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Biomedical subjects

A J de Beaufort

Publications and source records attributed to A J de Beaufort.

18 recordsLinked to original sources

Phospholipase A2 is present in meconium and inhibits the activity of pulmonary surfactant: an in vitro study.

UNLABELLED: Atelectasis, a major contributor to pulmonary dysfunction in meconium aspiration syndrome (MAS), is produced by bronchiolar obstruction and surfactant inactivation. It has been shown that substances in meconium, e.g. fatty acids, inhibit surfactant activity. However, the role of the enzyme phospholipase A2 (PLA2), which hydrolyses surfactant in adult respiratory distress syndrome (ARDS), has not yet been studied. Our objective was to investigate whether PLA2 is present in meconium and inhibits pulmonary surfactant activity in vitro. Therefore, the presence of PLA2 activity in meconium, collected from 10 newborns, was measured by the formation of lysophosphatidylcholine after incubation of meconium with radioactively labelled dipalmitoylphosphatidylcholine. Meconium was fractionated by Sephadex G-100 column chromatography and the fractions were assayed for PLA2 activity. Also, their effect on the surface tension of surfactant (Curosurf) was measured using a pulsating bubble surfactometer (PBS). PLA2 activity was present in all meconium samples. Addition of meconium to surfactant significantly increased surface tension (mean +/- SD: 1.7 +/- 1.6 mN/m to 24.3 +/- 6.7 mN/m, p = 0.0001) and only the addition of the PLA2 containing fraction from meconium to surfactant also significantly increased surface tension (mean 1.7 +/- 1.6 mN/m to 19.0 +/- 3.58 mN/m, p < 0.0001). CONCLUSION: PLA2 is present in meconium and inhibits the activity of pulmonary surfactant in vitro. Therefore, PLA2 in meconium may contribute to surfactant inactivation and alveolar atelectasis in MAS.

Biological Products↗

[Evaluation of gradual conversion to a less invasive therapeutic strategy for pregnant women with alloimmune thrombocytopenia in the fetus for prevention of intracranial hemorrhage].

OBJECTIVE: To evaluate a less invasive management strategy for pregnant women with neonatal alloimmune thrombocytopenia without a history of intracranial haemorrhage. DESIGN: Retrospective and descriptive. METHOD: In Leiden University Medical Centre, the Netherlands, in the period 1994-August 1999, 31 women with 32 pregnancies were treated. Six women had a history of a sibling with thrombocytopenia and intracranial haemorrhage and 26 a history of a sibling with (severe) thrombocytopenia without haemorrhage. Treatment options consisted of weekly administered intravenous immunoglobulin (ivIG) to the mother without diagnostic cordocentesis, cordocentesis with foetal blood sampling and intrauterine platelet transfusions to the fetus. In the group without history of intracranial haemorrhage fetal blood sampling and platelet transfusion were gradually abandoned as much as possible. RESULTS: In the children of the treated pregnant women there were no instances of intracranial haemorrhage. In addition, the platelet count in cord blood was higher, compared with patients treated before 1994 and with literature data. CONCLUSION: A less invasive management strategy in case of a history without intracranial haemorrhage seems justified based on results in our population. Administration of ivIG without diagnostic cordocentesis, however, results in a lost opportunity to verify the indication and the effectiveness of treatment.

Contraindications↗

The capacity of different infusion fluids to lower the prooxidant activity of plasma iron: an important factor in resuscitation?

BACKGROUND: Prooxidant activity of non-protein-bound iron (NPBI) is an important contributor to reactive oxygen species-induced injury after the resuscitation of critically ill patients. Plasma NPBI occurs in critically ill adults, children, and newborn babies, who often require resuscitation. The ability of the resuscitation fluids to bind iron and lower the patients' NPBI levels in vitro has not previously been studied. STUDY DESIGN AND METHODS: In an in vitro model, highly iron-saturated cord blood plasma from 10 preterm and 10 term babies was mixed with FFP, pasteurized plasma protein solution, and 0.9-percent saline. Plasma from 10 healthy adult volunteers was used as a control. Before and after the mixing with any resuscitation fluid, NPBI levels and ceruloplasmin iron-oxidizing and transferrin iron-binding antioxidant capacities were measured. RESULTS: After the in vitro mixing with FFP, the incidence and concentration of NPBI were markedly decreased and the iron-binding antioxidant capacity was increased in the plasma of the preterm and term babies. Being mixed with pasteurized plasma protein solution and 0.9-percent saline did not influence the iron-binding antioxidant capacity of newborn babies' plasma. In the control plasma, results were not changed after the mixing with any resuscitation fluid. In every group, the iron-oxidizing antioxidant capacity was not changed after the mixing with any fluid. CONCLUSION: Iron-induced oxidative tissue damage may be influenced by resuscitation fluids. In the ongoing debate over the choice of crystalloid or colloid resuscitation fluids, the influence of each fluid on the patient's antioxidant capacity warrants more attention.

