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Biomedical subjects

J C Jackson

Publications and source records attributed to J C Jackson.

At least 19 recordsLinked to original sources

Breech extraction of low-birth-weight second twins: can cesarean section be justified?

The outcomes of 54 breech-extracted second twins weighing between 750 and 2000 gm were compared with the outcomes of their siblings and of 43 sets of twins delivered by cesarean section for malpresentation. Vaginally delivered first twins had fewer days of mechanical ventilation and oxygen therapy than their breech-extracted siblings (p = 0.004). There were no significant differences in any measures of neonatal outcome when breech-extracted twins were compared with second twins delivered by cesarean section. We conclude that routine cesarean section is not justified for nonvertex second twins expected to weigh less than 2000 gm.

Breech Presentation

Acute changes in vasoactive lipid mediators in experimental hyaline membrane disease.

Endothelial release of the arachidonate derivative PGI2 may be increased in response to cyclic lung stretching. We therefore sought to determine if the stable metabolite of PGI2, 6-keto-PGF1 alpha, would be found in increased quantities in primates ventilated with conventional mechanical ventilation (CMV) compared to treatment with high frequency oscillatory ventilation (HFOV). We also sought to determine if other membrane-derived vasoactive substances such as LTC4, PAF and TXB2 would be elevated in plasma and lung tissue of animals developing hyaline membrane disease (HMD) and if the levels would correlate with the severity of the respiratory distress. Twenty prematurely delivered monkeys were treated with either CMV or HFOV from the first breath after Cesarean delivery until sacrifice at 6 h of age. We found a significant increase from birth to 5 min and from 5 min to 5 h in 6-keto-PGF1 alpha, and a significant increase from 5 min to 5 h in TXB2. We found a significant decline from cord blood to 5 min of LTC4, without further change by 5 h. PAF was present in all plasma samples but showed no upward or downward trend. There was no difference in the 5-h plasma level or in the lung homogenate level of any of the lipid mediators between the two types of assisted ventilation. There was no correlation between any lipid mediator level and severity of the HMD, as measured by gas exchange, radiographic or histologic criteria, when assessed by each ventilator group alone or with both groups combined. We conclude that the immediate postnatal increases in TXB2 and PGI2 and decrease in LTC4 are not altered substantially by use of HFOV.

6-Ketoprostaglandin F1 alpha

Alternative modes of ventilation in the prevention and treatment of bronchopulmonary dysplasia.

Recent technologic innovations and refinements have increased and enhanced the armamentarium that potentially can prevent or ameliorate bronchopulmonary dysplasia. Short of altering the most important factor in the development of BPD--premature delivery--these new tools should allow individualization of ventilator treatment plans with a degree of sophistication not previously possible. By so doing, these techniques may shorten the often prolonged and uncertain course of recovery from BPD, and by so doing, limit the ongoing injury associated with BPD. The results of studies designed to test the utility of this new technology in the management of BPD are eagerly awaited.

Airway Resistance

Pathophysiology and histopathology of group B streptococcal sepsis in Macaca nemestrina primates induced after intraamniotic inoculation: evidence for bacterial cellular invasion.

Four pregnant Macaca nemestrina dams at 140-145 days of gestation received an intraamniotic inoculation of group B streptococci (GBS). All four premature infants were born by cesarean delivery, were bacteremic at birth, and showed symptoms of GBS sepsis similar to infected human infants with early-onset disease. Three infants did not receive antibiotics and died of GBS sepsis by 10 h of age despite mechanical ventilation and fluids for blood pressure support. Penicillin treatment of the fourth infant prolonged survival and decreased the requirement for supportive therapy. Quantitative cultures and histopathology were done on all four infants. Transmission electron microscopy of lung tissue demonstrated GBS within membrane-bound vacuoles of type I and II alveolar epithelium and interstitial fibroblasts. This model should be useful for studying the early steps in the pathogenesis of early-onset GBS infections. GBS may enter alveolar epithelial cells to transit this barrier and ultimately disseminate via the blood-stream.

Animals

Effect of high-frequency ventilation on the development of alveolar edema in premature monkeys at risk for hyaline membrane disease.

