A genome screen of families at high risk for Hodgkin lymphoma: evidence for a susceptibility gene on chromosome 4.
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Adult↗
Biomedical subjects
G Lalonde
Publications and source records attributed to G Lalonde.
Tako-tsubo cardiomyopathy.
A 48-year-old woman presented to her local hospital with chest pain. Her electrocardiogram showed incomplete right bundle branch block, diffuse ST segment elevation and QTc prolongation. Shortly after admission, she became hypotensive and was referred for a coronary angiogram. Her coronary arteries were normal, but left ventriculography showed morphological changes typical of apical ballooning, as found in tako-tsubo cardiomyopathy. An echocardiogram confirmed complete akinesis of the left ventricular apex, with hyperkinesis of basal segments and an ejection fraction of 35% to 40%. Dynamic left ventricular outflow tract obstruction was also noted. After temporary support with intra-aortic balloon counterpulsation, fluids and noradrenaline, she recovered promptly. The present paper reviews the characteristic features of tako-tsubo cardiomyopathy.
Cardiomyopathies↗
Verapamil intoxication after substitution of immediate-release for extended-release verapamil.
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Adult↗
Acute pericarditis with transient constriction.
Transient constrictive pericarditis is a rare entity. It is characterized by clinical and echocardiographic features similar to constrictive pericarditis, but is distinguished by its transient nature. This feature is important to recognize for avoiding unnecessary pericardectomy. The case of a patient who presented with acute myopericarditis and typical echocardiographic features of constriction is described. Within weeks, all signs of constriction disappeared spontaneously.
Acute Disease↗
Oral anticoagulant therapy for heart disease: results in actual cardiology practice.
OBJECTIVE: To determine whether the success and complication rates of oral anticoagulation obtained in large, well controlled trials, upon which recommendations are based, are comparable with routine cardiology practice. DESIGN: An observational, prospective cohort study collected data on all patients followed at an anticoagulant clinic over one calendar year. PATIENTS: One thousand and seventy-eight patients anticoagulated for cardiovascular indications, mainly atrial fibrillation, prosthetic valves and ventricular dysfunction, were followed for 804 patient-years of treatment. No patient was lost to follow-up. INTERVENTIONS: Telephone conversations and regular verification of medical files were used to record and classify all bleeding and thromboembolic events according to severity. International normalized ratios (INR) were compared with target ranges. RESULTS: One hundred and twelve bleeding events, ie, 13.9/100 patient-years (% p-y), were recorded, of which 61 required medical attention. Major hemorrhages, defined as those requiring treatment or hospital observation for more than 24 h, occurred in 15 instances (1.9% p-y). Among these, 9 (1.1% p-y) were classified as life threatening, with four being fatal (0,5% p-y). Twenty-two thromboembolic events (2.7% p-y) occurred, of which 10 were major (1.2% p-y), leaving three patients (0.4% p-y) with long term sequelae and causing two deaths (0.25% p-y). INRs were within target range 62.3% of the time, with 2.2% of values recorded above 5 and 0.3% above 10. CONCLUSION: The low failure and complication rates obtained in large, controlled trials are similar to those observed in actual cardiology practice.
Administration, Oral↗
Pharmacokinetics and hematological effects of the PEGylated thrombopoietin peptide mimetic GW395058 in rats and monkeys after intravenous or subcutaneous administration.
GW395058, a potent PEGylated peptide human thrombopoietin receptor (HuTPOr) agonist in vitro, is being evaluated for the treatment of thrombocytopenia. GW395058 shares no sequence homology with TPO. In this report the pharmacokinetics and hematological effects of GW395058 in rats and monkeys are described. Doses eliciting thrombocytosis in rodents (2 or 10 microg/kg s.c.) produced insufficient plasma concentration data for pharmacokinetic parameter estimate calculations. At higher i.v. doses in rats (500, 1,000 or 2,000 microg/kg) serum t1/2 (half-life) values were >20 h, and the area under the concentration time curve increased proportionally with dose. In cynomolgus monkeys GW395058 plasma t1/2 values ranged from 37 to 68 h after s.c. or i.v. dosing, and similar values were observed in rhesus monkeys following s.c. dosing. Rat platelet counts increased following 2 (1.6-fold) or 10 microg/kg (fourfold) s.c. doses. Cynomolgus and rhesus monkey platelet counts did not change significantly at comparable s.c. doses, but did increase slightly (<twofold) in cynomolgus monkeys following a 25 microg/kg s.c. dose and twofold following a 100 microg/kg s.c. dose. Because the plasma t1/2 of GW395058 is long in mouse, rat, dog, and monkey, yet the dose required to double platelet levels in monkeys is 50-fold that required in rats, differences in hematological responses may be due to interspecies differences in the interaction of GW395058 with the TPOr.
