Risk factors for a medically inappropriate admission to a Department of Internal Medicine

OBJECTIVE: To identify patient- and admission-related risk factors for a medically inappropriate admission to a department of internal medicine. METHODS: Cross-sectional study of a systematic sample of 500 admissions to the department of internal medicine of an urban teaching hospital. The appropriateness of each admission and reasons for inappropriate admissions were assessed using the Appropriateness Evaluation Protocol. Risk factors included the time (day of week and holidays) and manner (through emergency department or direct admission) of admission, patient age and sex, health status of patient and spouse, living arrangements, formal home care services, and informal support from family or friends. RESULTS: Overall, 76 (15.2%) hospital admissions were rated as medically inappropriate by the Appropriateness Evaluation Protocol. In multivariate analysis, the likelihood of an inappropriate admission was increased by better physical functioning of the patient (odds ratio [OR], 1.5; 95% confidence interval [CI], 1.1-2.1 [for 1 SD in Physical Functioning scores]), lower mental health status of the patient's spouse (OR, 2.6; 95% CI, 1.3-5.6), receipt of informal help from family or friends (OR, 3.3; 95% CI, 1.5-7.2), and hospitalization by one's physician (OR, 3.6; 95% CI, 1.7-7.5). Receiving formal adult home care was not associated with inappropriateness of hospitalization. CONCLUSIONS: Inappropriate admissions to internal medicine wards are determined by a mix of factors, including the patient's health and social environment. In addition, the private practitioners' discretionary ability to hospitalize their patients directly may also favor medically inappropriate admissions.     

The ability of the rat to metabolize myristoyl-methionine: an acylamino acid with potentially useful antibacterial properties

Two experiments with Sprague Dawley rats tested their ability to hydrolyse myristoyl-methionine (M-M) into myristic acid and L-methionine (M). In the first experiment, lasting for 3 days. male rats were orally administered [9,10-3H]myristoyl-L-[35S]methionine. The recovery of radioactivity was approximately 90% for both isotopes; 19% of the administered 3H was recovered in the urine and 16% in the faeces, while the recovered 35S activity was 13 and 12%, respectively. The balance of the radioactivity was found among the tissues, organs and blood. In the second experiment, male and female rats received soybean-based diets which were supplemented with either 0.305% M-M or 0.2% M (both diets contained equal amounts of M) for periods up to 4 weeks. The growth rate of the rats receiving the 0.305% M-M diets was slightly slower than that for the rats on the 0.2% M diet, but the difference was not statistically significant (P > 0.05). The M-M rats had a transitory decrease in feed consumption, suggesting that palatability may have contributed to the growth difference and that a somewhat greater amount of M-M was necessary for the rat to attain the same growth rate as that produced by 0.2% M. When the amount of dietary M-M was increased to 3.05% M-M, a greater reduction in feed consumption and body weight gain was observed. This latter diet was an initial attempt to study the potential toxicity of M-M. None of the haematological, clinical chemistry or organ weight data suggested that M-M was overtly toxic per se, but longer-term feeding studies are needed to evaluate the potential toxicity of M-M more fully.     

Kinetic analysis of the coding properties of O6-methylguanine in DNA: the crucial role of the conformation of the phosphodiester bond

