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Biomedical subjects

A Salmon

Publications and source records attributed to A Salmon.

At least 19 recordsLinked to original sources
PubMed2007

Non-invasive restrained ECG recording in conscious small rodents: a new tool for cardiac electrical activity investigation.

In vivo electrophysiology remains a suitable method to monitor cardiac activity; however, surface electrocardiogram (ECG) monitoring remains complicated in the case of small animals. Sedation has helped to maintain the animal still; however, it is known that anesthetic drugs impair the regulation of the cardiac electrical activity. To circumvent this problem, ECG monitoring using telemetry or restraints has been developed. This study reports a new methodology, based on a restraining system without further sedation, for recording ECGs on small animal models. We investigated its efficacy in Syrian hamsters and in several strains of mice, and we compared these data to those obtained with telemetry devices. We show that this new system can easily be used in animals of different sizes ranging from adult hamsters to newborn mice. When compared to telemetry, this restrained ECG monitoring method shows a very good yield, as 65% of total beats can be used for further analysis. When recorded in the same animals, RR intervals distributions are identical for both techniques. In conclusion, this restrained ECG monitoring technique is a well-suited tool for exploring various aspects of cardiac electrophysiology in a wide variety of small animals including very young mice.

Animals↗
PubMed2006

Intrapericardial administration of novel DNA formulations based on thermosensitive Poloxamer 407 gel.

Inherited cardiopathies are leading to life-threatening conditions such as heart failure. Moreover, treatments currently available fail in altering the cardiac phenotype. Thus, gene therapy appears as an attracting alternative to conventional treatments. However, gene delivery remains a major hurdle in achieving this goal. To obtain regional delivery of plasmid DNA, intrapericardial administration seems to be an interesting approach. In order to improve retention time at the site of injection, formulations based on a thermosensitive gel of Poloxamer 407 were assessed. Protection and condensation of plasmid DNA was initially performed through complexation with polyethyleneimine (PEI), a widely used polymer. Characterization of the size and zeta potential of the complexes suggested interactions between the polyplexes and the Poloxamer gel through significant increase of the size of the polyplexes and shielding of the surface charges. In vivo evaluation has highlighted the toxicity of PEI/DNA polyplexes toward the myocardium. However, feasibility of intrapericardial injection of Poloxamer based formulations as well as their very low toxicity has been established.

Cardiomyopathies↗
PubMed2006

Increased level of chromosomal damage after irradiation of lymphocytes from BRCA1 mutation carriers.

Deleterious mutations in the BRCA1 gene predispose women to an increased risk of breast and ovarian cancer. Many functional studies have suggested that BRCA1 has a role in DNA damage repair and failure in the DNA damage response pathway often leads to the accumulation of chromosomal aberrations. Here, we have compared normal lymphocytes with those heterozygous for a BRCA1 mutation. Short-term cultures were irradiated (8Gy) using a high dose rate and subsequently metaphases were analysed by 24-colour chromosome painting (M-FISH). We scored the chromosomal rearrangements in the metaphases from five BRCA1 mutation carriers and from five noncarrier control samples 6 days after irradiation. A significantly higher level of chromosomal damage was detected in the lymphocytes heterozygous for BRCA1 mutations compared with normal controls; the average number of aberrations per mitosis was 3.48 compared with 1.62 in controls (P=0.0001). This provides new evidence that heterozygous mutation carriers have a different response to DNA damage compared with noncarriers and that BRCA1 has a role in DNA damage surveillance. Our finding has implications for treatment and screening of BRCA1 mutation carriers using modalities that involve irradiation.

Chromosome Aberrations↗
PubMed2005

Muscarinic modulations of neuronal anticholinesterase responses.

