PubMed Health⌕ Search

Biomedical subjects

Paul Cullen

Publications and source records attributed to Paul Cullen.

35 records · Page 2Linked to original sources
PubMed2003

Rupture of the atherosclerotic plaque: does a good animal model exist?

By its very nature, rupture of the atherosclerotic plaque is difficult to study directly in humans. A good animal model would help us not only to understand how rupture occurs but also to design and test treatments to prevent it from happening. However, several difficulties surround existing models of plaque rupture, including the need for radical interventions to produce the rupture, lack of direct evidence of rupture per se, and absence of convincing evidence of platelet- and fibrin-rich thrombus at the rupture site. At the present time, attention should therefore focus on the processes of plaque breakdown and thrombus formation in humans, whereas the use of animal models should probably be reserved for studying the function of particular genes and for investigating isolated features of plaques, such as the relationship between cap thickness and plaque stability.

Aged↗
PubMed2003

Severity of Irukandji syndrome and nematocyst identification from skin scrapings.

OBJECTIVES: (1) To identify the causative jellyfish species by examining skin scrapings in patients presenting to Cairns Base Hospital with marine stings, and (2) to describe clinical outcomes of those with Irukandji syndrome and those in whom nematocysts were identified from skin scrapings. DESIGN AND SETTING: (1) A retrospective case series of 128 patients, identified from Cairns Base Hospital emergency department records with discharge diagnoses of marine stings between 1 July 2001 and 30 June 2002. (2) A prospective study of skin scrapings from 50 patients presenting with marine stings from the same period. MAIN OUTCOME MEASURES: Number of patients with Irukandji syndrome, their opioid requirements and cardiac findings (where available); identification of causative species from nematocysts isolated from skin scrapings. RESULTS: 116 patients retrospectively identified with marine stings had Irukandji syndrome. Of 50 patients who had skin scrapings, 39 had nematocysts consistent with Carukia barnesi. Symptoms experienced ranged from local pain alone to severe Irukandji syndrome with elevated troponin I levels, changes on electrocardiogram, cardiac dysfunction on echocardiography, and high opioid dose requirements. One patient had an unidentified cnidome on his skin scraping. He developed severe Irukandji syndrome and subsequently died from its complications. CONCLUSION: This is the first published report of Carukia barnesi being successfully identified from skin scrapings. Most patients with identifiable cnidomes experiencing Irukandji syndrome were stung by Carukia barnesi, which we show causes a wide range of illness, including cardiac dysfunction. Our finding of a cnidome not consistent with Carukia barnesi in the setting of Irukandji syndrome makes it possible that other species of jellyfish may also cause this syndrome.

Adult↗
PubMed2003

Endogenous glycosides in critically ill patients.

OBJECTIVE: To determine the incidence of critically ill patients displaying endogenous digitalis-like-immunoreactive substances (DLIS) and to examine the relationship of these hormones to routine laboratory variables, the underlying disease, myocardial function, hemodynamic status, severity of illness, systemic inflammation, and mortality rate. DESIGN: Sera of 401 consecutive critically ill patients, not treated with cardiac glycosides, were analyzed for DLIS (digitoxin and digoxin, TDx; Abbott Diagnostics, North Chicago, IL) and endogenous ouabain. Normal values of endogenous ouabain were determined in 62 healthy volunteers. We measured pro- and anti-inflammatory mediators (L-selectin, tumor necrosis factor-alpha, interleukin-1beta, interleukin-2, interleukin-6, interleukin-10), C-reactive protein, and serum amyloid A protein as well as patients' Acute Physiology and Chronic Health Evaluation II and Goris scores. In a subgroup of patients with a pulmonary artery catheter (n = 95), we determined cardiac output, pulmonary artery occlusion pressure, systemic and pulmonary vascular resistance, left ventricular stroke volume, and right and left stroke work. SETTING: Two surgical intensive care units of an university hospital. SUBJECTS: Sera of 401 consecutive critically ill patients. INTERVENTIONS: Blood sampling. MEASUREMENTS AND MAIN RESULTS: Of the 401 patients tested, 343 had nonmeasurable DLIS concentrations (DLIS-negative), and 58 (14.5%) had positive digoxin (n = 18) or digitoxin (n = 34) concentrations (DLIS-positive) or were positive in both tests (n = 6). Mean endogenous ouabain concentrations were nine-fold increased in DLIS-positive (3.59 +/- 1.43 nmol/L) and three-fold increased in DLIS-negative (1.34 +/-.81 nmol/L) patients compared with controls (0.38 +/- 0.31 nmol/L). DLIS and ouabain concentrations closely correlated with the Acute Physiology and Chronic Health Evaluation II and Goris score and were associated with increased concentrations of transaminases, bilirubin, aldosterone, cortisol, serum creatinine, fractional sodium excretion, proinflammatory mediators, C-reactive protein, and serum amyloid A (p <or=.009). The hospital mortality rates of DLIS-positive and DLIS-negative patients were 12% and 3.2%, respectively, and for patients with ouabain concentrations above and below 2 nmol/L 38.6% and 0.6%, respectively. In DLIS-positive patients with pulmonary artery catheter (n = 23), cardiac output, stroke volume, and left ventricular stroke work were decreased, and pulmonary artery occlusion pressure and central venous pressure were increased (p <or=.009). CONCLUSIONS: Different types of endogenous glycosides including endogenous ouabain are elevated in a significant proportion of critically ill patients. The occurrence of these substances is associated with increased morbidity and hospital mortality rates, possibly due to systemic inflammatory processes. DLIS but not endogenous ouabain concentrations were found to be related to left ventricular function.

