Is Electron Beam Intraoperative Radiotherapy (ELIOT) Safe in Pregnant Women with Early Breast Cancer? In Vivo Dosimetry to Assess Fetal Dose

Electron beam intraoperative radiotherapy (ELIOT) is a new technique permitting breast radiotherapy to be completed in a single session. Since ELIOT is associated with much reduced irradiation to nontarget tissues, we carried out a study on nonpregnant breast cancer patients to estimate doses to the uterus during ELIOT to better evaluate the possible use of ELIOT in pregnant breast cancer patients. We performed in vivo dosimetry with thermoluminescence radiation detectors (TLDs) in 15 premenopausal patients receiving ELIOT to the breast (prescribed dose 21 Gy) using two mobile linear accelerators. The TLDs were positioned subdiaphragmatically on the irradiated side, at the medial pubic position, and within the uterus. A shielding apron (2 mm lead equivalent) was placed over the viscera from the subcostal to the subpubic region. TLDs showed mean doses of 3.7 mGy (range 1–8.5 mGy) at subdiaphragm, 0.9 mGy (range 0.3–2 mGy) pubic, and 1.7 mGy (range 0.6–3.2 mGy) in utero, for beam energies in the range 5–9 MeV. These findings indicate that ELIOT with a mobile linear accelerator and shielding apron would be safe for the fetus, as doses of a few mGy are not associated with measurable increased risk of fetal damage, and the threshold dose for deterministic effects is estimated at 100–200 mGy. We conclude that studies on the use of ELIOT in pregnant women treated with conservative breast surgery are justified.     

International Study of Asthma and Allergies in Childhood: Validation of the rhinitis symptom questionnaire and prevalence of rhinitis in schoolchildren in São Paulo, Brazil

Written questionnaires (WQ) have been widely used in epidemiologic studies. In order to yield comparable results, they must be validated after translation to another language. The International Study of Asthma and Allergies in Childhood (ISAAC) WQ has been previously validated by a comprehensive study, but its validation in Brazil has not been performed. Our objectives were to validate the rhinitis component of the ISAAC's self-applicable WQ following its translation to Portuguese, and to determine the prevalence of rhinitis and related symptoms among Brazilian children living in the city of São Paulo. A group of 10 pediatricians and 10 pediatric allergists graded the questions from 0 to 2 and established a maximum score for each question. The WQ was answered by parents or guardians of children 6–7 years of age with rhinitis (R) (n = 27) and of control children of the same age without rhinitis (C) (n = 27). The WQ was also completed by adolescents 13–14 years of age with rhinitis (R) (n = 32) and without rhinitis (C) (n = 32). Half of these individuals answered the same WQ after 2–4 weeks, to ensure reproducibility. Cut-off scores of 4 and 3 were identified for the 6–7- and 13–14-year-old groups, respectively, as scores predictive of rhinitis. The prevalence of rhinitis was 28.8% in the group of 3005 children 6–7 years of age and 31.7% in the group of 3008 children 13–14 years of age, respectively. Using the global cut-off score, these prevalences were even higher, in the order of 34.7% and 40.7%, respectively. In conclusion, the rhinitis component of the ISAAC WQ was proven to be reproducible, adequate and able to discriminate children and adolescents with and without rhinitis, and revealed that the prevalence of rhinitis among Brazilian children living in the city of São Paulo was as high as the prevalence of rhinitis in other areas of the world.     

Circadian rhythm of plasma testosterone in men with idiopathic hypogonadotrophic hypogonadism before and during pulsatile administration of gonadotrophin-releasing hormone

OBJECTIVE: The aim was to investigate whether a pulsatile discharge of LH from the pituitary is necessary to achieve the circadian secretion of testosterone. DESIGN: The daily rhythm of the androgen has been studied in patients with idiopathic hypogonadotrophic hypogonadism (IHH) both in the absence of therapy and during pulsatile administration of gonadotrophin releasing hormone (GnRH). PATIENTS: Six patients with IHH and ten normal subjects were analysed. Blood sampling was performed at 2-hourly intervals, for 24 hours. The IHH patients then received synthetic GnRH i.v. at the rate of one pulse every 2 hours (10 micrograms/pulse). On day 11 of treatment, blood samples were taken for the rhythm analysis every 2 hours, for 24 hours. MEASUREMENTS: Plasma testosterone and LH were measured in the individual samples by radioimmunoassay. Evaluation of the rhythm was performed by cosinor analysis. RESULTS: A significant circadian rhythm of plasma testosterone was statistically validated in the normal subjects, whereas no rhythm was detected in the IHH patients in the absence of therapy. On day 11 of GnRH pulsatile administration the IHH patients showed normal testosterone levels and a statistically significant circadian rhythm of the androgen was evident, with acrophase between 0700 and 0800 h. Moreover, the amplitude, acrophase and mesor of testosterone rhythm in IHH patients in the course of treatment were statistically indistinguishable from the corresponding values in the normal subjects. Plasma LH did not show statistically significant circadian variations, either in the control group or in the IHH patients before or during therapy. CONCLUSIONS: We conclude that a physiological circadian rhythm of plasma testosterone can be obtained, in IHH men, by treatment with GnRH. Since the pulsatile administration of exogenous GnRH at constant doses induced a circadian rhythm in testosterone and no daily variations in LH were evident, we suggest that, although a pulsatile secretion of LH is probably necessary for the synchronization of the circadian rhythm with acrophase in the morning, the testosterone variations might be the results of a local testicular modulation of LH action.     

