Classification tree analysis of second neoplasms in survivors of childhood cancer

Background  

Reports on childhood cancer survivors estimated cumulative probability of developing secondary neoplasms vary from 3,3% to 25% at 25 years from diagnosis, and the risk of developing another cancer to several times greater than in the general population.     

Non-linear tissue binding of amikacin in rats: the effect of renal impairment

Amikacin levels in serum and tissues were determined in 115 Wistar rats, 70 with normal renal function (NRF) and the remaining 45 with terminal renal impairment (TRI). The results obtained in the animals with NRF show an accumulation of the antibiotic in all the tissues studied as compared with plasma levels, specially in the renal cortex and medulla. In the rats with TRI important alterations in the plasma and tissue kinetics of the antibiotics were observed. The plasma kinetics of amikacin in rats with TRI are characterised by significant alterations in the pharmacokinetic parameters, specially those defining the distribution processes of the antibiotic. In the tissues of the latter, a significant increase in the antibiotic concentration takes place, particularly in the renal cortex. The average half-lives of the antibiotic in the tissues of rats with TRI increase compared with the group of rats with NRF, though the difference are not so significant as in the case of the plasma half-life. The use of a specific kinetic distribution model, with linear and non-linear tissue binding, showed that significant variations occur in the partition coefficient and in the Michaelis-Menten parameters, which characterize the saturable binding of Amikacin to tissue in rats with NRF and TRI.     

Familial stenosis of the pulmonary artery branches with a JAG1 mutation.

Although most congenital heart defects are isolated abnormalities of embryonic development, with little genetic contribution, a small number are components of syndromes. In such cases, an accurate diagnosis has important implications for individual prognosis and familial genetic counseling. Alagille syndrome (AGS) is a dominantly inherited multisystem developmental disorder, which primarily affects the liver, heart, eyes, skeleton, and face. In recent years, the identification of the AGS gene has drawn attention to the existence of subclinical carriers, and broadened the spectrum of phenotypical variation associated with this syndrome. The authors present a case of mother and son with benign stenosis of the pulmonary artery branches. Subtle facial aspects suggested the diagnosis of AGS, which was confirmed by molecular analysis. Relevant clinical investigations and diagnostic implications are discussed.     

Repeat pregnancy associated with cardiac pacemaker.

Two pregnancies in a patient with a fixed-rate pacemaker are reported. The first pregnancy was uneventful. The second had no maternal complications either. A moderate tachysystolia was detected during the second period. The newborn was delivered with forceps applied under spinal anesthesia. Newborn infant evolution presented no hazards, but umbilical cord analysis revealed a severe acidosis, in spite of a normal scalp analysis 45 min earlier. Epidural anesthesia is recommended for such patients.     

Opposite effects of angiotensin-II and corticotropin on bovine adrenocortical cell steroidogenic responsiveness.

The long-term effects of angiotensin-II (A-II) and corticotropin (ACTH) on bovine adrenal fasciculata cells (BAC) were studied. Cells were pretreated for 3 days with either A-II or ACTH followed by an examination of the acute steroidogenic response to both hormones as well as the ability to convert several steroid precursors to cortisol and corticosterone. ACTH pretreatment caused a marked increase in cortisol output associated with a decrease in corticosterone secretion in response to both hormones leading to a 50-fold decrease in the corticosterone/cortisol ratio compared to control cells. After incubation with saturating concentrations (5 X 10(-5) M) of 22 R-hydroxycholesterol, pregnenolone or progesterone, ACTH-pretreated cells produced more cortisol than corticosterone whereas the contrary was observed in control cells. However, the conversion of 17 alpha-hydroxyprogesterone and 11-deoxycortisol to cortisol by ACTH-pretreated cells was lower than by control cells. Thus, the main effects of ACTH were a marked increase of 17 alpha-hydroxylase and a small but significant decrease of 21-hydroxylase and 11 beta-hydroxylase activities. A-II pretreatment produced, in a concentration-dependent manner, a down-regulation of its own receptors and homologous and heterologous steroidogenic desensitization. At maximal concentrations (10(-6) M) A-II reduced by 70% its own receptors while the steroidogenic response to A-II and ACTH was reduced by 95% and 75%, respectively. However, the coupling of A-II receptors to phosphoinositide pathway and to Ca2+ influx, as well as its potentiation effect on ACTH-induced cAMP production were similar in control and A-II pretreated cells. Moreover, the conversion of several steroid precursors to corticosterone was similar in control cells and A-II-pretreated cells, whereas the conversion to cortisol was reduced by approximately 30% due mainly to a decrease of 17 alpha-hydroxylase activity. Thus, the marked steroidogenic desensitization induced by A-II is most likely related to some alteration located beyond the activation of the two branches of the phosphoinositide pathway and before the first steps of steroidogenesis.     

