An amalgamation of four specialty hospitals. Lessons learned.
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Canada↗
Biomedical subjects
A Baumann
Publications and source records attributed to A Baumann.
An evaluation of WHA resolution 45.5: health human resource implications.
The World Health Assembly approved resolution WHA45.5 in 1992. This paper reports the findings of an evaluation of the implementation of this resolution using a survey technique. A total of 150 WHO Member States responded, for a 79% response rate. Findings suggest that the greatest strides worldwide have been made in education. While the data show that progress has been made at the country level, far more action is needed to strengthen nursing and midwifery if these cost-effective resources are to play a decisive role in improving the extent and quality of services, especially as delivered to people in the greatest need.
Cross-Sectional Studies↗
Molecular determinants of dofetilide block of HERG K+ channels.
The human ether-a-go-go-related gene (HERG) encodes a K+ channel with biophysical properties nearly identical to the rapid component of the cardiac delayed rectifier K+ current (IKr). HERG/IKr channels are a prime target for the pharmacological management of arrhythmias and are selectively blocked by class III antiarrhythmic methanesulfonanilide drugs, such as dofetilide, E4031, and MK-499, at submicromolar concentrations. By contrast, the closely related bovine ether-a-go-go channel (BEAG) is 100-fold less sensitive to dofetilide. To identify the molecular determinants for dofetilide block, we first engineered chimeras between HERG and BEAG and then used site-directed mutagenesis to localize single amino acid residues responsible for block. Using constructs heterologously expressed in Xenopus oocytes, we found that transplantation of the S5-S6 linker from BEAG into HERG removed high-affinity block by dofetilide. A point mutation in the S5-S6 linker region, HERG S620T, abolished high-affinity block and interfered with C-type inactivation. Thus, our results indicate that important determinants of dofetilide binding are localized to the pore region of HERG. Since the loss of high-affinity drug binding was always correlated with a loss of C-type inactivation, it is possible that the changes observed in drug binding are due to indirect allosteric modifications in the structure of the channel protein and not to the direct interaction of dofetilide with the respective mutated site chains. However, the chimeric approach was not able to identify domains outside the S5-S6 linker region of the HERG channel as putative candidates involved in drug binding. Moreover, the reverse mutation BEAG T432S increased the affinity of BEAG K+ channels for dofetilide, whereas C-type inactivation could not be recovered. Thus, the serine in position HERG 620 may participate directly in dofetilide binding; however, an intact C-type inactivation process seems to be crucial for high-affinity drug binding.
Amino Acid Sequence↗
Protein phosphatase type-2C isozymes present in vertebrate retinae: purification, characterization, and localization in photoreceptors.
Posttranslational modification of proteins by kinases and phosphatases plays an important role in the regulation of cellular signaling in general and neurochemistry in particular. This also applies to vertebrate photoreceptors where phosphorylation of rhodopsin causes uncoupling from the signal transduction cascade. Functional activity of rhodopsin is restored after substitution of the bleached photopigment 11-cisretinal and by dephosphorylation of the opsin moiety. Phosphatases type-1 and type-2A have been identified in vertebrate retinae. Recently, we have shown by molecular cloning that two isozymes of protein phosphatase type-2C (PP2C, PPM) do exist in retinal tissue. In this report, we have purified PP2Calpha and PP2Cbeta from bovine retinae. Thirty to 40% of PP2C was recovered in the cytosolic fraction. Biochemical properties of native and heterologously expressed recombinant enzymes were similar. Enzymatic activity is strictly dependent on the presence of Mg2+. Addition of Ca2+ ions inhibits Mg2+-sustained activity. Antiserum raised against a C-terminal peptide of PP2Cbeta specifically labeled the outer segments of rod photoreceptor cells. PP2C protein levels were significantly reduced in RCS rats, which develop age-dependent photoreceptor degeneration comparable to the hereditary disease retinitis pigmentosa. Although the retinal substrate(s) remain to be identified, the results suggest that PP2C modulates cellular components of the phototransduction machinery.
