Temporal-lobe structures and autism.
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Biomedical subjects
Publications and source records attributed to C P White.
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A four-year-old boy developed complex visual hallucinations consisting of moving figures, animals and other familiar objects one week after becoming totally blind. This followed a six-month period of gradually deteriorating vision and was precipitated by the debulking of a large optic nerve glioma. Although visual hallucinations are well recognised in adults with visual loss, secondary to both ophthalmological and neurological causes, they have not been reported in young children.
The induction of 1-hydroxylase in alveolar macrophages by tumor necrosis factor-alpha (TNF) was examined in view of recent evidence suggesting that local production of 1,25-(OH)2D3 may play a role in the regulation of immune functions. Incubation of pulmonary alveolar macrophages from normal human subjects with recombinant TNF caused a 2- to 10-fold increase in 25-hydroxyvitamin D3-1-hydroxylase activity. The dose-response curve was linear over the range 0.05-5.0 IU/ml, and no further increase was seen at higher concentrations. The increase in 1-hydroxylase activity was present after 12 h and reached a maximum after 3 days. The effect of TNF was inhibited in a dose-dependent manner by the presence of 1,25(OH)2D3 (10(-10)-10(-8) M) in the incubation media for 5 days but was unaffected by 10(-9) M 1,25(OH)2D3 after 12 h. The enhancement of macrophage 1-hydroxylase activity by TNF was comparable to that induced by gamma interferon (IFN) but the effects of maximal doses of both agents were not additive. The presence of antibody to TNF resulted in a 76% inhibition of TNF-induced 1-hydroxylase but had no significant effect on IFN-induced 1-hydroxylase activity.
This report describes a systematic effort to test all functions of a large 3-D radiation therapy planning program, including graphics and user interaction. Previous studies in quality assurance for radiation therapy programs do not adequately address the problem of programming errors. They compare dose estimates calculated by planning programs to actual doses measured in phantoms, so they cannot distinguish programming errors from measurement errors or physical unsoundness of the beam model. Moreover, they fail to exercise graphics and user interaction functions. This report describes a different methodology: test cases are derived from the program specification, results are calculated by an independent technique, and compared to program output. Derivation of test cases is described in detail. Effectiveness of testing is assessed by reporting the number of errors revealed by testing and comparing to the number of errors discovered during routine use in five successive program versions. The size of the test set is related to the total program size, and the effort devoted to deriving and performing tests is compared to the total program development effort. We conclude that systematic testing can reveal errors that are not found by informal testing, routine program use, or comparison with measurements. However, additional errors remain that are only discovered during use. This study suggests that a typical large planning system may include more than 100 errors when it is released for clinical use. Methods for increasing testing effectiveness are recommended.
This article shall highlight several areas where recent developments have made, and may make in the future, practical advances to diabetes care. These advances have been in the areas of insulin therapy, glucose monitoring, identifying pre-diabetics and using immunosuppressive agents in pre-diabetes and early diabetes, pancreatic transplantation, and managing acute and chronic complications of diabetes.
Short-latency somatosensory evoked potentials elicited by stimulation of the posterior tibial nerve at the ankle were studied in 75 preterm infants. Normative data for the latency of the first cortical component (P1) were obtained for infants from 27 weeks gestation to term, and showed a linear decrease with increasing gestational age. As the pathway of this response traverses areas of the brain likely to be affected by ischaemic and haemorrhagic lesions, abnormalities in the response might indicate later motor disorder.
As part of a U.S. multi-regional pilot study conducted by the six Centers for Radiological Physics, 12-mm-diameter by 0.4-mm-thick CaSO4:Dy Teflon-embedded discs were evaluated and used to measure patient entrance exposure on 60 "average" patients at 12 clinical centers. The discs were found to have adequate sensitivity, reproducibility and linearity up to 69.7 microC kg-1 (270 mR). The minimum measurable exposure was estimated as 0.4 microC kg-1 (1.5 mR). All responses were corrected for energy dependence, which varied +/- 20% from 1.7 to 6.5 mm Al half-value layer. Patient entrance exposure values ranged from 1.3 to 28 microC kg-1 (5 to 110 mR), with a median value of 5.2 microC kg-1 (20 mR). This value agreed with exposure measurements made on the chest radiography equipment using an ionization chamber and a phantom which simulated an "average" patient, and with published Nationwide Evaluation of X-Ray Trends (NEXT) data for the same period.
