Alessandro Giannattasio

Epidemiology and Clinical Course of Burkholderia cepacia Complex Infections, Particularly Those Caused by Different Burkholderia cenocepacia Strains, among Patients Attending an Italian Cystic Fibrosis Center

ABSTRACT In this study, the epidemiology of Burkholderia cepacia complex (Bcc) recovered from the sputum of 75 patients attending the Genoa Cystic Fibrosis (CF) Center at the Gaslini Childrens Hospital (Genoa, Italy) was investigated, and the clinical course of the CF patients infected with the different species and genomovars of Bcc was evaluated. All isolates were analyzed for genomovar status by recA gene polymorphism and subsequently random amplified polymorphic DNA fingerprinting. Burkholderia cenocepacia is the predominant species recovered from the CF patients infected with Bcc at the Genoa CF Center. Of the other eight species comprising the Bcc, only a few isolates belonging to B. cepacia genomovar I, Burkholderia stabilis, and Burkholderia pyrrocinia were found. Of the four recA lineages of B. cenocepacia, most patients were infected by epidemic strains belonging to lineages IIIA and IIID, whereas only a few patients harbored IIIB strains. Patient-to-patient spread of Bcc among CF patients was mostly associated with B. cenocepacia, in particular with strains belonging to recA lineages IIIA and IIID. The mortality of CF patients infected with Bcc at the Genoa CF Center was significantly higher than mortality among CF patients not infected with Bcc. All of the deaths were associated with the presence of B. cenocepacia, except the case of a patient infected with B. cepacia genomovar I. Within B. cenocepacia, infection with epidemic strains belonging to lineages IIIA and IIID was associated with higher rates of mortality than was infection with lineage IIIB strains. No significant differences in lung function, body weight, and mortality rate were observed between patients infected with epidemic strains belonging to either B. cenocepacia IIIA or B. cenocepacia IIID.

In type 1 diabetes a subset of anti-coxsackievirus B4 antibodies recognize autoantigens and induce apoptosis of pancreatic beta cells.

Type 1 diabetes is characterized by autoimmune destruction of pancreatic beta cells. The role played by autoantibodies directed against beta cells antigens in the pathogenesis of the disease is still unclear. Coxsackievirus B infection has been linked to the onset of type 1 diabetes; however its precise role has not been elucidated yet. To clarify these issues, we screened a random peptide library with sera obtained from 58 patients with recent onset type 1 diabetes, before insulin therapy. We identified an immunodominant peptide recognized by the majority of individual patients’sera, that shares homology with Coxsackievirus B4 VP1 protein and with beta-cell specific autoantigens such as phogrin, phosphofructokinase and voltage-gated L-type calcium channels known to regulate beta cell apoptosis. Antibodies against the peptide affinity-purified from patients’ sera, recognized the viral protein and autoantigens; moreover, such antibodies induced apoptosis of the beta cells upon binding the L-type calcium channels expressed on the beta cell surface, suggesting a calcium dependent mechanism. Our results provide evidence that in autoimmune diabetes a subset of anti-Coxsackievirus antibodies are able to induce apoptosis of pancreatic beta cells which is considered the most critical and final step in the development of autoimmune diabetes without which clinical manifestations do not occur.

Type 1 diabetes and epilepsy: more than a casual association?

To the Editors: In 2006, McCorry et al. reported a strong epidemiologic association between type 1 diabetes mellitus (T1DM) and idiopathic generalized epilepsy (IGE) and claimed that this link would support an autoimmune pathogenesis for IGE (McCorry et al., 2006). However, O’Connel and coworkers did not confirm an increased risk of epilepsy among a series of patients with T1DM (O’Connell et al., 2008). We reviewed 249 T1DM patients (145 male; mean age 16.3 € 7.02 years, range 1.7–34.5 years; mean age at disease onset 7.7 € 6.9 years; range 0.8–18 years) attending the Diabetes Clinic at G. Gaslini Institute, Genoa, where a collaborative network provides epidemiologic data by an active surveillance model (Cotellessa et al., 2003). Extensive research was undertaken through the electronic database and subjects not followed up during the previous year were excluded. Epilepsy was diagnosed when ‡2 unprovoked euglycemic seizures (blood glucose >3.9 and <11.1 mmol/L) and syndromic classification (Commission on Classification and Terminology of the ILAE, 1989) was confirmed by reviewing clinical (family history, seizures type onset and frequency, response to treatment) and instrumental [electroencephalography (EEG), neuroimaging] data. Among 249 T1DM patients, 6 showed the electroclinical features of idiopathic epilepsy (4 IGE, 2 focal idiopathic epilepsy) (Table 1). In this group, mean age of T1DM onset was 4.6 € 2.7 years; mean age at first seizure was 6.7 € 4.4 years. None of these patients had a family history of epilepsy in firstand second-degree relatives. In all patients but one (case 4), T1DM preceded epilepsy onset, with a mean of 2.8 years (range 0.7–6.9 years). Patient 1 had concomitant celiac disease. Dosage of glutamic-acid decarboxylase antibodies (GADA) was available in two patients at T1DM diagnosis and in all cases at the last follow-up (Table 1). The high proportion of IGE observed in our series (4 of 249, 1.6%) (Hauser & Banerjee, 2008) confirms the data reported by McCorry et al. (McCorry et al., 2006). In all patients but one, T1DM manifested years before epilepsy. This may simply reflect different age of onset of the two conditions. Alternatively, it could support an autoimmune mechanism starting with T1DM and then affecting the central nervous system (McCorry et al., 2006). We did not perform GADA evaluation methodically at epilepsy onset in our patients, so that no definitive conclusion can be drawn about the existence of a pathogenetic link between GADA and epilepsy in T1DM patients (Striano et al., 2008). Interestingly, the patient with partial response to antiepileptic therapy (case 4) is the only one with recent GADA positivity. Because of the retrospective analysis, epilepsy could be underrecognized or overestimated in our T1DM population, but this is unlikely to explain the higher than expected degree of the association. Because both epilepsy and T1DM are serious worldwide problems with high medical and social management costs, this possible association deserves further investigation by prospective studies involving multiple centers.

