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Biomedical subjects

L Mahony

Publications and source records attributed to L Mahony.

At least 19 recordsLinked to original sources
PubMed2003

Impact of increasing parenteral protein loads on amino acid levels and balance in critically ill anuric patients on continuous renal replacement therapy.

OBJECTIVES: We wanted to establish optimum protein and glucose intakes during total parenteral nutrition by using a constant caloric but changing protein intake in critically ill, ventilated, anuric patients on continuous renal replacement therapy and measuring amino acid and glucose losses across the hemofilter. METHODS: Eleven consecutive, critically ill patients (eight male, age, 43.5 +/- 21.8 y; Acute Physiology and Chronic Health Evaluation II score, 20.5 +/- 7.0; Acute Physiology and Chronic Health Evaluation risk of death: 36.5% +/- 23.0 and 6 +/- 1 impaired organ systems) entered this study. Patients were fed by continuous infusion of a total parenteral mixture consisting of Synthamin (a mixture of essential and non-essential amino acids), 50% dextrose, and intralipid (long-chain triglycerides) to meet caloric requirements as predicted by Schofield's equation corrected by stress factors. The amount of protein infused was varied (1 to 2.5 g. kg(-1). d(-1)) by increments of 0.25 g. kg(-1). d(-1). Patients were stabilized on each feeding regimen for at least 24 h before paired samples of blood and dialysate were taken for amino acid and glucose measurements. Continuous renal replacement therapy was performed by using a blood pump with a blood flow of 100 to 175 mL/min. Dialysate was pumped in and out counter-currently to the blood flow at 2 L/h. A biocompatible polyacrylonitrile hemofilter was used in all cases. RESULTS: With protein intakes below 2.5 g. kg(-1). d(-1), blood levels of 14% to 57% of the measured amino acids were below the lower limits of the normal range. At 2.5 g. kg(-1). d(-1), all measured amino acids were within the normal range. Amino acid balance became more positive as protein input increased (P = 0.0001). Glucose and amino acid losses were dependent on blood concentration. Overall, 17% (range, 13% to 24%) of infused amino acids and 4% of infused glucose were lost in the dialysate. CONCLUSIONS: This study of critically ill, ventilated, anuric patients on continuous renal replacement therapy suggested that increases in protein and glucose are required to account for the increased losses across the hemofilter. A protein intake of 2.5 g. kg(-1). d(-1) appeared to optimize nitrogen balance and correct amino acid deficiencies.

Adult↗
PubMed2001

Perinatal renal ischemia resulting in hypertensive cardiomyopathy.

Three neonates presented with malignant hypertension during the first week of life; 2 of them had congestive heart failure. Although none had indwelling umbilical artery catheters, unilateral renovascular lesions were diagnosed by nuclear perfusion scans. Angiotensin-converting enzyme inhibitor therapy produced rapid recovery. Hypertension must be included in the differential diagnosis of infants presenting with congestive heart failure and acidosis. Ultrasonography is not sensitive enough to exclude renovascular lesions. We emphasize the importance of early diagnosis and treatment.

Acidosis↗
PubMed2001

Comparison of acute swelling and function in subjects with lateral ankle injury.

STUDY DESIGN: Prospective correlational study involving a convenience sample. OBJECTIVES: To investigate the relationships among figure-of-eight girth measurements and functional level in patients with acute lateral ankle sprains to determine the appropriate use of these clinical measures. BACKGROUND: Research has shown that subjective scales of perceived athletic ability and measurements of swelling are useful in assessing clinical improvement following an acute ankle sprain; however, the relationship between ankle swelling and level of function is not known. METHODS AND MEASURES: Twenty-nine subjects (20 men, 9 women) varying in age from 18-59 years of age (mean age, 30.8 +/- 11.37) with acute lateral ankle sprains were included in this study. Each subject was evaluated by 1 of 3 raters for ankle girth, weight-bearing status, and functional level as determined by a modified Ankle Osteoarthritis Scale (AOS) and the Foot and Ankle Ability Index (FAAI). This study also investigated the relationship between these measures and the sport subscale of the FAAI (FAAI sport). This is an 8-item subscale which includes questions on running, jumping, landing, quick starts and stops, cutting or lateral movements, low impact activities, ability to perform an activity with normal technique, and ability to participate in desired sports. RESULTS: No significant correlations were found between figure-of-eight girth measurements and functional level. However, we did find moderate to good correlations between the FAAI vs. weight-bearing (rho = 0.73), FAAI vs. AOS (rho = -0.79), FAAI sport vs. weight-bearing (rho = 0.68), FAAI vs. FAAI Sport (rho = 0.73), weight-bearing vs. AOS (rho = -0.57), and FAAI Sport vs. AOS (rho = -0.50). CONCLUSIONS: The figure-of-eight method is highly reliable and is appropriate for measuring ankle swelling; however, it does not correlate with functional level as determined by the modified AOS, FAAI, or observed weight-bearing status during gait. Therefore, clinicians should refrain from making assumptions about function based on ankle swelling.

