Superflow 5F catheters in ischemic heart disease: a vote of confidence.
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Biomedical subjects
Publications and source records attributed to E Domingo.
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In order to compare 5 French versus 8 French catheters for assessing ischemic heart disease, we prospectively studied 2 groups of 100 patients each, one with 5 French (group I) and the other with 8 French (group II) catheters by the Judkins technique. Significant differences were found in the greater easiness to catheterize LV (p less than 0.05) and LCA (p = 0.01) in group II and in better quality image for LCA in group II (p less than 0.05), although all patients in both groups had acceptable image quality. Pressure curves quality was better in group II (p less than 0.01); X-ray exposure time was longer in group I (p less than 0.001) and arterial compression time in group II (p less than 0.0001). Group I showed 3 and group II 10 mild hematomas (p less than 0.05). The procedure could be completed by the elected first artery and type of catheter in 95 patients in group I and in 96 in group II. Thus, the Judkins technique with 5 French catheters is as valid as with 8 French for assessing ischemic patients, reducing arterial morbidity, although mildly increasing technical difficulty and mildly decreasing quality image.
The antigenic behavior of 46 field isolates of foot-and-mouth disease virus (FMDV) of serotype C has been studied with a panel of 24 monoclonal antibodies (MAbs) prepared against FMDV C1 or FMDV C3 Indaial. Reactivities were assayed by immunodot, immunoelectrotransfer blot, and neutralization of infectivity. The epitopes recognized by the 10 nonneutralizing MAbs are conserved in all isolates analyzed. In contrast, extreme antigenic heterogeneity is documented with regard to reactivity with 14 MAbs that, on this basis, define at least 12 epitopes involved in neutralization of FMDV of serotype C. The 31 isolates from South America were divided into 17 distinct antigenic groups and the 15 isolates from Europe into 7 groups. Lack of correspondence between antigenic composition and the origin--date and place of isolation--of the viruses was noted in several instances. Antigenic heterogeneity is shown among epidemiologically closely related FMDVs. In most--but not all--cases tested, a good correlation was found between binding of a neutralizing MAb to virions and its ability to neutralize infectivity. It is concluded that variation of epitopes involved in neutralization of FMDV is extensive among subtypes of serotype C and also among individual isolates of one subtype.
Genetic heterogeneity among closely related isolates of foot-and-mouth disease virus (FMDV) has been measured by direct sequencing of the VP1-coding-region RNA for three new FMDVs of serotype C1 and by additional sequences of RNA from previously reported isolates, all belonging to a single episode of disease [Sobrino et al., Gene 50 (1986) 149-159]. In the ten viruses compared, eight different VP1 are represented. The changes include amino acid substitutions at a critical antigenic determinant of VP1. We document that variations present in such natural isolates result in changes of the immunogenic properties of the viruses. Vaccines prepared with two of the FMDV C1 analyzed induce complete protection against an homologous virus but only partial protection against an heterologous virus in swine, the host from which these viruses were isolated.
A phylogenetic tree relating the VP1 gene of 15 isolates of foot-and-mouth disease virus (FMDV) of serotypes A, C, and O has been constructed. The most parsimonious tree shows that FMDV subtypes and isolates within subtypes constitute sets of related, nonidentical genomes, in agreement with a quasispecies mode of evolution of this virus. The average number of nucleotide replacements per site for all possible pairs of VP1 coding segments is higher among representatives of serotype A than serotype C or O. In comparing amino acid sequences, the values of dispersion index (variance/mean value) are greater than 1, with the highest values scored when all sequences are considered. This indicates an accumulation of mutations at a limited number of residues, suggesting that distributions of sequences fluctuate around points of high stability. Evolution of FMDV follows a path very distant from that of a star phylogeny, and it has not been possible to derive conclusions on constancy of evolutionary rates with the test applied to the analysis. FMDVs, as other RNA viruses, are of limited genetic complexity and their population sizes are extremely large. Their evolution concerns complex, indeterminate mixtures of genomes rather than a single, determinate species.