Adult↗

[The stumbling toddler].

Four previously healthy children, two boys aged 5 and one boy and one girl aged 4 more or less acutely developed a stumbling gait. The causes varied from benign such as postviral acute cerebellar ataxia and benign paroxysmal vertigo to potentially life-threatening such as intoxication with benzodiazepines and medulloblastoma. Treatment led to complete or partial recovery. (Sub)acute balance disorders in previously healthy children can be due to cerebellar ataxia, vestibular disorders and abnormal proprioception. Ancillary investigations are warranted in case of gradually developing ataxia, accompanying neurological deficits, suspicion of intoxication, recurrent or familial ataxia, no spontaneous remission or even progression. In children with an isolated cerebellar ataxia without these features, ancillary investigations may be avoided, although in such cases careful follow-up remains necessary.

Anti-Anxiety Agents↗

Acinetobacter junii causes life-threatening sepsis in preterm infants.

Acinetobacter junii caused sepsis in six preterm infants in our neonatal unit within 48 h. Each infant with clinical signs of systemic infection and activation of the acute phase response had two positive blood cultures with Acinetobacter junii. The sudden onset, the short duration of the outbreak and the fact that none of the infants were colonized by A. junii suggested a common source of A. junii administered directly into the blood. The only feature shared by all six affected newborns was an intravenous fat emulsion (Intralipid 10%), which was shown to be an excellent growth medium for A. junii. Sepsis did not occur in four infants with 20% fat emulsion or amino acids only. Vaminolact did not support growth of the outbreak strain. The immediate source of the outbreak could not be identified: samples of the actual feeds given were not available for investigation, but A. junii was not isolated from parenteral solutions with identical batch numbers used in the septic infants. We conclude that Acinetobacter junii can cause a life-threatening infection in preterm neonates. Contaminated intravenous fat emulsion is implicated as a possible source of the infection. As a part of rigid infection control, intravenous feedings should be prepared under aseptic conditions.

Acinetobacter Infections↗

Effect of interleukin 8 in meconium on in-vitro neutrophil chemotaxis.

BACKGROUND: Pneumonitis, characterised by large numbers of neutrophils in the lung, is an important feature of the meconium aspiration syndrome. The mechanism underlying the neutrophil influx is not known. We have investigated whether meconium has chemotactic activity and whether such activity is related to the presence of interleukin 8. METHODS: The chemotactic activity of meconium on neutrophils from newborn infants was assessed in a Boyden-chamber assay. Interleukin 8 and formyl-methionyl-leucyl-phenylalanine (f-MLP) served as positive controls. Inhibition of chemotaxis was assessed with monoclonal antibody to interleukin 8. The interleukin-8 concentration was measured by ELISA. FINDINGS: Sterile meconium suspension from seven unrelated newborn babies increased migration of neutrophils from neonates in comparison with random migration (79, 72, 70, 50, 58, 88 microm vs 46 microm; p<0.001). This effect was greatest at a meconium concentration of 5 g/L, although differences between samples from individual babies were observed. Interleukin 8 was present in all meconium suspensions (480-3980 ng/L). Anti-interleukin-8 inhibited neutrophil migration. INTERPRETATION: Interleukin 8 is present in meconium and it induces chemotaxis of neutrophils in vitro. This mechanism may have a role in the pathogenesis of pneumonitis in meconium aspiration syndrome.

Chemotaxis, Leukocyte↗

[Nitric oxide inhalation in newborn infants with pulmonary hypertension].

