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Biomedical subjects

P Anderson

Publications and source records attributed to P Anderson.

At least 433 records · Page 24Linked to original sources

Evaluating visual loss with multi-flash campimetry.

Multi-flash campimetry is a computer-implemented psychophysical technique that allows temporal resolution to be assessed in 120 points per eye in a half hour. It has previously been reported that the results can serve to distinguish between multiple sclerosis patients and control subjects. We have now used this technique to measure temporal resolution in patients with amblyopia, cataracts, optic neuritis or macular degeneration. Our results indicate that multi-flash campimetry is at least as sensitive to visual loss in patients with amblyopia or cataracts as visual acuity testing with the Snellen chart and kinetic visual field testing with the Goldmann perimeter. Further, multi-flash campimetry may be more sensitive than the other two techniques to subtle residual loss in patients who have had optic neuritis and to early loss in patients with macular degeneration.

Adult↗

Delivering educational programs via telephone: teleconferencing.

Professionals participating in poison network programs not only need to maintain technical and scientific updatedness but also need to develop colleagual relationships between and among themselves regardless of geographic location. In an effort to achieve both objectives in a cost-effective and cost-efficient manner, we have explored the use of telephone conferencing. With the "speaker" located in Seattle, and the connecting bridge established and manned in Boise, Idaho, three one and one half hour presentations were brought to 90 sites scattered throughout rural and semi-rural Idaho; and received by more than 1,200 attendees. Hosting groups of 8-20, each location had a speaker phone enabling two-way communication to take place, i.e. they could hear the speaker and individuals could interrupt and address the speaker. Moreover, each location had a slide projector and duplicated set of slides used by the speaker in the presentation. Post presentation evaluations were obtained and the actual costs of the entire program have been determined. As a group utilizing telephones as a way of life, members of the AAPCC have an opportunity to lead the way in validating and verifying the effectiveness and potential cost savings of telephone conferences.

Education, Medical, Continuing↗

Effects of glycosidase treatment on the physicochemical properties and biological activity of human interferon-gamma.

Highly purified human interferon (IFN)-gamma was treated with a preparation of mixed glycosidases in order to evaluate the effect of carbohydrate depletion on its biological activity, isoelectric point, and molecular size. Glycosidase treatment did not reduce the antiviral activity of IFN-gamma in cultures of human fibroblasts and in bat lung cells. No antiviral activity was observed before or after treatment with glycosidases in pig, mink, bovine, murine, and monkey cells. The degree of neutralization of IFN-gamma activity with specific antibody was also not significantly affected by glycosidase treatment. Several components of IFN-gamma activity were resolved by nonequilibrium pH gradient electrophoresis, with major peaks of activity at pI 8.5 and 8.7. Glycosidase treatment of IFN-gamma resulted in a reduced charge heterogeneity and a higher pI of 9.3. 125I-labeled IFN-gamma was resolved by sodium dodecyl sulfate-polyacrylamide gel electrophoresis into two bands with molecular weights of 25,000 and 20,000. Glycosidase treatment reduced the apparent molecular weight of these bands to 18,500 and 16,000, respectively. The results suggest that both the Mr = 25,000 and 20,000 bands, thought to be monomeric forms of IFN-gamma, are glycosylated.

Cell Line↗

Human interferon-gamma is internalized and degraded by cultured fibroblasts.

Human interferon-gamma (IFN-gamma) binds specifically and with high affinity to receptors on the surface of cultured fibroblasts (GM-258). At 37 degrees C about 50% of the receptor-bound IFN-gamma was rapidly internalized (t 1/2 = 4-5 min) by these cells. Following an initial lag of 15-30 min, internalized IFN-gamma was continuously degraded over a period of at least 8 h. The total uptake of IFN-gamma over this time period was found to exceed by 5 times the number of occupied IFN receptors present on the surface of these cells, suggesting that either there is a large intracellular pool of IFN-gamma receptors, or that receptors are recycled during the course of incubation. Cycloheximide (100 micrograms/ml) inhibited uptake only after the first 2 h of incubation and then only moderately. It is therefore unlikely that de novo receptor synthesis plays a major role in the observed uptake process. Both sodium azide (15 mM) and methylamine (20 mM) inhibited both the uptake and degradation of IFN-gamma at all times up to 6 h. While uptake was only slightly reduced in the presence of chloroquine (25 microM), degradation was markedly inhibited, suggesting that degradation occurs intracellularly, probably within lysosomes.

Azides↗

Lymphocyte subpopulations in the skin of patients with chronic urticaria.

