Second neoplasms in survivors of childhood and adolescent cancer are often treatable.

PURPOSE: To estimate the incidence and types of second neoplasms in survivors of childhood and adolescent cancer, as well as the characteristics of those who developed second neoplasms. METHODS: Survivors who were under age 21 years at initial diagnosis, off therapy, and in remission for 2 years are referred to the Long Term Survivors' Clinic (LTSC) at Children's National Medical Center (CNMC). This review includes patients entered in the clinic database from January 1, 1997 to August 30, 2002. RESULTS: Twenty-three (2.3%) of 987 childhood cancer survivors followed in the LTSC had 26 (2.6%) second and third neoplasms. The mean age was 6.7 years at initial diagnosis, 20.3 years at diagnosis of the second neoplasm, and 20.5 years at diagnosis of the third neoplasm. Of 10 female and 13 male patients, 15 were white, six black, one Hispanic, and one Asian. All but two of the patients received radiation. Nineteen neoplasms, including seven thyroid carcinomas, six central nervous system tumors (three meningiomas), three basal cell carcinomas, two breast cancers, and one soft tissue sarcoma, occurred at sites within or contiguous to radiation sites. Five patients died, but the majority of neoplasms were treatable and most patients had good outcomes. CONCLUSION: Indefinite follow-up in a long-term survivors' clinic is indicated for adolescent and adult survivors of childhood cancer, with routine examination and screening for recurrence of the initial cancer as well as late effects, including second neoplasms.     

Partial isolation of an endogenous norepinephrine uptake inhibitor in canine plasma

We have previously reported that homologous plasma inhibits the accumulation of [3H]norepinephrine ( [3H]NE) by the canine saphenous vein. The purpose of this study was to extract the inhibitory substance(s) from plasma and to examine some of its properties. The net accumulation of tritium by saphenous vein strips following incubations in [3H]NE was inhibited 34.4 +/- 6.1% by a 60% plasma in Krebs solution. An acetone extract of this plasma reconstituted to 83% of its original unextracted volume also significantly inhibited net tritium accumulation by 24.5 +/- 4.7%. After lyophilization of this extract, the inhibitor was not readily solubilized in dilute acetic acid but was soluble in dilute sodium bicarbonate solutions. This extract solution, reconstituted to 66% of the original plasma volume, significantly inhibited the accumulation of [3H]NE by 35.0 +/- 9.8%. Kinetic analysis using this preparation suggests that the inhibition may be competitive in nature. The activity was not sensitive to heat but was abolished by the neuronal uptake blocker cocaine. Further purification with gel chromatography produced a small molecular weight fraction that inhibited tritium accumulation. When this sample was reconstituted in a volume equivalent to that of the unextracted plasma, the contractile response of the isolated canine saphenous vein to electrical stimulation was significantly enhanced. Thus the inhibitory activity of plasma on the uptake of [3H]NE by the canine saphenous vein is due in part to a heat-stable small molecule that inhibits the initial rate of [3H]NE uptake.     

Effects of a neutral endoprotease enzyme inhibitor, thiorphan, on hemodynamics and renal excretory function in four models of experimental hypertension

Thiorphan, a neutral endoprotease (NEP) enzyme inhibitor, has been shown to enhance the effects of atrial natriuretic peptide (ANP) in vivo. In this study, we examined the effects of an intravenous (iv) infusion of thiorphan on cardiovascular hemodynamics and excretion of urine volume (UV), sodium (U(Na)V) and potassium (UKV) in four different models of experimental hypertension, namely: 1) SHR, 2) two-kidney, one clip (2K1C),3) one-kidney, 1 clip (1K1C) and. 4) 70% reduced renal mass-salt (RRM-S) hypertensive rats. SHR has normal plasma renin activity, 2K1C is renin dependent, and 1K1C and RRM-S are low renin volume dependent models of hypertension. Rats were divided into experimental and control groups. Under inactin (120 mg/kg, body weight) anesthesia, rats were instrumented to record blood pressure and dP/dt (Millar catheter) and urine was collected through a suprapubic urinary bladder catheter. Experimental animals received an iv infusion of thiorphan, 0.5 mg/kg/min for 120 minutes. Control animals received vehicle only. In some animals, vascular smooth muscle cell membrane potentials (Em) was measured in vivo. In another series of experiments, using the identical protocol, cardiac output was recorded. The thiorphan infusion produced a similar progressive decrease in blood pressure in all models of hypertension. Cardiac output did not change relative to vehicle infused control animals. Thus pressure decreased because of a decrease in total peripheral resistance. The contractility index (dP/dt/P, where P = left ventricular pressure) did not change but vascular smooth muscle cells in tail arteries hyperpolarized in all four models. In spite of a significant decrease in blood pressure, thiorphan infusion either increased or produced no change in urinary volume (UV) and sodium (U(Na)V) excretion. These data show that thiorphan, an NEP inhibitor, decreases the blood pressure of hypertensive rats due to a decrease in total peripheral resistance, perhaps by hyperpolarizing vascular smooth muscle cells. These effects are independent of the mechanism of the hypertension. Increased UV and U(Na)V in the face of decreased pressure suggests a direct renal effect.     

Cancers secondaires des radiothérapies

For more than 20 years, cancer survival rates have been increasing. In spite of efforts to target only cancerous cells, chemotherapy and radiotherapy reach healthy tissue and have carcinogenic effects. A large number of studies, with and without precise dosimetric evaluations, have investigated malignancies secondary to radiation therapy, but their results have often been contradictory. There is still no model able to predict the risk of secondary cancer associated with a given radiotherapy, implying that it is impossible to anticipate the consequences of new radiotherapy techniques such as IMRT.