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F Kronenberg

Publications and source records attributed to F Kronenberg.

At least 19 recordsLinked to original sources
PubMed2000

Low apolipoprotein A-IV plasma concentrations in men with coronary artery disease.

OBJECTIVES: The objective of this study was to evaluate the relation between apolipoprotein A-IV (apoA-IV) plasma concentrations and coronary artery disease (CAD). BACKGROUND: Experimental in vitro and in vivo studies favor apoA-IV to be protective against the development of atherosclerosis. Mice that overexpress either human or mouse apoA-IV demonstrated a significant reduction of aortic atherosclerotic lesions compared with control mice. Data on apoA-IV plasma concentrations and CAD in humans are lacking. METHODS: We determined in two independent case-control studies of a Caucasian and an Asian Indian population whether apoA-IV plasma concentrations are related to the presence of angiographically assessed CAD. RESULTS: Plasma apoA-IV levels were significantly lower in 114 male Caucasian subjects with angiographically defined CAD when compared with 114 age-adjusted male controls (10.2 +/-3.8 mg/dL vs. 15.1 +/- 4.0 mg/dL, p < 0.001). Logistic regression analysis indicated that the association between apoA-IV levels and CAD was independent of the high-density lipoprotein cholesterol and triglyceride concentrations. The inverse relationship between plasma levels of apoA-IV and the presence of CAD was confirmed in an independent sample of 68 male Asian Indians with angiographically documented CAD and 68 age-matched controls. CONCLUSIONS: The results of this cross-sectional study demonstrate for the first time an association between low apoA-IV concentrations and CAD in humans and suggest that apoA-IV may play an antiatherogenic role in humans.

Apolipoproteins A↗
PubMed2000

Use of complementary and alternative medicine among Dominican emergency department patients.

This small, pilot study examined presenting complaint, brief health history, use of complementary and alternative medicine (CAM), and sociodemographic characteristics, among patients attending the emergency department (ED) of a large urban hospital. The sample (n = 50) was primarily Dominican and of low socioeconomic status. Almost half had used CAM for their presenting complaint or another health problem during the past year, most commonly in the form of medicinal plants made into herbal teas. CAM users were more likely to be female, longer-term residents of the United States, and to have also used religious practices for health problems. Subjects who had used CAM for any problem other than the presenting complaint during the past year rated its effectiveness higher than subjects who had used CAM for their presenting complaint. In conclusion, it is likely that a significant proportion of Dominican ED patients use CAM, suggesting that they should be asked about their CAM use during triage.

Adult↗
PubMed2000

Insulin and hypertension in the NHLBI Family Heart Study: a sibpair approach to a controversial issue.

The association between insulin and hypertension remains equivocal. We therefore investigated insulin levels in 3037 normotensive and 1067 hypertensive subjects from the National Heart, Lung and Blood Institute (NHLBI) Family Heart Study (FHS) by two different approaches. First, we compared insulin levels between normotensive and 275 untreated hypertensive subjects. Insulin levels unadjusted as well as adjusted for age, sex, and center were significantly higher in hypertensives. After adjustment for body mass index (BMI), insulin remained significantly higher only in the diastolic hypertensive group (mean +/- SD 77.0 +/-36.7 pmol/L, P < .01) but not in the isolated systolic hypertensive group (67.0 +/- 38.2 pmol/L) when compared to normotensives (63.2 +/- 29.1 pmol/L). A sibpair analysis was then used that compared the intra-sibpair differences in insulin concentrations to the intra-sibpair differences in blood pressure (BP) levels. This approach was intended to control for the effects of genetic and residual shared environmental variance upon insulin levels. The intra-sibpair difference in insulin concentrations between concordant (diastolic and systolic deltaBP < 5 mm Hg) and discordant sibpairs (diastolic and systolic deltaBP > 15 and > 20 mm Hg, respectively) was no longer significantly different when adjusted for BMI (2.7 v 5.9 pmol/L for diastolic and -1.7 v -1.8 pmol/L for systolic BP). Even the random selection of one sibpair from each of the 326 families independently of insulin and BP levels did not result in a significant correlation between the intrasibpair differences in insulin and BP. Using an insulin resistance index instead of insulin did not change our findings. Our investigation in the FHS sample of families suggests that there is only a small, if any, influence of insulin levels on BP after adjustment for obesity-related sources of variation.