Nitric oxide (NO) is an important endogenous vasodilator. NO, produced in the endothelial cell, causes vasodilation by relaxation of the vascular smooth muscle cell. Inhalation of NO plays a role in the treatment of persistent pulmonary hypertension of the newborn, a syndrome with considerable morbidity and mortality. NO inhalation specifically leads to pulmonary vasodilation without systemic hypotension, since NO binds avidly to haemoglobin. Neonates with pulmonary hypertension associated with lung hypoplasia, meconium aspiration syndrome, infantile inspiratory distress syndrome due to surfactant deficiency, and sepsis have been treated with inhaled NO. Literature data on NO inhalation and experience in our units with NO inhalation show an improvement in arterial oxygen tension and a decreased need for extracorporeal membrane oxygenation, but no reduction in mortality. NO toxicity as a result of NO inhalation in the newborn has not been reported yet.

Administration, Inhalation↗

Outbreak of septicaemia in neonates caused by Acinetobacter junii investigated by amplified ribosomal DNA restriction analysis (ARDRA) and four typing methods.

Septicaemia caused by Acinetobacter occurred in six infants in the neonatal unit. A total of 18 acinetobacters were isolated from blood cultures, cultures of intravascular catheters, and surveillance cultures. Twelve isolates from the six affected infants were identified as Acinetobacter junii by the use of a novel method, amplified ribosomal DNA restriction analysis (ARDRA). Typing of the organisms using the biochemical profiles of the API 20NE system, antibiogram typing, cell envelope protein electrophoresis, and PCR fingerprinting with two primer sets, ERIC1/ERIC2 and ERIC2/ 1026, showed that these 12 isolates were indistinguishable, whereas the remaining six isolates were different. The six infants recovered after therapy with ciprofloxacin alone in five cases and with a combination of ciprofloxacin and gentamicin in one case. This study showed that A. junii is capable of causing a serious, though non-fatal infection in neonates. The combined use of genotypic and phenotypic methods allowed the rapid separation of epidemic from non-epidemic isolates. It is concluded that for a better understanding of the role of the various Acinetobacter genomic species in human pathology, identification of acinetobacters according to the recent taxonomy is imperative.

Acinetobacter↗

Uric acid and ascorbic acid redox ratios in plasma and tracheal aspirate of preterm babies with acute and chronic lung disease.

This study compared plasma redox ratios of uric acid and ascorbic acid in well preterm babies with those with respiratory distress syndrome (RDS) and chronic lung disease (CLD), and investigated the relationship between these ratios and their respective measurements in tracheal aspirate. On day 1 after birth, plasma allantoin and allantoin/uric acid ratio were elevated in CLD (p < .05), and both markers of oxidative stress enabled early prediction of development of CLD (sensitivity and specificity: 54 and 83%, respectively). The relation between allantoin production and oxidative stress is supported by the correlation between the allantoin level and oxygen therapy in both RDS and CLD (p < .05). Reduced and oxidize ascorbic acid in plasma decreased postnatally in all groups and their redox ratio remained stable. Uric acid and ascorbic acid redox ratios were significantly elevated in tracheal aspirates compared to plasma samples (p < .05), and there was a strong positive correlation between both ratios (p < .005). These markers may be useful in monitoring babies with respiratory distress.

Antioxidants↗

Difference in binding of killed and live Streptococcus pneumoniae serotypes by C-reactive protein.

The binding and opsonic properties of C-reactive protein (CRP) for various species of bacteria were investigated. CRP bound more avidly to killed than to live Streptococcus pneumoniae, the binding varying among various serotypes; CRP hardly bound to a number of other bacterial species studied. CRP enhanced complement-dependent phagocytosis of live S. pneumoniae by granulocytes but did not enhance the phagocytosis of live Staphylococcus aureus or group B streptococci. We suppose that CRP may serve as an opsonin for killed bacteria and bacterial debris but is probably not an important opsonin for live bacteria other than S. pneumoniae.

Adult↗

Nitric oxide inhibition after hypoxia-ischemia elevates pulmonary arterial pressure and increases oxygen need.