Anticholinesterases (antiChEs) are increasingly used for treating patients with neurodegenerative diseases, but the dependence of their effects on the integrity of cholinergic functions has not yet been analyzed at the molecular level. Here, we report that manipulation of muscarinic neurotransmission confers drastic changes on antiChE responses in the rat brain. In the brains of naïve, un-stressed rats, the irreversible organophosphate antiChE, diisopropylfluorophosphonate (DFP) induced post-treatment accumulation of catalytically active G1 monomers of acetylcholinesterase (AChE). Pre-treatment with the selective M1 muscarinic antagonist, pirenzepine, but not the general muscarinic antagonist, scopolamine, attenuated this G1 increase. DFP-enhanced AChE gene expression was accompanied by diverted splicing from the primary AChE-S mRNA variant, encoding G4 synaptic membrane AChE-S tetramers, to "readthrough" AChE-R mRNA, which encodes soluble G1 monomers. Both the mRNA increase and the shifted splicing were long lasting (>24 h) and common to the parietal cortex and hippocampal CA1 and CA3 neurons. Importantly, the splicing shift was maximal under DFP alone, as compared with sham-injected rats, and virtually preventable by pre-treatment with pirenzepine. In contrast, induction of AChE transcription was less dependent on muscarinic function, resulting in AChE-S but not AChE-R increases. Our findings demonstrate distinct regulation of the enhanced transcription and the alternative splicing reactions to antiChE treatment and shed new light on the differential responses to antiChEs of demented patients with increasingly impaired cholinergic neurotransmission.

Acetylcholinesterase↗
PubMed2005

[Treatment of febrile neutropenia episodes in children, with a piperacillin-tazobactam and netilmicin combination].

OBJECTIVES: The authors had for aim to assess the effectiveness and toxicity of a piperacillin-tazobactam-netilmicin combination, and the possibility of avoiding using glycopeptide, in children with febrile neutropenic episodes induced by chemotherapy. METHODS: A retrospective study was made, including children treated for a febrile neutropenic episode (absolute neutrophile count < 0.5 x 10(9)/l) by a piperacillin-tazobactam-netilmicin combination. If fever persisted 48 hours after the beginning of antibiotic therapy, a glycopeptide could be added. The responses to the treatment were defined as follows: 1) total success (no fever or documented infection) at 48 hours and at 72 hours following the beginning of treatment; 2) partial success (apyrexia beyond 72 hours without any therapeutic change); 3) failure (persistent infectious signs 48 hours after the introduction of glycopeptide). RESULTS: Sixty-nine episodes were assessable, corresponding to 41 patients, treated for a solid tumour (29), an acute leukaemia in remission (11), or a metabolic disease (1). The febrile episodes were divided into fever of unknown origin (71%), microbiologically documented fever (12%), and clinically documented fever (17%). No death occurred, no toxicity was reported. With this antibiotic therapy, total success at 72 hours was observed in 72% in case of fever of unknown origin and 45% in case of documented infections. The success rate reached 84% when a glycopeptide was added (30% of the cases). CONCLUSION: The piperacillin-tazobactam-netilmicin combination is very effective and well tolerated in probabilistic treatment of febrile neutropenia induced by chemotherapy, but does not allow to decreasing the frequency of glycopeptide administration.

Adolescent↗
PubMed2005

Rewarming of healthy volunteers after induced mild hypothermia: a healthy volunteer study.

OBJECTIVES: The study compares the efficacy of two active and one passive warming interventions in healthy volunteers with induced mild hypothermia. METHODS: Eight volunteers were studied in a random order crossover design. Each volunteer was studied during re-warming from a core temperature of 35 degrees C with each of: a radiant warmer (Fisher & Paykel); a forced air warmer (Augustine Medical), and a polyester filled blanket, to re-warm. RESULTS: No significant differences in re-warming rates were observed between the three warming devices. It was found that the subject's endogenous heat production was the major contributor to the re-warming of these volunteers. Metabolic rates of over 350 W were seen during the study. CONCLUSIONS: For patients with mild hypothermia and in whom shivering is not contraindicated our data would indicate that the rate of re-warming would be little different whether a blanket or one of the two active devices were used. In the field, this may provide the caregiver a useful choice.

Adult↗
PubMed2001

Structural properties of docosahexaenoyl phospholipid bilayers investigated by solid-state 2H NMR spectroscopy.

