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Biomedical subjects

D C Schwartz

Publications and source records attributed to D C Schwartz.

At least 19 recordsLinked to original sources

Midterm results with cryopreserved allograft valved conduits from the right ventricle to the pulmonary arteries.

From 1985 to 1990, 89 patients underwent placement of 41 aortic and 54 pulmonic cryopreserved allograft valved conduits between the right ventricle and the pulmonary arteries. Six patients underwent replacement with a second allograft conduit. Median age at operation was 4.3 years, and 20 patients were infants less than 1 year of age. Conduit sizes averaged 11 mm in the conduits placed in 20 infants and 20 mm in the 75 placed in patients more than 1 year of age. There were 7 early deaths in 89 patients (7.8%, 70% confidence levels 5.4% to 11.3%) and 9 late deaths in 82 hospital survivors (11%, 70% confidence levels 8% to 15%). Actuarial survival was 81% (70% confidence levels 75% to 86%) at 33 months, and no deaths were due to conduit problems. Late reoperation was required in 13 patients (7 for conduit obstruction, 1 for conduit valve insufficiency, and 5 for nonconduit-related problems). Six of the eight reoperations were done in patients who had small (< or = 13 mm) conduits placed during infancy. Conduit failure was similar between pulmonic and aortic allografts. There were no deaths in the eight patients who required conduit reoperation. Actuarial freedom from reoperation for conduit dysfunction was 80.5% (70% confidence levels 72% to 86%) at 53 months for the entire group and 94% (confidence levels 88% to 97%) at 44 months for patients more than 1 year of age. Cryopreserved allograft conduits have good early and midterm results and are comparable to porcine xenograft conduits. Despite a likely need for replacement within 3 years, we continue to favor the use in infants of an allograft valved conduit over a xenograft Dacron conduit. The need to replace a cryopreserved allograft conduit appears similar for conduits of aortic or pulmonic origin.

Actuarial Analysis

Effect of digoxin on contractility and symptoms in infants with a large ventricular septal defect.

The effect of digoxin on contractility and symptoms in infants with a large ventricular septal defect (VSD) is controversial. Nineteen infants with symptoms of congestive heart failure due to a VSD were studied with load-independent indexes during 4 study periods: (1) before any medication; (2) while on chronic diuretics; (3) while on both diuretics and digoxin; and (4) while on diuretics alone, to determine if digoxin: (a) increases "contractility" when added to diuretic therapy; and (b) improves symptoms. Symptoms, signs (heart and respiratory rates, and weight gain), shortening fraction, preload (left ventricular end-diastolic dimension), afterload (left ventricular end-systolic wall stress) and contractility were measured at each period. The difference between the measured and predicted velocities of circumferential fiber shortening for the measured left ventricular end-systolic wall stress served as an index of contractility. Eighteen infants also underwent catheterization. Mean pulmonary-to-systemic blood flow ratio was 3:1. When digoxin was added to diuretics, contractility index was significantly greater than in control subjects (0.13 +/- 0.15 vs 0.0 +/- 0.12 circ/s, p = 0.04). When patients were again on diuretics alone (after discontinuation of digoxin), contractility index was no longer different. Symptoms and signs were not significantly improved by either diuretics or digoxin. It is concluded that in infants with a large left-to-right VSD shunt and receiving digoxin and diuretics, contractility index was significantly greater than in control subjects. However, neither diuretics alone nor in combination with digoxin improved symptoms significantly.

Digoxin

CA 15-3 and carcinoembryonic antigen in the clinical evaluation of breast cancer.

The individual and combined value of CA 15-3 and carcinoembryonic antigen (CEA) as breast cancer tumor markers was investigated in longitudinal studies. Patients included women at high risk for recurrence after primary therapy or undergoing treatment for metastatic disease. During follow-up, recurrent disease was documented in 33 of 39 (85%) patients including 11 with local recurrence and 22 with distant metastases. At the time recurrence was first documented by objective criteria 23 of 33 (70%) of the patients presented with abnormal CA 15-3 levels (greater than 36.7 U/ml) compared with 19/33 (58%) with abnormal CEA levels (5 ng/ml). Tumor marker elevations predominated in patients with advanced disease indicating that CA 15-3 and CEA are not reliable for the detection of early breast cancer. Both markers were helpful in monitoring therapeutic response since antigen levels correlated closely with disease status.

