Bioimpedance spectroscopy is not associated with a clinical diagnosis of breast cancer-related lymphedema.

The objective of this study was to evaluate the accuracy of bioimpedance spectroscopy measurements (L-Dex) in the diagnosis of breast cancer-related lymphedema. A retrospective review of a prospectively maintained database was performed of all patients that underwent surgical treatment for breast cancer at a tertiary medical center. Patients who had preoperative and postoperative evaluation for possible lymphedema by limb circumference measurements and bioimpedance were eligible for inclusion in the study. No significant demographic differences were found between the group of patients clinically diagnosed with lymphedema (N=134) and those without a clinical diagnosis of lymphedema (N=261). The ability of bioimpedance to diagnose lymphedema based on the manufacturer's criteria demonstrated low sensitivity, which was 7.5% when lymphedema was defined as an absolute L-Dex value greater than 10, and 24.6% when defined as a relative change of >10 between preoperative and postoperative measurements. This corresponded with a positive predictive value of 61-71% and a negative predictive value of 67-70%. We are unable to recommend the use of bioimpedance as a screening tool or for measurement of breast cancer-related lymphedema.

Vega is a rapidly rotating star.

Vega, the second brightest star in the northern hemisphere, serves as a primary spectral type standard. Although its spectrum is dominated by broad hydrogen lines, the narrower lines of the heavy elements suggested slow to moderate rotation, giving confidence that the ground-based calibration of its visible spectrum could be safely extrapolated into the ultraviolet and near-infrared (through atmosphere models), where it also serves as the primary photometric calibrator. But there have been problems: the star is too bright compared to its peers and it has unusually shaped absorption line profiles, leading some to suggest that it is a distorted, rapidly rotating star seen pole-on. Here we report optical interferometric observations that show that Vega has the asymmetric brightness distribution of the bright, slightly offset polar axis of a star rotating at 93 per cent of its breakup speed. In addition to explaining the unusual brightness and line shape peculiarities, this result leads to the prediction of an excess of near-infrared emission compared to the visible, in agreement with observations. The large temperature differences predicted across its surface call into question composition determinations, adding uncertainty to Vega's age and opening the possibility that its debris disk could be substantially older than previously thought.

The combined effects of novel tocotrienols and lovastatin on lipid metabolism in chickens.

Both lovastatin (a fungal product) and a tocotrienol rich fraction (TRF(25), a mixture of tocols isolated from stabilized and heated rice bran containing desmethyl [d-P(21)-T3] and didesmethyl [d-P(25)-T3] tocotrienols) are potent hypocholesterolemic agents, although they suppress cholesterol biosynthesis by different mechanisms. To determine additive and/or synergistic effects of both agents, chickens were fed diets supplemented with 50 ppm TRF(25) or d-P(25)-T3 in combination with 50 ppm lovastatin for 4 weeks. Combinations of d-P(25)-T3 with lovastatin were found most effective in reducing serum total cholesterol and low-density lipoprotein (LDL) cholesterol compared to the control diet or individual supplements. The mixture of TRF(25)+lovastatin inhibited the activity of beta-hydroxy-beta-methylglutaryl coenzymeA reductase (21%) compared to lovastatin alone, which did not change its activity. Cholesterol 7alpha-hydroxylase activity was increased by lovastatin (11%) and by lovastatin plus TRF(25) (19%). TRF(25)+lovastatin decreased levels of serum total cholesterol (22%), LDL cholesterol (42%), apolipoprotein B (13-38%), triglycerides (19%), thromboxane B(2) (34%) and platelet factor 4 (26%), although high-density lipoprotein (HDL) cholesterol, and apolipoprotein A1 levels were unaffected. The mixture of TRF(25)+lovastatin showed greater effects than did the individual treatments alone, reflecting possible additive pharmacological actions. The effects, however, of the d-P(25)-T3/lovastatin combination were no greater than that of d-P(25)-T3 alone, possibly indicating that d-P(25)-T3 produced a maximum cholesterol lowering effect at the concentration used.

Novel tocotrienols of rice bran suppress cholesterogenesis in hereditary hypercholesterolemic swine.

