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Biomedical subjects

C Harris

Publications and source records attributed to C Harris.

At least 181 records · Page 10Linked to original sources

Topical nitroglycerin: a potential treatment for impotence.

The effect of 2 per cent nitroglycerin paste applied to the penile shaft of impotent subjects was evaluated in a placebo controlled double-blind study under laboratory conditions. After application of nitroglycerin paste or a placebo ointment base, penile tumescence was recorded through a strain gauge transducer while subjects viewed an erotic video presentation. Relative to the placebo paste the number of subjects demonstrating an increase in penile circumference after nitroglycerin (18 of 26) was significantly different than all other outcome possibilities (p less than 0.05). Noninvasive vascular assessment by ultrasonography demonstrated an increase in diameter and blood flow in the cavernous arteries after application of nitroglycerin paste. Nitroglycerin paste increases blood flow in the cavernous arteries and improves tumescence after erotic stimulation. This agent may represent a new therapy for impotence.

Administration, Topical↗

Quality assurance for HIV-related care.

Now that models of care for numerous HIV-related conditions have been defined, a knowledge base exists for developing protocols of appropriate, high-quality care for HIV-infected patients. Bronx Municipal Hospital Center in New York City plans to implement a monitoring and evaluation program for HIV-related care that would establish protocols and indicators of quality and appropriateness, monitor compliance with protocols, and generate recommendations for improving care. At present, Bronx Municipal's AIDS consultation service has drafted guidelines for developing indicators of appropriate diagnosis, clinical course, and drug usage for HIV-infected patients, as well as guidelines for reviewing medical records.

Acquired Immunodeficiency Syndrome↗

Nuclear medicine from Becquerel to the present.

During a period of a little over ninety years, the use of radioactive materials has moved from the discovery of natural radioactivity by Becquerel to the use of highly sophisticated equipment for in-house production of biologically important molecules labeled with radionuclides, for the measurement of body functions. Radiation detectors have progressed from photographic plates and the gold leaf electroscope to the routine use of improved scintillation detectors for imaging the three-dimensional distribution of radioactive materials in the body as a function of space and time. It is expected that future improvements will be along the line of instruments with better spatial resolution, contrast, and sensitivity. Advances in hardware and software will be more than matched by developments in radiopharmaceuticals, including the use of monoclonal antibodies and receptor mapping agents which promise the exquisite specificity and sensitivity of radioimmunoassay procedures.

Europe↗

Noninvasive determination of coronary artery bypass graft patency by cine magnetic resonance imaging.

Cine magnetic resonance imaging (MRI) is a gradient-recalled, retrospectively gated, fast-scan technique that depicts laminar flowing blood as bright signal and has been proposed as a useful method for determination of coronary artery bypass graft (CABG) patency. Therefore, we performed a blinded prospective study to assess the value of cine MRI determination of CABG patency in 20 patients with 45 CABG proximal anastomoses who were undergoing repeat angiography. Ten normal subjects served as controls to define normal intrathoracic vascular patterns. There were 21 left anterior descending (LAD) grafts, of which four were left internal mammary (LIMA), 12 left circumflex (Cx), and 12 right coronary (RCA) grafts. After localizing spin-echo coronal images were obtained, multiple axial multislice interleaved cine MRI acquisitions, each consisting of two to four 5-10-mm-thick slices at eight to 24 frames per cardiac cycle, were obtained from the superior main pulmonary artery to the inferior left ventricle. Each acquisition took 5-8 minutes with a subsequent 5-10 minutes of computer image reconstruction. Total study time per patient was 50-75 minutes. Known to cine MRI interpreters were the original surgical CABG insertions but not the angiographic findings. A graft was called patent if a bright graft flow signal, not corresponding to a normal vessel, was identified on multiple frames at multiple levels abutting the great vessels or epicardial surface of the heart. Angiographically, there were 33 patent grafts, of which 29 were identified as patent by cine MRI (sensitivity, 88%).(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

Auditory dysfunction in children with school problems.