Polyunsaturated lipids in cellular membranes are known to play key roles in such diverse biological processes as vision, neuronal signaling, and apoptosis. One hypothesis is that polyunsaturated lipids are involved in second messenger functions in biological signaling. Another current hypothesis affirms that the functional role of polyunsaturated lipids relies on their ability to modulate physical properties of the lipid bilayer. The present research has employed solid-state 2H NMR spectroscopy to acquire knowledge of the molecular organization and material properties of polyunsaturated lipid bilayers. We report measurements for a homologous series of mixed-chain phosphatidylcholines containing a perdeuterated, saturated acyl chain (n:0) at the sn-1 position, adjacent to docosahexaenoic acid (DHA, 22:6omega3) at the sn-2 position. Measurements have been performed on fluid (L(alpha))-state multilamellar dispersions as a function of temperature for saturated acyl chain lengths of n = 12, 14, 16, and 18 carbons. The saturated sn-1 chains are therefore used as an intrinsic probe with site-specific resolution of the polyunsaturated bilayer structure. The 2H NMR order parameters as a function of acyl position (order profiles) have been analyzed using a mean-torque potential model for the chain segments, and the results are discussed in comparison with the homologous series of disaturated lipid bilayers. At a given absolute temperature, as the sn-1 acyl length adjacent to the sn-2 DHA chain is greater, the order of the initial chain segments increases, whereas that of the end segments decreases, in marked contrast with the corresponding disaturated series. For the latter, the order of the end segments is practically constant with acyl length, thus revealing a universal chain packing profile. We find that the DHA-containing series, while more complex, is still characterized by a universal chain packing profile, which is shifted relative to the homologous saturated series. Moreover, we show how introduction of DHA chains translates the order profile along the saturated chains, making more disordered states accessible within the bilayer central region. As a result, the area per lipid headgroup is increased as compared to disaturated bilayers. The systematic analysis of the 2H NMR data provides a basis for studies of lipid interactions with integral membrane proteins, for instance in relation to characteristic biological functions of highly unsaturated lipid membranes.

Deuterium↗
PubMed2001

Mutations in the gamma(2) subunit of AMP-activated protein kinase cause familial hypertrophic cardiomyopathy: evidence for the central role of energy compromise in disease pathogenesis.

Familial hypertrophic cardiomyopathy (HCM) has been widely studied as a genetic model of cardiac hypertrophy and sudden cardiac death. HCM has been defined as a disease of the cardiac sarcomere, but mutations in the known contractile protein disease genes are not found in up to one-third of cases. Further, no consistent changes in contractile properties are shared by these mutant proteins, implying that an abnormality of force generation may not be the underlying mechanism of disease. Instead, all of the sarcomeric mutations appear to result in inefficient use of ATP, suggesting that an inability to maintain normal ATP levels may be the central abnormality. To test this hypothesis we have examined candidate genes involved in energy homeostasis in the heart. We now describe mutations in PRKAG2, encoding the gamma(2) subunit of AMP-activated protein kinase (AMPK), in two families with severe HCM and aberrant conduction from atria to ventricles in some affected individuals (pre-excitation or Wolff-Parkinson-White syndrome). The mutations, one missense and one in-frame single codon insertion, occur in highly conserved regions. Because AMPK provides a central sensing mechanism that protects cells from exhaustion of ATP supplies, we propose that these data substantiate energy compromise as a unifying pathogenic mechanism in all forms of HCM. This conclusion should radically redirect thinking about this disorder and also, by establishing energy depletion as a cause of myocardial dysfunction, should be relevant to the acquired forms of heart muscle disease that HCM models.

Amino Acid Sequence↗
PubMed2001

A clinical comparison of radiant warmer and incubator care for preterm infants from birth to 1800 grams.