A tocotrienol-rich fraction (TRF(25)) and novel tocotrienols (d-P(21)-T3 and d-P(25)-T3) of rice bran significantly lowered serum and low density lipoprotein cholesterol levels in chickens. The present study evaluated the effects of novel tocotrienols on lipid metabolism in swine expressing hereditary hypercholesterolemia. Fifteen 4-mo-old genetically hypercholesterolemic swine were divided into five groups (n = 3). Four groups were fed a corn-soybean control diet, supplemented with 50 microg of either TRF(25), gamma-tocotrienol, d-P(21)-T3 or d-P(25)-T3 per g for 6 wk. Group 5 was fed the control diet for 6 wk and served as a control. After 6 wk, serum total cholesterol was reduced 32-38%, low density lipoprotein cholesterol was reduced 35-43%, apolipoprotein B was reduced 20-28%, platelet factor 4 was reduced 12-24%, thromboxane B(2) was reduced 11-18%, glucose was reduced 22-25% (P<0.01), triglycerides were reduced 15-19% and glucagon was reduced 11-17% (P<0.05) in the treatment groups relative to the control. Insulin was 100% greater (P<0.01) in the treatment groups than in the control group. Preliminary data (n = 1) indicated that hepatic activity of the 3-hydroxy-3-methylglutaryl-coenzyme A reductase was lower in the treatment groups, and cholesterol 7alpha-hydroxylase activity was unaffected. Cholesterol and fatty acid levels in various tissues were lower in the treatment groups than in control. After being fed the tocotrienol-supplemented diets, two swine in each group were transferred to the control diet for 10 wk. The lower concentrations of serum lipids in these four treatment groups persisted for 10 wk. This persistent effect may have resulted from the high tocotrienol levels in blood of the treatment groups, suggesting that the conversion of tocotrienols to tocopherols may not be as rapid as was reported in chickens and humans.

Isolation and identification of novel tocotrienols from rice bran with hypocholesterolemic, antioxidant, and antitumor properties.

Two novel tocotrienols were isolated from stabilized and heated rice bran, apart from the known alpha-, beta-, gamma-, and delta-tocopherols and tocotrienols. These new tocotrienols were separated by HPLC, using a normal phase silica column. Their structures were determined by ultraviolet, infrared, nuclear magnetic resonance, circular dichroism, and high-resolution mass spectroscopies and established as desmethyl tocotrienol [3, 4-dihydro-2-methyl-2-(4,8,12-trimethyltrideca-3'(E),7'(E), 11'-trienyl)-2H-1-benzopyran-6-ol] and didesmethy tocotrienol [3, 4-dihydro-2-(4,8,12-trimethyltrideca-3'(E),7'(E), 11'-trienyl)-2H-1-benzopyran-6-ol]. These tocotrienols significantly lowered serum total and LDL cholesterol levels and inhibited HMG-CoA reductase activity in chickens. They had much greater in vitro antioxidant activities and greater suppression of B16 melanoma cell proliferation than alpha-tocopherol and known tocotrienols. Results indicated that the number and position of methyl substituents in tocotrienols affect their hypocholesterolemic, antioxidant, and antitumor properties.

Antioxidant capacity of oat (Avena sativa L.) extracts. 2. In vitro antioxidant activity and contents of phenolic and tocol antioxidants.

Oat milling fractions were examined for concentrations of total phenolics, tocols, and phenolic acids and in vitro antioxidant activity to determine their potential as dietary antioxidants. Methanolic extracts of pearling fractions, flour and aspirations from flaking, and trichomes had high, intermediate, and low antioxidant activities, respectively, evaluated by the beta-carotene bleaching method. Pearling fractions were also highest in total phenolics and tocols. p-Hydroxybenzoic acid, vanillic acid, caffeic acid, vanillin, p-coumaric acid, and ferulic acid were identified and quantified by HPLC. Three avenanthramides and an unidentified ferulate derivative were also detected. Total phenolic content was significantly correlated with antioxidant activity, and regression equations that predicted antioxidant activity from phenolic and tocol concentrations were calculated. Antioxidant activity, evaluated by beta-carotene bleaching, was correlated with measures of oxygen radical absorbance capacity and low-density lipoprotein oxidation. These data indicate a potential for oat products, especially those enriched in outer layers of the groat, to contribute to dietary intakes of antioxidant phytonutrients.

Application of a birdcage coil at 3 Tesla to imaging of the human knee using MRI.

A transceive RF birdcage coil designed for very high field with a novel matching scheme was implemented with the specific geometry chosen for the human knee. This coil design incorporates a hinge for greater patient accessibility. Volunteer human subjects were studied using spin-echo and 3D gradient echo sequences for image acquisition. The higher signal-to-noise and improved tissue contrast obtained from this high-field system, coupled with the optimized coil design, improves visualization of the structural detail in articular cartilage, which is not seen well at conventional field strengths. This has important clinical implications, as newer medical and surgical treatments become available for the treatment of early cartilage degeneration. Magn Reson Med 42:215-221, 1999.

