A new mutation in two siblings with cystinosis presenting with Bartter syndrome

Nephropathic cystinosis is a severe autosomal recessive inherited metabolic disease characterized by accumulation of free cystine in lysosomes. Cystinosis can lead to renal failure and multiorgan impairment. Only five cases of cystinosis with associated Bartter syndrome are reported in the literature, and no genetic evaluation has been reported. We describe two siblings with nephropathic cystinosis presenting with features of Bartter syndrome and their genetic pattern.     

Immediate breast reconstruction with definitive anatomical implants after skin-sparing mastectomy.

One-stage breast reconstruction with definitive implants was the original method of breast reconstruction. It gave a round breast with a fixed shape. Lack of skin after mastectomy was the main concern who led to the development of techniques to provide 'new' breast skin such as autogenous reconstruction and tissue expanders. This made the use of definitive implants almost obsolete. Since skin-sparing mastectomy (SSM) basically removes the mammary gland and the nipple-areolar complex preserving almost all mammary skin, it makes the use of definitive implants in immediate breast reconstruction possible again. Moreover, the advent of anatomically shaped implants overcomes the drawback of round shape: the anatomical implant with hyperprojected lower pole and short upper pole matches very well the profile of a real breast. The authors report their experience in 36 immediate breast reconstruction after SSM with short upper pole-hyperprojected silicone gel prostheses carried out between October 2001 and October 2003. In most cases SSM is performed through a circumareolar incision. Axillary dissection is preferably performed through the same incision. The anatomical implant is placed in a submuscular position superiorly and in a subfascial pocket inferiorly. Because of skin redundancy and easy distension of subfascial tissue in the inferior pole of the breast, the implant fills the skin of the inferior mammary pole without needing any skin expansion. Whenever possible, the skin incision is closed with a purse-string suture. The skin will look very wrinkled at the end of the surgery, but it will flatten out in a few weeks. The contralateral breast is simultaneously corrected, if needed. Outcome was assessed by evaluation of photographs performed by the authors, by the patients themselves and by a blinded group of surgeons who evaluated breast volume and shape, breast symmetry, and overall outcome. More than 90% of each of these parameters was scored as good or excellent. Complication rates was low with a 8.3% rate. The use of definitive implants in immediate breast reconstruction after SSM is a one-stage breast reconstruction with low morbidity and very good results, and it is associated with high level of patient and surgeon satisfaction.     

Modulation of immune response to group C meningococcal conjugate vaccine given intranasally to mice together with the LTK63 mucosal adjuvant and the trimethyl chitosan delivery system

Previous work had shown that the immunogenicity of conjugate vaccine against group C meningococci (CRM-MenC) is enhanced when it is delivered intranasally (inl) with mucosal adjuvants, such as mutants of the Escherichia coli enterotoxin (LT), and with delivery systems such as chitosan derivatives. We show, in mice, that the concomitant use of limiting doses of the fully nontoxic LTK63 mutant as a mucosal adjuvant and of the trimethyl derivative of chitosan as a delivery system allows the reduction of each of the components for the induction of antibody and bactericidal responses to CRM-MenC conjugate vaccine delivered inl at titers similar to or higher than those induced by parenteral immunization. These data could affect the design of efficacious mucosal vaccines and their safety.     

A subset of anti-rotavirus antibodies directed against the viral protein VP7 predicts the onset of celiac disease and induces typical features of the disease in the intestinal epithelial cell line T84

Celiac disease (CD) is an autoimmune disorder of the small intestine triggered by environmental factors in genetically predisposed individuals. A strong association between type 1 diabetes (T1DM) and CD has been reported. We have previously shown that rotavirus infection may be involved in the pathogenesis of CD through a mechanism of molecular mimicry. Indeed, we identified a subset of anti-transglutaminase IgA antibodies that recognize the rotavirus viral protein VP7. In this study, we aimed at evaluating whether such antibodies may predict the onset of CD in children affected by T1DM. Moreover, to further analyze the link between rotavirus infection and pathogenesis of CD, we analyzed the effect of anti-rotavirus VP7 antibodies on T84 intestinal epithelial cells using the gene-array technique, complemented by the analysis of molecules secreted in the supernatant of stimulated cells. We found that anti-rotavirus VP7 antibodies are present in the vast majority (81 %) of T1DM-CD tested sera, but are detectable also in a fraction (27 %) of T1DM children without CD. Moreover, we found that anti-rotavirus VP7 antibodies are present before the CD onset, preceding the detection of anti-tTG and anti-endomysium antibodies. The gene-array analysis showed that purified anti-rotavirus VP7 antibodies modulate genes that are involved in apoptosis, inflammation, and alteration of the epithelial barrier integrity in intestinal epithelial cells, all typical features of CD. Taken together, these new data further support the involvement of rotavirus infection in the pathogenesis of CD and suggest a predictive role of anti-rotavirus VP7 antibodies.     

Molecular and Serological Diversity of Neisseria meningitidis Carrier Strains Isolated from Italian Students Aged 14 to 22 Years

Neisseria meningitidis is an obligate human commensal that commonly colonizes the oropharyngeal mucosa. Carriage is age dependent and very common in young adults. The relationships between carriage and invasive disease are not completely understood. In this work, we performed a longitudinal carrier study in adolescents and young adults (173 subjects). Overall, 32 subjects (18.5%) had results that were positive for meningococcal carriage in at least one visit (average monthly carriage rate, 12.1%). Only five subjects tested positive at all four visits. All meningococcal isolates were characterized by molecular and serological techniques. Multilocus sequence typing, PorA typing, and sequencing of the 4CMenB vaccine antigens were used to assess strain diversity. The majority of positive subjects were colonized by capsule null (34.4%) and capsular group B strains (28.1%), accounting for 23.5% and 29.4% of the total number of isolates, respectively. The fHbp and nhba genes were present in all isolates, while the nadA gene was present in 5% of the isolates. The genetic variability of the 4CMenB vaccine antigens in this collection was relatively high compared with that of other disease-causing strain panels. Indications about the persistence of the carriage state were limited to the time span of the study. All strains isolated from the same subject were identical or cumulated minor changes over time. The expression levels and antigenicities of the 4CMenB vaccine antigens in each strain were analyzed by the meningococcal antigen typing system (MATS), which revealed that expression can change over time in the same individual. Future analysis of antigen variability and expression in carrier strains after the introduction of the MenB vaccine will allow for a definition of its impact on nasopharyngeal/oropharyngeal carriage.