Human peripheral blood monocytes secrete a soluble factor that enhances the ability of human epithelial tumor cell lines to clone in soft agar. Monocytes increased colony growth in a concentration-dependent manner, although inhibition of cell growth was observed in the presence of high concentrations of monocytes. Addition of indomethacin to monocytes did not abrogate this inhibition. Exposure of monocytes to endotoxin increased their ability to secrete stimulatory factors. Nonadherent lymphocytes were unable to support colony growth. Conditioned media from unstimulated monocytes also increased colony growth. Growth-promoting activity was detected in the media within the first 24 hr of culture, reaching a peak at 72 hr. Activity was not observed in monocyte lysates. Monocytes released this activity when cultured in the presence of both serum-free and serum-containing media. The activity was nondialyzable, relatively heat stable, and failed to adhere to CM-Sephadex. The demonstration of a monocyte-derived factor that enhances growth of epithelial tumor colonies supports findings indicating that inflammatory products may enhance tumor cell growth in vitro.
We previously demonstrated that macrophages isolated from human malignant effusions support colony formation of autologous tumor cells in soft agar. We now demonstrate that macrophages (derived from effusions of patients with ovarian, breast, colon, or lung adenocarcinomas) secrete a soluble factor(s) that enhances the ability of a human epithelial tumor cell line (SW-13) to clone in soft agar. Macrophages increased colony growth 5 to 10-fold in a concentration dependent manner, although inhibition of cell growth was observed in the presence of high concentrations of macrophages. We attempted to increase production of tumor colony stimulating factor by exposing macrophages to lipopolysaccharide, concanavalin A, or phytohemagglutinin. Exposure of macrophages to these agents failed to increase their ability to secrete stimulatory factors. Macrophages were cultured for 1 day to 6 weeks in the presence of GCT-CM, a source of granulocyte-macrophage colony stimulating factor and the ability of these cultured macrophages to support colony growth assessed. The ability of macrophages to support colony growth declined gradually with time in culture reaching 50% of control values at 14 days, but remained at this level until 5 weeks of culture. The results of this study indicate the SW-13 cells may provide a quantitative assay for studying monocyte-derived tumor colony stimulating factors.
A human epithelial-derived cell line, SW-13, releases a soluble substance that functions as an autocrine growth factor. SW-13 cells, derived from a human adenocarcinoma of the adrenal cortex, form a few small colonies when suspended in soft agar at low densities. The number of colonies increased significantly when either viable SW-13 cells or serum-free medium conditioned by SW-13 cells (CM) was added to agar underlayers. CM increased colony formation in a dose-dependent fashion. Clonal growth at low cell densities was dependent on the presence of both horse serum and SW-13 CM. Neither activity alone was capable of sustaining growth. Even when cells were plated at high densities CM could not substitute for serum, but could reduce the threshold serum concentration. The results suggest that autocrine and serum-derived factors act in concert to maintain clonal growth of epithelial tumor cells in soft agar.
We examined the ability of primary human tumour cells to secrete diffusible factors capable of stimulating anchorage independent growth of normal rat kidney fibroblast (NRK) cells. Conditioned media (CM) prepared from cells derived from 31/43 patients with adenocarcinoma of the breast, colon, ovary or lung were found to induce growth of NRK cells in soft agar. The ability of the CM to induce anchorage independent growth was enhanced in 25/35 cases by the presence of epidermal growth factor (EGF). The CM did not compete with EGF for binding to the EGF receptor site. CM from cells derived from nonmalignant effusions also supported the growth of NRK cells in soft agar. There was no significant difference in the ability of the CM derived from malignant or normal cells to support NRK colony growth. The ability of primary human tumour cells to clone in soft agar was compared to the ability of these cells to produce diffusible colony stimulating factors for NRK cells. No correlation was observed between the ability of the primary human tumour cells to clone in soft agar and their ability to induce anchorage independent growth of NRK cells. The secretion of substances with TGF like activity may be a property of many types of primary human cells.
A simple method is described for the separation of cells derived from effusions of patients with adenocarcinomas in discontinuous density gradients of Percoll. After separation, cells from different fractions were analyzed by morphologic, histochemical and immunologic criteria. Total cell recovery from 27 experiments was 67 +/- 4%. Macrophages (82%) were recovered in the intermediate density fraction (1.056-1.067 g ml-1) with a purity of 90%. Recovered lymphocytes (98%) were found in the high density fraction (1.067-1.077 g ml-1) with a purity of 92%. The majority of the lymphocytes recovered were T cells. Malignant adenocarcinoma cells (90%) were recovered in the lowest density fractions (up to 1.056 g ml-1) with a purity of 79%. Use of effective cell separation procedures should facilitate the analysis of the functional capacities of both normal and neoplastic cells derived from human malignant effusions.
