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Biomedical subjects

K B Gupta

Publications and source records attributed to K B Gupta.

At least 37 records · Page 2Linked to original sources

Use of sonomicrometry and multidimensional scaling to determine the three-dimensional coordinates of multiple cardiac locations: feasibility and initial implementation.

We describe a new method which uses sonomicrometry and the statistical technique of multidimensional scaling (MDS) to measure the three-dimensional (3-D) coordinates of multiple cardiac locations. We refer to this new method as sonomicrometry array localization (SAL). The new method differs from standard sonomicrometry in that each piezoelectric transducer element is used as both transmitter and receiver and the set of intertransducer element distances is measured. MDS calculates the 3-D coordinates of each sonomicrometry transducer element from the set of intertransducer element distances. The feasibility of this new method was tested with mathematical simulations which demonstrated the ability of MDS to compensate for signal error and missing intertransducer element distances. We describe the design elements of a modified digitally controlled sonomicrometer in which a single transducer element can sequentially broadcast to as many as eight receiver elements. That design is used to validate SAL in a water bath and in ex vivo and living hearts. Correlation with caliper measurement in the water bath (y int. = 3.91 +/- 3.36 mm, slope = 1.04 +/- 0.05, r2 = 0.969 +/- 0.027) and with radiography in ex vivo (y int. = -0.87 +/- 0.92 mm, slope = 0.97 +/- 0.02, r2 = 0.960 +/- 0.023) and in vivo hearts (y int. = 2.98 +/- 2.59 mm, slope = 1.01 +/- 0.06, r2 = 0.953 +/- 0.031) was excellent. Sonomicrometry array localization is able to accurately measure the 3-D coordinates of multiple cardiac locations. It can potentially measure myocardial deformation and remodeling after ischemic or valvular injury.

Algorithms↗

Pulmonary thromboembolism: recent developments in diagnosis with CT and MR imaging.

Recent technical advances in computed tomography (CT; helical and electron beam) and magnetic resonance (MR) imaging have spurred a renewed interest in these modalities for the diagnosis of acute and chronic pulmonary embolism (PE). These techniques can enable accurate clot detection down to segmental pulmonary arteries, with CT currently allowing more accuracy than that with MR imaging. Ongoing technical advances, particularly in MR angiography, will likely increase diagnostic accuracy. Inability to reliably detect subsegmental acute emboli may not prove to be a clinically significant limitation if lung imaging is coupled with evaluation for deep venous thrombosis. MR imaging can potentially accomplish this within a single examination. Incorporation of CT and MR imaging into diagnostic algorithms for suspected PE can be cost-effective. Evaluation of these new modalities should be based on patient outcome, not solely on clot detectability. Well-designed clinical trials are warranted before CT and MR imaging can be used routinely in the diagnosis of acute PE.

Acute Disease↗

Regional wall motion and strain analysis across stages of Fontan reconstruction by magnetic resonance tagging.

To determine whether systolic regional wall deformation and motion, which may be used as an index of mechanical function, change with surgical intervention in patients with a functional single ventricle, a noninvasive magnetic resonance tagging technique was used to examine 33 such patients at all stages of Fontan reconstruction. The systolic motion of the intersection points was tracked to determine regional twist and radial shortening. Finite strain analysis was applied to the grid lines, and principal E1 strains were derived. The results were as follows. 1) Fontan and prebidirectional cavopulmonary anastomosis (hemiFontan) groups had the highest compressive strains, and regional heterogeneity of strain was least in the Fontan group. 2) Fontan patients had endocardial/epicardial strain different from the other surgical subgroups as well as the normal left ventricle, while the pre- and post-hemiFontan groups had basal/apical short-axis strain different from Fontan patients and normal subjects. 3) Functional single left ventricles had a different strain distribution across wall regions and surgical subgroup from functional single right ventricles. 4) Contrary to the normal human adult studied by the same method, which twists uniformly counterclockwise, 31 of 33 single ventricles, regardless of ventricular morphology or surgical subgroup, twisted counterclockwise in one region, clockwise in another, and met at a "transition zone" of no twist, which had the highest strains of all regions. 5) Radial contraction was greatest in the superior walls and least at the inferior walls of single-ventricle patients regardless of morphology. In the Fontan group, the inferior walls moved paradoxically. In conclusion, markedly different strain characteristics are noted at each stage of Fontan reconstruction, across various wall regions, and between ventricular morphological groups. Differences in regional wall motion were demonstrated in functional single ventricles throughout Fontan reconstruction regardless of morphology, and differences in associated strains and radial contraction were noted across various wall regions and surgical subgroups. These may play an important role in the energetics of the heart and the long-term viability of the single ventricle.