The nucleotide sequences of the VP1-coding regions of several isolates of serotype C3 foot-and-mouth disease virus (FMDV) were determined. The deduced amino acid sequences were compared with those of serotype C1 FMDV. The results provide evidence for two different lineages of FMDV C3 and document the potential for both long-term conservation and rapid evolution of FMDV.
Rapid evolution of foot-and-mouth disease virus (FMDV) is documented during persistent infections of cattle. The carrier state was established experimentally with plaque-purified FMDV of serotype C3. Virus was recovered from the esophageal pharyngeal area of the animals up to 539 days postinfection. Analysis of capsid proteins by electrofocusing and by electrophoretic mobility of the genomic poly(C)-rich tract suggested heterogeneity in several isolates and sequential dominance of viral subpopulations. Nucleotide sequences of the VP1-coding region of the parental FMDV C3 clones and of seven isolates from the carrier cattle showed point mutations that represented rates of fixation of mutations of 0.9 X 10(-2) to 7.4 X 10(-2) substitutions per nucleotide per year; 59% of the base changes led to amino acid substitutions, some of which were located within residues 135 to 151, a region involved in neutralization of FMDV. In the esophageal pharyngeal fluid samples, FMDV C3-neutralizing activity was present. Antigenic variation was demonstrated with monoclonal antibodies raised against FMDV C3. Two isolates from carrier cattle differed from the parental virus by 10(2)- or 10(3)-fold decreased reactivity with neutralizing monoclonal antibodies. We suggest that persistent, inapparent infections of ruminants, in addition to being a reservoir of virus, may promote the rapid selection of antigenically variant FMDVs.
Virus and cells evolve during serial passage of cloned BHK-21 cells persistently infected with foot-and-mouth disease virus (FMDV). These carrier cells, termed C1-BHK-Rc1 (J.C. de la Torre, M. Dávila, F. Sobrino, J. Ortín, and E. Domingo, Virology 145:24-35, 1985), become constitutively resistant to the parental FMDV C-S8c1. Curing of late-passage C1-BHK-Rc1 cells of FMDV by ribavirin treatment (J.C. de la Torre, B. Alarcón, E. Martínez-Salas, L. Carrasco, and E. Domingo, J. Virol. 61:233-235, 1987) did not restore sensitivity to FMDV C-S8c1. The resistance of C1-BHK-Rc1 cells to FMDV C-S8c1 was not due to an impairment of attachment, penetration, or uncoating of the particles but to some intracellular block that resulted in a 100-fold decrease in the amount of FMDV RNA in the infected cells. FMDV R59, the virus isolated from late-passage carrier cells, partly overcame the cellular block and was more cytolytic than FMDV C-S8c1 for BHK-21 cells. Sequencing of the VP1 gene from nine viral clones from C1-BHK-Rc1 cells showed genetic heterogeneity of 5 X 10(-4) substitutions per nucleotide. Mutations were sequentially fixed during persistence. In addition to resistance to FMDV C-S8c1, C1-BHK-Rc1 cells showed a characteristic round cell morphology, and compared with BHK-21 cells, they grew faster in liquid culture, were less subject to contact inhibition of growth, and had an increased ability to form colonies in semisolid agar. Reconstitution of a persistent infection was readily attained with late-passage C1-BHK-Rc1 cells and FMDV C-S8c1 or FMDV R59. The results suggest that coevolution of BHK-21 cells and FMDV contributes to the maintenance of persistence in cell culture.
