Frequency and reliability of alarms in the monitoring of cardiac postoperative patients

Postoperative monitoring of cardiac operated patients requires appropriately functioning monitor alarms as well as intensive nursing activity. The limit alarms can be used for detection of life-threatening situations and monitoring of physiological changes in the patient's state. We studied the significance and the frequency of audible alarms during the postoperative intensive care of ten cardiac patients. Of 1307 occasions when such an alarm was activated during the study period of approximately 26 hours per patient, only 139 (10.6%) were significant. The highest proportion of significant audible limit alarms was found during the immediate postoperative period. Heart rate alarms were more reliable than alarms of the other parameters monitored in the study. Possibilities for improving the physiological monitoring and alarm system are discussed.     

Frequency and reliability of alarms in the monitoring of cardiac postoperative patients

Postoperative monitoring of cardiac operated patients requires appropriately functioning monitor alarms as well as intensive nursing activity. The limit alarms can be used for detection of life-threatening situations and monitoring of physiological changes in the patient's state. We studied the significance and the frequency of audible alarms during the postoperative intensive care of ten cardiac patients. Of 1307 occasions when such an alarm was activated during the study period of approximately 26 hours per patient, only 139 (10.6%) were significant. The highest proportion of significant audible limit alarms was found during the immediate postoperative period. Heart rate alarms were more reliable than alarms of the other parameters monitored in the study. Possibilities for improving the physiological monitoring and alarm system are discussed.     

Estrogen replacement therapy in combination with continuous intrauterine progestin administration reduces the amount of circulating oxidized LDL in postmenopausal women: dependence on the dose of progestin

BACKGROUND: Oxidized low density lipoprotein (LDL) plays a key role in processes leading to atherosclerosis. Recent studies show that LDL oxidation in vitro is effectively prevented by estrogen. Yet, the effect of hormonal therapy (HT) on in vivo LDL oxidation has remained open. AIM: We used a novel methodology for the measurement of oxidized LDL in vivo in order to investigate the effects of HT. METHODS: The subjects were derived from two separate trials. In trial 1 (24 months) women (n = 32) used intra-uterine system releasing 10 micrograms/day levonorgestrel, and 2 mg oral estradiol. Trial 2 (12 months) consisted of two groups of subjects. One group (n = 30) used an intrauterine system releasing 20 micrograms/day levonorgestrel, and 2 mg estradiol; the other group (n = 32) received orally a combination of 1 mg norethisterone acetate and 2 mg estradiol. Blood samples were taken at 6 months intervals. Estimation of in vivo LDL oxidation was based on determination of baseline diene conjugation in isolated LDL. RESULTS: Hormonal therapy in trial 1 decreased markedly in vivo LDL oxidation. The effect was seen after 6 months' HT and became more pronounced towards the end of study (41% decrease; P < 0.0001). Contrary to this, in trial 2 the two different kinds of hormonal therapy schemes did not affect in vivo LDL oxidation. CONCLUSIONS: The strong effect seen in trial 1 shows that intrauterine levonorgestrel with 2 mg estradiol can lower LDL oxidation in vivo. The results show that this effect depends on dosage of the progestin.     

Localization of the Rev-ErbA orphan receptors in the brain

In the present study, we report the localization of the Rev-ErbAα and β nuclear orphan receptors, two closely related members of the nuclear hormone receptor superfamily, in the brain. Both Rev-ErbA variant mRNAs were highly expressed in the olfactory bulb, the hippocampus, and in the granular cells of the cerebellum, areas enriched also in other nuclear orphan receptors. Furthermore, the α-isoform was found in high amounts in the frontal cortex, the superficial gray layer of the superior colliculus, and the stria terminalis. Lower expression was observed in the nucleus accumbens, the caudate-putamen, and in some thalamic and brainstem nuclei. The β-variant, in contrast, was only moderately expressed in the cortex, mainly in the striate and retrosplenial cortices. In addition, moderate levels of Rev-ErbAβ mRNA were seen in various thalamic, pontine and brainstem nuclei. We conclude that the two Rev-ErbA isoforms share a partly similar pattern of expression in the brain, especially in areas that also contain other nuclear orphan receptors and that otherwise the localization of the two receptor subtypes is differential.     

The effect of hormone replacement therapy on atherosclerotic severity in relation to ESR1 genotype in postmenopausal women

OBJECTIVE: The atheroprotective action of estrogen is mediated by estrogen receptors (ESR) 1 and 2, expressed in atherosclerotic lesions. The effects of hormone replacement therapy (HRT) and ESR1 PvuII genotypes on atherosclerosis have not previously been studied prospectively in postmenopausal women. METHODS: We investigated the effect of HRT on the progression of atherosclerosis in a 5-year follow-up study of 88 postmenopausal women aged 45-71 years at baseline allocated into three groups based on the use of HRT. The HRT-EVP group (n=26) used sequential estradiol valerate (EV) plus progestin (P), the HRT-EV group EV alone (n=32), and a control group (n=30) was without HRT. The atherosclerosis severity score (AS) of the abdominal aorta and carotid arteries were determined by sonography and the ESR1 PvuII genotypes (P/P, P/p and p/p) by PCR. RESULTS: HRT, time and ESR1 PvuII genotype had a statistically significant or borderline significant main effect on AS during 5-year follow-up (P=0.004, P<0.001 and P=0.090, respectively), when analyzed by repeated measures analysis of variance. There was a significant genotype-by-treatment (HRT-EVP and control groups) interaction for AS (P=0.034). In response to HRT-EVP, subjects with P/P, compared with those with P/p and p/p genotypes, had a less increase in AS (1.61+/-1.14 vs. 1.71+/-1.27 vs. 2.43+/-1.27). Baseline AS as covariate in similar model does not change the significant interaction effect between HRT-EVP and control groups (P=0.036). But this effect was not found between HRT-EV and control groups. CONCLUSIONS: Our results suggest that the effect of HRT-EVP in postmenopausal women on progression of AS may be determined in part by the genotype of ESR1 PvuII.     

