Biomedical subjects

T G Baumgartner

Publications and source records attributed to T G Baumgartner.

At least 19 recordsLinked to original sources

PubMed2001

Deficiencies of folate and vitamin B(6) exert distinct effects on homocysteine, serine, and methionine kinetics.

Folate and vitamin B(6) act in generating methyl groups for homocysteine remethylation, but the kinetic effects of folate or vitamin B(6) deficiency are not known. We used an intravenous primed, constant infusion of stable isotope-labeled serine, methionine, and leucine to investigate one-carbon metabolism in healthy control (n = 5), folate-deficient (n = 4), and vitamin B(6)-deficient (n = 5) human subjects. The plasma homocysteine concentration in folate-deficient subjects [15.9 +/- 2.1 (SD) micromol/l] was approximately two times that of control (7.4 +/- 1.7 micromol/l) and vitamin B(6)-deficient (7.7 +/- 2.1 micromol/l) subjects. The rate of methionine synthesis by homocysteine remethylation was depressed (P = 0.027) in folate deficiency but not in vitamin B(6) deficiency. For all subjects, the homocysteine remethylation rate was not significantly associated with plasma homocysteine concentration (r = -0.44, P = 0.12). The fractional synthesis rate of homocysteine from methionine was positively correlated with plasma homocysteine concentration (r = 0.60, P = 0.031), and a model incorporating both homocysteine remethylation and synthesis rates closely predicted plasma homocysteine levels (r = 0.85, P = 0.0015). Rates of homocysteine remethylation and serine synthesis were inversely correlated (r = -0.89, P < 0.001). These studies demonstrate distinctly different metabolic consequences of vitamin B(6) and folate deficiencies.

Adult↗

PubMed2000

Primed, constant infusion with [2H3]serine allows in vivo kinetic measurement of serine turnover, homocysteine remethylation, and transsulfuration processes in human one-carbon metabolism.

BACKGROUND: One-carbon metabolism involves both mitochondrial and cytosolic forms of folate-dependent enzymes in mammalian cells, but few in vivo data exist to characterize the biochemical processes involved. OBJECTIVE: We conducted a stable-isotopic investigation to determine the fates of exogenous serine and serine-derived one-carbon units in homocysteine remethylation in hepatic and whole-body metabolism. DESIGN: A healthy man aged 23 y was administered [2,3,3-(2)H(3)]serine and [5,5,5-(2)H(3)]leucine by intravenous primed, constant infusion. Serial plasma samples were analyzed to determine the isotopic enrichment of free glycine, serine, leucine, methionine, and cystathionine. VLDL apolipoprotein B-100 served as an index of liver free amino acid labeling. RESULTS: [(2)H(1)]Methionine and [(2)H(2)]methionine were labeled through homocysteine remethylation. We propose that [(2)H(2)]methionine occurs by remethylation with [(2)H(2)]methyl groups (as 5-methyltetrahydrofolate) formed only from cytosolic processing of [(2)H(3)]serine, whereas [(2)H(1)]methionine is formed with labeled one-carbon units from mitochondrial oxidation of C-3 serine to [(2)H(1)]formate to yield cytosolic [(2)H(1)]methyl groups. The labeling pattern of cystathionine formed from homocysteine and labeled serine suggests that cystathionine is derived mainly from a serine pool different from that used in apolipoprotein B-100 synthesis. CONCLUSIONS: The appearance of both [(2)H(1)]- and [(2)H(2)]methionine forms indicates that both cytosolic and mitochondrial metabolism of exogenous serine generates carbon units in vivo for methyl group production and homocysteine remethylation. This study also showed the utility of serine infusion and indicated functional roles of cytosolic and mitochondrial compartments in one-carbon metabolism.

Adult↗

PubMed1999

Enteral nutrition in clinical practice.