Amino Acid Sequence↗
Characterization of a 3-dehydroquinase gene from Actinobacillus pleuropneumoniae with homology to the eukaryotic genes qa-2 and QUTE.
A gene was cloned from Actinobacillus pleuropneumoniae strain 4074 by complementation of an aroD strain of Escherichia coli. The E. coli gene aroD codes for a 3-dehydroquinase enzyme of type I, active in the aromatic biosynthesis pathway. The A. pleuropneumoniae gene, termed aroQ, displays no base or amino acid sequence homology to aroD of E. coli. It is instead homologous to the QUTE and qa-2 genes, respectively of Aspergillus nidulans and Neurospora crassa. These genes code for 3-dehydroquinase enzymes of type II, involved in the catabolism of quinic acid. The 1.8 kb fragment, which includes aroQ, carries four overlapping or adjacent open reading frames: a dapD gene; aroQ; one without homology to sequences in GenBank; and one with homology to the C-terminal 40% of chIN of E. coli.
Actinobacillus pleuropneumoniae↗
Alpha-hemolysin contributes to the pathogenicity of piliated digalactoside-binding Escherichia coli in the kidney: efficacy of an alpha-hemolysin vaccine in preventing renal injury in the BALB/c mouse model of pyelonephritis.
Digalactoside-binding (Gal-Gal) pili and alpha-hemolysin of Escherichia coli have been implicated as important virulence determinants in the pathogenesis of human ascending, nonobstructive pyelonephritis. The pathogenic significance of these determinants was evaluated in vitro and in the BALB/c mouse pyelonephritis model by employing wild-type, avirulent laboratory, and genetically defined cosmids, transformants, and recombinant strains. In vitro data suggest that the cytolytic activity of hemolysin is significantly (P less than 0.05) enhanced among digalactoside-binding strains which agglutinate erythrocytes. The basis of increased hemolysis is related presumably to more efficient delivery of the toxin to target lipid substrate in the host plasma membrane. Intravesicular administration of bacteria that express both digalactoside binding and hemolysin generally resulted in greater mortality and renal parenchymal injury in mice than strains that expressed none or only one of these determinants. Analyses convincingly demonstrate that digalactoside-binding pili are correlated with upper urinary tract colonization and that hemolysin is correlated with septicemia and renal parenchymal damage. These determinants collectively constitute the minimal virulence factors to produce disease in this model. Their efficacy as vaccines for the prevention of pyelonephritis was also assessed. A purified Gal-Gal pilus vaccine prevented (P less than 0.05) subsequent colonization by a challenge wild-type strain that exhibited homologous pili. The hemolysin vaccine did not abrogate subsequent bacterial renal colonization on challenge, but it did protect (P less than 0.05) mice which survived challenge from subsequent renal injury compared with those in the saline control group. The combination of these determinants was also protective. The combination of Gal-Gal pili and hemolysin in a vaccine preparation represents a potentially worthwhile strategy for human immunoprophylaxis against pyelonephritis by interdicting several steps in the pathogenesis of a bacterial mucosal infection.
Animals↗
Sustained beneficial effect of a seventy-two hour intravenous infusion of nitroglycerin in patients with severe chronic congestive heart failure.
To determine whether a 72-hour infusion of nitroglycerin produces hemodynamic improvement in patients with severe congestive heart failure and to assess the contributing role of various possible causes of hemodynamic tolerance to nitroglycerin, 19 patients received an infusion of nitroglycerin 1.5 micrograms/kg/min for 72 hours. In a subgroup of patients (n = 10), there was an increase in stroke work index and a decrease in ventricular filling pressures throughout the infusion and even after it was discontinued. Tolerance to the hemodynamic effects of nitroglycerin was partially reversed 8 hours after the infusion was stopped. Neurohumoral changes occurred but appeared to play only a minor role in the development of nitroglycerin tolerance. However, hematocrit fell 9 +/- 5%, which suggests that an increased intravascular volume contributed to tolerance. In summary: (1) a 72-hour infusion of nitroglycerin improves ventricular function in some patients with severe heart failure; (2) volume shifts from the extravascular to the intravascular compartments may, at least in part, be responsible for nitroglycerin tolerance; and (3) reflex neurohumoral activation may also play a small role in nitrate tolerance.
Administration, Sublingual↗
Tolerance to intravenous nitroglycerin in patients with congestive heart failure: role of increased intravascular volume, neurohumoral activation and lack of prevention with N-acetylcysteine.
