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Biomedical subjects

Francesco Chiarelli

Publications and source records attributed to Francesco Chiarelli.

71 records · Page 4Linked to original sources
PubMed2003

Camps for children with T1DM.

Summer camps for children and adolescents with Type I Diabetes Mellitus (T1DM) represent an alternative setting to improve DSME (Diabetes Self Management Education) which is the cornerstone of care for all individuals with diabetes who want to achieve a successful health related outcome. Since the first camp was set up, summer camps have become widespread throughout the world. In literature, there are many studies that involve diabetes camps but none show enough evidence to assess the their effectiveness. The examined outcome does not involve the evaluation of quality of life enough which represents a multidimensional construct covering micro e macro cultural behaviours that underline different aspects between different regions. It is necessary to improve studies in this way. In any case present day camping experiences are invaluable.

Adolescent↗
PubMed2003

Treatment of diabetic ketoacidosis in children and adolescents.

Diabetic ketoacidosis (DKA) may be defined as a metabolic derangement characterized by hyperglycemia, acidosis and ketonuria. It is a crucial pediatric medical emergency. DKA may occur in children with diabetes at onset due to severe insulin deficiency, in established patients from failing to take insulin, acute stress, and poor sick-day management. The treatment of DKA has undergone a radical transformation over recent years. Among the major innovations the early adjustment of the hydroelectrolyte imbalance and the continuous i.v. infusion of microdoses of insulin are the most interesting. Despite appropriate use of insulin and fluids, and continuous clinical observation, the mortality rate has not improved, and has remained the same as that reported in the 1970s. DKA can be prevented by shortening the period of carbohydrate intolerance that usually precedes the diagnosis of Type 1 diabetes. Its prevention decreases morbidity and mortality and allows to save on the hospital costs. The aim of this paper is to review the main aspects of the treatment and prevention of DKA.

Adolescent↗
PubMed2002

Insulin injection regimens and metabolic control in an international survey of adolescents with type 1 diabetes over 3 years: results from the Hvidore study group.

UNLABELLED: The optimal insulin regimen for paediatric patients with type 1 diabetes remains controversial. Therefore this multicentre study was performed in adolescents over a 3-year period to assess metabolic control, severe hypoglycaemia, and weight gain in relation to insulin injection regimens. Out of 2873 children and adolescents in an international survey in 1995, 872 adolescents (433 boys, 439 girls, mean age in 1995 11.3+/-2.2 years) were restudied in 1998, relating insulin regimens to HbA(1c) measured in a central laboratory. In addition, the daily dose of insulin, changes in body mass index (BMI), and events of severe hypoglycaemia were evaluated. Over 3 years, the use of multiple injection regimens increased from 42% to 71%: 251 patients remained on twice daily insulin, 365 remained on multiple injections and 256 shifted from twice daily insulin to multiple injections. In all three subgroups an increase in insulin dose, a deterioration of metabolic control, and an increase in BMI were observed. Metabolic control deteriorated less than expected over 3 years during adolescence (HbA(1c) 1995: 8.7+/-1.6%; 1998 observed: 8.9+/-1.6%, HbA(1c) expected for 1998: 9.0%). BMI increased more than expected, the increase was greatest in patients switching from twice daily to multiple injections, and higher in females compared to males. CONCLUSION: in this international study, metabolic control was unsatisfactory in many adolescents with type 1 diabetes irrespective of the insulin regimen. No improvement in metabolic control was observed in this cross-sectional survey, over 3 years in any of the subgroups. Even the group switching from twice to multiple injections did not improve blood glucose control and the increase in body mass index was most pronounced in this group. Conclusive evidence, however, should be based on prospectively planned, randomised therapeutic trials in paediatric patients.

Child↗
PubMed2002

Identification of STAT-1 as a molecular target of IGFBP-3 in the process of chondrogenesis.

