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Biomedical subjects

M Wallis

Publications and source records attributed to M Wallis.

At least 19 recordsLinked to original sources

Effect on MRSA transmission of rapid PCR testing of patients admitted to critical care.

We report a significant reduction in the rate of meticillin-resistant Staphylococcus aureus (MRSA) transmission on a critical care unit when admission screening by culture was replaced with a same-day polymerase chain reaction (PCR) test. This was an observational cohort study, set in a 19-bed mixed medical and surgical adult critical care unit in southwest England. We studied 1305 patients admitted between April 2005 and February 2006. Standard MRSA culture methods were used to screen 612 patients between April 2005 and August 2005, and the IDI MRSA PCR test was used to screen 693 patients between September 2005 and February 2006. Standard infection control precautions were instituted when positive results were obtained by either method. Outcome measures included carriage rate, turnaround time for results and rate of subsequent MRSA transmission on the unit. The overall carriage rate on admission to the unit was 7.0%. Culture results were available in three working days, PCR results within one working day. The mean incidence of MRSA transmission was 13.89/1000 patient days during the culture phase and 4.9/1000 patient days during the PCR phase (relative risk reduction 0.65, 95% CI 0.28-1.07). PCR screening for MRSA on admission to critical care units is feasible in routine clinical practice, provides quicker results than culture-based screening and is associated with a significant reduction in subsequent MRSA transmission.

Bacterial Typing Techniques↗

Randomized controlled trial of melatonin for children with autistic spectrum disorders and sleep problems.

BACKGROUND: Melatonin is often used for autistic children with sleep disorders, despite a lack of published evidence in this population. METHODS: A randomized, placebo-controlled double-blind crossover trial of melatonin was undertaken in 11 children with autistic spectrum disorder (ASD). RESULTS: Seven children completed the trial. Sleep latency was 2.6 h [95% confidence intervals (CI) 2.28-2.93] baseline, 1.91 h (95% CI 1.78-2.03) with placebo and 1.06 h (95% CI 0.98-1.13) with melatonin. Wakings per night were 0.35 (95% CI 0.18-0.53) baseline, 0.26 (95% CI 0.20-0.34) with placebo and 0.08 (95% CI 0.04-0.12) with melatonin. Total sleep duration was 8.05 h (95% CI 7.65-8.44) baseline, 8.75 h (95% CI 8.56-8.98) with placebo and 9.84 h (95% CI 9.68-9.99) with melatonin. CONCLUSIONS: Although the study was small owing to recruitment difficulties, it still provides evidence of effectiveness of melatonin in children with sleep difficulties and ASD, which we predict a larger study would confirm.

Adolescent↗

Characterisation of the GH gene cluster in a new-world monkey, the marmoset (Callithrix jacchus).

In most mammals pituitary GH is encoded by a single gene with no close relatives. However, in man the GH gene has been shown to be one of a cluster of five closely related genes, four of which are expressed in the placenta. Rhesus monkey also expresses at least five closely related GH-like genes, although the genomic organisation of these has not been fully reported. Here we describe the cloning and characterisation of GH-like genes in a new-world monkey, the marmoset (Callithrix jacchus). This species possesses a cluster of eight GH-like 'genes'. The gene at the 5' end of this cluster encodes pituitary GH and is similar to that encoding human GH. Five of the eight marmoset 'genes' are probably pseudogenes, since they include mutations which would prevent normal expression, including stop codons and small insertions/deletions that would change the reading frame. In one case a large part of a gene is deleted, and in another a large insertion is introduced into an exon. The remaining two marmoset genes are potentially expressible, as proteins with sequences substantially different (at 25-30% of all residues) from that of marmoset GH itself; whether and in which tissue(s) such expression actually occurs is not yet known. None of the marmoset genes is clearly equivalent to any of the human GH-like genes expressed in the placenta, and this and phylogenetic analysis suggest that the duplications that gave rise to the marmoset GH gene cluster occurred independently of those that gave rise to the corresponding cluster in man. Although it includes more 'genes', the marmoset cluster extends over a shorter region of chromosomal DNA (about 35 kb) than does the human GH gene cluster (about 50 kb).

