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Biomedical subjects

K Hogan

Publications and source records attributed to K Hogan.

At least 19 recordsLinked to original sources
PubMed2006

Muscarinic type 1 receptors mediate part of nitric oxide's vagal facilitatory effect in the isolated innervated rat right atrium.

We investigated whether vagal cardiac cholinergic facilitation by nitric oxide (NO) is mediated by cardiac muscarinic receptor subtypes in the vagally innervated rat right atrium in vitro. Experiments were carried out in the presence of atenolol (4 microM). The right vagus was stimulated at 4, 8, 16, 32 Hz; pulse duration 1 ms at 20 V for 20s; vagal postganglionic activation was achieved using nicotine (0.1, 0.3, 0.5, 1mM) and the effect on cardiac interval (ms) assessed. Pirenzepine (1 microM), a M1 antagonist, attenuated vagally induced increase in cardiac interval. L-Arginine (0.34 mM) superfused with pirenzepine failed to reverse this attenuation, however, L-arginine applied alone reversed the reduction vagal cardiac slowing. Similarly, sodium nitroprusside (10 microM) applied alone, and not together with pirenzepine, was able to reverse the attenuation of vagal effects caused by pirenzepine. Synthetic MT7 (1 nM) toxin, a selective M1 antagonist confirmed these results. M3 antagonism using para-fluorohexahydrosiladifenidol (p-F-HHSiD) (300 nM) and M4 antagonism with PD 102807 (200 nM) did not affect the vagally induced increase in cardiac interval. Nicotine induced increase in cardiac interval was not altered by pirenzepine. These results show that antagonism of M1 receptors on cardiac vagal preganglionic fibres reduces vagal efficacy which can be recovered by either a nitric oxide synthase substrate or a NO donor.

Analysis of Variance↗
PubMed2006

Vasoactive intestinal polypeptide receptor antagonism enhances the vagally induced increase in cardiac interval of the rat atrium in vitro.

The effect of vasoactive intestinal polypeptide (VIP) receptor antagonism on preganglionic vagal electrical stimulation and on vagal postganglionic activation using nicotine and 1,1-dimethyl-4-phenylpiperazinium iodide on cardiac interval was evaluated in the isolated innervated rat right atrium. The vagus was stimulated at 4, 8, 16 and 32 Hz, pulse duration 1 ms, 20 V, for 30 s. All experiments were carried out in the presence of atenolol (4 microM). Vagal stimulation caused a frequency-dependent increase in cardiac interval which was amplified significantly at each frequency, except at 32 Hz, following application of the VIP receptor antagonist VIP(6-28) at 2 nM in 15 rats. Application of the ganglionic antagonist hexmethonium (28 microM, n = 7 rats) prior to 2 nM VIP(6-28) abolished this effect. Increasing the concentration of VIP(6-28) 10-fold to 20 nM did not result in a greater increase in cardiac interval than that obtained at 2 nM. Nicotine (0.1, 0.3, 0.5, 1.0 and 2.0 mM) increased cardiac interval by direct activation of postganglionic vagal fibres, but 2 nM VIP(6-28) did not affect the nicotine concentration response (n = 6 rats). 1,1-Dimethyl-4-phenylpiperazinium iodide (25, 50, 100 and 200 microM; n = 6 rats) was also used to induce an increase in cardiac interval; again it was not significantly altered by 2 nM VIP(6-28). Therefore, VIP receptor antagonism enhances the magnitude of vagally induced cardiac slowing, probably via an action at the preganglionic-postganglionic synapse.

Animals↗
PubMed2006

The safety of single-physician procedural sedation in the emergency department.

BACKGROUND: Previous research has shown the safety of procedural sedation in the emergency department in university settings involving multiple emergency physicians. OBJECTIVE: To examine sedation in the emergency department conducted by a single emergency physician with monitoring by the emergency nurse. METHODS: The Procedural Sedation in the Community Emergency Department Registry is a prospective observational database of procedural sedation cases directed by the emergency physicians. Among other parameters, the registry tracts whether emergency physicians or emergency nurses monitored patient sedation. The incidence of complications and outcomes were compared between these two monitoring groups. RESULTS: 1028 procedural sedations were performed on 977 patients at 14 sites. In 885 (86.1%) cases the emergency physician directed the sedation, and performed the procedure with monitoring by the emergency nurse. Complications occurred in 42 (4.1%) patients, 35 (4.0%) EN monitored patients and 6 (4.2%) EP monitored patients (p>0.7). Procedures were successful in 863 (97.5%) cases monitored by emergency nurses and in 140 (97.9%) patients monitored by emergency physicians (p>0.7). CONCLUSION: Procedural sedation in the emergency department performed by a single emergency physician is safe and effective.

