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Biomedical subjects

C F Anderson

Publications and source records attributed to C F Anderson.

At least 55 records · Page 3Linked to original sources

Changes in umbilical arterial and venous blood flow velocity waveforms during late decelerations of the fetal heart rate.

OBJECTIVE: To compare umbilical arterial and venous Doppler velocity waveforms during labor in fetuses with normal heart rate tracings and fetuses with late decelerations. METHODS: During labor, umbilical arterial and venous Doppler flow velocity waveforms were obtained between and during contractions in 20 fetuses (ten with normal heart rate tracings and ten with late decelerations). The umbilical arterial systolic-diastolic (S/D) velocity ratios were compared, and umbilical venous velocities were examined for the presence or absence of venous pulsations. RESULTS: Fetuses with late decelerations had a significant increase in the umbilical arterial S/D ratio between contractions compared to normal fetuses (2.43 +/- 0.74 versus 1.56 +/- 0.27, P = .003). There was no significant difference in S/D ratios obtained between contractions compared with those obtained during contractions in either the normal or late deceleration group. Umbilical venous pulsations were significantly more common (90 versus 0%, P < .00001) during contractions in fetuses with late decelerations; umbilical venous pulsations were not seen in these fetuses between contractions and were not present at any time in fetuses with normal heart rate tracings. CONCLUSIONS: Increased umbilical arterial velocity ratios and the presence of umbilical venous pulsations during contractions in fetuses with late decelerations suggest that the cardiovascular pathophysiology of late decelerations involves changes in placental resistance as well as cardiac performance. The presence of umbilical venous pulsations during late decelerations is consistent with the hypoxic fetal cardiovascular changes (hypertension and myocardial depression) previously reported from animal studies.

Apgar Score↗

Hyperlipoproteinemia in adults with renal disease.

Hyperlipoproteinemia is common in patients with renal disease, but increased lipids are only one of several risk factors frequently identified for coronary artery disease. Before treatment options are instituted, renal disease status, current medications, and possible interactions between drugs must be considered. Hypertriglyceridemia is common in patients with renal failure; therapeutic options are influenced by the levels of serum triglycerides and high-density lipoprotein cholesterol. If nonsteroidal drugs improve renal function and decrease proteinuria in patients with renal disease, hyperlipidemia frequently abates. Interactions between drugs are important considerations when lipid-lowering drug treatment is prescribed in recipients of renal transplants.

Adult↗

Weight change and serum lipoproteins in recipients of renal allografts.

Hyperlipoproteinemia is common in recipients of renal allografts. In this study, serum lipids and some possible contributing factors--weight gain, weight relative to ideal body weight, daily dose of prednisone, serum creatinine, 24-hour urinary protein, and diabetes mellitus--were assessed in 100 patients. At the end of the first year after transplantation, 57 of the 100 patients had total serum cholesterol concentrations of 240 mg/dl or more--40 of 75 patients without diabetes and 17 of 25 with diabetes. The mean values for weight gain (11.2 kg) and actual weight relative to ideal body weight (19.4 kg) were significantly greater (P = 0.029 and P = 0.01, respectively) in the subgroup of patients without diabetes who had total serum cholesterol values of 240 mg/dl or more at 1 year after transplantation than in those with values of less than 240 mg/dl. The daily dose of prednisone and the serum creatinine levels were similar in these two subgroups. The 24-hour urinary protein measurements were greater at 1 month than at 1 year in both patients with and those without diabetes. Perhaps the initial dietary advice for patients who have undergone renal transplantation should emphasize control of total caloric intake; subsequently, intake of cholesterol and fat can be modified in those patients who have persistent hyperlipoproteinemia.

Adult↗

Relative affinities of divalent polyamines and of their N-methylated analogues for helical DNA determined by 23Na NMR.

