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.     

Guanylnucleotide specificity for muscarinic receptor inhibitory coupling to cardiac adenylate cyclase.

The guanylnucleotide specificity of muscarinic acetylcholine receptor (MR) inhibitory coupling to cardiac adenylate cyclase (AC) was investigated under low MgCl2 (i.e., 0.5 mM) conditions. In purified cardiac sarcolemma, carbachol maximally inhibited AC activity 60% in the presence of GTP. Carbachol-dependent inhibition in the presence of guanosine 5'-O-(3-thiotriphosphate (GTP gamma S) or guanylylimidodiphosphate [Gpp(NH)p] was of lesser magnitude (i.e., 30%) and was evident only during short incubation periods. Of greater interest, carbachol maximally inhibited AC activity in the presence of GDP and guanosine 5'-O-(2-thiodiphosphate (GDP beta S) by 35 and 60%, respectively. Control studies ruled out transphosphorylation of GDP and GDP beta S by nucleoside diphosphate kinase or guanylnucleoside triphosphate contamination as reasons for the inhibitory effects of GDP and GDP beta S. Furthermore, isoproterenol stimulated AC in the presence of GTP, GTP gamma S, and Gpp(NH)p but not in the presence of GDP or GDP beta S. Therefore, GDP and GDP beta S may serve as agonists on MR-activated Gi but not on beta-adrenergic receptor-activated Gs in these membranes. Time course studies revealed that carbachol-dependent inhibition of AC in the presence of either GTP or GDP occurred without a detectable lag period, and this inhibition was rapidly reversed by atropine. In contrast, a 1-2-min lag time was required for carbachol- and GDP beta S-dependent inhibition of AC to occur, and inhibition, once developed, was only partially and slowly reversed by atropine. Preincubation of sarcolemma with carbachol and GDP beta S, in the absence of ATP or under nonphosphorylating conditions, eliminated the lag time for inhibition of AC activity. Although it is unlikely that GDP and GDP beta S have physiological relevance of MR-Gi-AC coupling, these studies provide unique insights into this coupling mechanism in cardiac membranes.     

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.     

Qualitative microscopy of implanted vein grafts. Effects of graft integrity on morphologic fate.

This is an investigation of the relationship between graft preparation techniques and the subsequent fate of vein grafts. Vein grafts intentionally injured by warm saline storage demonstrated endothelial and smooth muscle cell damage. In the acute postimplantation period, platelet adhesion/activation and white cell infiltration were present. By 7 days the endothelium had "healed," but the underlying smooth muscle cells had modulated and were of the synthetic phenotype. This persisted at 30 days, but by 60 days the graft wall remodeled with smooth muscle cells that were of the contractile phenotype, with an organized extracellular matrix. None of these injurious responses were noted in optimally prepared papaverine-treated vein grafts. Optimal preparation of vein grafts is effective in minimizing endothelial and smooth muscle cell injury before and after arterial reconstruction. Prevention of vein graft injury during harvesting prevents the morphologic changes characteristic of the "arterialization response."     

Women supporting women: Supportive/educative groups for ethnically diverse,urban, impoverished women dealing with depression and anxiety

Depression and anxiety are mental health issues that disproportionately affect urban, ethnically diverse, impoverished women. Using community based participatory research and in the context of long-term partnerships between a nursing department and underserved neighborhoods that are predominately Black, Hispanic, and White respectively, supportive/educative groups were offered. The study employed a quasi-experimental, nonequivalent comparison group pretest-posttest design. Seventy-two women aged 17–88?years participated. Repeated measures ANOVA indicated a significant increase in knowledge for self-care for depression and anxiety and a significant decrease in anxiety and depression symptomatology from before to after the group sessions.