Evaluation of high dose N- Acetylcysteine on airway inflammation and quality of life outcomes in adults with bronchiectasis: A randomised placebo-controlled pilot study.

BACKGROUND: High dose N acetylcysteine (NAC), a mucolytic, anti-inflammatory and antioxidant agent has been shown to significantly reduce exacerbations, and improve quality of life in placebo controlled, double blind randomised (RCT) studies in patients with COPD, and in an open, randomised study in bronchiectasis. In this pilot, randomised, double-blind, placebo-controlled study, we wished to investigate the feasibility of a larger clinical trial, and the anti-inflammatory and clinical benefits of high dose NAC in bronchiectasis. AIMS: Primary outcome: to assess the efficacy of NAC 2400 mg/day at 6 weeks on sputum neutrophil elastase (NE), a surrogate marker for exacerbations. Secondary aims included assessing the efficacy of NAC on sputum MUC5B, IL-8, lung function, quality of life, and adverse effects. METHODS: Participants were randomised to receive 2400 mg or placebo for 6 weeks. They underwent 3 visits: at baseline, week 3 and week 6 where clinical and sputum measurements were assessed. RESULTS: The study was stopped early due to the COVID pandemic. In total 24/30 patients were recruited, of which 17 completed all aspects of the study. Given this, a per protocol analysis was undertaken: NAC (n = 9) vs placebo (n = 8): mean age 72 vs 62 years; male gender: 44% vs 50%; baseline median FEV11.56 L (mean 71.5 % predicted) vs 2.29L (mean 82.2% predicted). At 6 weeks, sputum NE fell by 47% in the NAC group relative to placebo (mean fold difference (95%CI: 0.53 (0.12,2.42); MUC5B increased by 48% with NAC compared with placebo. Lung function, FVC improved significantly with NAC compared with placebo at 6 weeks (mean fold difference (95%CI): 1.10 (1.00, 1.20), p = 0.045. Bronchiectasis Quality of life measures within the respiratory and social functioning domains demonstrated clinically meaningful improvements, with social functioning reaching statistical significance. Adverse effects were similar in both groups. CONCLUSION: High dose NAC exhibits anti-inflammatory benefits, and improvements in aspects of quality of life and lung function measures. It is safe and well tolerated. Further larger placebo controlled RCT's are now warranted examining its role in reducing exacerbations.

Use of a leucocyte filter to remove tumour cells from intra-operative cell salvage blood.

SUMMARY: The intra-operative blood loss of 50 consecutive gynae-oncology patients undergoing surgery for endometrial, cervical or ovarian cancer was cell salvaged and filtered. In each case blood samples were taken from the effluent tumour vein, a central venous line, the cell saver reservoir, the cell salvage re-transfusion bag after processing but before filtration and from the cell salvage re-transfusion bag after processing and filtration. Samples were examined using immunohistochemical monoclonal antibody markers for epithelial cell lines. Viable, nucleated malignant cells were detected in 2/50 central venous samples, 34/50 reservoir samples and 31/50 unfiltered cell salvaged samples. After passage through a Pall RS leucocyte depletion filter no remaining viable, nucleated malignant cells were detected in any sample. The clinical risks of cell salvage in these circumstances should be reviewed in the light of the risks of allogeneic blood transfusion.

Gynaecological oncology perspective on management of the menopause.

UNLABELLED: Treatment for gynaecological cancer may ablate ovarian function through surgery (oophorectomy), radiotherapy or chemotherapy. Bilateral oophorectomy or surgical menopause results in an immediate menopause which may be intensely symptomatic in young women. Also oestrogen deficiency before the age of 40 increases the risk of osteoporosis and cardiovascular disease. This article will describe the use of oestrogen and non-oestrogen-based treatments as well as alternative and complementary therapies in gynaecological cancer survivors. AIMS: To review the use of oestrogen and non-oestrogen-based treatments as well as alternative and complementary therapies in gynaecological cancer survivors in whom ovarian function has been ablated through surgery (oophorectomy), radiotherapy or chemotherapy. METHODS: Literature search using PubMed for indexed articles. RESULTS: Ovarian, cervical, vaginal and vulval cancers are not oestrogen dependent conditions and oestrogen replacement is not contraindicated. However, there is some doubt with regard to endometrioid ovarian cancer and endometrial carcinoma is often listed in data sheets as an absolute contra-indication to hormone replacement therapy. Progestogens may be effective in treating vasomotor symptoms. A variety of agents are available for the prevention and treatment of osteoporosis and all except parathyroid hormone and strontium ranelate act mainly by inhibiting bone resorption. There is little scientific evidence that complementary and alternative therapies can help menopausal symptoms or conserve bone mass and there are no safety data in women with gynaecological cancer. CONCLUSIONS: Oestrogen-based therapies are the treatments of choice in young women with a premature menopause since oestrogen deficiency before the age of 40 increases the risk of osteoporosis and cardiovascular disease.

