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M Kirk

Publications and source records attributed to M Kirk.

At least 73 records · Page 4Linked to original sources

Analysis of plasma isoflavones by reversed-phase HPLC-multiple reaction ion monitoring-mass spectrometry.

A HPLC-MS procedure for the rapid, sensitive and specific measurement of the isoflavones, daidzein, dihydrodaidzein, O-desmethylangolensin and genistein, in human plasma has been developed. Synthetic radiolabeled genistein conjugates were used for evaluation of optimum conditions for solid phase extraction. Biochanin A was added to plasma as a recovery marker for isoflavones and phenolphthalein glucuronide and 4-methylumbelliferone sulfate were added to ensure completeness of hydrolysis with beta-glucuronidase/sulfatase. Isoflavones in plasma extracts were separated using an isocratic HPLC method and analyzed by negative ion multiple reaction ion monitoring-mass spectrometry using a heated nebulizer-atmospheric pressure chemical ionization interface. Using plasma samples from four subjects consuming two servings a day of an isolated soy protein beverage for 14 days, the mean plasma genistein and daidzein concentrations were 556 and 345 nM, respectively. Within assay and between assay coefficients of variation for measurement of daidzein and genistein in five aliquots of the same plasma sample were 8.51% and 7.76%, and 5.98% and 6.12%, respectively.

Beverages↗

Selective detection and site-analysis of O-GlcNAc-modified glycopeptides by beta-elimination and tandem electrospray mass spectrometry.

Over the past decade, a number of nuclear and cytoplasmic proteins have been identified that are modified by single N-acetylglucosamine residues attached to the hydroxyl side chain of serines or threonines (O-GlcNAc). O-GlcNAc is a dynamic modification and therefore may act in a regulatory capacity analogous to phosphorylation. To undertake site-directed mutagenesis studies of O-GlcNAc's function, it is necessary to identify the sites of glycosylation on various proteins. The current method of site mapping, which involves galactosyltransferase labeling, generation of glycopeptides by proteolysis, purification by several rounds of HPLC, and gas-phase and manual Edman sequencing, is very tedious and requires about 10 pmol of pure, labeled glycopeptide. In this report, synthetic glycopeptides were generated and used to demonstrate that O-GlcNAc-modified peptides can be rapidly identified in complex mixtures by HPLC-coupled electrospray mass spectrometry due to the partial loss of the O-linked glycan (204 amu) at a modest orifice potential. Furthermore, the exact site of glycosylation was directly identified in the low picomole range by collision-induced dissociation (CID) of the glycopeptide after removal of the O-GlcNAc by alkaline beta-elimination. The conversion of glycosylserine to 2-aminopropenoic acid (2-ap) by beta-elimination both decreased the mass of the glycopeptide by 222 amu and resulted in a CID fragment ion representing the loss of 69 amu (2-ap) instead of 87 amu (Ser) at the position of the glycosylserine. Finally, we tested this method on an identical synthetic, alpha-linked O-GalNAc-modified peptide. Like O-GlcNAc, the O-GalNAc moiety was selectively removed at a modest orifice potential; however, the beta-elimination conditions that efficiently removed the O-GlcNAc only liberated about 20% of the O-GalNAc. We conclude that the selectivity and the sensitivity of this method will make it a powerful tool for determining the sites of O-GlcNAc modification on proteins of low abundance such as transcription factors and oncogenes.

Acetylglucosamine↗

The role of type I collagen in the regulation of the osteoblast phenotype.