Correlation of quantitative bone marrow and blood cultures in AIDS patients with disseminated Mycobacterium avium complex infection.

The relationship between Mycobacterium avium complex (MAC) infection of blood and bone marrow was studied in human immunodeficiency virus-infected patients before and during treatment. Quantitative cultures were obtained at baseline from 17 persons with newly detected MAC bacteremia. Serial blood cultures were obtained, and a second bone marrow sample was obtained at 4 or 8 weeks. At baseline, the median MAC load in bone marrow core samples was 3 log10 higher than in blood. Bone marrow MAC loads ranged widely (866-847,315 cfu/g), and no significant correlation was found between MAC load in blood and that in bone marrow core samples. MAC loads in bilateral bone marrow biopsy samples from 7 subjects were highly correlated. MAC loads declined in blood and bone marrow at similar rates during therapy, but blood was sterilized before bone marrow. Length of survival was inversely associated with initial bone marrow core MAC load but not with blood MAC load. Initiation of treatment when tissue MAC load is low may increase the likelihood of favorable clinical outcome.

HIV-1-specific CD4+ T cells are detectable in most individuals with active HIV-1 infection, but decline with prolonged viral suppression.

The role of HIV-1-specific CD4+ T-cell responses in controlling HIV-1 infection remains unclear. Previous work has suggested that such cells are eliminated in the early stages of infection in most subjects, and thus cannot substantially contribute to host defense against HIV-1. Here, using flow cytometric detection of antigen-induced intracellular cytokines, we show that significant frequencies of gag specific, T-helper-1 CD4+ memory T cells are detectable in most subjects with active/progressive HIV-1 infection (median frequency, 0.12% of memory subset; range, 0-0.66%). Median frequencies of these cells were considerably higher in nonprogressive HIV-1 disease (0.40%), but there was substantial overlap between the two groups (range of nonprogressors, 0.10-1.7%). Continuous HIV-1 suppression with anti-retroviral therapy was associated with a time-dependent reduction in median frequencies of gag-specific CD4+ memory T cells: 0.08% in subjects treated for 4-24 weeks, and 0.03% in subjects treated for 47-112 weeks. Thus, functional HIV-1-specific CD4+ T cells are commonly available for support of anti-HIV-1 effector responses in active disease, but their decline with anti-retroviral therapy indicates that immunologic participation in long-term HIV-1 control will probably require effective vaccination strategies.

Integrated RF coil with stabilization for fMRI human cortex.

Functional brain imaging of the human cortex is limited by poor contrast to noise ratio (CNR) and image degradation due to subject motion during the acquisition period. The work described here combines the use of closely coupled phased array receiver coils with a stabilization system to address these needs. Several phased array designs are evaluated and compared with the conventional "birdcage" design. Coil performance is reported in terms of relative SNR and fMRI results. Relative improvements of up to 360% are obtained for the occipital region and 180% in the temporal region. More modest gains of 10-30% were obtained for a "dome"-shaped birdcage volume coil covering the entire cortex.

Determination of antigen-specific memory/effector CD4+ T cell frequencies by flow cytometry: evidence for a novel, antigen-specific homeostatic mechanism in HIV-associated immunodeficiency.

The highly regulated secretion of effector cytokines by CD4+ T cells plays a critical role in immune protection against pathogens such as cytomegalovirus. Here, we directly compare the frequency and functional characteristics of cytomegalovirus-specific CD4+ memory/effector T cells in normal and HIV+ subjects using a novel, highly efficient multiparameter flow cytometric assay that detects the rapid intracellular accumulation of cytokine(s) after short-term (6 h) in vitro antigen stimulation. Responses in this assay correlate precisely with independent measures of sensitization history (e.g., seroreactivity), and allow the simultaneous assessment of multiple cytokines in single effector T cells. Healthy HIV- individuals manifested an average of 0.71, 0.72, 0.38, and 0.06% CD4+ T cells responding to cytomegalovirus with gamma-IFN, TNF-alpha, IL-2, and IL-4 production, respectively, with the simultaneous production of gamma-IFN, TNF-alpha, and IL-2 being the most common effector phenotype. Significantly, overall cytomegalovirus-specific CD4+ effector frequencies were markedly higher among 40% of HIV+ subjects (2.7-8.0%), and demonstrated a predominately polarized gamma-IFN+/TNF-alpha+/IL-2-/IL-4- phenotype. In contrast, CD4+ effector frequencies for heterologous, nonubiquitous viruses such as the mumps virus were low or absent in the HIV+ group. These data suggest the existence of homeostatic mechanisms in HIV disease that selectively preserve memory T cell populations reactive with ubiquitous pathogens such as cytomegalovirus-likely at the expense of T cell memory to more sporadically encountered infectious agents.

