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Biomedical subjects
Publications and source records attributed to L Stern.
When small companies can't get, or afford, health insurance, large companies must foot some of the bill. Reform will help both.
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Based on encouraging preliminary findings, cannabidiol (CBD), a major nonpsychotropic constituent of Cannabis, was evaluated for symptomatic efficacy and safety in 15 neuroleptic-free patients with Huntington's Disease (HD). The effects of oral CBD (10 mg/kg/day for 6 weeks) and placebo (sesame oil for 6 weeks) were ascertained weekly under a double-blind, randomized cross-over design. A comparison of the effects of CBD and placebo on chorea severity and other therapeutic outcome variables, and on a Cannabis side effect inventory, clinical lab tests and other safety outcome variables, indicated no significant (p greater than 0.05) or clinically important differences. Correspondingly, plasma levels of CBD were assayed by GC/MS, and the weekly levels (mean range of 5.9 to 11.2 ng/ml) did not differ significantly over the 6 weeks of CBD administration. In summary, CBD, at an average daily dose of about 700 mg/day for 6 weeks, was neither symptomatically effective nor toxic, relative to placebo, in neuroleptic-free patients with HD.
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The Defense Department has health care costs in its bombsights. There may be strategic lessons here for employers.
The effects of IL-1 and cortisol, and their interactions on the density of beta-adrenergic receptors (beta AR), cell proliferation, and the adherence of cells to plastic were studied in cultured human A549 lung tumor cells. The density of beta AR, assayed by 125I-pindolol binding, was increased two- to threefold by a 24-h incubation of the cells with IL-1 alpha, IL-1 beta, and TNF-alpha (EC50: 2.7, 8.2, and 24 pM, respectively), although a series of other cytokines and growth factors did not have this effect. Cortisol also increased beta AR density (EC50: 30 nM) and markedly potentiated the effects of IL-1 alpha, IL-1 beta, and TNF-alpha. Neither IL-1 nor cortisol influenced the proportion of cell surface vs internalized beta AR. The IL-1-induced increase in beta AR density was half-maximal after 6 h, was reversible at a similar rate, and was blocked by 1 microM of cycloheximide. The effect of IL-1 on beta AR was specific, as the density of glucocorticoid receptors, measured by 3H-dexamethasone binding, was reduced by IL-1. Both cortisol and IL-1 potentiated the isoproterenol-induced increase in cAMP accumulation. IL-1 inhibited cell proliferation and thymidine uptake, and increased the adherence of A549 cells to the plastic culture flask, as quantified by a cell detachment assay. The effect of IL-1 on cell adherence was not inhibited by cycloheximide. Cortisol decreased cell adherence and prevented the IL-1-induced increase in adherence. The results indicate that multiple effects of IL-1 in a cultured tumor cell line involve different mechanisms, suggesting heterogeneity of IL-1R and/or coupling of IL-1R to distinct, nuclear, and nonnuclear, effector pathways.
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On the basis of the concentration of unconjugated bilirubin and available albumin for the binding of bilirubin it is possible to calculate the level of unbound bilirubin in a serum sample. The solubility of bilirubin can further be calculated when the pH is known. In cases of threatened kernicterus the free bilirubin concentration in serum samples from newborn infants surpasses the solubility by a factor close to one hundred. It is hypothesized that deposition of bilirubin in tissues takes place as an ongoing event, the deposited pigment being eliminated by bilirubin oxidase in healthy infants. Kernicterus results when the rate of deposition becomes overwhelming as a result of high bilirubin concentration, low albumin reserve, low pH, after administration of a displacing drug, or if the bilirubin oxidase system has been compromised by preceding birth asphyxia or other forms of central nervous system injury.
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Improved outcome (1 to 10 years) of 140 asthmatic children retrospectively correlated with 8 of 49 variables in admission evaluation: (1) age of onset, (2) IgE, (3) night/early AM bronchospasm, (4) aggression, (5) severely disrupted family circumstances, (6) severe psychopathology, (7) psychotic signs, and (8) I.Q. Patients with fatal outcome (6% to 12%) deviated in the last three variables; most were 12.1 to 16.5 years, male, Black/Hispanic, aggressive, depressed and/or anxious. Clinical implications include high-risk identification on the basis of psychologic and physiologic variables, preventative measures, and consideration of residential treatment.