In order to characterize the nature of the mononuclear cells in the perivascular infiltrates in the skin of 11 patients with CU, skin biopsy specimens were analyzed in situ by an avidin-biotin immunoperoxidase technique. Serial frozen sections were stained for total T cells, helper-inducer T cells, suppressor-cytotoxic T cells, B cells, monocytes/macrophages, and HLA-DR antigen. The infiltrates were found to consist mainly of T cells, whereas B cells and macrophages were rarely seen. Most of the T cells possessed the T4+ helper phenotypes, whereas smaller numbers of infiltrating cells were defined as suppressor-cytotoxic cells. Most of the helper-inducer T cells coexpressed the Ia (HLA-DR) antigen. Several potential pathogenic mechanisms could be implicated in CU based on these observations.

Avidin↗

Antibody responses to Haemophilus influenzae type b and diphtheria toxin induced by conjugates of oligosaccharides of the type b capsule with the nontoxic protein CRM197.

Oligosaccharides were made from Haemophilus influenzae type b capsular polysaccharide and conjugated to CRM(197) by reductive amination. Conjugates were made with a range of lengths and multiplicities of saccharide chains. All elicited a strongly enhanced anti-H. influenzae type b capsular polysaccharide response when injected into weanling rabbits. One series of conjugates also elicited antibodies to diphtheria toxin.

Animals↗

Specific binding of 125I-human interferon-gamma to high affinity receptors on human fibroblasts.

Highly purified human interferon-gamma (IFN-gamma) was iodinated with 125I-Bolton-Hunter reagent to a specific activity of 34 microCi/micrograms of protein. After iodination, molecular sieve chromatography was used to isolate fractions containing IFN-gamma at approximately 80-90% radioactive purity. This preparation of 125I-IFN-gamma bound specifically to high affinity binding sites on human GM-258 fibroblasts. Scatchard analysis of binding data revealed the presence of 2400 binding sites/cell, each binding with an apparent Kd of 1.5 X 10(-10) M. Binding was competitively inhibited in the presence of unlabeled IFN-gamma and, to a lesser degree, by IFN-beta, but not by IFN-alpha. Neutralizing antibodies specific for IFN-gamma efficiently inhibited the specific binding of 125I-IFN-gamma to cells. We conclude that the specific high affinity binding site is the receptor for IFN-gamma.

Cell Line↗

Alcohol.

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Activities of Daily Living↗

The effects of calcium on protein turnover in skeletal muscles of the rat.

Several experimental procedures were used to increase the intracellular concentration of Ca2+ and determine its effects on protein turnover in isolated extensor digitorum longus and soleus muscle. These methods included the use of ionophore A23187, caffeine, dibucaine, thymol and procaine, all agents known to induce the release of calcium by acting either on the sarcolemma and/or on the sarcoplasmic reticulum. Another approach involved varying the external concentration of Ca2+ in the media in which the muscles were incubated. The changes in muscle Ca2+ concentrations after exposure to the various calcium-releasing agents were in keeping with accepted modes of action of these agents on muscle membranes. The findings suggest that increasing the sarcoplasmic concentration of Ca2+ inhibits protein synthesis and enhances protein breakdown. These catabolic effects of Ca2+ are compared with the changes induced in muscle protein turnover after exposure to insulin or cyclic nucleotides, and in myopathic muscle and situations of work overload. Attention is also drawn to some of the difficulties involved in definitively implicating Ca2+ as a factor involved in the normal regulation of protein turnover.

Animals↗

Clinical pharmacokinetics of verapamil in patients with atrial fibrillation.

The pharmacokinetic parameters and oral bioavailability of the antiarrhythmic drug verapamil were determined in six patients with atrial fibrillation. Plasma samples were taken following i.v. injection of verapamil 10 mg (Isoptin 2 ml), and oral verapamil 80 mg (Isoptin 2 tablets of 40 mg). Verapamil and its N-demethylated metabolite, norverapamil, were analyzed to 1 ng/ml plasma by gas chromatography-mass spectrometry using deuterated standards. Following intravenous injection, the disposition of verapamil followed a biexponential pattern with a fast distribution phase and a slower elimination of phase (t 1/2 beta = 5.79 h), corresponding to a plasma clearance of 0.26 l/kg/h. After oral administration, only an elimination phase was evident, with the same elimination rate (t 1/2 beta = 5.53 h). The oral bioavailability was 10.5% +/- 7.5%. The norverapamil formed after i.v. and oral administration of verapamil had plasma half-lives of 5.86 h and 6.77 h, respectively. The elimination of verapamil in patients with atria fibrillation was decreased compared to that in healthy young volunteers and the oral bioavailability was lower. Very good correlation between the percentage reduction in heart rate and the log plasma concentration of verapamil was found in every patient during the elimination phase, irrespective of the route of administration. There was also a high correlation when the plasma concentration -- effect data from the patients were pooled (r = 0.59, n = 71; p less than 0.0005).