Amaranth and its oil inhibit cholesterol biosynthesis in 6-week-old female chickens.

All amaranth varieties contain tocotrienols and squalene compounds which are known to affect cholesterol biosynthesis. Therefore, in the present study, the influence of dietary supplementation of whole seed, popped, and milled amaranth and amaranth oil on cholesterogenesis was studied in 6-wk-old female chickens. Serum total cholesterol and LDL-cholesterol were lowered 10-30% and 7-70% (P < 0.01), respectively, in birds fed amaranth-containing diets. HDL-cholesterol was not affected by amaranth supplementation. Activities of liver cholesterol 7alpha-hydroxylase (the enzyme responsible for cholesterol breakdown into bile acids) were 10-18% higher (P < 0.01) than those of controls for birds fed most forms of amaranth and its oil, whereas activities of liver 3-hydroxy-3-methylglutaryl coenzyme A reductase (the rate-limiting enzyme for cholesterol biosynthesis) were lowered by about only 9% (P < 0.01) by popped, milled amaranth and its oil. This lack of marked inhibition of this enzyme suggests the presence of some other potent cholesterol inhibitor(s) apart from tocotrienols and squalene in amaranth.

Dietary alpha-tocopherol attenuates the impact of gamma-tocotrienol on hepatic 3-hydroxy-3-methylglutaryl coenzyme A reductase activity in chickens.

The concentration-dependent impact of gamma-tocotrienol on serum cholesterol can be traced to the posttranscriptional down-regulation of 3-hydroxy-3-methylglutaryl coenzyme A reductase activity. gamma-Tocotrienol also suppresses tumor growth. Palmvitee, the tocopherol and tocotrienol-rich fraction of palm oil, is the sole commercial source of gamma-tocotrienol. Contrary to the universal findings of the efficacy of gamma-tocotrienol there are conflicting reports of the impact of Palmvitee on 3-hydroxy-3-methylglutaryl coenzyme A reductase activity, serum cholesterol concentrations and tumor development. These conflicting reports led us to examine the impact of alpha-tocopherol on the cholesterol-suppressive action of gamma-tocotrienol. Control and experimental diets were fed to groups of White Leghorn chickens (n = 10) for 26 d. The control diet was supplemented with 21 nmol alpha-tocopherol/g. All experimental diets provided 141 nmol of blended tocols/g diet. The alpha-tocopherol and gamma-tocotrienol concentrations of the experimental diets ranged from 21 to 141 and 0 to 120 nmol/g, respectively. We now report that including alpha-tocopherol in tocol blends containing adequate gamma-tocotrienol to suppress 3-hydroxy-3-methylglutaryl coenzyme A reductase activity results in an attenuation of the tocotrienol action (P < 0.001). A summary of results from studies utilizing different Palmvitee preparations shows that effective preparations consist of 15-20% alpha-tocopherol and approximately 60% gamma- (and delta-) tocotrienol, whereas less effective preparations consist of > or = 30% alpha-tocopherol and 45% gamma- (and delta-) tocotrienol.

Response of hypercholesterolemic subjects to administration of tocotrienols.

The cholesterol-suppressive actions of Palmvitee and gamma-tocotrienol were assessed in hypercholesterolemic subjects after acclimation to the American Heart Association Step 1 dietary regimen for four and eight weeks, respectively. The four-week dietary regimen alone elicited a 5% decrease (P < 0.05) in the cholesterol level of the 36 subjects. Subjects continuing on the dietary regimen for a second four-week period experienced an additional 2% decrease in their cholesterol levels. Dietary assessments based on unanticipated recalls of 24-h food intake records suggest that significant reductions in energy and fat, predominantly in saturated fat, intakes are responsible. The subjects experienced significant Palmvitee- and gamma-tocotrienol-mediated decreases in cholesterol. The group of subjects acclimated to the dietary regimen for four weeks responded to Palmvitee (a blend of tocols providing 40 mg alpha-tocopherol, 48 mg alpha-tocotrienol, 112 mg gamma-tocotrienol, and 60 mg delta-to-cotrienol/day for four weeks) with a 10% decrease in cholesterol (P < 0.05). Dietary assessments showed no further change in energy and fat intakes. alpha-Tocopherol attenuated the cholesterol-suppressive action of the tocotrienols. The second group of subjects, acclimated to the dietary regimen for eight weeks, received 200 mg gamma-tocotrienol/d for four weeks. The cholesterol-suppressive potency of this alpha-tocopherol-free preparation was calculated to be equivalent to that of the mixture of tocotrienols (220 mg) used in the prior study. Cholesterol levels of the 16 subjects in the second group decreased 13% (P < 0.05) during the four-week trial. Plasma apolipoprotein B and ex vivo generation of thromboxane B2 were similarly responsive to the tocotrienol preparations, whereas neither preparation had an impact on high density lipoprotein cholesterol and apolipoprotein A-1 levels.