Adult↗
PubMed2000

Research on complementary/alternative medicine for patients with breast cancer: a review of the biomedical literature.

PURPOSE: This article reviews English-language articles published in the biomedical literature from 1980 to 1997 that reported results of clinical research on complementary and alternative medical treatments (CAM) of interest to patients with breast cancer. METHODS: We searched 12 electronic databases and the bibliographies of the retrieved papers, review articles, and books on CAM and breast cancer. The retrieved articles were grouped by end point: breast cancer (eg, tumor size, survival), disease-related symptoms, side effects of treatment, and immune function. Within each end point, we organized the articles by modality and assessed study design, findings, and qualitative aspects. RESULTS: Of the more than 1,000 citations retrieved, 51 fit our criteria for review. Of the articles reviewed, 17 were randomized clinical trials; three of these were trials of cancer-directed interventions, two of which involved the same treatment (melatonin). Seven articles described observational studies, and the remainder were reports of phase I or II trials. Relatively few CAM modalities reportedly used by many breast cancer patients were mentioned in articles retrieved by this process. Most articles had shortcomings. CONCLUSION: Although many studies had encouraging results, none showed definitively that a CAM treatment altered disease progression in patients with breast cancer. Several modalities seemed to improve other outcomes (eg, acupuncture for nausea, pressure treatments for lymphedema). If CAM studies are well-founded, well-designed, and meticulously conducted, and their hypotheses, methods, and results are reported clearly and candidly, research in this controversial area should acquire credibility both in the scientific community and among advocates of unconventional medicine.

Breast Neoplasms↗
PubMed2000

Preparative free-solution isotachophoresis for separation of human plasma lipoproteins: apolipoprotein and lipid composition of HDL subfractions.

We have previously shown that plasma lipoproteins can be separated by analytical capillary isotachophoresis (ITP) according to their electrophoretic mobility in a defined buffer system. As in lipoprotein electrophoresis, HDL show the highest mobility followed by VLDL, IDL, and LDL. Chylomicrons migrate according to their net-charge between HDL and VLDL, because ITP has negligible molecular sieve effects. Three HDL subfractions were obtained which were designated fast-, intermediate-, and slow-migrating HDL. To further characterize these HDL subfractions, a newly developed free-solution ITP (FS-ITP)-system was used, that allows micro-preparative separation of human lipoproteins directly from whole plasma (Böttcher, A. et al. 1998. Electrophoresis. 19: 1110-1116). The fractions obtained by FS-ITP were analyzed for their lipid and apolipoprotein composition and by two-dimensional nondenaturing polyacrylamide gradient gel electrophoresis (2D-GGE) with subsequent immunoblotting. fHDL are characterized by the highest proportion of esterified cholesterol of all three subfractions and are relatively enriched in LpA-I. Together with iHDL they contain the majority of plasma apoA-I, while sHDL contain the majority of plasma apoA-IV, apoD, apoE, and apoJ. Pre-beta-HDL were found in separate fractions together with triglyceride-rich fractions between sHDL and LDL. In summary, ITP can separate the bulk of HDL into lipoprotein subfractions, which differ in apolipoprotein composition and electrophoretic mobility. While analytical ITP permits rapid separation and quantitation for diagnostic purposes, FS-ITP can be used to obtain these lipoprotein subfractions on a preparative scale for functional analysis. As FS-ITP is much better suited for preparative purposes than gel electrophoresis, it represents an important novel tool for the functional analysis of lipoprotein subclasses.

Electrophoresis↗
PubMed1999

Role of lipoprotein(a) and apolipoprotein(a) phenotype in atherogenesis: prospective results from the Bruneck study.

