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The febrile response in critical care: state of the science.

Fever is a dynamic alteration in thermal balance caused by effects of pyrogens on the hypothalamic thermostatic set point. Thermoregulatory function remains intact during fever, but temperatures are maintained at higher levels. Shivering and vasoconstriction drive temperatures higher while causing physical exertion and distress to the patient. Biomedical research reveals potential benefits of fever, because fever-producing cytokines stimulate host defense responses. Nursing care is aimed at making rational decisions for comfort and energy conservation while maximizing the immune response. In this article the pathophysiologic process and benefits of fever are reviewed and a conceptual approach to nursing care based on knowledge of thermoregulatory responses is proposed. Nursing care measures include assessment of alterations in thermal balance, selection of appropriate measures to modify or support physiologic responses, and evaluation of outcomes of therapy. Research-based direction for care is presented, as well as gaps in scientific knowledge.

Clinical Protocols↗

Association of Fcgamma receptor IIa (CD32) polymorphism with severe malaria in West Africa.

Malaria continues to claim the lives of more children worldwide than any other infectious disease, and improved understanding of disease immunology is a priority for the development of new therapeutic and vaccination strategies. FcgammaRIIa (CD32) contains a polymorphic variant (H/R131) that has been associated with variability in susceptibility to both bacterial diseases and Plasmodium falciparum parasitemia. We investigated the role of this polymorphism in West Africans with mild and severe malarial disease. The HH131 genotype was significantly associated with susceptibility to severe malaria (P = 0.03, odds ratio = 1.40, 95% confidence interval = 1.02-1.91). In contrast to studies of parasitemia, the presence of the R131 allele, rather than the RR131 genotype, appeared to be the important factor in protection from disease. This is the first evidence for an association between CD32 polymorphism and severe malaria and provides an example of balancing selective pressures from different infectious diseases operating at the same genetic locus.

Animals↗

Genetic variation within exon 2 of the MHC B-LB // gene in Tibetan chicken.

Genetic variation within exon 2 of chicken major histocompatibility complex B-LB // genes was investigated by PCR amplification, cloning and sequencing of a 374 bp fragment of the indigenous Tibetan chicken genomic DNA. Fifteen novel B-LB // alleles were found. Alignment and comparison of 18 allelic sequences from the individuals sampled revealed a total of 62 variable sites (total of 80 mutations) in exon 2, of which 41 were parsimony informative sites. The nucleotide diversity (pi) within the sequence of exon 2 was calculated to be 0.0718. Analysis of nucleotide variation confirmed a lower level of divergence (0.056 +/- 0.008) as estimated by average pairwise distance within the Tibetan chicken population than the five exotic breeds detected. The relative frequencies of synonymous and non-synonymous nucleotide substitutions within the region were 3.25 +/- 0.94% and 15.61 +/- 2.69% , respectively. These results indicated that the genetic variation within exon 2 seemed to have arisen largely by gene recombination and balancing selection. Alignment of the deduced amino acid sequences of beta1 domain coded by exon 2 revealed 11 synonymous mutations and 27 non-synonymous substitutions at the 38 separate sites. Fifty percent (12/24) of the proposed peptide-binding sites were variable within beta1 domain of chicken MHC B-LB // molecules, of which 11 were unique non-synonymous amino acid substitutions. These particular non-synonymous substitutions are considered to be associated with immunological specificity of MHC B-LB // molecule in Tibetan chicken, and they can provide a molecular biological basis for the study of disease resistance in chicken.

Animals↗

[Allozyme polymorphism of Swiss stone pine Pinus cembra L. in mountainous populations of the Alps and the Eastern Carpathians].