OBJECTIVE: The objective of this study was to compare radiant warmer and incubator care for preterm infants from birth with respect to temperature control and weight gain. METHODS: Sixty preterm infants <33 weeks' gestation were randomized at birth to radiant warmer or incubator care. The initial goal was to maintain abdominal temperature at 36.8 degrees C in both groups and axillary temperature at 36.8 to 37.3 degrees C; air servocontrol was used for incubator infants. Infants in both groups received added humidity for 5 days if their weight was <1000 g and for 3 days if they weighed between 1000 and 1249 g. During a 3-hour period on days 1 to 7, recordings of abdominal, forehead, and foot temperatures were obtained. The percentage of the recording time during which the abdominal temperature was in the target range of between 36 degrees C and 37.5 degrees C was determined as an indicator of temperature control. Weight gain from birth to 1800 g was compared. Secondary outcomes included fluid balance and clinical events. RESULTS: There were 30 infants in each group; 48 were <1500 g (of whom 17 were <1000 g). There were no significant differences in birth weight, gestation, gender, or illness severity scores in the 2 groups. Significant differences in temperature control were noted on day 1. Although admission temperatures were similar, lower abdominal temperatures were noted in the first 2 hours of life in the incubator group (medians were 36.6 degrees C and 35.9 degrees C in the radiant warmer and incubator groups, respectively). Similarly, mean abdominal temperatures during the 3-hour recording on day 1 were lower in the incubator group, and infants in this group spent a significantly greater percentage of the recording time with temperatures outside the target range (17.3% compared with 0.88%). Other temperature recordings from the forehead and foot were not significantly different in the groups. Fluid intakes were higher for infants under radiant warmer on days 2, 3, and 4, and the difference amounted to a mean of 12.8 mL/kg/d. Maximum sodium levels in the first week were similar in the 2 groups. Mean weight gain was 17.4 g/kg/d for the radiant warmer group and 17.1 g/kg/d for the incubator group; days to regain birth weight and length of hospital stay were not significantly different. Greater numbers of infants in the radiant warmer group required phototherapy, and adverse events (which included death, necrotizing enterocolitis, chronic lung disease, grade 3 or 4 intraventricular hemorrhage, periventricular leukomalacia, or retinopathy requiring laser treatment) were less frequent in the radiant warmer group (1 infant compared with 8 in the incubator group; relative risk 0.1; 95% confidence intervals: 0.01-0.82). CONCLUSIONS: This study has shown differences in abdominal temperatures on day 1 and outcome, although the latter finding should be viewed with caution because of the sample size. The results indicate benefits for the initial use of the radiant warmer after birth. Although fluid requirements were higher in the radiant warmer group for days 2 through 4, the increased fluid volumes were given without apparent adverse effect.

Body Temperature↗
PubMed2000

The Australian National Workplace Health Project: design and baseline findings.

BACKGROUND: This paper describes the study design, recruitment, measurement, and initial recruitment outcomes of Australia's largest workplace intervention trial, the National Workplace Health Project. METHODS: This was a cluster-randomized trial of socio-behavioral and environmental interventions focusing on key behaviors of physical activity, healthy food choices, cigarette smoking, and alcohol consumption, as well as motivational readiness for change. Twenty worksites were randomized separately for each intervention using a two-by-two factorial design. All participants underwent a health risk appraisal and measurements were made at baseline and at 1 and 2 years. RESULTS: The overall response rate for the baseline survey was 73% with 61% attending the health risk appraisal. The sample was predominantly male, English-speaking, married, blue-collar workers. Overall, 12% reported unsafe alcohol consumption, 26% were current smokers, 44% were physically inactive, 74% ate at most one piece of fruit per day, and 26% ate at most one serving of vegetables per day. Intervention and control conditions were similar at baseline for the primary outcomes, except that a higher proportion of the sociobehavioral intervention condition was more physically active (59%) than the corresponding control condition (53%). CONCLUSIONS: This study will permit the rigorous evaluation of the efficacy of sociobehavioral and environ mental intervention approaches to workplace health promotion. Although participants were randomized by worksite, intervention and control conditions were similar at baseline; any differences in the primary out come variables will be controlled for in the analysis.

Adult↗
PubMed2000

Evaluation of a (pilot) stage-tailored brief smoking cessation intervention among hospital patients presenting to a hospital pre-admission clinic.

Despite the significant benefits of advising all smokers to quit, hospital patients who smoke do not systematically receive this advice. This study sought to determine the prevalence of smoking, attitudes of patients towards not smoking while in hospital, and the feasibility and effectiveness of a brief smoking cessation intervention in a pre-admission clinic context. Over 230 smokers received a brief smoking cessation intervention, while a control group (n = 114) received only a free Quit Kit. The age-standardised smoking prevalence was 19%; a further 3% of patients were recent quitters. Most smokers do not expect or experience problems with not smoking while in hospital. Brief smoking cessation advice tailored to stage-of-change by a health worker in a hospital pre-admission clinic significantly increased the quit rates for females.

Adolescent↗
PubMed1999

Gene delivery to the myocardium by intrapericardial injection.

