PubMed HealthSearch

Biomedical subjects

M Kohlmeier

Publications and source records attributed to M Kohlmeier.

At least 19 recordsLinked to original sources

Bone fracture history and prospective bone fracture risk of hemodialysis patients are related to apolipoprotein E genotype.

This investigation of 219 hemodialysis patients relates the history and prospective risk of bone fractures to apolipoprotein E (apoE) genotype. A greater percentage of the 41 patients with the E3/4 and E4/4 genotypes than of the 38 patients with the E2/3 and E2/2 genotypes had a history of bone fractures at the time of recruitment (44% versus 16%, P < 0.005). During the 4 years following recruitment, more of the patients with apoE genotypes E3/4 and E4/4 than with apoE genotypes E2/3 and E2/2 suffered bone fractures, but this difference was not statistically significant (17.1 versus 5.3%, P < 0.1). ApoE genotype appears to be an important genetic risk factor for bone fracture, possibly due to its previously reported influence on vitamin K concentrations in blood.

Adult

Deficient dietary iron intakes among women and children in Russia: evidence from the Russian Longitudinal Monitoring Survey.

OBJECTIVES: This study evaluated the iron sufficiency of the Russian diet. METHODS: Data were obtained from 24-hour dietary recalls conducted in 4 rounds (1992 through 1994) of a nationally representative longitudinal survey of 10,548 women and children. Iron bioavailability was estimated via algorithms adjusting for enhancers (heme, vitamin C) and inhibitors (tannins in tea, phytates in grains) consumed at the same meal. RESULTS: Dietary iron intakes were deficient in the most vulnerable groups: young children and women of reproductive age. Poverty status was strongly associated with deficiency. After adjustment for enhancers and inhibitors, estimated bioavailable iron intakes at 3% to 4% of total iron were inadequate in all women and children. CONCLUSIONS: These dietary data suggest that Russian women and children are at high risk of iron deficiency. Grain products rich in phytates, which inhibit absorption, were the major food source of iron in Russia. High intakes of tea and low consumption of vitamin C also inhibited iron bioavailability. Since changes in eating behavior could potentially double iron bioavailability, educational programs should be explored as a strategy for improving iron nutriture.

Adolescent

Bone health of adult hemodialysis patients is related to vitamin K status.

This investigation of 68 hemodialysis patients (ages 33 to 91) analyzed the association of biochemical indicators of vitamin K nutriture and bone metabolism, and related both to past bone fracture history and prospective bone fracture risk. Phylloquinone concentrations were significantly lower in the 23 patients with previous fractures compared to those without (0.93 vs. 1.50 nmol/liter, P < 0.003) and a smaller percentage of their serum osteocalcin was carboxylated (48.8 vs. 53.6%, P < 0.03). The 41 patients who never had fractures had nearly three times higher phylloquinone concentrations than the nine patients with fractures during a four-year follow-up period (1.59 vs. 0.55 nmol/liter, P < 0.002) and more carboxylated serum osteocalcin (55.2 vs. 42.0%, P < 0.01). None of the patients with phylloquinone concentrations over 2.2 nmol/liter had elevated intact parathyroid hormone (iPTH) concentrations, and only patients with less than 1 nmol/liter phylloquinone had severe hyperparathyroidism (iPTH > 300 ng/liter). Our data thus indicate that suboptimal vitamin K nutriture in hemodialysis patients is associated both with increased bone fracture risk and with a high prevalence of hyperparathyroidism.

Adult

Chemistry, nutritional sources, tissue distribution and metabolism of vitamin K with special reference to bone health.