Amino Acid Sequence↗
[Family status and social integration as predictors of mortality: a 5-year follow-up study of 55- to 74-year-old men and women in the Augsburg area].
The relation between marital status, social integration and the mortality from all causes was examined in a population based cohort study. The 5-year-cohort consisted of 1,030 men and 957 women, aged 55-74 years who participated in the second MONICA Survey Augsburg, F.R.G., 1989/90 (MONICA = Monitoring of trends and determinants of cardiovascular disease). They were followed for mortality until 1995. Altogether 120 men and 45 women had died. Social integration was measured by an index of social ties. The index of social ties examined in these analyses includes (a) presence of a spouse, (b) number of close friends and relatives, (c) reported contact with close friends and relatives. Age standardized mortality rates (per 10,000 person years) were computed for men and women. Sex-specific Cox-proportional hazard models were used and hazard rate ratios (HRR) were calculated adjusting for age, hypertension, cigarette smoking, cholesterol, drinking alcohol, number of chronic diseases and self-reported health. Mortality rates were higher for men who were living alone (437.3) than for married men (235.3). Respectively in women the rates were 121.6 compared to 80.7. After controlling for age and self-reported health a HRR of 1.5 (95% CI: 1.0-2.4) was observed for single, divorced or widowed men and a HRR of 1.6 (95% CI: 0.8-3.0) for women living alone. Low mortality rates were observed in people with many social ties (men: 180.1, women: 29.9). Mortality rates of people who gave no informations about social ties (men: 349.5, women: 124.9) were similar to those who had only few social ties (men: 321.1, women: 132.5). The findings showed that people with few social ties were more likely to die in the follow-up period than those with more extensive contacts. After adjusting for age and self-reported health the HRR for those with few ties compared to those with many social ties were 1.6 (95% CI: 1.1-2.5) for men and 2.7 (95% CI: 1.1-6.6) for women. Similar results were found for people who gave no informations about their social ties (men: HRR = 1.4, 95% CI: 0.9-2.3; women: HRR = 2.6, 95% CI: 1.0-6.9). Social relationships were shown to be important predictors of mortality in elderly women and men. These findings confirm the need for further research, which enables to take steps against high mortality of the social isolated elderly.
Aged↗
Characterization of a dopamine D1 receptor from Apis mellifera: cloning, functional expression, pharmacology, and mRNA localization in the brain.
The neurotransmitter dopamine is an important regulator of physiological and behavioral functions in both vertebrates and invertebrates. We have isolated a homologue of the vertebrate dopamine D1 receptor subfamily from the honeybee Apis mellifera. [3H]Lysergic acid diethylamide specifically binds to the heterologously expressed receptor with K(D) approximately 5 nM. Dopaminergic receptor ligands compete for this high-affinity binding, with the following order of potency: R(+)-lisuride > chlorpromazine = cis(Z)-flupentixol > dopamine > S(+)-butaclamol > R(+)-SCH 23390 > haloperidol. Activation of the heterologously expressed receptor of Apis mellifera leads to cyclic AMP production. Receptor mRNA is expressed in perikarya of different brain neuropils, including those of mushroom body intrinsic neurons. These results suggest that this dopamine receptor is involved in signal processing of visual and olfactory information in the honeybee.
Amino Acid Sequence↗
D alpha3, a new functional alpha subunit of nicotinic acetylcholine receptors from Drosophila.
Nicotinic acetylcholine (ACh) receptors (nAChRs) are important excitatory neurotransmitter receptors in the insect CNS. We have isolated and characterized the gene and the cDNA of a new nAChR subunit from Drosophila. The predicted mature nAChR protein consists of 773 amino acid residues and has the structural features of an ACh-binding alpha subunit. It was therefore named D alpha3, for Drosophila alpha-subunit 3. The d alpha3 gene maps to the X chromosome at position 7E. The properties of the D alpha3 protein were assessed by expression in Xenopus oocytes. D alpha3 did not form functional receptors on its own or in combination with any Drosophila beta-type nAChR subunit. Nondesensitizing ACh-evoked inward currents were observed when D alpha3 was coexpressed with the chick beta2 subunit. Half-maximal responses were at approximately 0.15 microM ACh with a Hill coefficient of approximately 1.5. The snake venom component alpha-bungarotoxin (100 nM) efficiently but reversibly blocked D alpha3/beta2 receptors, suggesting that D alpha3 may be a component of one of the previously described two classes of toxin binding sites in the Drosophila CNS.
