Search

Bisphenol A is an industrial chemical compound, pervasively polluting the environment and diet, classified as an endocrine disruptor because of its interference effects on the endocrine system. In zebrafish, BPA exposure induces follicular atresia. To acquire knowledge on this atretic effect, using a qualitative and quantitative histomorphological approach, we studied zebrafish ovarian follicular stage development in response to low BPA concentrations. Results show that BPA interferes with follicular progression by affecting the previtellogenic and vitellogenic phases. In particular, BPA exposure (i) increases follicular recruitment by acting on primary stage follicles, (ii) forces the follicular transition from stage III to stage IV producing enlarged stage IV follicles, and (iii) induces atresia by producing atretic follicles that are peculiarly enlarged (i.e., big atretic follicles). We suggest that BPA induces atresia by the primary effect on recruitment of stage I follicles. This forces follicular progression and produces stage IV follicles that are peculiarly enlarged that undertake the atretic development.

Posterior reversible encephalopathy syndrome is a recently described cliniconeuroradiological syndrome reported in children with several predisposing conditions such as transplantation, autoimmune, hematological, infectious, renal, and neoplastic diseases or administration of chemotherapeutic immunosuppressive drugs. Seizures are one of the most frequent manifestations of posterior reversible encephalopathy syndrome; status epilepticus has been described more frequently in adults but rarely in children. We report on the case of a 6-year-old healthy boy who presented status epilepticus as the main manifestation of posterior reversible encephalopathy syndrome in the absence of other underlying conditions. This is the first report of posterior reversible encephalopathy syndrome in a previously healthy child. Our case reminds us that pathogenesis of this condition is far from being completely understood and may include both genetic and environmental factors. Moreover, posterior reversible encephalopathy syndrome should always be suspected by clinicians in cases of status epilepticus with a prolonged neurological failure., (Copyright © 2013 Elsevier Inc. All rights reserved.)

The rate of late preterm delivery has increased in the general population, and the late preterm infants have a higher incidence of morbidity compared to term newborns. Late preterm data are lacking in born to HIV-infected mother. We showed that, among 202 live births, late preterm delivery was higher in born to HIV-infected mothers than in the general population while their morbidity was lower.

Importance of the Field: HIV-infection has become a chronic disease in paediatric patients with the potential for long-term survival and exposure to antiretroviral (ARV) therapies for 2 decades longer than HIV-infected adults. On the other hand, the administration of ARV to HIV-infected pregnant women has greatly increased both treatment of HIV infection and prevention of perinatal HIV transmission. Therefore, researches aiming to evaluate the safety of ARV therapies in HIV-infected children as well as in HIV-uninfected infants born to HIV-infected mothers are emerging as a new challenge and urgent priority., Areas Covered in This Review: The purpose of this review is to describe some of the more concerning metabolic complications associated with ARV in paediatric population: hyperlactataemia (HLA) syndromes, body shape abnormalities, disorders of glucose homeostasis and dyslipidaemia in HIV-infected children and adolescents. Frequency, risk factors, clinical findings, prevention and intervention strategies of the previously described abnormalities are discussed in depth., What the Reader Will Gain: This review covers our current understanding of HLA syndromes in ARV-exposed uninfected infants born to HIV-infected mothers., Take Home Message: Prevention of these metabolic complications should assume prominence and future researches should address several of the existing treatment gaps.