The dynamic behavior of fixed LV outflow tract stenosis partly resembles that of OCM. To analyze their differences we studied basal and postextrasystolic (post-PVC) peak-to-peak LV aortic gradients, aortic systolic pressure, and pulse pressure in 14 OCM and in 36 pure VAS without two-dimensional echocardiographic findings of OCM. Fifteen mild VAS had basal gradients similar to those of OCM (39 +/- 17 mm Hg vs 24 +/- 16 mm Hg). Patients with OCM show a post-PVC gradient (109 +/- 41 mm Hg) similar to that of VAS (110 +/- 50 mm Hg). However, the latter were departing from much higher gradients (VAS 72 +/- 30 mm Hg vs OCM 24 +/- 16 mm Hg). Decrement of post-PVC aortic systolic pressure and pulse pressure were frequent in both groups, but decrement of pulse pressure greater than 5 mm Hg were more frequent in OCM. We concluded that (1) post-PVC increased aortic gradients and decreased aortic systolic pressure occurred in both VAS and OCM; (2) post-PVC decreased aortic pulse pressure might occur in VAS; and (3) association of post-PVC gradient increment greater than 75 percent and pulse pressure decrement greater than 5 mm Hg are strongly suggestive of OCM.
A serial cell plating experiment has been designed to determine the minimum number of cells, isolated from a culture persistently infected with a virus, required to reconstruct the carrier state. For cell line C1-BHK-Rc1, consisting of BHK-21 cells persistently infected with foot-and-mouth disease virus type C (isolate C-S8c1), more than 10(3) cells derived from one monolayer were needed to reinitiate a stable, FMDV-producing carrier culture. Thus, the FMDV-BHK-21 cell system cannot be explained merely as a sum of its individual components. The results suggest, instead, that the behaviour of C1-BHK-Rc1 cultures is the result of complex interactions acting at the population level. Implications for viral persistence are discussed.
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We herein report the case of a 53-year-old white acromegalic patient with an abdominal mass due to massive cardiomegaly. The patient suffered from long lasting acromegaly refractary to bromocriptine, transsphenoidal surgery and radiotherapy. He had been previously diagnosed as having systemic hypertension, ischemic chest pain and congestive heart failure with marked cardiomegaly. The present admission was due to asthenia, anorexia and weight loss that were finally attributed to adrenal insufficiency secondary to radiotherapy. Plain abdomen X-ray suggested the presence of supramesocolic mass. A large cold area in the left hepatic lobe was detected on the radionuclide liver scan. Radionuclide angiography surprisingly identified the cold area as a vascular structure corresponding to the heart. A body CT scan revealed the heart was expanding between stomach and liver. Two-dimensional echocardiography showed marked enlargement of left ventricle. Cardiomegaly was probably multifactorial (chronic hypertension, ischemic heart disease and acromegaly). To our knowledge, this is the first reported case of massive cardiomegaly behaving as an intraabdominal mass. This possibility must be considered when invasive intraabdominal diagnostic procedures are to be done, particularly in an acromegalic patient.
A panel of 12 monoclonal antibodies (MAbs) raised against foot-and-mouth disease virus (FMDV) of serotype C1 (FMDV C-S8c1) and 11 MAbs raised against other FMDVs have been used to evaluate the reactivity of 14 isolates of FMDV of serotype C1 (series FMDV C-S), 12 of them from one disease episode (Spain 1979-1982). The assays used were immunoelectrotransfer blot, immunodot and neutralization of infectivity. None of the isolates could be clearly distinguished by its reactivity with 6 non-neutralizing and 2 neutralizing MAbs raised against FMDV C-S8c1. In contrast, the isolates were distinguished in two groups by a 10(2)-fold difference in their reactivity with 6 neutralizing MAbs. The reactivity of MAbs with synthetic peptides indicated that conserved and non-conserved epitopes recognised respectively by neutralizing MAbs 4G3 and SD6 are localized in the immunogenic region (amino acids 138-156) of VP1. Thus, epidemiologically related FMDVs differ in at least one epitope critical for virus neutralization.