Clinical Competence↗
PubMed2005

An investigation into the presence of a vagal tachycardia and the effect of vasoactive intestinal polypeptide on rat heart rate in vitro.

The presence of the vagal tachycardia and the effect of vasoactive intestinal polypeptide in the isolated innervated rat atrium were investigated. The right vagus, or cardiac branch, were stimulated at 4, 8, 16 and 32 Hz, pulse duration 1 ms, 20 V, 30 s before atropine and for 1 min after atropine (3 micromol/l), experiments were carried out in the presence of atenolol (4 micromol/l). No significant vagal tachycardia was observed in the presence of atropine, the greatest increase in heart rate was at 16 Hz which was 3+/-1 beats/min (n = 12 rats) (p = 0.052). Baseline heart rates for the control, 226+/-11 beats/min (n = 12 rats) and atropine experiments, 210+/-8 beats/min (n = 12 rats), were not significantly different (p = 0.24). VIP (0.06, 0.12, 0.24 micromol/l) caused a maximum increase of 27+/-13 beats/min (n = 5 rats) after 6 micromol/l VIP which was not significant, two higher concentrations of VIP failed to increase heart rate further. These results show that the vagal tachycardia is not present and that VIP does not cause a significant tachycardia in the rat.

Animals↗
PubMed2004

Evidence for synergistic modulation of early information processing by nicotinic and muscarinic receptors in humans.

Impairments in early information processing are a hallmark feature of diverse neuropsychiatric disorders including schizophrenia and Alzheimer's disease (AD). Several lines of evidence implicate a dysfunction of the cholinergic system in these disorders, particularly in AD where there is known degeneration in major cholinergic pathways. Inspection time (IT), a measure of early visual information processing speed, has been shown to be sensitive to cholinergic manipulation. The current study employed the IT task to (1) examine the independent roles of nicotinic and muscarinic receptors in modulating information processing and (2) investigate the interaction of nicotinic and muscarinic receptor systems in modulating information processing. Twelve healthy participants completed a randomized, double-blind, placebo-controlled study under four drug conditions; (1) placebo, (2) mecamylamine (15 mg; oral), (3) scopolamine (0.4 mg, s.c.), (4) mecamylamine (15 mg) + scopolamine (0.4 mg). IT measures were examined at baseline and 2.5 h post drug administration. Selective blockade of nicotinic receptors with mecamylamine did not significantly impair IT, whereas selective blockade of muscarinic receptors with scopolamine produced a significant but small impairment in IT. Combined blockade of both receptor types with scopolamine and mecamylamine produced a large impairment in IT performance. The results indicate that both nicotinic and muscarinic receptors are involved in modulating IT, and that the two systems may function synergistically to modulate early visual information processing. These findings suggest that functional abnormalities in both nicotinic and muscarinic systems may underlie deficits in early visual information processing seen in disorders such as Alzheimer's disease and schizophrenia.

Adult↗
PubMed2001

Identification of the Arg1086His mutation in the alpha subunit of the voltage-dependent calcium channel (CACNA1S) in a North American family with malignant hyperthermia.

Individuals from a large North American population were screened for the presence of the mutation in the alpha1 subunit of the voltage-dependent calcium channel (CACNA1S) that has recently been associated with malignant hyperthermia (MH). This Arg1086His mutation was screened for in 154 MH normal (MHN) individuals and 112 MH susceptible (MHS) individuals, who were diagnosed by the North American protocol of the in vitro contracture test. PCR and restriction enzyme analysis was used to test for the mutation. The Arg1086His mutation in the CACNA1S was not found in any of the MHN individuals. In contrast, two related individuals (grandfather and grandson, father and son of the MH proband) among the MHS group exhibited this mutation. However, a third MHS individual in the same family (granddaughter, cousin of the grandson) did not exhibit this mutation. These results indicate that this mutation may be associated with MH in this family. Genetic alterations in the CACNA1S associated with MH are present in approximately 1% of this North American MHS population.

Animals↗
PubMed2001

Autosomal dominant canine malignant hyperthermia is caused by a mutation in the gene encoding the skeletal muscle calcium release channel (RYR1).