Interactions of divalent polyamines with double-helical DNA in aqueous solution are investigated by monitoring the decrease in 23Na NMR relaxation rates as NaDNA is titrated with H3N(+)-(CH2)m-+NH3, where m = 3, 4, 5, or 6. Analogous measurements are made for the same homologous series of methylated polyamines (methonium ions). The dependence of the 23Na relaxation rates on the amount of added divalent cation (M2+) is analyzed quantitatively in terms of a two-state model. The sodium ions are assumed to be in rapid exchange between a "bound" state, where they are close enough to DNA so that it affects their relaxation rate, and a "free" state in bulk solution, where their relaxation rate is the same as in solutions containing no DNA. The distribution of Na+ and M2+ between these states is described quantitatively in terms of an ion-exchange parameter: DM = (pMB)(1-pNaB)n/(pNaB)n(1-pMB), where pNaB and pMB are the fractions of Na+ and M2+ that are close enough to DNA to be considered bound (by the NMR criterion), and n is the number of sodium ions displaced from DNA by the binding of one M2+ ion. For each of the polyamines and methonium ions investigated here, equations derived from this two-state model yield acceptable fittings of the titration curves if roNa, the number of sodium ions bound per DNA phosphate when no competing cations are present, is assigned a value between 0.6 and 1.00. Within this range, changing the value assigned to roNa does change the best-fitted values of DM determined for these polyamines (DH) and for the methonium ions (DMe) but does not alter the following conclusions about the trends in these parameters. (1) For polyamines and methonium ions of the same m, DH exceeds DMe by factors that are significantly larger for m = 3 and 4 than for m = 5 and 6. (2) DH for m = 3 and 4 is larger than DH for m = 5 and 6. (3) DMe for m = 3 and 4 is smaller than DMe for m = 5 and 6.

Bis-Trimethylammonium Compounds↗

Importance of oligoelectrolyte end effects for the thermodynamics of conformational transitions of nucleic acid oligomers: a grand canonical Monte Carlo analysis.

Effects of salt concentration on the stabilities of oligonucleotide helices are analyzed directly in terms of delta gamma N----yN identical to gamma denyN - gamma natN, the difference in the salt-nucleotide phosphate preferential interaction coefficients for the denatured state, having yN phosphate charges, and for the native state, having N phosphate charges (y = 1 for hairpin denaturation and y = 0.5 for dimer denaturation). Previous experimental studies of the denaturation of hairpin oligonucleotides (having 18 less than N less than 44) indicate significant differences between delta gamma N----N and delta gamma infinity, the value determined for the denaturation of the corresponding polynucleotide. These differences are thermodynamic manifestations of the oligoelectrolyte end effect. In contrast, the available data on the denaturation of oligonucleotide dimer helices (N less than or equal to 22) imply that differences between delta gamma infinity and delta gamma N----0.5N, and hence oligoelectrolyte end effects, are small or negligible. To determine the origin of these apparently conflicting implications concerning the importance of oligoelectrolyte end effects, we have calculated the N dependence of gamma N from grand canonical Monte Carlo simulations for an idealized model of the structure and charge distribution of each oligomer conformation. Our calculations are in quantitative agreement with the experimental finding for d(TA) hairpin oligomers that -delta gamma N----N decreases linearly as N-1 increases, and with the extant experimental determinations of delta gamma N----0.5N. These results provide an illustration of how the large electrostatic end effects exhibited by the hairpin denaturation data are masked when delta gamma infinity is compared with values of delta gamma N----0.5N for short dimer helices (N less than or equal to 22). For 0.5N greater than 24, -delta gamma N----0.5N is predicted to be a linear function of N-1 whose slope has the opposite sign from, and is more salt-concentration dependent than, the corresponding slope of -delta gamma N----N as a function of N-1. Our calculations also yield predictions about the N dependences of the individual values of gamma N that can be tested by determining Donnan coefficients from membrane dialysis equilibrium experiments. For long enough hairpin and dimer oligonucleotides (yN greater than or equal to 24), in either native or denatured forms, we predict that the (positive) difference gamma infinity - gamma N increases linearly with increasing N-1. For smaller values of N the difference gamma infinity - gamma N continues to increase with increasing N-1.