Swiss stone pine Pinus cembra L. is a species with fragmented range, occurring in the Alpine-East Carpathian mountain system. Seeds of P. cembra are dispersed by nutcrackers, which offers potential possibilities for gene exchange among populations. Using isozyme analysis, we have examined five samples from two parts of the Swiss stone pine range: the Alps (Switzerland and Austria) and the Carpathians (two samples from the northern macroslope of the Gorgany Ridge, Eastern Carpathians, Ivano-Frankovsk oblast and one sample from Trans-Carpathian oblast of Ukraine). The allele frequencies of 30 isozyme loci, coding for enzymes ADH, FDH, FEST, GDH, GOT, IDH, LAP, MNR, MDH, PEPCA, 6PGD, PGI, PGM, SDH, SKDH, SOD, were analyzed using cluster analysis and methods of principal components. Two clusters, corresponding to the isolated Alpine and Carpathian parts of the range, were found. The main contribution to these differences were made by loci Adh-1, Adh-2, Fest-2, Lap-3, Mdh-4, and Sod-4. The interpopulation differentiation proved to be somewhat higher than that typical for pines (F(ST) = 7.4%), but within the limits characteristic for taxonomically close species. Thus, isolation of the populations did not lead to their marked differentiation, which may be explained by gene flow and balancing selection, which equalizes gene frequencies across the fragmented species area. Interlocus F(ST) heterogeneity (from 0.003 to 0.173) suggests adaptive significance of some of the allozyme polymorphisms or linkage of some loci with adaptive genes. The Carpathian populations were shown to have higher gene diversity than the Alpine ones (expected heterozygosities 0.095-0.114 and 0.060-0.080, respectively). A deficit of heterozygotes (as compared to the Hardy-Weinberg proportions), observed in the embryo sample, was probably explained by inbreeding. The reduction in the area of Carpathian pine forests in Holocene, caused by the global climatic changes and the anthropogenic impact, is hazardous for the gene pool of the species. The maintenance of genetic uniqueness of both Carpathian populations of P. cembra in general, and individual stands in particular, requires special measures for protection of Swiss stone pine in the Eastern Carpathians.

Environment↗

[Dynamics of allozyme heterozygosity in Siberian dwarf pine Pinus pumila (Pall.) Regel populations of the Russian Far East: comparison of embryos and maternal plants].

Siberian dwarf pine, or Japanese stone pine, Pinus pumila (Pall.) Regel is widespread in eastern Siberia and the Russian Far East; the species is bird-dispersed and has a unique spreading or shrub living form. A mixed mating system (predominant outcrossing with self-pollination and matings of close relatives) leads to the formation of partly inbred progenies in P. pumila, as in the majority of other conifers. The question arises as to whether inbred individuals persist in the reproductive part of a population, which can have negative genetic consequences. The ADH, FDH, FEST, GDH, GOT, IDH, LAP, MNR, MDH, PEPCA, 6-PGD, PGI, PGM, SKDH, and SOD isozyme systems were analyzed to study the dynamics of heterozygosity in four P. pumila natural populations from the Pacific region, optimal for the species. Samples were collected in northern Koryakia, southern Kamchatka (two samples), and the Kunashir Island (Kurils). Wright's fixation index was used to estimate the level of inbreeding in embryos from dormant seeds resulting from free pollination and in maternal plants. A substantial level of inbreeding (F(IS) = 0.124-0.342) was observed in the embryo samples but not in three out of the four adult samples. The inbreeding level at the reproductive age was high only in the sample from Koryakia, which was explained by a relatively young age of plants in the population frequently affected by fires. A general increase in heterozygosity, characteristic of other conifers as well, was attributed to elimination of inbred progenies and by balancing selection for heterozygotes, which is a key factor maintaining allozyme polymorphism in populations.

Breeding↗

The Holt-Oram syndrome: a case presentation and review of management parameters.

Holt-Oram syndrome (HOS) is a dominant inherited disorder which causes skeletal defects of the arms and heart disease. This report describes a 2-year-old child with HOS whose skeletal anomalies affected his functional capabilities and developmental sequence. A comprehensive evaluation of the child, which included radiographic, cardiac, gross and fine motor assessment, electrodiagnosis and consideration of surgery, resulted in a carefully formulated treatment plan. Review of the literature emphasizes the importance of selectively balancing conservative management with surgery for a satisfactory cosmetic result and optimal function.

Child Development↗

Lack of correlation between mating activity and EST-1 polymorphism in three natural and laboratory populations of Drosophila bipectinata.

Est-1 polymorphism and mating activity have been studied in three natural populations of D. bipectinata and after 10 generations of their maintenance in the laboratory. The results indicate that the enzyme Est-1 variation was not significant within natural populations within F10 generation and also between different natural populations and F10 generation indicating the role of balancing selection in the maintenance of enzyme polymorphism in both natural and laboratory conditions. On the other hand, there was variability in the mating activity within natural populations and within F10 generation and also between natural population and F10 generation. However, there was no correlation between Est-1 polymorphism and mating activity.