Vitamin K occurs in nature as a series of compounds with a common 2-methyl- 1,4 naphthoquinone nucleus and differing isoprenoid side chains at the 3 position. They comprise a single major plant form, phylloquinone with a phytyl side chain and a family of bacterially synthesized menaquinones (MKs) with multiprenyl side chains. The major dietary source to humans is phylloquinone for which the chief food contributors are green, leafy vegetables followed by certain vegetable oils (soybean, rapeseed and olive oils). Recent analyses by high pressure liquid chromatography are now providing a wide-ranging database of phylloquinone in foods. Menaquinones are found in moderate concentrations in only a few foods such as cheeses (MK-8 and MK-9). A wider spectrum of MKs is synthesized by the gut microflora, and their intestinal absorption probably accounts for most of the hepatic stores, particularly those with very long side chains (MKs-10--13) synthesized by members of the genus Bacteroides. The site of absorption of floral MKs is not known, but reasonable concentrations are found in the terminal ileum where bile salt-mediated absorption is possible. Both phylloquinone and menaquinones are bioactive in hepatic gamma-carboxylation but long-chain MKs are less well absorbed. Liver stores of vitamin K are relatively small and predominantly MKs-7--13. The hepatic reserves of phylloquinone (approximately 10% of the total) are labile and turn over at a faster rate than menaquinones. Trabecular and cortical bone appear to contain substantial concentrations of both phylloquinone and menaquinones. A majority (approximately 60-70%) of the daily dietary intake of phylloquinone is lost to the body by excretion, which emphasizes the need for a continuous dietary supply to maintain tissue reserves.

Animals

Transport of vitamin K to bone in humans.

Molecules with vitamin K activity are important for optimal bone health. The major compound of this group in bone is vitamin K1 (phylloquinone), which is derived exclusively from plant foods in the diet. Vitamin K1 is absorbed along with dietary fat from the small intestine and transported by chylomicrons in blood. In serum obtained after an overnight fast from healthy men more than half of the vitamin K1 was recovered from the density fraction that contains chylomicrons and chylomicron remnants (CR), and only a quarter was associated with the major lipoprotein in serum, low density lipoprotein. The concentration of vitamin K1 in serum is closely related to the triglyceride concentration. Another determinant of vitamin K1 concentration in serum is the presence of specific variants of apolipoprotein E (apoE). ApoE is a small protein through which the vitamin K-rich CR bind to lipoprotein receptors. The three most common variants of apoE promote CR clearance from circulation with very different efficiency, in the order E2>E3>E4. The variant that promotes CR clearance best is associated with low vitamin K1 concentration in serum and increased response to vitamin K antagonists. Vitamin K1 concentration in serum is linked to vitamin K status of bone. The bone protein osteocalcin tends to be less completely carboxylated in people with low vitamin K concentrations in serum. Many hemodialysis patients with a history of bone fractures have indications of poor vitamin K status. The same patients also appear to have a greatly increased prospective bone fracture risk.

Biological Transport

Adipose tissue as a medium for epidemiologic exposure assessment.

In the United States, adipose tissue is rarely used as a medium for assessment of prior exposures in epidemiologic studies. Adipose tissue aspirations are in general less invasive and carry less risk than phlebotomy. Tissue samples can be analyzed for a wide number of epidemiologically important exposures. Beyond reflecting long-term energy balance, this tissue offers a relatively stable depot of triglyceride and fat-soluble substances, such as fat-soluble vitamins, and pesticides. As a tissue it represents the greatest reservoir of carotenoids in the body. Halogenated hydrocarbons may be measured in concentrations of hundreds-fold greater than those in blood of the same individuals. The composition of adipose tissue also reflects the long-term dietary intakes of a number of essential fatty acids. The turnover times of all of these substances in adipose tissue remain under-researched. Sampling and storage of adipose tissue, homogeneity of sampling sites, turnover times, and the effects of diet, age, gender, race, hormones, and disease on adipose tissue composition are discussed in this review of current knowledge about adipose tissue stability. Experience in the use of adipose tissue sampling in epidemiologic studies in various countries has shown that it is simple to conduct, requires little training, carries little risk, and does not result in excessive participant refusal.