BACKGROUND: Malignant hyperthermia (MH) is an inherited disorder of skeletal muscle characterized by hypercarbia, rhabdomyolysis, generalized skeletal muscle contracture, cardiac dysrhythmia, and renal failure, that develops on exposure to succinylcholine or volatile anesthetic agents. All swine and up to 50% of human MH events are thought to be associated with mutations in the calcium release channel of the sarcoplasmic reticulum, also known as the ryanodine receptor (RYR1). Events resembling MH have been reported in other species, but none have undergone genetic investigation to date. METHODS: To determine the molecular basis of canine MH, a breeding colony was established with a male, mixed-breed, MH-susceptible (MHS) dog that survived an in vivo halothane-succinylcholine challenge. He was mated to three unaffected females to produce four litters and back-crossed to an affected daughter to produce one litter. One of his MHS sons was mated to an unaffected female to produce an additional litter. Forty-seven dogs were phenotyped with an in vitro contracture test and diagnosed as MHS or MH normal based on the North American in vitro contracture test protocol. Nine microsatellite markers in the vicinity of RYR1 on canine chromosome 1 (CFA01) were tested for linkage to the MHS phenotype. Mutational analysis in two MHS and two MH-normal dogs was performed with direct sequencing of polymerase chain reaction products and of cloned fragments that represent frequently mutated human RYR1 regions. A restriction fragment length polymorphism was chosen to detect the candidate mutation in the pedigree at large. RESULTS: Pedigree inspection revealed that MHS in this colony is transmitted as an autosomal dominant trait. FH2294, the marker closest to RYR1, is linked to MHS at a theta = 0.03 with a LOD score of 9.24. A T1640C mutation gives rise to an alanine for valine substitution of amino acid 547 in the RYR1 protein, generating a maximum LOD score of 12.29 at theta = 0.00. All dogs diagnosed as MHS by in vitro contracture test were heterozygous for the mutation, and all MH-normal dogs were homozygous for the T1640 allele. CONCLUSIONS: These results indicate that autosomal dominant canine MH is caused by a mutation in the gene encoding the skeletal muscle calcium release channel and that the MHS trait in this pedigree of mixed-breed dogs is in perfect cosegregation with the RYR1 V547A mutation.

Amino Acid Sequence↗
PubMed2000

The 'price' of Olympic Gold.

In 1981 the Commonwealth Government established the Australian Institute of Sport (AIS). The Australian Sports Commission (ASC) which administers the AIS has 2 objectives: (1) excellence in sports performances; and (2) increased participation in sports and sports activities. State-based institutes of sport have also been established with the same or very similar objectives. Federal policy directs the bulk of the ASC budget to elite athlete programs. A smaller proportion goes towards community participation. The official reason is based on the notion of the 'trickle-down' or 'demonstration' effect. That is, a flow-on of benefits to the broader community in the form of increased participation as a direct result of elite sports success. The aims of this study were to determine the (1) spending pattern to elite sports programs for the 5 Olympics 1976/77 to 1995/96, (2) evidence for the two ASC objectives having been met, and (3) expected medal tally at the 2000 Olympic Games. Results show funding (in 1998 dollars), has accelerated from about $1.2 million (1976/77) to $106 million in (1997/98), particularly since the Games were awarded to Sydney. The total amount spent on elite athletes was $0.918 billion. In the period 1980-96 Australia won 25 gold and 115 total Olympic medals. This equates to approximately $37 million per gold and $8 million per medal in general. There was a significant linear relationship between money spent and total medals won. This was also found when all medal types were analysed independently. The predicted medal tally in 2000 (based on the cost per medal and the expenditure towards Sydney) indicates the medal count will be about 14+/-1 gold, 15+/-2 silver and 33+/-4 bronze. Based on our nation's record of international sporting achievement, there is little doubt we have fulfilled the ASC's first objective. Current data on physical activity patterns of Australians suggest the second objective has not been met. Focusing attention on and achieving the first objective does not appear to have any bearing on the second objective. It is time to revisit the notion that elite sporting success leads to greater mass participation as a result of the so-called 'trickle-down' effect.

Australia↗
PubMed2000

Stroke-specific FIM models in an urban population.

Data from the Functional Independence Measure (FIM) are important outcome measures in the stroke population undergoing rehabilitation. The FIM consists of 18 scales scored from 1 to 7; higher numbers mean greater ability. Several different scores can be obtained from the FIM: a total score (sum of all the scales), individual scale scores, and a physical and cognitive score (a two-dimensional interpretation). Research has shown that FIM data can have multidimensional components. That implies different groupings of scales may exist and with this the possibility of developing more sophisticated and robust measures within stroke populations. This study examined the multidimensional aspects of FIM using an urban sample of ischemic and hemorrhagic stroke patients. We found a three-dimensional FIM solution for both stroke groups that included self-care, cognitive function, and toileting as the major grouping of scales. These findings confirm a multidimensional nature of FIM scores and show a condition-specific pattern of FIM scores in stroke patients. This knowledge will help nurses, clinicians, and researchers develop more sensitive ways of recording care outcomes; improved prediction of stroke outcomes may also emerge from this knowledge.

Activities of Daily Living↗
PubMed1999

Structure and alternative splicing of the gene encoding the human beta1 subunit of voltage dependent calcium channels.

