Delayed and significant hypercalcaemia due to teriparatide therapy: a case report and review.

INTRODUCTION: Transient hypercalcaemia due to teriparatide occurs in up to 11% of patients though delayed hypercalcaemia (> 24 h post injection) is rare. We report the case of a female who developed significant delayed hypercalcaemia after teriparatide treatment for osteoporosis and review other cases in the literature to date. CASE REPORT: A 72-year-old female on teriparatide for the treatment of osteoporosis was found to have hypercalcaemia (3.30 mmol/l) on routine testing approximately 3 months after starting therapy. Serum calcium pretreatment was normal at 2.39 mmol/l. She was admitted to the hospital for investigations which identified a serum 25-hydroxyvitamin D of 94 nmol/l, a low parathyroid hormone of 6.0 pg/ml, and normal test results for 1,25 dihydroxyvitamin D (115 pmol/l), parathyroid hormone-related peptide (< 1.4 pmol/ml), serum electrophoresis and angiotensin-converting enzyme (39 IU/l). CT abdomen, pelvis, and thorax revealed no evidence of malignancy and an isotope bone scan ruled out skeletal metastases. Serum calcium normalised (2.34 mmol/l) several days after stopping teriparatide and calcium supplements and administering intravenous fluid. On restarting teriparatide, delayed hypercalcaemia reoccurred and treatment was switched to denosumab. DISCUSSION: Delayed moderate to severe hypercalcaemia (serum calcium > 3.0 mmol/l) due to teriparatide is rare but may lead to therapy withdrawal. The underlying predisposing risk factors remain unclear and highlight the importance of a routine serum calcium assessment on therapy.

Folate and clefts of the lip and palate--a U.K.-based case-control study: Part I: Dietary and supplemental folate.

OBJECTIVES: We sought to determine the associations between nonsyndromic cleft lip with or without cleft palate (CL-P) and cleft palate only (CP) and maternal intake of dietary folate and supplemental folic acid, in an area where the prevalence at birth of neural tube defects has been high and flour is not fortified with folic acid. METHODS: Interviews regarding periconceptional dietary intake and supplement use were completed with the mothers of 112 CL-P cases, 78 CP cases, and 248 unaffected infants. The data were analyzed by logistic regression methods. RESULTS: There was no overall association between CL-P and CP and either energy-adjusted total folate intake or supplemental folic acid use, irrespective of dosage. CONCLUSION: Overall, higher intakes of total folate do not appear to prevent oral clefts in this population.

Calcification inhibitors and Wnt signaling proteins are implicated in bovine artery smooth muscle cell calcification in the presence of phosphate and vitamin D sterols.

Administration of active vitamin D sterols to treat secondary hyperparathyroidism in patients with chronic kidney disease receiving dialysis has been associated with elevated serum calcium and phosphorus levels, which may lead to increased risk of vascular calcification. However, calcimimetics, by binding to the parathyroid gland calcium-sensing receptors, reduce serum parathyroid hormone, calcium, phosphorus, and the calcium-phosphorus product. Using cultured bovine aorta vascular smooth muscle cells (BASMCs), an in vitro model of vascular calcification, we compared calcification levels and gene expression profiles after exposure to the phosphate source ss-glycerolphosphate (BGP), the active vitamin D sterols calcitriol and paricalcitol, the calcimimetic R-568, or BGP with the active vitamin D sterols or R-568. Cells exposed to BGP (10 mM) alone or with calcitriol or paricalcitol showed dose-dependent BASMC calcification. No change in calcification was observed in cultures exposed to BGP with R-568, consistent with the observed lack of calcium-sensing receptor expression. Microarray analysis using total cellular RNA from cultures exposed to vehicle or BGP in the absence and presence of 10(-8) M calcitriol or paricalcitol for 7 days showed that cells exposed to BGP with calcitriol or BGP with paricalcitol had virtually identical gene expression profiles, which differed from those of cells treated with BGP or vehicle alone. Several osteoblast- and chondrocyte-associated genes were modulated by BGP and vitamin D exposure. In this study, exposure of BASMCs to phosphate and active vitamin D sterols induced calcification and changes in expression of genes associated with mineralized tissue.

Ovarian cancer--the need for change in service delivery in Northern Ireland.

