. RESEARCH DESIGN AND METHODS: In January 1989, Na+/Li+ CT was measured in 170 normoalbuminuric diabetic adolescents and young adults (age 12-23 years; onset of diabetes before age 18 years; duration of diabetes longer than 7 years). Participants were clinically examined at baseline and biennially thereafter. Na+/Li+ CT activity was measured every 2 years during the 8-year follow-up period. Na+/Li+ CT activity was measured also in parents of diabetic offspring. RESULTS: Over 8 years, 18 (10 male, 8 female) out of 170 patients (10.5%) developed persistent microalbuminuria; no patient developed overt nephropathy. The risk of developing microalbuminuria was higher in children with increased Na+/Li+ CT (using 300 mumol.1 erythrocytes-1.h-1 as the arbitrary cutoff point) (group 1) compared with those with normal Na+/Li+ CT at the beginning of the study (group 2) (18.98 vs. 3.29%, P < 0.01; sensitivity 96.7%; specificity 57.9%). Sex did not influence predictive value, sensitivity, or specificity. Na+/Li+ CT was not significantly correlated with HbA1c or duration of type 1 diabetes. The percentage of offspring with both parents having Na+/Li+ CT activity above the median values was significantly higher in patients in group 1 than in group 2. The odds ratio for the occurrence of microalbuminuria after adjustment for confounding variables (albumin excretion rate [AER], sex, HbA1c, mean blood pressure, cholesterol, triglycerides) in type 1 diabetic adolescents with elevated baseline erythrocyte Na+/Li+ CT was 4.5 (95% CI of 2.1-11.4). CONCLUSIONS: These results confirm those of previous studies and suggest that Na+/Li+ CT may be one of the predictors and risk factors for incipient diabetic nephropathy in adolescents and young adults with onset of diabetes during childhood. Persistently increased Na+/Li+ CT activity may help to identify normotensive, normoalbuminuric patients with type 1 diabetes who are predisposed to develop microalbuminuria and incipient diabetic nephropathy.

Adolescent↗

Growth hormone and IGF-I in diabetic children with and without microalbuminuria.

In order to evaluate the relationship between urinary GH, urinary IGF-I and plasma IGF-I levels and presence of incipient diabetic nephropathy in paediatric age, we studied fifty (25 male and 25 female) prepubertal patients with insulin-dependent diabetes mellitus (T1DM). The patients were subdivided into two groups according to the presence of persistent microalbuminuria defined as albumin excretion rate (AER) >20 microg/min in at least 5 urine collections in the 6 months prior to the beginning of the study: Group A: 18 patients with microalbuminuria; Group B: 32 patients without microalbuminuria. A group of 20 healthy subjects, sex-, age- and pubertal stage-matched, served as control. No difference was observed between the urinary output of IGF-I and GH and plasma IGF-I values between normoalbuminuric and control subjects (normoalbuminuric vs controls: urinary GH: mean+/-SD 7.9+/-0.7 ng/day vs 8.1+/-0.6; urinary IGF-I: 178.3+/-19.7 ng/day vs 175.5+/-20.3; plasma IGF-I: 203.9+/-31.2 ng/ml vs 199.4+/-43.2), but a significant difference was observed between the urinary output of IGF-I and GH and plasma IGF-I levels between microalbuminuric patients and normoalbuminuric and controls (microalbuminuric subjects: urinary GH: 13.1+/-1.4 p<0.01; urinary IGF-I: 451.3+/-45.9 p<0.001; plasma IGF-I: 326.5+/-63.2 p<0.01). Moreover, plasma IGF-I, urinary GH and urinary IGF-I were not significantly associated with microalbuminuria, while plasma IGF-I levels were positively related to glomerular filtration rate (GFR) (p<0.05). In conclusion, our study demonstrates that microalbuminuric patients have higher levels of urinary IGF-I, urinary GH, plasma IGF-I than normoalbuminuric diabetic subjects. These data support the hypothesis that IGF-I can have a role in the changes of renal function observed in patients with persistent microalbuminuria.

Adolescent↗

Confirmation of the colobomatous macrophthalmia with microcornea syndrome: report of another family.

We report on the occurrence of microcornea, coloboma, and macrophthalmia in 4 generations of an Italian family. The patients had no additional physical anomalies, were of normal intelligence, and had a normal karyotype. This condition has been reported in only 1 family [Bateman and Maumenee, 1984: Ophthalmol Pediatr Genet 4:59-66]. The recurrence of this distinctive ocular pattern in our opinion confirms the existence of a new syndrome, with autosomal dominant inheritance.

Adult↗