Background and Objectives: Few and mainly cross-sectional studies of glucose homeostasis are available in HIV-infected children treated with highly active antiretroviral therapy (HAART). The aim of the present study was to describe a 4-year course of glucose homeostasis in a cohort of HAART-treated children and adolescents, using glucose and insulin levels during an oral glucose tolerance test (OGTT) as outcome measures. In addition, we investigated possible risk factors, both related and unrelated to antiretroviral therapy, associated with insulin resistance., Methods: We assessed glucose metabolism yearly for 4 consecutive years in 37 HIV-infected children receiving a protease inhibitor (PI)-based HAART regimen containing lamivudine/stavudine plus indinavir or ritonavir or nelfinavir or a non-nucleoside reverse transcriptase inhibitor (NNRTI)-based HAART regimen containing lamivudine/tenofovir/efavirenz. Generalized estimating equations were used to evaluate the relationship between the loge-transformed area under the serum concentration-time curve (AUC) of insulin during OGTT and antiretroviral therapy, controlling for time, sex, baseline age, puberty, body mass index and CD4+ T cells percentage., Results: Ritonavir-unboosted PI-based HAART regimens were administered to most children at baseline; however, their use decreased during follow-up in favour of an NNRTI-based regimen. The nelfinavir/lamivudine/stavudine (regression coefficient=-0.69, p<0.05) and efavirenz/lamivudine/tenofovir (regression coefficient=-0.93, p<0.05) regimens, but not the ritonavir/lamivudine/stavudine regimen, were negatively associated with loge-transformed insulin AUC compared with indinavir/lamivudine/stavudine. Puberty was positively associated with loge-transformed insulin AUC., Conclusions: This 4-year prospective study of HAART-treated HIV-infected children shows that: (i) the nelfinavir/lamivudine/stavudine and the efavirenz/lamivudine/tenofovir regimens but not the ritonavir/lamivudine/stavudine regimen were associated with higher insulin sensivity, i.e. lower insulin AUC, compared with indinavir/lamivudine/stavudine; (ii) the treatment switched substantially in favour of NNRTI from the third year on and this change was associated with an improvement in insulin sensitivity compared with the previous HAART-based regimens; and (iii) puberty is a primary determinant of insulin sensitivity.

An increasing prevalence of antiretroviral therapy (ART) resistance in ART-experienced and ART-naive pregnant women has been reported. Some studies suggest that antiretroviral drug-resistant viruses might have decreased replication capacity and transmissibility. However, cases of perinatal transmission of multidrug-resistant HIV type-1 (HIV-1) have been described. Here, we report the case of one child with vertically-acquired multidrug-resistant HIV-1 and the outcome of a rescue therapy with a darunavir/ritonavir- and etravirine-containing antiretroviral regimen. During the 15 months of therapy, the child showed clinical improvement, including no side effects, persistent suppression of viral replication and a great increase in CD4+ T-cell count. Paediatric HIV specialists should be prepared to manage a small, but increasing, number of babies with a 'nightmare' multidrug-resistant virus with no available treatment options. The use of experimental agents might become a compelling issue in vertically HIV-infected children born in the era of highly active ART.

Purpose: To determine the feasibility of neoadjuvant docetaxel, cisplatin, and 5-fluorouracil (TPF) followed by concurrent chemoradiotherapy (CHT-RT) compared with the same CHT-RT regimen alone in locally advanced head-and-neck squamous cell carcinoma., Methods and Materials: We treated 24 patients (20 men and 4 women) who had Stage III-IVM0 squamous cell carcinoma of the oral cavity, oropharynx, nasopharynx, or hypopharynx. The median patient age was 59 years (range, 41-73 years). The stage distribution was as follows: Stage II, 1 patient; Stage III, 6 patients; and Stage IV, 17; 18 patients had a performance status of 0 and 6 had a performance status of 1. None had undergone previous CHT or RT. Group 1 underwent three cycles of CHT (carboplatin area under the curve 1.5 on Days 1-4 and 5-fluorouracil 600 mg/m(2)/d continuous infusion for 96 h) starting on Days 1, 22, and 43 during RT (one daily fraction, 66-70 Gy within 33-35 fractions). Group 2 underwent three cycles of neoadjuvant TPF (docetaxel 75 mg/m(2), cisplatin 80 mg/m(2), 5-fluorouracil 800 mg/m(2)/d continuous infusion for 96 h) followed by the same CHT-RT regimen., Results: After the first 16 patients, 8 in Group 1 and 8 in Group 2, the concomitant CHT-RT schedule was modified. The limiting toxicity observed during concomitant CHT-RT was similar in Groups 1 and 2, independent of neoadjuvant TPF administration. An excess of G3-G4 mucositis and other relevant toxicity that did not allowing completion of CHT-RT without interruption occurred in 44% of the patients. A reduction of at least one cycle of concurrent CHT was required in 31% of patients. On the basis of these data, the next 8 patients (Group 3) received three cycles of neoadjuvant TPF followed by two cycles only of CHT (cisplatin 20 mg/m(2) on Days 1-4 and 5-fluorouracil 800 mg/m(2)/d continuous infusion for 96 h) (PF) during Weeks 1 and 6 of the planned 7 weeks of RT. In Group 3, 25% of the patients developed World Health Organization G3-G4 mucositis. No World Health Organization hematologic G3-G4 toxicity was seen. RT interruption was required for 2 patients (25%). In 1 patient (12%), one cycle of CHT was omitted. During neoadjuvant TPF (Groups 2 and 3), the principal toxicities were G3-G4 neutropenia (37.5%) and G2 mucositis (44%). At the end of therapy, the CR rate was 62.5% for CHT-RT alone (Group 1) and 80% for neoadjuvant TPF followed by CHT-RT (Groups 2 and 3)., Conclusion: Three cycles of neoadjuvant TPF followed by two cycles of PF during RT are feasible without limiting toxicity. Three cycles of TPF were well tolerated and did not compromise subsequent concomitant CHT-RT. A randomized multicenter Phase III study has been started with the aim of comparing two cycles of PF during RT as standard treatment vs. the experimental arm with three cycles of neoadjuvant TPF followed by two cycles of PF during RT.

