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Biomedical subjects

J B Philips

Publications and source records attributed to J B Philips.

At least 37 records · Page 2Linked to original sources
PubMed1993

Age-related differences in responses to endotoxin infusion in unanesthetized piglets.

Newborn endotoxic shock syndrome is associated with high morbidity and mortality, yet presents with different clinical manifestations than in older patients. To determine the influence of age on hemodynamic and metabolic responses to endotoxin, we developed a chronically instrumented endotoxic shock model using eight 1-3-day-old and seven 2-3-week-old piglets. Three days after surgery, 10 mg/kg of endotoxin was infused intravenously over 10 min in the younger group, and 5-10 mg/kg was given to the older animals. Two older piglets died immediately after infusion of 5 mg/kg of endotoxin, and five of the seven died within 4 hr, while all eight younger animals lived longer than 4 hr. Pulmonary artery pressure increased significantly after endotoxin in both groups, and there were no differences between groups. Systemic artery pressure and cardiac index fell by 44 +/- 10% and 70 +/- 15%, respectively, 5 min after endotoxin infusion in the older group, while these values did not change significantly in the younger group. Endotoxin infusion also caused greater elevation in pulmonary vascular resistance index in the older animals. In the later phase, which began 30 min after endotoxin, both groups displayed systemic hypotension and pulmonary hypertension, and the groups did not differ from one another in this regard. With progression of endotoxic shock, more severe metabolic acidosis developed in the older animals than in the younger animals. Plasma thromboxane B2 levels in the older group were about double those in younger piglets. Plasma 6-keto-PGF1 alpha and TNF alpha levels in both groups were similar and were significantly increased in the later phase.(ABSTRACT TRUNCATED AT 250 WORDS)

6-Ketoprostaglandin F1 alpha↗
PubMed1992

Delayed thromboxane synthesis inhibition, but not cholinergic blockade, reverses group B streptococcus-induced pulmonary hypertension.

Anisodamine, an anticholinergic drug, is widely used in China for treatment of infants with septic shock and has been reported to inhibit thromboxane synthesis in cultured cells. Thromboxane A2 plays an important role in the early pulmonary hypertension in sepsis; however, the role of thromboxane A2 later in sepsis is unclear. We tested the hypothesis that thromboxane A2 synthesis inhibition with dazmegrel, and cholinergic blockade with anisodamine, would attenuate the later phase of pulmonary hypertension induced by 4 h of group B streptococcus (GBS) infusion. 1 mg/kg of dazmegrel reversed the pulmonary hypertension and slightly increased cardiac output; these hemodynamic improvements persisted for 30-60 min. Plasma thromboxane B2 levels returned toward pre-GBS baseline values after dazmegrel treatment. Thus, thromboxane A2 is still a major mediator of pulmonary hypertension in piglets after 4 h of continuous GBS infusion. 0.5 mg/kg of anisodamine had no significant hemodynamic effect. 2 and 4 mg/kg of anisodamine each caused transient, dose-related decreases in systemic artery pressure; cardiac output also fell after the highest anisodamine dose. Pulmonary hypertension was not alleviated by anisodamine. All hemodynamic changes induced by anisodamine were short-lived and returned to preanisodamine values within 10 min. Anisodamine did not ameliorate thromboxane-mediated pulmonary hypertension in this animal model, and therefore may not inhibit thromboxane synthesis in vivo. The results of this study do not support the use of anticholinergic therapy to improve hemodynamics in GBS sepsis, but do suggest that thromboxane synthesis inhibition may be a clinically useful therapy in advanced GBS sepsis.

Animals↗
PubMed1992

Role of capsule in pulmonary hypertension induced by group B streptococcus.