Adipose Tissue

Variation of phylloquinone (vitamin K1) concentrations in hemodialysis patients.

Intra- and interindividual variation of phylloquinone (vitamin K1) concentrations was investigated by repeat analysis of serum from 28 hemodialysis patients with different apolipoprotein E genotypes. Phylloquinone concentrations ranged from 0.1 to 9.0 nM, with a mean of 1.08 nM (standard deviation 1.90 nM). Most of the variation in serum phylloquinone concentrations was due to differences between patients; the ratio of intra- to interindividual variation was 0.17. Serum triglyceride concentrations and apoE genotype together accounted for 64% of interindividual variation; in contrast, only 6% of intraindividual variation could be attributed to differences in triglyceride concentrations. The small residual variance implies that different phylloquinone consumption levels contributed relatively little to the variation of serum concentrations ( < 36% of interindividual variance). The results suggest that individual disposition is a more important determinant of serum phylloquinone concentrations than dietary phylloquinone intake.

Aged

Lipoprotein metabolism and coffee intake--who is at risk?

Data from a representative health and nutrition survey of German adults (sample of 1073 women and 806 men) were used to investigate the relationship between coffee consumption and the concentration of cholesterol in serum as well as other lipoprotein constituents. For these outcome variables multivariate analyses were conducted separately for men and women. Differences in age, body mass index, smoking habits, use of oral contraceptives, physical activity, alcohol, fish, fat, milk and tea consumption were controlled for in the models. Interactions between coffee drinking behavior and smoking habits as well as between coffee and the use of oral contraceptives in their relationship with serum cholesterol were of special interest in the analyses. Higher coffee intake (> 400 ml/d) showed higher total cholesterol, LDL cholesterol and lower triglyceride rich lipoprotein (TRL) and triglyceride concentrations in serum compared to lower intake (< 200 ml/d). Smoking appeared to be an aggravating factor in these relationships. Results of the linear regression analysis demonstrated an increase of 1.66 mg/dL LDL-C per cup of coffee daily consumed for men and of 1.58 mg/dL for women. The combination of high coffee intake, smoking and no oral contraceptive use ever was associated with the highest total and LDL-C and lowest TRL concentrations in this population. The observed differences may be explained by an increase of lipoprotein lipase activity due to coffee consumption.

Adult

[Lipid adjustment of alpha-tocopherol concentrations in plasma].

Measurement of alpha-tocopherol concentrations circulating either in plasma or serum is the most common method of measuring the vitamin E status in men. The analytical determination with a suitable HPLC method produces precise and reliable results. The interpretation of the measured alpha-tocopherol values is complicated by the strong positive correlation with different blood lipids. A considerable misinterpretation of the data will occur if these confounding factors are not taken into account by a suitable adjustment. Different methods have been described in the literature which tried to control the confounding effect of blood lipids. These methods were not completely satisfying. Therefore, a mathematical regression model, based on residuals, is introduced and applied to the data of the VERA-study (Verbundstudie Ernährungserhebung und Risikofaktoren Analytik) and the consequences of the lipid-adjustment of the tocopherol values are studied in further statistical procedures. Thereafter, lipid-adjusted tocopherol concentrations can be subjected to more extensive statistical evaluations without the requirement of special stratification.

Adult

Phylloquinone transport and its influence on gamma-carboxyglutamate residues of osteocalcin in patients on maintenance hemodialysis.