Aims and Background: In spite of the fact that ductal carcinoma in situ (DCIS) of the breast is a frequently encountered clinical problem, there is no consensus about the optimal treatment of clinically occult (i.e., mammographic presentation only) DCIS. Interest in breast conservation therapy has recently increased. Few data are available in Italy on the conservative treatment with surgery and adjuvant postoperative radiotherapy., Methods: A retrospective multi-institutional study was performed in 15 Radiation Oncology Departments in northern Italy involving 112 women with subclinical DCIS of the breast treated between 1982 and 1993. Age of the patients ranged between 32 and 72 years (median, 50 years). All of them underwent conservative surgery: quadrantectomy in 89, tumorectomy in 11, and wide excision in 12 cases. The most common histologic subtype was comedocarcinoma (37%). The median pathologic size was 10 mm (range 1 to 55 mm). Axillary dissection was performed in 83 cases: all the patients were node negative. All the patients received adjunctive radiation therapy with 60Co units (77%) or 6 MV linear accelerators (23%) for a median total dose to the entire breast of 50 Gy (mean, 49.48 Gy; range, 45-60 Gy). Seventy-six cases (68%) received a boost to the tumor bed at a dose of 8-20 Gy (median 10 Gy) for a minimum tumor dose of 58 Gy., Results: At a median follow-up of 66 months, 8 local recurrences were observed, 4 intraductal and 4 invasive. All recurrent patients had a salvage mastectomy and are alive and free of disease at this writing. The 10-year actuarial overall, cause-specific, and recurrence-free survival was of 98.8%, 100%, and 91%, respectively., Conclusions: The retrospective multicentric study, with a local control rate of more than 90% at 10 years with 100% cause-specific survival, showed that conservative surgery and adjuvant radiation therapy is a safe and efficacious treatment for patients with occult, non-palpable DCIS.

In 225 primary breast carcinomas the concentrations of carcinoembryonic antigen (CEA), ferritin, and tissue polypeptide antigen (TPA) were determined by radioimmunometric assays both in serum and in cytosol. The relationship of the three markers with the receptor content of the tumor was evaluated. No relationships were found between the serum level of each marker and the receptor status. In the cytosol, ferritin was higher in receptor-negative than in receptor-positive cases, whereas CEA and TPA showed significantly higher values in receptor-positive than in receptor-negative patients. Moreover, a direct relationship was found between estrogen receptor and both CEA and TPA and between progesterone receptor and TPA. Even if the significance of these findings is still unclear, from our data it can be concluded that there exists a noncasual relationship between the receptor status and the cytosol content of CEA and, particularly, TPA.

Since 1983 we have studied the relationship, in the same patient, between receptor status in breast carcinoma and in nonmalignant breast tissue. Fifty patients have been evaluated to date. The total unoccupied cytosol estrogen and progesterone receptors were determined by a dextran-coated charcoal method. In nonmalignant breast tissue we found a measurable receptor concentration above the sensitivity of the method in 62% of cases for estrogen receptors and in 44% of cases for progesterone receptors. No relationships were found between the receptor level of each tumor and that of the corresponding benign tissue. The data suggest that the levels of the receptors in the tumor and in the nonmalignant tissue are totally independent.