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Coculturing IM9 human lymphocytes and A549 human lung adenocarcinoma cells results in a 2-3-fold increase in the density of beta-adrenergic receptors in the latter, as quantified by 125I-cyanopindolol binding. Lymphocyte-conditioned medium (LCM) has the same effect, which is moderately sensitive to heat, is retained by ultrafiltration over a Mr 10,000 cut-off filter, and is reduced by trypsin treatment or by preincubation of lymphocytes with 0.3 micrograms/ml cycloheximide. Treatment of lung cells with cycloheximide also prevents the effect of LCM. Glucocorticoids, which also increase beta-receptor density in A549 cells, markedly potentiate the effect of LCM. Gel permeation high pressure liquid chromatography of LCM yields three peaks of biological activity with Mr 70,000, 35,000, and 15,000. Monocytic interleukin-1 (IL-1) mimics the effect of LCM in that it increases beta-receptor density in A549 cells (EC50 0.3 pM), and its effect is potentiated by cortisol. Recombinant IL-1 alpha is somewhat more potent than IL-1 beta, while interleukin-2 and interferon-alpha are ineffective. Tumor necrosis factor alpha causes a small increase in beta-receptors, which is not influenced by glucocorticoids. A polyclonal anti-IL-1 antibody inhibits the effect of IL-1 and the effect of the 15-kDa but not the 35- and 70-kDa fractions of LCM. The activity of the latter two fractions is also unaffected by anti-tumor necrosis factor alpha antibody. These results indicate that lymphocytes release protein factors including IL-1 that up-regulate pulmonary beta-adrenergic receptors by an action that involves protein synthesis. The possible relevance of this regulatory mechanism for the pathomechanism of certain respiratory diseases is discussed.
In a multicenter, randomized, double-blind, parallel trial, the efficacy and tolerability of two regimens of naproxen sodium were compared in a two-day treatment of moderate to severe pain following open surgery of the hip, shoulder, knee, and ankle joints. Of 147 patients enrolled, the data of 99 were valid for efficacy analysis, 45 in the low-dose regimen (day 1, 1,100 mg; day 2, 825 mg) and 54 in the high-dose regimen (1,650 mg/day). At 12 interviews each day, patients evaluated intensity of pain using numerical scales and recorded complaints. At the end of the study, overall efficacy was evaluated. Although there were no statistically significant differences between the two regimens for efficacy or tolerability, the high-dose regimen achieved greater pain relief in patients who had hip or shoulder surgery, suggesting that this regimen had greater cumulative efficacy for these patients.
The development of surgical procedures for increasingly complex and hitherto considered to be fatal and noncorrectible congenital heart disease has resulted in a re-evaluation of the ethical and social issues raised by the availability of such procedures. Three specific cases are used to illustrate some of the problems that may arise in different socioeconomic and geographic groups. It is suggested that the mere availability of the procedure does not necessarily either allow for or permit its logistical use without attention to the underlying ethical and social conditions.
A number of imaging techniques has been used in Duchenne muscular dystrophy and other neuromuscular conditions. Ultrasound reflects the changes occurring in muscle and allows differentiation between myopathies and neuropathies. It may also be of help in deciding where to take a needle biopsy. Computerized tomography (CT) has been used to assess progression over a 6 month period in Duchenne dystrophy. The density changes observed on CT scans give an accurate indication of progression and will be a useful tool in clinical trials. CT scans of obligate carriers of Duchenne dystrophy showed lower muscle densities than male controls. Magnetic resonance imaging also accurately reflects pathological changes in muscle. A pilot project to improve respiratory muscle strength and endurance showed that it was possible to improve endurance. A longer term project is currently being carried out to improve respiratory muscle endurance by the use of computer games connected to a thermistor. A certain inspiratory effort is required to continue the games, which provide the motivating factor.
77 unselected patients were examined synchronously by impedance and radiocardiography in recumbent position during dynamic exercise. In all cases the load of evaluable impedance curves was possible till 100 watts. Stroke volume, estimated by impedance cardiography, is lower about 30% at rest and during exercise compared to its estimation by radiocardiography. But the percentual increase during exercise is not significantly different between the methods. The stroke volumes, estimated by both methods, correlate significantly at rest and during exercise. This fact shows the usefulness of impedance cardiography for estimating central haemodynamics during dynamic exercise.