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Biomedical subjects

R Niven

Publications and source records attributed to R Niven.

11 recordsLinked to original sources
PubMed2001

Use of perfluorocarbon (fluorinert) to enhance reporter gene expression following intratracheal instillation into the lungs of Balb/c mice: implications for nebulized delivery of plasmids.

Perfluorocarbons combine high respiratory gas dissolving capabilities with extreme chemical and biological inertness and therefore offer an attractive option as an excipient in the area of pulmonary therapeutics. Perfluorocarbons have also been shown to "float" mucus, because of their high densities (1.9-2.5 g/mL), which may hold potential in gene delivery for cystic fibrosis patients, in terms of enhancing penetration through highly viscous mucus and thereby providing access to target epithelial cells to correct the gene defect. Additionally, their low surface tension allows for better dispersion. A commonly available perflurocarbon, heptacosafluorotributylamine (Fluorinert), was used to deliver either plasmid DNA (pDNA) alone or cationic-lipid-complexed plasmid DNA to the lungs of Balb/c mice by direct intratracheal instillation. The complexes consisted of supercoiled (SC) plasmid DNA (4.7 Kb, 0.625 mg/mL) and lipid (ethyldimyristoyl phosphatidylcholine [EDMPC]/cholesterol [1:1 mole ratio], with pDNA (3:1 mg pDNA/mM EDMPC in 20 mM Tris-HCl pH 8.0) expressing chloramphenicol acetyl transferase (CAT) or beta-galactosidase (beta-Gal). pDNA alone was supplemented with 14% w/v Fluorinert. Cationic lipid/pDNA complexes were supplemented with 3, 8, and 14% w/v Fluorinert. Results showed that the CAT expression from pDNA alone was enhanced 24 x using 14% w/v Fluorinert, whereas that from the cationic-lipid-formulated pDNA was enhanced 7 x using 14% w/v Fluorinert. Immunohistochemistry showed that beta-Gal expression was primarily from epithelial cells and not from F4/80 or MAC3 antigen-stained cells (predominantly macrophages), indicating efficient delivery.

Animals↗
PubMed1999

Attempting to control mite allergens with mechanical ventilation and dehumidification in British houses.

BACKGROUND: Allergen avoidance is of considerable interest in the treatment and even prevention of asthma. Attempts to control house dust mites have included environmental manipulation in homes in an attempt to reduce humidity below a level that favors mite survival. This appears to have some benefit in Scandinavia, but a previous attempt with mechanical ventilation heat pump recovery (MVHR) units in the UK failed to achieve the desired results. OBJECTIVE: We report a study using an additional central dehumidification modification of the MVHR (MVHRcd) in an attempt to reduce allergen levels in houses of asthmatic subjects. METHODS: Ten houses of asthmatic patients allergic to dust mites and 10 architectural control houses were studied. The active houses were fitted with an MVHRcd unit in November/December 1994 and activated in January 1995. The active and control houses were monitored continuously for internal temperature and humidity by using digital sensors in the asthmatic and control bedrooms. Dust samples were collected to determine allergen levels at baseline (January 1994) and 3, 6, 9, and 15 months after switching on the units. RESULTS: The winter seasonal average humidity fell from 50% relative humidity (RH) in control bedrooms to 37% RH in asthmatic bedrooms compared with 72% RH in the ambient air as measured on the intake of the MVHRcd systems. There was no corresponding change in seasonal mean temperature within the houses. Although the temperature and humidity weekly and seasonal means remained below the study target of 45% RH or 7 g/kg absolute humidity at 21 degrees C, there were transient rises in humidity detected by the sensors in the houses with MVHRcd systems. Allergen levels fell both in active and control houses during the study period, but there was no significant advantage gained from the installation of MVHRcd systems. CONCLUSION: The MVHRcd system failed to confer a benefit in terms of mite allergen reduction despite apparently adequate control of temperature and humidity.

Air Pollution, Indoor↗
PubMed1998

Biodistribution of radiolabeled lipid-DNA complexes and DNA in mice.