Administration, Oral↗

Treatment of uremic hypertriglyceridaemia with bezafibrate.

Elevated triglycerides (TG) in serum and in very low density lipoproteins (VLDL), and a high cholesterol concentration in VLDL but low concentration in high density lipoproteins (HDL), are some characteristics of chronic, non-nephrotic renal failure (CRF). We have given the clofibrate analogue bezafibrate in a reduced dosage, calculated from individual single dose administrations of bezafibrate, to 12 patients with CRF, to treat their abnormal lipid levels. Serum TG were lowered by 40% due to a decrease in the VLDL fraction by 49%. High levels of LDL cholesterol were lowered, while low levels increased during treatment. HDL cholesterol increased by 17%. Studies of the removal rate of TG-rich particles from the blood and of adipose tissue metabolism could not explain the changes in serum lipids. No subjective or objective side effects from the drug were seen. An individualized dosage of bezafibrate and repeated checks of the serum concentrations of the drug are recommended during long-term treatment of uremic patients.

Bezafibrate↗

Histologic and staging classification of breast cancer: implications for therapy.

Breast cancer has 20 different histologic descriptions grouped into four categories, A, B, C, and D, based on prognosis. An analysis of 3,902 patients has revealed significant differences in outcome. Class A disease--for the most part in situ--was relatively benign, with a frequency distribution of 5%. Positive nodes were found in 1.6%, and five-year survival curves exceeded 91%. Class B (mucinous, medullary, etc) occurred in 4.1% of patients. Fewer advanced stages indicated less aggressive tumors, and survival at five years was 75%. The most common class, C (85%), had a five-year survival of 66%, closely related to stage. Class D tumors, 4.3% with ill defined, wildly infiltrative borders, and undifferentiation, were ominous with 33% demonstrating distant spread at first diagnosis. The five-year survival was only 46%. Epidemiologic findings revealed a high incidence of bilaterality and high family risk in some categories, but not in others. Mammography should be done in all class A lesions. A complete pretreatment metastatic survey is recommended for class D patients, as well as those with advanced stage II and III lesions. Indications for various surgical and adjuvant therapies are described.

Breast↗

Single-dose kinetics and bioavailability of ketobemidone.

The single-dose kinetics and the oral and rectal bioavailability of ketobemidone have been studied in patients after surgery. Plasma concentrations were determined following intravenous administration of Ketogin 2 ml, containing ketobemidone chloride 10 mg and the spasmolytic substance N, N-dimethyl-3, 3-diphenyl-l-methylallylamine chloride 50 mg and following oral or rectal administration of Ketogin. Ketobemidone was analyzed by gas chromatography-mass spectrometry using a deuterated internal standard. Ketobemidone disappeared rapidly from plasma after i.v. or oral administration, yielding a mean plasma half-life between 2.25 and 2.45 h. After rectal administration the plasma half-life was somewhat prolonged (3.27 h), probably due to late absorption., The bioavailability of oral ketobemidone was 34% +/- 16% s.d. (n = 6), and when given rectally 44% +/- 9% s.d. (n = 5). In contrast to earlier investigations performed without plasma analysis, ketobemidone was found to have a rapid elimination when given intravenously, orally or rectally.

Administration, Oral↗

Inhibition of Neisseria gonorrhoeae isolates by Martin-Lewis medium. Epidemiology, susceptibility profile, and plasma analysis.

A study was undertaken on the premise that if an increase of 1 microgram/ml in the concentration of vancomycin in Martin-Lewis medium (MLM) could improve inhibition of Gram-positive cocci, then a concomitant increase in the inhibition of gonococci could also occur. Isolates of Neisseria gonorrhoeae that failed to grow on MLM accounted for 18-5% of all positive culture results for gonorrhoea. The incidence of isolates susceptible to vancomycin was 14% and of those susceptible to trimethoprim 2.4%; one isolate was susceptible to both vancomycin and trimethoprim. The antibiotic-susceptible isolates were more frequently isolated from asymptomatic white men. Plasmid analysis showed that the 2.4-megadalton cryptic plasmic was absent in the vancomycin-susceptible isolates. The large proportion of isolates failing to grow on selective MLM has important clinical implications for the diagnosis of gonorrhea.

Culture Media↗

Home versus clinic blood pressure measurements.

To evaluate the cost effectiveness of home versus clinic blood pressure 11 patients with mild untreated hypertension were instructed in self-measurement of blood pressure with mercury manometers. The lower total cost of using home readings as well as problems of bias and blinding are discussed. Home blood pressure is a promising technique for clinical and epidemiologic research.

Blood Pressure Determination↗