High-frequency oscillatory ventilation (HFOV) permits adequate gas exchange but avoids the large phasic pressure-volume excursions of conventional mechanical ventilation (CMV); such avoidance may reduce the lung injury associated with hyaline membrane disease (HMD). We hypothesized that premature monkeys ventilated from birth with HFOV would have reduced lung injury compared to those assigned to CMV. Macaca nemestrina were delivered at 134 days (80% of term gestation) and ventilated from the first breath with either HFOV (n = 10) or CMV (n = 10). The mean airway pressure (Paw) was kept at 15 cm H2O pressure in HFOV animals; in CMV animals Paw was increased from 8 cm H2O at 2 h to 13 cm H2O at 6 h to prevent hypoxemia. At the conclusion of the 6-h experiment the HFOV animals had better oxygenation (p less than 0.05) and less evidence of HMD by chest radiograph (p less than 0.05). At 6 h of age a piece of the right middle lung lobe was removed, divided, and placed in fixatives for light and transmission electron microscopy. The lungs were subsequently inflated to 30 cm H2O pressure, and the right lower lobe was rapidly frozen in situ for morphometric studies. The proportion of peripheral lung tissue occupied by clear alveoli was greater in HFOV animals (66.3 +/- 14.8%) than in those assigned to CMV (44.2 +/- 16.9%, p less than 0.01); less alveolar debris and fluid was present in the HFOV animals (12.7 +/- 9.9%) compared with CMV animals (27.1 +/- 12.5%, p less than 0.02).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Predictors of neurodevelopmental outcome following bronchopulmonary dysplasia.

In infants with bronchopulmonary dysplasia, the influence of the severity of their pulmonary disease on neurodevelopmental outcome is unknown. Neurodevelopmental outcomes at a mean age of 36 months were assessed in 27 premature subjects who had bronchopulmonary dysplasia. Subjects had a mean birth weight of 940 g (range, 540 to 1690 g) and a mean gestational age of 27 weeks (range, 25 to 31 weeks). The duration of mechanical ventilation ranged from 22 to 128 days, and the duration of requirement of supplemental oxygen ranged from 34 to 1033 days. No significant correlations were found between duration of mechanical ventilation or oxygen therapy and overall neurodevelopmental outcome. In contrast, cranial ultrasound findings of intracranial hemorrhage and/or periventricular echodensity related specifically to poorer cognitive outcome. By age 3 years, severity of bronchopulmonary dysplasia is not a sufficient predictor of neurodevelopmental outcome. Intracranial hemorrhage and periventricular echodensity continue to be important predictors.

Bronchopulmonary Dysplasia

Estimation of mortality risk in chronically ventilated infants with bronchopulmonary dysplasia.

Bronchopulmonary dysplasia is a chronic, sometimes fatal lung disease, which primarily affects premature infants and often leads to a dependence on mechanical ventilation lasting many months. To identify prognostic factors of mortality at 1 and 2 months of age, the authors reviewed the medical records of the 144 neonates admitted to two neonatal intensive care units in Seattle from January 1, 1986, through December 31, 1988, who required mechanical ventilation throughout the first month of life. Likely predictors of mortality were tested by logistic regression analysis. The calculated mean airway pressure at 30 days of age (MAP30) and the diagnosis of bacterial sepsis at any time during the first month of life (Bact 0-30) were statistically significant predictors of mortality (P less than .001 and P = .018, respectively) and had the lowest deviance in the regression model. The probability of mortality was estimated by 1/(1 + e-chi), where chi = -6.510 + 0.4588 (MAP30) + 1.475 (Bact 0-30), and where MAP30 is expressed as centimeters of water pressure (1 cm H2O = 0.0978 kPa) and the presence or absence of bacteremia is 1 and 0, respectively. The records of the 57 infants who still required mechanical ventilation at 60 days of age were reanalyzed with clinical data available during the first 2 months of life. Mean airway pressure (MAP 60) and the fraction of inspired oxygen (F60) at 60 days of age combined to form the best predictors of mortality, where chi = 7.668 + 0.2940 (MAP 60) + 5.935 (F60).(ABSTRACT TRUNCATED AT 250 WORDS)

Bronchopulmonary Dysplasia

Improved neonatal survival following multiple doses of bovine surfactant in very premature neonates at risk for respiratory distress syndrome.

