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Biomedical subjects

M J Rice

Publications and source records attributed to M J Rice.

At least 19 recordsLinked to original sources

Evaluation of systolic and diastolic ventricular performance of the right ventricle in fetuses with ductal constriction using the Doppler Tei index.

Fetal ductal constriction (DC) can depress right ventricular (RV) function. However, noninvasive assessment of fetal RV function remains difficult. We evaluated RV and left ventricular (LV) performance in fetuses with DC using the Doppler-derived Tei index. The Tei index measures the ratio of total time spent in isovolumic contraction and relaxation (isovolumic time) to the ejection time. Tricuspid inflow and RV outflow Doppler traces for the derivation of RV Tei indexes and mitral inflow and LV outflow traces for LV Tei indexes were measured in 78 fetuses of pregnant women who received indomethacin and 70 normal fetuses (gestational ages ranging from 20 to 39 weeks). DC occurred in 23 fetuses, defined as pulsatility index <1.9. In fetuses with DC, the RV isovolumic time was prolonged and RV ejection time was shortened, and the RV Tei index was high compared with those in fetuses that received indomethacin without DC and normal fetuses. Also, the RV Tei index clearly separated the fetuses with DC from normal and fetuses that received indomethacin without DC (0.74 +/- 0.14 vs 0.35 +/- 0.07 and 0.37 +/- 0.06, respectively; p <0.0001). The LV Tei index was not affected by DC. Serial study in 7 fetuses with DC showed that the RV Tei index decreased from 0.69 +/- 0.12 to 0.38 +/- 0.04 (p = 0.0002) after discontinuation of indomethacin coincident with ductal relaxation, although it remained elevated in 2 cases at the time of ductal relaxation. Thus, the Tei index is a useful and sensitive indicator for detecting abnormal RV performance in fetuses with DC.

Echocardiography, Doppler↗

Interstitial duplication of the short arm of chromosome 1 in a newborn with congenital heart disease and multiple malformations.

Interstitial duplications of chromosomes 1p are rare, with only 14 cases previously reported in the literature, and those have not revealed a unique syndrome. The phenotypes include multiple congenital abnormalities and both intra- and extra-uterine growth retardation. In general, the patients do poorly and do not survive beyond the age of several months. We report a newborn male with karyotype 46, XY, inv dup(1)(qter--> p34.3::p34.3-->p32.3::34.3-->pter) with multiple congenital abnormalities including congenital heart disease and co-existing portal and pulmonary hypertension. The chromosome 1 origin of the extra material was confirmed with fluorescent in situ hybridization (FISH). Review of the GDB [Human Genome Database, 1990] reveals that the duplicated region includes the locus EDN2 that encodes endothelin-1, a potent vasoconstrictor, making genetic overdosage of this protein a likely etiology of the pulmonary hypertension. The diffuse abnormalities show effects in multiple cell lines and suggest that this region of chromosome 1p could be involved in determining cell migration and/or differentiation during organogenesis.

Abnormalities, Multiple↗

A novel serine protease inhibition motif involving a multi-centered short hydrogen bonding network at the active site.

We describe a new serine protease inhibition motif in which binding is mediated by a cluster of very short hydrogen bonds (<2.3 A) at the active site. This protease-inhibitor binding paradigm is observed at high resolution in a large set of crystal structures of trypsin, thrombin, and urokinase-type plasminogen activator (uPA) bound with a series of small molecule inhibitors (2-(2-phenol)indoles and 2-(2-phenol)benzimidazoles). In each complex there are eight enzyme-inhibitor or enzyme-water-inhibitor hydrogen bonds at the active site, three of which are very short. These short hydrogen bonds connect a triangle of oxygen atoms comprising O(gamma)(Ser195), a water molecule co-bound in the oxyanion hole (H(2)O(oxy)), and the phenolate oxygen atom of the inhibitor (O6'). Two of the other hydrogen bonds between the inhibitor and active site of the trypsin and uPA complexes become short in the thrombin counterparts, extending the three-centered short hydrogen-bonding array into a tetrahedral array of atoms (three oxygen and one nitrogen) involved in short hydrogen bonds. In the uPA complexes, the extensive hydrogen-bonding interactions at the active site prevent the inhibitor S1 amidine from forming direct hydrogen bonds with Asp189 because the S1 site is deeper in uPA than in trypsin or thrombin. Ionization equilibria at the active site associated with inhibitor binding are probed through determination and comparison of structures over a wide range of pH (3.5 to 11.4) of thrombin complexes and of trypsin complexes in three different crystal forms. The high-pH trypsin-inhibitor structures suggest that His57 is protonated at pH values as high as 9.5. The pH-dependent inhibition of trypsin, thrombin, uPA and factor Xa by 2-(2-phenol)benzimidazole analogs in which the pK(a) of the phenol group is modulated is shown to be consistent with a binding process involving ionization of both the inhibitor and the enzyme. These data further suggest that the pK(a) of His57 of each protease in the unbound state in solution is about the same, approximately 6.8. By comparing inhibition constants (K(i) values), inhibitor solubilities, inhibitor conformational energies and corresponding structures of short and normal hydrogen bond-mediated complexes, we have estimated the contribution of the short hydrogen bond networks to inhibitor affinity ( approximately 1.7 kcal/mol). The structures and K(i) values associated with the short hydrogen-bonding motif are compared with those corresponding to an alternate, Zn(2+)-mediated inhibition motif at the active site. Structural differences among apo-enzymes, enzyme-inhibitor and enzyme-inhibitor-Zn(2+) complexes are discussed in the context of affinity determinants, selectivity development, and structure-based inhibitor design.

