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Biomedical subjects

J Lancaster

Publications and source records attributed to J Lancaster.

At least 55 records · Page 3Linked to original sources
PubMed1996

Diagnostic efficiency of the disposable Monotest in detecting tuberculosis infection by setting objective-specific cut-off points for positivity.

The disposable multiple-puncture tuberculin test device, Monotest, was recently introduced in South Africa for tuberculin test screening of tuberculosis infections. Three studies were carried out to compare the intradermal Mantoux test with the Monotest. In the first study, conducted on confirmed hospitalised tuberculosis patients, 307 subjects underwent a 2 TU RT 23 (Statens Seruminstitut, Copenhagen) Mantoux test, 155 a 5 TU test of the same antigen, and 111 a Monotest. In the second study, another group of 98 confirmed tuberculosis patients was double-tested with 5 TU RT 23 by Mantoux test and Monotest. In the first study, 100% of 5 TU Mantoux tests resulted in indurations > or = 5 mm, 97% of 2 TU Mantoux indurations were > or = 10mm, and 96% of Monotests produced indurations > or = 2 mm (manufacturer's recommended cut-off point). In the second study, 99% of the 5 TU Mantoux tests measured > or = 5 mm, and 100% of Monotest indurations were > or = 2 mm. In both studies, raising the cut-off point for the Monotest to > or = 4 mm produced sensitivities of 95% and and 100% respectively. All these tests may therefore be regarded as highly sensitive. In a third study, 58 healthy schoolchildren were double tested with 2 TU RT 23 and with Monotest. Results indicated that if the positivity cut-off point of the Monotest is set a 8 mm instead of at 2 mm, sensitivity suffers slightly, decreasing from 100% to 90%, while specificity increases considerably from 8% to well over 80%. Receiver operating characteristic analysis indicated the high likelihood that the Monotest as well as the Mantoux test could discriminate between infected and uninfected subjects. For both tests the Wilcoxon statistic exceeded 0.8. The Monotest is a useful alternative to the Mantoux test. It is recommended that if tuberculosis is suspected, reaction > or = 4 mm be interpreted as positive. For screening purposes, a cut-off point of 8 mm seems to distinguish best between the infected and the uninfected individual.

Adult↗
PubMed1995

Receptor binding profile suggests multiple mechanisms of action are responsible for ibogaine's putative anti-addictive activity.

The indole alkaloid ibogaine (NIH 10567, Endabuse) is currently being examined for its potential utility in the treatment of cocaine and opioid addiction. However, a clearly defined molecular mechanism of action for ibogaine's putative anti-addictive properties has not been delineated. Radioligand binding assays targeting over 50 distinct neurotransmitter receptors, ion channels, and select second messenger systems were employed to establish a broad in vitro pharmacological profile for ibogaine. These studies revealed that ibogaine interacted with a wide variety of receptors at concentrations of 1-100 microM. These included the mu, delta, kappa, opiate, 5HT2, 5HT3, and muscarinic1 and 2 receptors, and the dopamine, norepinephrine, and serotonin uptake sites. In addition, ibogaine interacted with N-methyl-D-aspartic acid (NMDA) associated ion and sodium ion channels as determined by the inhibition of [3H]MK-801 and [3H]bactrachotoxin A 20-alpha-benzoate binding (BTX-B), respectively. This broad spectrum of activity may in part be responsible for ibogaine's putative anti-addictive activity.

Animals↗
PubMed1995

Nitro containing L-arginine analogs interfere with assays for nitrate and nitrite.

