Biomedical subjects

G R Sutherland

Publications and source records attributed to G R Sutherland.

At least 127 records · Page 7Linked to original sources

PubMed1998

Identification of a human HECT family protein with homology to the Drosophila tumor suppressor gene hyperplastic discs.

Use of the differential display technique to isolate progestin-regulated genes in T-47D human breast cancer cells led to identification of a novel gene, EDD. The cDNA sequence contains a 2799 amino acid open reading frame sharing 40% identity with the predicted 2894 amino acid product of the Drosophila melanogaster tumor suppressor gene hyperplastic discs, while the carboxy-terminal 889 amino acids show 96% identity to a rat 100 kDa HECT domain protein. EDD mRNA was progestin-induced in T-47D cells and was highly abundant in testes and expressed at moderately high levels in other tissues, suggesting a broad role for EDD. Anti-EDD antibodies immunoprecipitated an approximately 300 kDa protein from T-47D cell lysates. HECT family proteins function as E3 ubiquitin-protein ligases, targeting specific proteins for ubiquitin-mediated proteolysis. EDD is likely to function as an E3 as in vitro translated protein bound ubiquitin reversibly through a conserved HECT domain cysteine residue. EDD was localized by FISH to chromosome 8q22, a locus disrupted in a variety of cancers. Given the homology between EDD and the hyperplastic discs protein, which is required for control of imaginal disc growth in Drosophila, EDD potentially has a role in regulation of cell proliferation or differentiation.

Amino Acid Sequence↗

PubMed1998

Structural organization and chromosomal localization of three human galanin receptor genes.

Human galanin receptor subtypes GALR1, GALR2, and GALR3 are encoded by separate genes that are located on human chromosomes 18q23, 17q25.3, and 22q13.1, respectively. The exon:intron organization of the gene encoding GALR2 (GALNR2) and GALR3 (GALNR3) is conserved, with exon 1 encoding the NH2-terminus to the end of transmembrane domain 3 and exon 2 encoding the remainder of the receptor, from the second intracellular loop to the COOH-terminus. This conservation of structural organization is indicative of a common evolutionary origin for GALNR2 and GALNR3. The exon:intron organization of the gene encoding GALR1 (GALNR1) is different from that of GALNR2 and GALNR3, with exon 1 encoding the NH2-terminus to the end of transmembrane domain 5, exon 2 encoding the third intracellular loop, and exon 3 encoding the remainder of the receptor, from transmembrane domain 6 to the COOH-terminus. The structural organization of GALNR1 suggests convergent evolution for this gene and represents a structural organization that is unique among genes encoding G-protein-coupled receptors.

Amino Acid Sequence↗

PubMed1998

Characterization of postischemic behavioral deficits in gerbils with and without hypothermic neuroprotection.

Five minutes of global ischemia in gerbil results in delayed hippocampal CA1 neuronal degeneration, which is accompanied by working memory impairments and hyperactivity in novel environments. In this study, postischemic activity was characterized in familiar and in novel environments to determine whether hyperactivity was due to impaired spatial habituation or another form of motor hyperactivity. This study also determined whether 6-h delayed hypothermia, which reduces CA1 neuronal injury, would attenuate functional impairments. Gerbils were subjected to 5 min of normothermic ischemia or sham operation 2 days following implantation of brain temperature probes. One of two ischemic groups was cooled (>48 h) starting at 6-h postischemia. Locomotor activity in a familiar cage was measured for 6 days while activity in three novel environments was intermittently measured on days 4, 5 and 6. Open field behavior and working memory in a T-maze were also assessed. Untreated ischemia caused marked hyperactivity in the familiar cage on day 1, which reverted to near-normal by day 2. Nonetheless, these gerbils showed hyperactivity during novel environment sessions on days 4-6. This maze behavior, which predicted hippocampal CA1 injury, was not due to different habituation rates nor baseline hyperactivity. Conversely, open field sessions on day 8 revealed ischemic habituation rate deficits. Ischemia also impaired working memory in the T-maze. Delayed hypothermia, which reduced neuronal loss in the CA1 sector to 12% from 81%, reduced all functional impairments. Ischemic gerbils quickly developed spontaneous locomotion hyperactivity that returned to near-normal after 1 day. This motor hyperactivity did not explain the elevated activity found with delayed testing in novel environments. Regardless, only the open field test on day 8 revealed a habituation-like deficit.