Alleles↗

Characterization of the phosphoglucose isomerase gene from crickets: an analysis of phylogeny, amino acid conservation and nucleotide composition.

Although electrophoretic variation in phosphoglucose isomerase (PGI) is often detected in allozyme studies, the Pgi gene has rarely been characterized. Here, I present the cDNA sequence of the Pgi gene from two species of field cricket, Gryllus pennsylvanicus (U65475) and G. veletis (U65476), in which the PGI protein is suspected of being under balancing selection. Phylogenetic analyses support the conclusion that these sequences are truly cricket Pgi. The cricket amino acid sequences are compared to sequences from other taxa to determine conserved residues that may be essential for the function of the protein. Such analysis is necessary as there is no well-resolved structure of the PGI protein. In addition, the compositional bias of cricket Pgi is different from the other animal Pgi genes characterized to date.

Amino Acid Sequence↗

Social sex selection and the balance of the sexes: empirical evidence from Germany, the UK, and the US.

Preconception sex selection for nonmedical reasons is one of the most controversial issues in bioethics today. The most powerful objection to social sex selection is based on the assumption that it may severely distort the natural sex ratio and lead to a socially disruptive imbalance of the sexes. Based on representative social surveys conducted in Germany, the United Kingdom, and the United States, this paper argues that the fear of an impending sex ratio distortion is unfounded. Given the predominant preference for a "gender balanced family," a widely available service for social sex selection is highly unlikely to upset the balance of the sexes in Western societies.

Adult↗

Effects of balance training on selected skills.

The purpose of this study was to determine the effect of a 4-week balance training program on specified functional tasks. Thirty-six subjects (age = 22.7 +/- 2.10 years; height = 168.30 +/- 9.55 cm; weight = 71.15 +/- 16.40 kg) were randomly placed into control (C; n = 19) and experimental groups (Tx; n = 17). The Tx group trained using a commercially available balance training device (BOSU). Postural limits (displacement and sway) and functional task (time on ball, shuttle run, and vertical jump) were assessed during a pretest (T1), a posttest (T2), and 2 weeks posttraining (T3). Multivariate repeated measures analysis (alpha = 0.05) revealed significant differences in time on ball, shuttle run, total sway, and fore/aft displacement after the exercise intervention (T2). T3 assessment revealed that total sway and time on ball remained controlled; however, no other measures were retained. Balance training improved performance of selected sport-related activities and postural control measures, although it is unclear whether the effect of training would transfer to general functional enhancement.

Adult↗

The effect of short-term (21-day) orlistat treatment on the physiologic balance of six selected macrominerals and microminerals in obese adolescents.

OBJECTIVES: Orlistat is a gastrointestinal lipase inhibitor used to reduce dietary fat absorption and could be used to treat overweight and obesity in adolescents. The primary objective was to assess whether orlistat has an effect on the physiologic balance of three macrominerals (calcium, phosphorus and magnesium) and three microminerals (iron, zinc and copper). METHODS: This was a 21-day, double-blind, randomized, parallel-group, placebo-controlled mineral balance study conducted in adolescent obese volunteers (BMI >or=85th percentile, adjusted for age and gender). Subjects were maintained on a hypocaloric diet with a normal daily mineral content in both treatment groups and received oral treatment with orlistat 120 mg (n = 16) or placebo (n = 16) three times daily for 21 days. Following a 14-day equilibration period, balances for calcium, phosphorus, magnesium, iron, copper and zinc were measured for days 15-21. Serum and urine electrolytes were also measured at baseline and at the end of treatment. RESULTS: On average, orlistat inhibited dietary fat absorption by approximately 27%. This degree of dietary fat inhibition caused no significant changes in mineral balance between orlistat and placebo groups. In addition, serum and urine electrolytes (sodium and potassium) as well as urinary creatinine excretion were not affected by orlistat treatment. Orlistat was well tolerated; adverse events occurred mainly in the gastrointestinal tract and were of mild or moderate intensities. CONCLUSIONS: Administration of orlistat had no significant effect on the balance of six selected minerals in adolescent obese patients.

Adolescent↗

Preimplantation sex selection for family balancing in India.