Macrophages, isolated from malignant effusions, were cultured in vitro in media containing GCT/CM as a source of granulocyte-macrophage (GM) colony-stimulating factor (CSF). Cells were periodically examined for macrophage-specific cell surface antigens and functional activity. The number of macrophages increased sixfold during 15 days in culture. Autoradiographic studies confirmed that macrophages were incorporating 3H-Tdr. Macrophage-specific cell surface markers were retained up to five weeks in culture. Cells were also able to express macrophage-specific functions including phagocytosis and secretion of lysozyme. The results indicate that human tumor-derived macrophages may be expanded in short-term culture in the presence of GM CSF.
We examined the effect of human interferon (HuIFN) -alpha and -beta on the proliferation and differentiation induced by dimethyl sulfoxide (DMSO) of HL-60 human promyelocytic leukemia cells into mature granulocytes. Neither HuIFN-alpha nor -beta, alone, from 1 to 1000 IU/ml, nor the homologous mock HuIFN preparations affected HL-60 cell differentiation or proliferation. Whereas the combination of HuIFN-alpha (10 to 1000 IU/ml) with DMSO also did not affect the proliferation or differentiation of HL-60 cells, the addition of HuIFN-beta (1000 IU/ml) and DMSO (1.25%) to growing cultures reduced cell viability as much as 14% of that observed for cells treated with DMSO alone or to 4% of that observed for either untreated cells or those treated with HuIFN-beta alone. The cytotoxic effect declined with decreasing concentrations of HuIFN-beta. The cytotoxic effect of DMSO and HuIFN-beta was exerted only as cells began to differentiate. Removal of HuIFN-beta at Day 2 did not reverse the cytotoxic effect, and addition of HuIFN-beta at Day 2 did not inhibit cell proliferation. Addition of HuIFN-beta to postmitotic cells on Day 4 after DMSO treatment did not affect proliferation but did slow differentiation. The cytotoxic and antidifferentiative effects of naturally produced HuIFN-beta were confirmed with highly purified recombinant HuIFN-beta. Undifferentiated HL-60 cells were resistant to the antiviral effects of HuIFN-beta, requiring 4 to 6 times the concentration to protect 50% of the cells against vesicular stomatitis virus as that needed to produce a cytotoxic or antidifferentiative effect. The profoundly cytotoxic effects of HuIFN-beta reported here may provide a model to study this interferon in combination with inducers of leukemic cell differentiation as a possible strategy in cancer therapy.
The potential cost of discarding unused drugs packaged in multiple-dose containers for patients in long-term-care facilities (LTCFs) was studied. Data were collected during 1982-83 for patients in 12 LTCFs in the state of Washington that used modified unit dose drug distribution systems. When drugs were supplied in multiple-dose containers--by the Veterans Administration, a health maintenance organization, or another pharmacy--for patients in the LTCFs, the pharmacy providing services to the LTCFs routinely repackaged these drugs for unit dose distribution to these patients. The number of drug doses per month administered to all patients in each LTCF was recorded. The numbers of patients with multiple-dose prescriptions and the numbers of those whose medications were changed or discontinued were recorded, and the dollar value of the unused drugs, which would have been wasted if these patients' medications had been dispensed in multiple-dose containers, was calculated based on average wholesale prices. Based on approximately 100 patients per month for whom one or more medications were supplied in multiple-dose containers, annual average wholesale costs of drugs that would have been wasted were $56.50 per patient in 1982 and $67.57 per patient in 1983. Based on the 1983 average number of drug doses per patient in the 12 LTCFs and the pharmacy's cost of $0.02 per dose for unit-of-use packaging, the average cost of unit-of-use packaging per patient was $50.37.(ABSTRACT TRUNCATED AT 250 WORDS)
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Apnea is a known complication of the Chiari II malformation presenting in infancy. Obstructive apnea secondary to bilateral abductor palsy or laryngomalacia and centrally mediated expiratory apnea with cyanosis can occur. Observations of 9 patients suggest that these forms of apnea may represent stages in a continuum of brain stem dysfunction due to the combined effects of the hindbrain malformation and its compression, hydrocephalus and progressive arachnoiditis. Obstructive apnea in some patients may be reversed by optimal control of hydrocephalus with or without cervical decompression. These patients may also develop episodes of cyanotic expiratory apnea of central origin (PEAC). This form of apnea does not respond to surgical or medical treatment and may show progressive worsening over time. Five of 6 patients with this form of apneic spell died suddenly, 2 of these died despite full recuscitative efforts. It is recommended that reports of treatment address results for both forms of apnea.