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Biomedical subjects

J S Ferguson

Publications and source records attributed to J S Ferguson.

At least 19 recordsLinked to original sources
PubMed2006

Characteristics of 5-aminolaevulinic acid-induced protoporphyrin IX fluorescence in human skin in vivo.

BACKGROUND/PURPOSE: Topical photodynamic therapy (PDT) is increasingly being used to treat skin cancers. Knowledge of the detailed characteristics of 5-aminolaevulinic acid (ALA)-induced protoporphyrin IX (PpIX) fluorescence in diseased and normal skin is incomplete. Understanding the characteristics of PpIX fluorescence in normal skin may facilitate optimization of PDT regimes while minimizing side effects in the surrounding normal skin. We investigated the characteristics of ALA-induced PpIX fluorescence in normal skin. METHODS: ALA was applied to the arm, back and leg skin of 21 healthy volunteers for 1-6 h, and PpIX fluorescence was measured for up to 24 h after ALA application using a fluorescent spectrometer. The effect of tape stripping on fluorescence was also examined. RESULTS: Considerable inter-subject variation was observed in the time to reach peak PpIX fluorescence. Intra-subject variation in the time to peak fluorescence was dependent on ALA application time. Six hours after ALA application, no significant difference was observed in the degree of fluorescence achieved irrespective of ALA application times ranging between 1 and 6 h. PpIX fluorescence was reduced on the leg and increased by tape stripping. CONCLUSIONS: Marked inter- and intra-subject variation in ALA-induced PpIX fluorescence occurs in normal human skin. ALA application time, body site and the state of the stratum corneum are all determinants of PpIX fluorescence within subjects and these factors need to be taken into account in optimization of PDT regimes.

Adult↗
PubMed2000

New treatments for advanced cancer: an approach to prioritization.

The allocation of funding for new anticancer treatments within the UK has not kept pace with demand. Clinicians find themselves restricted in the use of licensed drugs which they feel are in the best interests of individual patients. Against this, health authorities have a duty to ensure that scarce resources are used equitably to meet the needs of the local population as a whole. Differential levels of funding for new treatments across the country have led to concerns about rationing by postcode. This paper outlines an approach to the prioritization of new treatment for advanced cancer developed jointly by clinicians and health authorities in South London. The approach involves evidence reviews and consensus meetings. Existing and new treatments are rated on a four-point 'relative effectiveness scale', which takes account of the impact of the treatment on quality of life and on survival. The strength of evidence supporting each effectiveness rating is also classified. Health Authorities have used these ratings to determine overall funding levels, while leaving decisions on individual patients to the relevant Trusts.

Antineoplastic Agents↗
PubMed2000

Pulmonary surfactant in innate immunity and the pathogenesis of tuberculosis.

Components of the innate immune system serve to protect the host from invading pathogens prior to the generation of a directed immune response, and influence the manner in which the directed immune response develops. The pulmonary surfactant system consists of a complex array of proteins and lipids that reduce surface tension of the alveoli, and appears to play an essential role in innate immunity. Investigators have recently gained insight into the interactions between components of the surfactant system and the respiratory pathogen Mycobacterium tuberculosis. It is likely that pulmonary surfactant and other innate immune determinants play significant roles in the pathogenesis of tuberculosis.

Animals↗
PubMed1999

Surfactant protein D binds to Mycobacterium tuberculosis bacilli and lipoarabinomannan via carbohydrate-lectin interactions resulting in reduced phagocytosis of the bacteria by macrophages.

Surfactant protein-D (SP-D) is a collectin produced in the distal lung airspaces that is believed to play an important role in innate pulmonary immunity. Naive immunologic responses to Mycobacterium tuberculosis (M.tb) are especially important in the lung, since entry of this inhaled pathogen into the alveolar macrophage is a pivotal event in disease pathogenesis. Here we investigated SP-D binding to M.tb and the effect of this binding on the adherence of M. tb to human macrophages. These studies demonstrate specific binding of SP-D to M.tb that is saturable, calcium dependent, and carbohydrate inhibitable. In addition to purified SP-D, SP-D in bronchoalveolar lavage fluids from healthy donors and patients with alveolar proteinosis also binds to M.tb. Incubation of M.tb with SP-D results in agglutination of the bacteria. In contrast to its binding to M.tb, SP-D binds minimally to the avirulent Mycobacterium smegmatis. SP-D binds predominantly to lipoarabinomannan from the virulent Erdman strain of M.tb, but not the lipoarabinomannan from M. smegmatis. The binding of SP-D to Erdman lipoarabinomannan is mediated by the terminal mannosyl oligosaccharides of this lipoglycan. Incubation of M.tb with subagglutinating concentrations of SP-D leads to reduced adherence of the bacteria to macrophages (62.7% of control adherence +/- 3.3% SEM, n = 8), whereas incubation of bacteria with surfactant protein A leads to significantly increased adherence to monocyte-derived macrophages. These data provide evidence for specific binding of SP-D to M. tuberculosis and indicate that SP-D and surfactant protein A serve different roles in the innate host response to this pathogen in the lung.

