Clinical stage I nonseminomatous germ cell tumors of the testis in childhood and adolescence: an analysis of 31 cases

A 20-year single-institution experience of clinical stage I nonseminomatous germ cell tumors of the testis (NSGCTT) in childhood and adolescents was reviewed in relation to clinical characteristics, treatment modalities, and survival. Thirty-one patients with clinical stage I NSGCTT were seen between 1980 and 2000: 14 children and 17 adolescents. Yolk sac tumors and/or teratomas occurred in the children, whereas mixed histologies, including embryonal carcinoma, were predominant in the adolescents. After orchiectomy, the children were assigned to surveillance and the adolescents to active treatment: 16 underwent retroperitoneal lymph node dissection (RPLND) and 1 had adjuvant cisplatin-based chemotherapy because of a high-risk histology. Three of the 14 children (21.4%) relapsed 3, 7, and 8 months after orchiectomy: all 3 had yolk sac tumors and presented with increased alpha-fetoprotein levels. No patients had retroperitoneal relapse; two recurred locally and one in the lung. All three children were treated with cisplatin-based chemotherapy with or without surgery. Among the 16 adolescents undergoing RPLND, 4 (25%) had nodal metastases. Three of the 12 patients (25%) who had negative nodes at RPLND relapsed in the lung 3, 7, and 8 months after RPLND. All were treated with cisplatin-based chemotherapy with or without surgery. Five-year relapse-free and overall survival rates for the whole series were 80.6% and 100%, respectively. This series enabled the authors to pinpoint several important aspects of stage I NSGCTT in children and adolescents. In particular, almost all the childhood cases had the same yolk sac tumor histology, the children tended to have localized disease, and an increased alpha-fetoprotein level had a very high predictive value, suggesting that follow-up should include AFP measurements. A conservative approach is the best option in children, while adolescent NSGCTT behaves like the adult disease and management must include similar treatment strategies.     

Evaluation of the residual antigenicity and allergenicity of cow's milk substitutes by in vitro tests

BACKGROUND: This study aimed the to investigate presence of residual allergenic cow's milk proteins (CMP) in some milk substitutes employed in the treatment of cow's milk allergy (CMA). These allergens may interfere with the treatment, and elicit allergic reactions in sensitized individuals. METHODS: The protein composition of the different extracts was evaluated by Lowry's method and tricine SDS-PAGE. Different immunoenzymatic methods were used (ELISA, EAST and immunoblotting) to quantify total serum IgE and specific serum IgE, as well as to detect the presence of antigenic and allergenic components. RESULTS: The results showed a higher protein content in mammalian milks (cow, sheep, mare, goat, and human) than in hydrolyzed substitutes (partially or extensively hydrolyzed casein or whey proteins). Residual native, processed, or contaminant polypeptides have been identified in the moderate hydrolysates, whereas extensive hydrolysates did not show the presence of residual components by immunoblotting. However, specific antibodies with capacity to bind to peptides have been detected by EAST and ELISA, suggesting that extensive hydrolysates contain residual peptides that preserve immunoreactive epitopes. We were unable to demonstrate either residual antigenicity or allergenicity in an amino-acid-based formula. CONCLUSIONS: Immunoenzymatic methods were used to detect the presence of cross-reactive components in mammalian milks. Residual allergenic components from cow's milk could be identified in both the moderate and extensive hydrolysates analyzed. This information may be relevant to the treatment of CMA.     

A DNA vaccine encoding lumazine synthase from Brucella abortus induces protective immunity in BALB/c mice

This study was conducted to evaluate the immunogenicity of the Brucella abortus lumazine synthase (BLS) gene cloned into the pcDNA3 plasmid, which is driven by the cytomegalovirus promoter. Injection of plasmid DNA carrying the BLS gene (pcDNA-BLS) into BALB/c mice elicited both humoral and cellular immune responses. Antibodies to the encoded BLS included immunoglobulin G1 (IgG1) IgG2a, IgG2b, IgG3, and IgM isotypes. Animals injected with pcDNA-BLS exhibited a dominance of IgG2a over IgG1. In addition, spleen cells from vaccinated animals produced interleukin-2 and gamma interferon but not IL-10 or IL-4 after in vitro stimulation with recombinant BLS (rBLS), suggesting the induction of a Th1 response. Protection was evaluated by comparing the levels of infection in the spleens of vaccinated mice challenged with B. abortus 544. Immunization with pcDNA-BLS- reduced the bacterial burden relative to those in the control groups. Mice immunized with rBLS produced a significant humoral response but did not show a specific cellular response or any protection from challenge. Altogether, these data suggest that pcDNA-BLS is a good immunogen for the production of humoral and cell-mediated responses in mice and is a candidate for use in future studies of vaccination against brucellosis.     

Brucella abortus invasion of osteoblasts inhibits bone formation

Osteoarticular brucellosis is the most common presentation of the active disease in humans. Loss of bone is a serious complication of localized bacterial infection of bones or the adjacent tissue, and brucellosis proved not to be the exception. The skeleton is a dynamic organ system which is constantly remodeled. Osteoblasts are responsible for the deposition of bone matrix and are thought to facilitate the calcification and mineralization of the bone matrix, and their function could be altered under infectious conditions. In this article, we describe immune mechanisms whereby Brucella abortus may invade and replicate within osteoblasts, inducing apoptosis, inhibiting mineral and organic matrix deposition, and inducing upregulation of RANKL expression. Additionally, all of these mechanisms contributed in different ways to bone loss. These processes implicate the activation of signaling pathways (mitogen-activated protein kinases [MAPK] and caspases) involved in cytokine secretion, expression of activating molecules, and cell death of osteoblasts. In addition, considering the relevance of macrophages in intracellular Brucella survival and proinflammatory cytokine secretion in response to infection, we also investigated the role of these cells as modulators of osteoblast survival, differentiation, and function. We demonstrated that supernatants from B. abortus-infected macrophages may also mediate osteoblast apoptosis and inhibit osteoblast function in a process that is dependent on the presence of tumor necrosis factor alpha (TNF-α). These results indicate that B. abortus may directly and indirectly harm osteoblast function, contributing to the bone and joint destruction observed in patients with osteoarticular complications of brucellosis.     

Moderate clinical improvement with maintenance ECT in a 17-year-old boy with intractable catatonic schizophrenia

The use of electro-convulsive therapy (ECT) in adolescents is controversial, and few studies have been conducted to assess its efficacy and safety in this population. We report the case of a 19-year-old boy who received two series of ECT, one at 15 and another at 16, for intractable catatonic schizophrenia. Since the age of 17, he has required treatment combining clozapine and maintenance ECT. The course showed a sustained moderate improvement. The treatment permitted the patient to regain some autonomy with moderate adverse effects. ECT remains an uncommon treatment in adolescents, and the current case supports the view that it should not be banned in young people.