Potential drug-drug and drug-disease interactions in well-functioning community-dwelling older adults.

WHAT IS KNOWN AND OBJECTIVE: There are few studies examining both drug-drug and drug-disease interactions in older adults. Therefore, the objective of this study was to describe the prevalence of potential drug-drug and drug-disease interactions and associated factors in community-dwelling older adults. METHODS: This cross-sectional study included 3055 adults aged 70-79 without mobility limitations at their baseline visit in the Health Aging and Body Composition Study conducted in the communities of Pittsburgh PA and Memphis TN, USA. The outcome factors were potential drug-drug and drug-disease interactions as per the application of explicit criteria drawn from a number of sources to self-reported prescription and non-prescription medication use. RESULTS: Over one-third of participants had at least one type of interaction. Approximately one quarter (25·1%) had evidence of had one or more drug-drug interactions. Nearly 10·7% of the participants had a drug-drug interaction that involved a non-prescription medication. % The most common drug-drug interaction was non-steroidal anti-inflammatory drugs (NSAIDs) affecting antihypertensives. Additionally, 16·0% had a potential drug-disease interaction with 3·7% participants having one involving non-prescription medications. The most common drug-disease interaction was aspirin/NSAID use in those with history of peptic ulcer disease without gastroprotection. Over one-third (34·0%) had at least one type of drug interaction. Each prescription medication increased the odds of having at least one type of drug interaction by 35-40% [drug-drug interaction adjusted odds ratio (AOR) = 1·35, 95% confidence interval (CI) = 1·27-1·42; drug-disease interaction AOR = 1·30; CI = 1·21-1·40; and both AOR = 1·45; CI = 1·34-1·57]. A prior hospitalization increased the odds of having at least one type of drug interaction by 49-84% compared with those not hospitalized (drug-drug interaction AOR = 1·49, 95% CI = 1·11-2·01; drug-disease interaction AOR = 1·69, CI = 1·15-2·49; and both AOR = 1·84, CI = 1·20-2·84). WHAT IS NEW AND CONCLUSION: Drug interactions are common among community-dwelling older adults and are associated with the number of medications and hospitalization in the previous year. Longitudinal studies are needed to evaluate the impact of drug interactions on health-related outcomes.

Tyrosine requirement of healthy men receiving a fixed phenylalanine intake determined by using indicator amino acid oxidation.

BACKGROUND: The currently accepted total aromatic amino acid requirement for adults is based on nitrogen balance measurements in individuals who received their intake of aromatic amino acids solely as phenylalanine. OBJECTIVE: The objective of this study was to determine the requirement for the amino acid tyrosine in healthy men receiving an adequate, but not excessive, intake of phenylalanine (9 mg x kg(-1) x d(-1)). DESIGN: The effect of a graded intake of tyrosine was determined in 6 healthy men consuming energy-sufficient diets containing 1 g protein x kg(-1) x d(-1). The tyrosine requirement was determined by using indicator amino acid oxidation methodology with L-[1-13C]lysine as the indicator. Subjects were studied at each of 7 tyrosine intakes. RESULTS: A graded intake of tyrosine had no effect on lysine flux. The mean tyrosine requirement was determined from the response of the oxidation of L-[1-13C]lysine to breath 13CO2. A 2-phase linear regression crossover analysis of breath 13CO2 identified the breakpoint and upper 95% confidence limit, which represents the mean and safe intakes, to be 6.0 and 7.0 mg x kg(-1) x d(-1), respectively. CONCLUSIONS: The safe intake of total aromatic amino acids calculated from the present results for tyrosine and our previous estimate for phenylalanine is estimated to be 21 mg x kg(-1) x d(-1). This intake is 1.5 times the currently recommended total aromatic amino acid intake of the FAO/WHO/UNU (1985), 14 mg x kg(-1) x d(-1). Furthermore, the absolute aromatic amino acid requirement may be dependent on the proportional balance of these amino acids in the diet.

Effect of tyrosine intake on the rate of phenylalanine hydroxylation in adult males.

This study evaluated the effect of varying levels of tyrosine intake on the estimation of phenylalanine hydroxylation. Healthy men were fed 1 g protein kg(-1) x d(-1) for a 2-day period. On the third day, subjects consumed a formula diet containing 1 g protein kg(-1) x d(-1) hourly over 10 hours, and primed hourly oral doses of L-[15N]phenylalanine and L-[3,3-2H2]tyrosine for the last 6 hours. Each subject was studied at 7 levels of tyrosine intake (3.0, 4.5, 6.0, 7.5, 9.0, 10.5, and 12.0 mg x kg(-1) x d(-1)) at a constant intake of phenylalanine (9 mg x kg(-1) x d(-1), 4.55 micromol x kg(-1) x h(-1)). Phenylalanine hydroxylation was estimated from the ratio of plasma amino acid isotope enrichment of [15N]phenylalanine and [15N]tyrosine and the tyrosine flux estimated from [2H2]tyrosine enrichment. Phenylalanine and tyrosine fluxes showed no significant response to alterations in the intake of tyrosine. Linear regression analysis showed a significant response such that the rate of phenylalanine hydroxylation decreased as tyrosine intake increased (R2 = .21; P = .003). The mean rates of phenylalanine hydroxylation were 3.89 to 8.06 micromol x kg(-1) x h(-1). Given model uncertainties, the apparent protein breakdown observed at tyrosine intake levels less than 10.5 mg x kg(-1) x d(-1), and the significant differences observed between the present data and our prior data, we cannot estimate the tyrosine requirement with any degree of certainty with the present hydroxylation results.