This paper provides local data on the provision of services for patients diagnosed with ovarian cancer in 1996 prior to the reorganisation of cancer services. It documents a service for 140 patients provided by 80 consultant teams and illustrates the need for reorganisation to meet the evidence base already in existence for improvement in survival and will serve as a baseline for future audits in this area.

Effect of concentrate feed level in late gestation on subsequent milk yield, milk composition, and fertility of dairy cows.

The effects of level of concentrate feeding in late gestation on feed intake, milk yield, milk composition, and fertility in the subsequent lactation were evaluated in a randomized block design experiment involving 60 cows. Grass silage was offered ad libitum for the last 28 d of gestation either as the sole diet (OC) or supplemented with 5 kg/d of concentrates (5C). Following calving, the cows were offered the same grass silages supplemented with 7 kg/d of concentrates. For treatments OC and 5C, total dry matter intakes were 9.28 and 11.03 kg/d of dry matter, respectively, during the last 4 wk of gestation. During wk 1 to 12 of the subsequent lactation, treatment 5C increased milk fat concentration but did not alter feed intake, milk yield, or protein concentration relative to treatment OC. Treatment 5C increased the interval to first progesterone rise and the number of services per conception relative to treatment OC. Cow parity, BF depth assessed at d 28 before parturition, and treatment provided the best fit relationships for the yields of fat and fat plus protein (R2 relationships = 0.65 and 0.64, respectively) during wk 1 to 4 of lactation. It was concluded that, other than milk fat concentration, supplementation with additional concentrates in late gestation did not alter milk yield or composition and dairy cow fertility. Furthermore, despite the very large differences in cow characteristics at d 28 before parturition, there was no evidence of any interaction between treatment and specific cow characteristics on animal performance in the first 12 wk of lactation.

Tuning to interaural time differences across frequency.

Interaural time differences (ITDs) are an important cue for azimuthal sound localization. Sensitivity to this cue depends on temporal synchrony to the waveform (i.e., phase locking) that begins in the hair cells and is relayed to the neural comparators. The synchrony function is low-pass. Therefore, it is expected that neural tuning to ITDs will become narrower with frequency according to a 1/frequency function. To test this, we measured ITD tuning across frequency in neurons from the superior olivary complex, the dorsal nucleus of the lateral lemniscus, the inferior colliculus, the auditory thalamus, and the auditory cortex. For some neurons in each nucleus, the ITD tuning width did become systematically narrower by the expected 1/frequency relationship. However, in other neurons the ITD tuning width was nearly constant across frequency. Constant ITD tuning width was infrequently observed in neurons of the superior olivary complex but was common in neurons in structures above the superior olivary complex. The nearly constant ITD tuning was caused both by sharper ITD tuning at low frequencies and broader tuning at higher frequencies within the low-frequency band. Neurons with nearly constant tuning to ITDs may be the mechanism underlying the perception of ITDs in humans in which just-noticeable differences to changes in ITD decrease by less than the 1/frequency prediction.

Effects of supplementation of dairy cattle with fish oil on silage intake, milk yield and milk composition.

The effects of level of fish oil inclusion in the diet on grass silage intake, and milk yield and composition of dairy cows offered either 5 or 10 kg concentrates/d were evaluated in a ten treatment, partly balanced, changeover design experiment involving 50 cows in early lactation. Concentrates were prepared to provide 0, 150, 300 or 450 g fish oil/cow per d or 300 g fish oil/cow per d from a premix when each animal was offered 5 kg/d. The fish oil was predominantly from herring and mackerel caught in the North Atlantic while the fish oil premix was obtained from a commercial source and used palm kernel expeller as a carrier. Increasing fish oil supplementation decreased silage dry matter intake and the concentrations of milk fat and protein, and increased milk yield and diet digestibility. There were significant interactions between concentrate feed level and level of fish oil for silage intake and milk yield. Other than for the concentrations of milk fat and protein, and 20:4n-6 fatty acids, the source of fish oil did not affect forage intake or animal performance. Fish oil supplementation also decreased the concentrations of milk protein by 0.9 g/kg for each 100 g increase in fish oil supplementation, the depression being similar at each level of concentrate feeding. Supplementing the feed of dairy cows with 450 g fish oil/cow per d decreased the concentration of milk fat by 15 g/kg. This study also showed that feeding dairy cattle with fish oil is an efficient method of increasing eicosapentaenoic acid in the human diet through transfer into milk.