Antigens, Neoplasm

Relation of symptoms to contractility and defect size in infants with ventricular septal defect.

Forty-two infants with a ventricular septal defect (VSD) (21 asymptomatic and 21 symptomatic) were compared with 17 control infants to determine if symptoms of congestive heart failure (i.e., tachypnea/poor growth) were due to depressed contractility or defect size, or both. Echocardiographic indexes of defect size, left ventricular performance (shortening fraction), preload (left ventricular end-diastolic dimension), afterload (left ventricular end-systolic wall stress) and contractility (the relation between velocity of circumferential fiber shortening and wall stress) were measured. Clinical assessment included measurement of weight and respiratory rate. Pulmonary and systemic blood flow were assessed in 17 symptomatic and 3 asymptomatic patients by cardiac catheterization. Although there was no significant difference in age, the symptomatic group had significantly lower weight (5.5 +/- 2.9 vs 7.3 +/- 2.3 kg, p less than 0.05) and a higher respiratory rate (53 +/- 14 vs 43 +/- 6 breaths/min, p less than 0.05), compared with control subjects. The mean pulmonary to systemic blood flow ratio in the symptomatic group was 2.9:1. Preload indexed for body surface area was significantly higher in the groups with a VSD compared with control subjects (asymptomatic, 8.5 +/- 1.7 cm/m2; symptomatic, 9.1 +/- 1.7 cm/m2; control subjects, 6.8 +/- 1.1 cm/m2; p less than 0.05). Shortening fraction, afterload and contractility were not significantly different among all groups. A defect size greater than 0.5 cm (or defect size indexed for body surface area greater than 1.8 cm/m2) was predictive of the presence of symptoms. It is concluded that contractility is normal in infants with a VSD. Symptoms may be related to pulmonary congestion.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Flow Velocity

Analysis of DNA restriction fragments greater than 5.7 Mb in size from the centromeric region of human chromosomes.

Pulsed electrophoresis was used to study the organization of the human centromeric region. Genomic DNA was digested with rare-cutting enzymes. DNA fragments from 0.2 to greater than 5.7 Mb were separated by electrophoresis and hybridized with alphoid and simple DNA repeats. Rare-cutting enzymes (Mlu I, Nar I, Not I, Nru I, Sal I, Sfi I, Sst II) demonstrated fewer restriction sites at centromeric regions than elsewhere in the genome. The enzyme Not I had the fewest restriction sites at centromeric regions. As much as 70% of these sequences from the centromeric region are present in Not I DNA fragments greater than 5.7 and estimated to be as large as 10 Mb in size. Other repetitive sequences such as short interspersed repeated segments (SINEs), long interspersed repeated segments (LINEs), ribosomal DNA, and mini-satellite DNA that are not enriched at the centromeric region, are not enriched in Not I fragments of greater than 5.7 Mb in size.

Centromere

Left ventricular mass in childhood dilated cardiomyopathy: a possible predictor for selection of patients for cardiac transplantation.

To determine the relationship of left ventricular hypertrophy (as assessed by mass) to symptoms and cardiac function in chronic childhood dilated cardiomyopathy, 17 long-term survivors (12 asymptomatic, 5 symptomatic) were studied at a median follow-up of 6.25 years (1.25 to 16.8 years). Left ventricular mass, dimension, wall stress, and contractility (relationship between velocity of circumferential fiber shortening and end-systolic wall stress) were assessed by echocardiography. These data were compared to measurements at the onset of disease. At follow-up, mass decreased significantly from the onset in the asymptomatic patients but remained elevated in the symptomatic patients (101 +/- 35 gm/m2 to 54 +/- 12 gm/m2, p = 0.001; 122 +/- 55 gm/m2 to 198 +/- 115 gm/m2, p = 0.23, respectively). Shortening fraction and contractility were both significantly lower in the symptomatic group compared with the asymptomatic group at follow-up (shortening fraction = 21 +/- 7% vs 29 +/- 5%, p = 0.02; contractility = -0.24 +/- 0.14 circ/sec vs -0.05 +/- 0.11 circ/sec, p = 0.01). Follow-up wall stress was slightly higher in symptomatic patients compared with asymptomatic patients. Three symptomatic patients had progressive hypertrophy and either died or required transplantation. Higher left ventricular mass is associated with the presence of symptoms, depressed contractility, and slightly higher wall stress. Persistence or progression of hypertrophy may be a poor prognostic sign in survivors of childhood dilated cardiomyopathy. Measurement of mass may be useful to indicate the necessity for closer follow-up to select patients for cardiac transplantation before hemodynamic decompensation.

