The connective 'and': do older children use it less as they learn other connectives?
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Biomedical subjects
Publications and source records attributed to C Peterson.
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Explanatory style is an individual difference that influences people's response to bad events. The present article discusses the possibility that a pessimistic explanatory style makes illness more likely. Several studies suggest that people who offer internal, stable, and global explanations for bad events are at increased risk for morbidity and mortality. We tentatively conclude that passivity, pessimism, and low morale foreshadow disease and death, although the process by which this occurs is unclear.
Combined rapid atrial flutter/fibrillation and recurrent ventricular tachycardia occurred in an 82 year old man with acute myocardial infarction. Both arrhythmias were promptly terminated by intravenous sotalol, suggesting another use for this unique drug in the absence of hypotension, heart block or cardiac failure.
We used insurance claims from enrollees in the Rand Health Insurance Experiment to determine the amount of selected components of preventive care received by a representative sample of the non-aged population in the United States and to determine whether insurance coverage was an important determinant of that amount. Only 45 percent of infants received timely immunization for DPT and polio; 93 per cent received some well child care by 18 months of age. In the three-year experimental period, only 4 per cent of adults had a tetanus shot, 66 per cent of women aged 17-44 and 57 per cent aged 45-65 received a Pap smear, and 2 per cent of women aged 45-65 had a mammogram. Cost sharing was associated with even less preventive care: 60 per cent of children on the free plan and 49 per cent on cost sharing plans received preventive care of any type. For adults, women on the free plan received more preventive care of several kinds, and those aged 45-65 received more Pap smears than those on cost-sharing plans. Even with free care, most enrollees did not receive adequate preventive care. Thus, free care alone, while significant, is not a sufficient incentive to providing recommended levels of preventive care. The average per person insurance charge for increasing the amount of preventive care to a level consistent with that recommended would be $22 for a complete set of immunizations by age 18 months, $9 for a Pap smear every three years, and $97 for a Pap test and mammogram every three years.
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The brindled mouse is an X-linked mutant with alterations in copper homeostasis. Ultrastructural analysis of the cerebellum and neocortex reveals several dendritic abnormalities, including the formation of Hirano bodies and other cytoskeletal alterations. Immunocytochemical evidence demonstrates that actin is a component of these microfilament lattices.
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Blood and tissue concentrations of doxorubicin (DOX) were assayed after an intraoperative IV test dose of either free DOX 10 mg or its DNA complex 10 mg to patients with gastrointestinal cancer. After administration of the free drug, blood DOX levels decreased in an at least biphasic way, while DOX-DNA gave higher blood concentrations, which decreased slowly with no clear inflexion point on the concentration-time curve within the first hour. Tissue concentrations of DOX did not differ significantly after the two forms of the drug, liver being the tissue with the highest levels, followed by lymph node metastases, tumor tissue, muscle, and normal intestinal mucosa. If skeletal muscle can be used as a substitute for myocardium, lower cardiotoxicity of DOX-DNA than of DOX is not likely to be due to a difference in tissue uptake and retention between the two forms of DOX.
During early development normal and brindled mouse brain use 3-hydroxy-butyrate preferentially to glucose as a source for biosynthetic carbon units. On postnatal days 5-60, CO2 and acetylcholine production from 3-hydroxybutyrate decrease while that from glucose increases. Glucose metabolism exceeds that of 3-hydroxybutyrate after weaning (day 21). These findings indicate that the immature brain uses 3-hydroxybutyrate to support effectively oxidative metabolism and acetylcholine synthesis. Deficits in oxidative and acetylcholine metabolism occur in the developing brindled mouse, a genetic mutant with a defect in copper homeostasis. In the brindled mouse forebrain and cerebellum, the incorporation of either substrate into CO2 and acetylcholine was decreased 15%, 50% and 80% at days 5, 10 and 15 postnatal, respectively, when compared to the normal littermates. The brindled mouse demonstrates deficits in both oxidative metabolism and acetylcholine synthesis before the appearance of neuropathology.
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Aging and Alzheimer disease lead to alterations in calcium homeostasis. The concentration of cytosolic free calcium in cultured skin fibroblasts during aging and Alzheimer disease was determined with the calcium-sensitive fluorescent dyes quin-2 and fura-2. The Alzheimer donors showed a decline of 70% when compared to age-matched controls (P less than 0.001) and 81% when compared to cells from young adult donors (P less than 0.001). This reduction in quin-2-calcium fluorescence does not appear to be due to quenching by heavy metals or alterations in intracellular pH. Similar decreases in free cytosolic calcium were observed with fura-2. In addition, cells from aged and Alzheimer donors spread more slowly than those from young donors, and this deficit can be partially reversed by treatment with the calcium ionophore A23187. These studies agree with accumulating evidence that, at the cellular level, Alzheimer disease is a systemic, as well as cerebral, disease. The precise molecular basis of the decreased cytosolic calcium in fibroblasts is unknown, but there is evidence that it may be pathophysiologically important.