The type-specific polysaccharide capsule of group B streptococcus (GBS) is thought to be an important factor in the pathogenesis of disease. We used an acutely instrumented piglet model to assess the hemodynamic effects of rapid infusions of two heat-killed GBS type Ib strains isolated from the spinal fluid of an infant with late-onset meningitis and from the vaginal culture of his mother. These strains expressed different amounts of capsule, as determined by buoyant density centrifugation and electron micrographs, and they produced different hemodynamic effects in the piglets. The mother's strain, which had a smaller capsule, caused significantly higher increases in pulmonary artery pressure and vascular resistance than did the infant's strain, which had a larger capsule. Transposon mutants were then made from the infant's isolate to further study the role of capsule in pulmonary hypertension. Two mutants lacking detectable capsular type-specific polysaccharide were compared with the original isolate and with an isogenic mutant containing transposons but having a large capsule. The nonencapsulated mutants caused significantly higher changes in pulmonary artery pressure and resistance than did the encapsulated strains. Pulmonary hypertension may play a role in the pathophysiology of GBS sepsis, but the presence of a large capsule may partially cloak the hemodynamically active component(s) of the bacteria. The lower initial host response to heavily encapsulated GBS may play a role in pathogenesis by helping the organisms avoid host defense mechanisms.

Animals↗
PubMed1991

Fused eyelids, airway anomalies, ovarian cysts, and digital abnormalities in siblings: a new autosomal recessive syndrome or a variant of Fraser syndrome?

We describe two siblings of unlike gender born to non-consanguineous parents, with similar and unique congenital malformations. These include fused eyelids, craniofacial anomalies, ovarian cyst, subglottic stenosis, specific digital abnormalities, and no detected chromosomal abnormality. The specific digital abnormalities in both patients are characterized by extension of metacarpophalangeal joints with flexion of the proximal interphalangeal joint of both index fingers with resulting overlap of the second digit over the third. Similar changes were noted in both second toes. The brain weight of both infants was less than that expected for their birth weights. We reviewed the differential diagnosis of fused eyelids, airway anomalies, and ovarian cysts, and the manifestations resemble those seen in Fraser syndrome. We conclude that the dissimilarities warrant considering that our patients have a distinct autosomal recessive syndrome.

Congenital Abnormalities↗
PubMed1991

Perspectives on perinatal asphyxia: pathophysiology, presentation, and prognosis.

Perinatal asphyxia is a common and potentially serious problem in the management of labor and delivery. Severe perinatal asphyxia can cause significant short- and long-term sequelae. While the pathophysiology and sequelae of perinatal asphyxia in animals is understood fairly well, asphyxiation cannot be reliably prevented or effectively treated once it occurs in the newborn human. However, with a better understanding of what perinatal asphyxia is and its expected clinical symptoms and outcomes, perinatal nurses can better care for asphyxiated infants.

Apgar Score↗
PubMed1990

Effects of position changes on transcutaneous carbon dioxide tension in neonates with respiratory distress.

Routine neonatal care includes frequent position changes. Recent research has concluded that positions other than supine may result in beneficial physiologic responses. Specifically, several studies suggest that neonates may ventilate more effectively in a prone rather than in a supine position. This study tested the hypothesis that transcutaneous carbon dioxide tension (TcPCO2) would be lower in the prone than in the supine position in neonates with respiratory distress. Fourteen ventilated infants were studied. TcPCO2 was measured and recorded in prone, supine, and right-side-lying positions for each subject. There were no statistically significant differences in mean TcPCO2 values between the three positions (F = .45; df 2,39; P = .64). The relationship between TcPCO2 and PaCO2 values was stable (r = .88) during the studies. The results indicate that changing a neonate's position does not significantly alter transcutaneous carbon dioxide tension.

Blood Gas Monitoring, Transcutaneous↗
PubMed1989

Intraventricular haemorrhage and the renin-angiotensin-aldosterone system in very low birthweight infants.

Blood volume, plasma renin activity (PRA) and urine aldosterone excretion (UAE) were measured in ten very low birthweight infants who had a Grade 3 or 4 intraventricular haemorrhage (IVH) during the first 2 days after birth. Mean (range) birthweight was 950 (630-1500) g and gestational age was 27 (23-31) weeks. Nine infants were receiving assisted ventilation and one was breathing spontaneously. Eight IVH occurred on the first postnatal day and two on the second; seven were symptomatic and three asymptomatic. PRA was significantly higher than control values on Day 1 only; median 244 (range 91-654) ng/ml per h vs. 64 (4-259) ng/ml per h (P less than 0.01). Infants with symptomatic IVH in the preceding 8 h (n = 6) all had PRA greater than 300 ng/ml per h; none of these infants had received transfusions or volume expansion between IVH and PRA measurement. PRA was less than 100 ng/ml per h in the three infants with asymptomatic IVH and one infant with greater than 24 h interval between IVH and PRA measurement; three of these four had received transfusions prior to PRA measurement. UAE was not significantly different from control values on either Day 1 or Day 2. Blood volume at 22 +/- 3 h postnatal age ranged from 75 to 107 ml/kg. There was an inverse logarithmic correlation between PRA and blood volume (r = 0.883; P less than 0.005), with PRA values exceeding 300 ng/ml per h when blood volume was less than 90 ml/kg. UAE did not correlate with either PRA or blood volume.(ABSTRACT TRUNCATED AT 250 WORDS)