The chondrogenesis process requires the ordered proliferation and differentiation of chondrocytes. Insulin-like growth factor-binding protein (IGFBP)-3, well characterized as the carrier of insulin-like growth factor (IGF), has been reported to have intrinsic bioactivity that is independent of IGF binding. The mechanisms involved in this IGF-independent action are still unclear. Using the RCJ3.1C5.18 chondrogenic cells, which in culture progresses from undifferentiated to terminally differentiated chondrocytes, we have shown previously that IGFBP-3 has an IGF-independent, antiproliferative effect in undifferentiated and early differentiated but not in terminally differentiated chondrocytes. In the present study, cDNA microarray analysis was used to screen for genes: 1) that were regulated by IGFBP-3 in early but not in terminally differentiated chondrocytes; 2) that were regulated specifically by IGFBP-3, but not by IGF-I; and 3) whose regulation was abolished by coincubation of IGFBP-3 with IGF-I. Signal transducer and activator of transcription (STAT)-1 was the gene that, fulfilling the screening criteria, exhibited the greatest up-regulation by IGFBP-3 (>40-fold). STAT-1 gene up-regulation was confirmed by Northern analysis of cells treated with IGFBP-3 or transfected with an IGFBP-3 expression vector. Remarkably, similar results were obtained when cells were transfected with an IGFBP-3 mutant unable to bind IGFs, definitively demonstrating the IGF-independent action of IGFBP-3. Consistent with the up-regulation of STAT-1 mRNA, IGFBP-3 also increased STAT-1 protein expression. Furthermore, both IGFBP-3 and the IGFBP-3 mutant induced STAT-1 phosphorylation and its nuclear localization. An antisense STAT-1 oligonucleotide abolished the IGF-independent cell apoptosis induced by IGFBP-3. We have demonstrated that STAT-1 is a major intracellular signaling and transcriptional target of the IGF-independent apoptotic effect of IGFBP-3 in chondrogenesis.

Apoptosis↗
PubMed2002

Typical and atypical rolandic epilepsy in childhood: a follow-up study.

Atypical features of rolandic epilepsy are not uncommon, although the long-term prognosis of this condition is not known. Eighty-five children (50 male and 35 female) attending the Department of Pediatrics of the University of Chieti, the Department of Pediatrics of Brindisi Hospital, and the Department of Neurology of San Valentino Hospital were selected for the study; these patients were subdivided into two groups according to their clinical presentation. Group A consisted of children who suffered from typical rolandic epilepsy and Group B consisted of children with atypical features of rolandic epilepsy. All patients of both groups were re-evaluated after at least 8 years from the first evaluation, and the frequency of seizures and the response to treatment were similar in the two groups of children. In spite of this fact, in patients who suffered from atypical rolandic epilepsy, we found a significantly higher percentage of learning and behavioral disabilities than in children affected by the classical form of rolandic epilepsy (45.5% vs 7.8%; P < 0.0001). In conclusion, atypical rolandic epilepsy seems to be associated with a high percentage of learning and behavioral disorders.

Anticonvulsants↗
PubMed2002

Valproate-induced hyperammonemic encephalopathy.

Valproic acid (VPA) is an effective anticonvulsant useful in many types of epilepsy and, although it is usually well tolerated, it has been associated with many neurological and systemic side effects. Among these, one of the most important is VPA-induced hyperammonemic encephalopathy (VHE): its typical signs are acute onset of impaired consciousness, focal neurologic symptoms, and increased seizure frequency. The pathogenesis of VHE is still unclear, but it has been suggested that hyperammonemia can produce encephalopathy via inhibition of glutamate uptake by astrocytes which may lead to potential neuronal injury and perhaps cerebral edema. Glutamine production is increased, whereas its release is inhibited in astrocytes exposed to ammonia. The elevated glutamine increases intracellular osmolarity, promoting an influx of water with resultant astrocytic swelling. This swelling could compromise astrocyte energy metabolism and result in cerebral edema with increased intracranial pressure. Moreover, VHE seems to be more frequently in patients with carnitine deficiency or with congenital urea cycle enzymatic defects.