Child↗

Upper airway and soft tissue anatomy in normal subjects and patients with sleep-disordered breathing. Significance of the lateral pharyngeal walls.

The geometry and caliber of the upper airway in apneic patients differs from those in normal subjects. The apneic airway is smaller and is narrowed laterally. Examination of the soft tissue structures surrounding the upper airway can lead to an understanding of these apneic airway dimensional changes. Magnetic resonance imaging was utilized to study the upper airway and surrounding soft tissue structures in 21 normal subjects, 21 snorer/mild apneic subjects, and 26 patients with obstructive sleep apnea. The major findings of this investigation in the 68 subjects were as follows: (1) minimum airway area was significantly smaller in apneic compared with normal subjects and occurred in the retropalatal region; (2) airway narrowing in apneic patients was predominantly in the lateral dimension; there was no significant difference in the anterior-posterior (AP) airway dimension between subject groups; and (3) distance between the rami of the mandible was equal between subject groups, and thus the narrowing of the lateral dimension was not explained by differences in bony structure; (4) lateral airway narrowing was explained predominantly by larger pharyngeal walls in apneic patients (the parapharyngeal fat pads were not closer together as one would expect if the airway walls were compressed by fat); and (5) fat pad size at the level of the minimum airway was not greater in apneic than normal subjects. At the minimum airway area, thickness of the lateral pharyngeal muscular walls rather than enlargement of the parapharyngeal fat pads was the predominant anatomic factor causing airway narrowing in apneic subjects.

Adult↗

Epidermal growth factor (EGF) receptor carboxy-terminal domains are required for EGF-induced glucose transport in transgenic 3T3-L1 adipocytes.

Insulin-stimulated glucose transport in adipocytes is mediated by the insulin receptor. To ascertain whether a related receptor could also trigger this response, the epidermal growth factor (EGF) receptor (EGFR) was introduced into adipocytes. 3T3-L1 fibroblasts were infected by a retroviral construct encoding either the full-length (WT) or a carboxy-terminal truncated (c'973) human EGFR; truncation of the amino acids distal to 973 removes all autophosphorylation motifs. After selection and conversion to adipocytes, the level of EGFR expression was retained in infectant adipocytes (150,000 and 250,000/cell, respectively), but not in the parental 3T3-L1 adipocytes (< 5000/cell). WT and c'973 EGFR exhibited ligand-dependent tyrosine kinase activity and stimulated mitogen-activated protein kinase activity equivalently; neither phosphorylated insulin receptor substrate-1. WT EGFR, but not c'973 EGFR, underwent ligand-induced autophosphorylation. EGF did not stimulate tyrosine phosphorylation of the insulin receptor or insulin receptor substrate-1. EGF had a minimal effect on glucose transport by parental 3T3-L1 adipocytes. Glucose transport in the WT EGFR adipocytes was stimulated equivalently by insulin and EGF; exposure to insulin and EGF in combination did not result in augmented transport. Glucose transport in the c'973 EGFR adipocytes was stimulated by insulin, but not by EGF. GLUT4 was translocated to the plasma membrane to a similar extent in response to insulin or EGF in the WT EGFR adipocytes; only insulin caused a significant GLUT4 translocation in the parental or c'973 EGFR adipocytes. These data suggest that the insulin and EGF signaling pathways that lead to glucose transport converge in these adipocytes down-stream of the insulin receptor, and that activation of this pathway requires signaling motifs in the carboxy-terminus of the EGFR. This model system represents a novel approach with which to dissect signal transduction pathways in terminally differentiated adipocytes.