Enteral nutrition has, at long last, found its place in the modulation of disease. Because of its importance in terms of both anabolic and catabolic processes, today's clinician must have a working knowledge of the types of enteral formulations, their delivery and the therapeutic considerations (particularly concomitant medications) that impact on the safety and efficacy of enteral nutrition. The advantages and disadvantages of this therapeutic intervention must be carefully weighed by the clinician, in concert with sound medical principles. Despite the widespread belief that enteral nutrition is superior to parenteral nutrition in humans, data does suggest that there is little difference between the two. Also, associated costs of enteral nutrition in contrast to parenteral nutrition need to be reappraised based on more invasive enteral access and falling parenteral nutrition prices. Although the enteral route is presumed to be the best feeding modality, the clinician must be ever vigilant about the shortcomings of using the gut, especially in the setting of severe inflammation, stenosis or sepsis. The best feeding modality, then, must blend a knowledge of the patients' anatomy, physiology, and disease with considerations of enteral access, timing of delivery, complications, and a myriad of other therapeutic variables (to include concurrent medication administration) that impact on the enteral feeding regimen. This article reviews the basic principles of enteral nutrition in clinical practice. It describes nutritional assessment, routes of administration, selection of feeding formulas based on nutritional needs, interactions with medications, as well as possible complications of enteral feeding.

Cost-Benefit Analysis↗

PubMed1997

Stability of ranitidine and thiamine in parenteral nutrition solutions.

Our objectives were to ascertain the stability of thiamine HCl (3 mg/L) and ranitidine HCl (150 mg/L) at room and refrigeration temperatures in a central vein formula of parenteral nutrition (PN) solution (containing 6% amino acid, 25% carbohydrate, macro- and microminerals, and multivitamins) and to determine the effect of ranitidine on the stability of thiamine. Stability of thiamine and ranitidine in PN solutions was also compared with PN-salt solutions, which contained no amino acids or carbohydrates, to indirectly ascertain the impact of these macronutrients on the stability of these moieties. High-pressure liquid chromatography (HPLC) methods were developed to measure thiamine and ranitidine in the PN mixture. Stability studies were conducted in triplicate and each sample was assayed in duplicate using newly developed HPLC methods. Refrigeration provided stability for both ranitidine and thiamine for extended periods of time. At room temperature, ranitidine was also shown to be stable for about 188 h; there was, however, significant degradation of thiamine at 24 h with, and without, addition of ranitidine. The time required for 10% of thiamine to degrade was calculated to be 12.9 h for the PN mixture containing multivitamins and ranitidine; 11.1 h for the PN mixture containing multivitamins alone; and 33.4 h for the PN mixture containing only thiamine HCl. This work suggests that the concentration of thiamine in this central vein PN formula, with or without ranitidine, falls below the 90% acceptable stability within 24 h.

Chromatography, High Pressure Liquid↗

PubMed1994

Natural history and course of acquired lactic acidosis in adults. DCA-Lactic Acidosis Study Group.

STUDY OBJECTIVE: To determine the pathogenesis and clinical course of lactic acidosis in adults receiving standard medical care. DESIGN: Placebo arm of a 5-year prospective, randomized, blinded study comparing placebo and dichloroacetate as specific lactate-lowering therapy. Each patient received intravenous saline placebo in addition to conventional therapy. SETTING: Intensive care units of 10 tertiary care hospitals in North America. PATIENTS: One hundred twenty-six patients with lactic acidosis, defined as arterial blood lactate greater than or equal to 5 mmol/L and either arterial pH of less than or equal to 7.35 or base deficit greater than 6 mmol/L. Patients were followed for up to 6 months. MEASUREMENTS AND MAIN RESULTS: Mean +/- SD demographic entry data for 126 patients included: age 56 +/- 17 years, lactate 10.4 +/- 5.5 mmol/L, pH 7.24 +/- 0.14, calculated base deficit 14.1 +/- 5.4, arterial systolic blood pressure 103 +/- 29 mm Hg, Glasgow Coma score 7.9 +/- 4.9, and APACHE II score 19.2 +/- 8.1. Despite fluids and pressors, 32% of patients had systolic blood pressures of less than or equal to 90 mm Hg in association with sepsis (59%), cardiac failure (18%), or hemorrhage (18%). The most common causes of lactic acidosis in the absence of shock were sepsis (49%), liver disease (15%), and respiratory failure (12%). The median survival was 38.5 hours. Survival at 24 hours was 59%. Arterial pH predicted 24-hour survival better than base deficit or bicarbonate level. Percent survival was 41% at 3 days and 17% at 30 days. Only 21% of patients survived to leave the intensive care unit, and 17% were discharged from the hospital. In patients receiving sodium bicarbonate, neither acid-base nor hemodynamic status improved. CONCLUSIONS: In this first prospective study of the clinical course of acute lactic acidosis in adults, nearly all subjects had both hemodynamic and nonhemodynamic (metabolic) underlying causes, many of which independently predicted survival and most of which were refractory to standard care.