Amino Acid Sequence↗

Actions of monoclonal antibodies on the activity of human growth hormone (GH) in an in vitro bioassay.

An in vitro bioassay for GH was established, based on the response of the 3T3-F442A mouse preadipocyte cell line, together with a parallel receptor-binding assay using the same cells. The effects of monoclonal antibodies on the biological activity of human GH in vitro were then explored. Antibodies that did not bind GH had no effect on the bioassay or on receptor binding. Antibodies EB1 and EB2, which strongly enhance growth-promoting actions in vivo, inhibited the actions of human GH in the in vitro bioassay, and blocked binding of human GH to receptors. Antibody NA71, which weakly enhances growth promotion by human GH in vivo, enhanced biological activity in vitro but did not affect receptor binding. Thus, enhancement of the biological activity of human GH has been shown in this in vitro system, but the effect does not correlate completely with the established enhancement effects in vivo. Of the various mechanisms that have been proposed to explain the enhancement effect these results support the 'restriction hypothesis'--the idea that monoclonal antibodies may enhance GH action in vivo by preventing binding of GH to receptors/binding sites that are not involved in growth promotion.

3T3 Cells↗

Molecular evolution of growth hormone (GH) in Cetartiodactyla: cloning and characterization of the gene encoding GH from a primitive ruminant, the chevrotain (Tragulus javanicus).

In mammals the sequence of pituitary growth hormone (GH) is generally strongly conserved, indicating a slow basal rate of molecular evolution. However, on two occasions, during the evolution of primates and that of cetartiodactyls, the rate of evolution has increased dramatically (25 to 50-fold) so that the sequences of human and ruminant GHs differ markedly from those of other mammalian GHs. To define further the burst of GH evolution that occurred in cetartiodactyls, the GH gene of the chevrotain (Tragulus javanicus) has been cloned and characterized by use of genomic DNA and a polymerase chain reaction technique. Two very similar gene sequences, which probably reflect allelic variation, were isolated. The deduced sequence for the mature chevrotain GH differs from that of the bovine or red deer GH at only two to three residues, and phylogenetic analysis shows that the burst of rapid evolution of GH that occurred in the Cetartiodactyla must have been completed before the divergence of the Tragulidae and the advanced ruminants (Pecora). The rate of evolution during this burst must therefore have been greater than previously estimated. In other aspects (including signal sequence, 5' upstream sequence, and synonymous substitutions in the coding sequence), the chevrotain GH gene differs considerably from the GH genes of other ruminants and here there is no evidence for the period of accelerated evolution that is seen for GH itself.

Amino Acid Sequence↗

Episodic evolution of protein hormones in mammals.

Pituitary growth hormone (GH) and prolactin have been shown previously to display a pattern of evolution in which episodes of rapid change are imposed on a low underlying basal rate (near-stasis). This study was designed to explore whether a similar pattern is seen in the evolution of other protein hormones in mammals. Seven protein hormones were examined (with the common alpha-subunit of the glycoprotein hormones providing an additional polypeptide for analysis)--those for which sequences from at least four eutherian orders are available with a suitable non-eutherian outgroup. Six of these (GH, prolactin, insulin, parathyroid hormone, glycoprotein hormone alpha-subunit, and luteinizing hormone beta-subunit) showed markedly variable evolutionary rates in each case with a pattern of a slow basal rate and bursts of rapid change, the precise positions of the bursts varying from protein to protein. Two protein hormones (follicle-stimulating hormone beta-subunit and thyroid-stimulating hormone beta-subunit) showed no significant rate variation. Based on the sequences currently available, and pooling data from all eight proteins, the phase of slow basal change occupied about 85% of the sampled evolutionary time, but most evolutionary change (about 62% of the substitutions accepted) occurred during the episodes of rapid change. It is concluded that, in mammals at least, a pattern of prolonged periods of near-stasis with occasional episodes of rapid change provides a better model of evolutionary change for protein hormones than the one of constant evolutionary rates that is commonly favored. The mechanisms underlying this episodic evolution are not yet clear, and it may be that they vary from one group to another; in some cases, positive selection appears to underlie bursts of rapid change. Where gene duplication is associated with a period of accelerated evolution this often occurs at the end rather than the beginning of the episode. To what extent the type of pattern seen for protein hormones can be extended to other proteins remains to be established.