Base Sequence↗

Doppler flow velocities in single umbilical arteries.

Fetal compromise has been associated with an umbilical artery waveform pattern of low or absent diastolic velocity relative to systolic velocity. Fetuses with single umbilical arteries have an increased risk of major malformations, mortality, retarded fetal growth, and prematurity. In this study Doppler flow velocities were obtained in 13 fetuses (four twin fetuses and nine singletons) with a single umbilical artery. Five (38%) fetuses, consisting of four singletons and one twin, had anomalies. Six (46%) fetuses were small for gestational age, including two twin fetuses and three singleton fetuses with anomalies. Three (23%) of the 13 systolic-to-diastolic velocity ratios were abnormally high. Whereas this is a higher rate of abnormal ratios than the reported 2% to 3% in control populations, it is interesting to note that 77% of fetuses with single umbilical arteries had normal systolic-to-diastolic ratios.

Abnormalities, Multiple↗

Significance of oligohydramnios complicating pregnancy.

Oligohydramnios is a serious complication of pregnancy that is associated with a poor perinatal outcome. Eighty pregnancies complicated by oligohydramnios constitute the basis for this retrospective study. Forty patients had premature rupture of the membranes; of these, outcomes were good in 25. Twelve of 14 fetuses with oligohydramnios and intrauterine growth retardation survived. None of the nine fetuses with severe renal anomalies lived. None of the twins with twin-twin transfusion and oligohydramnios survived. Six pregnancies with oligohydramnios and premature separation of the placenta were identified; all of these resulted in fetal or neonatal death during the second trimester.

Blood Flow Velocity↗

Doppler studies of vena cava flows in human fetuses. Insights into normal and abnormal cardiac physiology.

We examined vena cava Doppler flow velocity tracings from 69 fetuses between 22 and 40 weeks' gestation. Twenty-three fetuses had arrhythmias. Fifteen fetuses had absent end-diastolic Doppler velocities in the umbilical artery, a condition associated with intrauterine growth retardation, and 15 normal fetuses with normal umbilical artery Doppler velocity ratios were matched by gestational age. In studies in 16 additional fetuses, inferior vena cava Doppler velocity waveforms were compared with superior vena cava Doppler velocity waveforms. Peak velocities and time-velocity integrals of forward or reverse flow during systole, early diastole, and atrial contraction were measured. In addition, the time-velocity integral during flow coincident with atrial contraction (a wave) was expressed as a percent of the time-velocity integral of total forward flow during both systole and early diastole. Systolic-to-diastolic ratios of inferior vena cava forward time-velocity integrals were not significantly different from systolic-to-diastolic ratios of superior vena cava forward time-velocity integrals (p = 0.86), but the percent of blood moving in a reverse direction during atrial contraction in the inferior vena cava was greater than the percent of blood moving in a reverse direction in the superior vena cava (p less than 0.05). Relative forward flow in early diastole in the group of normal fetuses increased with advancing gestational age (r = 0.60, p less than 0.05). During premature atrial contractions flow in the inferior vena cava was reversed, and the percent of reverse flow during atrial systole increased significantly from 4.5 +/- 0.3% to 28.3 +/- 3.7% (mean +/- SEM, p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Arrhythmias, Cardiac↗

On the cooperative binding of large ligands to a one-dimensional homogeneous lattice: the generalized three-state lattice model.

We present the general secular equation for three-state lattice models for the cooperative binding of large ligands to a one-dimensional lattice. In addition, a closed-form expression for the isotherm is also obtained, that can be used with all values of the cooperativity parameter omega(0 less than omega less than infinity) thus eliminating the need for multiple equations.

Chemical Phenomena↗

Fetal pericardial effusion.