Activities of Daily Living↗
PubMed1999

Is captopril useful in decreasing pleural drainage in children after modified Fontan operation?

We performed a retrospective cohort study to assess the relation between administration of angiotensin-converting enzyme inhibitors and duration of pleural drainage in the early postoperative period in patients who underwent a modified Fontan operation at our institution from 1990 through 1996. This study failed to show that administration of captopril decreased the duration of pleural drainage in patients after a modified Fontan operation.

Adolescent↗
PubMed1998

Usefulness of Doppler echocardiography in diagnosing right ventricular coronary arterial communications in patients with pulmonary atresia and intact ventricular septum and comparison with angiography.

Direct and indirect evidence of right ventricular coronary arterial communications has been detected by use of 2-dimensional and Doppler echocardiography in patients with pulmonary atresia and intact ventricular septum. We describe additional consistent and reproducible Doppler echocardiographic findings that were useful for identifying patients in whom abnormal coronary arterial flow patterns were detected angiographically.

Coronary Angiography↗
PubMed1997

Enalapril does not enhance exercise capacity in patients after Fontan procedure.

BACKGROUND: Angiotensin-converting enzyme inhibitors improve exercise capacity in adults with congestive heart failure by decreasing systemic vascular resistance and improving ventricular diastolic function. Patients who have undergone the Fontan procedure have decreased cardiac output, increased systemic vascular resistance, abnormal diastolic function, and decreased exercise capacity compared with normal people. METHODS AND RESULTS: To test the hypothesis that afterload reduction therapy alters hemodynamic variables and augments exercise capacity in patients after a Fontan procedure, we compared the results of graded exercise with maximal effort from 18 subjects (14.5+/-6.2 years of age, 4 to 19 years after Fontan procedure) in a randomized, double-blind, placebo-controlled crossover trial using enalapril (0.2 to 0.3 mg x kg[-1] x d[-1], maximum 15 mg). Each treatment was administered for 10 weeks. Diastolic filling patterns at rest were assessed by Doppler determination of the systemic atrioventricular valve flow velocity at the conclusion of each therapy. No difference was detected in resting heart rate, blood pressure, or cardiac index. Diastolic filling patterns were also similar. Exercise duration was not different (6.4+/-2.6 [enalapril] versus 6.7+/-2.6 minutes [placebo]). The mean percent increase in cardiac index from rest to maximum exercise was slightly but significantly decreased in subjects after 10 weeks of enalapril therapy (102+/-34% [enalapril] versus 125+/-34% [placebo]; P<.02). At maximal exercise, cardiac index (3.5+/-0.9 [enalapril] versus 3.8+/-0.9 L x min[-1] x m2 [placebo]), oxygen consumption (18.3+/-9 [enalapril] versus 20.5+/-7 mL x min[-1] x kg[-1] [placebo]), minute ventilation (57.5+/-17 [enalapril] versus 55.4+/-19 L/min [placebo]), and total work (247+/-181 [enalapril] versus 261+/-197 W [placebo]) were not different. CONCLUSIONS: We conclude that enalapril administration for 10 weeks does not alter abnormal systemic vascular resistance, resting cardiac index, diastolic function, or exercise capacity in patients who have undergone a Fontan procedure.

Adolescent↗
PubMed1996

Calcium homeostasis and control of contractility in the developing heart.

The Ca2+ concentration within the myocyte is an important determinant of myocardial contractility. Substantial changes in the cellular processes responsible for transport of Ca2+ ions across the sarcolemmal and sarcoplasmic reticulum membranes occur during maturation of the heart. In this article, the mechanisms underlying these changes and their impact on myocardial performance are discussed in detail.

