Troubleshooting maldeployed aortic endografts.
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Angiography↗
Biomedical subjects
R White
Publications and source records attributed to R White.
European multicentre experience with modular device (Medtronic Aneurx) for the endoluminal repair of infrarenal abdominal aortic aneurysms.
OBJECTIVE: Transfemoral endoluminal repair of AAA, introduced for the first time in the early 90's, has become a very promising alternative to conventional open repair and more and more centers are reporting satisfactory postoperative results in a high percentage of cases. Straight and bifurcated grafts represent the devices available on the market at present and aortic, as well as iliac aneurysmal lesions can be safely treated through a transfemoral approach. The possibility to indicate an endovascular AAA repair is related to the configuration (length and size) of the proximal and distal necks, tortuosity and calcification of the access arteries and to vascular and non-vascular comorbidities, which afflict the patients. The objective of our study was to evaluate the early and late postoperative results in a series of patients affected by infrarenal AAA, who underwent endoluminal repair. MATERIALS AND METHODS: From December 1996 to 31 October 1997 in 5 different European Centers, 100 Medtronic AneuRx bifurcated stent grafts were implanted for infrarenal abdominal aortic aneurysms. The diameter of the AAA varied from 33 to 77 mm (average 64 mm) and the mean age of the patients was 70.8 years (51-87 years). In one patient with a 33 mm diameter of the aneurysm, the surgical procedure was indicated because the size of the aneurysm had increased by 5 mm, compared to the previous control made 2 months before. In addition the aneurysm became symptomatic. There were 92 male and 8 female patients. The average time of the surgical procedure was 150 minutes (75-480 minutes) with an average blood loss of 570 ml (100-2,600 ml).
Aged↗
Function of Estrogen Receptors in Breast Cancer.
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Journal Article↗
Endothelium and cannabinoid receptor involvement in levcromakalim vasorelaxation.
Levcromakalim was more potent at relaxing rat small mesenteric arteries with endothelium (EC50, 84+/-10 nM) than denuded vessels (EC50, 779+/-101 nM). The cannabinoid receptor antagonist SR 141716A (N-(piperidin-1-yl)-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-me thyl-1H-pyrazole-3-carboxamide hydrochloride; 1 microM) shifted the levcromakalim concentration/response curve 7.6-fold rightwards in intact vessels but had no effect in de-endothelialised vessels. Similar effects occurred with pinacidil. Combination of the K+ channel blockers apamin (1 microM) and charybdotoxin (100 nM) shifted the levcromakalim concentration/response curve 3-fold rightwards only in intact vessels. It is concluded that levcromakalim and pinacidil relax mesenteric arteries partly by releasing a relaxing factor from endothelium, possibly an endogenous cannabinoid.
Animals↗
In vitro infection and replication of hepatitis E virus in primary cynomolgus macaque hepatocytes.
An in vitro model was developed to replicate hepatitis E virus (HEV) in normal primary cynomolgus macaque hepatocytes using a hormonally defined, serum-free medium formulation. Primary hepatocytes were infected in tissue culture following isolation by collagenase treatment of liver wedge biopsy material. Viral replication was monitored by a highly strand-specific reverse transcription-polymerase chain reaction (RT-PCR) assay, which could detect the positive- and negative-strands of HEV RNA independently in a sensitive and specific manner. Several infectious HEV (Burma strain) inocula were titered by this RT-PCR assay, and a minimum effective infectious dose was determined. Appearance of newly replicated virus was demonstrated by detection of both strands of HEV RNA in experimentally infected hepatocytes as well as the genomic positive-strand viral RNA in the culture medium. Infectivity of the virus particles present in the media was confirmed by serial passage and replication of the virus in culture. Using this in vitro infection system, a neutralization assay was developed to assess the ability of anti-HEV antibodies to block virus infection of liver cells. Results presented in this report represent the first in vitro demonstration of a neutralizing anti-HEV antibody directed against the ORF2-encoded putative capsid protein.
Animals↗
Toxicity evaluation of petroleum blending streams: reproductive and developmental effects of hydrodesulfurized kerosine.