Pharmacokinetics and tumor concentration of intraarterial and intravenous cisplatin in patients with head and neck squamous cancer

Summary Tumor-tissue platinum levels and major pharmacokinetic parameters were determined in 11 patients with head and neck squamous cancer (HNSC) who were given cisplatin (50 mg/m² daily x 2 days) and 5-fluorouracil (5-FU; 1000 mg/m², continuous infusion x 5 days) either i.a. or i.v. The plasma peak platinum concentrations (c _max) and the areas under the curve for total platinum concentration versus time (AUC) during i.a. infusions were lower than the i.v.c _max (mean, 1.92±0.28 and 4.08±2.80 mg/l, for i.a. and i.v. infusions, respectively) and AUC values (mean, 22.55±4.96 and 40.66±10.71 mg h^–1 l^–1 for i.a. and i.v. treatment, respectively), suggesting a first-passage extraction of the drug by the tumor mass during i.a. infusion. However, no statistically significant difference was found in platinum tumor concentrations after i.a. administration versus i.v. infusion. The lack of a difference in tumor platinum concentrations between the i.a. and the i.v. administration routes might be explained either by a relatively high blood supply to the tumor area, enabling efflux of the surplus free platinum from the tissue, or by the delay between drug infusion and biopsy. After three cycles of i.a. treatment good tumor remission was obtained with minimal local toxicity. Larger clinical studies testing the advantages of the i.a. administration route over i.v. infusion appear to be necessary.Abbreviations HNSC head and neck squamous cancer - AUC area under the total platinum concentration versus time curve - OS overall survival - 5-FU 5-fluorouracil - DFS disease-free survival - CR complete response - PR partial response - SD stable disease - PRO progression This study was supported by grants from the AIRC (Italian Association for Cancer Research) and by grant from the Regione Veneto. One of the Authors (P.A.) is the recipient of an MPI 40% grant     

Screening for fra(x) mutation and Klinefelter syndrome in mental institutions

A total of 9153 male subjects in mental institutions from six different Italian districts were screened for the presence of bilateral microorchidism, in order to detect Klinefelter syndrome. Among the 212 microorchidic patients found, 33 had an XXY karyotype (15.5%). Ninety-one Klinefelter patients with normal intelligence were also examined as a control group. Cytogenetical and clinical findings were compared in these two groups of patients and no difference was found. Two fra(x)positive subjects were found, one for each group of XXY patients; the influence of fra(x) mutation on their phenotype is discussed.     

Respiratory chain deficiency presenting as congenital nephrotic syndrome

Nephrotic syndrome (NS) in infancy includes NS of Finnish type (mutation of the nephrin gene), diffuse mesangial sclerosis (idiopathic or linked to WT1 mutation), idiopathic NS, most often steroid resistant, and NS related to infections during pregnancy (virus, syphilis, toxoplasmosis). Later in life, NS has a large variety of etiologies. It has been described in association with neuromuscular symptoms, deafness, and diabetes in a few children and adults with respiratory chain (RC) disorders. To date, however, NS has never been observed in neonates with RC disorders. Here, we report RC deficiency in one infant with certain congenital NS and two siblings with acute neonatal cardiac and renal disease with probable NS. Although clinical and histopathological presentations were initially close to congenital NS of Finnish type, clinical outcome was atypical and nephrin mutation was excluded. Mitochondrial RC complex II+V deficiency was identified in the three patients. Based on these observations, we suggest that RC disorders should be considered in patients with congenital NS.     

Concurrent radiotherapy does not affect adjuvant CMF delivery but is associated with increased toxicity in women with early breast cancer

We evaluated whether concurrent radiotherapy (RT) affected delivery and toxicity of adjuvant intravenous CMF (cyclophosphamide, methotrexate and 5-fluorouracil) in women with operable breast cancer. The medical charts of 321 consecutive breast cancer patients who received CMF either alone for 6 cycles, or for 4 cycles following of an anthracycline (A-CMF) were reviewed. One hundred forty-four women underwent radiotherapy concurrently with CMF. Optimal CMF delivery (success as opposite to failure) was defined as the combined achievement of an average relative dose intensity (aRDI) > or = 85% and an average percent of the total dose (aPTD) > or = 90% for the three drugs in the CMF regimen. Multivariate logistic regression analysis showed that concurrent-RT did not affect CMF delivery (OR for success 1.391 p=0.230). The sequential A-CMF regimen (OR for success 0.208, 95% C.I. 0.120-0.360, p<0.001) and age > or = 56 (OR for success 0.351, 95% C.I. 0.200-0.161, p<0.001) were independently associated with suboptimal CMF delivery. Moreover, concurrent RT was independently associated with increased leukopenia, thrombocytopenia, upper abdominal pain, mucositis and fatigue. Our retrospective analysis suggests that concurrent-RT has no impact on optimal CMF delivery, but it increases the burden of CMF-related toxicity.     

Supernumerary ring chromosome 8: clinical and molecular cytogenetic characterization in a case report

We report on a 3-year-old male with developmental delay, autistic behavior, and minor abnormalities consistent with trisomy 8 syndrome whose cytogenetic analysis revealed mosaicism for a supernumerary ring chromosome (SRC). Fluorescence in situ hybridization (FISH) studies, using centromeric and yeast artificial chromosome (YAC) probes, were performed to characterize further the supernumerary chromosome. The ring origin has been detected from the short arm of chromosome 8, resulting in r(8)(p10p23.1). Moreover, uniparental disomy (UPD) using microsatellite analysis was excluded. To our knowledge a total of 25 cases, confirmed by FISH, have been reported with either supernumerary marker or ring chromosome 8. We present a detailed clinical and molecular cytogenetic characterization of this additional case in order to better define the genotype-phenotype correlation.