Echocardiographic analysis of rejection in the infant heart transplant recipient.

Eleven children who received transplants at less than 2 years of age underwent 59 echocardiograms at the time of endomyocardial biopsy for the assessment of the ability of echocardiography to predict acute rejection in the infant heart transplant recipient. Two patients died of acute rejection and autopsy findings were compared with premortum echocardiograms. Biopsy specimens were graded as no rejection (n = 46), mild rejection (cellular infiltrate, n = 5), or moderate-severe rejection (myocyte necrosis/edema, n = 8). Echocardiographic indexes measured included the following: left ventricular mass, left ventricular volume, ejection fraction, heart rate, and peak rate of posterior wall thinning. Compared with controls, patients during mild rejection had slower posterior wall diastolic thinning (p < 0.01). No significant change was noted in left ventricular mass until endomyocardial biopsy specimens showed severe rejection. No significant changes were noted in heart rate or ejection fraction in any of the groups. In conclusion, decrease in the peak rate of posterior wall diastolic thinning may be a sensitive indicator of acute rejection in the infant heart transplant recipient.

Supravalvular aortic stenosis cosegregates with a familial 6; 7 translocation which disrupts the elastin gene.

Supravalvular aortic stenosis (SVAS) is an autosomal dominant disorder characterized by abnormalities of development of the great vessels. SVAS is also commonly part of Williams syndrome. Linkage to the elastin gene on chromosome 7q11 has recently been reported in two kindreds with SVAS. Previous reports of patients with 7q11 deletions have noted great vessel abnormalities in some. We report on a family in which SVAS is cosegregating with a balanced reciprocal translocation, t(6:7) (p21.1;q11.23), providing further evidence that SVAS is the result of a mutation of elastin at 7q11.23 region. The propositus of the translocation family has some minor anomalies which occur in Williams syndrome, suggesting that elastin abnormalities may cause some of the abnormalities found in Williams syndrome.

A human vascular disorder, supravalvular aortic stenosis, maps to chromosome 7.

The pathogenesis of vascular disease is unclear, but genetic factors play an important role. In this study we performed linkage analyses in two families with supravalvular aortic stenosis, an inherited vascular disorder that causes narrowing of major arteries and may lead to cardiac overload and failure. DNA markers on the long arm of chromosome 7 (D7S371, D7S395, D7S448, and ELN) were linked to supravalvular aortic stenosis in both families with a combined logarithm of likelihood for linkage (lod score) of 5.9 at the ELN locus. These findings indicate that a gene for supravalvular aortic stenosis is located in the same chromosomal subunit as elastin, which becomes a candidate for the disease gene.

Enzyme-linked immunosorbent assay for measurement of allergen-specific IgE antibodies in canine serum.

A micro-ELISA, using horseradish peroxidase-conjugated anti-canine IgE and polystyrene microtitration wells for detection of allergen-specific IgE in canine serum, was developed. Specificity of anti-canine IgE was confirmed by reversed cutaneous anaphylaxis evaluations, gel-precipitation reactions, immunoelectrophoresis, immunoaffinity chromatography, and heat inactivation. Individual allergen blanks were used to account for variable nonspecific binding among various allergens, and results were normalized using 4 reference sera. Coefficients of variation for intra-assay and interassay variability ranged from 0.77 to 5.66% and 3.15 to 9.83%, respectively. Results observed with wells coated with mixtures of various allergen extracts yielded results approximately equal to results (average) of wells containing individual components. Agreement between ELISA and skin test results ranged from 43 to 64%, depending on allergen used.

Effect of immunotherapy on the serum concentrations of allergen-specific IgG antibodies in dog sera.

An ELISA assay which uses horseradish peroxidase conjugated anti-canine IgG and polystyrene microtiter wells for detection of allergen-specific IgG in the serum of dogs is described. Individual allergen blanks were used to account for the variable nonspecific binding among various allergens, and the results observed in milliunits of absorbance were normalized using four reference sera. The coefficients of variation for the intraassay and interassay variability ranged from 1.34 to 12.50% and 4.62 to 9.77%, respectively. The relationship between ELISA results and serum concentrations of allergen-specific IgG was quantified. IgG antibodies with specificity for various allergens were found in the majority of non-atopic individuals and in all atopic subjects. Specific immunotherapy resulted in a rise in the serum concentration of allergen-specific IgG.