Agglutination↗
PubMed1996

Aggressive behavior on an inpatient geriatric unit.

1. Violent or aggressive behavior may be a consequence of poor frustration tolerance, ineffective individual coping, impulsivity, and real or imagined threats to the individuals territory, body space, or life. 2. It is ironic that at the same time that the numbers of elderly are increasing, available services are decreasing and the number of beds in nursing homes and rest homes are lower than in the past. 3. Nurses must look at the environment in which these patients function to develop strategies and techniques to maximize independence while decreasing aggression.

Aged↗
PubMed1996

Patients with an abnormal chest radiograph and latent tuberculosis.

Patients with latent tuberculosis characterized by a positive tuberculin (purified protein derivative) skin test and radiographic evidence of fibronodular changes or silicosis are at increased risk for the development of active tuberculosis. Before preventive therapy is initiated, the radiographic abnormalities must be differentiated from those representing active disease. According to recommendations from the American Thoracic Society and the Centers for Disease Control and Prevention, patients with latent tuberculosis who exhibit fibronodular changes or silicosis on chest radiographs should be given either isoniazid alone for one year or the combination of isoniazid and rifampin for four months, preferably with pyrazinamide for the first two months. Patients with similar radiographic findings and sputum or culture evidence of active tuberculosis require full multidrug therapy.

Algorithms↗
PubMed1991

Long term pulmonary impairment following a single exposure to methyl isocyanate.

Groups of guinea pigs were exposed for 3 hr to 6, 13, 19, 27, or 37 ppm of methyl isocyanate (MIC). Pulmonary performance was evaluated immediately postexposure and for a period of 1 year in the animals surviving 19 or 37 ppm of MIC. At 6 and 13 ppm deterioration of pulmonary performance was observed but complete recovery occurred within a few weeks. In those animals surviving 19 or 37 ppm some recovery occurred but a long lasting impairment of pulmonary performance was observed. One year after a single exposure to MIC these animals presented a condition best described as chronic obstructive lung disease. Using flow-volume measurements during air breathing and during CO2 challenge, animals surviving at 19 or 37 ppm presented typical abnormalities associated with airflow limitation along the conducting airways. One year after exposure lung hyperinflation was also present. At this time the poor ventilatory response to CO2 was due to mechanical limitation of lung expansion during inspiration and airflow limitation during expiration. The findings were similar to humans with severe obstructive lung disease. Microscopic examination substantiated the flow-volume measurements in that the main bronchi, small bronchi, and bronchioles were found to have an increase in dense fibrous tissue, while the alveolar level was characterized by destruction of alveolar walls and an increase in septal thickness. Thus a single exposure to MIC, if the concentration is high enough, is sufficient to induce permanent pulmonary toxicity.

Administration, Inhalation↗
PubMed1988

Uptake and distribution of 14C during and following exposure to [14C]methyl isocyanate.

Guinea pigs were exposed to [14C]methyl isocyanate (14CH3-NCO, 14C MIC) for periods of 1 to 6 hr at concentrations of 0.5 to 15 ppm. Arterial blood samples taken during exposure revealed immediate and rapid uptake of 14C. Clearance of 14C was then gradual over a period of 3 days. Similarly 14C was present in urine and bile immediately following exposure, and clearance paralleled that observed in blood. Guinea pigs fitted with a tracheal cannula and exposed while under anesthesia showed a reduced 14C uptake in blood indicating that most of the 14C MIC uptake in normal guinea pigs occurred from retention of this agent in the upper respiratory tract passages. In exposed guinea pigs 14C was distributed to all examined tissues. In pregnant female mice similarly exposed to 14C MIC, 14C was observed in all tissues examined following exposure including the uterus, placenta, and fetus. While the form of 14C distributed in blood and tissues has not yet been identified, these findings may help to explain the toxicity of MIC or MIC reaction products on organs other than the respiratory tract, as noted by several investigators.

