A solid-phase approach to analogues of the antibiotic mureidomycin.
A library of 80 analogues of the antibacterial compound mureidomycin was prepared using solid-phase chemistry techniques.
Anti-Bacterial Agents↗
Biomedical subjects
G Kennedy
Publications and source records attributed to G Kennedy.
Team management of patients with heart failure: A statement for healthcare professionals from The Cardiovascular Nursing Council of the American Heart Association.
Explore the source record for details and available documents.
Heart Failure↗
Studies on the novel anti-staphyloccal compound nematophin.
A number of analogues of the recently described compound nematophin were prepared and studied for antibacterial activity. The 2-phenyl derivative was found to exhibit exceptional activity against methicillin resistant Staphylococcus aureus (MRSA) whereas the isosteric benzimidazole analogue was much less active.
Anti-Bacterial Agents↗
Pulse loss and counting statistics with a digital spectrometer
A commercially available digital gamma-ray spectrometer is tested at high count rates using a germanium detector and appropriate pulse processing parameters. Correction for pulse loss due to dead time and pileup is done by extending the live time according to the Gedcke-Hale method. The accuracy of this count-loss correction technique is tested experimentally up to saturation count rates. Also the statistical uncertainty applicable to the total number of counts in arbitrary regions of interest in gamma-ray spectra is studied experimentally, for measurements at fixed real time as well as at fixed live time. The results are similar to those found with traditional spectrometers using analog technology.
Journal Article↗
Identification of neonates at risk of developing feeding problems in infancy.
The increased survival of sick and preterm neonates may be associated with long-term problems which must be recognised and managed if outcome is to be optimised. In a prospective study of 35 neonates (median gestational age at birth 34 weeks) admitted to a neonatal intensive care unit over a 3-month period, we have documented a high incidence (14 of 35) of immature or abnormal feeding patterns when infants were assessed at 36 to 40 weeks postmenstrual age. Neonates with prolonged respiratory support and delayed enteral and oral feeding were most affected. Compared with neonates who have normal initial feeding assessments, neonates with disorganised or dysfunctional feeding were six times more likely to vomit and three times more likely to cough when offered solid food at 6 months of age. At 12 months of age significant differences were also found in tolerating lumpy food and enjoying mealtimes. We hypothesise that these feeding problems contribute to failure to thrive and psychosocial distress after discharge from the neonatal unit and propose potential neonatal measures to reduce their incidence.
Enteral Nutrition↗
Assessment of exposure to manganese in welding operations during the assembly of heavy excavation machinery accessories.
Welder exposure to metals in various industrial sectors is poorly characterized. We had the opportunity to carry out an exploratory study to characterize manganese exposure in welding operations in a recently established Quebec factory that assembled accessories for heavy excavation machinery. Ten workers were sampled for total manganese for at least two consecutive days out of three followed by two consecutive days for respirable manganese (with a size selective sampler with a median cut-off of 4 microns), during a typical week in the summer of 1998. Parts being welded were characterized as large or small. Small parts were those being welded on tables during subassembly. Workers were divided into two groups according to the parts they were welding. Seventy-eight percent of the total manganese exposure levels of welding operations during the assembly of large accessories of heavy excavation machinery exceeded the manganese American Conference of Governmental Industrial Hygienists (ACGIH) threshold limit value (TLV) of 0.20 mg/m3 (GM 0.24 mg/m3, n = 14) while none exceeded the TLV during the assembly of small pieces (GM 0.06 mg/m3, n = 8). Welding operations during the assembly of large heavy excavation machinery accessories may pose a significant health hazard. Considering the importance of task-related variables affecting exposure among workers, further studies are needed to better characterize exposure determinants of welding operations during the assembly of heavy excavation machinery accessories.
Adult↗
A controlled clinical trial of sertraline in the treatment of depression in nursing home patients with late-stage Alzheimer's disease.
A sample of 31 female nursing home patients with late-stage Alzheimer's disease participated in a double-blind clinical trial of the antidepressant medication sertraline. Measures of depression included various objective scales and two measures of facial expressions of emotion coded during a semistructured interview using a facial affect coding system. Repeated-measures ANOVAs at baseline and at the 8-week endpoint indicated that on all measures, both the treatment and placebo groups improved over time, with three of six measures showing a significant time effect. The "knit-brow" facial measure approached significance for a Treatment x Time effect. Thus, sertraline had no significant benefits over placebo. However, if, as we hypothesize, the knit-brow response is more sensitive to signs of depression in advanced dementia, our study justifies the further investigation of the use of sertraline in this population.