3T3 Cells↗

Changes in passive mechanical stiffness of myocardial tissue with aneurysm formation.

BACKGROUND: Myocardium undergoes complex cellular and histochemical alterations after acute myocardial infarction. These structural changes directly affect the mechanical stiffness of infarcted and remote myocardia. Previous investigations of infarct stiffness have been limited to uniaxial testing, which does not provide a unique description of the tissue's three-dimensional material properties. This study describes the first serial measurements of biaxial mechanical properties of sheep myocardium after anteroapical infarction. METHODS AND RESULTS: Anteroapical infarctions of 23.7 +/- 2.5% of the left ventricular mass were produced by coronary arterial ligation in sheep. Biaxial force-extension measurements were made on freshly excised squares (6.45 cm2) of remote, noninfarcted, and infarcted myocardia before and 4 hours, 1 week, 2 weeks, and 6 weeks after ligation. Adjacent myocardial samples were assayed for hydroxyproline content. Force-extension data and a derived constitutive equation were used to describe stresses and strains and material properties of each sample. In sheep, anteroapical infarctions evolve into thin left ventricular aneurysms that consist of predominantly fibrous tissue with disrupted groups of muscle cells encased in scar. In the infarct, Cauchy stresses at 15% extensions (control stresses: circumferential, sigma C, 19.4 +/- 3.3 g/cm2; longitudinal, sigma L, 54.8 +/- 34.8 g/cm2) increase within 4 hours, peak at 1 to 2 weeks (sigma C, 338.5 +/- 143.6 g/cm2; sigma L, 310.7 +/- 45.9 g/cm2), and then decrease 6 weeks after infarction (sigma C, 115 +/- 47.2 g/cm2; sigma L, 53.2 +/-28.9 g/cm2). Stresses in the remote myocardium follow a similar time course but to a lesser extent than the infarcted region. Hydroxyproline content, a measure of collagen content, does not correlate with infarct stiffness but progressively increases to 69.7 +/- 7.6 micrograms/mg after 6 weeks. Stress-extension curves demonstrate directional anisotropy of both infarcted and remote myocardia. CONCLUSIONS: The findings indicate that infarcted myocardium becomes more stiff during the first 1 to 2 weeks after anteroapical infarction and then more compliant. The infarct also exhibits directional anisotropy. These observations underscore the importance of ventricular material properties during the remodeling process after acute myocardial infarction and may partially explain the progressive left ventricular dilatation and functional deterioration that occur in some patients after anteroapical infarction.

Animals↗

Gynaecological neoplasms in postmenopausal women of Himachal Pradesh.

A controlled prospective study was conducted on 300 postmenopausal women attending the Kamla Nehru Hospital from November, 1990 to August, 1992. The incidence of gynaecological neoplasms was 31.3% in both the study group (300 postmenopausal women) and the control group (300 premenopausal women). The incidence of malignant neoplasms was 24.6% in study group and 8.6% in control group. This difference was highly significant (p < 0.001). Carcinoma cervix (16%) was the commonest gynaecological malignancy followed by ovarian cancer (6%). The incidence of benign neoplasms was lower in the study group (6.6%) as compared to the control (22.6%).

Female↗

Perinatal outcome of pregnancies complicated by threatened abortion.

One hundred and two cases of viable pregnancies with threatened abortion were studied in the department of obstetrics and gynaecology, Kamla Nehru Hospital, IG Medical College, Shimla between November 1987 and February 1989 and their perinatal outcome was evaluated. The pregnancies continued beyond 28 weeks in 61.7% of the cases. The incidence of prematurity was 19.0%. The incidence of low birth weight (LBW) babies was 23.8%. Apgar score was less than 7 in 22.3%. The incidence of neonatal complications was 25.3%. There was no perinatal mortality. In a control group of 50 cases, the incidence of prematurity and LBW was 8% and 4% respectively. Apgar score less than 7 was noted in 4% and neonatal complications were observed only in 4% of newborns.