Amino Acid Sequence↗
Characterization of ether-à-go-go channels present in photoreceptors reveals similarity to IKx, a K+ current in rod inner segments.
In this study, we describe two splice variants of an ether-à-go-go (EAG) K+ channel cloned from bovine retina: bEAG1 and bEAG2. The bEAG2 polypeptide contains an additional insertion of 27 amino acids in the extracellular linker between transmembrane segments S3 and S4. The heterologously expressed splice variants differ in their activation kinetics and are differently modulated by extracellular Mg2+. Cooperativity of modulation by Mg2+ suggests that each subunit of the putative tetrameric channel binds a Mg2+ ion. The channels are neither permeable to Ca2+ ions nor modulated by cyclic nucleotides. In situ hybridization localizes channel transcripts to photoreceptors and retinal ganglion cells. Comparison of EAG currents with IKx, a noninactivating K+ current in the inner segment of rod photoreceptors, reveals an intriguing similarity, suggesting that EAG polypeptides are involved in the formation of Kx channels.
Amino Acid Sequence↗
Molecular cloning of protein phosphatase type 2C isoforms from retinal cDNA.
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Animals↗
Sharing the Canadian experience. Interview by Anne Manchester.
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Canada↗
Nucleolar protein B23 stimulates nuclear import of the HIV-1 Rev protein and NLS-conjugated albumin.
Nucleolar phosphoprotein B23 is a putative ribosome assembly factor with a relatively high affinity for peptides containing sequences of nuclear localization signals (NLSs) of the SV40 T-antigen type [Szebeni, A., Herrera, J. E., & Olson, O. J. (1995) Biochemistry 34, 8037-8042]. The effects of protein B23 on nuclear import were determined by an in vitro assay [Dean, D. A., & Kasamatsu, H. (1994) J. Biol. Chem. 269, 4910-4916] using NLS peptide-conjugated bovine serum albumin (NLS-BSA) or the HIV-1 Rev protein as substrates for import into isolated rat liver nuclei. The import was ATP-dependent and inhibited by wheat germ agglutinin or by an antibody against p97, a component of the nuclear import system. The rate of import of either substrate was increased if protein B23 was added to the incubation medium. Similar enhancements of import were seen with both isoforms (B23.1 and B23.2). The stimulatory effect on Rev protein import was saturable with maximum stimulation (2-3-fold) at a molar ratio of protein B23:Rev of approximately 1:1. Phosphorylation of protein B23.1 by casein kinase II produced an additional doubling of the import rate. This effect was not seen if protein B23.1 was phosphorylated with a cdc2 type protein kinase. Mutant forms of protein B23.1 in which the nuclear localization signal was either deleted or altered did not stimulate import of the substrates. These results suggest that protein B23 plays a role as an accessory factor in the nuclear import of the NLS-containing proteins and that phosphorylation at sites in the highly acidic segments of the protein enhances the stimulatory effect.
Adenosine Triphosphate↗
Computer-aided navigation in secondary reconstruction of post-traumatic deformities of the zygoma.
Augmented reality technology was used in 5 patients for secondary reconstruction of post-traumatic unilateral deformities of the zygomaticomaxillary complex. Three electromagnetic sensors interfaced to a computer-aided navigation system (ARTMA Biomedical Inc.) were utilized. The computer navigation procedure was planned by drawing graphic lines on the CT scan at the level of the zygomatic arch, representing the outer surface of the zygoma. The desired position of the displaced zygoma was planned by mirroring from the healthy side, using a virtual mid-sagittal plane. These virtual graphics were presented intraoperatively on a TV monitor and also on the surgeon's see-through head-mounted display. Correct reduction was assumed when the virtual line representing the position of the zygoma before the osteotomy reached the virtual line defined preoperatively as the desired position. The advantages of the technique presented are that a complete exposure of the zygomatic bone is no longer necessary, and coronal and subciliary incisions may be avoided unless enophthalmos correction has to be carried out, which was in fact necessary in 2 patients. The results of zygomatic reconstruction have been satisfactory in all 5 patients.