Acidosis, Lactic↗

PubMed1993

Trace elements in clinical nutrition.

Although the nearly 20 essential trace elements in humans constitute a small fraction of total body weight (less than 4%), the effect of their presence on well-being is enormous. Enteral nutrition, whether oral or by tube, is fraught with problems that influence nutrient absorption, distribution, metabolism, and ultimately, excretion. Parenteral nutrition, although delivered to the intravascular milieu, carries with it no guarantee that the trace mineral will indeed reach the target site for action. With the questionable nature of dietary histories and their unavailability in the setting of relatively emergent nutrition therapy, it behooves the clinician to begin complete nutrition and to include recommended trace elements early on. The clinician must also be ever vigilant about delivering sufficient full-strength commercially available enteral formula to provide the recommended dietary allowances of trace minerals.

Enteral Nutrition↗

PubMed1992

A controlled clinical trial of dichloroacetate for treatment of lactic acidosis in adults. The Dichloroacetate-Lactic Acidosis Study Group.

BACKGROUND: Mortality is very high in lactic acidosis, and there is no satisfactory treatment other than treatment of the underlying cause. Uncontrolled studies have suggested that dichloroacetate, which stimulates the oxidation of lactate to acetyl-coenzyme A and carbon dioxide, might reduce morbidity and improve survival among patients with this condition. METHODS: We conducted a placebo-controlled, randomized trial of intravenous sodium dichloroacetate therapy in 252 patients with lactic acidosis; 126 were assigned to receive dichloroacetate and 126 to receive placebo. The entry criteria included an arterial-blood lactate concentration of > or = 5.0 mmol per liter and either an arterial-blood pH of < or = 7.35 or a base deficit of > or = 6 mmol per liter. The mean (+/- SD) arterial-blood lactate concentrations before treatment were 11.6 +/- 7.0 mmol per liter in the dichloroacetate-treated patients and 10.4 +/- 5.5 mmol per liter in the placebo group, and the mean initial arterial-blood pH values were 7.24 +/- 0.12 and 7.24 +/- 0.13, respectively. Eighty-six percent of the patients required mechanical ventilation, and 74 percent required pressor agents, inotropic drugs, or both because of hypotension. RESULTS: The arterial-blood lactate concentration decreased 20 percent or more in 83 (66 percent) of the 126 patients who received dichloroacetate and 45 (36 percent) of the 126 patients who received placebo (P = 0.001). The arterial-blood pH also increased more in the dichloroacetate-treated patients (P = 0.005). The absolute magnitude of the differences was small, however, and they were not associated with improvement in hemodynamics or survival. Only 12 percent of the dichloroacetate-treated patients and 17 percent of the placebo patients survived to be discharged from the hospital. CONCLUSIONS: Dichloroacetate treatment of patients with severe lactic acidosis results in statistically significant but clinically unimportant changes in arterial-blood lactate concentrations and pH and fails to alter either hemodynamics or survival.

Acidosis, Lactic↗

PubMed1992

Relative bioavailability of deuterium-labeled monoglutamyl tetrahydrofolates and folic acid in human subjects.

The bioavailability of orally administered monoglutamyl folic acid and various (6S)-tetrahydrofolates was examined in humans with stable-isotope methods. Folic acid (PteGlu), tetrahydrofolate (H4folate), 5-formyl-H4folate, 10-formyl-H4folate, and 5-methyl-H4folate were prepared for oral administration in 3',5'-2H2 labeled (d2) form, and [glu-2H4]folic acid (d4-PteGlu) was prepared for intravenous injection. In each of five trials, fasting adult males (n = 7) on a folate saturation regimen (2 mg/d) were given a single oral dose of one of the d2-folates in apple juice, as well as an intravenous injection of d4-PteGlu as a control. Urine was collected for 48 h and the isotope labeling of urinary folates determined by mass spectrometry. Isotope excretion ratios of urinary folates were used as criteria of bioavailability (pooled SE = 0.10): PteGlu (1.53, least squares mean), 10-formyl-H4folate (1.02), 5-methyl-H4folate (0.99), 5-formyl-H4folate (0.1.13), and H4folate (0.71). These results indicate that differences exist in the bioavailability of monoglutamyl folates under these experimental conditions. This variation, whether due to differences in absorption or postabsorptive events, must be considered in quantitative studies of folate utilization with this type of protocol.