Animals↗
PubMed1993

Cardiac contractile and calcium transport function after burn injury in adult and aged guinea pigs.

Cardiac dysfunction occurs after a major burn injury regardless of age; whether burn trauma causes greater myocardial contractile depression in the older subject due to reduced cardiac reserves that normally occur with adult aging is not known. The cellular basis for burn-induced cardiac dysfunction is not known, but several studies have suggested that alterations occur in the rate of Ca2+ delivery to the contractile proteins as well as in the rate of Ca2+ removal from the sarcoplasm by the sarcoplasmic reticulum (SR). To determine if age-related differences in the cardiac contractile response to burn injury are associated with differences in SR Ca2+ transport, an isolated heart preparation was used to examine mechanical function, and myocardial homogenate preparations were used to assess SR Ca2+ transport. Guinea pigs from both age groups (adult, 6-8 months, and senescent, 34-36 months of age) were divided into two subgroups--control and 45% cutaneous scald burn. Cardiac dysfunction associated with adult aging alone was indicated by lower systolic pressure and lower rates of left ventricular (LV) pressure rise and fall, as well as decreased responses to isoproterenol, exogenous Ca2+, increased coronary flow rate, and electrical pacing. Myocardial depression in senescent control hearts was accompanied by a decreased maximal Ca2+ uptake in myocardial homogenates, suggesting that altered SR calcium transport may contribute to the diminished contractile function associated with aging. Burn injury impaired cardiac function in all animals regardless of age as evidenced by a leftward shift of LV function curves and altered responses to receptor- and nonreceptor-mediated inotropic interventions. However, the percentage change in cardiac function after burn injury was similar in both age groups compared to those of their respective controls. Significant alterations in SR Ca2+ transport were observed in myocardial homogenates isolated from both adult and senescent hearts after burn injury. Our data confirm that burn injury induced cardiac contractile dysfunction as well as alterations in SR Ca2+ transport function regardless of age, and we conclude that altered SR Ca2+ transport function contributes, in part, to the diminished cardiac function after burn injury.

Aging↗
PubMed1992

Oxygen desaturation during sleep in infants and young children with congenital heart disease.

Oxygen saturation (SaO2) during sleep and pulmonary functions were evaluated in 19 infants with congenital heart disease, aged 6 +/- 4 months, and in 11 normal infants, aged 8 +/- 5 months, to determine whether infants with congenital heart disease have more frequent oxygen desaturation during sleep and, if so, its relationship to underlying pulmonary function. Infants with congenital heart disease were classified as acyanotic (n = 11) or cyanotic (n = 8) on the basis of their aortic SaO2 at the time of cardiac catheterization (greater or less than 90% SaO2). Pulmonary function tests included respiratory rate, functional residual capacity, total respiratory system compliance, and maximal flows at functional residual capacity. Significant differences were found in the values for the lowest SaO2 of each 5-minute epoch (SaO2L) averaged during the entire sleep time (normal 94% +/- 2%, acyanotic 90% +/- 3%, and cyanotic 74% +/- 4%; p less than 0.01). The three groups also differed significantly in frequency distributions of percentage of total sleep time with SaO2L less than 90% (SaO2%T) (normal 10% +/- 17%, acyanotic 36% +/- 34%, and cyanotic 97% +/- 4%; p less than 0.05). Compared with the control group, the acyanotic group had a higher respiratory rate (66 +/- 19 breaths/min vs 35 +/- 6 breaths/min; p less than 0.01), a lower tidal volume (65% +/- 29% predicted vs 105% +/- 18% predicted; p less than 0.01), and a lower total respiratory compliance (59% +/- 18% predicted vs 106% +/- 30% predicted; p less than 0.01). A negative correlation existed between SaO2%T and aortic SaO2 (R2 = 0.64; p less than 0.01). We conclude that oxygen desaturation occurs during sleep in infants with congenital heart disease; the presence of desaturation appears to be related to the initial degree of hypoxemia and the presence of abnormal pulmonary function.

Cyanosis↗
PubMed1990

Age-related changes in myocardial relaxation and sarcoplasmic reticulum function.