Hydrodesulfurized kerosine (HDS kerosine), applied dermally, was tested for reproductive and developmental toxicity in Sprague-Dawley rats, using a modified OECD Guideline 421, Reproductive/Developmental Toxicity Screening Protocol. A preliminary acute dermal irritancy test demonstrated that dilution of HDS kerosine in either a light (100 Saybolt universal seconds, SUS) or moderate viscosity (340 SUS) USP mineral oil reduced irritation of the neat material comparably. Similar dermal absorption was observed in vitro for neat HDS kerosine or diluted in either of the mineral oils. HDS kerosine diluted to 494 (60%), 330 (40%), or 165 (20%) mg/kg/day in Squibb mineral oil (340 SUS) was applied daily at 1 ml/kg to the shaved backs of rats for 7 wk (premating, mating to d 19 of gestation) to females and 8 wk to males. Dams and litters were sacrificed on postpartum d 4 and males were sacrificed within the following week. HDS kerosine produced slight to moderate skin irritation at the highest dose in both sexes but no apparent maternal, reproductive, or developmental toxicity. No clinical signs of toxicity and no effects on body weight, food consumption, or absolute organ weights were observed. Relative kidney weights were heavier in male rats at the high dose. Skin changes were observed microscopically in male rats in all groups and in females at the high dose. No microscopic changes were observed in reproductive organs of parental animals. There were no differences in mean number of corpora lutea, implantation sites, and live pups per litter, and no gross anomalies were observed. Pups born from treated dams showed comparable body weights and weight gains to controls. The viability index on postpartum d 4 was > or = 93%. In conclusion, the no observable adverse effect level (NOAEL) for HDS kerosine for reproductive and developmental toxicity in rats is 494 mg/kg/d.
Administration, Topical↗
Incidence of and risk factors for atrial fibrillation in older adults.
BACKGROUND: This study aimed to describe the incidence of atrial fibrillation (AF) among older adults during 3 years of follow-up. METHODS AND RESULTS: In this cohort study, 5201 adults > or = 65 years old were examined annually on four occasions between June 1989 and May 1993. At baseline, participants answered questionnaires and underwent a detailed examination that included carotid ultrasound, pulmonary function tests, ECG, and echocardiography. Subjects with a pacemaker or AF at baseline (n=357) were excluded. New cases of AF were identified from three sources: (1) annual self-reports, (2) annual ECGs, and (3) hospital discharge diagnoses. Cox proportional-hazards models were used to assess baseline risk factors as predictors of incident AF. Among 4844 participants, 304 developed a first episode of AF during an average follow-up of 3.28 years, for an incidence of 19.2 per 1000 person-years. The onset was strongly associated with age, male sex, and the presence of clinical cardiovascular disease. For men 65 to 74 and 75 to 84 years old, the incidences were 17.6 and 42.7, respectively, and for women, 10.1 and 21.6 events per 1000 person-years. In stepwise models, the use of diuretics, a history of valvular heart disease, coronary disease, advancing age, higher levels of systolic blood pressure, height, glucose, and left atrial size were all associated with an increased risk of AF. The use of beta-blockers and high levels of alcohol use, cholesterol, and forced expiratory volume in 1 second were associated with a reduced risk of AF. CONCLUSIONS: The incidence of AF in older adults may be higher than estimated by previous population studies. Left atrial size appears to be an important risk factor, and the control of blood pressure and glucose may be important in preventing the development of AF.
Adult↗
Ligand-independent activation of the oestrogen receptor by mutation of a conserved tyrosine.
The oestrogen receptor is a member of the nuclear receptor family of transcription factors which, on binding the steroid hormone 17beta-oestradiol, interacts with co-activator proteins and stimulates gene expression. Replacement of a single tyrosine in the hormone-binding domain generated activated forms of the receptor which stimulated transcription in the absence of hormone. This increased activation is related to a decrease in hydrophobicity and a reduction in size of the side chain of the amino acid with which the tyrosine is replaced. Ligand-independent, in common with ligand-dependent transcriptional activation, requires an amphipathic alpha-helix at the C-terminus of the ligand-binding domain which is essential for the interaction of the receptor with a number of potential co-activator proteins. In contrast to the wild-type protein, constitutively active receptors were able to bind both the receptor-interacting protein RIP-140 and the steroid receptor co-activator SRC-1 in a ligand-independent manner, although in the case of SRC-1 this was only evident when the receptors were prebound to DNA. We propose, therefore, that this tyrosine is required to maintain the receptor in a transcriptionally inactive state in the absence of hormone. Modification of this residue may generate a conformational change in the ligand-binding domain of the receptor to form an interacting surface which allows the recruitment of co-activators independent of hormone binding. This suggests that this tyrosine may be a target for a different signalling pathway which forms an alternative mechanism of activating oestrogen receptor-mediated transcription.
Amino Acid Sequence↗
Developmental toxicity study in rats and rabbits administered an emulsion containing medium chain triglycerides as an alternative caloric source.