Animals↗

PubMed1998

Labeling of N-acetylaspartate and N-acetylaspartylglutamate in rat neocortex, hippocampus and cerebellum from [1-13C]glucose.

Both N-acetylaspartate (NAA) and N-acetylaspartylglutamate (NAAG) are localized almost exclusively to neurons, and have become important markers of neuronal viability in a number of cerebral pathological conditions. Using nuclear magnetic resonance spectroscopy combined with [1-13C]glucose administration (200 min infusion) we show that the synthesis of both NAA and NAAG can be observed. Label was incorporated into NAA from labeled acetate and from labeled aspartate, while NAAG was labeled from labeled glutamate. The low fractional enrichment of NAA (ca. 3%) relative to aspartate (20%) suggests a slow turnover rate, while NAAG (20.0%) and glutamate (25.2%) labeling were nearly equal, suggesting that NAAG labeling is near steady state. The rapid turnover of NAAG suggests an important role in glutamate delivery, while the slow rate of NAA turnover implies that its major role is as substrate for the formation of NAAG.

Animals↗

PubMed1998

Molecular characterization, pharmacological properties and chromosomal localization of the human GALR2 galanin receptor.

The neuropeptide galanin mediates a diverse spectrum of biological activities by interacting with specific G protein-coupled receptors. We have used homology genomic library screening and polymerase chain reaction (PCR) techniques to isolate both genomic and cDNA clones encoding the human homolog of the recently cloned rat GALR2 galanin receptor. By fluorescence in situ hybridization, the gene encoding human GALR2 (GALNR2) has been localized to chromosome 17q25.3. The two coding exons of the human GALNR2 gene, interrupted by an intron positioned at the end of transmembrane domain III, encode a 387 amino acid G protein-coupled receptor with 87% overall amino acid identity with rat GALR2. In HEK-293 cells stably expressing human GALR2, binding of [125I]porcine galanin is saturable and can be displaced by galanin, amino-terminal galanin fragments and chimeric galanin peptides but not by carboxy-terminal galanin fragments. In HEK-293 cells, human GALR2 couples both to Galphaq/11 to stimulate phospholipase C and increase intracellular calcium levels and to Galphai/o to inhibit forskolin-stimulated intracellular cAMP accumulation. A wide tissue distribution is observed by reverse transcriptase (RT)-PCR analysis, with human GALR2 mRNA being detected in many areas of the human central nervous system as well as in peripheral tissues.

Amino Acid Sequence↗

PubMed1998

Construction of a high-resolution physical and transcription map of chromosome 16q24.3: a region of frequent loss of heterozygosity in sporadic breast cancer.

A breast cancer tumor suppressor gene has been localized to chromosome 16q24.3 by loss of heterozygosity (LOH) studies of breast tumor DNA. To identify candidate genes for this suppressor function, we have constructed a detailed physical map extending approximately 940 kb from the telomere of the long arm of chromosome 16 that encompasses the minimum LOH interval. This contig consists of a minimum overlapping set of 35 cosmids and a single PAC clone that were aligned by restriction enzyme site mapping. Cosmids were initially identified by screening filters with markers localized to the region by physical mapping using mouse/human somatic cell hybrids, and subsequently cosmid ends were used to complete the contig. A total of seven known genes, including PRSM1, PISSLRE, and the recently cloned Fanconi anemia A (FAA) gene, and potential transcripts from exon-trapping experiments have been located to this contig. A minimum of 14 new transcripts have been identified based on homology of trapped exons with database sequences. This contig and expressed sequence map will form the basis for the identification of the breast cancer tumor suppressor gene in this region.

Breast Neoplasms↗

PubMed1998

Complex organisation of the 5'-end of the human glycine tRNA synthetase gene.

Glycine tRNA synthetase (glyRS) catalyses the addition of the amino acid glycine to its cognate tRNA molecules. In the silk moth worm Bombyx mori, this gene is subject to complex transcriptional regulation because of the predominance of glycine in silk. In vertebrates, glycine is a major constituent of collagen but there have been no studies of glyRS regulation. In this study we have isolated and mapped a genomic clone containing the 5'-end of glyRS. Primer extension studies identified only one transcriptional start point (TSP) in three different cell lines. Expression of the transcript identified may be regulated translationally because it contains five potential initiation codons, three of which are in good context for initiation. The most 3' of the potential initiation codons has previously been predicted to be the initiating codon for cytoplasmic glyRS. Two of the upstream codons are in-frame with this codon, and both are predicted to extend the N-terminus of glyRS to include a mitochondrial targeting sequence. Sequencing of genomic DNA surrounding the TSP showed features common to the promoters of housekeeping genes, as well as a canonical TATA box at the unusual position of +9. Surprisingly, promoter activity in vitro was not specified by a 1.9 kb genomic fragment containing the TSP and TATA box, but by a contiguous 0.4 kb fragment immediately downstream. These studies suggest that the transcription of glyRS from a single start point requires downstream promoter elements.