We describe our experience with the use of embryo biopsy and fluorescent in-situ hybridization (FISH) in order to sex embryos for the purpose of family balancing in a private IVF clinic in India from April 1999-April 2001. Embryos were biopsied and analysed on day 3, cultured in sequential media, and then transferred on day 4 or day 5 after morphological selection of the best embryos. From a total of 42 cycles started, we achieved 14 clinical pregnancies and have had nine live births so far with five ongoing pregnancies. This is the first report of the use of preimplantation sex selection for family balancing in India, where couples place a premium on having baby boys, and the social and ethical aspects of the use of this technology in this setting are discussed.

Biopsy↗

The use of preimplantation genetic diagnosis in sex selection for family balancing in India.

This paper describes the use of preimplantation genetic diagnosis (PGD) in sexing embryos for family balancing in a private IVF clinic in India from April 1999 to April 2001. Embryos were biopsied and analysed on day 3, cultured in sequential media and then transferred on day 4 or day 5 after morphological selection of the best embryos. From a total of 42 cycles started, 14 clinical pregnancies and nine live births have been achieved so far, with five ongoing pregnancies. The benefits of delayed transfer 24-48 h after the embryo biopsy are that PGD centres could use the extra time available to confirm the diagnosis or introduce additional diagnostic tests for the same embryo. The selection of blastocysts for transfer should also permit the transfer of fewer embryos, thus reducing the risk of multiple gestations and increasing the pregnancy rate as a consequence of the expected higher implantation rate. This is the first report of the use of PGD in sex selection for family balancing in India, where couples place a premium on having baby boys, and the social and ethical aspects of the use of this technology in this setting are briefly discussed.

Family Planning Services↗

The occupancy of ions in the K+ selectivity filter: charge balance and coupling of ion binding to a protein conformational change underlie high conduction rates.

Potassium ions diffuse across the cell membrane in a single file through the narrow selectivity filter of potassium channels. The crystal structure of the KcsA K+ channel revealed the chemical structure of the selectivity filter, which contains four binding sites for K+. In this study, we used Tl+ in place of K+ to address the question of how many ions bind within the filter at a given time, i.e. what is the absolute ion occupancy? By refining the Tl+ structure against data to 1.9A resolution with an anomalous signal, we determined the absolute occupancy of Tl+. Then, by comparing the electron density of Tl+ with that of K+, Rb+ and Cs+, we estimated the absolute occupancy of these three ions. We further analyzed how the ion occupancy affects the conformation of the selectivity filter by analyzing the structure of KcsA at different concentrations of Tl+. Our results indicate that the average occupancy for each site in the selectivity filter is about 0.63 for Tl+ and 0.53 for K+. For K+, Rb+ and Cs+, the total number of ions contained within four sites in the selectivity filter is about two. At low concentrations of permeant ion, the number of ions drops to one in association with a conformational change in the selectivity filter. We conclude that electrostatic balance and coupling of ion binding to a protein conformational change underlie high conduction rates in the setting of high selectivity.

Animals↗

Pleiotropic models of polygenic variation, stabilizing selection, and epistasis.

We show that in polymorphic populations many polygenic traits pleiotropically related to fitness are expected to be under apparent "stabilizing selection" independently of the real selection acting on the population. This occurs, for example, if the genetic system is at a stable polymorphic equilibrium determined by selection and the nonadditive contributions of the loci to the trait value either are absent, or are random and independent of those to fitness. Stabilizing selection is also observed if the polygenic system is at an equilibrium determined by a balance between selection and mutation (or migration) when both additive and nonadditive contributions of the loci to the trait value are random and independent of those to fitness. We also compare different viability models that can maintain genetic variability at many loci with respect to their ability to account for the strong stabilizing selection on an additive trait. Let Vm be the genetic variance supplied by mutation (or migration) each generation, Vg be the genotypic variance maintained in the population, and n be the number of the loci influencing fitness. We demonstrate that in mutation (migration)-selection balance models the strength of apparent stabilizing selection is order Vm/Vg. In the overdominant model and in the symmetric viability model the strength of apparent stabilizing selection is approximately 1/(2n) that of total selection on the whole phenotype. We show that a selection system that involves pairwise additive by additive epistasis in maintaining variability can lead to a lower genetic load and genetic variance in fitness (approximately 1/(2n) times) than an equivalent selection system that involves overdominance. We show that, in the epistatic model, the apparent stabilizing selection on an additive trait can be as strong as the total selection on the whole phenotype.

Alleles↗