Increased urinary excretion of inorganic sulfate in premature infants fed bovine milk protein.

We report measurements of urinary inorganic sulfate (iSO4) in 38 very low birth weight (VLBW) premature infants receiving various protein intakes in the first 2 months of life. The primary source of urinary iSO4 is the metabolism of amino acids containing sulfur (methionine, cysteine, taurine). It was hypothesized that urinary iSO4 excretion would be increased in VLBW infants fed the relatively high concentrations of protein in mother's own milk (HM), mother's own milk fortified with 0.85 gm/dl bovine whey (fortified HM), and a special formula for premature infants (Similac Special Care, 20 cal/oz), and that urinary iSO4 excretion would correlate with calcium excretion. VLBW premature infants fed HM (protein intake 3.3 gm/kg day) excreted very small amounts of urinary iSO4 compared with infants fed fortified HM (4.5 gm/kg/day protein), Similac SC (2.9 gm/kg/day protein), or Similac (2.7 gm/kg/day protein), all three of which contain bovine whey. Unlike the case in adults, there was no correlation between either total protein intake and urinary calcium excretion or urinary iSO4 excretion. There was, however, a significant correlation between methionine intake and urinary iSO4 excretion (r = 0.48). We speculate that increased urinary iSO4 excretion is indicative of an overload of sulfur-containing amino acids, namely methionine, present in bovine whey protein. The data also support the ability of premature infants to catabolize relatively large quantities of sulfur-containing amino acids after 2 weeks of age.

Changes in fat concentration of human milk during delivery by intermittent bolus and continuous mechanical pump infusion.

The changes in fat concentration and cumulative fat losses that occur during the delivery of human milk using two different continuous infusion systems were compared with the changes in fat concentration during simulated intermittent gavage or bolus feedings. With both mechanical pumps the largest cumulative fat losses and the greatest decreases in fat concentrations occurred at the slowest infusion rates. State of homogenization of the milk generally made little difference in the changes in fat concentration using the syringe pump, whereas homogenizing the milk increased the fat concentration significantly with the roller pump. With the syringe pump the positioning of the syringe tip (horizontal or vertical) made no difference in fat concentration at an infusion rate of 1 ml/hr, whereas at 4 and 7 ml/hr the fat concentration was increased significantly by keeping the syringe tip vertical. With either mechanical pump a large fat bolus was delivered during the eighth and final hour of infusion if the milk remaining in the tubing was recovered by using air infusion at the same infusion rate. Intermittent bolus delivery of human milk resulted in no significant loss of human milk fat, no changes in fat concentration, and no terminal delivery of a large fat load. Thus intermittent bolus feedings are preferred over continuous mechanical pump infusion systems for the delivery of human milk to low-birth-weight infants.

Inspiratory airway CO2 loading in the pony.

To determine if CO2-sensitive airway receptors are important in the control of breathing, CO2 was preferentially loaded into the respiratory airways in conscious ponies. The technique involved adding small amounts of 100% CO2 to either the latter one-third or latter two-thirds of the inspiratory air in an attempt to raise CO2 concentrations in the airway dead space independent of the arterial blood. Arterial blood gas tensions (PCO2 and PO2) and pH, as well as respiratory output (minute volume, tidal volume, and respiratory rate), were measured in a series of 20 experiments on 5 awake ponies. Elevation of airway CO2 to approximately 12% by addition of CO2 to the latter portion of the inspiratory tidal volume did not alter either ventilation or arterial blood gases. When CO2 was added earlier in the inspiratory phase to fill more of the airway dead space, a small but significant increase in minute volume (2.1 l X min-1 X m-2) and tidal volume (0.1 l X m-2) was accompanied by an increase in arterial PCO2, arterial PO2, and a fall in pH (0.96 Torr, 10.5 Torr, 0.007 units, respectively). A second series of 12 experiments on 6 awake ponies using radiolabeled 14CO2 determined that the increases in breathing were minimal when compared with the large increase that occurred when these animals inhaled 6% 14CO2 (12.7 l X min-1 X m-2). Also, stimulation of systemic arterial or central nervous system chemoreceptors cannot be eliminated from the response since significant amounts of 14CO2 were present in the arterial blood when this marker gas was added to the latter two-thirds of the inspiratory tidal volume. The results, therefore, provide no evidence for CO2-sensitive airway receptors that can increase breathing when stimulated during the latter part of the inspiratory cycle.