Assessment of enamel hypoplasia in autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED)

The features of enamel hypoplasia in a small group of patients with autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) are described. Using a recently developed method, the authors evaluated quantitatively the amount of defect in each tooth by measuring the width of the hypoplastic lesions and dividing the value by the crown height. They then assessed the degree of damage in each tooth type (from central incisors to second premolars) and patient. Canines were the most severely affected among maxillary and mandibular teeth, but all tooth types were involved. Analysing both the differences between patients and their age at the beginning of the defect, the authors observe that hypoparathyroidism is not responsible for the onset of enamel hypoplasia in APECED, although it may contribute to the damage.     

Third-generation assays for hepatitis C antibodies: a four-year study of pattern changes in patients with chronic and past infection

BACKGROUND: Many advances have been made in the sensitivity of assays for hepatitis C virus antibodies (HCV-Ab). Nevertheless, polymerase chain reaction (PCR) is still the best method to establish if infection has become chronic. In this study we utilised third-generation assays for HCV-Ab in a four-year follow-up to determine the trend in antibody levels in currently and past infected patients. METHODS: Seventy-two multitransfused subjects were enrolled. All the patients were reactive at the first test with third-generation screening and confirmatory assays (ELISA-3 and RIBA-3) for HCV-Ab. They were subsequently retested in a follow-up ranging from 41 to 47 months. Viraemia was investigated with a standardised PCR kit; negative samples were reevaluated with nested PCR. Differences in antibody trend were calculated with the Wilcoxon signed-rank test. RESULTS: No statistical variation in antibody titre was found in the 41 HCV-RNA positive patients, although some of these showed a decrease in anti-c100p level. In contrast, anti-c22p, anti-c33c and anti-c100p levels decreased significantly in the 19 past infected patients. Twelve patients were HCV-RNA negative or intermittently positive with commercial PCR test, and consistently or intermittently positive in nested PCR: in these patients, antibody trend varied. CONCLUSIONS: Although resolving hepatitis is associated with a decrease in antibody titre, the trend should be observed for a long period to distinguish between chronic and past infection. However, the evaluation in a single patient can be unreliable. Since a doubtful response for HCV-RNA is in some cases obtained, further improvements in the diagnosis of chronic HCV infection are needed.     

Sulfide Enhancement of Pmn Apoptosis

Hydrogen sulfide is a toxic metabolite released by several bacterial agents under anaerobic conditions.

In the present paper, we investigated the effects of sulfide on polymorphonuclear cell (PMN) apoptosis, a mechanism suggested for limiting the toxic potential of neutrophils in inflammatory sites. We showed that 1 mM sulfide (concentration not conditioning PMN viability) is able to enhance the apoptotic fate of human granulocytes by increasing, i) the number of cells containing pyknotic nuclei, ii) the internucleosomal cleavage, and, iii) the intensity of tubulin immunofluorescence staining.

The sulfide effect is partially prevented by ionomycin and this finding is consistent with the hypothesis of the inhibiting role played by high levels of cytosolic calcium in PMN apoptosis modulating.     

Neutrophil recruitment and airway epithelial cell involvement in chronic cystic fibrosis lung disease.

The pathological hallmark of cystic fibrosis (CF) chronic inflammatory response is the massive neutrophil influx into the airways. This dysregulated neutrophil emigration may be caused by the abnormal secretion of chemoattractants by respiratory epithelial cells and polarised lymphocyte T-helper response. Neutrophils from CF patients have a different response to inflammatory mediators than neutrophils from normal subjects, indicating that they are primed in vivo before entering the CF airways. CF neutrophils secrete more myeloperoxidase and elastase, mobilise less opsonin receptors and release less L-selectin than non-CF neutrophils. Moreover, they show altered cytokine production and a dysregulated chemotaxis response. Laboratory studies now suggest that CFTR is involved in regulating some neutrophil functions and indicate that altered properties of CF neutrophils may depend on genetic factors. Current gene therapy approaches are targeted to the respiratory epithelium, but many hurdles oppose an efficient and efficacious CFTR gene transfer. The possibility of CFTR gene therapy-based approach targeting CF neutrophils at the hematopoietic stem cell level is discussed.     

Septo-optic dysplasia-plus and dyskinetic cerebral palsy in a child

Septo-optic dysplasia (SOD), also called De Morsier’s syndrome, is a highly heterogeneous condition comprising a spectrum of central nervous system malformations that involves in various degrees the optic nerves, the hypothalamic–pituitary axis, and other midline structures such as the septum pellucidum and the corpus callosum. In a discrete number of cases, schizencephaly, agenesis of the corpus callosum or other cortical malformations are associated (SOD-plus). The authors present a 6-year-old boy with dyskinetic cerebral palsy (athetoid-dystonic subtype) associated with SOD-plus. Cranial magnetic resonance imaging (cMRI) revealed the total absence of septum pellucidum, optic nerve hypoplasia, hypoplasia of the corpus callosum and right occipital cortical dysplasia. The patient was diagnosed with septo-optic dysplasia-plus syndrome based on the cMRI findings. To the best of our knowledge, this is the first reported case in which defects of midline brain structures, like in SOD-plus, are associated with a significant hyperkinetic movement disorder such as dyskinesia.     