Aged↗
A search for trace elements in some human intracranial tumors by instrumental neutron activation analysis.
A investigation was undertaken to measure the presence of trace elements in some intracranial tumors using the instrumental neutron activation analysis technique. The following 20 minor and trace elements were investigated: Na, Mg, Al, P, Cl, K, Ca, Cr, Mn, Fe, Co, Cu, Zn, As, Se, Br, Rb, Sb, I, and Cs. Our results are compared with other trace element analyses in human brain tissue.
Adult↗
Ankylosing spondylitis and the shoulder: commonly involved but infrequently disabling.
OBJECTIVE: To undertake 2 independent studies of shoulder involvement in patients with ankylosing spondylitis (AS) and assess the frequency of shoulder pain, stiffness, and loss of movement and function. To evaluate and correlate shoulder symptoms, function, range of movement, and radiology. METHODS: A cross sectional design was used in both studies. In Study A, a self-administered questionnaire was sent to members of the National Ankylosing Spondylitis Society of the UK and patients attending the Royal National Hospital for Rheumatic Diseases. In Study B, a clinical assessment of 88 patients with AS was undertaken that included a radiological assessment of 26 consecutive patients. RESULTS: In Study A, 15.2% and 13.8% of subjects had severe/very severe shoulder pain or stiffness, respectively. In Study B the corresponding findings were 9.6% and 17.6%. Patient reported disability associated with shoulder involvement was uncommon. Study A revealed that patients with severe/very severe shoulder pain were more likely to have significant hip and knee involvement. Significant shoulder involvement appears to be as common as involvement of the hip joint. In Study B radiological changes were common, being present in 31% of patients, but were often minor. There was a significant correlation between the sum of the stiffness, abduction, and flexion scores for both shoulders and the total radiological score (r = 0.87; p<0.001). CONCLUSION: The results suggest that shoulder symptoms and loss of shoulder mobility are common in patients with AS, and correlate with higher pain scores and influence of AS on their lives as assessed by the Arthritis Impact Measurement Scale, but are rarely disabling. Involvement of the shoulder joint in AS correlates with involvement of other peripheral joints as well as the extent of radiographic change on shoulder radiographs.
Adult↗
Elevated levels of soluble E-selectin in diabetic patients with severe symptomatic peripheral arterial occlusive disease requiring angioplasty. A possible role in diabetic vascular disease?
BACKGROUND: To study levels of E-selectin in patients with peripheral arterial occlusive disease who were undergoing percutaneous transluminal angioplasty. METHODS: Experimental design and setting: Cross sectional case control study, conducted in a teaching hospital. SUBJECTS: Seven patients with type-2 (non-insulin dependent) diabetes mellitus undergoing transluminal angioplasty for symptomatic peripheral arterial occlusive disease, had blood tests for sE-selectin measurement, and were compared to a similar groups of age and sex matched non-diabetic patients with arteriopathy who are undergoing the same procedure. Also evaluated were a group of diabetic patients and healthy non-diabetics with no peripheral arterial disease. RESULTS: The levels of sE-selectin in the two diabetic groups were significantly higher than the non-diabetic groups measuring at 77 ng/ml (53-120) and 79 ng/ml (43-98) (median, range) vs 54 ng/ml (24-104) in the non-diabetic with arteriopathy, and 42 ng/ml (35-66) in the normal healthy controls, p<0.04, p<0.003 respectively, Mann Whitney "U" test. CONCLUSIONS: We have demonstrated significantly high values of soluble E-selectin in patients with diabetes mellitus requiring angioplasty for symptomatic peripheral arterial occlusive disease. This suggests that sE-selectin may be involved in the diabetic angiopathic process. It may act as a precursor for smooth muscle proliferation.
Angioplasty, Balloon↗
A case-control study of toenail selenium and cancer of the breast, colon, and prostate.
To study the possible role of dietary and supplementary selenium intake in the etiology of cancer, we carried out a case-control study of breast, colon, and prostate cancer in Montreal between 1989 and 1993. In this study, we were able to interview a total of 1,048 incidence cases of colon (402), breast (414) and prostate (232) cancer subjects and 688 population-based controls matched for age and gender. Of these, a total of 501 cancer cases and 202 controls produced toenail samples for their selenium concentrations, which were determined by neutron activation analysis. We found no association between toenail selenium and breast cancer (odds ratio [OR], 0.72; 95% confidence interval [CI], 0.4-1.31) or prostate cancer (OR, 1.14; 95% CI, 0.46-2.83), though we did observe a statistically significant inverse association between toenail selenium level and the risk of colon cancer for both genders combined (OR, 0.42; 95% CI, 0.19-0.93; P = .009) and for female subjects (P = .050). We also found that nonsmoker case and control subjects had higher selenium in their toenail samples. This could be due either to the nature of tobacco, which reduces selenium absorption, or to smokers' consumption of certain foods containing less selenium. Further epidemiologic studies are required to clarify the role of selenium in the etiology of certain cancers.