BACKGROUND: Experimental studies have suggested both atherogenic and thrombogenic properties of lipoprotein(a) [Lp(a)], depending on Lp(a) plasma concentrations and varying antifibrinolytic capacity of apolipoprotein(a) [apo(a)] isoforms. Epidemiological studies may contribute to assessment of the relevance of these findings in the general population. METHODS AND RESULTS: This study prospectively investigated the association between Lp(a) plasma concentrations, apo(a) phenotypes, and the 5-year progression of carotid atherosclerosis assessed by high-resolution duplex ultrasound in a random sample population of 826 individuals. We differentiated early atherogenesis (incident nonstenotic atherosclerosis) from advanced (stenotic) stages in atherosclerosis that originate mainly from atherothrombotic mechanisms. Lp(a) plasma concentrations predicted the risk of early atherogenesis in a dose-dependent fashion, with this association being confined to subjects with LDL cholesterol levels above the population median (3.3 mmol/L). Apo(a) phenotypes were distributed similarly in subjects with and without early carotid atherosclerosis. In contrast, apo(a) phenotypes of low molecular weight emerged as one of the strongest risk predictors of advanced stenotic atherosclerosis, especially when associated with high Lp(a) plasma concentrations (odds ratio, 6.4; 95% CI, 2.8 to 14. 9). CONCLUSIONS: Lp(a) is one of the few risk factors capable of promoting both early and advanced stages of atherogenesis. Lp(a) plasma concentrations predicted the risk of early atherogenesis synergistically with high LDL cholesterol. Low-molecular-weight apo(a) phenotypes with a putatively high antifibrinolytic capacity in turn emerged as one of the leading risk conditions of advanced stenotic stages of atherosclerosis.

Adult↗
PubMed1999

Genetics and metabolism of lipoprotein(a) and their clinical implications (Part 1).

The human plasma lipoprotein Lp(a) has gained considerable clinical interest as a genetically determined risk factor for atherosclerotic vascular diseases. Numerous (including prospective) studies have described a correlation between elevated Lp(a) plasma levels and coronary heart disease, stroke and peripheral atherosclerosis. Lp(a) consists of a large LDL-like particle to which the specific glycoprotein apo(a) is covalently linked. The apo(a) gene is located on chromosome 6 and belongs to a gene family including the highly homologous plasminogen. Lp(a) plasma concentrations are controlled to a large extent by the extremely polymorphic apo(a) gene. More than 30 alleles at this locus determine a size polymorphism. The size of the apo(a) isoform is inversely correlated with Lp(a) plasma concentrations, which are non-normally distributed in most populations. To a minor extent, apo(a) gene-independent effects also influence Lp(a) concentrations. These include diet, hormonal status and diseases like renal disease and familial hypercholesterolemia. The standardisation of Lp(a) quantification is still an unresolved problem due to the enormous particle heterogeneity of Lp(a) and homologies of other members of the gene family. Stability problems of Lp(a) as well as statistical pitfalls in studies with small group sizes have created conflicting results. The apo(a)/Lp(a) secretion from hepatocytes is regulated at various levels including postranslationally by apo(a) isoform-dependent prolonged retention in the endoplasmic reticulum. This mechanism can partly explain the inverse correlation between apo(a) size and plasma concentrations. According to numerous investigations, Lp(a) is assembled extracellularly from separately secreted apo(a) and LDL. The sites and mechanisms of Lp(a) removal from plasma are only poorly understood. The human kidney seems to represent a major catabolic organ for Lp(a) uptake. The underlying mechanism is rather unclear; several candidate receptors from the LDL-receptor gene family do not or poorly bind Lp(a) in vitro. Lp(a) plasma levels are elevated over controls in patients with renal diseases like nephrotic syndrome and end-stage renal disease. Following renal transplantation, Lp(a) concentrations decrease to values observed in controls matched for apo(a) type. Controversial data on Lp(a) in diabetes mellitus mainly result from insufficient sample sizes in numerous studies. Large studies and those including apo(a) phenotype analysis have come to the conclusion that Lp(a) levels are not or only moderately elevated in insulin-dependent patients. In non-insulin-dependent diabetics Lp(a) is not elevated. Several rare disorders, such as LCAT and LPL deficiency, as well as liver diseases and abetalipoproteinemia are associated with low plasma levels or lack of Lp(a).