Administration, Oral↗

PubMed1991

Relative bioavailability of deuterium-labeled monoglutamyl and hexaglutamyl folates in human subjects.

The bioavailability of orally administered mono- and polyglutamyl folates was examined in humans by using stable-isotope methods. [3',5'-2H2]Folic acid (d2-FA) and [3',5'-2H2]pteroylhexaglutamate (d2-PteGlu6) were prepared for oral administration and (glu-2H4)folic acid (d4-FA) was prepared for intravenous (iv) injection. In two trials, adult males (n = 7) on a folate saturation regimen (2 mg/d) were given a single 677-nmol oral dose of either d2-FA or d2-PteGlu6 in apple juice along with an iv injection of 502 nmol d4-FA as a control. Urine was collected for 48 h and the isotope labeling of urinary folates determined by mass spectrometry. The excretion ratio of urinary folates (% of d2-folate dose/% of d4-folate dose) resulting from oral d2-FA and iv d4-FA was 1.45 +/- 0.10 (mean +/- SEM) whereas the ratio for oral d2-PteGlu6 and iv d4-FA was 0.67 +/- 0.04. These results indicate that the d2-PteGlu6 is available to humans as a source of folate although its bioavailability is substantially less than that of d2-FA under these conditions.

Administration, Oral↗

PubMed1991

Bioavailability of pyridoxine-5'-beta-D-glucoside determined in humans by stable-isotopic methods.

Stable-isotopic methods were employed to evaluate the utilization of dietary pyridoxine-5'-beta-D-glucoside (PN-glucoside), a major form of vitamin B-6 in plant-derived foods, as a source of available vitamin B-6 for adult men (20-35 y old, n = 5). Deuterium-labeled forms of free pyridoxine (PN) and PN-glucoside were compared using the urinary excretion of labeled forms of the vitamin B-6 metabolite 4-pyridoxic acid as the main index of absorption and metabolism. When comparing orally administered, isotopically labeled PN and PN-glucoside in separate groups of subjects, similar bioavailability was observed although within-group variability was high. A dual-label study designed to examine the bioavailability of these compounds when administered simultaneously indicated that the utilization of deuterated PN-glucoside was 58 +/- 13% (mean +/- SEM) relative to that of deuterated PN. PN-glucoside was detected in all urine samples, which provided additional evidence of incomplete metabolic utilization. In contrast, intravenously administered PN-glucoside underwent approximately half the metabolic utilization of oral PN-glucoside. These studies indicate that the bioavailability of dietary PN-glucoside, although incomplete, is substantially greater in humans than previously found in rats. In addition, the difference between oral and intravenous routes suggests a role of beta-glucosidase(s) of the intestinal mucosa, microflora, or both in the release of free PN from dietary PN-glucoside.

Administration, Oral↗

PubMed1988

The effects of grapefruit pectin on patients at risk for coronary heart disease without altering diet or lifestyle.

Dietary intake of cholesterol has been linked to coronary heart disease. The effect of grapefruit pectin (Citrus paradisi) on plasma cholesterol, triglycerides, very low-density lipoprotein cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and the low-density lipoprotein:high-density lipoprotein cholesterol ratio was studied. The study design was a 16-week double-blind, crossover (placebo or pectin) using 27 human volunteers screened to be at medium to high risk for coronary heart disease due to hypercholesterolemia. The study did not interfere with the subjects' current diet or lifestyle. Grapefruit pectin supplementation decreased plasma cholesterol 7.6%, low-density lipoprotein cholesterol 10.8%, and the low-density lipoprotein:high-density lipoprotein cholesterol ratio 9.8%. The other plasma lipid fractions studied showed no significant differences. We conclude that a grapefruit pectin-supplemented diet, without change in lifestyle, can significantly reduce plasma cholesterol.

Adult↗

PubMed1988

Grapefruit pectin inhibits hypercholesterolemia and atherosclerosis in miniature swine.