Animals↗
PubMed1988

Inhibition of methyl isocyanate toxicity in mice by starvation and dexamethasone but not by sodium thiosulfate, atropine, and ethanol.

Effects of starvation (24 and 48 h), dexamethasone, sodium thiosulfate, atropine, and ethanol on the toxicity of methyl isocyanate (MIC) vapor, which escaped during the Bhopal accident of December 3, 1984, were studied in male Swiss-Webster mice. Toxicity to MIC appeared to be biphasic; majority of animals died between 1 and 2 d or between 7 and 21 d after exposure to 40 ppm MIC. Starvation (24 or 48 h) or an injection of 2 mg dexamethasone/kg prior to exposure inhibited the toxicity of MIC, especially during the first 6-7 d; administrations of sodium thiosulfate, alcohol, and atropine before or of dexamethasone after the exposure to MIC were ineffective. Starvation increased serum corticosterone levels. The antidotal effects of both starvation and dexamethasone might be due to suppression of the inflammatory response to MIC.

Animals↗
PubMed1987

Pulmonary effects of a polyisocyanate aerosol: hexamethylene diisocyanate trimer (HDIt) or Desmodur-N (DES-N).

Desmodur-N (DES-N) or hexamethylene diisocyanate trimer (HDIt), a biuret structure of hexamethylene diisocyanate, is a viscous liquid used for durable coatings and is applied by brushing or spraying. DES-N aerosol has been shown to be primarily a pulmonary irritant following a single exposure in mice. To explore the pulmonary effects of this agent further, groups of guinea pigs were exposed to concentrations ranging from 8 to 121 mg/m3 of DES-N for 3 hr. Prior to and following exposure, each animal was challenged with 10% CO2 in 20% O2 and 70% N2 to evaluate their pulmonary performance. Following a single exposure, these animals displayed a concentration-dependent increase in respiratory rate and decrease in tidal volume, as well as coughing and apnea. Their ventilatory response to 10% CO2 was abnormal and characteristic of a lung restriction response. Some airflow limitation was seen during expiration but this occurred more often during air breathing than during CO2 challenge. With daily exposures repeated for 11 consecutive days, guinea pigs began to adapt to the exposures as indicated by a return to a normal ventilatory response to CO2. This adaptation occurred within the first 5 days of exposures. From Days 6 to 11, there was a demonstrable effect, but the level of response was much less than that following the first exposure. No cumulative effect could be demonstrated with this polyisocyanate and the effect was found to be different than that for mono- or diisocyanates. Acceptable levels of exposure to this polyisocyanate for industrial workers are suggested.

Aerosols↗
PubMed1987

Reproductive toxicity of methyl isocyanate in mice.

The effects of methyl isocyanate (MIC) vapor on pregnancy and fertility were studied in mice in view of the reported increase in reproductive complications in Bhopal following the December 3, 1984, accident. The whole-body exposure of mice to 9 and 15 ppm MIC for 3 h on d 8 of gestation led to resorption of greater than 80% of implants. In more than 75% of MIC-exposed animals, all implants were lost. At these concentrations, MIC did not cause external malformations. However, there was evidence of an increase in visceral abnormalities and a decrease in fetal and placental weights and in fetal skeleton sizes. MIC disturbed the estrus cycle and decreased the mating and pregnancy rate of female mice. The mating performance of MIC-exposed male mice was also decreased. Exposure to MIC increased serum corticosterone levels of male and nonpregnant female mice. MIC exerted no significant effects on serum corticosterone and progesterone levels of pregnant mice if the pregnancy was retained but caused a significant decrease in the serum levels of these two hormones in animals that lost all the implants. These studies show that the effects of MIC in mice mimic many of the reproductive complications in Bhopal. The mechanism of the reproductive toxicity of MIC remains to be identified.

Adrenal Cortex Hormones↗
PubMed1987

Sensory and pulmonary irritation of methyl isocyanate in mice and pulmonary irritation and possible cyanidelike effects of methyl isocyanate in guinea pigs.