Abortion, Threatened↗

Dynamic upper airway imaging during awake respiration in normal subjects and patients with sleep disordered breathing.

The effects of respiration on upper airway caliber were studied using cine computed tomography (CT) in 15 normal subjects, 14 snorer/mildly apneic subjects, and 13 patients with obstructive sleep apnea. All subjects were scanned in the supine position during awake nasal breathing. Eight-millimeter-thick axial slices were obtained at four anatomic levels from the nasopharynx to the retroglossal region every 0.4 s during a respiratory cycle. Tidal volume measured from an integrated pneumotachograph signal was correlated with slice acquisition during inspiration and expiration to generate loops comparing upper airway area and tidal volume. In all three subject groups and at all anatomic levels studied, there were significant dimensional changes in upper airway caliber during the respiratory cycle. The major findings in this investigation include: (1) the upper airway was significantly smaller in apneic than normal subjects, especially at the retropalatal low and retroglossal anatomic levels; in apneic patients the airway had an anterior-posterior configuration unlike the normal airway, which had a horizontal configuration with the major axis in the lateral direction; (2) in all three subject groups, little airway narrowing occurred in inspiration, suggesting that the action of the upper airway dilator muscles balanced the effects of negative intraluminal pressure.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Turnover of synthetic class A amphipathic peptide analogues of exchangeable apolipoproteins in rats. Correlation with physical properties.

Peptide analogues of the class A amphipathic helixes from exchangeable apolipoproteins mimic apolipoprotein (apo) A-I in a number of ways, including the ability to activate the enzyme lecithin:cholesterol acyltransferase, to associate with high density lipoproteins (HDLs), and to form HDL-like particles in the presence of lipids. This study investigated the metabolic properties of several of these peptide analogues in the rat. Peptide analogues studied were 18A (referred to as L-18A to differentiate it from D-18A, and which mimics apolipoprotein amphipathic helical domains in its charge distribution), 37pA (a dimer of two 18A monomers separated by a proline), 18R (with reversed charge distribution compared with 18A), and D-18A (identical in amino acid sequence to 18A but synthesized from D-amino acids). Peptides were radiolabeled with 125I. In addition, metabolism of rat and human 125I-apo A-I and human 14C-apo A-I was studied; no significant differences in clearance of these preparations were seen. Clearance data were fitted to multiexponential equations to give half-times of clearance; biexponential equations consistently provided the best nonlinear least-squares curve fit. The order of relative lipid affinity determined in vitro was 37pA greater than apo A-I greater than D-18A = L-18A greater than 18R. Half-times of clearance were in the same approximate rank order: 37pA, 6.9 +/- 3.3 hours (mean +/- SD); apo A-I, 6.9 +/- 1.8 hours; D-18A, 4.0 +/- 1.0 hours; L-18A, 4.6 +/- 1.6 hours; and 18R, 0.9 +/- 0.1 hour.(ABSTRACT TRUNCATED AT 250 WORDS)

Adsorption↗

Repair of left ventricular aneurysm. Changes in ventricular mechanics, hemodynamics, and oxygen consumption.

Anteroapical left ventricular aneurysms were produced in 23 sheep by coronary arterial ligation. Plication of the aneurysm does not change stroke volume or cardiac output and does not significantly change left ventricular oxygen consumption from the preoperative value of 5.1 +/- 2.6 ml/100 gm per minute. Plication, however, does increase left ventricular end-systolic elastance from 3.2 +/- 0.9 to 4.4 +/- 1.5 mm Hg/mm (p = 0.005). In nine of these sheep the midsagittal plane of the left ventricle was imaged by means of an array of sonomicrometry crystals before and after plication of the aneurysm. Regional wall stresses at end-systole and end-diastole and changes in diastolic function were calculated for anterior and posterior ventricular walls in the border zone adjacent to the aneurysm and in more basilar myocardium remote from the infarct. Plication significantly reduced end-systolic wall stresses and systolic stress integrals in the posterior border zone and remote myocardium, but it did not significantly change anterior wall systolic stresses or stress integrals. Plication also decreased diastolic stretching of border zone myocardium. Plication of anteroapical left ventricular aneurysm produced a shorter, more spherical ventricle and removed the dyskinetic segments but altered deformation (strain) in both circumferential and longitudinal directions. The changes in ventricular wall geometry and deformation provide an explanation for the increased ventricular end-systolic elastance and unchanged stroke volume observed after aneurysm plication.

