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Biomedical subjects

R P Wennberg

Publications and source records attributed to R P Wennberg.

18 recordsLinked to original sources
PubMed1979

Increased systemic vascular resistance in neonates with pulmonary hypertension.

The time necessary for aortic diastolic pressure to decrease to 50 percent of an initially selected value after dissipation of the dicrotic notch (T 1/2) was determined in newborn infants with and without pulmonary hypertension. The mean T 1/2 was 671 +/- 167 msec in seven infants with clinical evidence of pulmonary hypertension and documented right to left ductus arteriosus shunting; 849 +/- 243 msec in nine infants with clinical evidence of pulmonary hypertension but no documented right to left ductus arteriosus shunting; and 457 +/- 66 msec in eight infants with hyaline membrane disease and no clinical evidence of pulmonary hypertension or a patent ductus arteriosus. The mean T 1/2 values in the former two groups were significantly different from that in the group with no pulmonary hypertension (P less than 0.01). An evaluation of factors affecting T 1/2 leads to the conclusion that the patients with pulmonary hypertension had increased systemic vascular resistance as well. This finding has important diagnostic, etiologic and therapeutic implications.

Ductus Arteriosus↗
PubMed1979

The pathochemistry of kernicterus.

The stoichiometry of bilirubin--albumin interaction has been analyzed and quantitated in several recent studies, confirming that albumin binding of bilirubin obeys the law of mass action [4, 5, 14, 16, 26, 36, 43, 46, 61, 65, 73, 92, 111]. These studies provide a basis for interpreting bilirubin transport, cell uptake and toxicity from physicochemical and pharmacologic perspectives [35, 42, 58, 59]. In this report, we propose a model of the pathogenesis of kernicterus which views serum albumin and tissue as competing with each other for binding the miscible bilirubin pool. Evidence is presented to show that bilirubin normally binds reversibly to cellular membranes and certain soluble enzymes just as it does to albumin; the unbound bilirubin concentration is the driving force for both albumin and tissue binding. We propose that albumin binding is determined by the concentration of free bilirubin anion (which is essentially unaffected by physiologic pH changes), and that tissue binding is mainly determined by the concentration of free bilirubin acid (which is greatly influenced by pH). When bilirubin--tissue complexes are formed, essential cell functions may be inhibited, producing cellular acidosis, irreversible intracellular aggregation of bilirubin, and cell death. In developing this argument, we will sequentially discuss relevant features of bilirubin chemistry, the binding of bilirubin to albumin, the formation of bilirubin--tissue complexes, bilirubin toxicity, alternative viewpoints of bilirubin transport, and, finally, the implications of this model to the clinical management of jaundiced infants. It should be emphasized that this paper is an attempt to analyze bilirubin transport and toxicity using basic chemical principles; it is an extension of previously published proposals [17, 77], and will undoubtedly require further modification as additional experimental data becomes available.

Bilirubin↗
PubMed1979

Assessment of patent ductus arteriosus shunting using diastolic pressure analysis.

Ductal shunting significantly affected the time necessary for aortic diastolic pressure to fall to one-half an initially selected value (t1/2). Fourteen premature infants with clinical evidence of left-to-right ductal shunting had a mean t1/2 of 277 msec (range 133 to 383 msec) compared with a mean t1/2 of 455 msec (range 332 to 567 msec) in 14 neonates with no clinical evidence of ductal shunting (P less than 0.01). Seven older infants with ductal shunting confirmed at cardiac catheterization had a mean t1/2 of 360 msec (range 240 to 392 msec). Infant catheterization data and animal studies are suggestive of an inverse relationship between the magnitude of shunt and the t1/2. The t1/2 determined by diastolic pressure analysis is a useful method for serial evaluation of ductus arteriosus shunting.

Child, Preschool↗
PubMed1979

Kinetics of bilirubin oxidation with peroxidase, as applied to studies of bilirubin-albumin binding.

In the determination of unbound bilirubin by rate of oxidation with peroxidase, errors may be caused by (1) phenol, propylparaben, and phenothiazines (free radical acceleration), (2) haemoglobin (peroxidase effect), and (3) ascorbate (inhibition). Such errors may be diminished by dilution 1:40, or with an anti-oxidant, tert-butyl-p-hydroxyanisole, and ascorbate oxidase.

Ascorbate Oxidase↗
PubMed1979

Effect of heparinization of fluids infused through an umbilical artery catheter on catheter patency and frequency of complications.