Several studies have demonstrated the feasibility of gene transfer into the heart muscle. However, all the available data also indicate that the extent of transfection remains limited. As an alternative method to intravascular administration, we have developed a novel strategy which uses the pericardial sac. When a replication-deficient adenovirus containing the cDNA encoding a bacterial beta-galactosidase is injected into the pericardial sac of adult Wistar rats the staining is exclusively restricted to the pericardial cell layers. However, injecting a mixture of collagenase and hyaluronidase together with the virus, leads to a large diffusion of the transgene activity, reaching up to 40% of the myocardium. Transgene expression is predominant in the left ventricle and the interventricular septum but limited in the right ventricle. In vivo echocardiographic measurements of the left ventricular diameters at end diastolic and end systolic times show no difference between virus- and sham-injected animals, thus indicating a good clinical tolerance to this strategy of virus delivery. The same protocol has been used with the same efficiency in mice, which leads us to propose injection into the pericardial sac as an effective and harmless method for gene transfer into the heart muscle.

Adenoviridae↗
PubMed1999

Prevention of stress fractures using custom biomechanical shoe orthoses.

In a prospective study of stress fractures the hypothesis that training with custom made biomechanical shoe orthoses could lessen the incidence of stress fractures in infantry recruits was tested. Recruits were assigned randomly to groups and given soft biomechanical orthoses or semirigid biomechanical orthoses and compared with a control group that did not train in biomechanical orthoses. All recruits wore infantry boots with soles designed like those of basketball shoes. Recruits were examined biweekly during 14 weeks of basic training. The incidence of stress fractures was 15.7% for the recruits with the semirigid biomechanical orthoses, 10.7% for the recruits with the soft biomechanical orthoses, and 27% for the control group. The soft biomechanical orthoses were tolerated better by the recruits than were the semirigid devices. Among trainees at high risk for stress fractures, prophylactic use of custom made biomechanical orthoses may be warranted.

Adult↗
PubMed1998

Tuberous sclerosis complex and Wolff-Parkinson-White syndrome.

This report highlights the association between tuberous sclerosis and Wolff-Parkinson-White syndrome. Ten patients with concurrent diagnoses of Wolff-Parkinson-White syndrome and tuberous sclerosis were identified. Wolff-Parkinson-White syndrome presented early in life, nine cases being diagnosed in the first year. Eight of the 10 cases were male. In eight cases, the syndrome was associated with supraventricular tachycardias, and in nine with cardiac rhabdomyomata. One child died from cardiac failure secondary to obstruction of the left ventricular outflow tract by a rhabdomyoma. Five of nine survivors showed resolution of Wolff-Parkinson-White syndrome on follow up. The accessory pathway was localised in nine patients from surface electrocardiograms: six children had left sided pathways and three had right sided pathways.

Electrocardiography↗
PubMed1995

Magic-angle spinning and solution 13C nuclear magnetic resonance studies of medium- and long-chain cholesteryl esters in model bilayers.

The incorporation of cholesteryl esters (CE) with saturated acyl chains into the lamellar structure of phospholipids was studied by 13C nuclear magnetic resonance (NMR) spectroscopy. The CE (octanoate, palmitate, and stearate) were 13C-enriched in the carboxyl carbon to enhance the signals of the small amounts of bilayer-incorporated CE. Magic-angle spinning (MAS) NMR was used to detect signals in unsonicated multilamellar phosphatidylcholine (PC), and solution NMR was used to detect signals in PC small unilamellar vesicles (SUV). All CE showed a carbonyl peak reflecting localization of the carbonyl at the aqueous interface (Hamilton & Small, 1982). The maximal incorporation decreased with chain length, from 5 mol % for octanoate to 1.4 mol % for stearate in multilayers; the stearate ester had a solubility slightly lower than that of cholesteryl oleate (2 mol %). The maximal incorporation of a specific CE was 1.2-2.0 times higher in SUV than in multilayers. Cholesteryl oleate did not prevent solubilization of cholesteryl stearate in the PC interface. CE in excess of the solubility maximum in multilayer samples was shown to be crystalline at 35 degrees C by MAS NMR; thus, in the bilayer the CE gained considerable mobility compared to its mobility in its pure bulk phase at body temperature. Furthermore, CE with two saturated chains were not distinguishable from esters with an unsaturated chain with respect to mobility and position in the interface. These fundamental interfacial properties assure utilization of CE with common dietary fatty acyl chains.

Carbon Isotopes↗