We studied the effect of dietary grapefruit pectin on plasma cholesterol and the development of atherosclerosis in 18 miniature swine. Pigs were randomized to one of three diets: no added fat (I), added fat/cellulose (II), and added fat/pectin (III). Plasma cholesterol was measured monthly. Arteries were examined for atherosclerosis at the termination of the experiment. Pectin supplementation of an added fat diet resulted in a significantly lower average plasma cholesterol than did cellulose supplementation (168 mg/dl vs. 249 mg/dl, p less than 0.05). The pectin-fed pigs also developed less atherosclerosis of their aortas (1.1% vs. 7.0%, p less than 0.05) and coronary arteries (2.9% vs. 26.2% cross-sectional narrowing, p less than 0.05). Plasma cholesterol levels correlated with the severity of aortic (r = 0.836) and coronary artery (r = 0.735) atherosclerosis. We conclude that dietary grapefruit pectin supplementation inhibits hypercholesterolemia and appears to be proportionately protective against atherosclerosis.

Animals↗

PubMed1987

Causative factors for decreased pulmonary metastasis in parenterally fed mice.

Total parenteral nutrition (TPN) with fat and/or glucose as the caloric source is associated with a decrease in pulmonary metastasis in mice bearing subcutaneously implanted Lewis lung carcinoma. Five groups of white mice bearing Lewis lung carcinoma were assigned to receive various isocaloric and isonitrogenous oral and parenteral feedings: TPN, utilizing all nonnitrogen energy from glucose; per os, utilizing all nonnitrogen calories from glucose; electrolyte, utilizing nonnitrogen calories provided from a balanced casein diet and receiving an isovolemic infusion of electrolytes in the same composition as the TPN formula; 1/4 normal saline, also consuming the casein diet and receiving an isovolemic infusion of 1/4 normal saline; and an oral casein control (CON) without infusion. Results showed that there were no significant differences in tumor volume changes or tumor doubling time among the groups. However, tumor weight was significantly lower in groups receiving the TPN solution either orally or parenterally in comparison to the oral casein control. Pulmonary metastases were significantly lower in all parenteral groups, irrespective of solution composition, compared to the CON group. Thus it appears that parenteral fluid load rather than composition of the solution is the causative factor for the decrease in pulmonary metastases.

Administration, Oral↗

PubMed1987

Decreased lung metastasis and tumor growth in parenterally fed mice.

The influence of alternate forms of nutritional support on primary tumor growth rate, tumor DNA synthesis rate, and number of lung metastases was examined in Swiss mice bearing subcutaneously implanted Lewis lung carcinoma (LLC). From Day 14 through 22 postimplant, mice were fed by continuous intravenous infusion of dextrose/amino acid (TPN), were offered the same solution from a feeding bottle (PO), were offered a casein-based, solid diet (CASEIN), or were infused with an electrolyte (ELECT) solution while energy and nitrogen were provided from the casein diet. Tumor weight and doubling time were decreased in the PO group compared to CASEIN; however, host weight decreased by 22% in the PO group. Tumor weight and DNA synthesis were decreased in the TPN group compared to CASEIN, and host weight increased by 4.6%. The decreased rate of tumor growth in the PO group was not reflected in a decrease in DNA synthesis, perhaps a result of the circadian pattern of DNA synthesis as previously reported for LLC. The number of metastatic lung nodules was significantly decreased in both the TPN and ELECT groups compared to PO and CASEIN, suggesting that intravenous fluid load rather than nutrient intake was the causative factor. In this host-tumor system, parenteral feeding was associated with a decrease in primary tumor weight and DNA synthesis rate, maintenance of host weight, and a decrease in pulmonary metastatic disease compared to mice fed a conventional diet.

Animals↗

PubMed1987

Dosage form and formulation effects on the bioavailability of vitamin E, riboflavin, and vitamin B-6 from multivitamin preparations.

