BREAST-FEEDING AND JAUNDICE

Clinically apparent jaundice occurs in up to 60% of newborns in the first week after birth and represents a significant proportion of prolonged infant hospitalization, increased health care costs, and anxiety for new parents. An association between breastfeeding and hyperbilirubinemia has been suggested by various researchers; however, the results of the studies have been inconclusive. The association of breast-feeding and jaundice appears to be the result of incomplete excretion of meconium and a relative low caloric intake by some breast-fed infants. Management strategies that have been proposed include unlimited suckling, temporary discontinuation of breast-feeding, supplementation, and phototherapy.     

Tumor targeting by an aptamer.

Aptamers are small oligonucleotides that are selected to bind tightly and specifically to a target molecule. We sought to determine whether aptamers have potential for in vivo delivery of radioisotopes or cytotoxic agents. METHODS: TTA1, an aptamer to the extracellular matrix protein tenascin-C, was prepared in fluorescent and radiolabeled forms. After in vivo administration, uptake and tumor distribution of Rhodamine Red-X-labeled aptamer was studied by fluorescence microscopy. In glioblastoma (U251) and breast cancer (MDA-MB-435) tumor xenografts, biodistribution and imaging studies were performed using TTA1 radiolabeled with (99m)Tc. Tenascin-C levels and tumor uptake were studied in a variety of additional human tumor xenografts. To assess the effect of radiometal chelate on biodistribution, mercapto-acetyl diglycine (MAG(2)) was compared with diethylenetriaminepentaacetic acid and with MAG(2)-3,400-molecular-weight PEG (PEG(3,400)). RESULTS: Intravenous injection of fluorescent aptamer TTA1 produced bright perivascular fluorescence in a xenografted human tumor within 10 min. In the ensuing 3 h, fluorescence diffused throughout the tumor. Labeled with (99m)Tc, TTA1 displayed rapid blood clearance, a half-life of less than 2 min, and rapid tumor penetration: 6% injected dose (%ID)/g at 10 min. Tumor retention was durable, with 2.7 %ID/g at 60 min and a long-lived phase that stabilized at 1 %ID/g. Rapid tumor uptake and blood clearance yielded a tumor-to-blood ratio of 50 within 3 h. Both renal and hepatic clearance pathways were observed. Using the (99m)Tc-labeled aptamer, images of glioblastoma and breast tumors were obtained by planar scintigraphy. Aptamer uptake, seen in several different human tumors, required the presence of the target protein, human tenascin-C. Modification of the MAG(2) radiometal chelator dramatically altered the uptake and clearance patterns. CONCLUSION: TTA1 is taken up by a variety of solid tumors including breast, glioblastoma, lung, and colon. Rapid uptake by tumors and rapid clearance from the blood and other nontarget tissues enables clear tumor imaging. As synthetic molecules, aptamers are readily modified in a site-specific manner. A variety of aptamer conjugates accumulate in tumors, suggesting imaging and potentially therapeutic applications.     

The Role of Instructional Set on Alcoholic Performance

This study was conducted to determine whether alcoholic and control subjects respond differently to manipulations that either enhance personal involvement (PI) or reduce negative affect (R, relaxation) on tests of neuropsychological function. In Phase 1, 48 male alcoholics and 36 male control subjects completed neuropsychological tasks under standard instructional sets. In Phase 2, subjects completed equivalent forms of these tests under one of three randomly assigned conditions; the PI condition in which subjects were encouraged to identify specific ways of improving their performance, the R condition in which subjects participated in a short relaxation exercise designed to reduce anxiety, or a No Treatment (NT) condition in which no attempt to manipulate the subjects' involvement or affect was made. Alcoholics were inferior to controls in both Phase 1 and Phase 2 [Fs (1,82) > 5.03, ps < 0.03]. The experimental manipulation differentially affected measures of negative affect and effort in the predicted direction. There were no group x condition interactions. Alcoholic and control subjects responded comparably to the experimental manipulations. This investigation, in combination with others using related manipulations, reinforces the hypothesis that alcohol-related cognitives dysfunction reflects an underlying deficit in brain states.     

Change in the oestrogen receptor status of breast cancer with age--comparison of two types of assay.