Adult↗
[Nonparticipation as a factor influencing the value of follow-up studies. Results of a telephone 5-year follow-up interview of 55-74-year-old participants of the Augsburg 1989/90 MONICA Survey].
In prospective cohort studies losses to follow-up are the major source of bias. This article describes the results of the investigation whether there are systematic differences in socio-economic and health-related factors between participants in a follow up study and those who are lost to follow-up. Subjects included were 1,030 men and 957 women aged 55-74 who participated in the second MONICA Survey Augsburg, F.R.G., 1989/90 (MONICA = Monitoring of trends and determinants of cardiovascular disease). They were reexamined in 1994-95. In 1994/95 910 men and 912 women of the baseline study were still alive, 1305 persons (663 men, 642 women) took part in the follow up by telephone. Altogether 120 men and 45 women had died since 1989/90. 144 persons were not eligible for the study (15 moved away, 5 severely ill persons, 124 without telephone). 373 persons were classified as eligible non-responders. The response rate was 77.8% concerning 1678 eligible persons (men 79.1%, women 76.4%). Non-response has led to an underrepresentation of the lower social class (workers, less than 10 years of education; household income less than 1500 DM) and of persons living alone (single, divorced, widowed; single-person households). In females, non-responders were overrepresented by "never employed persons" (odds ratio 3.02; 1.89-4.85). We found that the odds of being non-responder for single, divorced or widowed men was 3.40 (95 %-CI: 2.20-5.23) compared to married men. Men "without chronic diseases" at the baseline study compared with ill men had an odds for non-response of 1.54 (95%-CI: 1.00-2.37); the odds was 1.38 (95%-CI: 1.02-1.85) among women who had described their health status as "not so good/bad" in comparison with women with good self reported health. The reported distortions by non-response could be important in analyses of social conditions of morbidity and mortality. The underrepresentation of men without chronic diseases and women with bad self-assessment of their health is relevant for the estimates of morbidity as health outcome. Both aspects have to be taken into account in the interpretation of the results.
Aged↗
Do nurses have the information resources and skills for research utilization?
While access to information resources and the skills to use them do not ensure that nurses will use nursing research in their practice, they are important facilitators. Mailed questionnaires to assess existing information resources, the information management skills of nurses, and what additional resources and training are required were returned by 67 of the 71 vice-presidents or directors of nursing in hospitals in two regions of Ontario. The two regions have similar information resources, nursing staff with research expertise, and opportunities for training in research and information management but there is variation among hospitals. Most vice-presidents agreed that nurses need better information resources and skills to access and evaluate professional literature. The rapidly developing field of information technology, including the Internet, provides potential for sharing resources and expertise. Nursing administrators can minimize barriers and help staff nurses recognize that information management skills enhance professional development and improve patient care.
Computer User Training↗
Functional properties of Drosophila dopamine D1-receptors are not altered by the size of the N-terminus.
Molecular cloning revealed the existence of at least five pharmacologically different dopamine receptors in vertebrates. Functionally, dopamine receptors either activate (D1-type), inhibit or do not interact with adenylate cyclase (D2-type). A recently cloned dopamine receptor from Drosophila melanogaster shares many structural and functional properties with vertebrate D1-type receptors but the pharmacological properties are very different. In contrast to most aminergic receptors, DmDop1 contains a long N-terminal extension. Here we describe a deletion-mutagenesis approach to study whether the N-terminus of DmDop1 participates in receptor-ligand interactions. All mutants gave rise to functional receptors after heterologous expression in HEK 293 cells. The pharmacological properties, however, remained unchanged. A comparison of DNA and deduced amino acid sequences revealed that some Drosophila strains express a truncated version of the DmDop1 receptor.