The effects of formulation factors and pharmaceutical dosage form on the bioavailability of RRR-alpha-tocopherol (d-alpha-tocopherol), riboflavin, and pyridoxine hydrochloride were studied after administration of two capsule formulations and a tablet to 12 normal humans. Absorption of RRR-alpha-tocopherol was increased from the Aquabiosorb soft elastic gelatin (SEG) capsule formulation compared with the modified standard-SEG capsule and the commercial tablet. There were no significant differences in bioavailability of riboflavin and pyridoxine hydrochloride between the SEG formulation and the tablet albeit a trend toward consistent absorption was seen from the SEG formulation. The modified-SEG formulation exhibited significantly lower bioavailability for these water-soluble vitamins. The enhanced bioavailability of vitamin E and the trend towards faster and more consistent absorption of riboflavin and vitamin B-6 from the SEG formulation may be related to the surfactant vehicle employed and the attendant wetting properties. The results also suggest ethnic differences in vitamin bioavailability.

Adult↗

PubMed1986

Parenteral handling precaution: particulate introduction resulting from needle sheath contamination.

The purpose of this in vitro experiment was to determine if inadvertent needle cap nicking would introduce particulate contamination. After a preliminary observation (n = 21), a more thorough confirmatory experiment (n = 28) was performed. Twenty-four of 28 needles were contaminated before, and 18 of 28 needles after, entry into a Latex injection port; 5 of these 18 needles remained contaminated post sterile water injection and withdrawal from the port. Since 19 of 24 contaminated needles lost their contamination within the simulated injection system, it was proposed that inadvertent needle cap particulate contamination to needle shafts may be introduced into in vivo tissue or delivered intravascularly.

Equipment Contamination↗

PubMed1986

Bacterial endotoxin retention by inline intravenous filters.

Filters used in i.v. administration sets were tested for their ability to retain bacterial endotoxins for up to 96 hours of continuous infusion. Inline filters composed of cellulose ester, polyacrylate, polypropylene, polyethylene, or Posidyne Nylon 66 were used during continuous infusion of 5% dextrose injection at 83 mL/hr. One milliliter of inoculum containing 10(8) Escherichia coli was injected through a port upstream from the filter. A bacterial filter was used to monitor the sterility of effluent from the inline filters. The effluent was tested with limulus amebocyte lysate (LAL) that could detect endotoxin concentrations greater than 50 pg/mL. A control solution was monitored for viability of the bacteria throughout the course of the study, and positive endotoxin controls were used to confirm the sensitivity of the LAL. Samples of effluent were tested at 0, 4, 19, 24, 48, 72, and 96 hours. Effluent from all filters was sterile throughout the study. LAL assay indicated that only the effluent from filters containing Posidyne Nylon 66 was free of endotoxins for 96 hours. Effluent from the other filters contained endotoxins immediately after injection of the E. coli. Of the inline filters tested, only the one composed of Posidyne Nylon 66 was able to retain E. coli endotoxin for 96 hours. Further study is needed with E. coli and other microorganisms that are likely contaminants of i.v. infusions.

Drug Contamination↗

PubMed1985

The effect of energy substrate manipulation on tumor growth and metastasis and intermediary metabolism in the parenterally fed mouse.

The effect of N-free energy substrate manipulation on tumor growth and metastasis, host maintenance, and intermediary metabolism was studied in parenterally fed Swiss mice bearing subcutaneously implanted Lewis lung carcinoma. Non-N energy was provided from dextrose (CHO), lipid emulsion (FAT), or a 75:25 balanced (BAL) solution, infused from day 14 through day 22 postimplant. Control mice were offered equivalent energy and N from a balanced, casein-based solid diet (CAS). Tumor-doubling time was significantly prolonged in the CHO group compared to FAT and CAS. Pulmonary metastatic nodules were decreased in number in all parenterally fed mice compared to CAS, suggesting that the route of administration altered pulmonary physiology in such a way that the transmissability and/or growth of the tumor cells was inhibited. Tumor-free body weight was maintained in the CHO (+ 1.3%) and BAL (+ 0.3%) groups. However, significant weight loss occurred, despite equal intake, in the FAT (-4.7%) and CAS (-7.5%) groups. The energy appeared to be channeled into nonoxidative pathways, reflected by an increase in hepatic and adipose tissue lipogenesis and hepatic glycogen content. During the period studied, parenteral dextrose/amino acid infusion in this host-tumor system resulted in a decrease in primary tumor growth and optimal host maintenance compared to fat-based TPN and enteral feeding of a balanced, solid diet. Tumor metastasis was decreased in all parenterally fed mice, a phenomenon related to the route of administration and apparently independent of energy substrate.

Adipose Tissue↗