Amino Acid Motifs↗

Effect of left ventricular wall mass on Doppler filling patterns in the developing normal human heart.

To assess gestational age- and growth-related changes in left ventricular (LV) size, LV wall, and LV transmitral flow velocity patterns, 2-dimensional (2-D) and Doppler echocardiographic studies were performed in 89 normal fetuses aged 16 to 38 weeks. Serial studies were designed in 7 fetuses. Variables measured from 4-chamber views were chamber areas and myocardial wall areas. From these measurements, area shortening fraction and ratio of myocardial wall area to end-diastolic chamber area were calculated. LV end-diastolic chamber area and myocardial wall area increased exponentially with advancing gestational age (r = 0.88 and 0.90, respectively, p < 0.001). Area shortening fraction showed no significant changes with gestational age. Ratio of myocardial wall area to LV end-diastolic chamber area decreased gradually with increasing gestational age (r = -0.77, p < 0.001). With increasing gestational age, mitral peak velocities of early diastole increased (r = 0.82, p < 0.01) with little change in peak velocity during atrial contraction. Multiple regression analysis showed that age-related increases in peak velocity of early diastole were related to advancing gestational age and also to decreases in ratio of myocardial wall area to LV end-diastolic chamber area. Low peak filling velocities during early diastole in younger fetuses may be related partly to relative increase in LV wall mass. The gestational age-related decreases in LV wall mass may be one of the important mechanisms of gestational age-related alterations in diastolic properties, especially relaxation processes.

Blood Flow Velocity↗

Clinical use of Real-time three-dimensional echocardiography in pediatric cardiology.

Real-time three-dimensional echocardiography is a technique that allows three-dimensional imaging without any geometrical assumptions or need for reconstruction from two-dimensional images. This imaging technique should be particularly useful in the pediatric population, for whom a complex cardiac anatomy must be defined. We review the potential usefulness of real-time three-dimensional imaging in the pediatric population and the potential limitations associated with this technique.

Cardiology↗

Comparison of echocardiographic acoustic quantification with off-line manual tracing for determining left ventricular volume and ejection fraction in pediatric patients.

Echocardiographic measurement of left ventricular systolic and diastolic volume and ejection fraction in pediatric patients by acoustic quantification using automated border methods compares well with measurements done by manual trace. The time necessary for completion of measurements was similar for the two methods.

Adolescent↗

Regions of 16S ribosomal RNA proximal to transfer RNA bound at the P-site of Escherichia coli ribosomes.

Unmodified uridines have been randomly replaced by 4-thiouridines in transfer RNAPhe (tRNAPhe) transcribed in a T7 RNA polymerase system. These 4-thiouridines serve as conjugation sites for attachment of the cleavage reagent 5-iodoacetamido-1,10-o-phenanthroline (IoP). In a reducing environment, when complexed with Cu2+, 1,10-o-phenanthroline causes cleavage of nearby nucleic acids. We show here that tRNA-phenanthroline (tRNA-oP) conjugates, when bound at the P-site of 70S ribosomes and 30S ribosomal subunits, caused cleavage of ribosomal RNA (rRNA) mainly in domains I and II of 16S rRNA. Some positions were cleaved only when tRNA-oP was bound to 70S ribosomes or to 30S ribosomal subunits. In domain I, most cleavage sites occurred in or near the 530 pseudoknot region. In domain II, most nucleotides cleaved were near the 690 region and the 790 region. The only positions cleaved in domain III were near the 1050 region. There were no discernible nucleotides cleaved near the 1400 (decoding) region. Our results corroborated results of others, which have shown these sites to be protected from chemical modification by tRNA binding or to be cross-linked to P-site-bound tRNA. Use of cleavage reagents tethered to tRNA provides evidence for additional regions of rRNA that may be proximal to bound tRNA.

Base Sequence↗

Diagnostic accuracy and role of intraoperative biplane transesophageal echocardiography in pediatric patients with left ventricle outflow tract lesions.