Noncovalent binding of a mitomycin C metabolite, 2,7-diaminomitosene, to duplex DNA.

The major metabolite of mitomycin C, 2,7-diaminomitosene (DAM), interacts noncovalently with DNA. This was supported by ultraviolet-visible spectrum changes upon mixing with DNA and ethidium bromide displacement from DNA, measured as fluorescence changes. Moreover, DAM bound to DNA sufficiently strongly to hold DNA in a double stranded conformation under denaturing gel electrophoresis conditions commonly used to measure mitomycin C cross-links. These data show that generation of DAM and interaction with DNA represent a potential additional mechanism of DNA damage induced by mitomycin C.

Dose-related activity of stavudine in patients infected with human immunodeficiency virus.

In a multicenter, randomized, open-label, dose-ranging study to determine the relative effects of three dose levels of stavudine on CD4 lymphocyte count, weight gain, and hematologic variables in patients infected with human immunodeficiency virus (HIV), 152 patients with CD4 lymphocyte counts < or = 600/mm3 received stavudine at 0.1 mg/kg/day (n = 51), 0.5 mg/kg/day (n = 53), or 2.0 mg/kg/day (n = 48). The study was designed to evaluate the activity of stavudine after 10 weeks of therapy and permitted extended dosing and follow-up for long-term safety. A significant dose effect on increases in CD4 lymphocyte counts and declines in HIV titer in peripheral blood mononuclear cells was observed. Stavudine was well-tolerated; the only dose-related, dose-limiting adverse event was peripheral neuropathy, which usually was reversible. In this trial, the most favorable therapeutic index was seen at 0.5 mg/kg/day.

A review of 'The Health Security Act of 1993'.

The Health Security Act of 1993, which is now before Congress, holds the potential to effect major changes in the way health care is delivered in this country and in how that delivery is financed. This article reviews the principal provisions proposed to be contained in the act (as presented in the preliminary summary released in September 1993) and offers suggestions regarding the issues that hospital financial managers should begin addressing now.

Logarithmic relationship of the CD4 count to survival in patients with human immunodeficiency virus infection.

BACKGROUND: Survival, and the incidence of events that define the acquired immunodeficiency syndrome (AIDS), are known to be inversely related to the CD4 count in patients with human immunodeficiency virus infection. We wished to quantify this relationship more precisely, particularly for patients with CD4 counts of less than 50/mm3. METHODS: Prospective surveillance for survival and for all AIDS-defining events was performed on all 2682 patients with human immunodeficiency virus infection who had at least one CD4 count performed at a large urban public hospital during a 3-year period. Product-limit survival and incidence of AIDS-defining events were calculated as a function of baseline CD4 count. RESULTS: The 1-year product-limit survival was 17% +/- 6% for patients after a baseline CD4 count of 1 to 4/mm3; 44% +/- 6% after a count of 5 to 9/mm3; 48% +/- 5% after a count of 10 to 19/mm3; 51% +/- 4% after a count of 20 to 39/mm3; 62% +/- 5% after a count of 40 to 59/mm3; 71% +/- 4% after a count of 60 to 99/mm3; 79% +/- 3% after a count of 100 to 199/mm3; and 92% +/- 2% after a count of 200 to 499/mm3. One-year survival and baseline CD4 count were related by the following formula: percent 1-year survival = 10 + 32(log10 CD4 count) (R2 = .97; P < .001). The 1-year incidence of a first AIDS-defining event and baseline CD4 count were related by the following formula: percent developing AIDS in 1 year = 104-36(log10 CD4 count) (R2 = .89; P < .001). Similar relationships were calculated between the logarithm of the baseline CD4 count and the 1-year incidence of most AIDS-defining events. These relationships were linear over the CD4 range of 1 to 499/mm3 and over follow-up periods of 6 months to 2 years. CONCLUSIONS: The relationship of the CD4 count to survival, and to the incidence of AIDS-defining events, is logarithmic. This relationship helps explain the substantial differences in 1-year survival associated with baseline CD4 counts in the range below 50/mm3.