Prior protein intake may affect phenylalanine kinetics measured in healthy adult volunteers consuming 1 g protein. kg-1. d-1.

Study of the amino acid metabolism of vulnerable groups, such as pregnant women, children and patients, is needed. Our existing protocol is preceded by 2 d of adaptation to a low 13C formula diet at a protein intake of 1 g. kg-1. d-1 to minimize variations in breath 13CO2 enrichment and protein metabolism. To expand on our potential study populations, a less invasive protocol needs to be developed. We have already established that a stable background 13CO2 enrichment can be achieved on the study day without prior adaptation to the low 13C formula. Therefore, this study investigates phenylalanine kinetics in response to variations in prior protein intake. Healthy adult subjects were each fed nutritionally adequate mixed diets containing 0.8, 1.4 and 2.0 g protein. kg-1. d-1 for 2 d. On d 3, subjects consumed an amino acid-based formula diet containing the equivalent of 1 g protein. kg-1. d-1 hourly for 10 h and primed hourly oral doses of L-[1-13C]phenylalanine for the final 6 h. Phenylalanine kinetics were calculated from plasma-free phenylalanine enrichment and breath 13CO2 excretion. A significant quadratic response of prior protein intake on phenylalanine flux (P = 0.012) and oxidation (P = 0.009) was identified, such that both variables were lower following adaptation to a protein intake of 1.4 g. kg-1. d-1. We conclude that variations in protein intake, between 0.8 and 2.0 g. kg-1. d-1, prior to the study day may affect amino acid kinetics and; therefore, it is prudent to continue to control protein intake prior to an amino acid kinetics study.

Surface coordination chemistry: corrosion inhibition by tetranuclear cluster formation of iron with salicylaldoxime.

A tetranuclear iron cluster is the principal component of the purple coatings produced by treating a mild steel surface with a salicylaldoxime corrosion inhibitor. This was shown by comparison of the spectroscopic data with those of the cluster [{Fe(salH)(HsalH)}4 ], which was obtained from FeCl3 and salicylaldoxime (H2 salH) and has a distorted tetrahedral arrangement of Fe(III) atoms coordinated by terminal (1-) and bridging (2-) salicylaldoximate ligands (the central core of the cluster is depicted).

Surgical treatment of internal disc disruption: an outcome study of four fusion techniques.

Surgical treatment for internal disc disruption remains controversial in terms of efficacy of spinal fusion and optimal fusion method. The present study was carried out in 56 consecutive patients, with the diagnosis confirmed by computed tomographic (CT) discography, who were operated with one of four different lumbar fusion procedures. Outcomes were determined by postoperative pain questionnaires, independent clinical assessment, and radiographic evaluation. Simultaneous anterior interbody fusion using BAK cage and posterior facet fusion provided the highest rate of fusion (88%) and clinical satisfaction (63%). Pain scores were also significantly lower than facet screw augmented posterolateral fusion, and anterior interbody fusion with fibula allograft, but not significantly different from pedicle screw instrumented posterolateral fusion. Patients who achieved successful lumbar fusion had better clinical outcomes and a better chance of work resumption.

Evidence that phenylalanine hydroxylation rates are overestimated in neonatal subjects receiving total parenteral nutrition with a high phenylalanine content.

Recent publications have indicated that the parenterally fed neonate has a substantial ability to hydroxylate phenylalanine. Examination of these data suggests that, at high phenylalanine intakes, estimated rates of hydroxylation exceed rates of intake. This implies significant net tissue breakdown. However, the quantitative validity of the estimates of phenylalanine hydroxylation cannot be assessed without nitrogen balance data. We have recently developed a parenterally fed neonatal piglet model and have used this to study aromatic amino acid metabolism in piglets fed different amino acid solutions. Reappraisal of the data from these studies has allowed us to estimate both phenylalanine hydroxylation and tissue protein accretion. Piglets were parenterally fed Vamin [292 micromol of Phe x kg(-1) x h(-1), 26 micromol of Tyr x kg(-1) x h(-1)], Vaminolact + Phe [VLP, 277 micromol of Phe x kg(-1) x h(-1), 26 micromol Tyr x kg(-1) x h(-1)], or Vaminolact + glycyl-L-tyrosine [VLGT, 152 micromol of Phe x kg(-1) x h(-1), 159 micromol of Tyr x kg(-1) x h(-1)] for 8 d. Nitrogen balance was measured over the last 5 study d, and aromatic amino acid kinetics were determined using a primed continuous infusion of L-[1-4C]phenylalanine on d 8. Average body protein gain, derived from nitrogen balance, was 11 g x kg(-1) x d(-1). For the Vamin and VLP groups, the rates of phenylalanine hydroxylation were estimated to be 139 and 90% of intake, respectively. However, phenylalanine hydroxylation was only 16% of intake for the VLGT group. In view of the tissue protein accretion data, it appears that the rate of phenylalanine hydroxylation may be overestimated in neonates fed high phenylalanine parenteral nutrition. The extent to which the parenterally fed neonate can adapt to a high phenylalanine intake, by increasing the rate of phenylalanine hydroxylation, remains to be determined.