Rapid regulation of relaxation is essential to allow the heart to alter stroke volume in response to stress. Inasmuch as Ca2+ transport by the sarcoplasmic reticulum (SR) is an important determinant of relaxation, the purpose of this study was to examine developmental differences in the ability of isoproterenol to alter relaxation time and to determine if these differences were associated with age-related changes in Ca2+ transport by the SR in isolated, perfused adult and newborn guinea pig hearts. Control values of the time constant of isovolumic relaxation (tau) were 37.8 +/- 5.9 ms in adult hearts (n = 8) and 31.6 +/- 5.3 ms in newborn hearts (n = 6). With maximum isoproterenol stimulation, the decrease in tau was significantly greater in adult (51.1 +/- 8.8%, mean +/- SD) compared with that in newborn (26.3 +/- 3.1%, P less than or equal to 0.0001) hearts. Ca2+ uptake, Ca2(+)-dependent adenosinetriphosphatase activity, and Ca2+ pump density were all significantly greater in SR vesicles isolated from adult hearts compared with values measured in SR vesicles from newborn hearts. We conclude that developmental differences in the capacity of the SR to sequester Ca2+ may contribute to age-related differences in the functional response of the heart to isoproterenol.

Aging↗
PubMed1989

Analysis of the binding sites for the cardiotonic phosphodiesterase inhibitor [3H]LY186126 in ventricular myocardium.

The positive inotropic action of the newer cardiotonic phosphodiesterase inhibitors such as indolidan, milrinone, and imazodan has been previously attributed to selective inhibition of cGMP-inhibitable Type IV (high affinity) cAMP phosphodiesterase activity. However, the subcellular binding site(s) for this class of compounds has not been defined. We have characterized the binding of [3H]LY186126, an analogue of indolidan, in subcellular fractions prepared from rabbit and sheep ventricular myocardium. Binding required magnesium ion and exhibited rapid association and dissociation kinetics. Specific binding (defined by ligand displacement with 5 microM indolidan) to enriched rabbit sarcoplasmic reticulum (SR) membrane vesicles was saturable (Bmax = 714 +/- 77 fmol/mg of protein) and of high affinity (Kd = 6.2 +/- 1.4 nM). Linear and nonlinear analyses of the binding isotherms fit a single-site model. Mixed SR preparations from sheep myocardium exhibited binding characteristics (Bmax = 944 +/- 115 fmol/mg; Kd = 8.5 +/- 2.3 nM) comparable to those of rabbit cardiac SR. Further subfractionation of sheep SR indicated that the binding sites were equally distributed between free (Bmax = 630 fmol/mg; Kd = 4.4 nM) and junctional SR (Bmax = 569 fmol/mg; Kd = 10.9 nM). Specific binding of [3H]LY186126 was also demonstrated in the cytosolic subfraction of rabbit myocardium that contained Type IV phosphodiesterase activity (Peak III from anion exchange chromatography). Competition for [3H] LY186126 binding studied in rabbit SR showed that, of the compounds tested, lixazinone (RS 82856) competed most effectively (IC50 = 0.030 +/- 0.008 nM), followed by indolidan (0.14 +/- 0.05 nM), cGMP (17.8 +/- 2.6 nM), milrinone (39.3 +/- 13.2 nM), and imazodan (192 +/- 73 nM). In contrast, rolipram, which does not inhibit SR-associated Type IV phosphodiesterase activity, was not effective at competing for [3H]LY186126 binding (IC50 greater than 30 microM). These results indicate that [3H]LY186126 has specific binding sites in myocardial subcellular fractions that contain cGMP-inhibitable Type IV (high affinity) cAMP phosphodiesterase activity.

Animals↗
PubMed1988

Maturation of calcium transport in cardiac sarcoplasmic reticulum.