Aging and Alzheimer disease lead to alterations in several biochemical properties of cultured skin fibroblasts. Total bound calcium increases in fibroblasts due to normal aging (+52%) and is elevated even further with Alzheimer disease (+197%). Processes that require mitochondrial function, such as glucose and glutamine oxidation, declined in cells from aged donors (-25%) and decreased even further in Alzheimer disease (-46%). In addition, biosynthetic processes that depend upon mitochondrial function, such as glucose or glutamine incorporation into protein and lipid, paralleled the oxidative decreases. Cytosolic and nuclear processes such as leucine incorporation into protein and thymidine into DNA were depressed more by aging than Alzheimer disease. These findings suggest that calcium homeostasis and mitochondrial functions are altered more by Alzheimer disease than normal aging.
The concentrations of 6-mercaptopurine were studied in plasma and red blood cells from 10 children with acute leukaemia or non-Hodgkin lymphoma receiving oral maintenance therapy. The doses varied between 25 and 79 mg/m2 body surface once daily. Large interindividual differences were found in the concentrations both in plasma and in red blood cells. There was no clear relationship between the dose administered and the concentrations obtained. However, in each patient the concentrations in plasma and in red blood cells were very similar. In most patients, the peak concentrations were reached 1-2 hours after dose intake and the concentrations then declined with half-lives less than 1 hour. Further studies are necessary to evaluate the potential value of drug level monitoring in optimizing treatment with oral 6-mercaptopurine.
The levels of doxorubicin (DOX) and epirubicin (epi-DOX) in serum, tumors, and normal tissues were assayed by high-performance liquid chromatography after peroperative administration of test doses (10 mg) to 14 patients with gastrointestinal cancer. Large interindividual variations were found. The drug levels also varied markedly between tissues from the same patient, with normal liver consistently having the highest drug concentration, followed by tumors and striated muscle, which had similar levels. In serum, a rapid initial distribution phase, with a half-life of about 5 minutes for DOX and 4 minutes for epi-DOX, was followed by a slower decrease in the drug levels. The concentration versus time curves were not influenced by the presence of liver metastases. No metabolites of DOX or epi-DOX were found during the time period studied, in most cases 2 hours after drug administration. Our pharmacokinetic results give no explanation for the claimed superiority of epi-DOX in the treatment of gastrointestinal cancer.
Previous studies have demonstrated that human leukemic cells and certain cancer cells in culture have a higher uptake of plasma low-density lipoprotein (LDL) than the corresponding normal cells. Therefore LDL has been proposed as a drug carrier for anticancer agents. In the present investigation, we have developed a method to incorporate a lipophilic derivative of doxorubicin, N-trifluoroacetyladriamycin-14-valerate, into LDL. The method involves lyophilization of LDL in the presence of sucrose as protective agent and gives an N-trifluoroacetyladriamycin-14-valerate-LDL complex containing about 100 drug molecules per LDL particle. The in vivo fate of the complex in mice as judged from the disappearance from plasma and accumulation in organs was similar to that of native LDL. When cultured human fibroblasts were incubated with N-trifluoroacetyladriamycin-14-valerate-LDL, cellular drug accumulation was dependent on the LDL receptor activity of the cells. The covalent linkage of two anthracycline derivatives to lysine residues of LDL yielded conjugates with drug/LDL molar ratios ranging up to 80. With increasing substitution, there was a progressive decline in the affinity of the conjugate for the LDL receptor in vitro. The in vivo fate of such conjugates was quite similar to that of native LDL. We conclude that it is possible to associate cytotoxic agents with LDL without interfering with its in vivo behavior.
59 patients with acute leukaemia were examined to see if hypocholesterolaemia, which is commonly found in acute leukaemia, was due to the high low-density-lipoprotein (LDL)-receptor activity of leukaemic cells. LDL-receptor activity was found to be inversely correlated with plasma-cholesterol concentration. Patients with both a high LDL-receptor activity per cell and a high white-blood-cell count had the lowest cholesterol concentrations. During chemotherapy, cholesterol levels rose concomitantly with the disappearance from the peripheral blood of leukaemic cells. Hypocholesterolaemia in leukaemia and other neoplastic disorders may be due to increased LDL-receptor activity in the malignant cells. This high uptake and degradation of LDL by malignant cells could be utilised to target neoplastic cells with LDL-bound chemotherapeutic agents.