One hundred thirty-three children with school problems referred to a hospital-based multi-disciplinary clinic were screened audiologically to determine the frequency of auditory problems, and to determine whether one could predict auditory problems from clinical data. Ninety-three (69.9%) failed one or more parts of the screening procedure. Twenty-two children (7.9% of the total group) had abnormal hearing acuity, 33 (30.6%) abnormal speech discrimination in noise, and 73 (62.4%) abnormal short term auditory memory. These figures are significantly higher than those found in a representative sample of school children. Not one of 16 items from parent and teacher questionnaires and neurodevelopmental findings predicted auditory acuity or speech in noise problems; there were correlations between short term auditory memory items and parental and teacher rating of a language problem, teacher rating of reading and sequencing problem, and neurodevelopmental finding of auditory sequencing problem. In view of this inability to clinically predict auditory processing deficits, the authors suggest that a full audiological assessment, including short term memory and speech in noise testing, is warranted as part of the evaluation of children with learning difficulties.

Adolescent↗

Keeping rural facilities alive and well. Trustees must take action to ensure hospitals' future.

To remain financially viable while providing high-quality primary care, rural healthcare facilities must deal with financial, human resource, technology, quality assurance, and community issues. Fewer qualified workers are available in rural communities as more career opportunities, better pay, and more attractive living conditions draw them to urban areas. Trustees must find ways to attract and keep employees. Trustees must carefully manage referral relationships with physicians to ensure that patients receive primary care in the rural facility. Quality of care issues arise as rural facilities experience limited debt capacity, fewer qualified physicians and workers, limited in-house technology, and a deteriorating plant. Facilities must develop processes to monitor quality and address clinical and nonclinical quality issues. Trustees can influence the community on the hospital's behalf by encouraging dialog with business, providing public relations, announcing new services, and enlisting support for hospital programs.

Community-Institutional Relations↗

Stereoselectivity of styrene oxidation in microsomes and in purified cytochrome P-450 enzymes from rat liver.

The stereochemistry of the cytochrome P-450(P-450)-dependent oxidation of styrene to styrene 7,8-oxide (SO) enantiomers was evaluated with rat hepatic microsomes and with individual rat liver P-450 enzymes in reconstituted monooxygenase systems. The stereoselectivity of the monooxygenase reaction with styrene was determined by high-performance liquid chromatographic analysis of the glutathione conjugates formed quantitatively from SO, the product of the monooxygenase reaction. Hepatic microsomes from control rats oxidized styrene at a rate of 13.1 +/- 4.5 nmol/min/nmol of P-450 and with a ratio of the amount of the (R)-styrene 7,8-oxide enantiomer to the amount of the (S)-styrene 7,8-oxide enantiomer (R/S) SO ratio of 0.65 +/- 0.1. These values were determined under incubation conditions in which epoxide hydrolase activity was inhibited by cyclohexene oxide, and at least 95% of the SO formed was converted enzymatically to glutathione conjugates. Treatment of rats i.p. with phenobarbital (PB) or beta-naphthoflavone (beta NF) caused changes in both parameters. Whereas the rates of oxidation in hepatic microsomes prepared from PB-treated rats was unchanged at 15.4 +/- 7.5 nmol/min/nmol of P-450 and decreased in hepatic microsomes from beta NF-treated rats to 9.4 +/- 2.8 nmol/min/nmol of P-450, the preference for formation of the R-enantiomer increased as the R/S ratio changed to 0.92 +/- 0.1 for PB and 1.25 +/- 0.1 for beta NF.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Inhibition of early platelet-derived growth factor responses in BALB/c-3T3 cells by interferon.

Stimulation of total inositol phosphate production, alteration of cytosolic free calcium [( Ca++]i), vinculin disruption from adhesion plaques, and DNA synthesis caused by PDGF were examined in normal and INF pretreated density arrested BALB/c-3T3 fibroblasts. In normal cells, PDGF caused an increase in total inositol phosphates, a rapid, transient increase in [Ca++]i, disappearance of vinculin from adhesion plaques, and stimulation of DNA synthesis. Pretreatment of cells with INF inhibited PDGF-stimulated increases in [Ca++]i, vinculin disruption from adhesion plaques, and DNA synthesis, but had no effect on PDGF-induced increase in total inositol phosphate levels. These findings suggest that INF prevents entry of quiescent BALB/c-3T3 cells into G1 by inhibiting PDGF-induced release of Ca++ from intracellular stores.