Neural sensitivity to interaural time differences: beyond the Jeffress model.

Interaural time differences (ITDs) are a major cue for localizing the azimuthal position of sounds. The dominant models for processing ITDs are based on the Jeffress model and predict neurons that fire maximally at a common ITD across their responsive frequency range. Such neurons are indeed found in the binaural pathways and are referred to as "peak-type." However, other neurons discharge minimally at a common ITD (trough-type), and others do not display a common ITD at the maxima or minima (intermediate-type). From recordings of neurons in the auditory cortex of the unanesthetized rabbit to low-frequency tones and envelopes of high-frequency sounds, we show that the different response types combine to form a continuous axis of best ITD. This axis extends to ITDs well beyond that allowed by the head width. In Jeffress-type models, sensitivity to large ITDs would require neural delay lines with large differences in path lengths between the two ears. Our results suggest instead that sensitivity to large ITDs is created with short delay lines, using neurons that display intermediate- and trough-type responses. We demonstrate that a neuron's best ITD can be predicted from (1) its characteristic delay, a rough measure of the delay line, (2) its characteristic phase, which defines the response type, and (3) its best frequency for ITD sensitivity. The intermediate- and trough-type neurons that have large best ITDs are predicted to be most active when sounds at the two ears are decorrelated and may transmit information about auditory space other than sound localization.

Development of a fluorescent ligand-binding assay using the AcroWell filter plate.

One of the most powerful tools for receptor research and drug discovery is the use of receptor-ligand affinity screening of combinatorial libraries. Early work involved the use of radioactive ligands to identify a binding event; however, there are numerous limitations involved in the use of radioactivity for high throughput screening. These limitations have led to the creation of highly sensitive, nonradioactive alternatives to investigate receptor-ligand interactions. Pall Gelman Laboratory has introduced the AcroWell, a patented low-fluorescent-background membrane and sealing process together with a filter plate design that is compatible with robotic systems. Taken together, these allow the AcroWell 96-well filter plate to detect trace quantities of lanthanide-labeled ligands for cell-, bead-, or membrane-based assays using time-resolved fluorescence. Using europium-labeled galanin, we have demonstrated that saturation binding experiments can be performed with low-background fluorescence and signal-to-noise ratios that rival traditional radioisotopic techniques while maintaining biological integrity of the receptor-ligand interaction. In addition, the ability to discriminate between active and inactive compounds in a mock galanin screen is demonstrated with low well-to-well variability, allowing reliable determination of positive hits even for low-affinity interactions.

Risk factors for symptomatic otic and sinus barotrauma in a multiplace hyperbaric chamber.

This retrospective study examines the relationship of multiplace chamber compression rates and the influence of several predisposing factors on the risk of symptomatic barotrauma. Data were reviewed from a 3-yr period for 111 patients who received 2,394 routine hyperbaric oxygen treatments. A total of 35 patients reported symptoms of barotrauma, with an overall rate of 3.05 cases per 100 treatments. Most symptoms occurred during a patient's initial three treatments and with minimal increased pressure. The most frequently affected area was the ears (95%) with objective findings noted in 18% of patients reporting fullness compared to 39% of patients reporting pain. Referral diagnosis was not related to the incidence of barotrauma. Although the overall risk of symptomatic barotrauma increased as the compression rate increased, it was not significant (RR = 1.57, CI0.95 = 0.65, 3.80). Female patients were at significantly increased risk (RR = 2.14, CI0.95 = 1.37, 3.34) compared to males, and patients less than age 40 were at higher risk than those age 40 and older (RR = 3.00, CI0.95 = 1.80, 5.03). Well-designed prospective studies are needed to more clearly define risk factors and identify compression rates with the least risk of barotrauma.

Effects of the trichothecene mycotoxin T-2 toxin on neurotransmitters and metabolites in discrete areas of the rat brain.