Anticonvulsants↗
PubMed2002

Treatment of hypertension and microalbuminuria in children and adolescents with type 1 diabetes mellitus.

Nephropathy is the main cause of morbidity and mortality in patients with type 1 diabetes and, in adults, persistent microalbuminuria is the best marker of the consequent risk for its development. In the pediatric population, puberty represents the most important risk factor for the development of microangiopathic complications, although it is not necessarily associated with the progression to frank proteinuria. As many as 50% of subjects may revert to normoalbuminuria. Hypertension is a further risk factor and may accelerate the progression of micro- and macrovascular complications. There is evidence that angiotensin-converting enzyme (ACE) inhibitors reduce renal damage by one or more mechanisms independent of their antihypertensive effects--hence they represent the drug of choice for the treatment of diabetic nephropathy. However, as angiotensin II receptor antagonists are more specific, they may become the obvious treatment choice in the near future. There is no consensus as to who should be treated and when treatment with renoprotective drugs should begin in the pediatric population, due to the lack of a clear definition of the natural history of microalbuminuria in this age group. In this review some models and controversial aspects of this issue are presented and discussed.

Journal Article↗
PubMed2002

Increased bone turnover in prepubertal, pubertal, and postpubertal patients receiving carbamazepine.

PURPOSE: To study the markers of bone turnover in epilepsy patients in the different stages of the pubertal growth before and after the beginning of carbamazepine (CBZ) monotherapy. METHODS: We have investigated bone turnover in 60 epilepsy patients treated with CBZ. They were stratified according to pubertal stage and compared with a control group of 60 sex- and age-matched healthy children. RESULTS: After 2 years of therapy, we found higher values of the serum markers of bone formation [bone alkaline phosphatase (bone ALP), osteocalcin (OC), carboxy-terminal propeptide of type I procollagen (PICP), amino-terminal propeptide of type III procollagen (PIIINP)], and of bone resorption [carboxy-terminal telopeptide of type I collagen (ICTP) and the urinary cross-linked N-telopeptides of type I collagen (NTX)] in patients than in control subjects, in presence of a normal vitamin D metabolism. CONCLUSIONS: CBZ induces an increase of bone formation and of bone resorption that seems to be independent of the pubertal stage.

Adolescent↗
PubMed2002

Detection of HCV RNA in gastric mucosa-associated lymphoid tissue by in situ hybridization: evidence of a new extrahepatic localization of HCV with increased risk of gastric malt lymphoma.

OBJECTIVES: Mucosa-associated lymphoid tissue (MALT) is absent in the normal gastric mucosa but it can develop in several conditions, such as Helicobacter pylori infection. A certain correlation between hepatitis C virus (HCV) infection and low grade MALT lymphomas has recently been reported. The aim of this study was to investigate the presence of HCV RNA in acquired gastric MALT of HCV-infected patients using the in situ hybridization technique. METHODS: Twenty-five patients (16 male and nine female, average age = 56.6 yr [range = 33-75]) affected by chronic HCV hepatitis and with gastric MALT were studied. Giemsa stain and the rapid urease test were also used to evaluate the presence of H. pylori. A polymerase chain reaction product corresponding to the complete 5' noncoding region of the HCV genome was cloned directly in the pCR 1000 vector on gastric biopsies with acquired MALT. RESULTS: Twenty patients showed grade 2 gastric MALT and five showed grade 3, and H. pylori's presence was detected in 18 of 25 patients (72%). Using in situ hybridization, we detected HCV RNA in gastric acquired MALT of seven of 25 patients (28%): five showed grade 2 gastric MALT (two of these were H. pylori negative and the other three were positive), whereas two patients showed grade 3 gastric MALT (without H. pylori infection). CONCLUSIONS: This study shows that HCV not only may colonize gastric MALT but also may permit the development of a grade of acquired MALT, which may represent the first step toward a MALT lymphoma. However, further studies are needed to demonstrate the antigenic role of HCV in the progression of acquired MALT into MALT lymphoma.