Methyl isocyanate (MIC) was evaluated for sensory and pulmonary irritation in mice. MIC was found to be both a potent sensory and pulmonary irritant in this species. From these results, a safe level of exposure for a period of 8 hr was estimated to be about 0.02 ppm for humans. Guinea pigs were also exposed to MIC for a single 3-hr exposure at a concentration of 37 ppm. During exposure to MIC, coughing was observed in all animals. Pulmonary function was evaluated immediately following exposure and intermittently on the next 35 days using CO2 challenges and flow-volume loops. Highly abnormal responses to CO2 were observed immediately after exposure in all animals. Six of the eight animals exposed to MIC died. In the two survivors, an apparent recovery was seen during the 5 days following exposure, but a worsening effect was observed at days 21 and 28, with a partial recovery at day 35. The data clearly demonstrated that the primary pulmonary effect of MIC was one of airways obstruction. Oxygen uptake and carbon dioxide output were also measured in the guinea pigs following exposure to MIC. No evidence of a cyanidelike effect was observed, in contrast to a severe depression of oxygen uptake following exposure to hydrogen cyanide.

Airway Obstruction↗
PubMed1987

Evaluation of sister chromatid exchange and cytotoxicity in murine tissues in vivo and lymphocytes in vitro following methyl isocyanate exposure.

The purpose of this study was to assess sister chromatid exchange (SCE) levels and cell cycle kinetics in various murine tissues following MIC exposure. Following exposure of mice to MIC, these parameters were measured in bone marrow and alveolar macrophages labeled with BrdUrd in vivo and in peripheral blood and spleen lymphocytes cultured in the presence of BrdUrd in vitro. Target concentrations of MIC were 2, 15, and 30 ppm (3 hr). Neither elevated SCE frequencies nor inhibition of cell cycling were evident in lipopolysaccharide (LPS)- or concanavalin A (ConA)-stimulated spleen lymphocytes, or in LPS-stimulated peripheral blood lymphocyte (PBL) cultures from mice exposed for 3 hr to MIC concentrations as high as 30.5 ppm. Inhibition of cell cycling and poor culture success rates were apparent in ConA-stimulated PBLs following MIC exposures as low as 2.3 +/- 0.4 ppm for 3 hr. At the lowest MIC dose employed, the cycling characteristics of bone marrow and alveolar macrophages were not altered, and SCE frequencies were at control levels. However, severe cell cycle inhibition was observed in these tissues at MIC concentrations of 15 ppm or greater. A marker of cytotoxicity at this dose was a high frequency (approximately 33-90%) of occurrence of first division cells containing a late-replicating Y chromosome. Despite its apparent cellular toxicity, MIC is not genotoxic as measured by SCE analysis in the tissues examined in this study.

Animals↗
PubMed1986

Sensory and pulmonary irritation with exposure to methyl isocyanate.

Methyl isocyanate (MIC) was tested for its potency as a sensory irritant and as a pulmonary irritant in mice. To evaluate sensory irritation, animals were exposed to MIC at concentrations between 0.5 and 7.6 ppm for a period of 90 min. A characteristic reflex decrease in respiratory rate indicating sensory irritation was observed. The concentration evoking a 50% decrease in respiratory rate (RD50) was found to be 1.3 ppm. To evaluate pulmonary irritation, animals were first anesthetized and fitted with a tracheal cannula. Following recovery from anesthesia, they were exposed to MIC at concentrations between 0.4 and 7.3 ppm for a period of 90 min. A characteristic decrease in respiratory rate indicating pulmonary irritation in tracheally cannulated (TC) mice was observed. The concentration evoking a 50% decrease in respiratory rate (RD50TC) was found to be 1.9 ppm. Thus, MIC was found to be a potent sensory and pulmonary irritant.

Animals↗
PubMed1985

An overview of occupational safety and health guidelines for Superfund sites.

An overview of the NIOSH occupational safety and health guidelines for Superfund activities is presented. Critical elements are outlined for site safety plans, site surveys and monitoring plans. The gathering of accurate and adequate information to prepare a plan of action to clean up abandoned hazardous waste sites is the first step and continues throughout any Superfund activity. Major emphasis is placed on selecting personal protective equipment with consideration for preventing heat stress. Decontamination is stressed to prevent exposure of other site workers as well as off-site personnel and the public. Worker training and medical monitoring are key components in a comprehensive occupational safety and health program for hazardous waste workers.

Communication↗