To determine whether multiple doses of bovine surfactant would improve neonatal mortality in very premature neonates, we conducted two multicenter controlled trials under identical protocols; the results were combined for analysis. Four hundred and thirty neonates born between 23 and 29 weeks gestation and weighing 600 to 1250 g at birth were assigned randomly at birth to receive either 100 mg of phospholipids/kg of Survanta, a modified bovine surfactant (n = 210), or a sham air placebo (n = 220) within 15 minutes of birth. Neonates who developed respiratory distress syndrome and required mechanical ventilation with at least 30% oxygen could be given up to three more doses in the first 48 hours after birth. Dosing was performed by investigators not involved in the clinical care of the neonates; nursery staff were kept blinded as to the treatment assignment. Cause of death was determined by a panel of three independent, board-certified neonatologists after blindly reviewing case report forms and autopsy reports. Fewer Survanta-treated neonates died of any cause (11.4% vs 18.8%, P = .031), died of respiratory distress syndrome (1.9% vs 15.6%, P less than .001), and either died or developed bronchopulmonary dysplasia due to respiratory distress syndrome (39.5% vs 49.1%, P = .044). The incidence of respiratory distress syndrome was also lower in Survanta-treated neonates (28.0% vs 56.9%, P less than .001), and the Survanta-treated neonates' oxygenation and ventilatory status were improved significantly at 72 hours. Survanta-treated neonates were also at lowered risk of developing pulmonary interstitial emphysema (23.3% vs 36.9%, P = .002) and other forms of pulmonary air leaks (9.6% vs 20.8%, P .002).(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Inhalation

Collagen synthesis during lung development and during hyaline membrane disease in the nonhuman primate.

To assess maturational changes in collagen synthesis, lung tissue was obtained from healthy Macaca nemestrina monkeys at different ages, ranging from 68% of term gestation to adulthood. We hypothesized that infants delivered prematurely have a greater rate of collagen synthesis than do older animals because of their greater rate of lung growth during gestation. Secondly, we hypothesized that lung repair in infants with hyaline membrane disease (HMD) is associated with an additional increase in lung collagen synthesis rate. Therefore, lung tissue was obtained during the first week of life from monkeys delivered at 82% of term gestation, a stage at which half of them developed HMD. The rate of total protein synthesis in lung samples was determined by measuring the incorporation of [3H]proline; the rate of collagen synthesis was determined by measuring the conversion of proline into hydroxyproline. Premature monkeys had a higher rate of collagen synthesis (9.9 +/- 2.7 nmol/mg DNA/h) than did term infants (5.3 +/- 1.1) or older animals (2.1 +/- 0.4, p less than 0.05). There was no additional increase in rate of collagen synthesis in animals with HMD from 3 h (14.3 +/- 6.9) to 7 days of age (15.1 +/- 6.1); control premature animals also had no significant change during the first week of life (10.9 +/- 3.0 at 3 h; 11.6 +/- 4.6 at 7 days). The early stage of recovery from HMD in premature monkeys does not appear to be associated with an increase in collagen production beyond the already increased synthesis rate associated with lung growth.

Analysis of Variance

Mechanisms for reduced total lung capacity at birth and during hyaline membrane disease in premature newborn monkeys.

To determine whether the cause of reduced total lung capacity (TLC) in hyaline membrane disease (HMD) is due to alveolar collapse, alveolar edema, or both, TLC was measured by N2-washout in premature Macaca nemestrina monkeys during the first 3 h of life. The TLC of animals with HMD was only one-third that of healthy premature monkeys over the first 3 h of life (p less than 0.01). At 3.5 h, lung tissue was rapidly frozen in situ during lung inflation to TLC. Samples of frozen lung tissue were freeze dried, embedded, sectioned, and examined by point counting. Animals with HMD had alveolar saccules filled with the residue of proteinaceous fluid, but little alveolar collapse was noted. The proportion of points falling on empty alveolar spaces was 74% in the healthy animals but only 18% in animals with HMD (p less than 0.01); there was a 70-fold increase in the residue present in alveoli of animals with HMD (p less than 0.05). In a separate experiment, rapid serial measurements of TLC by N2-washout showed that healthy premature monkeys, but not those with HMD, have a steady increase in TLC during the first few minutes of life, presumably due to clearance of lung liquid. Although the initial cause of reduced TLC in HMD appears to be inadequate clearance of fetal lung liquid, by 3 h of age proteinaceous alveolar edema is primarily responsible.