Intra-operative blood salvage in abdominal trauma: a review of 5 years' experience.

We performed a retrospective audit of 1235 patients presenting between 1992 and 1997, following the introduction of intra-operative blood salvage at our hospital. Twenty-two cases of severe abdominal trauma requiring emergency laparotomy and intra-operative blood salvage were identified. The impact of intra-operative blood salvage in aiding resuscitation and reducing demand on allogeneic blood supplies is discussed.

Molecular characterization of a neuronal low-voltage-activated T-type calcium channel.

The molecular diversity of voltage-activated calcium channels was established by studies showing that channels could be distinguished by their voltage-dependence, deactivation and single-channel conductance. Low-voltage-activated channels are called 'T' type because their currents are both transient (owing to fast inactivation) and tiny (owing to small conductance). T-type channels are thought to be involved in pacemaker activity, low-threshold calcium spikes, neuronal oscillations and resonance, and rebound burst firing. Here we report the identification of a neuronal T-type channel. Our cloning strategy began with an analysis of Genbank sequences defined as sharing homology with calcium channels. We sequenced an expressed sequence tag (EST), then used it to clone a full-length complementary DNA from rat brain. Northern blot analysis indicated that this gene is expressed predominantly in brain, in particular the amygdala, cerebellum and thalamus. We mapped the human gene to chromosome 17q22, and the mouse gene to chromosome 11. Functional expression of the channel was measured in Xenopus oocytes. Based on the channel's distinctive voltage dependence, slow deactivation kinetics, and 7.5-pS single-channel conductance, we conclude that this channel is a low-voltage-activated T-type calcium channel.

Burial and seed survival in Brassica napus subsp. oleifera and Sinapis arvensis including a comparison of transgenic and non-transgenic lines of the crop.

The creation of transgenic plants through genetic engineering has focused interest on how the fitness of a plant species may be altered by small changes in its genome. This study concentrates on a key component of fitness: persistence of seeds overwinter. Seeds of three lines of oilseed rape (Brassica napus subsp. oleifera DC Metzger) and of charlock (Sinapis arvensis L.) were buried in nylon mesh bags at two depths in four habitats in each of three geographically separated sites: Cornwall, Berkshire and Sutherland. Seeds were recovered after 12 and 24 months. Charlock exhibited much greater seed survival (average 60% surviving the first year and 32.5% surviving the second year) than oilseed rape (1.5% surviving the first year and 0.2% surviving the second) at all sites. Charlock showed higher survival at 15 cm burial than 2 cm burial at certain sites, but oilseed rape showed no depth effect. Different genetic lines of oilseed rape displayed different rates of seed survival; non-transgenic rape showed greater survival (2%) than the two transgenic lines, one developed for tolerance to the antibiotic kanamycin (0.3%) and one for tolerance to both kanamycin and the herbicide glufosinate (0.25%). The absolute and relative performances of the different genetic lines of oilseed rape were context specific, illustrating the need to test hypotheses in a wide range of ecological settings.

Isolation of the major component in white snakeroot that is toxic after microsomal activation: possible explanation of sporadic toxicity of white snakeroot plants and extracts.