The effects of skin temperature on the detection and discrimination of tactile stimulation.

Detection thresholds and intensity-difference thresholds were measured on four subjects ranging in age from 19 to 22 years. The stimuli were 250-Hz bursts of vibration applied through a 3.0 cm2 contactor to the thenar eminence of the right hand. Detection thresholds were substantially higher at 20 degrees C than at 30 degrees or 40 degrees C and were only slightly higher at 40 degrees C than 30 degrees C. When the intensity-difference threshold was expressed in relative terms, as the proportion by which two stimuli must differ in amplitude to be discriminated (delta phi/phi), discrimination capacities were unaffected by surface-skin temperature. The results are consistent with the hypothesis that surface-skin temperature alters the sensitivity of tactile receptors, and that, because of the 'near miss' to Weber's law, the relative difference threshold is unaffected substantially by skin temperature. It was concluded that, at least a partial explanation of the 'near miss' lies in the fact that, at low to moderate sensation levels, the P channel is exclusively activated whereas, at moderate to high sensation levels, because of recruitment of activity in Non-Pacinian channels, neural information for intensity discrimination is additionally provided by channels with superior discriminative capacities.

Determinants of fetal heart rate response to vibroacoustic stimulation in labor.

To determine whether the fetal heart accelerates in response to a sound stimulus in labor, 40 women at various stages of labor were chosen at random to receive either a vibroacoustic stimulus or sham stimulus over the fetal head. Subsequent fetal heart rate (FHR) accelerations occurred to a significantly greater extent in study patients. One hundred thirty-two high- and low-risk patients were studied to determine correlations between the acceleration response and other maternal and fetal variables. There was a statistically significant negative correlation between the heart rate response to stimulation and three maternal variables: the degree of cervical dilation, the presence of ruptured membranes, and use of epidural anesthesia. The degree of fetal response did not correlate significantly with fetal distress at delivery or abnormal FHR tracings at the time of stimulation. Fewer than one-fifth of the fetuses manifested variable heart rate decelerations after the stimulation. In light of possible risks, the clinical use of the fetal acoustic stimulation test in labor should wait until its diagnostic value is better defined.

Tyrosine aminotransferase deficiency in mink (Mustela vision): a model for human tyrosinemia II.

Mink pseudodistemper, a recessive disease associated with high blood tyrosine levels, is an animal analogue of the human inborn error of metabolism, tyrosinemia II. Affected mink and man have eye and skin lesions. Affected mink have no hepatic tyrosine aminotransferase (TAT) activity, as measured immunologically and biochemically. Hepatic mitochondrial aspartate aminotransferase is increased to 188% of control. This new genetic animal model of TAT deficiency should allow new studies of tyrosine metabolism.

Skin sulfhydryl oxidase. Purification and some properties.

A sulfhydryl-oxidizing enzyme has been found in skin of young rats and a method for purifying the enzyme over 600-fold has been developed. Enzymatic activity was assayed either by its ability to oxidize dithiothreitol of by measuring its ability to renature reductively denatured ribonuclease A. Skin sulfhydryl oxidase catalyzed the oxidation of various thiols: dithiothreitol, dithioerythritol, D-penicillamine, and L-cysteine. Glutathione and 2-mercaptoethanol were very poor substrates for the enzyme. The enzyme also reactivated reductively denatured ribonuclease A, with neither the presence of a thiol nor prior reduction of the enzyme being necessary. The molecular weight of the enzyme was estimated to be 66 000 +/- 2000, and the isoelectric point was determined to be at pH 4.65. Alkylating reagents alone had some inhibiting effect on skin sulfhydryl oxidase; when the enzyme was preincubated with thiols which were substrates, inhibition by alkylating reagents was greatly increased. After preincubation with dithiothreitol, treatment of the enzyme with alkylating reagents or N-ethylmaleimide caused significant inhibition; preincubation with a poor substrate, reduced glutathione, did not enhance inhibition by alkylating reagents or N-ethylmaleimide.