Triglyceride-containing lipid emulsions have been designed as caloric sources that can be administered intravenously to patients that cannot meet their nutritional needs by conventional parenteral therapies. In their study, we evaluate the developmental toxicity of a 20% lipid emulsion that contains a 3:1 ratio of medium chain triglyceride (MCT) to one long chain containing lipid emulsion (LCT). This emulsion was administered by intravenous infusion to rats and rabbits at dosages of 1 and 4.28 g lipid/kg body weight (g lipid/kg) at dose volumes of 5 and 21.4 mL/kg, respectively, once daily during organogenesis to assess the potential developmental toxicity of the test article. The control group received 0.9% saline at a dose volume of 21.4 mL/kg. Animals were observed for clinical signs of toxicity and adverse effects on body weights and feed consumption. On Day 20 (rats) or Day 29 (rabbits), females were necropsied and examined for maternal and embryo/fetal toxicity. Fetuses were removed, weighed, and examined for external, soft tissue, and skeletal abnormalities. Dosages of 4.28 g lipid/kg resulted in lower feed consumption for rats and rabbits, an expected finding based on the high-caloric nature of the test article. Potentially test article-related gross necropsy findings, including enlarged lymph nodes and spleen, small thymus, and enlarged renal pelvis, for rats given 4.28 g lipid/kg were present at a low incidence. There were no adverse effects on fetal parameters for rats even in the presence of some maternal toxicity. However, embryo and fetal toxicity (i.e., resorptions) and skeletal abnormalities were present for rabbits given 4.28 g lipid/kg. Under the conditions of this study, the no-observable-effect level for developmental toxicity was greater than or equal to 4.28 g lipid/kg for rats and greater than or equal to 1 g lipid/kg but less than 4.28 g lipid/kg for rabbits.
Abnormalities, Drug-Induced↗
Increasing utilization of dermatologists by managed care: an analysis of the National Ambulatory Medical Care Survey, 1990-1994.
Patients with managed care are less likely to see dermatologists for skin problems than are patients with traditional insurance. Through 1992, increase in the demand for treatment of skin problems reduced the effect of managed care on dermatologists. We assessed the continued impact of managed care on visits to dermatologists. Skin disease visits from the National Ambulatory Medical Care Survey were analyzed for the years 1990-1994. We found that demand for treatment of skin problems did not rise between 1992 and 1994, but demand for dermatologists services within the managed care sector more than doubled. In 1994 patients with HMO/prepaid insurance with skin disease were just as likely to see a dermatologist as were patients with commercial insurance. Mean visit duration for skin problems was 19% longer for nondermatologists than for dermatologists (p < 0.001). We conclude that dermatologists are more efficient at treating skin disease than nondermatologists and that utilization of dermatologists within managed care is increasing.
Ambulatory Care↗
Respiratory function parameters in infants using inductive plethysmography.
A signal processing technique has been developed to determine respiratory function parameters by processing displacement data obtained from the abdomen and the rib cage of infants using respiratory inductive plethysmography. The technique transforms time-variant signals into the frequency domain, where they are filtered to reduce unwanted signal components. The phase relationship between the abdominal displacement and the rib cage displacement is determined from the phases of the filtered signals. Flow-volume loops, which are currently of great interest in respiratory medicine, are obtained from waveforms representing respiratory tidal flow and respiratory tidal volume. The index of respiratory timing is determined from a waveform representing respiratory tidal flow. The technique has been verified by statistical comparison with data simultaneously obtained using pneumotachography in a clinical study involving 49 infants.
Artifacts↗
A comparison of EDHF-mediated and anandamide-induced relaxations in the rat isolated mesenteric artery.