Evidence from a variety of sources indicates that the extracellular matrix forms an important part of a feedback loop governing the migration, proliferation, and differentiation of the cells that produce it. In keeping with this, we showed previously that the extracellular matrix of a multipotential mesenchymal clonal cell line (ROB-C26) induced to differentiate into a more osteoblastic cell type by the addition of exogenous retinoic acid produces an extracellular matrix capable of osteoinductive activity in vivo and of stimulating alkaline phosphatase activity in vitro. Since type I collagen is the major structural component of this extracellular matrix, we sought to determine whether and to what extent this protein is responsible for the previously observed inductive/stimulatory activity. To this end, C26 cells are cultured on plastic, in the presence of retinoic acid, on a type I collagen film, or on an extracellular matrix from retinoic acid-treated C26 cells, and cell differentiation is assessed by measuring changes in the abundance of a number of osteoblast-related mRNAs. These determinations are made by RNAse protection assay after 3 or 6 days of incubation and include measurements of the RNAs for type I collagen, alkaline phosphatase, osteopontin, transforming growth factor alpha 1 and beta 2, and Vgr-1/BMP-6. In addition, C26 cells are incubated in the presence of retinoic acid and several established inhibitors of the synthesis or assembly of extracellular matrix components and the effects on induced alkaline phosphatase activity determined. Our data show that while the collagen substrate mimics some of the effects of retinoic acid and the extracellular matrix, it cannot reproduce all of them. Specifically, while the latter two culture conditions increase the abundance of all six mRNAs, type I collagen film increases the levels of only three of the six (collagen I, alkaline phosphatase, and osteopontin). Moreover, while type I collagen film produces an increase in alkaline phosphatase message, it falls to produce a similar change in alkaline phosphatase activity, an effect seen with both retinoic acid and extracellular matrix. However, interruption of collagen I synthesis by cis-4-hydroxy-L-proline blocks the increase in alkaline phosphatase activity associated with retinoic acid treatment. Thus, it appears likely that type I collagen is a necessary but, by itself, insufficient factor to elicit the comprehensive expression of the osteoblastic phenotype in immature mesenchymal cells.

Alkaline Phosphatase↗

Soy isoflavonoids and cancer prevention. Underlying biochemical and pharmacological issues.

The isoflavonoids in soy, genistein and daidzein, have been proposed to contribute an important part of the anti-cancer effect of soy. Although there have been many interesting studies on the effects of isoflavones on biochemical targets in tissue culture experiments, in most cases the concentrations used by investigators have exceeded 10 microM. However, based on simple pharmacokinetic calculations involving daily intake of isoflavones, absorption from the gut, distribution to peripheral tissues, and excretion, it is unlikely that blood isoflavone concentrations even in high soy consumers could be greater than 1-5 microM. Experiments designed to evaluate these pharmacological principles were carried out in anesthetized rats with indwelling biliary catheters and in human volunteers consuming soy beverages. The data from these experiments indicate that genistein is efficiently absorbed from the gut, taken up by the liver and excreted in the bile as its 7-O-beta-glucuronide. Re-infused genistein 7-O-beta-glucuronide was also well absorbed from the gut, although this occurred in the distal small intestine. In human subjects fed a soy beverage for a period of two weeks, plasma levels of genistein and daidzein, determined by HPLC-mass spectrometry, ranged from 0.55-0.86 microM, mostly as glucuronide and sulfate conjugates. In summary, genistein is well absorbed from the small intestine and undergoes an enterohepatic circulation. Although the plasma genistein levels achievable with soy food feeding are unlikely to be sufficient to inhibit the growth of mature, established breast cancer cells by chemotherapeutic-like mechanisms, these levels are sufficient to regulate the proliferation of epithelial cells in the breast and thereby may cause a chemopreventive effect.

Animals↗

Peroxynitrite-dependent tryptophan nitration.

Peroxynitrite (ONOO-), the reaction product of superoxide (O2.-) and nitric oxide (.NO), nitrates tyrosine and other phenolics. We report herein that tryptophan is also nitrated by peroxynitrite in the absence of transition metals to one predominant isomer of nitrotryptophan, as determined from spectral characteristics and liquid chromatography-mass spectrometry analysis. At high peroxynitrite to tryptophan ratios, other oxidation products were detected as well. The amount of nitrotryptophan formed from peroxynitrite increased at acidic pH, with an apparent pKa of 7.8. High concentrations of Fe(3+)-EDTA were required to enhance peroxynitrite-induced nitrotryptophan formation, while addition of up to 15 microM Cu/Zn superoxide dismutase had a minimal effect on tryptophan nitration. Cysteine, ascorbate, and methionine decreased nitrotryptophan yield to an extent similar to that predicted by their reaction rates with ground-state peroxynitrite, and typical hydroxyl radical scavengers partially inhibited nitration. Plots of the observed rate constant of nitrotryptophan formation vs tryptophan concentration presented downward curvatures. Thus, the kinetics of metal-independent nitration reactions were interpreted in terms of two parallel mechanisms. In the first one, ground-state peroxynitrous acid nitrated tryptophan with a second-order rate constant of 184 +/- 11 M-1 s-1 at 37 degrees C. The activation enthalpy was 9.1 +/- 0.3 kcal mol-1, and the activation entropy was -19 +/- 1 cal mol-1 K-1. In the second mechanism, ONOOH*, an activated intermediate derived from trans-peroxynitrous acid formed in a steady state, was the nitrating agent.