We evaluated the effect of in vivo and in vitro administration of nitro-containing and nitro-deficient L-arginine-derived nitric oxide (NO) synthase inhibitors on the measurement of NO in plasma, urine and HEPES buffered physiologic salt solution (PSS) by ozone chemiluminescence and by the modified Griess reaction. In vivo administration of 1, 5, 25, 40 or 50 mg/kg of NG-nitro-L-or D-arginine methyl ester (LNAME, DNAME), NG-nitro-L-arginine (LNA) or aminoguanidine (AG) to rats and mice increased NO in urine and plasma as determined by chemiluminescence using 2.3% vanadium chloride in 2N HCI at 100 degrees C as the redox reagent. In vivo administration of 1 and 10 mg/kg/day of NG-imino-ethyl-L-ornithine (LNIO) or 3 amino-1,2,4 triazine (AT) reduced plasma and urine NO. Addition of LNAME, DNAME and LNA (100 nM to 1 mM) to the redox solution produced a concentration response curve for NO in the chemiluminescence assay similar to that produced by standard solutions of sodium nitrite and nitrate. LNMMA produced a small NO signal but only at concentrations equal to or exceeding 0.1 mM. LNIO, AT and AG did not give any NO signal even at concentrations exceeding 1 mM. Conversion of plasma or urine nitrate to nitrite with cadmium gave elevated values of plasma nitrite by the Greiss assay when LNAME or LNA was the NO synthase inhibitor. We conclude that in vivo and in vitro use of LNAME and LNA and in vivo use of high doses of aminoguanidine interfere with the assay of NO2- and NO3- with the modified Griess reaction and with chemiluminescence. We suggest that LNAME and LNA not be used in vivo or in vitro when total RNI is measured with these assays.

Animals↗
PubMed1995

Microcomputed tomography: an advanced system for detailed endodontic research.

This study evaluated the value of microcomputed tomography (MCT) for use in endodontic research. Four periodontally involved highly calcified maxillary first molars were extracted and then scanned for evaluation by a MCT system. The teeth were then instrumented, and 2 of the 4 obturated before rescanning for comparison evaluation. Several capabilities of the MCT to advance endodontic research significantly were observed: the ability of the MCT to present accurately the external and internal morphologies of the tooth without tooth destruction; the possibility of showing changes over time in surface areas and volumes of tissues; the ability to assess area and volume changes after instrumentation or obturation; and the capability of evaluating canal transportation following instrumentation or instrumentation and obturation. The tremendous potential of this scientific tool was discussed.

Dental Pulp Calcification↗
PubMed1995

Nitric oxide and its role in orthopaedic disease.

Nitric oxide (.NO) is synthesized by the enzyme nitric oxide synthase (NOS). There are 2 constitutive forms of NOS (cNOS) and 1 inducible form (iNOS). Cells containing cNOS rapidly and transiently produce small amounts of NO in response to agonists that raise cytosolic levels of free Ca2+, whereas cells expressing inducible iNOS produce large amounts of .NO for extended periods after a lag of several hours during which time the enzyme is induced. Until recently, the 2 constitutive isoforms of NOS were thought to be confined to endothelial cells (eNOS) and brain (bNOS or nNOS). However, eNOS and bNOS have been identified in an increasing variety of additional cells. Many, if not most, types of cells are capable of expressing iNOS in response to cytokines, endotoxin, and phagocytosis. Regulation of iNOS occurs at transcriptional, translational, and posttranslational levels. Because .NO is rapidly diffusible and soluble in hydrophobic and aqueous environments, it is well suited to its role as an intercellular messenger with the unique ability to penetrate solid tissue. However, it is rapidly inactivated by hemoglobin. The biochemistry of .NO is dominated by its rapid reaction with oxygen and transitional metals, notably iron. The former reaction may be protective, as when neutralizing superoxide (.O2-), or harmful in forming additional highly damaging radicals such as peroxynitrite. Interaction of .NO with iron-containing proteins has a number of sequelae, including the activation of guanylate cyclase, inhibition of mitochondrial respiration, and inhibition of cell division. Nitric oxide has been implicated in a number of conditions of orthopaedic interest, including inflammation, arthritis, osteoporosis, sepsis, ligament healing, and aseptic loosening of joint prostheses.

Amino Acid Oxidoreductases↗
PubMed1994

Interactions between N-acetylaspartylglutamate and AMPA, kainate, and NMDA binding sites.

The structure of N-acetylaspartylglutamate (NAAG) suggests this neuronal dipeptide as a candidate for interaction with discrete subclasses of ionotropic and metabotropic acidic amino acid receptors. A substantial difficulty in the assay of these interactions is posed by membrane-bound peptidase activity that converts the dipeptide to glutamate and N-acetylaspartate, molecules that will interfere with receptor assays. We have developed two sets of unique receptor assay conditions and applied one standard assay to measure the interactions, under equilibrium binding conditions, of [3H]kainate, [3H]amino-3-hydroxy-5-methylisoxazole-4-propionic acid ([3H]AMPA), and [3H]CGS-19755 with the three classes (kainate, quisqualate, and N-methyl-D-aspartate) of ionotropic glutamate receptors, while inhibiting peptidase activity against NAAG. Under these conditions, NAAG exhibits apparent inhibition constants (IC50) of 500, 790, and 8.8 microM in the kainate, AMPA, and CGS-19755 receptor binding assays, respectively. Glutamate was substantially more effective and less specific in these competition assays, with inhibition constants of 0.36, 1.1, and 0.37 microM. These data support the hypothesis that, relative to glutamate, NAAG functions as a specific, low potency agonist at N-methyl-D-aspartate subclass of ionotropic acidic amino acid receptors, but the peptide is not likely to activate directly the kainate or quisqualate subclasses of excitatory ionotropic receptors under physiologic conditions.