1. Relaxation of the methoxamine-precontracted rat small mesenteric artery by endothelium-derived hyperpolarizing factor (EDHF) was compared with relaxation to the cannabinoid, anandamide (arachidonylethanolamide). EDHF was produced in a concentration- and endothelium-dependent fashion in the presence of NG-nitro-L-arginine methyl ester (L-NAME, 100 microM) by either carbachol (pEC50 [negative logarithm of the EC50] = 6.19 +/- 0.01, Rmax [maximum response] = 93.2 +/- 0.4%; n = 14) or calcium ionophore A23187 (pEC50 = 6.46 +/- 0.02, Rmax = 83.6 +/- 3.6%; n = 8). Anandamide responses were independent of the presence of endothelium or L-NAME (control with endothelium: pEC50 = 6.31 +/- 0.06, Rmax = 94.7 +/- 4.6%; n = 10; with L-NAME: pEC50 = 6.33 +/- 0.04, Rmax = 93.4 +/- 6.0%; n = 4). 2. The selective cannabinoid receptor antagonist, SR 141716A (1 microM) caused rightward shifts of the concentration-response curves to both carbachol (2.5 fold) and A23187 (3.3 fold). It also antagonized anandamide relaxations in the presence or absence of endothelium giving a 2 fold shift in each case. SR 141716A (10 microM) greatly reduced the Rmax values for EDHF-mediated relaxations to carbachol (control, 93.2 +/- 0.4%; SR 141716A, 10.7 +/- 2.5%; n = 5; P < 0.001) and A23187 (control, 84.8 +/- 2.1%; SR 141716A, 3.5 +/- 2.3%; n = 6; P < 0.001) but caused a 10 fold parallel shift in the concentration-relaxation curve for anandamide without affecting Rmax. 3. Precontraction with 60 mM KCl significantly reduced (P < 0.01; n = 4 for all) relaxations to 1 microM carbachol (control 68.8 +/- 5.6% versus 17.8 +/- 7.1%), A23187 (control 71.4 +/- 6.1% versus 3.9 +/- 0.45%) and anandamide (control 71.1 +/- 7.0% versus 5.2 +/- 3.6%). Similar effects were seen in the presence of 25 mM K+. Incubation of vessels with pertussis toxin (PTX; 400 ng ml-1, 2 h) also reduced (P < 0.01; n = 4 for all) relaxations to 1 microM carbachol (control 63.5 +/- 7.5% versus 9.0 +/- 3.2%), A23187 (control 77.0 +/- 5.8% versus 16.2 +/- 7.1%) and anandamide (control 89.8 +/- 2.2% versus 17.6 +/- 8.7%). 4. Incubation of vessels with the protease inhibitor phenylmethylsulphonyl fluoride (PMSF; 200 microM) significantly potentiated (P < 0.01), to a similar extent (approximately 2 fold), relaxation to A23187 (pEC50: control, 6.45 +/- 0.04; PMSF, 6.74 +/- 0.10; n = 4) and anandamide (pEC50: control, 6.31 +/- 0.02; PMSF, 6.61 +/- 0.08; n = 8). PMSF also potentiated carbachol responses both in the presence (pEC50: control, 6.25 +/- 0.01; PMSF, 7.00 +/- 0.01; n = 4; P < 0.01) and absence (pEC50: control, 6.41 +/- 0.04; PMSF, 6.88 +/- 0.04; n = 4; P < 0.001) of L-NAME. Responses to the nitric oxide donor S-nitroso-N-acetylpenicillamine (SNAP) were also potentiated by PMSF (pEC50: control, 7.51 +/- 0.06; PMSF, 8.00 +/- 0.05, n = 4, P < 0.001). 5. EDHF-mediated relaxation to carbachol was significantly attenuated by the K+ channel blocker tetraethylammonium (TEA; 1 mM) (pEC50: control, 6.19 +/- 0.01; TEA, 5.61 +/- 0.01; n = 6; P < 0.01). In contrast, TEA (1 mM) had no effect on EDHF-mediated relaxation to A23187 (pEC50: control, 6.47 +/- 0.04; TEA, 6.41 +/- 0.02, n = 4) or on anandamide (pEC50: control, 6.28 +/- 0.06; TEA, 6.09 +/- 0.02; n = 5). TEA (10 mM) significantly (P < 0.01) reduced the Rmax for anandamide (control, 94.3 +/- 4.0%; 10 mM TEA, 60.7 +/- 4.4%; n = 5) but had no effect on the Rmax to carbachol or A23187. 6. BaCl2 (100 microM), considered to be selective for blockade of inward rectifier K+ channels, had no significant effect on relaxations to carbachol or A23187, but caused a small shift in the anandamide concentration-response curve (pEC50: control, 6.39 +/- 0.01; Ba2+, 6.20 +/- 0.01; n = 4; P < 0.01). BaCl2 (1 mM; which causes non-selective block of K+ channels) significantly (P < 0.01) attenuated relaxations to all three agents (pEC50 values: carbachol, 5.65 +/- 0.02; A23187, 5.84 +/- 0.04; anandamide, 5.95 +/- 0.02; n = 4 for each). 7. Apamin (1mu M), a selective blocker of small conductance, Ca2+-activated, K+ channels (SKCa), 4-aminopyridine (1mM), a blocker of delayed rectifier, voltage-dependent, K+ channels (Kv), and ciclazindol (10mu M), an inhibitor of Kv and adenosine 5'-triphosphate (ATP)-sensitive K+ channels (KATP), significantly reduced EDHF-mediated relaxations to carbachol, but had no significant effects on A23187 or anandamide responses. 