To better understand the mechanism of nitrate tolerance in patients with congestive heart failure, 13 patients received a 24 h infusion of nitroglycerin (1.5 micrograms/kg body weight per min) with or without N-acetylcysteine (225 mg/kg per 24 h). The infusions were separated by a 24 h nitrate-free interval. By the end of the nitroglycerin infusion, mean arterial pressure had returned to baseline values and there was a significant increase in ventricular filling pressures and systemic vascular resistance compared with values after 1 h of treatment. The simultaneous infusion of N-acetylcysteine had no effect on these changes. Although a strict fluid restriction of 1.5 liters/day was maintained for 1 week before and throughout the study, after 24 h of nitroglycerin infusion there was a significant and similar degree of hemodilution whether nitroglycerin was infused alone (9.1 +/- 4.3%) or with N-acetylcysteine (8.7 +/- 4.1%). This hemodilution corresponded to an increase in intravascular volume of 745 +/- 382 ml, most of which occurred during the 1st h. Plasma renin activity increased and plasma atrial natriuretic peptide decreased during the infusion. The results of this study suggest that nitrate tolerance is multifactorial. In addition to the previously described pharmacologic tolerance to the effect of nitroglycerin on vascular smooth muscle, a capillary fluid shift from the extravascular to intravascular space appears to be involved, especially during the 1st h of the infusion. A third mechanism, reflex neurohumoral activation, also seems to contribute to the genesis of nitroglycerin tolerance.
Acetylcysteine↗
Captopril does not prevent nitroglycerin tolerance in heart failure.
Tolerance to the continuous intravenous infusion of nitroglycerin is thought to be largely the result of a decrease in vascular responsiveness, possibly due to intra-smooth muscle sulfhydryl group depletion. Another mechanism proposed to contribute to tolerance is nitroglycerin-induced reflex neurohumoral activation resulting in vasoconstriction and sodium and water retention. It has been proposed that the sulfhydryl group-containing angiotensin converting enzyme (ACE) inhibitor captopril may be useful in preventing tolerance to nitroglycerin by repleting sulfhydryl groups and by decreasing reflex neurohumoral activation. However, by decreasing renal perfusion pressure, the combination of captopril and nitrates could also lead to renal dysfunction. The objectives of this study were to determine whether captopril prevented or significantly reduced hemodynamic tolerance to a 72 h infusion of nitroglycerin, and to determine whether the combination of nitroglycerin and captopril caused deterioration of renal function. Nineteen patients with congestive heart failure received nitroglycerin (1.5 micrograms/kg/min) alone (n = 11) or in combination with oral captopril (63 +/- 8 mg/day) (n = 8). In both groups, partial hemodynamic tolerance developed within the first 24 h of nitroglycerin infusion. Nitroglycerin therapy, with or without captopril, did not affect plasma adrenaline, noradrenaline, aldosterone or arginine vasopressin. However, plasma renin activity increased and atrial natriuretic peptide decreased in both groups, these changes being significant after 1 h of infusion but gradually returning towards baseline, in both groups, over the next 71 h. The nitroglycerin infusion did not alter body weight, urine output, creatinine clearance or fractional sodium excretion in either group.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
Cardiobacterium hominis endocarditis.
A 53-year-old man presented with nonspecific symptoms, evidence of aortic valve regurgitation and hepatosplenomegaly. Blood cultures grew Cardiobacterium hominis after 14 days of incubation. Endocarditis is caused by fastidious organisms such as C hominis in less than 5% of cases. To date approximately 40 cases of endocarditis due to this pleomorphic facultative anaerobic Gram-negative bacillus have been reported. C hominis is part of the normal human mouth flora.
Endocarditis, Bacterial↗
Development of a shuttle vector and a conjugative transfer system for Actinobacillus pleuropneumoniae.
An original genetic system for Actinobacillus pleuropneumoniae has been developed. A shuttle cloning vector, pYG53, was constructed from the wild-type plasmid pYG10. It permits, in conjunction with electroporation, the introduction of cloned genes into this species. A conjugal transfer system between Escherichia coli and A. pleuropneumoniae involving pYG54, a mobilizable derivative of pYG53, is also described. Conjugation efficiencies of 8.3 x 10(-3) exconjugants per donor can be obtained.
Cloning, Molecular↗
Identification of a hemolysin from Actinobacillus pleuropneumoniae and characterization of its channel properties in planar phospholipid bilayers.
A proteinaceous hemolysin secreted by strain 4074 of serotype 1 of Actinobacillus pleuropneumoniae was purified by diafiltration and ion exchange chromatographic techniques. The hemolytic activity is associated with a 107-kDa band as assessed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis and confirmed by Western blotting and immunoprecipitation. This hemolysin produces pores in membranes as demonstrated by osmotic protection studies using red blood cells and carbohydrate compounds of various molecular weights. These assays suggest a pore diameter in the order of 2 nm. Phospholipid bilayers composed of 1:1 w/w phosphotidylserine:phosphotidylethanolamine exposed to this toxin display discrete current flow events typical of transmembrane channels and consistent with the interpretation that this toxin acts by forming pores in phospholipid membranes. The linear relationship of current amplitude to holding potential when examined over the -60 to +60 mV range indicates that this pore has a constant mean single channel conductance level of 350-400 pS.