Animals↗

The nursing management of diarrhoea and constipation before and after the implementation of a bowel management protocol.

Intensive care unit (ICU) patients frequently suffer problems associated with both diarrhoea and constipation. Strategies to optimise the management of these conditions need to focus on improving the communication between staff and ensuring effective treatment is implemented. The team involved in this study developed a Bowel Management Protocol (BMP). The effect of this BMP on the documentation of assessment and management of diarrhoea and constipation was evaluated using a quasi-experimental research design. Data were collected via a retrospective audit of medical records. Two groups of patient records were randomly sampled. The records of 60 patients who were admitted to ICU in the 6 months before the introduction of the BMP were accessed together with the records of 60 patients admitted in the 6 months following the introduction of the BMP. Data were collected regarding patient demographics and the assessment and management of bowel function before and after BMP introduction. The results indicated that a BMP improved documentation of the assessment of bowel function. In addition, there was an improvement in the documentation of nursing intervention in the presence of constipation and diarrhoea. These results have to be interpreted with caution because, despite random sampling over two 6 month periods, there were statistically significant differences in age, length of stay, method of feeding and medical diagnosis between the two groups. Further research into the effectiveness of using a BMP is recommended.

Adolescent↗

Molecular evolution of GH in primates: characterisation of the GH genes from slow loris and marmoset defines an episode of rapid evolutionary change.

Pituitary growth hormone (GH), like several other protein hormones, shows an unusual episodic pattern of molecular evolution in which sustained bursts of rapid change are imposed on long periods of very slow evolution (near-stasis). A marked period of rapid change occurred in the evolution of GH in primates or a primate ancestor, and gave rise to the species specificity that is characteristic of human GH. We have defined more precisely the position of this burst by cloning and sequencing the GH genes for a prosimian, the slow loris (Nycticebus pygmaeus) and a New World monkey, marmoset (Callithrix jacchus). Slow loris GH is very similar in sequence to pig GH, demonstrating that the period of rapid change occurred during primate evolution, after the separation of lines leading to prosimians and higher primates. The putative marmoset GH is similar in sequence to human GH, demonstrating that the accelerated evolution occurred before divergence of New World monkeys and Old World monkeys/apes. The burst of change was confined largely to coding sequence for mature GH, and is not marked in other components of the gene sequence including signal peptide, 5' upstream region and introns. A number of factors support the idea that this episode of rapid change was due to positive adaptive selection. Thus (1) there is no apparent loss of function of GH in man compared with non-primates, (2) after the episode of rapid change the rate of evolution fell towards the slow basal level that is seen for most mammalian GHs, (3) the accelerated rate of substitution for the exons of the GH gene significantly exceeds that for introns, and (4) the amino acids contributing to the hydrophobic core of GH are strongly conserved when higher primate and other GH sequences are compared, and for coding sequences other than that coding for hydrophobic core residues the rate of substitution for non-synonymous sites (K(A)) is significantly greater than that for synonymous sites (K(S)). In slow loris, as in most non-primate mammals, there is no evidence for duplication of the GH gene, but in marmoset, as in rhesus monkey and man, the putative GH gene is one of a cluster of closely related genes.

Animals↗

Episodic evolution of protein hormones: molecular evolution of pituitary prolactin.

Previous studies have shown that pituitary growth hormone displays an episodic pattern of evolution, with a slow underlying evolutionary rate and occasional sustained bursts of rapid change. The present study establishes that pituitary prolactin shows a similar pattern. During much of tetrapod evolution the sequence of prolactin has been strongly conserved, showing a slow basal rate of change (approx 0.27x10(9) substitutions/amino acid site/year). This rate has increased substantially ( approximately 12- to 38-fold) on at least four occasions during eutherian evolution, during the evolution of primates, artiodactyls, rodents, and elephants. That these increases are real and not a consequence of inadvertant comparison of paralogous genes is shown (for at least the first three groups) by the fact that they are confined to mature protein coding sequence and not apparent in sequences coding for signal peptides or when synonymous substitutions are examined. Sequences of teleost prolactins differ markedly from those of tetrapods and lungfish, but during the course of teleost evolution the rate of change of prolactin has been less variable than that of growth hormone. It is concluded that the evolutionary pattern seen for prolactin shows long periods of near-stasis interrupted by occasional bursts of rapid change, resembling the pattern seen for growth hormone in general but not in detail. The most likely basis for these bursts appears to be adaptive evolution though the biological changes involved are relatively small.