Animals↗

Glutathione status and the incidence of neural tube defects elicited by direct acting teratogens in vitro.

Valproic acid (VPA), cytochalasin D (CD) and 7-hydroxy-2-acetylaminofluorene (7-OH-AAF) each caused abnormal closure of the anterior neuropore in rat embryos cultured in vitro in the absence of an exogenous bioactivation system. Morphological comparisons showed that although all three compounds prevented normal neural tube closure, each did so in a distinctive manner. Modulation of GSH in cultured rat conceptuses was evaluated to determine whether common responses occurred relative to the ability of different chemicals to elicit neural tube defects. Malformation incidence in embryos (10-14 somites) varied widely following exposure to CD (44%), 7-OH-AAF (29%) or VPA (17%). The incidence of CD-elicited malformations was increased by 50% following GSH depletion by L-buthionine-S, R-sulfoximine (BSO) and was decreased by nearly 60% when the cysteine pro-drug 2-oxothiazolidine-4-carboxylate (OTC) was added to the culture medium. GSH modulation also exerted significant effects on the incidence of abnormal neurulation caused by VPA or 7-OH-AAF. A relatively low incidence of open neural tubes produced by VPA or 7-OH-AAF alone was shown to be a function of the state of maturation in the embryos. Conceptuses cultured in the presence of VPA or 7-OH-AAF from an earlier gestational age (6-10 somites) showed 2-3 fold increases in the number of embryos with open neural tubes. Differential alterations in protein and DNA content were observed among embryos and yolk sacs after various treatments indicating possible differences in the site of embryotoxicity. These results demonstrate the role of GSH status on the capacity of three chemically diverse compounds to elicit abnormal neurulation in cultured rat embryos and suggest some possible mechanisms by which normal neurulation may be compromised.

2-Acetylaminofluorene↗

The application of immunoassays and fluorometry to the detection of polycyclic hydrocarbon-macromolecular adducts and anti-adduct antibodies in humans.

The metabolic activation of polycyclic aromatic hydrocarbons (PAH) to chemical species that form covalent adducts with cellular macromolecules (DNA and protein) is central to theories of carcinogenesis. Assays are currently being developed that will accurately reflect human macromolecular exposure to these carcinogens. Immunoassays are capable of detecting low levels of PAH-DNA adducts and antibodies directed against these adducts in humans and HPLC/spectrophotofluorimetry allows the detection of carcinogen-DNA or carcinogen-protein adducts in human peripheral blood. Both types of method have inherent advantages and disadvantages, and the use of more than one type of corroborative assay is a feature in our work. Simplified but highly specific synchronous fluorescence spectra have been obtained for BP-tetrols after mild acid hydrolysis and HPLC of sample materials. When using a wavelength difference of 34 nm to drive the excitation and emission monochromators simultaneously, the pyrene fluorophore, when present, has a signature peak at 345 nm (excitation). The results of immunoassays demonstrate human exposure to PAH as a class of carcinogen, since serological cross-reactivity of antibodies does not limit detection in this system to a single chemical compound. In addition the formation in humans of anti-PAH-DNA antibodies has been shown, presumably in response to both past and present exposure to the parent compounds. In summary the results of each assay can indicate human exposure to PAH and have the potential for molecular dosimetry of this exposure.

Antibodies↗

Cytomembranous inclusions in the brain of a patient with the acquired immunodeficiency syndrome.