Glyceraldehyde-3-phosphate dehydrogenase (GAPDH, E.C. 1.2.1.12.) gene expression in two malignant human mammary epithelial cell lines: BT-20 and MCF-7. Regulation of gene expression by 1,25-dihydroxyvitamin D3 (1,25-(OH)2D3).

Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) is a key enzyme in the control of glycolysis. Its gene expression was analyzed in two breast cancer cell lines of human origin, BT-20 and MCF-7. We used a cDNA probe of 1.3 kb for Northern blot hybridization. It is found that GAPDH mRNA is overexpressed only in the poorly differentiated BT-20 cell line and that treatment of these cells by 1,25-dihydroxyvitamin D3 (1,25-(OH)2D3) stimulates GAPDH mRNA expression in a dose-and time-dependent manner. The present investigation on the BT-20 cells indicates that the expression of GAPDH is sensitive to 1,25-(OH)2D3 and up-regulated by low doses of this steroid.     

Computed tomography in gunshot wounds to the neck: Can we predict vascular injury?

The purpose of this study was to evaluate the ability of helical computed tomography (CT) to detect arterial injuries in gunshot wounds to the neck. In a blinded retrospective review, 54 helical CT scans of the cervical spine were evaluated for bullet/bone fragments, subcutaneous air, bullet path, hematoma, spine fractures, and pharyngoesophageal compromise. The distance of fragments to a major vessel was calculated. CT findings that correlated significantly with major arterial injury included the presence of fragments (bullet/bone) close to a major vessel (2.5 mm) and spine fractures. Visualizing fragments <5 mm from a vessel or a transcervical bullet trajectory predicted 12 of 13 major arterial injuries. We conclude that CT clearly depicts anatomic damage. Specific findings, such as the location of fragments and bullet trajectory adjacent to a vessel and spine fractures, indicate a higher probability of vascular damage, thus directing more definitive evaluation.     

Determination of sex and Y chromosome]

Years of speculations about the nature of the elusive testis determining factor (TDF) of the Y chromosome have ended last year. A gene named SRY satisfies many criteria expected of the testis determining gene, and gives us a basis to understand molecular mechanisms of the testis differentiation. The different steps which gave rise to SRY cloning are described.     

Influence of cigarette smoking on pituitary and sex hormone balance in healthy premenopausal women

Plasma gonadotropin FSH and LH, PRL, sex steroids (17-beta E2, E1, and P), SBP binding capacity, and urine estrogens (E1, E2, and E3) were measured in 485 premenopausal healthy women, subdivided according to smoking habits. The aim of the study was to verify if cigarette smoking influences sex hormone balance. Baseline PRL levels were significantly lower (P less than 0.002) in smoker (n = 174) than in nonsmoker (n = 311) women. No difference was found in the other parameters of the two groups, particularly in plasma and urine estrogenic pattern. Our data suggest that smoking directly affects PRL levels by involving the hypothalamic mechanism that regulates PRL secretion.