Animals↗

PubMed1998

Three-dimensional echocardiographic evaluation of left ventricular volume: comparison of Doppler myocardial imaging and standard gray-scale imaging with cineventriculography--an in vitro and in vivo study.

BACKGROUND: Standard gray-scale imaging (GSI), three-dimensional (3D) echocardiography has been shown to be superior to two-dimensional echocardiography in measuring left ventricular volume. However, the often relatively poor quality of transthoracic gray-scale data can limit the potential application of this technique. Doppler myocardial imaging (DMI) is a new ultrasound technique that potentially offers higher-quality 3D images with a transthoracic approach than the 3D GSI technique. This study was designed to compare the accuracy of standard GSI and DMI 3D left ventricular volume measurements in vitro and in vivo. METHODS AND RESULTS: In vitro, the minimum and maximum volume of the contracting single-chamber, tissue-mimicking phantom was calculated by using both techniques. In vivo, GSI and DMI 3D left ventricular volume measurements were performed in 16 patients. End-diastolic and end-systolic left ventricular volumes were computed for both techniques and compared with those calculated by cineventriculography. In vitro, both methods tended to underestimate the true phantom volume, but the systematic error was smaller for DMI than for GSI (-1.2% +/- 1.5% vs. -4.3% +/- 3%; p < 0.01) and was more constant in the case of DMI over the range of different sizes of true volume. In vivo, for GSI the end-diastolic volume mean difference was -12.6 ml and the limits of agreement were +/-18 ml, and for DMI the corresponding values were -4.2 and +/- 10.6 ml, respectively. The difference for end-systole was -6.5 +/- 10.6 ml and -1.5 +/- 10 ml for GSI and DMI, respectively. The magnitude of the difference in volume measurement between 3D echocardiography and cineventriculography was significantly smaller when using the Doppler technique. CONCLUSIONS: The results of this in vitro and in vivo study indicate that DMI is superior to GSI as a transthoracic acquisition technique for 3 D volume computation.

Echocardiography, Three-Dimensional↗

PubMed1998

Diagnostic value of transesophageal echocardiography in the assessment of congenitally corrected transposition of the great arteries in adult patients.

This study was designed to evaluate the relative diagnostic values of transthoracic (TTE) and transesophageal (TEE) echocardiography in the assessment of congenitally corrected transposition of the great arteries in adult patients. Twelve patients (mean age 29 years, range 21 to 39 years) with congenitally corrected transposition of the great arteries underwent both TTE and TEE examinations to assess this complex cardiac lesion. Of the 12 patients evaluated, situs solitus and inversus were present in 8 and in 4 patients, respectively. TTE correctly identified atrial situs in only 10 patients, whereas TEE, directly evaluating the morphologic features of either appendage, correctly determined situs in every patient. In all 11 patients with intact inlet ventricular septum, the spatial relationship between the septal leaflets of atrioventricular valves was correctly evaluated by both techniques. However, the chordal attachments of both valves were clearly elucidated by TEE in all patients, whereas TTE could obtain images of these in only three patients. TTE was able to evaluate the discordant connection between the right ventricle and the anterior vessel (aorta) in 10 patients, whereas the connection between the left ventricle and the posterior vessel was clearly shown only in 7 patients. Transesophageal longitudinal planes better elucidated these two discordances in all patients irrespective of the position of the heart in the chest and atrial situs. Four patients had an associated ventricular septal defect (inlet defect in one, perimembranous in two, and muscular in one); the inlet defect was unrestrictive and could be easily detected by either imaging technique, whereas the membranous was detected by TTE and by the horizontal transesophageal planes; the muscular defect was recognized only by TTE. Three patients had an associated pulmonary stenosis; Doppler transthoracic echocardiography showed a left outflow peak gradient of 100 mm Hg in two patients and of 80 mm Hg in one but failed to adequately assess the morphologic features of the stenosis, whose features were clearly visualized by transesophageal longitudinal planes in all patients. In conclusion, in our experience TEE is superior to transthoracic imaging in studying congenitally corrected transposition of the great arteries in adult patients; the horizontal plane is best suited to the evaluation of atrial situs and the atrioventricular junction, whereas the longitudinal plane is most valuable in the study of the morphologic features of the ventriculoarterial connections. These findings should be equally applicable to multiplane transesophageal studies.