T-2 toxin has been shown to affect the central nervous system. Only recently have attempts been made to characterize the neurochemical perturbations associated with T-2 intoxication. To examine the effect of T-2 on regional brain biogenic monoamines and selected metabolites, male rats were dosed orally with T-2 toxin in corn oil at 0.1, 1.0 or 2.5 mg/kg body weight. At 2, 6 and 10 hr post-dosing, rats were killed, brains were collected and stored at -80 degrees until analysed. Brain nuclei, including nucleus raphe magnus, paraventricular nucleus, locus coeruleus, substantia nigra, medial forebrain bundle, nucleus accumbens and olfactory tubercle, were analysed. T-2 treatment increased 5-hydroxy-3-indoleacetic acid and serotonin throughout the brain, and produced a transient increase in norepinephrine in the nucleus raphe magnus and a temporary decrease in the substantia nigra. Regional dihydroxyphenylacetic acid concentration was affected, with increased DOPAC observed in the locus coeruleus, medial forebrain bundle and paraventricular nucleus of the hypothalamus, and decreased DOPAC in the olfactory tubercles. No regional changes in epinephrine or dopamine were observed. Few treatment differences were observed, with the 0.1 mg/kg body weight T-2, 2% of the LD50, significantly affecting brain monoamines. It had been suggested that neurological manifestations of T-2 toxin are the result of brain hypoxia; however, the altered brain monoamine profile observed at doses that do not alter heart function, suggests the brain is a primary site of trichothecene action.

Endothelium-dependent vascular effects of Pycnogenol.

Pycnogenol (P) is purported to exhibit effects that could be beneficial in terms of prevention of chronic age-related diseases such as atherosclerosis. The most studied of these effects is its antioxidant/free radical-scavenging activity. In this study, we investigated the possibility that this supplement might produce vascular effects by stimulation of nitric oxide (NO) production by vascular endothelial cells. In the in vitro experiments, P (1-10 microg/ml) relaxed epinephrine (E)-, norepinephrine (NE)-, and phenylephrine (PE)-contracted intact rat aortic ring preparations in a concentration-dependent manner. However, when the endothelial lining of the aortic ring was removed, P had no effect, indicating an endothelium-dependent relaxing (EDR) effect. This EDR response was caused by enhanced NO levels, because the NO synthase (NOS) inhibitor N-methyl-L-arginine (NMA) reversed (or prevented) the relaxation, and this response, in turn, was reversed by addition of L-arginine, the normal substrate for NOS. Pycnogenol-induced EDR persisted after exposure of intact rings to high levels of superoxide dismutase (SOD), suggesting that the mechanism of EDR did not involve scavenging of superoxide anion. In addition to causing relaxation, preincubation of aortic rings with P (1-10 microg/ml) inhibited subsequent E- and NE-induced contractions in a concentration-dependent manner. Fractionation of P by Sephadex LH-20 chromatography resulted in three fractions, one of which (fraction 3, oligomeric procyanidins) exhibited potent EDR activity. These results indicate that P, in addition to its antioxidant activity, stimulates constitutive endothelial NOS (eNOS) activity to increase NO levels, which could counteract the vasoconstrictor effects of E and NE. Furthermore, additional protective effects could result from the well-established properties of NO to decrease platelet aggregation and adhesion, as well as to inhibit low-density lipoprotein (LDL) cholesterol oxidation, all of which could protect against atherogenesis and thrombus formation.

Adjunctive treatment of compartment syndrome with hyperbaric oxygen.

Trauma-induced compartment syndrome and other acute traumatic peripheral ischemias have been effectively treated with hyperbaric oxygen therapy. We describe a case of compartment syndrome associated with an acute exertional injury. After surgical decompression, hyperbaric oxygen therapy reduced edema and improved tissue viability. The mechanisms of hyperbaric oxygen applicable to the pathophysiology of compartment syndrome are described. We believe that hyperbaric oxygen is a useful intervention in the management of compartment syndrome.

Connections among functional areas in the mustached bat auditory cortex.