Tremetone, the major toxic component in white snakeroot (Eupatorium rugosum Houtt) extracts, was isolated following an in vitro bioactivity assay. Microsomal activation was required to produce a product toxic to murine melanoma (B16F1) cells as well as five other mammalian cell cultures. The metabolic activation product(s) of tremetone is suspected to be responsible for the toxic activity of the plant. Tremetone is also smoothly converted to dehydrotremetone in the plant and cell free homogenates, and readily decomposes to dehydrotremetone in extracts. Dehydrotremetone is not toxic even after microsomal activation. The efficient conversion of tremetone to dehydrotremetone may explain why white snakeroot plant material and extracts have varied activities, and why a previous claim that tremetone was responsible for the toxic activity of white snakeroot was withdrawn. Rayless goldenrod extracts show the same toxic activity as white snakeroot and the toxic activity of rayless goldenrod is most likely due to tremetone.

Experimental analysis of sapphire contact probes for Nd-YAG laser angioplasty.

Laser angioplasty may offer percutaneous recanalization of occluded vessels where conventional guidewire and balloon techniques fail. Metal laser thermal angioplasty probes may, however, cause excessive thermal damage due to high tip temperatures (greater than 400.C). Therefore, contact probes made from artificial sapphire crystal designed for general laser surgery are currently being evaluated for use in laser angioplasty with continuous wave Nd-YAG energy. The sapphire modifies the laser energy in various ways, and this paper examines the physical characteristics of five types of rounded sapphire probe (SMTR, MTR, MTRL, OS, LT) and how these properties are affected by clinical usage. The laser beam profile emitted by these probes demonstrates a focal spot 1-2 mm in front of the tip. However, the forward transmission of Nd-YAG energy through the sapphires varied (SMTR, 85%; MTR, 83%; MTRL, 75%; OS, 54%; LT, 69%). Probe heating occurs owing to energy absorption within the sapphire. The surface temperature of the sapphires was measured in air by infrared thermography and the hottest region within the probes localized by an isothermographic technique. At energy settings used clinically (20 J, 10 watts for 2 s) the SMTR, MTR, and MTRL probes exhibited higher temperature rises (94-112.C) than the OS and LT probes (30.C), and heating was localized to the front surface of the former probes. Peak sapphire temperatures remained lower than those of metal probes even at higher energies. After clinical use, the MTR probe demonstrated reduced transmission, beam defocusing, and increased heating, due to surface pitting. Thus, recanalization with sapphire probes occurs by a combination of photothermal and contact thermal effects that are localized to the probe tip and may reduce the degree of thermal injury associated with metal probes. Understanding these basic properties is important to the application and development of contact probes for laser recanalization.

Identification of t-PA as the major active plasminogen activator in human milk.

Human colostrum and milk contain high levels of plasminogen activator when compared with blood. These levels are inversely related to the duration of lactation and the activity appears to be due to tissue type plasminogen activator present in multiple (65-190 Kd) molecular weight forms.

Fertilizer calcium as a factor affecting the voluntary intake, digestibility and retention time of pangola grass (Digitaria decumbens) by sheep.

1. Pangola grass (Digitaria decumbens) grown with and without calcium fertilizer was cut at three stages of regrowth to measure voluntary intake of dry matter (DM) and digestibility of various components of the dried-grass diet by sheep kept in metabolism crates. To determine the extent of a simple Ca deficiency half the sheep on each diet was supplemented with 1-4 g Ca/d. Retention times of the various dietary components in the reticulo-rumen were also determined. 2. Feeding a Ca supplement had no effect on voluntary intake or digestibility. 3. Ca fertilizer increased the Ca content of the grass from 2-2 to 3-8 g/kg DM and DM digestibility from 0-455 to 0-476 (P less than 0-01) due to an increase in the digestibility of the hemicellulose. 4. Voluntary intake was increased from 38-8 to 43-2 g/kg body-weight0.75 per d by Ca fertilizer due to an 18% reduction in the period of time the DM was retained in the reticulorumen. 5. Regressions relating voluntary intake to DM digestibility for the Ca-fertilized and control grass were significantly different (P less than 0-01). When compared at the same DM digestibility the voluntary intake of the Ca-fertilized grass was 2-6 g/kg body-weight0.75 per d higher than that of the control. 6. It was concluded that Ca fertilizer increased both DM digestibility and voluntary intake as a result of changes in the structural composition of the grass and not by a simple increase in the Ca content of the diet.