Prevalence and clinical features of cryoglobulinaemia in multitransfused β-thalassaemia patients

OBJECTIVE: The aim of the study was to determine the prevalence of cryoglobulinaemia and its clinical features among beta-thalassaemia patients. METHODS: Eighty eight multitransfused beta-thalassaemia patients were studied. They were physically examined and asked about the presence of cryoglobulinaemia related symptoms. Hepatitis C virus (HCV) serology, HCV-RNA, HCV subtypes, viraemia, serum ferritin, liver and kidney function tests, rheumatoid factor (RF), circulating immune complexes (CIC), complement levels and autoantibodies were all evaluated. The patients were divided into four groups: HCV-RNA positive patients with and without cryoglobulinaemia (groups A and B), HCV-Ab positive/HCV-RNA negative patients (group C), HCV-Ab negative patients (group D). RESULTS: Cryoglobulinaemia was present in 35 of 53 (66.0%) patients with chronic HCV infection. They had higher viraemia than non-cryoglobulinaemic viral carriers, but no statistical difference relating to sex or HCV subtypes was found. In comparison with the other groups, group A patients were older, had undergone transfusion therapy for a longer period, had received a higher number of transfusions, and had increased levels of RF and CIC, as well as consumption of C4; in addition, they had a higher prevalence of cirrhosis. Cutaneous lesions (purpura, Raynaud's phenomenon, nodules and leg rash), peripheral neuropathy and sicca syndrome symptoms were present only in group A. Musculoskeletal symptoms (bone pain, arthralgia and myalgia), weakness, splenomegaly, lymphadenopathy, skin ulcers and proteinuria were also commoner in group A, but the difference did not reach statistical significance, possibly because of partial overlap between cryoglobulinaemia and beta-thalassaemia syndromes. CONCLUSION: Because of its high prevalence in multitransfused beta-thalassaemia patients, cryoglobulinaemia needs to be systematically studied and considered in the differential diagnosis of various beta-thalassaemia manifestations.     

Immunophenotypic characterisation of peripheral blood lymphocytes in autoimmune polyglandular syndrome type 1: clinical study and review of the literature

Autoimmune endocrinopathies are characterised by an increased number of peripheral blood lymphocytes (PBL) expressing activation/ memory markers on their surface. The aim of this study was to determine whether a similar finding could be detected in a group of 11 paediatric and young adult patients suffering from autoimmune polyglandular syndrome type 1 (APS1), also called autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED), as very few data have previously been reported in this field. The control group was made up of 11 sex- and age-matched healthy subjects. Fifteen lymphocyte subsets were compared, in terms of percentage and absolute number, and statistical analysis was performed by the Mann-Whitney test. Measurement of T (CD3+), B (CD19+), natural killer (NK, CD3-CD16/56+), CD4+ and CD8+ T lymphocytes showed that patients with APS1 had a higher percentage and absolute count of T lymphocytes: this was entirely due to the statistically larger CD3+CD4+ fraction. Patients with APS1 also had slightly fewer B and NK lymphocytes, but the difference was negligible. Comparison of CD4+ subpopulations bearing activation and naive/memory antigens (marked by CD69, CD25, anti-HLA-DR, CD45RA and CD45RO) showed that patients with APS1 had generally larger percentages and absolute counts of these subsets: however, only the percentage and absolute size of the CD4+CD25+ subset (p = 0.0354 and p = 0.0151, respectively), and the absolute number of the CD4+ anti-HLA-DR+ and CD4+ CD45RO+ subsets (p = 0.0193 and p = 0.0209, respectively) were significantly higher. Interestingly, patients with APS1 also had significantly fewer CD8+CD11b+ and CD3-CD8+ cells. In conclusion, PBL distribution in APS1 resembles that of other autoimmune diseases. Further studies are needed to confirm and possibly extend these data.     

Factors influencing the stability of miniscrews. A retrospective study on 300 miniscrews

The aim of this study was to investigate, over a period of approximately 3 years, the reactions to orthodontic loading of a type V titanium miniscrew. In this retrospective study, conducted in a private practice, the records of 300 miniscrews inserted in 132 consecutive patients (80 females, 60.6 percent) by the same surgeon were evaluated. The mean age of the patients was 23.2 years. Three types of miniscrews (type A: diameter 1.5 mm, length 9 mm; type B: diameter 1.5 mm, length 11 mm; and type C: diameter 1.3 mm, length 11 mm) were used. The clinical variables evaluated included the loading time and location of the miniscrew in relation to the gingiva and root. The success rates with different variables were compared using chi-square or Fisher's exact test where appropriate. A cumulative survival rate of 81 percent (243/300) was found using Kaplan-Meier analysis, with an optimum success rate for the 1.3 mm wide miniscrew inserted in the attached gingiva, with immediate loading applied. Cox proportional hazard regression showed significant differences between success rate and the following parameters: gender, loading time, gingival or bone localization, and diameter of the miniscrews. Considering the clinically controllable parameters, and within the limits of this retrospective study, 1.3 mm diameter miniscrews inserted in attached gingiva and immediately loaded had the most favourable prognosis.     

Congenital hypotonia in a child with a de novo 22q13 monosomy and 2pter duplication: a clinical and molecular genetic study

The authors describe a 5-year-old girl with a neurological phenotype of 22q13 deletion syndrome (neonatal and persisting hypotonia, developmental delay, absence of language, decreased perception of pain) and minor dysmorphisms. Subtelomeric fluorescent in situ hybridization tests revealed de novo 22q13 monosomy and 2pter duplication. Numerous genetic and neurologic disorders of childhood are characterized by congenital hypotonia. This muscle tone disorder is often one of the symptoms that a neurologist is asked to evaluate. Recent advances in genetic testing can help provide a specific diagnosis for children with this symptom. Subtelomeric deletions are a category of disorders of which hypotonia can be a prominent feature. Deletions of chromosome 22q13 are some of the most commonly observed terminal deletions in humans, whereas duplications of chromosome 2p25.2 are very rare, and little is known about the phenotypic effect of these duplications. To the best of the authors' knowledge, this association has never been described before.