Deferoxamine↗

The role of metabolism in mammary epithelial cell growth inhibition by the isoflavones genistein and biochanin A.

The basis for the differential sensitivity of cultured normal human mammary epithelial (HME) cells and a transformed human breast cancer MCF-7 cell line to growth inhibition by the isoflavone genistein and its 4'-methyl ether derivative, biochanin A, was examined. In HME cells genistein is 5-fold more potent as a growth inhibitor than biochanin A, whereas in MCF-7 cells biochanin A and genistein are equally potent as growth inhibitors. Based on its properties as an in vitro protein tyrosine kinase (PTK) inhibitor, biochanin A would be expected to be a less potent growth inhibitor than genistein. To determine whether isoflavone metabolism could account for the observed differences in growth inhibition, metabolism experiments were conducted with HME and MCF-7 cells using [4-14C]genistein and [4-14C]biochanin A. MCF-7 cells extensively metabolized both isoflavones, producing two genistein metabolites with molecular weights of 350 and 380 and three biochanin A metabolites with molecular weights of 270, 350 and 380. In contrast, significant genistein or biochanin A metabolism was not observed in HME cells. Using mass spectrometry and nuclear magnetic resonance analysis, metabolite 350 from genistein and biochanin A experiments was identified as genistein 7-sulfate; biochanin A metabolite 270 was identified as genistein. Metabolite 380 was not unequivocally identified, but appeared to be a hydroxylated and methylated form of genistein sulfate. In MCF-7 cells, genistein 7-sulfate and metabolite 380 were detected primarily in the cell media fraction, suggesting that once formed these polar metabolites were excreted from the cells. These data show that isoflavone metabolism by transformed breast epithelial cells modulates the growth inhibitory effects of genistein and biochanin A. In MCF-7 cells, genistein metabolism was correlated with a decrease in growth inhibition, whereas biochanin A metabolism was associated with an increase in growth inhibition.

Anticarcinogenic Agents↗

Urine toxicology screens in drivers suspected of driving while impaired from drugs.

OBJECTIVE: Police departments, in conjunction with the National Highway Traffic Safety Administration, have developed a standardized evaluation aimed at identifying drivers impaired by drugs other than ethanol. These evaluations are performed by specially trained police officers known as Drug Recognition Experts. METHODS: We retrospectively reviewed the evaluations of 242 drivers detained for driving while impaired in the City and County of Denver from January 1, 1988 to June 30, 1990. RESULTS: All drivers had urine toxicology screens performed, which were positive for a mean 1.2 +/- 0.9 SD (range zero to four) for drugs having the potential for causing driving impairment. The 193/242 urine screens (79.8%) testing positive showed the following drugs: cannabis 162 (66.9%), stimulants (including cocaine metabolites) 80 (33.1%), depressants (benzodiazepines and barbiturates) 24 (9.9%), narcotics 12 (5.0%), inhalants (toluene) 1 (0.4%), hallucinogens (LSD) 1 (0.4%), and other 3 (1.2%). Drug Recognition Experts, based on their initial evaluation, were able to predict correctly some or all of the drugs found on the urine screens in 178/242 (73.6%) of cases. Overall agreement between the Drug Recognition Experts opinions and urine screen results had a kappa value (p < 0.05) of 0.41. CONCLUSIONS: There was a high rate (79.8%) of positive urine toxicology screens in drivers suspected of nonethanol drug impairment. In most cases, Drug Recognition Experts were able to reliably predict the results of these screens.