Forty-four fetuses with pericardial effusions have been identified by ultrasonographic examinations. The clinical histories and courses of these patients were reviewed. At least eight different clinical features accompanied and were probably responsible for the pericardial effusions. The most common cause of a fetal pericardial effusion was heart failure (13 fetuses). Fetal renal cystic dysplasia with oligohydramnios and other anomalies was present in six fetuses. Four of this group had microscopic evidence of pericarditis on postmortem examination. Fetal pericardial effusions are always a manifestation of another disease process often presenting as fetal hydrops. Some pericardial effusions are transient. The etiologic origin of fetal pericardial effusions differs from that in the child or adult.

Female↗

Human fetal tricuspid and mitral deceleration time: changes with normal pregnancy and intrauterine growth retardation.

Studies in instrumented adults have shown an association between Doppler echocardiography-derived atrioventricular valve deceleration times and ventricular function. To determine how gestational age affects deceleration time in the tricuspid and mitral valve, pulsed Doppler ultrasonographic examinations were performed in 54 normal human fetuses. In addition, 26 fetuses with growth retardation and the absence of end-diastolic Doppler velocities in the umbilical artery were examined. Measurements were obtained from strip chart recordings; between three and five beats were used to obtain an average heart rate, ratio of peak velocity at atrial contraction to peak velocity in early diastole, and deceleration time in early diastole. Deceleration times increased during gestation from 86 +/- 27 to 116 +/- 18 msec in the tricuspid valve and from 98 +/- 25 to 132 +/- 21 msec in the mitral valve. Fetuses with growth retardation and the absence of end-diastolic Doppler velocities in the umbilical artery had longer deceleration times than those of normal fetuses (p less than 0.01). The increase in deceleration time across both atrioventricular valves in normal fetuses may be related to heart rate, an increased rate of ventricular relaxation, or an increase in ventricular compliance. The fetuses with intrauterine growth retardation and the absence of end-diastolic velocities in the umbilical artery have abnormally increased deceleration times; in the abnormal fetus this may be a result of impaired ventricular relaxation or decreased ventricular compliance.

Blood Flow Velocity↗

Monte Carlo description of oligoelectrolyte properties of DNA oligomers: range of the end effect and the approach of molecular and thermodynamic properties to the polyelectrolyte limits.

Applications of the grand canonical Monte Carlo method demonstrate the importance of end effects on fundamental molecular and thermodynamic properties of oligoelectrolyte solutions. Simulations are carried out for a series of solutions containing double-helical DNA oligomers of varying numbers of phosphate charges N (8 less than or equal to N less than or equal to 100) and univalent electrolyte at fixed activity (a +/- = 1.76 mmol/dm3). These results are used to evaluate as follows: C+N(a), the local concentration of cations at various axial positions along the oligomer surface; C+N(a), the axial average of these concentrations; TN, the preferential interaction coefficient expressed per oligomer charge, which is directly related to the fractional thermodynamic extent of association of counterions. A sufficiently long oligomer (N greater than or equal to 48 under the conditions simulated) is characterized by an interior region over which C+N(a) is uniform and equal to C+ infinity (a), the polyion limit. This interior region is flanked by two symmetric terminal regions, in which C+N(a) varies linearly with axial position from the end of the oligomer to a distance approximately 18 monomer units (approximately 3.1 nm) from that end. For long oligomers, the characteristics of the terminal regions [length and axial profile of C+N(a)] do not vary with N and, by inference, also pertain to the polyion under the same conditions. Both C+N(a) and TN approach their polyelectrolyte limits as linear functions of 1/N. These linear dependences can be attributed to the increasing predominance of the contribution due to the polyion-like interior of the oligomer as N increases.

DNA↗

Interaction of an N-methylated polyamine analogue, hexamethonium(2+), with NaDNA: quantitative 14N and 23Na NMR relaxation rate studies of the cation-exchange process.