Animals

Ebstein's anomaly and extracardiac defects.

Ebstein's anomaly of the tricuspid valve occurs as an isolated defect with other forms of congenital heart disease such as transposition of the great arteries or tetralogy of Fallot or, rarely, in association with extracardiac malformations. Because so little is known about this latter group, we studied four cases clinically, at autopsy, and by means of a retrospective chart review. Major extracardiac changes most often involved the craniofacial region, central nervous system, and limbs. Karyotypes were normal, and no distinctive syndromes or anatomic patterns were identified. Since the timing of Ebstein's anomaly is quite precise, ascertainment of such cases on the basis of cardiac morphology may enhance the understanding of etiology and pathogenesis. Both causes and mechanisms may well be diverse, for the clinical histories and anatomic findings in present and previously reported cases vary considerably. Isolated Ebstein's anomaly may develop from topographically and temporally localized damage. Ebstein's anomaly with extracardiac defects may involve damage during a longer, and perhaps earlier, period.

Abnormalities, Multiple

In utero thrombosis and neonatal gangrene in an infant of a diabetic mother.

We report an infant of a diabetic mother (IDM) with in utero brachial artery thrombosis and neonatal gangrene to illustrate that there may be an increased risk for arterial as well as venous thrombosis in IDMs. The diagnosis of brachial artery thrombosis was made by using Doppler sonography flow studies and was confirmed with autopsy. The postnatal period was complicated by aortic and mesenteric artery thrombosis, with subsequent necrotizing enterocolitis, renal infarction, and death. Gangrene of a limb presenting at birth is rare, with 32 individuals reported in the literature, including this patient. Twenty-two percent (7/32) of the infants with peripartum limb gangrene were IDMs. This implies a marked increase in arterial thrombosis in IDMs over the general population. Changes in coagulation factors have been reported in newborn IDMs with poor control of maternal diabetes. Increased clotting and decreased fibrinolysis found in diabetics may lead to arterial thrombosis in IDMs in utero and postnatally. Use of anticoagulants in at-risk infants should be considered to prevent further thrombosis postnatally. Additionally, IDMs may be at increased risk for thrombotic complications from umbilical artery catheter. In utero thrombosis of the brachial artery may be one mechanism which leads to limb reduction defects in IDMs.

Aortic Diseases

Effects of hyperoxia and dimethylthiourea on neonatal pulmonary hemodynamics in piglets.

Exposure of piglets to 68-72 h of hyperoxia has previously been shown to blunt hypoxic pulmonary vasoconstriction (HPV). We tested the hypothesis that the administration of a scavenger of toxic oxygen radicals during exposure to hyperoxia would preserve HPV in piglets. Newborn piglets were kept in FIO2 greater than 0.90 for 68-72 h and compared to control animals kept in room air. Randomly selected animals from both groups were given the O2 metabolite scavenger, dimethylthiourea (DMTU) (500 mg/kg followed by 250 mg/kg/d), resulting in plasma levels of 2-6 mM. Following the oxygen or room air (RA) exposure period, piglets had pulmonary vascular resistance (PVR) measured following a 20 min exposure to alveolar hypoxia (FIO2 = 0.12). Both groups of RA-exposed animals (DMTU and saline treatment) as well as the hyperoxia-exposed saline group had almost 2-fold increases in PVR during exposure to hypoxia (P less than 0.05). Contrary to expectations, the PVR in the hyperoxia-exposed DMTU group did not rise significantly during hypoxia and the use of DMTU did not restore HPV by increasing PVR to levels greater than the hyperoxia/saline group (P = 0.70). Therefore DMTU does not appear to prevent hyperoxia-induced blunting of HPV in piglets.

Animals

Fetal and maternal considerations in the management of stage I-B cervical cancer during pregnancy.