Adolescent↗

Stimulatory influence of soy protein isolate on breast secretion in pre- and postmenopausal women.

Soy foods have been reported to have protective effects against premenopausal breast cancer in Asian women. No studies have been reported on potential physiological effects of dietary soy consumption on breast gland function. We evaluated the influence of the long-term ingestion of a commercial soy protein isolate on breast secretory activity. We hypothesized that the features of nipple aspirate fluid (NAF) of non-Asian women would be altered so as to resemble those previously found in Asian women. At monthly intervals for 1 year, 24 normal pre- and postmenopausal white women, ages 30 to 58, underwent nipple aspiration of breast fluid and gave blood and 24-h urine samples for biochemical studies. No soy was administered in months 1-3 and 10-12. Between months 4-9 the women ingested daily 38 g of soy protein isolate containing 38 mg of genistein. NAF volume, gross cystic disease fluid protein (GCDFP-15) concentration, and NAF cytology were used as biomarkers of possible effects of soy protein isolate on the breast. In addition, plasma concentrations of estradiol, progesterone, sex hormone binding globulin, prolactin, cholesterol, high density lipoprotein-cholesterol, and triglycerides were measured. Compliance was assessed by measurements of genistein and daidzein and their metabolites in 24-h urine samples. Excellent compliance with the study protocol was obtained. Compared with NAF volumes obtained in months 1-3, a 2-6-fold increase in NAF volume ensued during months 4-9 in all premenopausal women. A minimal increase or no response was found in postmenopausal women. No changes were found in plasma prolactin, sex hormone binding globulin, cholesterol, high density lipoprotein cholesterol, and triglyceride concentrations. Compared with concentrations found in months 1-3 (no soy), plasma estradiol concentrations were elevated erratically throughout a "composite" menstrual cycle during the months of soy consumption. No significant changes were seen in plasma progesterone concentrations. No significant changes were found in plasma estrogen levels in postmenopausal women. A moderate decrease occurred in the mean concentration of GCDFP-15 in NAF in premenopausal women during the months of soy ingestion. Of potential concern was the cytological detection of epithelial hyperplasia in 7 of 24 women (29.2%) during the months they were consuming soy protein isolate. The findings did not support our a priori hypothesis. Instead, this pilot study indicates that prolonged consumption of soy protein isolate has a stimulatory effect on the premenopausal female breast, characterized by increased secretion of breast fluid, the appearance of hyperplastic epithelial cells, and elevated levels of plasma estradiol. These findings are suggestive of an estrogenic stimulus from the isoflavones genistein and daidzein contained in soy protein isolate.

Adult↗

Nitric oxide inhibition of lipoxygenase-dependent liposome and low-density lipoprotein oxidation: termination of radical chain propagation reactions and formation of nitrogen-containing oxidized lipid derivatives.