Arteriosclerosis↗
PubMed1999

Is apolipoprotein(a) a susceptibility gene for type I diabetes mellitus and related to long-term survival?

AIMS/HYPOTHESIS: High lipoprotein(a) [Lp(a)] plasma concentrations are a genetically determined risk factor for atherosclerotic complications. In healthy subjects Lp(a) concentrations are mostly controlled by the apolipoprotein(a) [apo(a)] gene locus which determines a size polymorphism with more than 30 alleles. Subjects with low molecular weight apo(a) phenotypes on average have higher Lp(a) concentrations than those with high molecular weight apo(a) phenotypes. There are many opinions about whether and why Lp(a) is raised in patients with Type I diabetes (insulin-dependent) mellitus. METHODS: We investigated Lp(a) plasma concentrations and apo(a) phenotypes in 327 patients with Type I diabetes mellitus (disease duration 1-61 years) and in 200 control subjects matched for age and sex. RESULTS: Patients with a disease duration of up to 15 years had significantly higher Lp(a) concentrations (24.3 +/- 34.0 mg/dl vs 16.7 +/- 22.6 mg/dl, p = 0.014) compared with control subjects. This increase can be explained by a considerably higher frequency of low molecular weight apo(a) phenotypes (38.9% vs 23.5%, p < 0.005). The frequency of low molecular weight apo(a) phenotypes decreased continuously with disease duration from 41.7% in those with disease duration of up to 5 years to 18.2% in those with the disease lasting more than 35 years. CONCLUSIONS/INTERPRETATION: Our data show that an increase of Lp(a) in Type I diabetic patients can only be observed in groups with short diabetes duration and that this elevation is genetically determined. Therefore, the apo(a) gene, located at 6q26-27, might be a susceptibility gene for Type I diabetes mellitus which is supported by recently published studies reporting evidence for linkage of this region (6q27) with Type I diabetes mellitus. Furthermore, the decreasing frequency of low molecular weight apo(a) phenotypes with disease duration suggests a survivor effect.

Adult↗
PubMed1999

Lipoprotein(a) plasma concentrations after renal transplantation: a prospective evaluation after 4 years of follow-up.

The highly atherogenic lipoprotein(a) [Lp(a)] is significantly elevated in patients with renal disease. It is discussed controversially whether Lp(a) concentrations decrease after renal transplantation and whether the mode of immunosuppressive therapy influences the Lp(a) concentrations. In a prospective study the Lp(a) concentrations before and on average 48 months after renal transplantation were measured in 145 patients. The determinants of the relative changes of Lp(a) concentrations were investigated in a multivariate analysis. Patients treated by CAPD showed a larger decrease of Lp(a) than hemodialysis patients, reflecting their markedly higher Lp(a) levels before transplantation. The relative decrease of Lp(a) was higher with increasing Lp(a) concentrations before transplantation in combination with an increasing molecular weight of apolipoprotein(a) [apo(a)]. That means that the relative decrease of Lp(a) is related to the Lp(a) concentration and the apo(a) size polymorphism. With increasing proteinuria and decreasing glomerular filtration rate, the relative decrease of Lp(a) became less pronounced. Neither prednisolone nor cyclosporine (CsA) had a significant impact on the Lp(a) concentration changes. Azathioprine (Aza) was the only immunosuppressive drug which had a dose-dependent influence on the relative decrease of Lp(a) levels. These data clearly demonstrate a decrease of Lp(a) following renal transplantation which is caused by the restoration of kidney function. The relative decrease is influenced by Aza but not by CsA or prednisolone.

Adult↗
PubMed1999

Corticotropin-induced reduction of plasma lipoprotein(a) concentrations in healthy individuals and hemodialysis patients: relation to apolipoprotein(a) size polymorphism.