OBJECTIVES: To define the lesion-specific role of biplane transesophageal echocardiography in children with left ventricular outflow tract obstructive lesions, the diagnostic accuracy of transthoracic and transesophageal images were compared, and the impact of transesophageal echocardiography on perioperative management was evaluated. BACKGROUND: The reported high postoperative recurrence of left ventricular outflow tract obstructive lesion can be due to its incomplete surgical relief. A full preoperative definition of the lesions would aid in better surgical outcome. The complexity and spectrum of such lesions provide opportunity to evaluate the role of a recently available biplane transesophageal pediatric probe in its diagnosis and surgical management. METHODS: In 16 consecutive patients (11 male patients) with left ventricular outflow tract obstructive lesions and with a mean age of 7.9 +/- 5.7 years (range 0.25 to 20.0 years) and a mean weight of 29 +/- 19 kg (range 4 to 66 kg), the morphologic and hemodynamic findings of standard preoperative transthoracic and intraoperative biplane transesophageal echocardiography were compared with surgical and cardiac catheterization findings (in seven patients) for the diagnostic accuracy and impact on the surgical management of the lesions. RESULTS: Based on the levels of agreement, transesophageal echocardiography demonstrated higher diagnostic sensitivity (chi-squared analysis = 13.4 < 0.001) to the presence and extent of associated lesions (septal hypertrophy, multiple fibromuscular insertions, involvement of aortic and mitral valves not revealed by transthoracic imaging) and trend toward higher sensitivity (Fisher's exact p = 0.17) to primary morphologic diagnoses (abnormal chordal attachments, prolapsed aortic cusp, and tunnel-like outflow tract obstructive lesions missed by transthoracic imaging). As a result of these factors, intraoperative transesophageal imaging changed the surgical plan in 25% of the patients and modified it in an additional 25% of the patients. CONCLUSIONS: Transesophageal echocardiography can be a reliable diagnostic tool and has an important role in the surgical management of left ventricular outflow tract lesions in children.

Adolescent↗

Doppler echocardiographic evaluation of ventricular diastolic filling in fetuses with ductal constriction.

To assess ventricular diastolic filling in fetuses with constriction of ducts arterious, 43 fetuses of pregnant women receiving indomethacin (100 to 150 mg/day) were examined with Doppler echocardiography. Ductal constriction occurred in 21 fetuses, defined as maximal systolic velocity > 140 cm/s and diastolic flow velocity > 30 cm/s. The variables measured to assess diastolic function were peak velocity during early diastole (peak E wave), peak velocity during atrial contraction (peak A wave), and the velocity ratio (peak E/A ratio); these were compared to maximal ductal flow velocity during systole and diastole. The mitral peak E wave, peak A wave, and peak E/A ratio in fetuses with ductal constriction showed no significant difference from those in fetuses without ductal constriction. In fetuses with ductal constriction, the tricuspid A wave increased significantly without changes in the peak E wave (57 +/- 9 vs 50 +/- 6 cm/s, p < 0.01) and the peak E/A ratio was significantly lower than in fetuses without ductal constriction (0.57 +/- 0.10 vs 0.65 +/- 0.08, p < 0.05). In 9 fetuses with ductal constriction, we compared the Doppler tricuspid E wave, A wave, and E/A ratio during indomethacin administration with those after withdrawal of the drug for a mean of 24 hours. Both systolic and diastolic ductal flow velocities in the fetuses returned to normal range after discontinuation of indomethacin. The tricuspid peak A wave decreased (59 +/- 9 vs 50 +/- 11 cm/s) and the E/ A ratio increased significantly (0.56 +/- 0.07 vs 0.69 +/- 0.07) (both p < 0.01) without any significant change in peak E wave after discontinuation of indomethacin. This study suggests that ductal constriction influences Doppler patterns of right ventricular diastolic filling. These changes could be related to the increased afterload presented to the right ventricle which might affect diastolic function.

Anti-Inflammatory Agents, Non-Steroidal↗

Gestational age- and growth-related alterations in fetal right and left ventricular diastolic filling patterns.

To evaluate the effects of gestational age on left and right ventricular diastolic filling in human fetuses, we retrospectively reviewed the diastolic flow velocity patterns through mitral and tricuspid valves in 307 normal fetuses aged 17 to 39 weeks' gestation. The subjects were divided into 3 age groups; 17 to 24 weeks, 25 to 31 weeks, and 32 to 39 weeks. The variables measured were peak flow velocities of early diastole (peak E wave), of atrial contraction (peak A wave), and the velocity ratio (peak E/A ratio). As a whole, the transmitral peak E wave and peak E/A ratio correlated with age using a second-order polynomial curve fit. The strength of the linear correlation between age and transmitral peak E wave and peak E/A ratio and the slope of the relation were greater in the group aged 32 to 39 weeks than in group aged 25 to 31 weeks. Similar temporal change was observed in the relation between age, transtricuspid peak E wave, and peak E/A ratio. The peak A wave for both atrioventricular valves showed little change with gestational age. Contrary to the accepted concept that fetal peak E wave and peak E/A ratio increases linearly with aging, this study shows that early diastolic filling increases mainly after 25 weeks' gestation. We speculate that the maturational changes in ventricular properties in human fetuses accelerate after midgestation.