Aldosterone↗
PubMed1989

Ureaplasmal pneumonia and sepsis associated with persistent pulmonary hypertension of the newborn.

Ureaplasma urealyticum was isolated from the lower respiratory tract of three infants with persistent pulmonary hypertension of the newborn. In one, cultures positive for U urealyticum were obtained on multiple occasions from trachea, blood, and pleural fluid prior to the infant's death on postnatal day 6. Autopsy findings confirmed the presence of severe pneumonia and the organism was again recovered from multiple sites. A second infant had no apparent predisposing factors for development of persistent pulmonary hypertension of the newborn but U urealyticum and Staphylococcus epidermidis were recovered from the trachea antemortem and from lung tissue obtained during autopsy on the 12th postnatal day. The third infant had persistent pulmonary hypertension of the newborn and a pulmonary infiltrate within hours after birth with tracheal cultures positive for both U urealyticum and Mycoplasma hominis. Erythromycin was given for ten days, and the infant gradually improved. Prolonged ventilation with supplemental oxygen was necessary, and chronic lung disease developed. This is the first report of neonatal ureaplasmal pneumonia with sepsis and persistent pulmonary hypertension of the newborn as well as the first time a microorganism other than streptococci has been specifically implicated in the pathogenesis of persistent pulmonary hypertension of the newborn. Respiratory infections with U urealyticum or other bacteria should be considered as possible causative or contributory factors in infants with persistent pulmonary hypertension of the newborn.

Female↗
PubMed1988

Hemodynamic responses of chronically instrumented piglets to bolus injections of group B streptococci.

Group B beta-hemolytic Streptotocci cause pulmonary hypertension when injected into animals and may precipitate the persistent pulmonary hypertension syndrome in infected human neonates. We used chronically instrumented piglets to study the effects of repeated injections of heat-killed group B Streptococcus (GBS) type III. Daily exposure to GBS was associated with a 2-fold or greater potentiation of pulmonary and systemic hypertensive responses after 1 wk. Throughout experimentation, pulmonary pressure changes were more marked than systemic changes. After establishing a dose-response relationship, we chose a control dose that produced intermediate hypertensive responses. We then evaluated the effects of antibody and various drugs on the hypertensive responses. Preincubation of organisms with rabbit antiserum containing type-specific antibody enhanced the responses. Beta endorphin blockade with naloxone had little or no effect; leukotriene synthesis inhibition also did not affect responses. Both indomethacin, a cyclooxygenase inhibitor, and dazmegrel, a specific thromboxane synthesis inhibitor, blocked the hypertensive responses to GBS. It appears that repeated doses of GBS potentiate the hypertensive responses, a process that we hypothesize may be mediated by development of type-specific antibody as type-specific antibody levels rose during potentiation. It is likely that thromboxane A2 is the effector of the pulmonary and systemic hypertensive responses to GBS injection, because thromboxane inhibition by dazmegrel was as effective as indomethacin in blocking these effects. Thromboxane synthesis blockade may prove useful in management of hemodynamic disturbances accompanying severe bacterial infections in humans.

Animals↗
PubMed1987

Capillary and venous bilirubin values. Are they really different?

