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Biomedical subjects

R Smith

Publications and source records attributed to R Smith.

At least 469 records · Page 26Linked to original sources
PubMed1997

Effect of the calcium antagonist felodipine as supplementary vasodilator therapy in patients with chronic heart failure treated with enalapril: V-HeFT III. Vasodilator-Heart Failure Trial (V-HeFT) Study Group.

BACKGROUND: Despite therapy with diuretics, ACE inhibitors and digoxin morbidity and mortality in heart failure remain high and might respond favorably to an additional vasodilator. METHODS AND RESULTS: Male patients (n=450) with chronic heart failure (cardiac dysfunction and impaired exercise performance) on optimal current therapy (97% enalapril, 89% diuretics) were randomly assigned to double-blind treatment with felodipine extended release (5 mg BID) or placebo for 3 to 39 months (average, 18 months). Felodipine significantly reduced blood pressure and, at 3 months, increased ejection fraction (2.1% versus -0.1% units in the placebo group, P=.001) and reduced plasma atrial natriuretic peptide levels (-2.9 versus 26.9 pg/mL in the placebo group, P=.01) but did not improve exercise tolerance, quality of life, or the need for hospitalization. During long-term follow-up, the favorable effects on ejection fraction and atrial peptide did not persist, but felodipine prevented worsening exercise tolerance and quality of life. In the felodipine and placebo groups, mortality (13.8% versus 12.8%, respectively) and hospitalization (43% versus 42%) rates were similar, and a higher incidence of peripheral edema was the only apparent side effect of felodipine therapy. CONCLUSIONS: Felodipine exerts a well-tolerated additional sustained vasodilator effect in patients with heart failure treated with enalapril, but the only possible long-term benefit was a trend for better exercise tolerance and less depression of quality of life in the second year of treatment. The drug appears to be safe but not clearly efficacious in patients with heart failure.

Adult↗
PubMed1997

Separation of extracts from biological tissues into polycyclic aromatic hydrocarbon, polychlorinated biphenyl and polychlorinated dibenzo-p-dioxin/polychlorinated dibenzofuran fractions prior to analysis.

A low-pressure liquid chromatography method is presented for separating polycyclic aromatic hydrocarbons (PAHs), polychlorinated biphenyls (PCBs) and polychlorinated dibenzo-p-dioxins/polychlorinated dibenzofurans (PCDDs/PCDFs) from biological tissue extracts. After removing lipid from extracts, the PAHs are separated from PCBs and PCDDs/PCDFs on a deactivated 13-24 microns silica gel column. The PCBs are subsequently separated from PCDDs/PCDFs by collecting the first fraction from an automated three column cleanup procedure for PCDDs/PCDFs. The complete method has been used to obtain high recoveries of the three compound classes for analysis by GC-electron capture detection (PCBs) or GC-MS (PAHs and PCDDs/PCDFs).

Animals↗
PubMed1997

Quantitative gas chromatography-mass spectrometry isomer-specific measurement of hydroxy fatty acids in biological samples and food as a marker of lipid peroxidation.

We have developed a capillary gas chromatography-mass spectrometry method for the quantitative analysis of individual positional isomers of monohydroxy fatty acids derived from linoleic, arachidonic, eicosapentaenoic, or docosahexaenoic acid. Peroxidation of a particular polyunsaturated fatty acid results already in a complex mixture of positional isomers of hydroperoxy and hydroxy fatty acids. Catalytic hydrogenation of lipid extracts produces stable saturated hydroxy lipids from the complex mixtures typical of oxidized biological samples, simultaneously simplifying the analytical problem and eliminating oxidation artifacts. After saponification and methylation, monohydroxy fatty acid methyl esters are purified by solid-phase extraction and partially resolved using a CP Sil 19 column following on-column derivatization of the hydroxy groups with tetramethylammonium hydroxide. The resulting methoxy fatty acid methyl esters are subjected to electron impact mass spectroscopy. Two characteristic ions are produced for each positional isomer. Quantitative measurements were achieved by using odd chain C17 and C19 monohydroxy fatty acids as internal standards. The limit of detection of individual hydroxy fatty acid isomers is dependent on the total number of ions monitored. Monitoring 11 pairs of ions simultaneously gives limits of detection of 10 ng. Sensitivity is much higher by monitoring fewer ions and as little as 0.2 ng of a single isomer can be detected. The method has been applied for the quantitative analysis of hydroxy (plus hydroperoxy) fatty acids in plasma, adipose tissue, oils, and foods. To date over 1000 samples have been analyzed using the method described in this paper.