Lipoprotein(a) [Lp(a)], a strong independent cardiovascular risk factor, consists of the unique apolipoprotein(a) [apo(a)] covalently linked to a low-density lipoprotein particle. Apo(a) contains a widely differing number of the plasminogen-like kringle IV, a size polymorphism that is codominantly inherited. In addition to powerful genetic control, renal failure is known to influence the plasma Lp(a) concentration. There is still a lot to be learned about the mode and site of catabolism of Lp(a), and there is no readily applicable Lp(a)-lowering treatment available. Therefore, it was of interest to study further the Lp(a)-lowering effect of corticotropin (ACTH) that has been demonstrated in small studies. The main purpose of the present study was to investigate the influence of ACTH on different apo(a) isoforms. Short-term treatment with ACTH decreased the plasma Lp(a) concentration in all 26 study participants. The two study groups (12 healthy individuals and 14 hemodialysis patients) responded similarly, with a median decrease in plasma Lp(a) of 39% and 49%, respectively. In subjects with two clearly separable apo(a) bands, apo(a) phenotyping and densitometric scanning of the bands before and after treatment with ACTH revealed a change in the proportion of apo(a) isoforms, ie, a shift toward the isoform with lower molecular weight. This was observed in seven of nine investigated subjects (four of five healthy individuals and three of four hemodialysis patients).

Adrenocorticotropic Hormone↗
PubMed1999

Dopamine D4 receptor polymorphism and idiopathic Parkinson's disease.

Patients with idiopathic Parkinson's disease (IPD) are described as having markedly decreased novelty seeking characteristics. Since recent publications suggest an association between the dopamine D4 receptor polymorphism and novelty seeking, we investigated this polymorphism in a group of 122 patients with IPD and 127 healthy control subjects. We found similar allele and genotype frequencies in both groups and no association with the age of onset of symptoms. Therefore, the dopamine D4 receptor polymorphism does not confer genetic susceptibility to IPD and cannot explain the decreased novelty seeking in IPD patients.

Aged↗
PubMed1999

Evidence for a major gene accounting for mild elevation in LDL cholesterol: the NHLBI Family Heart Study.

Studies of rare Mendelian disorders of low density lipoprotein cholesterol (LDL-C) metabolism have identified specific genetic mutations in the LDL receptor and apolipoprotein B. Although these rare mutations account for a small proportion of LDL-C variation, twin and adoption studies indicate that at least 50% of the overall LDL-C observed variation is genetically determined. In a heterogeneous sample of 3227 subjects from the NHLBI Family Heart Study collected from four US centres, we find evidence for a common major gene accounting for mild elevations (1.25 standard deviations) in LDL-C. The analysis favored a recessive model with a frequency of 0.52 for the gene influencing elevated LDL-C, phenotypic means of 113 mg/dl for the normal genotypes and 146 mg/dl for the abnormal genotype, and a significant polygenic heritability. This statistically-inferred major gene accounted for 24% of the variation in LDL-C, with polygenes accounting for another 28% of the variation. Using parameters for major gene transmission estimated in the segregation analysis, LDL-C showed no linkage to the LDL receptor gene (LDLR), nor to the apolipoprotein E gene (APOE), nor to the cholesterol 7alpha-hydroxylase gene (CYP7A1), indicating the major gene effect influencing mild elevation in LDL-C is not explained by any of these candidate loci.

Adult↗
PubMed1999

The low molecular weight apo(a) phenotype is an independent predictor for coronary artery disease in hemodialysis patients: a prospective follow-up.