Ultrastructural studies of cells and tissues in the acquired immunodeficiency syndrome (AIDS) have revealed two distinct cytomembranous inclusions referred to as "tubuloreticular inclusions" (TRI) and "confronting cylindrical cisterns" (CCC). TRI are found most often in leukocytes and endothelial cells in conditions with elevated levels of alpha-interferon, such as viral infections, autoimmune diseases and certain neoplasms. On the other hand, CCC are detected almost exclusively in mononuclear inflammatory cells and are limited to a few conditions, of which AIDS is the most common. CCC have been proposed as an ultrastructural marker for human immunodeficiency virus (HIV) infection. We describe CCC in mononuclear inflammatory cells in the brain tissue with no other specific feature such as multinucleated giant cells, nevertheless, should alert the neuropathologist to the possibility that the patient might have AIDS.

Acquired Immunodeficiency Syndrome↗

A comparison of the persistence in a clay loam of single and repeated annual applications of seven granular insecticides used for corn rootworm control.

In May 1983, granular formulations of carbofuran, chlorpyrifos, disulfoton, fonofos, isofenphos, phorate, and terbufos were applied in incorporated bands to duplicate 2 m2 field plots of clay loam. Insecticide concentrations were determined in the bands at 0,1,2,3,4,6,8,10,12,16, and 20 wk. Following spring cultivation, the insecticides were applied to the same plots in 1984 and 1985. In addition, carbofuran was applied to previously untreated plots in 1984 and all 7 materials were applied to previously untreated plots in 1985. Sampling and analysis were carried out as in 1983. Persistence was assessed on the basis of the disappearance rates measured for the 1st 8 wk and of a calculated Effectiveness Potential (the ratio of the average residue in the upper 5 cm of the band at 8, 10 and 12 wk and the published LC95 for western corn rootworm in clay loam soil). Soils treated with carbofuran and isofenphos in 1984 and all soils treated in 1985 were tested for anti-insecticide activity. Soil cores from some carbofuran, chlorpyrifos and terbufos treated plots were sectioned vertically to establish the distribution of the insecticides during 1985. In addition, granular and pure chemical forms of isofenphos and carbofuran were applied at 10 ppm to anti-isofenphos and anti-carbofuran active and control soils (from field plots) maintained at 10 and 20% moisture in the laboratory to assess the effect of formulation and moisture on persistence in active soils. Insecticide concentrations were determined at 0,1,3,7, 10,14,21,28, and 35 days. The persistence of chlorpyrifos, terbufos and phorate was relatively constant over the 3 years and between plots receiving single and multiple treatments. Disulfoton and fonofos behavior was more variable and that of carbofuran and isofenphos was extremely variable. Anti-insecticide activity against carbofuran and isofenphos was detectable 2 wk after an initial application and was still present the following spring. Anti-insecticide activity against fonofos, terbufos sulfoxide, phorate sulfone and disulfoton sulfone was also generated in this soil. Anti-insecticide activity against chlorpyrifos, disulfoton, terbufos and phorate was not present. Carbofuran, chlorpyrifos and terbufos (+ metabolites) present in the upper 5 cm of soil averaged 93, 94 and 94%, respectively, of the total core contents over 12 wk. Significant moisture dependent differences were observed between the behavior of granular carbofuran and granular isofenphos in anti-insecticide active soils.(ABSTRACT TRUNCATED AT 400 WORDS)

Chromatography, Gas↗

In vitro assessment of antimicrobial agents against Toxoplasma gondii.

We have modified a method of quantitating growth of Toxoplasma organisms by measuring incorporation of [3H]uracil into Toxoplasma-infected, differentiated L6E9 rat myocytes and have found that low-dose pyrimethamine (0.1 microgram/ml) and sulfadiazine (25 micrograms/ml) are synergistic. Pyrimethamine at higher concentrations (0.5 and 1.0 micrograms/ml) inhibits uptake to the same degree as the low-dose pyrimethamine-sulfadiazine combination. Spiramycin was effective only at high concentrations (200 micrograms/ml) and with prolonged incubation of greater than 72 h. Clindamycin and several of its analogues, methotrexate and difluoromethylornithine, were all ineffective and showed no additive effect with either pyrimethamine or sulfadiazine. Spirogermanium, an experimental antineoplastic and antiprotozoan agent, was effective only at concentrations close to those toxic to the system. 5-Fluorouracil was effective even at 0.1 microgram/ml. At 0.01 microgram/ml it was synergistic with pyrimethamine (0.1 microgram/ml), and the combination was as effective as high-dose pyrimethamine (1.0 microgram/ml).

