Icons improve older and younger adults' comprehension of medication information

We examined whether timeline icons improved older and younger adults' comprehension of medication information. In Experiment 1, comprehension of instructions with the icon (icon/text format) and without the icon (text-only format) was assessed by questions about information that was (a) implicit in the text but depicted explicitly by the icon (total dose in a 24 hour period), (b) stated and depicted in the icon/text condition (medication dose and times), and (c) stated but not depicted by the icon (e.g., side effects). In a separate task, participants also recalled medication instructions (with or without the icon) after a study period. We found that questions about dose and time information were answered more quickly and accurately when the icon was present in the instructions. Notably, icon benefits were greater for information that was implicit rather than stated in the text. This finding suggests that icons can improve older and younger adults' comprehension by reducing the need to draw some inferences. The icon also reduced effective study time (study time per item recalled). In Experiment 2, icon benefits did not occur for a less integrated version of the timeline icon that, like the text, required participants to integrate dose and time information in order to identify the total daily dose. The integrated version of the icon again improved comprehension, as in Experiment 1, as well as drawing inferences from memory. These findings show that integrated timeline icons improved comprehension primarily by aiding the integration of dose and time information. These findings are discussed in terms of a situation model approach to comprehension.     

Feeding colostrum increases circulating insulin-like growth factor I in newborn pigs independent of endogenous growth hormone secretion

Our objective was to examine the influence of feeding and endogenous GH secretion on circulating IGF-I in colostrum-deprived newborn pigs fed colostrum (n = 4), formula (control, n = 4), or water (n = 4). In another four formula-fed pigs, GH was ablated (GRF-A) with two intravenous injections of a GH releasing-factor antagonist (N-Ac-Tyr1,D-Arg2)-GRF(1-29)-NH2. Blood was serially sampled in all pigs to measure plasma IGF-I and GH profiles. Feeding increased plasma IGF-I concentration two- to fourfold and decreased GH secretion. Despite a more than 80% decrease in the plasma GH in GRF-A pigs, the circulating IGF-I concentration was similar to that in control pigs. In colostrum-fed pigs, plasma IGF-I was higher than that in control pigs, despite equal nutrient intake and lower circulating GH. There were no differences in plasma IGF binding protein (IGFBP)-3 levels among the treatment groups. However, the relative abundance of plasma IGFBP-4 was lower, and that of IGFBP-1 higher, in unfed pigs than in any of the three fed groups. The plasma insulin concentration was not different among fed pigs, but it was lower in unfed pigs. Our results indicate that the circulating IGF-I concentration is more dependent on nutrient intake than on GH in newborn pigs, despite relatively high GH concentrations. However, because the nutrient content in the formula was designed to match that of colostrum, a factor other than nutrient intake and GH was responsible for the maximal increase in circulating IGF-I concentration observed in colostrum-fed pigs.     

Management of recurrent meningeal hemangiopericytoma

BACKGROUND: Meningeal hemangiopericytoma is an uncommon neoplasm with a high propensity for recurrence. The purpose of this study was to analyze the efficacy of different treatment options in patients with recurrent disease. METHODS: The records of all patients with recurrent meningeal hemangiopericytoma treated at the study institution between 1976 and 1996 were reviewed. RESULTS: Thirty-four consecutive patients were studied. The mainstay of treatment was brain surgery in 21 patients (62%); the median time to recurrence from surgery was 12 months. Ten patients (29%) had 20 recurrent central nervous system (CNS) lesions treated by stereotactic radiosurgery. Of these, 3 previously nonirradiated patients (all with lesion size < 25 mm) achieved a complete response, which persisted at a median of 3 years. In 14 lesions (70%) a partial response (PR) occurred with a median duration of 12 months, whereas 3 lesions (15%) remained stable. Two patients with inoperable CNS lesions received external beam radiation therapy and both had PRs lasting 14 and 24 months, respectively. Nine patients (26%) received radiation therapy for metastatic disease. Of these, seven patients remained stable with good symptomatic relief, and two patients experienced tumor progression. Chemotherapy with doxorubicin-containing regimens was administered in 7 patients (21%); there was only 1 PR that lasted 8 months. The median survival from first recurrence was 4.6 years. CONCLUSIONS: Surgical management is important for the successful treatment of patients with recurrent meningeal hemangiopericytoma. Radiosurgery plays a definite role in the treatment of smaller recurrent CNS lesions. Radiation therapy is helpful in the management of inoperable tumors. More effective chemotherapeutic agents are needed.     

Energy metabolism in sedentary and active 49- to 70-yr-old women

This study examined differences between long-term exercising (LE) and long-term nonexercising (LNE) women [n = 24; age 56.4 +/- 6.2 (SD) yr] for resting metabolic rate (RMR) and energy expenditure in the free-living state by using doubly labeled water (DLW). There was a statistically significant difference (P = 0.0002) between the 12 LE (94.85 +/- 8.44 kJ . kg-1 . day-1) and 12 LNE (81.16 +/- 6.62 kJ . kg-1 . day-1) for RMR, but this difference was only marginally significant (P = 0.06) when the data (MJ/day) were subjected to an analysis of covariance with fat-free mass as the covariate. The DLW data indicated that the eight most active LE (12.99 +/- 3.58 MJ/day) expended significantly (P = 0.01) more energy than did the eight least active LNE (9.30 +/- 1.15 MJ/day). Energy expenditures ranged from 7.64 to 18.15 MJ/day, but there was no difference (P = 0.96) between the LE and LNE in energy expenditure during activity that was not designed to either improve or maintain fitness. These cross-sectional data on 49- to 70-yr-old women therefore suggest that 1) aerobic-type training results in a greater RMR per unit of body mass and also when statistical control is exerted for the effect of the metabolically active fat-free mass, 2) there is a large range in the energy intake necessary to maintain energy balance, and 3) aerobic training does not result in a compensatory reduction in energy expenditure during the remainder of the day.     