Heparinization of fluids (1 unit/ml) infused through an umbilical artery catheter (UAC) was efficacious in prolonging catheter patency in a double-blind, randomized, controlled clinical study. On the basis of life-table analysis, the half-life of catheter function was seven days in the heparinized group as compared with just over two days in the nonheparinized group (P less than .01). UAC occlusion occurred in 4 of 32 patients in the heparinized and 19 of 30 in the nonheparinized group (chi 2 = 17.6, P less than .01). Blood transfusions, number of arterial blood gases drawn through the UACs, and fluid infusion rates were not related to catheter occlusion. Heparinization of the UAC infusion did not alter the partial thromboplastin time or the incidence of catheter-related thromboembolic phenomena in the extremities. Heparinization of fluids infused through a UAC appears to be useful in the care of critically ill neonates.

Blood Gas Analysis↗
PubMed1979

Mechanized determination of the apparent unbound unconjugated bilirubin concentration in serum.

The peroxidase method for determining the apparent unbound bilirubin concentration in serum has been automated by use of a programmable, computer-directed spectrophotometer. This mechanized assay determines the total bilirubin concentration and apparent unbound bilirubin concentration in serum samples and titrates the serum with bilirubin to estimate the effect of increasing total bilirubin concentrations on the apparent unbound bilirubin concentration. The entire analysis requires 0.1 mL of serum and 4 min operation time, as compared with about 30 min for the manual method. The coefficients of variation for determination of the apparent unbound bilirubin concentration in bilirubin-enriched commercial control serum were 2.8% within-day and 5.6% between-day. Bilirubin--albumin binding in serum samples from infants with severe hyperbilirubinemia was analyzed by the manual peroxidase method, the automated peroxidase method, and Sephadex gel filtration. Good correlation was found among all three methods.

Autoanalysis↗
PubMed1979

A homestyle delivery program in a university hospital.

The Homestyle Delivery Program, an alternative birth service at the University of California Davis Medical Center, Sacramento, is presented. The program was developed jointly by the departments of family practice, obstetrics, and pediatrics, in response to the needs and desires of patients and physicians to participate in a more natural family centered birthing process. A brief description of the program and data from the first 1 1/2 years of operation is given. This program, in contrast to many other alternative birthing programs, involves physicians in training; that is, residents in family practice and obstetrics who are being taught during their obstetrical training how to create and facilitate an intimate family oriented home-like birthing. Satisfaction with the program on the part of the participating families as well as physicians and program staff has been very high. Today, more families in this society are demanding this kind of alternative birthing experience; the Homestyle Delivery Program meets their needs and to data has demonstrated no increased risk to mother or infant.

California↗
PubMed1978

Transient hyperammonemia of the preterm infant.

We report on five preterm infants (34 to 36 weeks' gestation) in whom an overwhelming illness developed within the first 48 hours of life. Each had mild respiratory distress that progressed within 48 hours to deep coma requiring ventilatory assistance. Ammonia concentrations in the plasma ranged from 844 to 7640 microgram per deciliter. Four received exchange transfusion and peritoneal dialysis; ammonia values returned to the normal range (less than 150 mug per deciliter) within 72 hours and remained there even after protein challenge. These four subsequently fed and developed normally. The fifth infant died without an attempt to lower plasma ammonia. In this infant (and two of the others) urea-cycle enzymes measured in liver tissue were in the normal range. Transient hyperammonemia of unknown cause may be a relatively common variety of neonatal hyperammonemia; it responds well to prompt diagnosis and aggressive therapy.

Ammonia↗
PubMed1978

Displacement of bilirubin from albumin by indomethacin.

The primary albumin binding site of indomethacin is remote from the bilirubin binding site. Indomethacin is, at most, a weak displacer of bilirubin at low serum drug concentrations. When administered at dosages less than 1 mg/kg, indomethacin would appear to be safe with respect to serum binding of bilirubin in premature infants.

Bilirubin↗
PubMed1978

Indications for early exchange transfusion in patients with erythroblastosis fetalis.

The postnatal rate of rise of the undirect bilirubin concentration was compared with cord hematocrit and bilirubin values in 44 newborn infants with Rh isoimmune hemolytic disease. Cord blood values failed to predict the severity of hyperbilirubinemia with sufficient accuracy to warrant their use as therapeutic guidelines. A statistically significant positive correlation was found between the cord serum indirect bilirubin concentration and its subsequent rise in 19 infants who had received antenatal phenobarbital therapy, but this relationship was not observed in untreated infants. The phenobarbital-treated infants had a slower postnatal rise of indirect bilirubin than did nontreated controls. There was no reliable indicator of the severity of hyperbilirubinemia other than careful monitoring of the serum bilirubin concentration during the early hours of life.