Apoptosis in the human ovary

Programmed cell death or apoptosis is an essential component of human ovarian function and development. During early fetal life approximately 7 x 10(6) oocytes are formed in the human ovary. However, the number of oocytes is dramatically reduced already before birth through apoptotic cell death. In reproductive life, a number of primordial follicles start growing during each menstrual cycle. Usually only one will ovulate and the fate of the rest of the follicles is atresia through the mechanism of apoptosis. Ultimately, only around 400 follicles will ovulate during a woman's reproductive life. After ovulation, the dominant follicle forms the corpus luteum, a novel endocrine gland that is responsible for the production of progesterone and maintenance of endometrium during early pregnancy. If pregnancy does not occur, corpus luteum action must cease so that new follicles can resume growing during the next menstrual cycle. Apoptosis is also responsible for corpus luteum regression in the human ovary. In recent years, new knowledge of the role and regulation of apoptosis in the ovary has been acquired through the use of knockout and transgenic animals. Apoptosis seems to be the mechanism that makes the female biological clock tick. The following review will discuss the role of apoptosis and its regulation of human ovarian function.     

Molecular mechanisms of ligand-receptor interactions in transmembrane domain V of the alpha2A-adrenoceptor

1. The structural determinants of catechol hydroxyl interactions with adrenergic receptors were examined using 12 alpha2-adrenergic agonists and a panel of mutated human alpha2A-adrenoceptors. The alpha2ASer201 mutant had a Cys --> Ser201 (position 5.43) amino-acid substitution, and alpha2ASer201Cys200 and alpha2ASer201Cys204 had Ser --> Cys200 (5.42) and Ser --> Cys204 (5.46) substitutions, respectively, in addition to the Cys --> Ser201 substitution. 2. Automated docking methods were used to predict the receptor interactions of the ligands. Radioligand-binding assays and functional [35S]GTPgammaS-binding assays were performed using transfected Chinese hamster ovary cells to experimentally corroborate the predicted binding modes. 3. The hydroxyl groups of phenethylamines were found to have different effects on ligand affinity towards the activated and resting forms of the wild-type alpha2A-adrenoceptor. Substitution of Ser200 or Ser204 with cysteine caused a deterioration in the capability of catecholamines to activate the alpha2A-adrenoceptor. The findings indicate that (i) Cys201 plays a significant role in the binding of catecholamine ligands and UK14,304 (for the latter, by a hydrophobic interaction), but Cys201 is not essential for receptor activation; (ii) Ser200 interacts with the meta-hydroxyl group of phenethylamine ligands, affecting both catecholamine binding and receptor activation; while (iii) substituting Ser204 with a cysteine interferes both with the binding of catecholamine ligands and with receptor activation, due to an interaction between Ser204 and the para-hydroxyl group of the catecholic ring.     

Daily tea drinking is associated with a low level of depressive symptoms in the Finnish general population

Tea drinking has been suggested to be beneficial in neurodegenerative diseases where depressive mood is a common symptom. Nevertheless, it is not known whether there are any associations between tea drinking and depression in general populations. In this study we investigated these associations in a sample of the Finnish general population (n = 2011) using a postal questionnaire and the Beck Depression Inventory (BDI). Those who reported drinking tea daily were less depressed than the others. They had a lower mean BDI score and also a lower prevalence of depression. None of those whose daily tea intake was five cups or more had depression. Several potential confounding factors were included in the final sex- and age-adjusted multivariate logistic regression model which suggested that those who drink tea daily may have a significantly reduced risk of being depressed (adjusted odds ratio 0.47, 95 confidence interval 0.27–0.83). In conclusion, an inverse relationship between daily tea drinking and the risk of being depressed was found in a relatively large general population sample. Nevertheless, the underlying mechanisms are unresolved and further studies are needed.     

BRUTUS: optimization of a grid-based similarity function for rigid-body molecular superposition. 1. Alignment and virtual screening applications

We have developed a fast grid-based algorithm, BRUTUS, for rigid-body molecular superposition and similarity searching. BRUTUS aligns molecules using field information derived from charge distributions and van der Waals shapes of the compounds. Molecules can have similar biological properties if their charge distributions and shapes are similar, even though they have different chemical structures; that is, BRUTUS can identify compounds possessing similar properties, regardless of their structures. In this paper, we present two applications of BRUTUS. First, BRUTUS was used to superimpose five sets of inhibitors. Second, two sets of known inhibitors were searched from a database, and the results were analyzed using self-organizing maps. We demonstrate that BRUTUS is successful in superimposing compounds using molecular fields and, importantly, is fast and accurate enough for virtual screening of chemical databases using a standard personal computer. This fast and efficient molecular-field-based algorithm is applicable for virtual screening of structurally diverse, active molecules.