The structure of the gene encoding the human brain beta1 subunit of voltage dependent calcium channels (CACNB1) was determined by comparison of its genomic sequence with beta1 cDNA sequence. CACNB1 is distributed over 25 kb and contains 13 exons. Alternative splicing of CACNB1 RNA occurs within the central domain at exon 7, and the 3' domain at exon 13, producing the variably expressed beta1a, beta1b and beta1c isoforms. Exon/intron boundaries and exon lengths are conserved for the nine exons shared by the beta1 and related brain beta3 and beta4 genes.

Alternative Splicing↗
PubMed1998

Renal transplantation in a patient with methylmalonic acidaemia.

Renal insufficiency is frequently reported in mutase-deficient methylmalonic acidaemia. We present a case report of a patient with mut- methylmalonic acidaemia who developed chronic tubulointerstitial nephropathy during adolescence. At 24 years of age, she developed end-stage renal failure and underwent renal transplantation. Both plasma and urine methylmalonic acid levels decreased significantly with improved renal function following transplantation. Complications included cyclosporin toxicity and development of diabetes. Renal, metabolic, and clinical status remained improved at 3 years after the kidney transplant.

Adult↗
PubMed1998

The anesthetic myopathies and malignant hyperthermias.

Fatal destruction of skeletal muscle coincident with exposure to specific drugs used during anethesia has been recognized as a potentially heritable disorder for more than 30 years. Variable expressivity and incomplete penetrance of the clinical malignant hyperthermia phenotype, together with inherent drawbacks of the in-vitro contracture test confounded efforts to discover the underlying pathogenesis until the application of molecular genetic techniques. On the basis of linkage analysis and mapping of positional candidate genes, mutant alleles at loci on chromosomes 1q, (dihydropyridine-sensitive L-type calcium channel-A1S); 3q, 5p, 7q (dihydropyridine-sensitive L-type calcium channel-LA2), and 19q (ryanodine receptor) are now believed to account for up to 50% of human malignant hyperthermia susceptibility. Although inconsistent genotype-phenotype correlations and doubts regarding the causality of each mutant allele persist, the definition of malignant hyperthermia and relevance of molecular genetic data to the problems of family counseling, population screening, and improved resolution of the malignant hyperthermia phenotype must now be appraised in view of significant locus and allelic genetic heterogeneity.

Anesthetics↗
PubMed1998

The integrated exposure uptake biokinetic model for lead in children: independent validation and verification.

The U.S. Environmental Protection Agency employs a model, the integrated exposure biokinetic (IEUBK) model for lead in children, for the assessment of risks to children posed by environmental lead at hazardous waste sites. This paper describes results of an effort to verify the consistency of the documentation with the computer model and to test the computer code using a group that is independent from those involved in the model development. This review concluded that the IEUBK model correctly calculates the equations specified in the IEUBK model theory documentation. However, several issues were identified on model documentation, model performance, and the C++ programming language code (i.e., IEUBK model source code) documentation. These issues affect the ability of an independent reviewer to understand the workings of the IEUBK model but not the model's reliability. As a result of these findings, recommendations have been provided for updating documentation to the model as well as associated adjustments to the model documentation.

Child↗
PubMed1998

Integrated exposure uptake biokinetic model for lead in children: empirical comparisons with epidemiologic data.

The concept of model validation is evolving in the scientific community. This paper addresses the comparison of observed and predicted estimates as one component of model validation as applied to the integrated exposure uptake biokinetic (IEUBK) model for lead in children. The IEUBK model is an exposure (dose)-response model that uses children's environmental lead exposures to estimate risk of elevated blood lead (typically > 10 micrograms/dl) through estimation of lead body burdens in a mass balance framework. We used residence-specific environmental lead measurements from three epidemiologic datasets as inputs for the IEUBK model to predict blood lead levels, and compared these predictions with blood lead levels of children living at these residences. When the IEUBK modeling focused on children with representative exposure measurements, that is, children who spent the bulk of their time near the locations sampled, there was reasonably close agreement between observed and predicted blood lead distributions in the three studies considered. Geometric mean observed and predicted blood lead levels were within 0.7 microgram/dl, and proportions of study populations expected to be above 10 micrograms/dl were within 4% of those observed.

Age Factors↗
PubMed1998

Do IDSs really benefit from affiliating with managed care plans?

Integrated delivery systems (IDSs) affiliate with HMOs primarily to gain access to patients enrolled in managed care plans. Outright ownership of an HMO offers an IDS additional advantages, including opportunities to create a more seamless care process, improve patient outcomes, draw on the HMOs' experience in reducing costs, and administer health management and delivery at a significantly lower cost than the industry standard. The current trend toward IDS ownership of HMOs suggests that the line between providers and payers is blurring. Some states have encouraged this trend by enacting legislation that allows IDSs to act as insurers. Recent data indicate that IDSs with HMO components tend to be more vertically integrated than those without such components. These data suggest that close alignment with an HMO may be a key element in the effort to achieve vertical integration.

Delivery of Health Care, Integrated↗