Abnormalities, Multiple↗

PubMed1998

Fragile sites still breaking.

Rare fragile sites on chromosomes are the archetypal dynamic mutations. They involve large expansions of the microsatellite CCG or AT-rich minisatellites. The mutation process is an increase in repeat-unit number from within a normal range, through a premutation range, up to full mutation where the fragile site is expressed. Full mutations can inactivate genes and are regions of genomic instability. Common fragile sites, in particular, might have a role in oncogensis by facilitating gene inactivation through chromosomal deletion or amplification, but this requires further exploration. The mechanisms behind the changes that give rise to the cytogenetic manifestation of chromosomal fragility are now beginning to be understood.

Chromosome Fragile Sites↗

PubMed1998

Quantification of the enhanced backscatter phenomenon from an intravenous and an intra-arterial contrast agent.

The phenomenon of enhanced backscatter from myocardial contrast agents was studied using two examples, a robust thicker-walled, intra-arterial agent (AIP 201) and a smaller thinner-walled, intravenous agent (Quantison). Both agents are composed of albumin-encapsulated microbubbles. Samples of the agents were inserted into an in vitro phantom and insonated under different scanning regimes. Upon insonation, Quantison exhibited a pronounced increase in mean backscatter at medium and low concentrations, which decreased dramatically with increasing number of frames of insonation. At high concentrations, no dramatic decrease or increase in mean backscatter was observed over the period of the experiment. AIP 201 exhibited an overall decrease in mean backscatter with increasing number of frames of insonation. These results suggest that the difference in size and wall thickness of the contrast microcapsules can significantly affect the behaviour of the contrast agents in an ultrasound field.

Contrast Media↗

PubMed1998

FRA10B structure reveals common elements in repeat expansion and chromosomal fragile site genesis.

A common mechanism for chromosomal fragile site genesis is not yet apparent. Folate-sensitive fragile sites are expanded p(CCG)n repeats that arise from longer normal alleles. Distamycin A or bromodeoxyuridine-inducible fragile site FRA16B is an expanded AT-rich approximately 33 bp repeat; however, the relationship between normal and fragile site alleles is not known. Here, we report that bromodeoxyuridine-inducible, distamycin A-insensitive fragile site FRA10B is composed of expanded approximately 42 bp repeats. Differences in repeat motif length or composition between different FRA10B families indicate multiple independent expansion events. Some FRA10B alleles comprise a mixture of different expanded repeat motifs. FRA10B fragile site and long normal alleles share flanking polymorphisms. Somatic and intergenerational FRA10B repeat instability analogous to that found in expanded trinucleotide repeats supports dynamic mutation as a common mechanism for repeat expansion.

Alleles↗

PubMed1998

Ischemic neuronal injury is ameliorated by astrocyte activation.

BACKGROUND: The motivation of this study was to more precisely define the in vivo role of astrocytes in forebrain ischemia. Controversy exists in the literature as to whether they protect or injure neurons in this setting. METHODS: Astrocytes in the rat hippocampus were disabled with stereotactic administration of a gliotoxin, ethidium bromide, 3 days prior to induction of forebrain ischemia. The extent of neuronal injury in this group was compared to a control category receiving intrahippocampal saline only. RESULTS: Saline-injected animals demonstrated decreased hippocampal CA1 sector injury, and increased gliosis on the side of the injection compared to the contralateral side (P < 0.01) or ethidium bromide-treated animals (P < 0.05). CONCLUSIONS: The results suggest that activated astrocytes are protective to neurons subjected to an ischemic insult. This may result from their ability to elaborate neurotrophic factors, buffer potassium and metabolize a variety of neurotransmitters.

Animals↗

PubMed1998

Febrile seizures and generalized epilepsy associated with a mutation in the Na+-channel beta1 subunit gene SCN1B.