We measured total serum bilirubin values in paired capillary and venous samples from 79 untreated jaundiced newborn infants (group 1) and in 29 infants who were receiving phototherapy (group 2). While bilirubin values from the two sites correlated significantly for both groups, capillary samples underestimated venous bilirubin values when the latter exceeded 170 mumol/L (10 mg/dL) (mean and 95% confidence limits: group 1, -15.1 mumol/L [-0.9 mg/dL] and -24.7 to -5.5 mumol/L [-1 to -0.3 mg/dL]; group 2, -10.3 mumol/L [-0.6 mg/dL] and -17.1 to -3.4 mumol/L [-1 to -0.2 mg/dL]). Furthermore, capillary samples underestimated venous bilirubin levels by more than 17 mumol/L (1 mg/dL) in eight of 16 group 1 patients and five of 18 group 2 patients when venous bilirubin values exceeded 170 mumol/L (10 mg/dL). Lower capillary values at higher bilirubin levels might be due to the influence of environmental light. As clinical treatment decisions may be made on the basis of differences in serum bilirubin level of about 17 mumol/L (1 mg/dL) and as capillary samples may underestimate venous bilirubin levels by a similar amount, it may be prudent to measure venous rather than capillary bilirubin levels when the total serum bilirubin level exceeds 170 mumol/L (10 mg/dL).

Bilirubin↗
PubMed1987

Thromboxane synthesis inhibition reverses group B Streptococcus-induced pulmonary hypertension.

Group B Streptococcus (GBS) sepsis in humans may cause the persistent pulmonary hypertension syndrome. Infusions of GBS in animals elevate pulmonary artery pressure (PAP) and resistance and are associated with elevated thromboxane levels. We investigated the hemodynamic effects of the specific thromboxane synthesis inhibitor, dazmegrel, in a piglet model of GBS-induced pulmonary hypertension. PAP rose from 22 +/- 6 to 42 +/- 11 (SD) mm Hg during infusion of heat-killed GBS; pulmonary vascular resistance increased from 1440 +/- 400 to 4000 +/- 1040 dyne X sec/cm5. No significant changes in cardiac output, mean arterial pressure, or left atrial pressure were noted. Treatment with 1 mg/kg of dazmegrel resulted in a rapid return of PAP and resistance to control values. No other hemodynamic effects of either bacteria or drug were observed despite continued infusion of GBS.

Animals↗
PubMed1987

Low colloid osmotic pressure in very low birthweight infants receiving assisted ventilation.

Plasma colloid osmotic pressure (COP) was measured in three groups of very low birthweight infants. Babies in Group 1 (n = 8) were breathing spontaneously and had no respiratory disease. Those in Group 2 (n = 9) received assisted ventilation for hyaline membrane disease (HMD), and those in Group 3 (n = 7) received assisted ventilation for other reasons (five apnoea, two pneumonia). Both assisted ventilation groups had lower mean COP values than spontaneously breathing infants. Mean values (s.e.m.) for Groups 1, 2 and 3, respectively, were: 15.3 (0.6), 11.3 (0.4) and 11.9 mmHg (0.5) (P less than 0.001) on Day 1; and 15.2 (0.4), 12.9 (0.4) and 12.8 mmHg (0.3) (P less than 0.001) on Day 2. The increase from Day 1 to Day 2 was significant for those with HMD (P less than 0.05). Colloid osmotic pressure correlated with mean blood pressure (r = 0.51; P less than 0.001) but not with birthweight, gestation, crystalloid fluid intake or pH. The role of low COP in the pathogenesis of acute respiratory failure in infants with uncomplicated HMD is unclear, but such low COP may contribute to development of pulmonary oedema as a complication, particularly if the ductus arteriosus is still patent and the infants are given high volume intravenous fluids.

Blood Pressure↗
PubMed1986

Influence of prostaglandin D2 on hemodynamic effects of group B streptococcus in neonatal lambs.

Infusions of group B streptococci cause pulmonary hypertension in several neonatal animal models. A continuous infusion of prostaglandin D2 reduced the magnitude of this pulmonary hypertensive response; indomethacin completely blocked the response. Prostaglandin D2 or cyclooxygenase inhibitors may be important therapeutic agents for infants with group B streptococcal sepsis who manifest pulmonary hypertension.

Animals↗
PubMed1986

The effect of assisted ventilation on creatinine clearance and hormonal control of electrolyte balance in very low birth weight infants.