Animals↗

Inhibition of virus-induced cell fusion by apolipoprotein A-I and its amphipathic peptide analogs.

Apolipoprotein A-I (apoA-I), the major protein component of serum high-density lipoproteins (HDL), was found to inhibit herpes simplex virus (HSV)-induced cell fusion at physiological (approximately 1 microM) concentrations, whereas HDL did not exert any inhibitory effect. Lipid-associating, synthetic amphipathic peptides corresponding to residues 1-33 (apoA-I[1-33]) or residues 66-120 (apoA-I[66-120]) of apoA-I, also inhibited HSV-induced cell fusion, whereas a peptide corresponding to residues 8-33 of apoA-I (apoA-I[8-33]), which fails to associate with lipids, did not exert any inhibitory effect. These results suggest that lipid binding may be a prerequisite for peptide-mediated fusion inhibition. Consistent with this idea, a series of lipid-binding 22-amino-acid-residue-long synthetic amphipathic peptides that correspond to the amphipathic helical domains of apoA-I (A-I consensus series), or 18-residue-long model amphipathic peptides (18A series), were found to exert variable levels of fusion-inhibitory activity. The extent of fusion-inhibitory activity did not correlate with hydrophobic moment, hydrophobicity of the nonpolar face, helix-forming ability, or lipid affinity of the different peptides. Peptides in which the nonpolar face was not interrupted by a charged residue displayed greater fusion-inhibitory activity. Also, the presence of positively charged residues at the polar-nonpolar interface was found to correlate with higher fusion-inhibitory activity.

Amino Acid Sequence↗

A study of prolonged labour.

Two hundred and three consecutive cases of prolonged labour have been retrospectively reviewed from January 1984 to December 1986. The incidence of prolonged labour was 4.39%. It was noted that 66.5% of the patients with prolonged labour were unbooked emergency admissions, and 73.3% were primipara. The causes of prolonged labour were the occipitoposterior position (10.8%), relative cephalopelvie disproportion (18.2%), uterine dysfunction (44.5%), and in 26.1% an obstructive cause was present. A spontaneous vaginal delivery occurred in 34.4%, a forceps delivery in 22.6% and the caesarean section rate was 29%. The maternal mortality, febrile and non-febrile morbidity were 9.7 per 1000 total births, 42.8% and 17.2% respectively, which showed a direct relation to the duration of labour, and a significant increase in the patients with obstructed labour, and after an abdominal delivery. The corrected perinatal mortality was 165 per 1000 total births, which was also directly related to the duration of labour, and 74.3% of the perinatal deaths occurred in the patients with obstructed labour. The perinatal mortality in the study group was nearly three times higher than the overall hospital group. Neonatal morbidity occurred in 48.8% of the newborns.

Delivery, Obstetric↗

Effect of circulatory assist devices on stunned myocardium.