The tissue biodistribution and expression of [33P]DNA-1-[2-[9-(Z)-octadecenoyloxy]ethyl]]-2-[8](Z)-heptadece nyl]-3 -[hydroxyethyl]imidazolinium chloride (DOTIM):cholesterol complexes and 33P-radiolabeled DNA expressing chloramphenicol acetyl transferase (CAT; 4.7 kB) were studied after intravenous (iv) injection in ICR mice. Mice were injected with 200 microL of complex containing DNA at 3 mg/kg or DNA alone. One group received 8 microCi of radioactivity and were sacrificed at 5 and 20 min, and 1, 2, 4 and 24 h post-dose (n = 4/time point). A second group received the equivalent of 3.9 microCi of radioactivity and were sacrificed at 20 min, and 2 and 24 h for subsequent whole body autoradiographic analysis (WBA; n = 2/time point). The tissue distribution of intact DNA was assessed by Southern blot at 24 h post-dose, whereas the integrity of complexes and DNA incubated in heparinized whole blood was studied separately. In further studies, the time course of expression in lung tissue over a 48-h period was examined, and the relative lung-expression of purified open circular (OC) versus supercoiled (SC) DNA at 24 h was evaluated. Approximately 42% of the radioactivity was found in the lungs 5 min after injection and about half this percentage was found in the liver. By 2 h, only 5% remained in the lungs, but 48% was present in the liver. No other tissue accumulated >5% of the dose throughout the duration of the study. WBA radiograms confirmed the tissue distribution results and highlighted significant accumulation of radioactivity in bone over time. Southern Blot analysis demonstrated intact DNA in many tissues 24 h after dosing. In contrast, the majority of DNA incubated in blood was degraded within 2 h, although the complexes afforded some protection relative to DNA alone. The OC DNA expressed equivalently to SC DNA in lung tissue (OC = 1035 +/- 183 pg; SC = 856 +/- 257 pg/mg soluble protein, n = 6, mean +/- SEM) at 24 h, and detectable levels of CAT were present within 2 h of dosing (21.3 +/- 7.2 pg, n >/= 8, mean +/- SD). The results confirm that DNA-DOTIM:cholesterol complexes are initially deposited in the lungs after iv administration.

Animals↗
PubMed1997

Toward development of a non-viral gene therapeutic.

Gene therapy is an emerging field that has reached the early clinical stages of development for some disease states. However, the demonstration of safety in animals and the introduction of gene-based formulations in humans hides the fact that numerous developmental and basic research questions remain. This article highlights progress and emerging issues in the area of liposome-based non-viral gene delivery. The colloidal nature of these formulations render them complicated at the physico-chemical and biological levels. Instrumentation and methodologies need to be developed to better understand the subtleties of plasmid DNA, complexing agents, delivery mode and the route of entry into the cell and the nucleus. Major hurdles to entry include membrane binding, endosomal release, nuclear uptake and decomplexation. Each 'stage' is poorly understood but numerous approaches are being directed to increase cellular delivery. These research efforts, coupled with sensible formulation research and a multi-disciplinary, long-term effort, are necessary for success.

Journal Article↗
PubMed1997

Preface.

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Journal Article↗
PubMed1995

Chemotherapy in non-small cell lung cancer.

BACKGROUND: Non-small cell lung cancer can no longer be regarded as resistant to chemotherapy, and there have recently been considerable improvements in the use of the older agents and advances in the identification of new drugs. Recent meta-analysis has also confirmed the view that chemotherapy can have small but modest survival benefits. Although in the treatment of stage IV disease the criteria of efficacy have concentrated on tumour response rates, more recently it has become obvious that these patients can also benefit in terms of improved symptom control. RECENT ADVANCES: For patients with locally advanced stage III disease there have been important developments indicating the benefit of combined modality treatment with chemotherapy and thoracic irradiation. Furthermore, the use of neoadjuvant chemotherapy indicates that resection is possible in about half the patients, and on pathological examination of 15%-20% of the resected specimens there is no evidence of residual tumour. These results justify an increase in the use of systemic chemotherapy in this disease.

Antineoplastic Agents↗
PubMed1993

Financing and payment reform for primary health care and substance abuse treatment.

One of the most controversial areas for health care reform concerns the treatment of alcohol and other drug problems, which account for some of the most rapidly rising costs in the health care sector. There is arguably no other set of conditions that show such variation in accessibility to treatment on the basis of insurance status, present the same degree of difficulty in providing comprehensive care, or challenge as many public and professional assumptions about behavioral, social and economic determinants. The purpose of this article is to discuss some of the financing and coverage barriers to comprehensive treatment for alcohol and other drug abuse; to discuss some innovative mechanisms for providing and financing comprehensive services; and to suggest some directions for public policy to support the development of new practice models that emphasize cost-effectiveness and efficiency of care.

Alcoholism↗
PubMed1986

The cause of death.

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Death Certificates↗