Animals↗

Giardia carriage in aboriginal and non-aboriginal children attending urban day-care centres in South Australia.

A survey of Giardia lamblia prevalence was carried out in Adelaide, South Australia, among Aboriginal and non-Aboriginal children attending day-care centres. A single-stool examination in 178 children aged 6 years and under revealed an overall prevalence rate of 10.7% with all carriers being 1-4 years of age. Within this age group, Giardia prevalence among Aboriginal children (11/32) was significantly higher than that among non-Aboriginal children (eight of 99) (Chi-square analysis, P less than 0.001). Furthermore, among Aboriginal children, a significant association (P less than 0.05) was found between giardia carriage and the family's contact with rural Aboriginal settlements or people from these areas. Aboriginal children with no rural contact had a giardia prevalence similar to non-Aboriginal children.

Carrier State↗

Double-blind trial of yohimbine in treatment of psychogenic impotence.

48 subjects meeting strict diagnostic criteria for psychogenic impotence took part in a 10 week placebo-controlled, double-blind, partial crossover trial of yohimbine (18 mg a day) for restoring erectile function. At the end of the first arm of the trial 62% of the yohimbine group and 16% of the placebo group reported some improvement in sexual function (chi 2 = 10.41, df = 2, p less than 0.05). 21% of the originally placebo-treated group noticed some improvement over pre-treatment levels when they were put on yohimbine in the second arm of the trial. Overall 46% of those who received yohimbine reported a positive response to the drug, a response rate very similar to that observed in a previous study of patients with organic impotence. Response to yohimbine thus seems to be unrelated to current groupings of the cause of impotence. Yohimbine is a safe treatment for psychogenic impotence that seems to be as effective as sex and marital therapy for restoring satisfactory sexual functioning.

Adolescent↗

Embryotoxicity elicited by inhibition of gamma-glutamyltransferase by Acivicin and transferase antibodies in cultured rat embryos.

Acivicin (also known as AT-125) and IgG isolated from goat anti-gamma-glutamyltransferase antiserum were used to inhibit the activity of gamma-glutamyltransferase (GGT, EC 2.3.2.2) in rat conceptuses cultured from Days 10 to 11 of gestation. Inhibition of GGT by either Acivicin or anti-GGT IgG produced embryotoxicity and malformations, although each compound produced a unique spectrum of effects. Acivicin, at an initial concentration in the culture medium of 5 microM, produced a marked decrease in yolk sac vasculature and was associated with embryonic malformations such as neural tube necrosis, microophthalmia, and cephalic edema after 24 hr exposure. These malformations were accompanied by significant decreases in both embryonic and yolk sac protein, yolk sac GGT activity, as well as embryonic glutathione (GSH) levels. In contrast, anti-GGT IgG produced no apparent effects on yolk sac vasculature or protein after exposure of conceptuses to an initial concentration of 50 micrograms IgG/ml culture medium, even though equal inhibition of yolk sac GGT (30%) was achieved by each inhibitor. Exposure to IgG (50 micrograms/ml) for 24 hr was associated with decreased embryonic protein; decreased levels of GSH in the embryo were observed after both 3 and 24 hr. The dichotomy of effects on the yolk sac by the two compounds indicates that Acivicin produced these effects by mechanisms other than by GGT inhibition alone. These results demonstrate that inhibition of GGT in rat embryos undergoing organogenesis can elicit embryotoxic effects and produce alterations in GSH levels. The capacity of the anti-GGT antibody to inhibit the GGT activity in the yolk sac (while having no apparent effect on yolk sac morphology), and yet influence the embryo by decreasing protein and GSH levels, underscores the important role of the yolk sac during the highly sensitive stages of organogenesis.

Animals↗