Plasma concentrations of phylloquinone in 42 fasting hemodialysis patients showed a much wider range than in healthy adults. Phylloquinone concentrations were best predicted by the concentration ratio of beta-very-low-density-lipoprotein to low-density-lipoprotein cholesterol (r = 0.71), which is closely related to chylomicron-remnant clearance. Phylloquinone concentrations in plasma were related to apolipoprotein E genotype in the order E2 > E3 > E4. The percentage of carboxylated osteocalcin (HBC) was related to the plasma concentration of phylloquinone in patients with the apolipoprotein E genotype E3/3 (r = 0.52, P < 0.05), and in patients with the genotypes E2/3 and E2/2 (r = 0.23, P < 0.1). Overall, plasma triglyceride concentration was a better predictor for HBC than was the plasma concentration of phylloquinone. These results point to the overriding importance of chylomicrons for the transport of phylloquinone to liver and bone. Delivery to osteocalcin-producing osteoblasts seemed impaired in patients with the low receptor-affinity apolipoprotein variant E2, suggesting a major role of receptor-mediated chylomicron-remnant uptake in the transport of phylloquinone to bone.

1-Carboxyglutamic Acid

Analysis of haemoglobin variants using immobilized pH gradients.

We present a new method for analysis of haemoglobin variants in immobilized pH gradients. The isoelectric fractionation is performed in polyacrylamide gels with copolymerized pH gradients between pH 7.0 and 8.0. The common haemoglobin variants (HbA, HbF, HbS, HbC, HbE and HbA2) are clearly resolved within this pH range. The high resolving power and reproducibility of immobilized pH gradients combined with extremely short separation times make this fractionation technique superior to all electrokinetic procedures used for haemoglobin analysis. At present, isoelectric focusing in immobilized pH gradients is a complementary tool for haemoglobin analysis when classical electrophoretic techniques do not provide sufficient resolution. We hope that in the future this technique will gain the popularity it deserves.

Evaluation Studies as Topic

Rapid and simple method for the identification of apolipoprotein E isomorphic phenotypes from whole serum.

For the identification of apolipoprotein E isomorphic phenotypes, fresh or thawed serum was analyzed without prior delipidation or other pretreatment. Using 5% polyacrylamide gels with a 40 mm interelectrode distance, the isoforms were separated by isoelectric focusing in immobilized pH gradients ranging from pH 5 to 6.5, and transferred onto polyvinylidene difluoride membranes by contact blotting for 1 h. The apolipoprotein E isoforms were identified following immunostaining. The electrophoresis required less than 2 h and the entire procedure could be completed within 6 h.

Antibodies, Monoclonal

Lack of accumulation of midazolam in plasma and lipoprotein fractions during intravenous lipid infusions in patients on artificial respiration.

Severely ill patients often require total parenteral nutrition including intravenous lipid emulsions concurrently administered with lipophilic drugs. Therefore we investigated whether therapeutic application of a mixed medium chain/long chain triglyceride infusion affects the disposition of midazolam necessary for sedation in patients on artificial respiration. The concentrations of midazolam were measured in unfractionated plasma, and in lipoprotein fractions isolated from ex vivo blood samples, including determination of triglycerides and cholesterol; the albumin level was also analysed. Midazolam in the VLDL fraction was only 0.246 microgram.ml-1, whereas the total plasma concentration averaged 1.101 micrograms.ml-1, and the midazolam content of the LDL plus HDL fractions amounted to 1.771 micrograms.ml-1. Albumin in these lipoprotein fractions was just as unequally distributed. A lipid infusion resulted in a significant elevation of total triglycerides from 157 to 221 mg.dl-1 and VLDL-triglycerides from 77 to 155 mg.dl-1. The triglyceride content of the LDL plus HDL fraction rose from 102 to 139 mg.dl-1. At the same time the midazolam concentration in unfractionated plasma and in the VLDL and the LDL + HDL fractions decreased to 0.899 microgram.ml-1, 0.130 micrograms.ml-1, and 1.265 micrograms.ml-1, respectively. Cholesterol and albumin concentrations were not affected. The data show for the first time that a significant increase in plasma triglycerides during an intravenous lipid infusion does not result in accumulation of midazolam in lipoproteins, probably because albumin binding of the drug is very strong. The lack of midazolam trapping is important with respect to the safety of concurrent use of lipophilic drugs and intravenous lipid infusions.