Patients with end-stage renal disease treated by hemodialysis have a tremendous risk for cardiovascular complications that cannot be explained by traditional atherosclerosis risk factors. Lipoprotein(a) (Lp(a)), a risk factor for these complications in the general population, is significantly elevated in these patients. In this study, it was determined whether Lp(a) and/or the genetically determined apo(a) phenotype are risk predictors for the development of coronary artery disease in these patients. A cohort of 440 unselected hemodialysis patients were followed for a period of 5 yr independent of the cause of renal disease, duration of preceding treatment, and the preexistence of coronary artery disease at study entry. Coronary events defined as definite myocardial infarction, percutaneous transluminal coronary angioplasty, aortocoronary bypass, or a stenosis >50% in the coronary angiography were the main outcome measure. Sixty-six (15%) of the 440 patients suffered a coronary event during follow-up. In univariate analysis, patients with events were significantly older and showed a trend to lower HDL cholesterol concentrations, and higher apolipoprotein B and Lp(a) concentrations without reaching significance. Apo(a) phenotypes of low molecular weight, however, were significantly more frequent in patients with compared to those without events (43.9% versus 21.9%, P<0.001). The other lipids, lipoproteins, and apolipoproteins were similar in both groups. Multiple Cox proportional hazards regression analysis found age and the apo(a) phenotype to be the best predictors for coronary events during the observation period, independent of whether patients with a preexisting coronary artery disease or an age >65 yr at the study entry or both were excluded from the analysis. Diabetes mellitus was a risk factor only in presence of a low molecular weight apo(a) phenotype. The genetically determined apo(a) phenotype is a strong and independent predictor for coronary events in hemodialysis patients. Apo(a) phenotyping might be helpful to identify hemodialysis patients at high risk for coronary artery disease.

Adult↗
PubMed1999

Research on complementary and alternative therapies for cancer: issues and methodological considerations.

Recent evidence suggests that at least one cancer patient in three uses some form of complementary and alternative medicine (CAM). We conducted a review of the published research on the efficacy of these treatments for breast cancer, which resulted in some observations about the current state of research and guidelines for future research. Although many of the papers reported encouraging results, the preponderance of phase I and II trials and other limitations precluded definitive conclusions about the efficacy of the treatments reported in these studies. A growing institutional base in this country has begun to facilitate improved research on CAM for cancer, yet many gaps remain. For example, there are no published reports of clinical trials or observational studies with survival endpoints for treatment agents used by many cancer patients. Clinical trials of a few CAM treatments are now in progress, but the results will not be available for several years. More complex and customized treatments may require innovative study designs and practitioner-investigator collaborations. Given the mounting evidence that CAM treatments are biologically active as well as widely used, CAM research may affect cancer outcomes.

Breast Neoplasms↗
PubMed1999

Hormone-modulating herbs: implications for women's health.

Women in the United States are increasingly turning to botanical medicines to treat conditions throughout their life cycles. Many herbs traditionally used for women's health conditions have been found to contain phytoestrogens. Phytoestrogens and their metabolites can bind estrogen receptors and can have both estrogenic and anti-estrogenic effects. Many women are attracted to the idea of using phytomedicine as an alternative to hormone replacement therapy. It is unclear, however, whether these herbs are safe for women at risk for breast cancer or its recurrence. This paper considers the estrogenicity of herbs such as black cohosh (Cimicifuga racemosa) and the implications for women's health.

Breast Neoplasms↗
PubMed1999

Use of complementary and alternative medicine among African-American and Hispanic women in New York City: a pilot study.

OBJECTIVE: To explore the use of complementary and alternative medicine (CAM) among African-American and Hispanic women residing in New York City, including use of specific treatments and practitioners, perceived effectiveness of CAM, and culturally specific words or expressions for CAM. METHODS: Focus groups were conducted with two groups of African-American and two groups of Hispanic women (age 18-40 and 41-80) as preparation for the development of a quantitative instrument to assess the prevalence and determinants of CAM use among women of various ethnic backgrounds. Participants were recruited using a standard random digit dial procedure. RESULTS: The most commonly used CAM remedies were teas and herbs, vitamins and nutritional supplements, prayer and spiritual healing, meditation and relaxation techniques. Practitioners most frequently seen were chiropractors, herbalists, and acupuncturists. Use of alternative remedies and practitioners, particularly the latter, was most common among older women in both groups. Younger Hispanic women reported the most skepticism toward CAM, especially when it was used by relatives as a substitute for conventional medical care. Overall, these African-American and Hispanic women used CAM for a wide range of health conditions and for prevention. Few racial and ethnic differences emerged in patterns of CAM use for either self-care or treatment by practitioners, but there was a distinct age variation, especially in attitudes toward CAM.

Adolescent↗