APACHE↗
PubMed2003

BLASTing proteomes, yielding phylogenies.

We develop a procedure called RiPE (Retrieval-induced Phylogeny Environment) that automatically performs an evolutionary analysis of a protein (sub)family, (i) by retrieving the relevant sequences via a homology search, (ii) by using the search report to construct the alignment using only homologous subsequences (taking into account their neighborhood with a low chance of homology), (iii) by realigning, and (iv) by generating phylogenetic trees based on the alignment. In a first implementation of our scheme, we start with the available proteome data of model organisms, perform a PSI-BLAST search, use MView to convert hits into a multiple alignment, and perform realignment and tree building. As a test case, we have investigated the human ABC transporters of the subfamily G, starting with the five known human ABCG transporters. Our method retrieved homologous sequences not previously analyzed, generating a tree that is more plausible and better supported than previously published trees. The RiPE 0.1 prototype is available at the RiPE website, http://ifg-izkf.uni-muenster.de/fuellen/RiPE/ripe.html.

ATP Binding Cassette Transporter, Subfamily G, Mem↗
PubMed2002

Simple scoring scheme for calculating the risk of acute coronary events based on the 10-year follow-up of the prospective cardiovascular Münster (PROCAM) study.

BACKGROUND: The absolute risk of an acute coronary event depends on the totality of risk factors exhibited by an individual, the so-called global risk profile. Although several scoring schemes have been suggested to calculate this profile, many omit information on important variables such as family history of coronary heart disease or LDL cholesterol. METHODS AND RESULTS: Based on 325 acute coronary events occurring within 10 years of follow-up among 5389 men 35 to 65 years of age at recruitment into the Prospective Cardiovascular Münster (PROCAM) study, we developed a Cox proportional hazards model using the following 8 independent risk variables, ranked in order of importance: age, LDL cholesterol, smoking, HDL cholesterol, systolic blood pressure, family history of premature myocardial infarction, diabetes mellitus, and triglycerides. We then derived a simple point scoring system based on the beta-coefficients of this model. The accuracy of this point scoring scheme was comparable to coronary event prediction when the continuous variables themselves were used. The scoring system accurately predicted observed coronary events with an area under the receiver-operating characteristics curve of 82.4% compared with 82.9% for the Cox model with continuous variables. CONCLUSIONS: Our scoring system is a simple and accurate way of predicting global risk of myocardial infarction in clinical practice and will therefore allow more accurate targeting of preventive therapy.

Acute Disease↗
PubMed2002

The use of pressure immobilization bandages in the first aid management of cubozoan envenomings.

This study is aimed to evaluate whether the application of pressure results in additional release of venom from naturally discharged, vinegar soaked nematocysts of the box jellyfish Chironex fleckeri. The results show that large quantities of venom are expressed with the application of pressures similar to that applied by compression immobilization bandages. The volume of venom expressed by this pressure was similar to the quantity expressed upon initial natural discharge of the nematocysts. The current recommended practice of applying PIB to cubozoan stings might worsen the envenomation. As the existing data now show that PIB may be detrimental to victims envenomed by cubozoans, we suggest that the current practice of the use of PIB in cubozoan envenomings be discarded until there is direct experimental evidence to support its use.

Acetic Acid↗
PubMed2002

Prediction of risk of coronary events in middle-aged men in the Prospective Cardiovascular Münster Study (PROCAM) using neural networks.

BACKGROUND: Logistic regression (LR) is commonly used to estimate risk of coronary heart disease. We investigated if neural networks improved on the risk estimate of LR by analysing data from the Prospective Cardiovascular Münster Study (PROCAM), a large prospective epidemiological study of risk factors for coronary heart disease among men and women at work in northern Germany. METHODS: We used a multi-layer perceptron (MLP) and probabilistic neural networks (PNN) to estimate the risk of myocardial infarction or acute coronary death (coronary events) during 10 years' follow-up among 5159 men aged 35-65 years at recruitment into PROCAM. In all, 325 coronary events occurred in this group. We assessed the performance of each procedure by measuring the area under the receiver-operating characteristics curve (AUROC). RESULTS: The AUROC of the MLP was greater than that of the PNN (0.897 versus 0.872), and both exceeded the AUROC for LR of 0.840. If 'high risk' is defined as an event risk >20% in 10 years, LR classified 8.4% of men as high risk, 36.7% of whom suffered an event in 10 years (45.8% of all events). The MLP classified 7.9% as high risk, 64.0% of whom suffered an event (74.5% of all events), while with the PNN, only 3.9% were at high risk, 58.6% of whom suffered an event (33.5% of all events). CONCLUSION: Intervention trials indicate that about one in three coronary events can be prevented by 5 years of lipid-lowering treatment. Our analysis suggests that use of the MLP to identify high-risk individuals as candidates for drug treatment would allow prevention of 25% of coronary events in middle-aged men, compared to 15% and 11% with LR and the PNN, respectively.