The timing of treatment for stage I-B cervical carcinoma diagnosed during pregnancy is complicated by conflicting concerns for fetal survival and control of malignancy. There were 11 pregnant women with stage I-B cervical carcinoma diagnosed prior to fetal viability since 1969. Six patients were managed with termination of pregnancy and radical hysterectomy with pelvic lymphadenectomy. In 5 patients, treatment was delayed for 6 to 17 weeks and then delivery was accomplished by cesarean section followed directly by radical hysterectomy and pelvic lymphadenectomy. Two of the infants experienced complicated neonatal courses and would have benefited from additional delay. Benefits that could be achieved by delaying delivery for the fetus were calculated from a review of 600 inborn infants without congenital anomalies admitted to the neonatal intensive care (NICU) during 1984 and 1985. Neonatal mortality decreased from 32.8% at 26-27 weeks to 2.7% at 34-35 weeks gestation. Similar improvements in neonatal morbidity were demonstrated. Although adverse maternal outcomes were not associated with delay, an evaluation of risk cannot be derived from this series. Significant fetal benefit can accrue from relatively short delays in planned delivery dates. When stage I-B cervical carcinoma is diagnosed during pregnancy and when fetal survival is desired, delivery should be delayed to achieve fetal maturity, rather than only potential viability.

Adult

Increased survival of low birth weight infants: impact on the incidence of retinopathy of prematurity.

Retinopathy of prematurity is a retinal vascular disease that occurs only in premature infants. Because of concern that the occurrence of this potentially blinding disease is increasing, a retrospective chart review was undertaken to compare the incidence of retinopathy of prematurity at the University of Washington during the years 1981 to 1984 with previously published data collected at the same institution during the years 1968 to 1980. During 1981 to 1984, there was an increase in the annual numbers of admissions and survivors weighing 1750 g at birth; the survival rate increased significantly (P less than .000001). A trend toward an increased risk for proliferative retinopathy of prematurity (P = .057) during 1981 to 1984 period was noted, but the number of "excess cases" was calculated to be only 6 per year. The remainder of the additional cases, 19 annually, were due to increased survival of infants at risk. Thus, the "second epidemic" of retinopathy of prematurity is largely due to improved survival of low birth weight infants rather than to new iatrogenic factors. In infants with proliferative retinopathy of prematurity, there was a previously unreported association between increased severity of disease and lower birth weight (P = .015). There were four children with severe bilateral visual loss due to retinopathy of prematurity identified during the 1981 to 1984 period, whereas only one bilaterally blind infant was noted during the preceding 12.7 years.

Birth Weight

Specific uptake of serotonin by murine macrophages.

In view of the reported immunomodulatory properties of the monoaminergic neurotransmitter, serotonin (5HT), this study aimed to assess whether 5HT specifically associates with immunocompetent cells. Although murine splenocytes appear to lack high-affinity membrane binding sites for 5HT, they do possess a specific, active, 5HT uptake system similar in affinity (Km = 40 nM) to that described in platelets. This uptake system appears to be confined to macrophages. Further, macrophages rapidly metabolize 5HT to its 5-hydroxyindole acetic acid metabolite. Specific uptake of serotonin by macrophages may thus constitute an important mechanism whereby this amine is able to regulate immune function.

Animals

Postnatal changes in lung phospholipids and alveolar macrophages in term newborn monkeys.

In order to better understand the postnatal sequence of surfactant secretion and establishment of the alveolar macrophage (AM) population in newborn primates, healthy Macaca nemestrina monkeys were sacrificed during fetal life at term gestation (n = 5), or at 2 days (n = 5) or 3-4 weeks (n = 5) after term vaginal delivery. Excised lung tissue and left lung lavage were analyzed for phospholipid (PL) content, surface active material (SAM) extract, PL components, surface activity, pressure-volume characteristics, and AM number. Compared to term fetal animals, 2 day old term newborn monkeys were found to have a several-fold increase in lavage PL and SAM, and this was associated with greater maximal lung volume and drier lungs, but not improved deflation stability. During the subsequent 3-4 weeks of life, a 42% reduction in lung tissue stores of PL and SAM, and an 87% reduction in lavage PL and SAM were noted. Despite these major changes in quantity, there were relatively minor changes in the composition of the PL synthesized and released. The reduced quantity of SAM in the 3-4 week old animals led to a small decline in deflation stability. The several-fold increase in lavage PL and SAM during the first 2 days of life was accompanied by a 33-fold increase in AM; there was an additional 4-fold increase in AM number by 3-4 weeks of age. The abundance of lavage surfactant at 2 days of age may play a role in the influx of AM.

Animals