Phosphodiesterase 11A (PDE11A) and genetic predisposition to adrenocortical tumors.

PURPOSE: We have reported previously nonsense inactivating mutations of the phosphodiesterase 11A (PDE11A) gene in patients with micronodular adrenocortical hyperplasia and Cushing syndrome. The aim of this study is to investigate the presence of somatic or germ-line PDE11A mutations in various types of adrenocortical tumors: ACTH-independent macronodular adrenocortical hyperplasia (AIMAH), adrenocortical adenoma (ACA), and adrenocortical cancer (ACC). EXPERIMENTAL DESIGN: PDE11A was sequenced in 117 adrenocortical tumors and 192 controls subjects; immunohistochemistry for PDE11A and tumor cyclic AMP levels were studied in a subgroup of adrenocortical tumors. RESULTS: One PDE11A inactivating mutation (R307X) was found in one ACA, 22 germ-line missense variants (18.8%) were found in adrenocortical tumors, and only 11 missense variants (5.7%) were found in controls. By comparing the common mutations, a higher frequency of mutations in adrenocortical tumors than in age/sex-matched controls were observed [16% versus 10% in ACC, 19% versus 10% in ACA, and 24% versus 9% in AIMAH; odds ratio (OR), 3.53; P = 0.05]. Somatic DNA from adrenocortical tumors with missense variants showed a wild-type allelic loss. A significant difference between ACC and controls was observed for a polymorphism in exon 6 (E421E; OR, 2.1; P = 0.03) and three associated polymorphisms located in intron 10-exon 11-intron 11 (OR, 0.5; P = 0.01). In AIMAH/ACA, cyclic AMP levels were higher than in normal adrenals and decreased PDE11A immunostaining was present in adrenocortical tumors with PDE11A variants. CONCLUSIONS: The present investigation of a large cohort of adrenocortical tumors suggests that PDE11A sequence defects predispose to a variety of lesions (beyond micronodular adrenocortical hyperplasia) and may contribute to the development of these tumors in the general population.     

Early detection of hip dysplasia in the neonatal period

Several risk factors are associated with an increased incidence of congenital hip dysplasia. Since the introduction of hip sonography the understanding of correlation between risk factors and US have been studied to decrease the prevalence of the deformity. Regression analysis and chi-square test were used to study the incidence of factors associated with congenital hip dysplasia. Positive family history, breech presentation, positive Ortolani manoeuvre, abduction deficit, asymmetric skin folds, feet or neuromuscular abnormities were compared to ultrasound examination. No significant correlation was found with any of the studied risk factors. Mild congenital hip dysplasia can be diagnosed only by ultrasound. It was found that 1.7% of congenital hip dysplasia are clinically asymptomatic and cannot be recognized without ultrasonographic screening.     

Minoxidil (Mx) as a prophylaxis of doxorubicin - induced alopecia

BACKGROUND: Minoxidil (Mx) is known to induce hair growth in men with male-patternbaldness. Based on this potential, the effectiveness of Mx 2%topical solution was evaluated in cancer patients (pts) to preventdoxorubicin-induced alopecia. PATIENTS AND METHODS: 48 female pts with different types of solid tumors treated withdoxorubicin-based chemotherapy in a dose range of 50–60mg/m²/cycle were randomly assigned to receive Mx 2% topicalsolution or placebo. RESULTS: 88% and 92% of pts in both arms showed severe alopecia (p –ns). No adverse effects were observed. CONCLUSIONS: In this study Mx 2% topical solution was non-toxic but was noteffective in the prevention of chemotherapy-induced alopecia. alopecia, minoxidil, doxorubicin, chemotherapy     

Correlations between vocal qualities and mental retardation

This research is intended to verify the existence of vocal spectrographic alterations, with particular reference to the values of Fundamental Frequency, in patients with different levels of Mental Retardation. The results show the existence of a direct correspondence between the values of the Fundamental Frequency and the level of Mental Retardation: the spectrographic characteristics appear to be more altered in subjects with severe Mental Retardation. The spectrographics patterns are characterized by the presence of bi-phonation particularly at the onset time and at the end, and by a noise signal on constant frequency. The shifts of Fundamental Frequency and voice breakage are rarely detected.     

Urinary concentrations of beta core fragment of hCG throughout pregnancy.

OBJECTIVE: We sought to determine a reference range for urinary immunoreactive beta core fragment of hCG (beta C-hCG) in pregnancy, the ratio between beta C-hCG and intact hCG, and the earliest detectable rise of beta C-hCG in urine. METHODS: Urine was obtained from 741 pregnant women between 6-41 weeks' gestation, as well as from women undergoing donor insemination with timed ovulation peaks. RESULTS: The beta core fragment of hCG reached a maximum between 8-15 weeks, with a decrease between 20-29 weeks. The molar ratio of beta C-hCG to intact hCG was always greater than 1. CONCLUSION: In pregnancy, beta C-hCG concentrations increase in the urine in parallel to intact hCG but at a higher molar ratio, suggesting either placental production of beta C-hCG or enhanced metabolism of hCG to beta C-hCG in peripheral organs.     

Response to poliovirus immunization and type of feeding in babies of atopic families

The aim of the present study was to investigate the antibody response to oral poliovirus immunization, and to evaluate the infection morbidity in a group of infants with a positive family history of atopy who were soy-protein-formula fed during the first 6 months of life. We have selected and followed from birth to 4 yr, 107 babies, 18 of whom were exclusively soy-protein-formula fed during the first 6 months of life. All infants were seen at our clinic at the ages of 1, 3, 6, 9, and 12 months, and once-a-year afterwards. They regularly received the oral vaccine against polioviruses at the ages of 3, 5 and 12 months. At age 6, 12 and 24 months, poliovirus type 1, 2 and 3 antibodies were detected. There was no significant difference of seroconversion in the babies, breast, soy or breast and soy fed. Furthermore, no increase in infection morbidity was observed in the soy-protein-formula fed infants. Our data shows that soy-protein-formula feeding in the first 6 months of life does not induce any abnormal antibody response to the oral poliovirus vaccination, as well as no increase in infection morbidity.     

A phase I trial of intermittent high-dose {alpha}-interferon and dexamethasone in metastatic renal cell carcinoma

BACKGROUND: Evidence exists that the toxic effects of a-interferon can beameliorated by co-administration of dexamethasone without compromiseof therapeutic efficacy. We therefore conducted a phase I trialto determine the maximum tolerated dose of intermittent interferonwhen combined with oral dexamethasone PATIENTS AND METHODS: Thirty patients with metastatic renal cell carcinoma were enrolled.The starting dose of interferon was 20 million IU/m²/day givenas a subcutaneous injection days 1 to 4 of each 14 day cycle.Dose levels were escalated at increments of 5 million IU/m².Dexamethasone 4 mg was administered orally every 6 hours duringadministration of high-dose interferon. Low-dose maintenanceinterferon, 3 million lU/m²/day, was administered without doseescalation on days 5 to 14 of each cycle. RESULTS: The maximum tolerated dose of intermittent high-dose interferonwas 40 million IU/m²/day. The dose limiting toxicity was fatigue.EEG abnormalities developed in five patients and neuropsychiatricparameters deteriorated significantly in seventeen. CONCLUSIONS: We conclude that co-administration of dexamethasone improvesthe tolerance of intermittent high-dose interferon. The resultsof this trial may be useful in designing high-dose interferonregimens for renal cell carcinoma and other interferon-sensitivediseases. dexamethasone,