Adolescent↗
Potential of dandelion (Taraxacum officinale) as a bioindicator of manganese arising from the use of methylcyclopentadienyl manganese tricarbonyl in unleaded gasoline.
Methylcyclopentadienyl manganese tricarbonyl (MMT) is an organic manganese (Mn) compound currently added to unleaded gasoline in Canada. It has been suggested that the combustion of MMT containing Mn could cause various deleterious health effects in animals and humans at very high concentrations. This study evaluates the potential of dandelions (Taraxacum officinale) as bioindicators of Mn environmental contamination. Samples were picked at three different distances from a highway: a highly exposed site (E++), a lightly exposed site (E+) and a control site (E), located respectively at 10, 50 and 100 m. The total Mn, Mg, Ca, Al, Fe and Zn concentrations were measured in the soils and in the plants (flower, stem, leaves and root) by neutron activation analysis. Exchangeable Mn was measured in soils by atomic absorption spectrophotometry. Mn concentrations of the different parts of the plant and exchangeable Mn in soils were not correlated with distance from the roadway and, thus, do not seem to be a sensitive indicator of Mn contamination. Soil Mn concentrations were correlated with distance from the roadway. This suggests the hypothesis that the environmental fate of Mn from MMT sources could be associated with an increased total Mn in soil but does not lead to an increase in exchangeable Mn.
Air Pollutants↗
Analogues of 4,5-bis(3,5-dichlorophenyl)-2-trifluoromethyl-1H-imidazole as potential antibacterial agents.
A preliminary exploration of analogues of 4,5-bis(3,5-dichlorophenyl)-2-trifluoromethyl-1H-imidazole, 1, as novel antibacterial agents was carried out to determine the basic features of the structure responsible for the observed biological activity. The presence of two aryl rings, the imidazole NH and either a good electron withdrawing group or an aldehyde or amino group at C-2 were required for good levels of activity against methicillin resistant Staphylococcus aureus (MRSA).
Anti-Bacterial Agents↗
Comparison of the relative and k0 methods for the standardization of NAA with stable low-flux reactors.
The k0 standardization method was adapted for NAA with stable low-flux reactors where flux monitors are not needed. The modified k0 method offers the convenience of the use of libraries of sensitivity constants. It was compared to the relative method for 52 elements using a SLOWPOKE reactor and 6 counting geometries. The sensitivity constants determined from k0 values were found to be as accurate or more accurate than those measured with standards. NAA with this modified k0 method should be accurate to 3% for light elements and 5% for heavy elements.
Equipment and Supplies↗
Effects of reactor temperature and sample mass on the activation of biological and geological materials with a SLOWPOKE reactor.
Neutron activation analysis with a SLOWPOKE reactor relies on the stability of the neutron flux in the irradiation sites. Flux monitors were irradiated to measure the flux variation with the reactor temperature and with the amount of moderator in the irradiation vial. The thermal flux decreased by 2.7% for a 10 degrees C increase in reactor temperature. The thermal flux increased by up to 8% and the fast flux decreased by up to 13% depending on sample size and hydrogen content.
Biological Assay↗
Environmental contamination and human exposure to manganese--contribution of methylcyclopentadienyl manganese tricarbonyl in unleaded gasoline.
The organomanganese compound MMT (methylcyclopentadienyl manganese tricarbonyl), an antiknock additive in unleaded gasoline, has been used in Canada since 1976. Indeed, Canada is the only country where MMT is almost exclusively used. In October 1995, by court decision the Environmental protection Agency (EPA) granted Ethyl's waiver for the use of MMT in the United States. Paradoxically, in 1997 the federal government of Canada adopted a law (C-29) that banned both the interprovincial trade and the importation for commercial purposes of manganese-based substances, including MMT. However, MMT is currently widely used in Canada because of substantial stockpiling, and six Canadian provinces are challenging the law in the courts. Moreover, MMT has been approved for use in Argentina, Australia, Bulgaria, Russia, and conditionally, in New Zealand. It has been suggested by some scientists that combustion of MMT may be a significant source of exposure to inorganic Mn in urban areas. The crucial question is whether Mn contamination from industrial sources combined with the additional contamination that would result from the widespread use of MMT would lead to toxic effects. Our research efforts have attempted to assess the environmental/ecosystem Mn contamination arising from the combustion of MMT in abiotic and biotic systems as well as human exposure. The experimental evidence acquired so far provides useful information on certain environmental consequences of the use of MMT as well as raising a number of questions. Our results gave evidence indicating that roadside air, soils, plants, and animals may be contaminated by Mn. As well, some specific groups of the population could have a higher level of exposure to Mn. Nevertheless, the levels of exposure remain below international guide values. Further studies and further characterization of dose-response relationships are thus needed to provide successful implementation of evidence-based risk-assessment approaches.