Cardiomegaly

Changes in cardiac function during extracorporeal membrane oxygenation for persistent pulmonary hypertension in the newborn infant.

The effects of extracorporeal membrane oxygenation (ECMO) on cardiac function and its determinants (preload, afterload, contractility, and heart rate) are largely unknown, although some evidence exists that function may decrease. To determine whether cardiac function decreases and what changes in the determinants take place during and after ECMO, we observed 26 newborn infants with persistent pulmonary hypertension. Serial echocardiograms were performed before ECMO, during maximum cardiopulmonary bypass, and after ECMO. Cardiac function was assessed by using standard echographic ejection phase indices (shortening fraction and cardiac output). Heart rate, preload (left ventricular end-diastolic dimension and area), afterload (left ventricular end-systolic wall stress), and contractility (relationship between velocity of circumferential fiber shortening and wall stress) were also measured. Ejection phase indices significantly decreased during ECMO (shortening fraction 33% to 25%, cardiac output 205 to 113 ml/kg/min; p less than 0.05) and returned to normal after ECMO (shortening fraction 26% to 34%, cardiac output 107 to 240 ml/kg/per minute; p less than 0.05). Heart rate also significantly decreased during ECMO (158 to 118 beats/min; p less than 0.05). Preload significantly increased after ECMO (left ventricular end-diastolic dimension 1.4 to 1.6 cm, left ventricular end-diastolic area 1.9 to 2.2 cm2; p less than 0.05). There were no significant changes in contractility and afterload during any study period. We conclude that, although left ventricular ejection phase indices and heart rate decreased during ECMO, these changes were transient and resolved when bypass was terminated. Contractility and afterload did not appear affected by bypass.

Bacterial Infections

Evaluation of CA M26, CA M29, CA 15-3 and CEA as circulating tumor markers in breast cancer patients.

The clinical utility of CA M26 and CA M29 was studied in 116 breast cancer patients and compared with results for CA 15-3 and carcinoembryonic antigen (CEA). The highest sensitivities for breast cancer detection were achieved with CA 15-3 (0.60) and CEA (0.56), but this was compromised by a relative lack of specificity (0.87 and 0.88 for CA 15-3 and CEA, respectively). Sensitivities attained with CA M26 (0.47) and CA M29 (0.53) were lower, but there was an excellent specificity (1.00) for each assay in this series of benign patients. Tumor marker elevations were appreciable with advanced disease such that 82 of 91 patients (90%) with active metastatic breast cancer exhibited at least one abnormal test value. Longitudinal studies demonstrated that CA M26, CA M29, CA 15-3 and CEA complement each other and combinations of these markers reflect disease status better than individual tests.

Adult

Efficacy of adrenaline, lignocaine-adrenaline and isoprenaline as a test dose in halothane-anaesthetized lambs.

It has been shown that an epidural test dose with adrenaline does not always detect an intravascular injection in halothane-anaesthetized children. To ascertain whether test dosing with other agents might be more useful, we sought to determine if and at what dose levels three different intravenous drugs (adrenaline, isoprenaline and 1% lignocaine with 1/200,000 adrenaline) produced an increase in heart rate (HR) in halothane-anaesthetized lambs. Eight 2-week-old lambs were anaesthetized with 1% halothane in oxygen. The lambs were intubated and ventilated in order to maintain end-tidal and arterial CO2 within normal limits; HR and blood pressure before and 15-180 s after the injection of four increasing doses of each drug were recorded. The same set of measurements was repeated after the intravenous injection of atropine 10 micrograms kg-1. Adrenaline-containing doses produced a more sustained increase in HR (P less than 0.05, ANOVA) at lower doses of adrenaline when atropine was injected first. This increase did not occur in all lambs, and dysrhythmias were manifest in some. Isoprenaline always produced a significant increase in HR without dysrhythmias whether atropine was given or not. We conclude that in halothane-anaesthetized lambs, isoprenaline is a more reliable indicator of intravascular injection than adrenaline.