Animals↗

Temperature taking in the ICU: which route is best?

Temperature measurement in an intensive care environment requires accurate estimation of core temperature via reliable equipment. Intermittent rectal probes were routinely used to measure core temperature in all extubated patients admitted to the Intensive Care Unit (ICU) which was the setting for this project. The nursing and medical staff identified various problems associated with this practice and a quality improvement project was implemented to compare temperatures recorded using three different routes: rectal, infrared tympanic and nasopharyngeal. Forty-nine patients were included in the study. Nasopharyngeal temperature measurements were recorded for all intubated patients and rectal temperature measurements were recorded for all extubated patients. During data collection, infrared tympanic temperature measurements were recorded at the same time as all other temperature measurements. The main comparison was between the rectal route and the infrared tympanic route because of the problems with the rectal probes that had been identified by staff. The results indicated statistically significant correlations between temperatures measured at the different sites. These results confirmed previous literature and the ICU involved in this study replaced rectal temperature measurement via intermittent probe insertion with infrared tympanic thermometry for the measurement of core temperature in extubated patients.

Body Temperature↗

Mentorship in nursing: a literature review.

The recent increase in published work relating to the supervision of nurses and in particular mentorship suggests that nurses value the opportunities that such schemes present for developing practice. Much of the literature surrounding mentorship concerns the supervision of students in practice settings but more recently, especially following the changes to post-registration education, attention has shifted to the supervision of qualified nurses. Although the principles of supervision for students and qualified nurses are the same, differences do occur in supervisory practices. This review examines the literature associated with the supervision of student nurses and focuses on the nature and practice of mentorship in practice settings. The literature reveals that confusion exists regarding both the concept of mentorship and the role of the mentor. Many authors propose models or frameworks for mentoring activities. These tend to outline the stages of the mentoring process and the relationship between mentor and mentee. No one model is seen as more appropriate than another and choice usually depends upon the mentor's familiarity with a particular framework. It is also evident that there is inconsistency in the length and level of preparatory courses for mentors. As yet there is in the United Kingdom no national minimum requirement or common preparation route and in practice mentors are prepared by way of the appropriate National Board Teaching and Assessing module and/or short local 2-day course.

Education, Nursing↗

Cloning and characterisation of the gene encoding mole rat (Spalax ehrenbergi) growth hormone.

In mammals the structure of pituitary GH is generally strongly conserved, reflecting a slow basal rate of molecular evolution. However, on a few occasions the rate has increased - markedly during the evolution of primates and artiodactyls, and to a small extent during the evolution of rodents and rabbit - giving rise to marked differences between GH sequences of these species. In order to extend knowledge of rodent GHs we have cloned and characterised part of the GH gene of the Eurasian mole rat (Spalax ehrenbergi) using genomic DNA and a PCR technique. The sequence of all of the coding region and 5' untranslated region (UTR), most of the 3' UTR and part of the promoter region is described. The overall organisation of the mole rat GH gene is similar to that of GH genes from other mammals. The proximal Pit-1 sequence in the gene promoter differs somewhat from that of rat or mouse. The deduced sequence for the mature GH from mole rat differs from that of pig GH (thought to be identical to the ancestral placental mammal GH sequence) at 7 residues and from rat, mouse and hamster GHs at 9 to 12 residues. Only one or two of these substitutions involve residues close to the receptor-binding sites of the hormone.

Amino Acid Sequence↗

Production and characterisation of deletion mutants of ovine growth hormone.