Animals↗
Association of fallout radiocesium with soil constituents: effect of sterilization of forest soils by fumigation with chloroform.
The effect of soil sterilization by chloroform fumigation on the release of fallout radiocesium incorporated in the fungal biomass of the organic layer of two forest soils was investigated by applying a sequential extraction procedure for radiocesium. The amount of the biomass in all soil samples was estimated by determination of the dissolved organic carbon (DOC) before and after fumigation, and qualitatively also by the ergosterol test. The five fractions obtained by sequential extraction (modified Tessier procedure) were: (I) easily exchangeable, (II) bound to oxides, (III) bound to organic matter, (IV) persistently bound, (V) residual. For the samples from the soil under spruce trees, no significant effects were apparent in any of these five fractions as a result of chloroform fumigation, indicating that the amount of radiocesium in the biomass of this soil was obviously negligibly small compared with the radiocesium associated with other soil constituents. The results obtained for the soil samples from the beech stand, however, reveal that the destruction of the biomass by chloroform fumigation modified considerably the extent of the association (i.e., binding) of radiocesium with the various other soil constituents (especially the clay minerals). As a result of this rapid redistribution of radiocesium released by the fungal biomass, it is not possible, in general, to attribute the observed increase of radiocesium in fraction I (easily exchangeable) after soil sterilization quantitatively to radiocesium released by the biomass. A reliable method to determine the amount of radiocesium incorporated in the fungal biomass of the soil samples which also contain clay minerals has, therefore, still to be developed.
Biomass↗
Comparative pharmacokinetics of two new steroidal estrogens and ethinylestradiol in postmenopausal women.
It was the aim of the study to compare the pharmacokinetic properties of the two new estrogens, ZK 136295 and ZK 115194, with those of ethinylestradiol (EE2) after single intravenous (60 micrograms) and oral (120 and 240 micrograms) administration in 54 postmenopausal women. In particular, our objective was to examine whether one or both compounds were characterized by an improved oral bioavailability with less inter-subject variability than EE2. Drug serum concentrations were determined using specific radioimmunoassays for EE2 and ZK 136295, and a GC/MS/MS-method for ZK 115194. Following i.v. administration of the new estrogens and of EE2, the drugs were rapidly distributed in the body. The mean terminal half-lives were calculated to be 12.3 +/- 12.4, 28.7 +/- 9.6, and 26.1 +/- 11.1 h for ZK 136295, ZK 115194, and EE2 respectively. After oral administration of 120 micrograms, the absolute bioavailability was calculated to be about 40% for ZK 136295 as well as for EE2 with a high inter-individual variation (variation coefficient: 44 and 67%). By doubling the dose, the systemic availability increased dose-dependently for both drugs to about 70% with the same high inter-individual variation. Following single oral administration of 240 micrograms ZK 115194, the absolute bioavailability amounted to 33 +/- 19%. The present study clearly revealed that although the two new estrogens differed considerably in their pharmacokinetic behavior, they demonstrated a reduced and highly variable systemic availability similar to that of EE2.
Administration, Oral↗
Nursing curriculum content: an innovative decision-making process to define priorities.
Curriculum planning in the health sciences is becoming increasingly complex due to rapid societal change and scientific discovery. The half-life of most curricula is 5 years, which necessitates a periodic close examination and revision of both content and process. For nursing faculty, this exercise is often viewed as an arduous one and traditionally can lead to endless hours of circular debate. Planning is usually in two stages; the first stage being the development of or agreement about a theoretical framework and the second stage is deciding on core content and teaching methodologies. This article focuses on decisions in the second stage. Traditionally, decisions around curriculum are arrived at by much debate. Some argue that all health issues should be addressed in the curriculum in order that the graduate be prepared to deal with a breadth of issues. However, this approach often leads to what has been referred to as 'curriculum hypertrophy', where, in an attempt to be all-inclusive, the curriculum grows without bounds. Rarely is anything dropped from the curriculum when this approach is used. Sometimes priorities are established on the basis of what the individual teaching staff deems important. In other cases a consensus approach is chosen.
Curriculum↗