Animals↗
PubMed1994

Reform of primary health care: effective use of advanced practice nurses.

Never before has American society undergone such dramatic and pervasive changes as those currently effecting national health care needs. New strategies to meet the health care needs created by societal changes must be identified. Consumers, employers, providers, and third-party payers are calling for more cost effective health care, better access and better quality. Simultaneously, the United States has a shortage of primary care physicians. While many people claim that one strategy necessary for health care reform is to change the primary care physician/specialty mix of providers, there are some inherent fallacies in this argument. Training for primary care medicine has historically been available; however, the majority of physicians choose specialty practice. The financial rewards are much better in specialty practice than in primary care. If the U.S. were to alter the reward structure and make primary care more attractive to physicians, the objective of controlling costs could not be met. However, there is another alternative and that is to change the provider mix. Since advanced practice nurses (APNs) have a long and successful history of taking care of primary care patients, why not make them the point of first contact? APNs working collaboratively with physicians could more cost effectively manage care for large numbers of ambulatory patients than are being adequately handled at present. APNs, defined as nurse practitioners, certified nurse midwives and clinical nurse specialists, provide high quality, cost effective, and comprehensive primary care services. Increased use of APNs in disease prevention, illness management, and health education is one way of meeting health care needs of Americans. Innovative strategies for more effectively using APNs must also be identified and implemented. Also, artificial and politically imposed barriers to effective utilization of APNs must be removed.

Evaluation Studies as Topic↗
PubMed1993

The role of receptor binding in drug discovery.

Radioligand receptor binding has been used extensively to identify and characterize a host of receptors and enzymes targeting virtually every therapeutic area. Many drug discovery programs have been based on the utilization of radioligand receptor binding technology to identify lead compounds which interact with receptors likely to be important in neuronal, immunological, gastrointestinal, and cardiovascular function/dysfunction. There are several obvious advantages to using in vitro receptor binding as a first level screen when compared to in vivo pharmacometric screens. Scientifically, the structure activity data generated in binding assays is a direct reflection of the ligand/receptor interaction minus the complications which result from secondary events, bioavailability, and pharmacodynamic issues. Technically, the binding studies require only a small amount of test compound (< or = 1 mg), while whole animal studies routinely need gram quantities. Similarly, only a small amount of tissue is required, compared with the cost of purchase and maintenance of live animals for in vivo screening. Supply and labor costs are drastically reduced due to the limited volume and test tube based technology of receptor binding. For these reasons receptor binding assays have been utilized with considerable success to discover site specific lead compounds in virtually every therapeutic area.

Animals↗
PubMed1993

Women's experiences of gynaecological cancer treated with radiation.

The study explores women's experience of pelvic radiotherapy for gynaecologic cancers, with specific reference to sexual impairment. Fifty women were interviewed and their responses recorded, from which data emerged several features. Ignorance was the most striking: the women were neither prepared for the treatment nor subsequent side effects. Other concerns expressed were what had caused the cancer, fear of recurrence, where to find help, sexual dysfunction and future expectations. Some subjects chose to avoid sexual contact altogether, others elected to preserve the marriage by resorting to various strategies. Information from all categories of health care workers was inadequate leaving the women to make the best of a changed life-style. In the light of this study a number of recommendations are presented and further areas of research are suggested.

Adult↗
PubMed1992

Tracking patient satisfaction at an academic medical center.

Rising consumer expectations for convenient, quality health care is forcing many hospitals to focus increasing attention to measuring consumer perception and satisfaction with the care provided. At the University of Virginia Health Sciences Center, getting in close touch with the consumer has assumed a strategic position. As one part of the evolving Marketing Information System, a patient satisfaction tracking system is being designed to illicit patient feedback and hospital responses to service issues, assess patient satisfaction with various services, serve as a benchmark for evaluating changes in satisfaction over time, and provide necessary information for medical center planning, marketing and evaluation.