Lipoxygenase-induced lipid oxidation contributes to plasma lipoprotein oxidation and may be an underlying pathogenic mechanism of atherogenesis. Since inactivation of the vasorelaxant actions of nitric oxide (.NO) plays a critical role in the impaired function of atherosclerotic vessels and because .NO reacts rapidly with other radical species, we assessed the influence of .NO on lipoxygenase-catalyzed oxidation of linoleic and linolenic acid, 1-palmitoyl-2-arachidonyl-sn-glycero-3-phosphocholine (PC) liposomes, hypercholesterolemic rabbit beta-very-low-density lipoprotein, and human low-density lipoprotein. Soybean lipoxygenase (SLO)-induced lipid oxidation was assessed by accumulation of conjugated dienes, formation of lipid hydroperoxides, oxygen consumption, and liquid chromatography-mass spectrometry. Different rates of delivery of .NO to lipid oxidation systems were accomplished either by infusion of .NO gas equilibrated with anaerobic buffer or via .NO released from S-nitrosoglutathione. Nitric oxide alone did not induce lipid peroxidation, while exposure to SLO yielded significant oxidation of fatty acids, PC liposomes, or lipoproteins in a metal ion-independent mechanism. Low concentrations of .NO, which did not significantly inhibit the activity of the iron-containing lipoxygenase, induced potent inhibition of lipid peroxidation in a dose-dependent manner. Mass spectral analysis of oxidation products showed formation of nitrito-, nitro-, nitrosoperoxo-, and/or nitrated lipid oxidation adducts, demonstrating that .NO serves as a potent terminator of radical chain propagation reactions. The formation of Schiff's base fluorescent conjugates between SLO-oxidized linoleic or linolenic acid and bovine serum albumin (BSA) was also inhibited by .NO via reaction with lipid hydroperoxyl radicals (LOO.), thus preventing the reaction of LOO. with polypeptide amino groups. Mass spectrometry analysis showed that both lipid peroxidation products and nitrogen-containing oxidized lipid species decreased in the presence of BSA. We conclude that .NO can play a potent oxidant-protective role in the vessel wall by inhibiting lipoxygenase-dependent lipid and lipoprotein oxidation. This occurs via termination of lipid radical chain propagation reactions catalyzed by alkoxyl (LO.) and LOO. intermediates of lipid peroxidation rather than by inhibition of lipoxygenase-catalyzed initiation reactions.

Animals↗

Vgr-1/BMP-6 induces osteoblastic differentiation of pluripotential mesenchymal cells.

The transforming growth factor-beta (TGF-beta) superfamily is a group of secreted growth factors that appears to play a central role in mesenchymal differentiation, including cartilage and bone formation. The present study examines the role of one member of this family, vgr-1, also called bone morphogenetic protein-6, in mesenchymal cell differentiation. This factor may be considered as a prototype for the largest subgroup of related factors within the TGF-beta superfamily, the function of which has as yet been poorly defined. vgr-1 has been localized previously to hypertrophic cartilage and has been shown to induce endochondral bone formation in vivo. To further characterize the role of vgr-1 in bone and cartilage differentiation, we stably transfected the pluripotent mesenchymal cell line ROB-C26 with a vector to overexpress vgr-1. Overexpression of this factor did not affect cell shape or morphology, but it enhanced osteoblastic differentiation in vitro and altered cellular responsiveness to retinoic acid. Furthermore, the extracellular matrix produced by these vgr-1-overexpressing cells induced ectopic bone formation in vivo and osteoblastic differentiation in vitro, similar to the matrix produced by C26 cells treated with retinoic acid. The osteoinductive effect of the matrix from vgr-1-overexpressing cells was blocked using a neutralizing vgr-1 antibody but not with a neutralizing TGF-beta 1 antibody, indicating that vgr-1 alone was required for this osteogenic effect. In contrast, the osteoinductive effect of matrix from retinoic acid-treated cells was blocked with both vgr-1 and TGF-beta 1 antibodies, suggesting that TGF-beta 1 may act prior to vgr-1 during osteoblastic differentiation. We further demonstrated that osteoinduction by vgr-1 was dependent on presentation of vgr-1 within the matrix, because the osteoinductive effect of matrix from vgr-1-overexpressing cells could not be mimicked with the addition of soluble vgr-1 to parental C26 cells. Finally, overexpression of MyoD within the C26 cells overexpressing vgr-1 converted the cells to myoblasts, indicating that vgr-1 had induced early osteoblastic.

Alkaline Phosphatase↗

[The organization of veterinary services in African animal husbandry systems: chances for the exchange of interdisciplinary learning processes].

The structure of the veterinary services to date hinders--together with massive intervention in the land tenure systems and the animal keepers' rights in arid and semi-arid areas--the future organization of productive animal-keeping systems adapted to the ecological conditions. The consensus of the findings of research in the social as well as in the natural sciences, is that state (agrarian) policies and international development cooperation have led to centralism and authoritarian administrations which formalize formerly informal, locally specific rules for securing the health of the animals and the maintenance of grazing and water resources. As a result, the animal-keeping groups have lost their rights, social conflicts arose and the environment suffered. Thus, decentralization, subsidarity and--above all--comprehensive participation on the part of the animal keepers are regarded as the guidelines for the future organization of state and/or private services for maintaining the health of the animals. Thereby, the planning at the various administrative levels is faced by great challenges in view of the progressing differentiation in the animal-keeping systems (e.g. peri-urban systems; urban absentee herd owners; marginalized, subsistence-oriented households).