Production by N-nitroso compounds of O6-alkylguanine (O6-alkylG) in DNA directs the misincorporation of thymine during DNA replication, leading to G:C to A:T transition mutations, despite the fact that DNA containing O6-alkylG:T base pairs is less stable than that containing O6-alkylG:C pairs. We have examined the kinetics of incorporation by Klenow fragment (KF) of Escherichia coli DNA polymerase I of thymine (T) and of cytosine (C) opposite O6-MeG in the template DNA strand. Both T and C were incorporated opposite O6-MeG much slower than nucleotides forming regular A:T or G:C base pairs. Using various concentrations of dTTP, dCTP, or their phosphorothioate (Sp)-dNTP alpha S analogues, or a mixture of dTTP and dCTP, the progress of incorporation of a single nucleotide in a single catalytic cycle of a preformed KF-DNA complex was measured (pre-steady-state kinetics). The results were consistent with the kinetic scheme (Kuchta, R. D., Benkovic, P., & Benkovic, S. J. (1988) Biochemistry 27, 6716-6725): (1) binding of dNTP to polymerase-DNA; (2) conformational change in polymerase; (3) formation of phosphodiester between the dNTP and the 3'-OH of the primer; (4) conformational change of polymerase; (5) release of pyrophosphate. The results were analyzed mathematically to identify the steps at which the rate constants differ significantly between the incorporation of T and C. The only significant difference was the 5-fold difference in the rates of formation of the phosphodiester bond (for dTTP, kforward = 3.9 s-1 and kback = 1.9 s-1; for dCTP, kforward = 0.7 s-1 and kback = 0.9 s-1). These pre-steady-state progress curves were biphasic with a rapid initial burst followed by an apparently steady-state rise. Deconvolution of these curves gave direct evidence for the importance of the conformational change after polymerization by showing that the curves represented the sum of the rapid accumulation of the product of step 3 followed by the slow conversion of that to the product of step 5 (because of the rapidity of the release of pyrophosphate there was no significant accumulation of the product of step 4). The equilibrium constants for each step suggest that the greatest change in the Gibbs free energy occurs at the conformational change after polymerization and that while the formation of the phosphodiester bond to T is slightly exothermic, that to C is slightly endothermic.(ABSTRACT TRUNCATED AT 400 WORDS)     

Crystal structure of tyrosine hydroxylase at 2.3 A and its implications for inherited neurodegenerative diseases

Tyrosine hydroxylase (TyrOH) catalyzes the conversion of tyrosine to L-DOPA, the rate-limiting step in the biosynthesis of the catecholamines dopamine, adrenaline, and noradrenaline. TyrOH is highly homologous in terms of both protein sequence and catalytic mechanism to phenylalanine hydroxylase (PheOH) and tryptophan hydroxylase (TrpOH). The crystal structure of the catalytic and tetramerization domains of TyrOH reveals a novel alpha-helical basket holding the catalytic iron and a 40 A long anti-parallel coiled coil which forms the core of the tetramer. The catalytic iron is located 10 A below the enzyme surface in a 17 A deep active site pocket and is coordinated by the conserved residues His 331, His 336 and Glu 376. The structure provides a rationale for the effect of point mutations in TyrOH that cause L-DOPA responsive parkinsonism and Segawa's syndrome. The location of 112 different point mutations in PheOH that lead to phenylketonuria (PKU) are predicted based on the TyrOH structure.     

Constitutive expression in gal7 mutants of Kluyveromyces lactis is due to internal production of galactose as an inducer of the Gal/Lac regulon

The induction process of the galactose regulon has been intensively studied, but until now the nature of the inducer has remained unknown. We have analyzed a delta gal7 mutant of the yeast Kluyveromyces lactis, which lacks the galactotransferase activity and is able to express the genes of the Gal/Lac regulon also in the absence of galactose. We found that this expression is semiconstitutive and undergoes a strong induction during the stationary phase. The gal1-209 mutant, which has a reduced kinase activity but retains its positive regulatory function, also shows a constitutive expression of beta-galactosidase, suggesting that galactose is the inducer. A gal10 deletion in delta gal7 or gal1-209 mutants reduces the expression to under wild-type levels. The presence of the inducer could be demonstrated in both delta gal7 crude extracts and culture medium by means of a bioassay using the induction in gal1-209 cells. A mutation in the transporter gene LAC12 decreases the level of induction in gal7 cells, indicating that galactose is partly released into the medium and then retransported into the cells. Nuclear magnetic resonance analysis of crude extracts from delta gal7 cells revealed the presence of 50 microM galactose. We conclude that galactose is the inducer of the Gal/Lac regulon and is produced via UDP-galactose through a yet-unknown pathway.     

Heart rate variability: two eras of investigation

Changes in membrane potential are a regulatory signal for voltage-gated ion channels including the family of Ca2+ channels. This regulatory role includes the voltage-dependent opening, closing, and inactivation of ion channels and the control of drug access and affinity for discrete channels states. Membrane potential is both a short- and long-term regulatory signal controlling the number and function of these voltage-gated channels. Depolarization of neuronal and neurosecretory cells produces down-regulation of L-type voltage-gated Ca2+ channels. These processes are described and their relevance to physiologic and pathologic processes of neuronal development and neuroprotection are indicated.