Connections among functional areas in the mustached bat's auditory cortex were examined by placing anatomical tracers in physiologically defined locations. We identified at least two and probably three channels connecting the various areas. One channel is formed by interconnections among areas containing neurons sensitive to frequency-modulated components (FMs) of the pulse and echo. These neurons are tuned to echo delay, a cue for target range, and thus define a ranging channel. An additional one or two channels are formed by interconnections among areas that contain neurons sensitive to the constant frequency components (CFs) of echoes. These neurons are of two main types: either sensitive to CFs of both pulse and echo (CF/CF neurons) or sensitive to a pulse FM and echo CF (FM-CF neurons). There was only a weak connection between the largest area of each type, suggesting they lie in different channels. Connections among areas in the ranging channel and echo CF-sensitive channel(s) were weak. Thus, the interconnections among functional areas in the mustached bat's auditory cortex define parallel channels for processing different types of biosonar information. Most corticocortical connections were patchy, in a manner suggestive of a columnar organization. The average width of the patches was approximately 360 microm. Based on the sizes of the functional areas, we estimate the auditory cortex contains a total of approximately 150 columns. Individual areas contain from as many as approximately 20 to as few as 1-4 columns. Each area had abundant projections outside of the auditory cortex. Connections within the cortex included the frontal, anterior cingulate, retrosplenial and perirhinal cortices, and the claustrum. Subcortical targets included the amygdyla, auditory thalamus, pons, pretectum, superior and inferior colliculi, and central gray. Projections within the cortex were of modest strength compared with several of the subcortical projections. Thus, the auditory areas themselves are the primary source of cortically processed biosonar information to the rest of the brain.

Seizure control after stimulation of the vagus nerve: clinical outcome measures.

BACKGROUND: Currently, decreases in seizure frequency are the accepted efficacy outcome measure of therapeutic interventions in the management of patients with epilepsy. In a longitudinal randomized controlled trial of 10 subjects with intractable complex partial seizures who received left vagal nerve stimulation (VNS) to control seizures, it was found that the total number of consecutive seizure-free days is a significant efficacy outcome measure. Unlike measures in which percentage decreases in seizure frequency are calculated, measures of consecutive seizure days indicate improvement in the amount of time for which patients may function at a higher level in activities of daily living. METHODS: Fourteen day blocks of consecutive seizure-free days and 14 day blocks of consecutive days in which subjects had seizures were tabulated. RESULTS: A Pearson correlation coefficient showed that prior to VNS subjects had few, if any, seizure free blocks of time and after VNS they had more blocks of time seizure free r = -1.00 and r = -0.99. The blocks of seizure-free days increased tenfold (mean 0.85 to mean 8.00) from 1991-1995 while mean seizure frequency in those blocks in which subjects had seizures only decreased from (mean 20.14 to mean 17.59) for the same time period. Correlations between total number of seizures after 24 months of VNS and after 50 months of VNS were r = 0.85 showing a consistency in the effect of VNS. CONCLUSIONS: Monitoring the number of consecutive seizure-free days is a significant clinical outcome measure of VNS.

Chronic stimulation of the left vagus nerve in epilepsy: balance effects.

BACKGROUND: Stimulation of the left vagus nerve (VNS) has been shown to control seizures in double blinded crossover studies in man. Animal studies have reported vagal afferent induced depression of nociceptive and motor reflexes which may be caused by an effect on the descending reticular system controlling spinal cord function. Anticonvulsant drug therapy may cause postural instability. The effects of VNS are assessed not only from the perspective of seizure control but also from the view of potential harm to other bodily systems. Long term (2 1/4 years) effects of VNS were compared to postural stability analyses. METHODS: 8 subjects, 2 were females, mean age 34.5 +/- 8.23 SD years, with intractable complex partial seizures, taking 3 anticonvulsant drugs were assessed for postural stability in quiet standing and while moving forwards, backwards and sideways with eyes open (EO) and eyes closed (EC). Data were collected and collated using an AMTI Biomechanics immovable forceplate, Newton M.A. U.S.A. The study design was longitudinal with pre-operative baseline data collected prior to neurostimulation and at intervals post operatively. RESULTS: 4/8 balance measures showed significant changes from pre-operative values and after 2 1/4 years of stimulation. Area of sway (EO) in quiet standing p = .022 and total sway (EC) in the moving state p = .019 and total sway (EC) in quiet standing showed an increase in sway p = .003. Area of sway (EC) p = .004 tended to decrease. Regression analysis for frequency of stimulation showed an increase in sway with higher frequencies T = 1.99, P = .05. CONCLUSION: Chronic VNS does not augment postural instability.

Chronic stimulation of the left vagus nerve: cognitive motor effects.