Because renal function and electrolyte balance are commonly altered in premature infants, particularly those requiring ventilatory support, we studied the influence of assisted ventilation on renal electrolyte and water excretion in infants with birth weights less than 1501 g during the 2 days after birth. Twenty-two infants receiving assisted ventilation, either as intermittent mandatory ventilation or nasal continuous positive airway pressure, were compared with 21 spontaneously ventilating infants of similar birthweight and gestational age. Mean (and SEM) creatinine clearance was lower (p less than 0.05) in the assisted ventilation group on day 1 (2.9 +/- 0.4 versus 4.1 +/- 0.4 ml/min/1.73 m2) and on day 2 (4.1 +/- 1.0 versus 6.8 +/- 0.8 ml/min/1.73 m2, p = 0.05), and there was a correlation between creatinine clearance and mean blood pressure in both groups. Mean urine vasopressin was higher in the assisted ventilation group on the first day (360 +/- 86 versus 123 +/- 30 pg/mg creatinine; p less than 0.02) and correlated with higher urine osmolality. There were no differences in urine volume, in osmolar or free water clearances, or in the intake and urine excretion of sodium, potassium, and chloride. Plasma renin activity, urine aldosterone, and urine prostaglandin E2 were similar in both groups on both days. Neither the mode of assisted ventilation nor the cause of respiratory failure appeared to affect these results.

Creatinine↗
PubMed1985

Fatal meconium aspiration syndrome occurring despite airway management considered appropriate.

A combined obstetric-pediatric approach to tracheal toilet is said to prevent serious cases of the potentially fatal meconium aspiration syndrome. After delivery of the head a DeLee trap is used to suction the oropharynx and nasopharynx. Immediately following delivery, endotracheal suction is performed in an effort to remove any remaining meconium-stained amniotic fluid. Although routinely using this approach, we continue to have occasional cases of fatal meconium aspiration syndrome. Therefore, we reviewed the outcome of infants born through meconium-stained fluid. During a 5-year period, 1420 (15%) of 9299 live-born infants had meconium-stained fluid. Thirty (2.1%) of these 1420 developed meconium aspiration syndrome and 12 (40%) died; eight received a postmortem examination. Four had unequivocal evidence of meconium aspiration, two had large numbers of intra-alveolar squamous cells, and two had no evidence of aspiration. We conclude that aggressive airway management during and immediately after delivery does not always prevent fatal meconium aspiration syndrome.

Amniotic Fluid↗
PubMed1985

Diuresis and natriuresis following acute pneumothorax in very low birthweight infants.

Seven tension pneumothoraces developed in six very low birthweight infants receiving assisted ventilation for hyaline membrane disease. Mean values for blood pressure and creatinine clearance (Ccr) tended to increase following pneumothorax decompression, although neither increase was statistically significant. Urine volume, osmolar clearance and urine sodium excretion all increased significantly in the 8 h following diagnosis and decompression of pneumothoraces. However, when expressed as a percentage of Ccr, none of these variables changed significantly. Mean sodium balance changed from positive to negative despite a significant increase in urine aldosterone excretion. It is suggested that the increases in osmolar clearance and sodium excretion were consequences of the increase in Ccr following pneumothorax decompression. Developmental immaturity in the renal tubular response to aldosterone might also have contributed to development of negative sodium balance.

Acute Disease↗
PubMed1985

Alkalosis attenuates hypoxic pulmonary vasoconstriction in neonatal lambs.

Hyperventilation (respiratory alkalosis) is an important treatment for persistent pulmonary hypertension in neonates. The precise way that hyperventilation attenuates hypoxic pulmonary vasoconstriction is unclear. We studied the effect of alkalosis on hypoxia-induced pulmonary vasoconstriction in 13 acutely instrumented, pentobarbital anesthetized, neonatal lambs. We specifically examined the relative effects of a metabolic alkalosis versus a respiratory alkalosis on hypoxic pulmonary vasoconstriction and compared these results to the control response to hypoxia without alkalosis. Hypoxic pulmonary vasoconstriction was significantly milder whenever the animal was alkalotic, regardless of whether the alkalosis was respiratory of metabolic. Thus, the elevated pHa rather than decreased PaCO2 during hyperventilation appears to be the major factor in moderating the response of the pulmonary vessels to acute hypoxia in this neonatal lamb model.

Alkalosis, Respiratory↗