Bilirubin↗
PubMed1978

Nonsurgical management of renovascular hypertension in the neonate.

Over an 18-month period nine infants in a neonatal intensive care unit developed hypertension (blood pressure, 115/88 to 280/140 mm Hg) at 2 to 45 days of age. Eight of the nine infants had indwelling umbilical artery catheters prior to onset of hypertension; six of the nine infants had evidence of a patent ductus arteriosus. Peripheral plasma renin activity was greater than 300 ng/ml/3 hr in six of eight infants. Angiograms were abnormal in six of seven infants and computerized renal scans were abnormal in all nine infants. One infant had congenital renal artery stenosis. Eight of nine infants had evidence of unilateral or bilateral renal artery thrombi which were felt to have emanated from an umbilical artery catheter or a ductus arteriosus. Hypertension in all infants was successfully controlled medically (follow-up of 3 to 27 months; mean, 14.4 months). Blood pressures remained normal when medication was discontinued. In our experience, neonatal renovascular hypertension is no longer uncommon, responds to aggressive medical management, and rarely requires early nephrectomy. Neonatal renovascular hypertension was usually associated with umbilical artery catheters positioned above the level of the renal arteries.

Adult↗
PubMed1977

Neonatal listeriosis.

Five cases of neonatal listeriosis were diagnosed and treated in a 13-month period. Maternal fever and "greenish discoloration" or meconium staining of amniotic fluid complicated all deliveries. Amniotic membranes were intact until artificial rupture shortly before delivery. One infant, with the "granulomatous" form of the disease, died. Four infants required mechanical ventilation. Two survivors with pneumonia, who required mechanical ventilation and 100% inspired oxygen for persistent hypoxemia, responded to tolazoline hydrochloride therapy. Early institution of antibiotics and aggressive ventilatory and pharmacological support were considered to be important factors in survival.

Adolescent↗
PubMed1977

Displacement of bilirubin from human albumin by three diuretics.

The interaction of three diuretics with bilirubin-albumin complexes was studied using the peroxidase assay, erythrocyte uptake, and sephadex gel filtration. On a molar basis, each diuretic was as potent or more potent than sulfisoxazole in displacing bilirubin from albumin. Furosemide and ethacrynic acid, when used at the recommended dosage (1 mg/kg), would probably not produce a significant increase in free bilirubin in most infants. Chlorothiazide could introduce a significant risk to jaundiced infants because of the higher dosage required.

Bilirubin↗
PubMed1977

Influence of intravenous nutrients on bilirubin transport. I. Amino acid solutions.

The effects of synthetic amino acids on bilirubin transport were investigated with competitive binding assays, peroxidase assays, isotopic studies of bilirubin uptake by red cells, and difference spectroscopy. Results indicated that amino acids had no significant effect on the distribution of bilirubin at pigment to albumin molar ratios likely to be encountered in clinical situations.

Albumins↗
PubMed1977

Influence of intravenous nutrients on bilirubin transport. II. Emulsified lipid solutions.

The effects of an emulsified intravenous fat preparation (Intralipid) on bilirubin transport were analyzed by cholestyramine extraction, spectrophotometric analysis, Sephadex gel filtration, peroxidase assay, bilirubin uptake by red blood cells, and by toxicity in tissue culture (L-929) cells. Intralipid is capable of binding bilirubin, but does not compete effectively with bilirubin bound to high affinity sites on albumin. The emulsified fat appears to have a higher affinity for bilirubin than for cell membranes. Red blood cells become coated with Intralipid, resulting in an increased association of bilirubin with the cell surface, but a decrease in pigment actually incorporated into the red cell membrane. In tissue culture experiments, Intralipid protected the cells from bilirubin toxicity. It is concluded that Intralipid may enhance the carrying capacity of serum for bilirubin, and thus exert a protective effect on tissues.

Albumins↗
PubMed1975

Absence of pyruvate decarboxylase activity in man: a cause of congenital lactic acidosis.

A complete deficiency in the pyruvate dehydrogenase system activity contributed to the death of a 6-month-old infant with congenital lactic acidosis. The enzymatic block could be isolated to the first component, pyruvate decarboxylase (E1) of the pyruvate dehydrogenase complex. This enzymatic deficiency allowed a demonstration of an "intercomplex" exchange of the components of the mammalian pyruvate dehydrogenase system and indicated that the first component is normally present in an apparent excess.

Acidosis↗