The oestrogen receptor (ER) is considered to be an essential component of the mechanism of response of a breast tumour to endocrine therapy, but ER measurements have proved to have only modest predictive value. In the present study, we have examined ER status by both immunocytochemical assay (ER-ICA) on a fine needle aspirate and by radioligand-binding assay (DCC) on an excised portion of tumour. There was a correlation between the ER level detected by the two assays (Spearman's r = 0.77 for DCC versus ER-ICA staining intensity, r = 0.70 for DCC versus ER-ICA percentage of cells stained, P < 0.0001, n = 137 in each case). Each assay showed an increasing proportion of ER+ve results with increasing patient age. In the case of ER+ve tissues only, while ER concentration by DCC assay increased steadily with age (r = 0.39, P < 0.0001, n = 108), the ER-ICA assay revealed that, staining intensity increased with age (r = 0.26, P = 0.001, n = 149) but the percentage of cells stained did not (r = 0.08, P = NS, n = 149). It is concluded that increasing endocrine responsiveness with advancing age could reflect the increasing proportion of ER+ve tumours with increased levels of ER per cell (as indicated by staining intensity) rather than increasing proportion of ER+ve cells.     

Use of the internet to obtain cancer information among cancer patients at an urban county hospital.

PURPOSE: To evaluate rates, predictors, and barriers to use of the Internet to obtain cancer information among a cohort of cancer patients at an urban county hospital. PATIENTS AND METHODS: Of 208 cancer patients approached, 200 patients completed a structured interview study examining Internet use, perceptions of the accuracy of Internet information, and barriers to use. RESULTS: Only 10% of participants reported using the Internet themselves to obtain cancer information. Another 21% reported exposure to Internet information through proxies. The most common barrier to Internet use cited was lack of Internet access, with 44% reporting that they would use the Internet to obtain cancer information if they had Internet access. Younger age and more years of formal education were significantly associated with Internet use, although race and income were not. Less education, African American race, and female sex were associated with lower estimates of the accuracy of Internet information. Fewer years of formal education was associated with increased likelihood of reporting confusion after reading Internet information. CONCLUSION: Very few cancer patients in this study of a cohort of generally disadvantaged individuals used the Internet themselves to obtain cancer information, although many more desired to do so. Significant opportunities for Web-based interventions aimed at improving cancer care outcomes in this population of cancer patients exist. However, further study will be needed to determine how to make such intervention accessible, trustworthy, and understandable to the disadvantaged.     

A PACU crisis: a case study on the development and management of methemoglobinemia.

The development of methemoglobinemia requires rapid recognition, confirmation, and treatment. This case study describes the development, diagnosis, and management of a 63-year-old male scheduled for a laparoscopic cholecystectomy with an intraoperative cholangiogram who developed methemoglobinemia after benzocaine was given for intubation.     

Evaluation of hypothesis testing for comparing two populations using NONMEM analysis

In a simulation study of inference on population pharmacokinetic parameters, two methods of performing tests of hypotheses comparing two populations using NONMEM were evaluated. These two methods are the test based upon 95% confidence intervals and the likelihood ratio test. Data were simulated according to a monoexponential model and, in that context, power curves for each test were generated for (i)the ratio of mean clearance and (ii)the ratio of the population standard deviations of clearance. To generate the power curves, a range of these parameters was employed; other pharmacokinetic parameters were selected to reflect the variability typically present in a Phase II clinical trial. For tests comparing the means, the confidence interval tests had approximately the same power as the likelihood ratio tests and were consistently more faithful to the nominal level of significance. For comparison of the standard deviations, and when the volume of information available was relatively small, however, the likelihood ratio test was more able to detect differences between the two groups. These results were then compared to results on parameter estimation in order to gain insight into the question of power. As an example, the nonnormality of estimates of the ratio of standard deviations plays an important role in explaining the low power for the confidence interval tests. We conclude that, except for the situation of modeling standard deviations with only sparse information, NONMEM produces tests of significance that are effective at detecting clinically significant differences between two populations.Partial support from the Upjohn Company, NIH-BRSG SO RR 07066, and the Burroughs Wellcome Foundation.