BACKGROUND: Early studies of cognitive motor control have shown deficits in complex reaction time tests of epileptic subjects. The purpose of this efficacy study was to determine whether chronic (28 months) stimulation of the left vagus nerve (VNS) to control seizures increased these deficits in 6 epileptic subjects with intractable complex partial seizures. METHODS: Subjects were assessed for simple reaction time, Test A, and subsequent Tests B and C which involved more complex cognitive strategies. Tests were done pre-operatively (SI) and at intervals, 6-8 weeks (S2-S3), and at 6 month intervals (S4-S6) over a 28 month period. Data were collected and collated on an Apple II E computer (Apple, Cupertino CA. U.S.A.) and on electronic switch pad. Data were analyzed using a repeated measures analysis of covariance technique with 2 within subject factors, day, and time of day. RESULTS: 2/11 cognitive measures showed a statistically significant difference. Error rate associated with Test A (simple reaction time) significantly decreased for the factor of day (repeated visits) p = .01. For Test C, error rates decreased in the afternoon (p = .03). This test involved the subjects ability to respond quickly to one signal while simultaneously ignoring a second signal. Data analysis of the covariate showed that the effects of VNS are weak in comparison to baseline differences and the frequency of nerve stimulation negatively predicts the number of wrong errors. High frequency stimulation results showed fewer errors than low frequency stimulation T = -2.31, p = .03. CONCLUSION: Chronic stimulation of the left vagus nerve to control seizure activity does not impair cognitive motor control.

A neuronal population code for sound localization.

The accuracy with which listeners can locate sounds is much greater than the spatial sensitivity of single neurons. The broad spatial tuning of auditory neurons indicates that a code based on the responses of ensembles of neurons, a population code, must be used to determine the position of a sound in space. Here we show that the tuning of neurons to the most potent localization cue, the interaural time difference in low-frequency signals (< approximately 2kHz), becomes sharper as the information ascends through the auditory system. We also show that this sharper tuning increases the efficiency of the population code, in the sense that fewer neurons are required to achieve a given acuity.

Dietary Iodine and selenium interact to affect thyroid hormone metabolism of rats.

The interaction of dietary selenium and iodine on the activities of the selenoenzymes, selenium-dependent glutathione peroxidase (GSH-Px), and type I deiodinase (DI-I), and the thyroid hormones thyroxine (T4) and triiodothyronine (T3) were studied. Male weanling Sprague-Dawley rats were fed an AIN-93G diet for 6 wk with modified selenium and iodine concentration as follows: three levels each of iodine and selenium (0.03, 0.2 added and 1.0 added mg iodine/kg diet, and 0.05, 0.18 added and 1.0 added mg selenium/kg diet) were used in a 3 x 3 factorial design. Renal, but not hepatic, DI-I activity was lower in rats with low selenium intake than in controls. Circulating T3 concentration was not affected by the dietary levels of iodine or selenium. Unlike in liver, kidney and erythrocytes, thyroidal GSH-Px activity was not lower than in controls in rats with low selenium intake, but was significantly higher when iodine intake was low. Significant interactions of iodine and selenium on serum T4 and thyroidal GSH-Px activity were observed. Serum T4 was maintained at control levels when both dietary iodine and selenium were low, but not when iodine alone, or selenium alone, was low. Activity of thyroidal GSH-Px was lowest in rats fed a diet containing high iodine and low selenium. The results suggest that high iodine intake, when selenium is deficient, may permit thyroid tissue damage as a result of low thyroidal GSH-Px activity during thyroid stimulation. A moderately low selenium intake normalized circulating T4 concentration in the presence of iodine deficiency.

Endothelium-dependent vasorelaxation caused by various plant extracts.

In a previous study (Am J Physiol 1993;265: H774-8), we found that certain red wines and other grape products caused endothelium-dependent vasorelaxation. In the present study, aqueous extracts of a variety of vegetables, fruits, teas, nuts, herbs, and spices were tested for their endothelium-dependent relaxing ability in vitro. Rings of rat aorta, with or without an intact endothelium, were mounted in tissue baths, contracted with phenylephrine, and then exposed to diluted plant extracts. Many, but not all, extracts exhibited endothelium-dependent relaxations that were reversed by NG-monomethyl-L-arginine, a nitric oxide synthase inhibitor, which suggested involvement of nitric oxide, the endothelium-derived relaxing factor in the response. Furthermore, extracts that caused relaxation also increased tissue levels of cyclic GMP, the mediator of nitric oxide-induced vascular smooth-muscle relaxation. These results may lend further support to mounting evidence that plant foods contain compounds that, if absorbed intact and in sufficient quantities, could conceivably be beneficial in prevention of cardiovascular disease.