Adult

The relationship between coffee consumption and lipid levels in young and older people in the Heidelberg-Michelstadt-Berlin study.

The relationship between coffee consumption and serum lipid levels was studied in a randomly selected sample of 395 young and 385 elderly adults in the Federal Republic of Germany. Analyses were done separately for men and women and for young and older people. After adjustment for body mass index, activity level, smoking, total energy intake, dietary fat, fish, milk, tea and alcohol consumption and oral contraceptive use a statistically significant increase in total serum- and LDL-cholesterol levels with increased coffee consumption was observed in the group of young men only. In this subgroup a difference of 0.11 mmol.l-1 serum cholesterol and of 0.10 mmol.l-1 LDL cholesterol for each additional cup of coffee consumed daily was calculated. This is one of the few studies that includes elderly people. No significant trend was seen between coffee consumption and serum- or LDL-cholesterol levels in the elderly.

Adult

Treatment of coronary heart disease by diet and exercise: fasting and diurnal lipoproteins.

The effects of a combined exercise and low-fat dietary regimen were studied in 11 patients with angiographically documented coronary heart disease (cholesterol 233 mg/dl, triglycerides 158 mg/dl) and 13 comparable patients (cholesterol 224 mg/dl, triglycerides 174 mg/dl) on usual care. During one year, fasting serum lipoproteins were lowered to "ideal" levels in the intervention group (cholesterol 191 mg/dl, triglycerides 100 mg/dl, LDL-cholesterol 121 mg/dl). There was no change of triglycerides and cholesterol on usual care while LDL-cholesterol rose significantly. Neither regimen had any effect on HDL-cholesterol. Diurnal triglycerides as a presumptive measure of IDL in the intervention group were diminished by 39%. The study demonstrates the feasibility of a diet and exercise regimen to normalize mildly elevated plasma lipid levels and thus to possibly affect the course of coronary heart disease without drugs.

Cholesterol

Benzbromarone disposition and uricosuric action; evidence for hydroxilation instead of debromination to benzarone.

Benzbromarone is one of the main uricosuric drugs currently used. We determined plasma concentrations of benzbromarone, bromobenzarone, and benzarone and 24 hour uric acid excretion in ten healthy individuals following fasting application of two different non-micronised benzbromarone brands. In addition we explored the influence of adjusting urinary pH to near neutral values and of concomitant food intake. Benzbromarone was more rapidly absorbed from the test preparation than from the reference preparation; the extent of systemic availability did not differ significantly. Urinary pH adjustment had no clearcut effect, whereas food intake retarded drug absorption (even though not significant because of the variability of the data). Binding of benzbromarone to plasma proteins exceeded 99%. Bromobenzarone and benzarone were not detectable and are unlikely to be major metabolites of benzbromarone. Instead we found two other compounds suggestive of metabolites, one of them being monohydroxilated benzbromarone. The plasma concentrations of the parent compound in one subject exceeded those of the rest of the group, possibly indicating genetic differences in drug metabolism. The uricosuric effect was not related to benzbromarone plasma concentrations.

Adult

Plasma-triglycerides and exercise: a delicate balance.

Alimentary lipemia was studied in 12 healthy young men with and without exercise. Three sets of experiments were performed. While continuous exercise of 90 min duration significantly reduced postprandial triglycerides by 26% (study I), this effect could not be observed when exercise was interrupted for 5 min after each 25 min (study II). Plasma free fatty acid concentrations, in the latter experiment, were significantly higher (by 311%) than during rest. When, in a third experiment continuous exercise was compared with intermittent physical activity, the latter condition significantly increased postprandial triglyceridemia, most probably due to precipitous rises of free fatty acids on each interruption of ergometry. It is concluded that in the third experiment the balance between triglyceride removal and triglyceride synthesis was shifted toward the latter. Whether exercise lowers, leaves unaltered, or raises plasma triglyceride levels may depend on subtle changes of experimental design.

Adult