Canada↗
Evaluation of the fluorometric protein phosphatase inhibition assay in the determination of okadaic acid in mussels.
The protein phosphatase inhibition assay for okadaic acid, the major DSP toxin, modified to use the fluorescence substrates methylumbelliferyl phosphate (MUP) and fluorescein diphosphate (FDP), was compared to the assay using p-nitrophenylphosphate (p-NPP) and the bioluminescence assay using luciferin phosphate (L-P). Under the standard assay conditions used okadaic acid inhibited the enzyme activity dose-dependently with IC50 values of 1.5 nM (MUP) and 1.2 nM (FDP). This compares to IC50 values of 0.9 and 6 nM using L-P and p-NPP respectively. CDP-star, a chemiluminescence substrate, was not hydrolysed by the enzyme. Decreasing the enzyme concentration lowered the IC50 for the colorimetric method (IC50=2 nM [p-NPP], 0.75 nM enzyme) but no shift was observed with fluorimetry. However at enzyme concentrations < 1.5 nM (standard assay) the error margin was too great for routine analysis. The method using fluorimetry allowed detection of okadaic acid concentrations to levels < or = 1 microg/100 g of mussel tissue which is well below the limit of 20 microg/100 g (mouse bioassay) set by some regulatory agencies. Determination of the toxin content in naturally contaminated mussels in three separate experiments gave coefficients of variance ranging from 16 to 29% (MUP) and from 8 to78% (p-NPP). Multicomparison studies showed that concentrations of okadaic acid in naturally contaminated mussel samples determined by fluorescence generally agreed with those obtained using ELISA and LC-MS procedures, and with the mouse bioassay. However using the mouse bioassay as the standard, values determined by the ELISA, PP-2A and LC-MS all scored false negative results compared to those for the mouse bioassay in the range 20-40 microg/100 g mussel, and at the limit of the mouse bioassay the values by the other three methods were substantially less. With few exceptions the methods scored okadaic acid with highest to lowest values in the following order: mouse bioassay > ELISA > PP-2A > LC-MS. The fluorimetric assay was both more sensitive and accurate than the colorimetric assay (the latter showed a propensity towards false positives in the region 20 microg/100 g), and the moderate increase in equipment cost appears to be outweighed by the performance of the method.
Animals↗
Endothelial activation and response in patients with hand arm vibration syndrome.
BACKGROUND: Hand-arm vibration syndrome (HAVS) is a form of secondary Raynaud's phenomenon (RP) of occupational origin. In other forms of RP, blood and blood vessel wall interaction is one factor in the pathophysiology. Cytokines and cell adhesion molecules both play an important role in this interaction, and basal vascular tone and vasodilatation are regulated by nitric oxide. METHODS: Blood flow responses to acetylcholine (ACh) and sodium nitroprusside (SNP) and levels of soluble intercellular adhesion molecule-1 (sICAM-1) and the inflammatory cytokine interleukin 8 (IL-8) were measured in eight male patients with vibration white finger disease, which is part of HAVS, and in eight healthy matched male control subjects. RESULTS: sICAM-1 levels were statistically higher (P = 0.02, Mann-Whitney U-test) and IL-8 levels (P < 0.01, Mann-Whitney) were significantly lower in the patient group. The patients with HAVS had significantly reduced vascular responses to SNP (P < 0.05, ANOVA). CONCLUSIONS: In this study, we reveal differences in vascular responses to SNP that suggest there may be an impairment of the smooth muscle response to nitric oxide in patients with HAVS. The increase in sICAM-1 that occurs in patients with HAVS suggests that leucocyte adhesion is increased and that adherent neutrophils may contribute to the microvascular damage seen in this disease. The impeded flow of blood cells through the microcirculation may result in the low levels of circulating IL-8 due to the cytokine binding to erythrocytes. The possible role of NO activity in HAVS warrants further investigation.
Acetylcholine↗