Transduction of full-length TAT fusion proteins into mammalian cells: TAT-p27Kip1 induces cell migration

Human procathepsin L has been expressed in E. coli in the form of inclusion bodies. The recombinant protein was isolated, refolded and processed at pH 5.5 by the addition of dextran sulfate which increased the overall yield of cathepsin L almost 10-fold. After the auto-activation of the 38 kDa procathepsin L at least three processing sites were determined by N-terminal amino acid sequencing. After replacing the Ala205 residue by glutamic acid, cathepsin B-like specificity was introduced into cathepsin L. This mutation resulted in a 15-fold increased activity toward the substrate Z-Arg-Arg-AMC and in a 29-fold decreased activity toward Z-Phe-Arg-AMC. Residue 205 is thereby confirmed experimentally to be critical for the specificity of cathepsins B and L.     

Statistical modeling using preoperative prognostic variables in predicting extracapsular extension and progression after radical prostatectomy for prostate cancer

OBJECTIVE: To predict the risk of extracapsular extension and postoperative recurrence before radical prostatectomy (RP) for prostate cancer. METHODS: We performed multivariate Cox regression analysis on preoperative variables in 260 clinically localized prostate cancer patients who underwent RP. With these data, we constructed a relative risk of recurrence (Rr) equation and an equation to predict the probability of extracapsular extension (PECE) before RP. RESULTS: Rr is calculated as exp[(0.47 x race + 0.14 x PSAST) + (0.13 x worst biopsy Gleason sum) + (1.03 x stage T1c) + (1.55 x stage T2b,c)], where PSAST indicates a sigmoidal transformation of prostate-specific antigen. PECE is calculated as 1/[1 + exp(-Z)], where Z = -2.47 + 0.15 (PSAST) + 0.31 (worst biopsy Gleason sum) + 0.18 (race) + 0.16 (stage T1c) + 0.38 (stage T2b,c). CONCLUSION: These two equations can be used preoperatively to predict the probability of extracapsular disease and the risk of prostate-specific antigen recurrence in patients undergoing RP.     

Exploring structure-activity relationships around the phosphomannose isomerase inhibitor AF14049 via combinatorial synthesis

Phosphomannose Isomerase (PMI) has been shown by genetic methods to be an essential enzyme in fungal cell wall biosynthesis. The PMI inhibitor AF14049 was discovered as an unanticipated side product from high-throughput library screening against the enzyme from C, albicans. Solid-phase synthetic methods were developed and a series of libraries and discrete analogs synthesized to explore SAR around AF14049.     

Sustaining interventions in community systems: on the relationship between researchers and communities

Important goals of research-based community interventions include the long-term maintenance of effects and fostering of collaboration between researchers and community leaders. This article reviews the challenges associated with transferring innovations to community systems, changing program delivery from an experimental context controlled by researchers to program delivery controlled by community organizations, and sustaining long-term effects of interventions. It is suggested that researchers who develop and implement community interventions in diverse health areas need to confront several issues: (a) fostering effective long-term relationships between researchers and the communities they study and in which they intervene and (b) designing and implementing interventions that are useful to community systems after the formal phase of research ends.     

Use of a two-compartment model to assess the pharmacokinetics of human ethanol metabolism

The relationship between blood ethanol concentration and hepatic ethanol metabolism commonly is calculated using the Michaelis-Menten equation and a one-compartment model that assumes equality of blood and hepatic ethanol concentrations. However, at low blood concentrations, most of the ethanol arriving at the liver is metabolized, and hepatic ethanol concentrations may fall far below that of the entering blood. We have developed a two-compartment model of ethanol metabolism that accounts for the fall in ethanol concentration that may occur as blood traverses the liver and used this model to make predictions concerning ethanol metabolism at various blood ethanol concentrations. The two-compartment model predicts that near-complete saturation will occur more abruptly and at a lower blood concentration (approximately 3 mM) than is the case with the one-compartment model. Thus, the two-compartment model predicts a near-constant ethanol elimination rate for blood ethanol concentrations above 3 mM (as commonly observed in human subjects), whereas the one-compartment model predicts an increasing elimination rate over the range of concentrations observed in experimental studies. In agreement with observed data, the two-compartment model predicts that first-pass metabolism should be extremely sensitive to the rate of ethanol absorption. Application of this model to previously published data indicated that, when absorption was slowed via concomitant food ingestion, first-pass metabolism accounts for approximately 50% and 10% of ethanol dosages of 0.15 g/kg and 0.3 g/kg, respectively. When ingested without food, there is negligible first-pass metabolism of even very small ethanol dosages (0.15 g/kg). These findings suggest that first-pass metabolism is an unimportant determinant of the blood ethanol response to ingestion of potentially inebriating doses of ethanol.