Dietary Fats, Unsaturated↗
PubMed1997

Myelin proteolipid protein expressed in COS-1 cells is targeted to actin-associated surfaces.

The compact myelin sheath represents one of the largest expanses of membrane-membrane contact in the body and, in the central nervous system, requires the myelin proteolipid protein (PLP) for assembly. To determine whether the molecular properties of PLP promote membrane adhesion and direct its subcellular localization in the absence of oligodendrocyte-specific targeting mechanisms, PLP was expressed in COS-1 fibroblasts. Immunofluorescence staining indicated that PLP was translated effectively, transited the rough endoplasmic reticulum and Golgi apparatus, was delivered to the cell surface, and was endocytosed. In the plasma membrane, the PLP distribution was patchy and only sporadically coincided with sites of membrane-membrane contact between PLP-expressing cells. PLP was not randomly distributed, however, but correlated closely with microfilament locations in leading edge membranes and microvilli, as demonstrated by phalloidin double labeling. Our results indicate that even in non-myelinating cells, PLP can be concentrated in membranes associated with movement and growth, and suggest possible roles for the actin cytoskeleton in PLP localization. As PLP, DM20, and the DM20-like M6 protein all associate with actin-enriched membranes, this may be a common feature of PLP/DM20 gene family members.

Actins↗
PubMed1997

A recommended occupational exposure limit for formaldehyde based on irritation.

In recent years, several regulatory agencies and professional societies have recommended an occupational exposure limit (OEL) for formaldehyde. This article presents the findings of a panel of experts, the Industrial Health Foundation panel, who were charged to identify an OEL that would prevent irritation. To accomplish this task, they critiqued approximately 150 scientific articles. Unlike many other chemicals, a large amount of data is available upon which to base a concentration-response relationship for human irritation. A mathematical model developed by Kane et al. (1979) for predicting safe levels of exposure to irritants based on animal data was also evaluated. The panel concluded that for most persons, eye irritation clearly due to formaldehyde does not occur until at least 1.0 ppm. Information from controlled studies involving volunteers indicated that moderate to severe eye, nose, and throat irritation does not occur for most persons until airborne concentrations exceed 2.0-3.0 ppm. The data indicated that below 1.0 ppm, if irritation occurs in some persons, the effects rapidly subside due to "accommodation." Based on the weight of evidence from published studies, the panel found that persons exposed to 0.3 ppm for 4-6 h in chamber studies generally reported eye irritation at a rate no different than that observed when persons were exposed to clean air. It was noted that at a concentration of 0.5 ppm (8-h TWA) eye irritation was not observed in the majority of workers (about 80%). Consequently, the panel recommended an OEL of 0.3 ppm as an 8-h time-weighted average (TWA) with a ceiling value (CV) of 1.0 ppm (a concentration not to be exceeded) to avoid irritation. The panel believes that the ACGIH TLV of 0.3 ppm as a ceiling value was unnecessarily restrictive and that this value may have been based on the TLV Committee's interpretation of the significance of studies involving self-reported responses at concentrations less than 0.5 ppm. The panel concluded that any occupational or environmental guideline for formaldehyde should be based primarily on controlled studies in humans, since nearly all other studies are compromised by the presence of other contaminants. The panel also concluded that if concentrations of formaldehyde are kept below 0.1 ppm in the indoor environment (where exposures might occur 24 h/d) this should prevent irritation in virtually all persons. The panel could not identify a group of persons who were hypersensitive, nor was there evidence that anyone could be sensitized (develop an allergy) following inhalation exposure to formaldehyde. The panel concluded that there was sufficient evidence to show that persons with asthma respond no differently than healthy individuals following exposure to concentrations up to 3.0 ppm. Although cancer risk was not a topic that received exhaustive evaluation, the panel agreed with other scientific groups who have concluded that the cancer risk of formaldehyde is negligible at airborne concentrations that do not produce chronic irritation.

Animals↗