Association of low caregiver health literacy with reported use of nonstandardized dosing instruments and lack of knowledge of weight-based dosing.

OBJECTIVE: Caregivers of young children frequently measure doses of liquid medications incorrectly. Use of nonstandardized dosing instruments and lack of knowledge that dosing is weight-based contribute to dosing errors. We sought to assess whether low caregiver health literacy was associated with these outcomes. METHODS: This was a cross-sectional analysis of caregivers presenting to an urban pediatric emergency room. Dependent variables were caregiver reported use of nonstandardized dosing tools and knowledge of weight-based dosing. The independent variable was caregiver health literacy (Test of Functional Health Literacy in Adults [TOFHLA]). RESULTS: Two hundred ninety-two caregivers were assessed: 23.3% reported use of nonstandardized liquid dosing instruments, and 67.8% were unaware of weight-based dosing. Caregivers who were unaware of weight-based dosing were more likely to use nonstandardized dosing tools (28.3% vs 12.8%; P = .003). In unadjusted analyses, overall health literacy, reading comprehension, and numeracy were all associated with both dependent variables. In analyses adjusting for child age, health care experiences, and caregiver acculturation and education, inadequate/marginal overall health literacy was associated with lack of knowledge of weight-based dosing (adjusted odds ratio [AOR] 2.3; P = .03), whereas lower reading comprehension was associated with both lack of knowledge (AOR 2.0; P = .03) and reported use of nonstandardized instrument (AOR 2.4; P = .007). CONCLUSIONS: Low health literacy, in particular reading comprehension, was associated with reported use of nonstandardized dosing instruments and lack of knowledge regarding weight-based dosing. Both caregiver health literacy and sociodemographic factors should be considered in the design of interventions to prevent medication administration errors.     

Uric acid in the aqueous humor and tears of retinoblastoma patients

PURPOSE: Malignancy can be associated with high levels of catabolic products. We performed a two-part study. Part 1 measured levels of uric acid and xanthine in the aqueous humor of eyes with malignant and nonmalignant diagnoses. Part 2 measured the levels of uric acid in tears of retinoblastoma patients. If compounds in high concentrations inside the eye could be detected outside the eye, via diffusion, in high concentrations in the tears, then a tear screening test for retinoblastoma could be developed. METHODS: High-performance liquid chromatography measured levels of uric acid and xanthine in aqueous humor samples of patients with retinoblastoma, melanoma, Coats' disease, adult cataract, and congenital cataract. Tear sampling was performed on patients with retinoblastoma and on normal eyes, and samples were assayed for uric acid. RESULTS: Part 1--Uric acid was elevated in the aqueous humor of eyes with retinoblastoma, melanoma, and Coats' disease compared with eyes with cataracts. Xanthine was elevated in retinoblastoma and Coats' disease and was lower in adult and congenital cataracts and melanoma. Part 2-No significant difference was found in the concentrations of uric acid in the tears of patients with retinoblastoma and those of normal patients. CONCLUSIONS: High levels of uric acid and xanthine present in the aqueous humor of patients with malignancy are consistent with the destructive nature of these conditions. Although uric acid was not elevated in the tears of retinoblastoma patients, continued investigation into substances that might be measurably different in the tears may yield a useful screening test in the future.     

Ligand induced internalization of epidermal growth factor receptors by A431 cells decreases at high cell densities in culture.

Internalization of epidermal growth factor (EGF) receptors by human A431 epidermoid carcinoma cells was studied at various culture densities. The extent of EGF receptor internalization was measured by quantitation of internalized 125I-EGF during incubation at 37 degrees C for 30 min. When cell culture density was below 1 x 10(5) cells/cm2 receptor internalization was active; 30-40% excess moles of ligand over the moles of surface EGF receptors were internalized during this period. However, when culture density increased to above 1.5 x 10(5) cells/cm2 receptor internalization became less extensive, as only 30-50% of ligand bound to the cell surface underwent internalization during 30 min incubation. In parallel with this reduction in receptor internalization, the degradation rate of 35S-methionine labeled EGF receptors was reduced at a high culture density. In contrast with this regulation of receptor internalization, the affinity of EGF receptors for the ligand increased as culture density increased. The extent of EGF-dependent receptor phosphorylation was found to be constant at all culture densities tested. Thus, the observed low level of receptor internalization at high culture densities was not attributable to lower responsiveness of receptors to EGF. These data suggest the presence of an as yet unidentified cell density-dependent mechanism for regulating receptor internalization in cultured A431 cells.     

Report of a case of localized Castleman's disease with progression to malignant lymphoma.