A number of analogues of ovine growth hormone (GH), in which regions of the hormone had been deleted, were produced by site-directed mutagenesis, and characterised by radioimmunoassays and radioreceptor assays. These analogues were based on a previously described variant (oGH1) in which an 8-residue extension replaces the N-terminal alanine of pituitary-derived ovine GH. Three analogues with deletions near the N-terminus were studied, with shorter extensions of 7 or 1-2 residues (oGH14, oGH5) or with the N-terminal sequence Ala-Phe-Pro- of pituitary-derived ovine GH replaced by Thr-Met-Ile-Thr- (oGH11). These modifications had little effect on potency in radioimmunoassays based on a polyclonal antibody and five different monoclonal antibodies (MABs), or in a radioreceptor assay, indicating that the N-terminal sequence was not included in the epitope binding to any of the monoclonal antibodies, or a major epitope binding to the polyclonal antibody, or in receptor binding site 1. A variant in which residues 133-139 were deleted retained full binding to 4 of the 5 MABs, suggesting correct folding, but markedly reduced binding to MAB OA16, suggesting that the epitope for this MAB includes some or all of these residues. This variant also failed to displace about 35% of labelled hormone from the polyclonal antibody studied, suggesting that residues 133-139 may be involved in a major epitope for this antibody. This variant showed slightly lower receptor binding activity than ovine GH. Two other deletion variants - oGH1Delta33-46 (equivalent to the naturally occurring 20K variant of human GH) and oGH1Delta180-191 (lacking the C-terminal 12 residues) showed poor folding efficiency and solubility, and low binding to all MABs except OA15, which has a linear epitope. The results suggest that these variants were incorrectly folded, but interestingly they did retain some activity in the receptor-binding assay (respectively about 5% and 0.5% of the activity of ovine GH itself).

Animals↗

Patient problems and evaluation of patient discharge education after coronary artery bypass graft surgery.

Coronary artery bypass graft surgery (CABGS) patients who have a routine postoperative course are now being discharged as early as the fourth postoperative day. This descriptive and comparative study explored the postoperative problems experienced by CABGS patients after discharge from hospital and evaluated the patient discharge education program. No correlations were found between the length of hospital stay and the following factors: number and type of problems/concerns; whether patients felt ready to leave hospital on the discharge day; whether patients felt they were coping after discharge, and the number of and reasons for readmission to hospital after discharge. Continual review of the patient education program is recommended and further research into the discharge needs of rural patients is required.

Adult↗

Function switching as a basis for bursts of rapid change during the evolution of pituitary growth hormone.

Pituitary growth hormone shows a pattern of molecular evolution in which occasional bursts of rapid change are imposed on a slow basal rate. It is suggested that these bursts of rapid evolution are a consequence of acquisition by this protein hormone of a secondary function, the importance of which varies. As the function of the hormone switches to accommodate the changes in role, its structure will also alter, adapting it to acquisition or loss of the secondary function. Several rounds of such "function switching" could give a substantial change in structure (the sum of several small changes) with little overall change in function. A similar process could underlie rapid bursts of evolution in other proteins.

Animals↗

Cloning and characterisation of the gene encoding red deer (Cervus elaphus) growth hormone: implications for the molecular evolution of growth hormone in artiodactyls.

In mammals the structure of pituitary GH is generally strongly conserved, indicating a slow basal rate of molecular evolution. However, on two occasions, during the evolution of primates and of artiodactyls, the rate of evolution has increased dramatically (25- to 50-fold) so that the sequences of human and ruminant GHs differ markedly from those of other mammalian GHs. In order to define further the burst of GH evolution that occurred in artiodactyls we have cloned and characterised the GH gene of red deer (Cervus elaphus) using genomic DNA and a polymerase chain reaction technique. The deduced sequence for the mature GH from red deer is identical to that of bovine GH, indicating that the burst of rapid evolution of GH that occurred in Artiodactyla must have been completed before the divergence of Cervidae and Bovidae and suggesting that the rate of evolution during this burst must have been greater than previously estimated. In other aspects (signal sequence, 5' and 3' sequences, introns and synonymous substitutions in the coding sequence) the red deer GH gene differs considerably from the GH genes of other ruminants. Differences between the signal peptide sequences of red deer and bovid GHs probably explain why N-terminal heterogeneity is seen in bovine, ovine and caprine GHs but not GH from red deer, pig or most other mammals.

Amino Acid Sequence↗