Febrile seizures affect approximately 3% of all children under six years of age and are by far the most common seizure disorder. A small proportion of children with febrile seizures later develop ongoing epilepsy with afebrile seizures. Segregation analysis suggests the majority of cases have complex inheritance but rare families show apparent autosomal dominant inheritance. Two putative loci have been mapped (FEB1 and FEB2), but specific genes have not yet been identified. We recently described a clinical subset, termed generalized epilepsy with febrile seizures plus (GEFS+), in which many family members have seizures with fever that may persist beyond six years of age or be associated with afebrile generalized seizures. We now report linkage, in another large GEFS+ family, to chromosome region 19q13.1 and identification of a mutation in the voltage-gated sodium (Na+)-channel beta1 subunit gene (SCN1B). The mutation changes a conserved cysteine residue disrupting a putative disulfide bridge which normally maintains an extracellular immunoglobulin-like fold. Co-expression of the mutant beta1 subunit with a brain Na+-channel alpha subunit in Xenopus laevis oocytes demonstrates that the mutation interferes with the ability of the subunit to modulate channel-gating kinetics consistent with a loss-of-function allele. This observation develops the theme that idiopathic epilepsies are a family of channelopathies and raises the possibility of involvement of other Na+-channel subunit genes in febrile seizures and generalized epilepsies with complex inheritance patterns.

Amino Acid Sequence↗

PubMed1998

Regional mean systolic myocardial velocity estimation by real-time color Doppler myocardial imaging: a new technique for quantifying regional systolic function.

A new color Doppler myocardial imaging (CDMI) system with high spatial and temporal resolution and novel postprocessing modalities has been developed that could allow quantifiable stress echocardiography. The purpose of this study was to determine whether regional myocardial systolic velocities could be accurately and reproducibly measured both at rest and during bicycle ergometry by using CDMI. Thirty normal subjects were examined with CDMI at rest, and peak mean systolic myocardial velocities (MSV) were measured for 34 predetermined left ventricular myocardial segments. Interobserver variability and intraobserver variability were established for all segments. Submaximal bicycle ergometry was performed in 20 normal subjects by using standardized weight-related increases in workload. MSV were measured at each step of exercise for 16 left ventricular stress echo segments. At rest, a base-apex gradient in regional MSV was recorded with highest longitudinal shortening velocities at the base. A similar pattern was noted for circumferential shortening MSV. Measurements were predictable and highly reproducible with low interobserver and intraobserver variability for 26 of 34 segments. Reproducibility was poor for basal anteroseptal segments in all views and mid anterior, anteroseptal, and septal segments in the short-axis views. During exercise, mid and basal segments of all walls showed a significant increase of MSV between each workload step and for apical segments between alternate steps. The resting base-apex velocity gradient observed at rest remained in all walls throughout ergometry. Thus a CDMI system with improved spatial and temporal resolution and postprocessing analysis modalities provided reproducible and accurate quantification of segmental left ventricular circumferential and longitudinal contraction both at rest and during exercise.

Adult↗

PubMed1998

Characterisation of coronary atherosclerotic morphology by spectral analysis of radiofrequency signal: in vitro intravascular ultrasound study with histological and radiological validation.

OBJECTIVE: To determine whether spectral analysis of unprocessed radiofrequency (RF) signal offers advantages over standard videodensitometric analysis in identifying the morphology of coronary atherosclerotic plaques. METHODS: 97 regions of interest (ROI) were imaged at 30 MHz from postmortem, pressure perfused (80 mm Hg) coronary arteries in saline baths. RF data were digitised at 250 MHz. Two different sizes of ROI were identified from scan converted images, and relative amplitudes of different frequency components were analysed from raw data. Normalised spectra was used to calculate spectral slope (dB/MHz), y-axis intercept (dB), mean power (dB), and maximum power (dB) over a given bandwidth (17-42 MHz). RF images were constructed and compared with comparative histology derived from microscopy and radiological techniques in three dimensions. RESULTS: Mean power was similar from dense fibrotic tissue and heavy calcium, but spectral slope was steeper in heavy calcium (-0.45 (0.1)) than in dense fibrotic tissue (-0.31 (0.1)), and maximum power was higher for heavy calcium (-7.7 (2.0)) than for dense fibrotic tissue (-10.2 (3.9)). Maximum power was significantly higher in heavy calcium (-7.7 (2.0) dB) and dense fibrotic tissue (-10.2 (3.9) dB) than in microcalcification (-13.9 (3.8) dB). Y-axis intercept was higher in microcalcification (-5.8 (1.1) dB) than in moderately fibrotic tissue (-11.9 (2.0) dB). Moderate and dense fibrotic tissue were discriminated with mean power: moderate -20.2 (1.1) dB, dense -14.7 (3.7) dB; and y-axis intercept: moderate -11.9 (2.0) dB, dense -5.5 (5.4) dB. Different densities of fibrosis, loose, moderate, and dense, were discriminated with both y-axis intercept, spectral slope, and mean power. Lipid could be differentiated from other types of plaque tissue on the basis of spectral slope, lipid -0.17 (0.08). Also y-axis intercept from lipid (-17.6 (3.9)) differed significantly from moderately fibrotic tissue, dense fibrotic tissue, microcalcification, and heavy calcium. No significant differences in any of the measured parameters were seen between the results obtained from small and large ROIs. CONCLUSION: Frequency based spectral analysis of unprocessed ultrasound signal may lead to accurate identification of atherosclerotic plaque morphology.