8. Glibenclamide (10mu M), a KATP inhibitor and charybdotoxin (100 or 300nM), a blocker of several K+ channel subtypes, had no significant effect on relaxations to any of the agents. Iberiotoxin (50nM), an inhibitor of large conductance, Ca2+-activated, K+ channels (BKCa), had no significant effect on the relaxation responses, either alone or in combination with apamin (1muM). Also, a combination of apamin (1muM) with either glibenclamide (10muM) or 4-aminopyridine (1mM) did not inhibit relaxation to carbachol significantly more than apamin alone. Neither combination had any significant effect on relaxation to A23187 or anandamide. 9. A combination of apamin (1muM) with charybdotoxin (100nM) abolished EDHF-mediated relaxation to carbachol, but had no significant effect on that to A23187. Apamin (1muM) and charybdotoxin (300nM) together consistently inhibited the response to A23187, while apamin (1muM) and ciclazindol (10muM) together inhibited relaxations to both carbachol and A23187. None of these toxin combinations had any significant effect on relaxation to anandamide. 10. It was concluded that the differential sensitivity to K+ channel blockers of EDHF-mediated responses to carbachol and A23187 might be due to actions on endothelial generation of EDHF, as well as its actions on the vascular smooth muscle, and suggests care must be taken in choosing the means of generating EDHF when making comparative studies. Also, the relaxations to EDHF and anandamide may involve activation of cannabinoid receptors, coupled via PTX-sensitive G-proteins to activation of K+ conductances. The results support the hypothesis that EDHF is an endocannabinoid but relaxations to EDHF and anandamide show differential sensitivity to K+ channel blockers, therefore it is likely that anandamide is not identical to EDHF in the small rat mesenteric artery.
4-Aminopyridine↗
Monomeric behaviour of Mytilus edulis (mussel) glue protein in dilute solution.
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Animals↗
Longitudinal analyses for magnetic resonance imaging outcomes in multiple sclerosis clinical trials.
A basic feature of many clinical trials is the collection of longitudinal data on individual patients. Analysis of such data is often based on summaries over time. This allows use of standards methods to assess treatment effects but sacrifices information on patterns over time as well as potential greater efficiency of analysis. The purpose of this paper is to illustrate the utility of the generalized estimating equations (GEE) approach to the analysis of longitudinal binary, count, and continuous responses for the frequent magnetic resonance imaging (MRI) substudy of the 3-year pivotal trial of interferon beta-1 b in relapsing-remitting multiple sclerosis.
Clinical Trials as Topic↗
Variance of plasma human immunodeficiency virus type 1 RNA levels measured by branched DNA within and between days.
Previous studies have shown that CD4-positive T cells vary in a predictable manner over 24 h. This diurnal variance has significant clinical implications. Recently, viral RNA measurements have been increasingly used as a standard marker in the management of human immunodeficiency virus (HIV)-infected patients. Little detailed analysis of the variability of this marker has been conducted. To define the variance of plasma HIV-1 RNA levels within days, 11 clinically stable patients with established HIV infection and a baseline viral RNA level >40,000 copies/mL were studied. Following the patients' admission to an inpatient research unit, plasma samples were obtained frequently over 48 h and analyzed for HIV-1 RNA levels by use of a quantitative branched chain DNA assay (bDNA). No diurnal pattern was detected. In these clinically stable patients, viral RNA levels exhibited a variance of approximately 0.4 log.
Adult↗
Disruption of vascular signalling by the reaction of nitric oxide with superoxide: implications for cardiovascular disease.
Oxidation reactions are used in controlled enzymatic pathways to form intracellular messengers such as the prostaglandins, leukotrienes, and the simplest signalling molecule known, nitric oxide. In inflammation, non-enzymatic oxidation appears to produce compounds which compete with or inhibit the mediators derived from endogenous enzymatic oxidative processes. Many of these compounds could be derived from the reaction of NO with superoxide to form peroxynitrite and the ensuing oxidation, nitration and nitrosation reactions. In this short over-view we will describe some of these products and how they may modulate signal transduction events in the vasculature and so contribute to the pathogenesis of atherosclerosis.
Animals↗
Neutralizing antibodies and the efficacy of interferon beta-1b in relapsing-remitting multiple sclerosis.
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Adjuvants, Immunologic↗