Ribavirin (1-beta-D-ribofuranosyl-1H-1,2,4-triazole-3-carboxamide) eliminates foot-and-mouth disease virus from persistently infected cell cultures. The latter are 10-fold more sensitive to ribavirin than lytically infected cells. In treated cells no viral RNA or proteins could be detected by dot-blot hybridization to cDNA probes, virus and RNA infectivity assays, or immunofluorescence. A potential application of the drug for the treatment of animals carrying the virus is suggested.
Rates of fixation of mutations during the evolution of the foot-and-mouth disease virus (FMDV) C1 in nature have been estimated by hybridization of viral RNA to cloned cDNAs representing defined FMDV genome segments, and comparison of the selected RNAs by T1 RNase oligonucleotide fingerprinting. Values ranged from less than 0.04 X 10(-2) to 4.5 X 10(-2) substitutions per nucleotide per year (s/nt/yr), depending on the time period and the genomic segment considered. Rates for viral structural protein genes were up to sixfold higher than for nonstructural protein genes. Values in excess of 10(-2) s/nt/yr have been measured for the RNA region that encodes VP1-VP3. The nucleotide sequences of the major immunogenic region of capsid protein VP1 have been determined for six new FMDV C1 isolates, and they are compared with the two previously known sequences of FMDV C1 (C-S8 and C1-O). Both oligonucleotide fingerprinting of selected RNA fragments and direct nucleotide sequencing demonstrate that genetic heterogeneity exists among three viruses isolated on the same day, introducing a significant indetermination in the evaluation of fixation rates of mutations. During the FMDV C1 outbreak, amino acid substitutions did occur that are known to affect the immunological properties of the virus. The proportion of mutations between two viral RNAs does not increase significantly with the time elapsed between the two isolations, suggesting a cocirculation of multiple, related, nonidentical FMDVs ('evolving quasispecies') as the mode of evolution of this agent.
Digital angiography has been reported to be a valid technique for anatomical studies of the peripheral cardiovascular system and for dynamic studies of ventricular function. The purpose of the present study was to assess the usefulness and accuracy of venous digital angiography (2 images per second) for imaging coronary bypass grafts after coronary artery bypass surgery, comparing its results with those of selective angiography. Fifty-two patients with 108 grafts (101 venous grafts and 7 internal mammary artery grafts) were studied by venous digital angiography and selective angiography. Venous digital angiography correctly diagnosed 95 out of 97 patent grafts and the 11 occluded grafts visualized by selective angiography. These results are better than those obtained in the very few studies so far reported in the literature. We were not able to adequately visualize distal anastomoses in most patients although we could identify the distal portion of 7 out of 8 patent sequential bypass grafts. Thus, these results suggest that venous digital angiography is a useful and accurate technique for assessing coronary bypass graft patency.
A case of a transient and huge postanterior acute myocardial infarction left ventricular thrombus causing temporary intractability of severe heart failure is reported. Echographic and hemodynamic data suggest the restrictive-obliterative pattern of heart failure.
Influenza virus RNA segment 8 has been cloned into primer-vector pSLts1. This vector was designed to replicate in simian cells in a temperature dependent fashion by use of the SV40 tsA209 T-antigen gene. The oriented synthesis of cDNA on dT-tailed pSLts1 was performed on in vitro synthesized mRNA, and the second DNA strand was primed with an influenza-specific terminal oligodeoxynucleotide. Recombinant pSLVa232 contained the RNA segment 8 sequence directly fused to the SV40 late promoter contained in pSLts1, and followed by the SV40 polyadenylation signal. Expression of NS1 gene in transfected COS cells took place at a level comparable to that found in infected cells. When VERO cell cultures were transfected with recombinant pSLVa232, expression of the NS1 gene was temperature dependent. Close to one hundred fold increase in the amplification and expression of the cloned gene was observed after shift down of the transfected cells to permissive temperature. Vector pSLts1 and the cloning strategy described may be useful for the specific cloning and regulated expression of mRNAs of known 5'-terminal sequence.