Africa↗

Nitric oxide regulation of superoxide and peroxynitrite-dependent lipid peroxidation. Formation of novel nitrogen-containing oxidized lipid derivatives.

Superoxide (O2-.), nitric oxide (.NO), and their reaction product peroxynitrite (ONOO-) have all been shown to independently exert toxic target molecule reactions. Because these reactive species are often generated in excess during diverse inflammatory and other pathologic circumstances, we assessed the influence of .NO on membrane lipid peroxidation induced by O2-., H2O2, and .OH derived from xanthine oxidase (XO) and by ONOO-. Experimental conditions in lipid oxidation systems were adjusted to yield different rates of delivery of .NO, relative to rates of O2-. and H2O2 generation, by infusion of either .NO or via .NO released from S-nitroso-N-acetylpenicillamine or S-nitrosoglutathione. Peroxidation of phosphatidylcholine liposomes was assessed by formation of thiobarbituric acid-reactive products and by liquid chromatography-mass spectrometry. Liposomes exposed to XO-derived reactive species in the presence of .NO exhibited both stimulation and inhibition of lipid peroxidation, depending on the ratio of the rates of reactive oxygen species production and .NO introduction into reaction systems. Nitric oxide alone did not induce lipid peroxidation. Linolenic acid emulsions peroxidized by XO-derived reactive species showed similar dose-dependent regulation of lipid peroxidation by .NO. Mass spectral analysis of oxidation products showed formation of nitrito-, nitro-, nitrosoperoxo-, and/or nitrated lipid oxidation adducts, demonstrating that .NO serves as a potent terminator of radical chain propagation reactions. Electron spin resonance (ESR) analysis of incubation mixtures provided no evidence for formation of paramagnetic iron-lipid-nitric oxide complexes in reaction systems. Peroxynitrite-dependent lipid peroxidation, which predominantly occurs by metal-independent mechanisms, was also inhibited by .NO. Peroxynitrite-mediated benzoate hydroxylation was partially inhibited by .NO, inferring reaction between .NO and ONOOH. It is concluded that .NO can both stimulate O2-./H2O2/.OH-induced lipid oxidation and mediate oxidant-protective reactions in membranes at higher rates of .NO production, with the prooxidant versus antioxidant outcome critically dependent on relative concentrations of individual reactive species. Prooxidant reactions of .NO will occur after O2-. reaction with .NO to yield potent secondary oxidants such as ONOO- and the antioxidant effects of .NO a consequence of direct reaction with alkoxyl and peroxyl radical intermediates during lipid peroxidation, thus terminating lipid radical chain propagation reactions.

Hydroxyl Radical↗

The implementation of a quality management system in a department of diagnostic radiology.

The quality management systems of the Departments of Diagnostic Radiology of St George's Hospital, London, and Bristol Royal Infirmary (BRI) have been certified with the British Standard 5750. These were the first clinical departments in the UK to be certified to this internationally recognized quality assurance (QA) standard. Quality is a much used term; in this context it is defined as 'fitness for purpose', and quality assurance is the mechanism by which quality is achieved. The paper describes the features of the quality system which have been implemented at St George's Hospital, and how a management concept for manufacturing industries has been adapted successfully to a National Health Service Department. The paper also demonstrates how the quality system has led to the setting and achieving of departmental objectives.

England↗

The effects of changes in plasma nonesterified fatty acid levels on oxidative metabolism during moderate exercise in patients with non-insulin-dependent diabetes mellitus.