Patients with multicentric Castleman's disease have an increased risk of developing non-Hodgkin's lymphoma. However, development of lymphoma in the localized form of Castleman's disease has not been previously reported. This case study describes a patient with localized Castleman's disease, hyaline vascular type, whose course was complicated by follicular non-Hodgkin's lymphoma.     

Thiorphan and analogs: lack of correlation between potency to inhibit "enkephalinase A" in vitro and analgesic potency in vivo

The potencies of the R and S isomers of thiorphan and rigid analogs of thiorphan to produce analgesia in a mouse hot-plate assay have been compared with their potencies to inhibit enkephalin degradation by rat brain "enkephalinase A." The R and S isomers of thiorphan were equipotent as enzyme inhibitors (IC50 approximately 10(-9) M) but had significantly different analgesic profiles when injected i.c.v. Rigid analogs of thiorphan were less potent enzyme inhibitors (IC50 values of 10(-7) - 10(-4) M) but produced analgesia and potentiated Tyr-D-Ala-Gly-Phe-Met-NH2 induced analgesia at doses (i.c.v.) comparable to thiorphan. These observations suggest that inhibitors of enkephalinase A produce analgesia through a pharmacological mechanism which is not directly related to inhibition of enkephalin degradation.     

The effects of stimulating symbiotic fantasies on manifest pathology in schizophrenics: a revised formulation

This study was designed as a further investigation of the ameliorative effects of stimulating a symbiotic fantasy in schizophrenics. Fifty-four adult male schizophrenic subjects were each seen individually for three experimental sessions. In each session there was exposure to a neutral subliminal stimulus followed by a baseline assessment of thought disorder and behavioral pathology. This was followed by exposure to one of three critical stimuli: a) a neutral control stimulus; b) the stimulus "mommy and I are one," designed to activate a fantasy of symbiotic gratification, and found in past studies to lead to pathology reduction; and c) "mommy and I are two," designed as a test of the specificity of oneness fantasy in producing symptomatic improvement. Each subject was exposed to the three critical simuli by counterbalanced order. Assessments of pathology were repeated after exposure to the experimental stimuli and comparisons were made with baseline measures. Results were: a) the subliminal symbiotic stimulus produced improvement on one of the measures of pathology, replicating findings from previous studies; and b) unexpectedly, the "mommy and I are two" stimulus led to pathology reduction on both dependent measures and proved significantly more ameliorative than the oneness stimulus. Associations obtained from subjects on a post hoc basis, the relationship between responses of individual subjects to the two stimuli, and the way in which order of presentation of the critical stimuli affected results supported the view that the twoness message also gratified symbiotic wishes while simultaneously providing reassurance against dangers associated with boundary loss. Results were discussed with an eye toward sharpening and refining the formulation advanced in the past to account for the ameliorative effects of the "oneness" stimulus.     

Cell cycle effects of antifolate antimetabolites: implications for cytotoxicity and cytostasis

 Purpose: Cell cycle-related events in CCRF-CEM lymphocytic leukemia cells were examined subsequent to inhibition of thymidylate synthase (TS) or GAR formyltransferase (GARFT) and prior to cell death or stasis. Methods: Cell populations were treated with the GARFT inhibitors 6R-5,10-dideazatetrahydrofolate (lometrexol) or LY309887, the TS inhibitor ZD1694, or the multitargeted antifolate LY231514. DNA content, nucleoside precursor incorporation and proliferating cell nuclear antigen (PCNA) expression as functions of drug treatment were assessed by multiparameter flow cytometry. Cellular respiration was measured by MTT analysis and apoptosis was detected by extraction of DNA fragments. Results: Cell populations treated for up to 96 h with lometrexol or LY309887 did not replicate and maintained a cell cycle distribution with distinct G₁, S and G₂/M regions. The number of S phase cells in treated populations was slightly elevated relative to control as measured by DNA content and PCNA. However, these cells were unable to incorporate 5-bromodeoxyuridine (BrdU). Throughout treatment, cells incubated with GARFT inhibitors maintained intact membranes and respired at a level comparable to untreated cells. In contrast, ZD1694 as well as LY231514, induced synchronization of the treatment population at the G₁/S interface within 12 h of drug addition. This was followed by synchronous entry of the population into S phase. After 24 h of treatment, more than 90% of the cells were capable of incorporating BrdU and stained positive for PCNA. DNA fragmentation occurred in cells treated with ZD1694 or LY231514 but not in those treated with GARFT inhibitors. In addition, the viable cells remaining after 24–48 h of treatment with ZD1694 or LY231514 were respiring at twice the level of untreated cells. Conclusion: These results demonstrate that the distinct endpoints of GARFT and TS inhibition are preceded by distinct cell cycle and metabolic alterations. Received: 1 April 1996 / Accepted: 5 September 1996