Actinobacillus↗
Transformation of Actinobacillus pleuropneumoniae and analysis of R factors by electroporation.
An efficient method for DNA transfer is essential for the genetic manipulation of any organism. Such a capacity will be required for the genetic analysis of Actinobacillus pleuropneumoniae as a swine pathogen, as well as for its manipulation for vaccination purposes. For this reason, the use of electroporation as a means of plasmid DNA introduction into this species was examined. The multiple antibiotic-resistant strain 80-8141 of Actinobacillus pleuropneumoniae harbors 3 plasmids: pYG10, pYG15, and pYG12 of 5.0, 2.7, and 2.5 kb, respectively. Electroporation of A pleuropneumoniae strain 4074 with a plasmid extract of strain 80-8141 showed that pYG10 encodes chloramphenicol resistance and that pYG12 encodes ampicillin resistance. Electrical pulse conditions for efficient electroporation of strain 4074 were examined by use of pYG10 DNA isolated from a 4074 transformant. Efficiency, expressed as transformants per microgram of plasmid DNA, increased directly with pulse amplitude. However, high efficiencies were only observed in a narrow window of pulse duration (tau = 12 to 22 ms at 6.25 kV/cm). Longer pulse durations resulted in cell death. Electroporation efficiencies increased with cell density. Yield of transformants increased directly with DNA concentration. Results indicate that electroporation can be used to efficiently transform A pleuropneumoniae and that pYG10 and pYG12 are suitable plasmid vectors for use in the genetic manipulation of this organism.
Actinobacillus↗
The ELY-1 locus controls a di-allelic alloantigenic system on equine lymphocytes.
The ELY-1 locus controls the expression of a polymorphic cell surface antigen of equine lymphocytes which was detected using antibodies generated by alloimmunization with peripheral blood lymphocytes. The ELY-1 antigens were not detected on erythrocytes or platelets by absorption experiments. The two alleles, which have been designated ELY-1.1 and ELY-1.2, are expressed codominantly and appear to constitute a closed system at the population level. In family studies, the ELY-1 antigens segregated as products of an autosomal locus not linked to the major histocompatibility complex (MHC) of the horse. In the complement mediated lymphocyte microcytotoxicity test, antisera to the ELY-1 antigens selectively killed peripheral blood lymphocytes which did not express surface immunoglobulin. The ELY-1 antigens may be useful markers for equine T cells when assayed in this fashion. Three alloantisera were used in immune precipitation of iodinated and solubilized cell surface proteins from peripheral blood lymphocytes. Electrophoresis of the precipitates in sodium dodecyl sulphate (SDS)-polyacrylamide gels demonstrated strong bands in the Mr 180-190K range that were shared in the three different preparations. These results suggest that the ELY-1 allospecificities are expressed on an equine equivalent of the murine T200 molecule.
Alleles↗
Cytotoxic murine monoclonal antibody recognizing an ovine lymphocyte subpopulation similar to the human OKT4-positive set.
A cytotoxic murine immunoglobulin G2b monoclonal antibody was produced from immunization with ovine thymocytes. It reacts with a monomorphic determinant on ovine lymphocytes. This antibody 11.2 G11 does not react with B cells, lyses 50 to 60% of peripheral blood T cells, and precipitates a single chain protein with an apparent m.w. of 57,000. Its effect on mitogen- and antigen-driven lymphocyte proliferation supports its similarity in the sheep to the OKT4 antibody in humans.
Animals↗
Interventricular delay in severe aortic stenosis recognized by gated radionuclear blood pool scanning.
Twenty-four patients referred for cardiac catheterization for suspected aortic stenosis were investigated by equilibrium gated blood pool study. From the time-activity curves, end systole for each ventricle was determined and the delay between the two was calculated. The patients were divided into three groups according to their calculated aortic valve area. The mean delay in a control group of 20 normal subjects was 6 +/- 13 msec (mean +/- standard deviation). In group I (aortic valve area greater than 0.75 cm2) the delay was 16 +/- 25 msec (p = NS compared to controls); in group II (aortic valve area 0.5 to 0.75 cm2) the delay was 28 +/- 27 msec (p less than 0.01); and in group III (aortic valve area less than 0.5 cm2) the delay was 60 +/- 28 msec (p less than 0.001). Ten patients were restudied after valve replacement; their mean delay decreased markedly from 48 +/- 19 to 5 +/- 26 msec (p less than 0.001). Thus, this method appears to identify patients with severe aortic stenosis and may therefore be a useful adjunct to the noninvasive assessment of this disorder both before and after surgery.
Adult↗