Adult↗
PubMed2002

Insulin resistance in epileptic girls who gain weight after therapy with valproic acid.

Valproic acid is effective for treatment of many types of epilepsy, but its use in epileptic patients can be associated with an increase in body weight that could interfere with treatment compliance. The weight gain may result from different mechanisms, but the exact pathogenesis is still unknown. To evaluate insulin sensitivity in adolescents who gained weight during treatment with valproic acid, we studied 20 girls with different types of epilepsy: 15 patients had primary generalized seizures, including absence seizures (3 cases), and 5 patients had partial seizures. After 1 year of valproic acid treatment, the obese patients had serum insulin levels significantly higher than patients who did not gain weight (51.4 +/- 25.3 versus 28.2 +/- 12.9). Moreover, we observed that epileptic patients who gained weight were also insulin resistant in comparison with nonobese epileptic subjects. At the end of treatment, all patients showed normal levels of serum testosterone, androstenedione, dehydroepiandrosterone sulfate, follicle-stimulating hormone (FSH), and luteinizing hormone. We found no significant correlation between insulinemia and serum valproic acid concentrations in obese and nonobese patients treated with valproic acid. Our study demonstrates that basal hyperinsulinemia and insulin resistance can be present in patients who develop obesity during valproic acid treatment. Therefore, these obese patients could be exposed to the risks related to these metabolic abnormalities; if these data are confirmed in longer studies, these side effects may raise some concerns about the safety of valproic acid.

Androgens↗
PubMed2002

Endothelial dysfunction in children with type 1 diabetes mellitus.

Endothelial dysfunction is defined as the loss of endothelium properties, e.g. alteration of protein synthesis, increased vascular tone and permeability, acquisition of prothrombotic and antifibrinolytic properties. Endothelium, a primary target of unbalanced glycaemic control, is involved in the pathogenesis of vascular complications in patients with type 1 diabetes mellitus (DM). Vascular endothelium damage is characterised by an increase of endothelium-derived regulatory proteins. vWF and t-PA may be useful to investigate early endothelium involvement. However, impaired endothelium-dependent vasodilatation may be a more sensitive marker. Abnormal markers of endothelial cell activation and impaired endothelium-dependent vasodilatation have been observed in young patients with type I DM. Hyperglycaemia may alter normal endothelium functions, either directly or indirectly, by inducing different metabolic pathways. Complete understanding of the pathophysiology of endothelial dysfunction may lead to timely therapeutic intervention to prevent its development and to slow the progression of diabetic complications.

Animals↗
PubMed2002

New trends in the treatment of diabetic nephropathy in children.

Nephropathy is the main cause of morbidity and mortality in patients with Type 1 diabetes and persistent microalbuminuria is the best marker of the consequent risk for its development in adults. In the paediatric population, puberty has long been recognised as a major risk period for the development of microangiopathic complications, although it is not necessarily associated with the progression to frank proteinuria. In fact, as many as 50% of subjects might revert to normoalbuminuria. Hypertension is a further risk factor and accelerates the progression of micro and macrovascular complications. There is evidence that angiotensin-converting enzyme inhibitors reduce renal damage by one or more mechanisms independent of their antihypertensive effects and they are the drug class of choice for the treatment of diabetic nephropathy. However, as angiotensin II receptor antagonists are more specific they might become the obvious treatment choice in the near future. There is no consensus on who should be treated with reno-protective drugs in the paediatric population, and when this should occur, due to the lack of a clear definition of the natural history of microalbuminuria in this age group. In this review controversial aspects of this issue are presented and discussed.

Angiotensin Receptor Antagonists↗
PubMed2002

Anticonvulsant hypersensitivity syndrome in children: incidence, prevention and management.