Calcinosis↗

PubMed1998

Human cerebral neoplasms studied using MR spectroscopy: a review.

Of primary central nervous system tumors treated each year, the majority are glioma, followed by meningioma and then pituitary adenoma. While the use of magnetic resonance (MR) and computed tomographic imaging is well established in the diagnosis and management of such tumors, these techniques have a limited role in determining the metabolic state, either prior to or following therapy. Multinuclear MR spectroscopy, on the other hand, provides information on tumor metabolism and the effect of therapy on tumor viability. This paper reviews MR spectroscopic studies performed on patients with central nervous system tumors and discusses the impact that such studies have had on tumor diagnosis and management.

Adenoma↗

PubMed1998

A prospective echocardiographic study of the effects of balloon mitral commissurotomy on pre-existing mitral regurgitation in patients with mitral stenosis.

Mitral regurgitation which is more than mild in severity is usually regarded as a relative contraindication to balloon mitral commissurotomy (BMC) because it is commonly believed that it may be worsened by the procedure. The aim of this study was to investigate the effects of BMC on pre-existing mitral regurgitation. Transthoracic and biplane transoesophageal echocardiography (TTE, TEE) combined with colour flow mapping (CFM) were performed prospectively on 50 consecutive patients immediately before and within 24 h after Inoue BMC. Before BMC, mitral regurgitation (MR) was diagnosed by TEE and left ventriculography in 36 and 13 patients respectively. Angiographic MR was mild in all 13 cases. The precise origins of MR jets were carefully sought by scanning in multiple TTE and TEE views. The maximal area of colour flow MR jets detected by TEE was measured by planimetry. After BMC mean mitral valve area increased from 1.0 +/- 0.3 to 1.7 +/- 0.8 cm2, p < 0.0001, mean left atrial pressure and volume decreased from 23.7 +/- 5.6 mm Hg to 21.6 +/- 7.5 ml, p = 0.039, and from 105 +/- 56 to 90 +/- 46 ml, p = 0.002, respectively. MR jets as assessed by TEE CFM disappeared in 12 patients, in all of whom MR had been undetected by angiography. MR jets remained within 20% of their original sizes in 16 (44%) patients and more than doubled in only 3 patients. However, the latter had only mild angiographic MR after BMC. BMC created new MR jets, distinct from pre-existing ones, in 27 (75%) patients. Their aetiologies were commissural splitting in 24, leaflet tears in 2 and chordal rupture in 1 case. New MR jets were co-existent with old jets in 17 (47%) cases and in 10 (28%) cases old jets were replaced by new jets. The severity of angiographic MR was unchanged in 21 (58%) of the 36 patients; new jets, all originating from one or both commissures, were found in 13 (65%) patients on TEE. Angiographic MR increased by 1 grade in 11 (33%) patients; new jets were detected in 9 patients, 8 from the commissures and 1 due to chordal rupture; in only 1 of the 11 patients did the increase in MR appear to be due to a worsening of a pre-existing jet. Angiographic MR increased by 2 grades in 3 (8%) patients; new jets appeared in all 3, arising from the commissures in 2 and from a leaflet tear in 1 case. One patient with a leaflet tear sustained an increase of 3 grades in angiographic MR. The final degree of angiographic MR was nil in 13, mild in 15, moderate in 6 and severe in 2 patients. Leaflet tears were responsible for both cases of severe MR. BMC does not appear to affect pre-existing mitral regurgitation adversely in almost all patients. It may abolish trivial jets but in most cases it creates new jets alongside the old ones. Leaflet tears are responsible for severe mitral regurgitation after BMC and this is independent of pre-existing regurgitant jets.

Blood Flow Velocity↗