Anesthesia, Inhalation

Comparison of assays for prostatic and total acid phosphatase.

Total and tartrate inhibited acid phosphatase was determined on the Technicon Chem 1 and evaluated against a Cobas-Bio centrifugal analysis procedure and an immunochemical method. Precision and reference range studies were performed for the Chem 1 acid phosphatase procedure and correlation was established with the other methods. The Chem 1 method for measuring total and prostatic acid phosphatase is a sensitive method with good correlation to the centrifugal analysis and the immunochemical method. The assay is fully automated and requires no manual off-line sample preparation.

Acid Phosphatase

A rapidly rearranging retrotransposon within the miniexon gene locus of Crithidia fasciculata.

The tandemly arrayed miniexon genes of the trypanosomatid Crithidia fasciculata are interrupted at specific sites by multiple copies of an inserted element. The element, termed Crithidia retrotransposable element 1 (CRE1), is flanked by 29-base-pair target site duplications and contains a long 3'-terminal poly(dA) stretch. A single 1,140-codon reading frame is similar in sequence to the integrase and reverse transcriptase regions of retroviral pol polyproteins. Cloned lines derived from a stock of C. fasciculata have unique arrangements of CRE1s. In different cloned lines, CRE1s, in association with miniexon genes, are located on multiple chromosomes. By examining the arrangement of CRE1s in subclones, we estimate that the element rearranges at a rate of ca. 1% per generation. These results indicate that the C. fasciculata miniexon locus is the target for a novel retrotransposon.

Amino Acid Sequence

Conformational dynamics of individual DNA molecules during gel electrophoresis.

Gel electrophoresis is widely used in molecular biology to separate DNA molecules according to their sizes. The physical basis of this size separation is, however, poorly understood. Here we report observations of individual, fluorescently stained DNA molecules as they migrate during various kinds of gel electrophoresis. Their movement, under the influence of either a steady electric field or a pulsed-field, is characterized by cycles of elongation and contraction. Initially relaxed coils of DNA lengthen into 'hook-shaped' configurations which temporarily 'hang-up' on obstacles in the gel matrix before sliding off, contracting and entering another cycle. The effects of a new electrophoresis technique, termed 'pulse-oriented electrophoresis', which allows the effective angle of the electric field, and hence the molecular orientation of DNA, to be varied without electrode rearrangement, are also studied. In this case the DNA adopts a 'staircase' configuration showing that the net orientation in a direction is given by the vector sum of the pulses used.

DNA

Color flow mapping to document normal pulmonary venous return in neonates with persistent pulmonary hypertension being considered for extracorporeal membrane oxygenation.

This study investigated the value of color flow mapping in documenting normal pulmonary venous return in neonates with persistent pulmonary hypertension who were candidates for extracorporeal membrane oxygenation (ECMO). Forty newborn infants with persistent pulmonary hypertension underwent conventional (two-dimensional and Doppler) echocardiography and color flow mapping. Of 25 candidates for ECMO therapy, 18 subsequently received it. Conventional echocardiography demonstrated normal pulmonary venous return in only 21 of the 40 patients. In all 40, however, color flow mapping demonstrated normal right and left pulmonary venous drainage entering the left atrium. In three other patients with total anomalous pulmonary venous return, conventional echocardiography demonstrated the anomalous pulmonary venous pathways, and color flow mapping did not show jets emanating from the left atrial wall; the left atrium was shown to fill exclusively from right to left shunting through the foramen ovale. We conclude that color flow mapping is superior to conventional echocardiography for verifying normal pulmonary venous return in neonates with persistent pulmonary hypertension.

Color