Atrial Function↗

Intravascular ultrasound assessment of regional aortic wall stiffness, distensibility, and compliance in patients with coarctation of the aorta.

BACKGROUND: Impaired aortic pulsatility has been demonstrated by angiography in children and in studies of experimental animals with coarctation of the aorta. OBJECTIVES: The purpose of this study was to assess regional aortic stiffness, distensibility, and compliance before and after balloon dilation in patients with coarctation of the aorta. METHODS AND RESULTS: Intravascular ultrasound examination was performed in 13 pediatric patients with the diagnosis of coarctation of the aorta to yield aortic diameter. Area transverse sections at both systolic and diastolic period were measured at three aortic levels: the proximal, distal, and coarctation segments. Balloon dilation was also performed in eight of 13 patients. By using pressures measured in the same areas, an aortic stiffness index (beta) was calculated as In(Ps/Pd)/(Ds-Dd), where In is natural logarithm, Ps is systolic pressure, Pd is diastolic pressure, Ds is systolic diameter, and Dd is diastolic diameter. Aortic distensibility and an estimation of aortic compliance were also calculated. The beta stiffness index of the coarctation and the proximal segments of the aorta were significantly greater than that of the distal segment of the aorta (p < 0.01). The aortic wall stiffness beta index did not acutely change after successful balloon dilation, but the distensibility and compliance of distal aorta were nonetheless significantly decreased after balloon dilation (p < 0.01, p < 0.05) as a function of changes of pulsatility of flow. CONCLUSIONS: Abnormal proximal aortic stiffness may be a strong contributing factor that promotes the genesis of hypertension in patients with coarctation even after successful repair or balloon angioplasty.

Adolescent↗

Development of systemic to pulmonary collateral arteries in premature infants.

Infants with congenital heart disease and chronic lung disease are at risk for development of systemic-to-pulmonary collateral arteries (SPCA). This study characterizes associated clinical findings in 20 premature infants without CHD who were diagnosed as having SPCA with echocardiography. SPCA can occur in premature infants without chronic lung disease and may represent a transient phenomenon.

Collateral Circulation↗

Two-dimensional echocardiographic evaluation of ventricular systolic function in human fetuses with ductal constriction.

Ventricular systolic function was assessed in fetuses, 18 with and 18 without constriction of the ductus arteriosus by serial two-dimensional and Doppler echocardiographic studies. Ductal constriction was defined as maximum systolic velocity of > 140 cm/s and diastolic flow velocity of > 30 cm/s. Ventricular end-diastolic and end-systolic areas were measured from a four-chamber view and area shortening fraction (SF) was calculated: area SF = (area in end-diastole--area in end-systole)/area in end-diastole. In fetuses with ductal constriction, right ventricular end-diastolic and end-systolic areas were significantly increased and right ventricular area SF decreased significantly compared with those values in fetuses without ductal constriction (186 +/- 48 vs. 150 +/- 30 mm2, 112 +/- 34 vs. 81 +/- 19 mm2 and 0.40 +/- 0.05 vs. 0.47 +/- 0.03, respectively, p < 0.01) without any significant changes in left ventricular area SF. Serial studies were available in eight ductal constriction fetuses before and during indomethacin administration, and after withdrawal of the drug for a mean of 24 h. Both systolic and diastolic ductal flow velocities in all fetuses returned to normal range after discontinuation of the drug. During ductal constriction during indomethacin therapy, right ventricular end-diastolic and end-systolic cavity areas were significantly larger and area SF was significantly less than those values before and after the therapy (179 +/- 38 vs. 157 +/- 30 and 154 +/- 27 mm2, 108 +/- 33 vs. 82 +/- 15 and 83 +/- 15 mm2 and 0.40 +/- 0.07 vs. 0.48 +/- 0.03 and 0.46 +/- 0.03, respectively, p < 0.01). This study suggests that ductal constriction influences right ventricular systolic performance.

Blood Flow Velocity↗

Intraoperative transesophageal echocardiography using high-resolution biplane 7.5 MHz probes with continuous-wave Doppler capability in infants and children with tetralogy of Fallot.

This study reports the role of biplane transesophageal echocardiography in monitoring surgical repairs of tetralogy of Fallot. In our patients, 3 repairs were revised based on transesophageal echocardiography and continuous-wave Doppler results, and intraoperative management was altered in 2 others.

Adolescent↗