Epilepsia partialis continua in type 1 diabetes: evolution into epileptic encephalopathy with continuous spike-waves during slow sleep.

Hyperglycemic status may be rarely complicated by Epilepsia partialis continua (EPC) that usually responds to metabolic normalization. Anti-glutamic acid decarboxylase antibodies (GAD-Ab) play a pivotal role in the autoimmune process that leads to clinical onset of type 1 diabetes mellitus (T1DM). GAD-Ab have been recently reported in association with rare forms of refractory epilepsy, with or without association to T1DM. Here we describe a young patient who developed EPC five months after T1DM onset; GAD-Ab were detected in his cerebrospinal fluid with evidence of oligoclonal bands. His epileptic disorder evolved over time into drug-resistant epilepsy with continuous spike-waves during slow sleep and severe behavioral impairment. The role of both metabolic imbalance and GAD autoimmunity is discussed.

β-Cell Autoimmunity in Pediatric Celiac Disease: The Case for Routine Screening?

OBJECTIVE—To evaluate the prevalence of β-cell autoimmunity and the usefulness of a type 1 diabetes screening in patients with celiac disease. RESEARCH DESIGN AND METHODS—We measured GAD antibodies (GADAs), insulinoma-associated protein 2 antigens (IA-2As), and insulin autoantibodies (IAAs) in 188 young Italian patients with celiac disease (66 male [35.1%]). Mean age at celiac disease diagnosis was 5.4 years (0.5–17.1), and mean celiac disease duration was 4.2 years (0–28.8). Celiac disease was diagnosed by jejunal biopsy after positivity for endomysial and tissue transglutaminase antibody was confirmed. RESULTS—GADAs were positive in seven patients (3.7%), and IA-2As were positive in two patients. IAAs were negative in all cases. Metabolic evaluation was normal, and no patients developed diabetes during follow-up. There was no significant association among β-cell autoimmunity and sex, age, pubertal stage, family history, or coexistence of other autoimmune disorders; compliance to a gluten-free diet was confirmed. CONCLUSIONS—Our results showed a low prevalence of β-cell autoimmunity and do not support a precocious screening for β-cell autoimmunity in young celiac disease patients.

Amyand’s hernia in a child with permanent neonatal diabetes due to pancreatic agenesis.

Acute or perforated appendicitis within inguinal hernia is rarely encountered and it is known as Amyands hernia. We report on the first case occurring in a 4-year-old boy affected by permanent neonatal diabetes mellitus due to pancreatic agenesis, an extremely rare condition. The initial suspicion of inguinal hernia was confirmed by ultrasound examination of the right inguinal region which revealed omental layers inside a swollen inguinal canal; this finding and the clinical presentation allowed a prompt and appropriate surgical management. The careful evaluation of this patient and early recognition of this unique presentation of appendicitis allowed trans-hernial appendectomy and immediate herniorrhaphy. Ultrasonography played a pivotal role to reach the correct diagnosis and to start a prompt treatment.

Strong Association Between Time Watching Television and Blood Glucose Control in Children and Adolescents With Type 1 Diabetes Response to Margeirsdottir et al.

We reply to Margeirsdottir et al. (1), reporting our experience in 237 type 1 diabetic Italian patients (139 male), aged (mean ± SD) 16.8 ± 7.1 years (range 1.8–36.3) with mean disease duration 9.0 ± 6.3 years (1.0–27.6), mean A1C 7.7 ± 1.1% (5.2–13.5), and mean insulin requirement 0.82 ± 0.24 units · kg−1 · day−1 (0.24–1.58). Between January and March 2007, in all patients we evaluated by direct or telephone interviews the influence of leisure time in TV watching …

Neonatal diabetes mellitus due to pancreatic agenesis and pervasive developmental disorder

Recent studies suggested a link between type 1 diabetes mellitus and pervasive developmental disorder. Moreover, permanent neonatal diabetes mellitus due to pancreatic agenesis can be associated with neurological deficit involving cerebellar functions, but no association with pervasive developmental disorder has been described so far. Clinical and neuropsychological evaluation of a child with pancreatic agenesis, mental retardation and pervasive developmental disorder is reported.