Blood levels of intermediary metabolites were measured and indirect calorimetry was performed in 10 otherwise healthy, non-insulin-dependent diabetic (NIDDM) patients before, during, and after 30 minutes of moderate exercise on three occasions in random order at weekly intervals with (1) heparin treatment to increase preexercise plasma nonesterified fatty acid (NEFA) levels (HEPARIN); (2) acipimox, a nicotinic acid analogue, to reduce preexercise plasma NEFA levels (ACIPIMOX); and (3) no manipulation of preexercise plasma NEFA levels (NIL). With ACIPIMOX, preexercise blood levels were significantly reduced for NEFAs and glycerol (P < .01) and marginally reduced for acetoacetate and 3-hydroxybutyrate (NS) compared with preexercise levels for the other two treatments; these low levels seen with acipimox treatment increased only slightly during exercise and the postexercise period. Plasma NEFA levels increased by approximately 150% (P < .001) with HEPARIN at the same times. The levels of ketone bodies during either NIL or HEPARIN increased rapidly postexercise by approximately 90% to 110% for both acetoacetate and 3-hydroxybutyrate (both P < .01). Plasma insulin levels tended to be lowest (despite similar plasma glucose levels during the three treatments) with ACIPIMOX, while growth hormone (hGH) and, perhaps, noradrenaline levels were highest both during and after exercise. The respiratory quotient (RQ) was highest with ACIPIMOX (P < .05 for exercise and postexercise periods compared with the other two treatments), which, compared with NIL, reduced fat oxidation by 27% and 60% and increased carbohydrate oxidation by 29% and 74% during and after exercise, respectively (all P < .05). These changes in substrate oxidation due to ACIPIMOX were almost opposite to those observed with HEPARIN.(ABSTRACT TRUNCATED AT 250 WORDS)

3-Hydroxybutyric Acid↗

Immediate and sustained reduction in serum cholesterol achieved in 4-week Heart Tune program.

Currently, there is limited information about educational models effective in assisting individuals to lower their serum cholesterol. Dietitians and nutritionists involved in cholesterol-reduction programs need to inform other health professionals about programs utilized and the success of those programs. The National Cholesterol Education Program has published guidelines for the detection, evaluation, and treatment of high blood cholesterol in adults. Educational programs should be systematically evaluated to confirm their success in cholesterol reduction. The Heart Tune program is a 4-week class developed by a dietitian to assist clients in cholesterol reduction. An evaluation of the lipoprotein levels of 49 program participants demonstrated that serum total cholesterol levels significantly decreased at the completion of the 4-week class (0.65 mmol/L) and after 1 year (0.80 mmol/L).

Adult↗

Bromocriptine-associated headache: possible life-threatening sympathomimetic interaction.

We present two cases of severe headache associated with the use of bromocriptine for lactation suppression in otherwise healthy women. In each case, the additional use of a therapeutic sympathomimetic agent resulted in extreme worsening of symptoms with development of hypertension and life-threatening complications (ventricular tachycardia and cardiac dysfunction in one case, seizures and cerebral vasospasm in the other). Sympathomimetics in combination with bromocriptine in patients with a bromocriptine-associated headache during the puerperium may be dangerous.

Adult↗

The validity and reliability of the navicular fat stripe as a screening test for detection of navicular fractures.

STUDY OBJECTIVE: The purpose of this study was to determine if the navicular fat stripe (NFS) is a valid and reliable screening tool in assessing potential navicular fractures. DESIGN: Retrospective analysis. SETTING: Minor trauma section of the Los Angeles County-University of Southern California Medical Center emergency department. TYPE OF PARTICIPANTS: Study population included patients seen for wrist injury between January 1987 and December 1988. The individuals who interpreted the radiographs included eight observers with varying degrees of radiographic experience. INTERVENTIONS: None MEASUREMENTS AND MAIN RESULTS: The positive predictive value averaged 12% or 15% depending on how we counted a straight NFS, and the negative predictive value averaged 93% or 95%, again depending on how we counted a straight NFS. A straight NFS was ten times as likely to occur among normal wrists than among those with navicular fractures. Interobserver reliability was found to be high with a Hoyt reliability coefficient of .79. CONCLUSIONS: An abnormal NFS is a poor predictor of a navicular fracture while both a straight and a normal NFS are good predictors of no navicular fracture. A normal NFS may allow less stringent treatment by the emergency physician. Extremes of radiographic experience were found to have no significant effect on NFS interpretation.

Adipose Tissue↗