The interactions of the divalent hexamethonium (Hex2+) cation with double-helical calf thymus DNA are investigated by means of 14N NMR and, indirectly, by means of 23Na NMR. During a titration of NaDNA with HexBr2, the displacement of Na+ from DNA by Hex2+ is monitored by concurrent measurements of the Lorentzian 14N signals and the bi-Lorentzian 23Na signals. The variations in the quadrupolar relaxation rates of 14N and 23Na are analyzed according to a simple two-state model for the competition between Hex2+ and Na+ associated with DNA. From this analysis parameters characterizing the exchange process are evaluated, and the following conclusions are drawn: (1) The association of one Hex2+ displaces 1.7-2.0 sodium ions from the vicinity of the DNA. (2) Cation accumulation near DNA neutralizes approximately half of the phosphate charge at all points in the titration. (3) The exchange coefficient characterizing the displacement of Na+ by Hex2+ is of the same order of magnitude as the exchange coefficients determined by NMR for other divalent cations such as Mg2+ and putrescine. These findings imply that the interaction of Hex2+ with DNA is primarily electrostatic in character. The transverse and longitudinal relaxation rates observed for 14N are analyzed under the assumption that the quadrupolar relaxation processes of 14N in Hex2+ associated with DNA can be characterized by a single-exponential correlation function with correlation time tau NB. The resulting value of tau NB, 7.8 +/- 0.8 ns, is 3 orders of magnitude greater than that estimated for Hex2+ in the absence of DNA and is only 3-4 times greater than correlation times reported for 23Na and other quadrupolar cations near DNA. These comparisons indicate that the observed enhancements in the relaxation rates of 14N are due mainly to slowing of the motions that modulate its quadrupolar interactions in Hex2+ near DNA. The magnitudes of tau NB and of the quadrupolar coupling constant of Hex2+ associated with DNA are consistent with the conclusion that this association is primarily electrostatic.

Animals↗

Fetal cardiac Doppler flow studies in prenatal diagnosis of heart disease.

The prenatal diagnosis of fetal cardiac disease has become increasingly accurate as the technology of ultrasound has improved. Although two-dimensional real-time ultrasound remains the primary method of diagnosis, Doppler blood flow velocity estimates can provide valuable pathophysiologic information to support the anatomic diagnosis. We present six cases in which Doppler studies contributed to the accuracy of the diagnosis of fetal heart disease, including tetralogy of Fallot, right and left ventricular hypoplasia, atrioventricular canal defect, double-outlet right ventricle, and pulmonic stenosis. Velocities in these cases are compared with those in normal fetuses. If Doppler flow velocities are not consistent with the observed morphologic changes, further observations are indicated. Inasmuch as most anatomical heart lesions result in altered flow patterns, Doppler investigations of intracardiac and extracardiac flow should be a routine component of the fetal echocardiogram when structural abnormalities are found.

Adolescent↗

Cyclosporine nephrotoxicity is minimized by adjusting dosage on the basis of drug concentration in blood.

Two immunosuppressive regimens-cyclosporine plus prednisone and azathioprine plus prednisone-were compared in 78 renal transplantation patients (39 in each treatment group) who were successfully managed for more than 15 months. In patients who received cyclosporine, the dosage was adjusted to achieve trough whole blood concentrations of 100 to 250 ng/ml measured by liquid chromatography. A greater number of haplotypes matched in the azathioprine-treated group than in the cyclosporine-treated group (P less than 0.026). Graft survival was similar in patients who received azathioprine (95%) and those given cyclosporine (94%). The azathioprine group had a higher mortality (7%) than the cyclosporine group (2%). In a comparison of the two treatment groups, no statistically significant difference was found in posttransplant renal function, based on either serum creatinine or iothalamate clearance. We conclude that renal toxicity due to cyclosporine can be minimized to statistical nonsignificance by using cyclosporine dosages that provide trough whole blood concentrations in the range of 150 to 250 ng/ml during the first 4 months of therapy and 80 to 200 ng/ml thereafter.

Adult↗