Adult↗
PubMed2002

Dietary mono- and polyunsaturated fatty acids similarly affect LDL size in healthy men and women.

The goal of this study was to investigate the effect of the dietary fat composition on LDL peak particle diameter. Therefore, we measured LDL size by gradient gel electrophoresis in 56 (30 men, 26 women) healthy participants in a controlled dietary study. First, all participants received a baseline diet rich in saturated fat for 2 wk; they were then randomly assigned to one of three dietary treatments, which contained refined olive oil [rich in monounsaturated fatty acids (MUFA), n = 18], rapeseed oil [rich in MUFA and (n-3)-polyunsaturated fatty acids (PUFA), n = 18], or sunflower oil [rich in (n-6)-PUFA, n = 20] as the principal source of fat for 4 wk. Repeated-measures ANOVA revealed a small, but significant reduction in LDL size during the oil diet phase (-0.36 nm, P = 0.012), which did not differ significantly among the three groups (P = 0.384). Furthermore, affiliation with one of the three diet groups did not contribute significantly to the observed variation in LDL size (P = 0.690). In conclusion, our data indicate that dietary unsaturated fat similarly reduces LDL size relative to saturated fat. However, the small magnitude of this reduction also suggests that the composition of dietary fat is not a major factor affecting LDL size.

Adult↗
PubMed2002

GTPase-activating proteins for Cdc42.

The Rho-type GTPase, Cdc42, has been implicated in a variety of functions in the yeast life cycle, including septin organization for cytokinesis, pheromone response, and haploid invasive growth. A group of proteins called GTPase-activating proteins (GAPs) catalyze the hydrolysis of GTP to GDP, thereby inactivating Cdc42. At the time this study began, there was one known GAP, Bem3, and one putative GAP, Rga1, for Cdc42. We identified another putative GAP for Cdc42 and named it Rga2 (Rho GTPase-activating protein 2). We confirmed by genetic and biochemical criteria that Rga1, Rga2, and Bem3 act as GAPs for Cdc42. A detailed characterization of Rga1, Rga2, and Bem3 suggested that they regulate different subsets of Cdc42 function. In particular, deletion of the individual GAPs conferred different phenotypes. For example, deletion of RGA1, but not RGA2 or BEM3, caused hyperinvasive growth. Furthermore, overproduction or loss of Rga1 and Rga2, but not Bem3, affected the two-hybrid interaction of Cdc42 with Ste20, a p21-activated kinase (PAK) kinase required for haploid invasive growth. These results suggest Rga1, and possibly Rga2, facilitate the interaction of Cdc42 with Ste20 to mediate signaling in the haploid invasive growth pathway. Deletion of BEM3 resulted in cells with severe morphological defects not observed in rga1delta or rga2delta strains. These data suggest that Bem3 and, to a lesser extent, Rga1 and Rga2 facilitate the role of Cdc42 in septin organization. Thus, it appears that the GAPs play a role in modulating specific aspects of Cdc42 function. Alternatively, the different phenotypes could reflect quantitative rather than qualitative differences in GAP activity in the mutant strains.

Amino Acid Sequence↗
PubMedDate not supplied

Temperature effects on box jellyfish venom: a possible treatment for envenomed patients?

OBJECTIVE: To determine the effect of temperature on lethality of venom from Chironex fleckeri (the potentially fatal box jellyfish). DESIGN: Venom extracted from nematocysts of mature Chironex fleckeri specimens was exposed to temperatures between 4 degrees C and 58 degrees C for periods of two, five or 20 minutes, and then injected into freshwater crayfish (Cherax quadricarinatus) to assess lethality. MAIN OUTCOME MEASURE: Venom lethality, assessed as time to cardiac standstill in crayfish after intramuscular injection. RESULTS: Venom lethality was significantly affected by both temperature (F(7,34) = 21915; P < 0.0001) and time of exposure (F(2,34) = 9907; P < 0.0001). No significant loss of lethality was seen after exposure to temperatures or= 43 degrees C, venom lost its lethality more rapidly the longer the exposure time. Venom was non-lethal after exposure to 48 degrees C for 20 minutes, 53 degrees C for five minutes, and 58 degrees C for two minutes. CONCLUSION: Exposure to heat dramatically reduces the lethality of extracted C. fleckeri venom. Although heat application may be of limited use in treating C. fleckeri envenoming because of the speed of symptom onset, its use in other box-jellyfish envenomings, such as Irukandji syndrome, requires investigation.

Animals↗