Academic Medical Centers↗
PubMed1991

Regulation of Agrobacterium tumefaciens T-cyt gene expression in leaves of transgenic potato (Solanum tuberosum L. cv. Désirée) is strongly influenced by plant culture conditions.

The promoter region of the Agrobacterium tumefaciens T-cyt gene was linked in a translational fusion to the coding DNA of the reporter gene uidA (for beta-glucuronidase or GUS protein; EC 3.2.1.31) and to nos 3' flanking DNA. The chimaeric gene was introduced by Agrobacterium transformation into potato (Solanum tuberosum L. cv. Désirée). In nine transgenic lines, the average GUS levels were highest in extracts from stems and roots of in vitro grown plants (ca. 11,000 GUS activity units per pmol MU per mg protein per min) but lower in leaves of the in vitro grown plants (ca. 7000 units). GUS activity was intermediate in stems and roots of plants grown in soil as well as in in vitro crown galls (ca. 3000 units). Activity was low in tubers, irrespective of whether these developed in vitro or in soil (both ca. 100 units), and lowest of all in leaves of soil-grown plants (ca. 10-15 units). However, in shoot cultures reestablished from soil-grown plants, GUS activity in the leaves increased to that determined in the original shoot cultures. Hence, plant culture conditions strongly influenced the expression of the T-cyt-uidA-nos gene. In particular, it was silenced in leaves of soil-grown plants. The results are compared with previous analyses of the promoter region of the wild-type T-cyt gene and with the growth properties of a large number of crown gall cell lines and crown-gall-derived plants, including over forty S. tuberosum cv. Désirée cell lines isolated in the present study that were transformed with the wild-type T-cyt gene and six promoter-mutated derivatives. A number of implications are discussed for crown gall formation and for control of expression of plant genes which contain Activator or G-box type 5' expression control sequences.

Agrobacterium tumefaciens↗
PubMed1990

Effect of cyclic estrone sulfate treatment on lipid profiles of postmenopausal women with elevated cholesterol levels.

The effects of two doses of cyclic unopposed estrone sulfate therapy on the lipid profiles of 153 healthy postmenopausal women with baseline total cholesterol levels above 219 mg/dL were compared in a multicenter, double-blind, placebo-controlled study. Patients were assigned randomly to one of three treatment groups: estrone sulfate 0.625 mg (N = 59) or 1.25 mg (N = 43), or placebo (N = 51). The median baseline total cholesterol levels of the three treatment groups were 262, 269, and 262 mg/dL, respectively. Total cholesterol, triglycerides, high-density lipoprotein cholesterol (HDL), low-density lipoprotein cholesterol (LDL), and the HDL/LDL ratio were assessed after 6, 9, and 12 months of treatment. There was a significant monotonic dose-response relationship of estrone sulfate in raising HDL levels, lowering LDL levels, and raising the HDL/LDL ratio at all intervals measured. These results indicate that estrone sulfate is effective in creating a beneficial change in the lipid profile of postmenopausal women with elevated baseline total cholesterol.

Cholesterol, HDL↗
PubMed1989

About radiotherapy--Part II. Side effects and staff protection.

Special side effects which relate to specific areas are discussed. Head and neck radiation produces acute problems related to swallowing, dry mouth, sore throat and thickened saliva which all require medication. Alteration of taste may last for months after radiation is completed. Radiation to lungs may cause worsening breathlessness and coughing which may necessitate interruption of treatment. Radiation to pelvis and abdomen result in nausea and diarrhoea which usually respond to treatment. Proctitis, vaginal discharge and urinary problems all need attention. With cranial radiation, hair loss is a major problem and unlike chemotherapy induced alopecia, there is poor recovery. Patients must be informed that their condition will improve when radiation ceases, and not attribute all symptoms to underlying disease. Protection in this country is in line with international standards and strict adherence protects the work force. Patients with radioactive sources in situ e.g. radium or implants such as gold seeds, iridium wires, or being treated by radioactive iodine all require special nursing and are nursed in a protected ward. Staff wear film badges to detect radiation absorbed. If in doubt about safety measures contact superiors or radiophysics department of hospital. Patients already isolated from visitors must not be neglected and nurses must observe instructions and then proceed with safety.

Abdomen↗