Developmental changes in myocardial function have been described by a number of investigators. To further define the cellular basis for these changes, the present study was designed to characterize age-related changes in Ca2+ transport in sarcoplasmic reticulum (SR) vesicles isolated from six groups of sheep: group (Sp) I (100-105 days gestation), Gp II (128-132 days gestation), Gp III (postnatal, 0-3 days), Gp IV (4 wk), Gp V (8 wk), and Gp VI (maternal sheep). The maximal Ca2+ uptake for vesicles isolated from Gp I-V was significantly (p less than 0.01) decreased as compared to that measured for Gp VI (maternal) vesicles. However, Ca2+-dependent ATP hydrolysis was decreased only in the fetal SR vesicles (Gp I-II). Thus, decreased ATP hydrolysis only partially explained the decreased Ca2+ uptake. In contrast, calculation of apparent Ca2+ pump coupling ratios (mol of Ca2+ transported/mol of ATP hydrolyzed) showed that there was a marked increase in the coupling of Ca2+ transport to ATP hydrolysis during maturation of the heart. Inasmuch as the contractile state of the heart depends on precise regulation of Ca2+ concentration by the SR, these age-related changes in SR function may contribute to developmental changes in myocardial function.

Adenosine Triphosphate↗
PubMed1987

Preoperative two-dimensional echocardiographic prediction of prosthetic aortic and mitral valve size in children.

Preoperative two-dimensional echocardiograms (2D-ECHOs) were done on 18 patients to determine the accuracy of assessing the mitral and aortic anulus diameter in children undergoing valve replacement. Fourteen patients underwent primary valve replacement and four underwent repeat valve replacement. The mean age was 11.5 years (range 2 to 17 years). The 2D-ECHO measured mitral or aortic valve anulus was compared with the external diameter of the largest prosthetic valve that could be inserted. There was a strong correlation (r = 0.99, p less than 0.001, SEE = 1.0 mm) between the 2D-ECHO measurements and the prosthetic valve size in patients undergoing primary valve replacement, but the correlation (r = 0.16, p = NS) was poor for those undergoing repeat valve replacement. In conclusion, 2D-ECHO prediction of prosthetic mitral and aortic valve size is accurate in children undergoing primary valve replacement but is poor in those undergoing repeat valve replacement.

Adolescent↗
PubMed1986

Developmental changes in cardiac sarcoplasmic reticulum in sheep.

Physiologic studies suggest that the myocardium from fetal and newborn sheep functions at a higher contractile state with decreased contractile reserve when compared to the myocardium of adult sheep. To investigate the role of Ca2+ transport by the sarcoplasmic reticulum (SR) in this phenomenon, we studied functional properties and protein composition of cardiac SR vesicles isolated from fetal and maternal sheep. Active accumulation of Ca2+ and the density of the Ca2+ pump protein were decreased 60% (p less than 0.01) in fetal SR vesicles; however Ca2+-dependent ATPase activity was decreased only 30% (p less than 0.01). This decreased difference in Ca2+-dependent ATPase activities was accounted for by the higher turnover number measured for the Ca2+ pump of fetal SR vesicles (1.6-fold increased, p less than 0.01). Ryanodine, an alkaloid which blocks Ca2+ efflux from cardiac SR vesicles, stimulated Ca2+ uptake more effectively in fetal SR vesicles, suggesting that these vesicles had a higher passive Ca2+ permeability during conditions of active Ca2+ transport. Protein compositional studies showed that the content of phospholamban was decreased in fetal SR vesicles and was correlated with the decrease in the density of Ca2+ pumps. In contrast, the content of calsequestrin and the density of [3H]nitrendipine-binding sites were increased approximately 2-fold in fetal SR vesicles. These functional and compositional differences between SR vesicles isolated from fetal and maternal sheep may indicate that there is relatively more junctional SR in fetal hearts. Since the SR regulates muscle contraction by modulating intracellular Ca2+ concentration, it is possible that developmental alterations in cardiac SR may contribute to the decreased myocardial contractile reserve noted in fetal sheep.

Animals↗
PubMed1986

Role of radionuclide shunt studies in management of infants and children.

The utility of radionuclide-shunt quantitation in children was assessed by examination of the outcome of 128 patients who underwent shunt study over a two-year period. The possibility of cardiac catheterization was eliminated in 87. Fifty of these had undergone previous cardiac catheterizations, which suggested the necessity for further invasive study or surgery; after radionuclide evaluation, 28 were shown to have had enough spontaneous closure of the defect to cancel planned surgery, 12 were scheduled for surgery without repeat catheterization, and ten had nuclear rather than catheterization estimates of residual shunting following surgical repair of septal defects. Thus, radionuclide shunt study provides a relatively noninvasive technique to quantitate left-to-right shunts, supplementing or supplanting cardiac catheterization in the management of infants and children with such lesions.

Adolescent↗