Anticonvulsant hypersensitivity syndrome (AHS) is a rare, but potentially fatal, adverse reaction that occurs in patients, including children, who are treated with anticonvulsants. During metabolism of the anticonvulsant, toxic arene-oxide compounds are produced. AHS is associated with both cutaneous and systemic symptoms and is associated with multiorgan involvement. Liver damage, in particular, seems to be associated with fatal outcomes. The pathophysiology of AHS is still uncertain but it may be linked to a genetically determined inability to detoxify reactive drug metabolites. The prompt recognition of the first clinical signs of AHS, and the rapid withdrawal of the anticonvulsant, often avoids the progression of symptoms. Pharmacological treatment is essentially based on systemic corticosteroids in association with enteral nutrition, intravenous fluid augmentation, pain relief and ocular care. Intravenous immunoglobulins may also have a possible therapeutic role in some cases. Diagnostic tests, such as patch tests or in vitro assays, for AHS could help to identify patients at risk of developing the syndrome and could represent a first step of primary prevention when applied to relatives of patients.

Anticonvulsants↗
PubMed2002

Circulating monocyte chemoattractant protein-1 and early development of nephropathy in type 1 diabetes.

OBJECTIVES: To investigate the possible role of hyperglycemia-dependent monocyte chemoattractant protein (MCP)-1 biosynthesis in the pathophysiology of early nephropathy in type 1 diabetes. RESEARCH DESIGN AND METHODS: We studied 30 patients with type 1 diabetes (15 with and 15 without microalbuminuria) compared with matched healthy control subjects. Plasma MCP-1 and plasma oxidant status (vitamin E, fluorescent products of lipid peroxidation [FPLPs], malondialdehyde [MDA]), HbA(1c), and albumin excretion rate [AER]) were evaluated at baseline. Furthermore, MCP-1, vitamin E, AER, and HbA(1c) were also analyzed in the microalbuminuric diabetic patients and in the healthy volunteers after 8 weeks of high-dose (600 mg b.i.d.) vitamin E treatment. RESULTS: FPLPs, MDA, and MCP-1 were significantly higher, whereas vitamin E was significantly lower in patients with microalbuminuria and poorer glycemic control as compared with normoalbuminuric patients and healthy control subjects. Plasma MCP-1 was positively correlated with HbA(1c), FPLPs, MDA, and AER, whereas plasma MCP-1 showed an inverse correlation with vitamin E. Interestingly, both MCP-1 and AER decreased significantly after vitamin E treatment, despite no changes in HbA(1c) values. CONCLUSIONS: This study suggests that prolonged hyperglycemia may lead to early renal complications in type 1 diabetes by inducing MCP-1 biosynthesis via enhanced oxidative stress. Long-term treatment of high-dose vitamin E significantly decreased MCP-1, thus providing a rationale basis for evaluating vitamin E supplementation as therapy adjuvant to conventional insulin treatment in type 1 diabetic patients in whom an acceptable glycemic control is difficult to achieve despite appropriate insulin treatment.

Adult↗
PubMedDate not supplied

Functional assessment of allergic asthmatic children while asymptomatic.

The aim of this study was to detect the best test lung function to identify abnormalities in asthmatic children while asymptomatic. We studied 200 asthmatic children. Patients were evaluated by questionnaire to evaluate the presence of symptoms and drug consumption in the previous 3 months. Allergological evaluation by skin-prick tests and seric-specific IgE determination for relevant local inhalant allergens was made. Lung function was studied evaluating expiratory flows and measuring lung volumes by nitrogen washout technique. One hundred twenty-seven of 200 (63%) children showed functional abnormalities: 21 (10.5%) children had flow reductions, 56 (28%) children had volume modifications, and 50 (25%) children had either flow and lung volume alterations, respectively. We observed increased total lung capacity (TLC), residual volume (RV), and ratio RV/TLC values more often in patients with mild and moderate persistent asthma than in patients with intermittent asthma. No significant difference was detected considering expiratory flows. Measurements of lung volumes are an important tool to evaluate "air trapping" in asthmatic patients and this could be related to disease severity. According to the literature, our data suggest that an increase of RV, functional residual capacity RV/TLC could be the only functional airway dysfunction present in asthmatic children during asymptomatic period.

Anti-Asthmatic Agents↗