We studied the effects of mechanical circulatory assist devices on left ventricular oxygen consumption, the integrals of systolic left ventricular wall stress (SSI), and end-systolic elastance (Ees) in 8 sheep after 25 minutes of global ischemia. Extracorporeal membrane oxygenation at 35 mL/kg/min, intraaortic balloon counterpulsation, and an intraaortic double-balloon pump were studied alone or in combination. Left ventricular oxygen consumption, SSI, and Ees were measured before and during mechanical circulatory assistance. Left ventricular oxygen consumption was calculated from transit-time measurements of left main coronary artery blood flow and fiberoptic measurements of coronary sinus blood oxygen saturation. Three pairs of sonomicrometry crystals placed across three orthogonal ventricular axes were used to calculate instantaneous ventricular volumes and pressure-volume loops from which the SSI data were derived. The Ees was measured using a new single-beat aortic occlusive method. Extracorporeal membrane oxygenation alone increased SSI and did not change Ees in postischemic poorly contracting hearts. Intraaortic balloon counterpulsation alone significantly reduced SSI and increased Ees. The combination of extracorporeal membrane oxygenation and either the intraaortic balloon pump or the intraaortic double-balloon pump reduced SSI, increased Ees, and reduced left ventricular oxygen consumption. In postischemic dilated, poorly contracting hearts, the combination of extracorporeal membrane oxygenation and intraaortic balloon counterpulsation has important advantages over extracorporeal membrane oxygenation alone.

Animals↗

Measurement of end-systolic pressure-volume relations by intra-aortic balloon occlusion.

A new situ technique has been developed for measuring peak end-systolic elastance, Emax, that does not alter intrinsic or reflex-stimulated cardiac contractility. Afterload is varied by the inflation of an intra-aortic balloon catheter positioned in the ascending aorta. Balloon inflation is timed to interrupt ventricular ejection transiently at different times during the ejection phase, therefore, producing contraction at different ventricular volumes. Simultaneous measurement of left ventricular pressure and aortic flow during the occlusion sequence allows pressure versus ejected volume loops to be generated, from which the end-systolic pressure-volume relation is determined. End-systolic pressure-volume relation (ESPVR) was measured in six anesthetized Dorsett sheep with normal and enhanced contractile states. ESPVR was analyzed using both linear and nonlinear techniques. Although nonlinear components were seen in ESPVR, for the pressure-volume data range produced by the transient occlusions, linear approximations of ESPVR fit the end-systolic data points well. In the normal state, Emax, the slope of the linear ESPVR, was 1.01-5.08 mm Hg/ml in animals with body weights of 23-32 kg. After epinephrine infusion, Emax increased from 3.07 +/- 1.49 to 5.79 +/- 1.97 mm Hg/ml, which is consistent with previous investigations. Linear and nonlinear volume intercepts had a small increase with positive inotropic stimulation. Furthermore, serial measurements of Emax tracked cardiac function in depressed hearts with rapidly changing contractility.

Animals↗

Changes in left ventricular systolic wall stress during biventricular circulatory assistance.

Extracorporeal membrane oxygenation (ECMO) reduces the systolic stress integral (SSI) in the normal left ventricle. We tested the hypothesis that the SSI does not decrease in poorly contracting, dilated, ejecting hearts during ECMO. In 14 sheep, four pairs of ultrasonic crystals measured changes in left ventricular (LV) wall thickness and three LV diameters. Volume calculations were validated by balloon distention of the ventricles after death (slope = 0.85; r = 0.85). SSI was measured during ECMO flows of 20 to 100 ml/kg/min in both normal and dilated, poorly contracting hearts produced by 30 minutes of warm ischemia. After warm ischemia, end-systolic elastance, an index of contractility, decreased from 8.3 +/- 0.6 mm Hg/ml to 2.9 +/- 0.4 mm Hg/ml (p = 0.001) and peak systolic pressure decreased from 47.4 +/- 0.7 mm Hg to 37.5 +/- 0.08 mm Hg (p = 0.01). In normal hearts, as ECMO flow increased, SSI decreased from 10.5 +/- 2.2 mm Hg.sec to 7.7 +/- 0.8 mm Hg.sec at 60 ml/kg/min (p = 0.001). However, in postischemic hearts, SSI progressively increased from 6.6 +/- 0.3 mm Hg.sec before ECMO to 12.4 +/- 1.8 mm Hg.sec at ECMO = 100 ml/kg/min. These studies indicate that the initial effect of ECMO on the poorly contracting, dilated heart increases LV wall stress and that the increase in stress is proportional to ECMO flow. The increase in stress is primarily due to an increase in afterload, which more than offsets decreases in systolic and diastolic volumes.

Animals↗