Inhibition of nitric oxide (NO) production may reduce post-hypoxic-ischemic (HI) neonatal brain damage, but may also induce pulmonary hypertension by inhibiting endogenous NO production in the pulmonary vascular bed. The aim of this study was to evaluate the effect of nitric oxide inhibition on pulmonary artery pressure and oxygen need after hypoxic ischemia. Severe HI was produced in 18 newborn lambs. After completion of HI the lambs were divided into three groups of 6 animals receiving either placebo (Cont), low dose N omega-nitro-L-arginine (10 mg/kg i.v., NLA-10) or high dose (40 mg/kg i.v., NLA-40) to block NO production. Pulmonary artery pressure (Pap), aortic pressure, blood gases, inspiratory oxygen concentration and ventilator settings were recorded before and 15, 60, 120 and 180 min after HI. Mean Pap rose initially significantly as compared to baseline in all groups at 15 min post-HI, decreased to normal in Cont but not in treated animals; 180 min post-HI mean Pap was significantly higher in both treated groups as compared to control (NLA-10: 32 mm Hg, NLA-40: 34 mm Hg, Cont: 25 mm Hg, p < 0.05 for NLA-10 and NLA-40 vs. Cont). Moreover, in both NLA-treated groups the oxygenation index was significantly elevated 120 and 180 min post-HI as compared to those of the Cont group. NO synthase inhibition after HI causes a prolonged increase in pulmonary artery pressure leading to a higher oxygen need.

Animals↗

Foregoing intensive care treatment in newborn infants with extremely poor prognoses. A study in four neonatal intensive care units in The Netherlands.

Within the framework of the broader ethical discussion on end-of-life decision making in neonatology and the need to obtain more quantifiable data, we performed a multicenter study in four Dutch neonatal intensive care units. All infants who died in these units in 1993 were included in the study. Aside from cases in which foregoing treatment was not under discussion, cases in which death appeared inevitable (A cases) and cases in which foregoing treatment because of extremely poor prognosis was the decisive factor (B cases) were distinguished. A total of 181 neonatal deaths occurred. Thirty-five infants died even after full continuation of treatment. In 98 A cases and 48 B cases, which together represented 81% of all deaths, treatment was foregone either because the infants had no chance to survive or because of extremely poor prognoses. In these cases, the medical team ultimately achieved consensus of opinion, although in some instances several sessions were required. In three cases, the parents did not agree with the team advice. In one A case death appeared inevitable. In two B cases, the parents' wish to continue treatment was followed. In a large majority of B cases, the decisions to forego treatment were based on the presence of severe cerebral damage. In A cases there was no real choice because death appeared inevitable. However, in B cases neonatologists were obliged to determine whether continuation of treatment was justifiable or if withdrawal of treatment in view of extremely poor prognoses was preferred.

Decision Making↗

Inhalation of nitric oxide: effect on cerebral hemodynamics and activity, and antioxidant status in the newborn lamb.

Ventilation with nitric oxide (NO) is increasingly being used to treat pulmonary hypertension in the newborn. In the brain, NO has vasoactive properties and is involved in neurotransmission. However, the effect of inhaled NO on the cerebral blood flow (CBF) and on the cerebral activity is not known. Furthermore, there is little information on the influence of this free radical gas on the redox status in pulmonary vessels. We therefore investigated the effect of inhaled NO (2-60 ppm) on CBF, cerebral activity and redox status in blood effluent from the pulmonary circulation in 6 ventilated newborn lambs before and during group B streptococci (GBS)-induced pulmonary hypertension. Blood pressure in the pulmonary artery (P(ap)) and aorta (Pao), carotid artery blood flow (Qcar) to assess changes in CBF, and electrocortical activity were measured. Blood gases, indices of free radical status and methemoglobin were determined in blood samples obtained from the left ventricle. Inhalation of NO, before and during GBS-induced pulmonary hypertension, decreased P(ap) and PCO2 and increased PO2. Multiple linear regression revealed that Qcar was positively related to PCO2, but not to inhaled NO or PO2 before or during GBS conditions. Electrocortical activity and indices of antioxidative capacity and lipid peroxidation did not change significantly. Methemoglobin was not detected. In conclusion, inhalation of NO (up to 60 ppm) lowered P(ap) without directly affecting CBF, electrocortical activity, and redox status in the pulmonary vessels. CBF, however, can indirectly be influenced by NO-mediated changes in PCO2.

Administration, Inhalation↗

[Nitric oxide to combat pulmonary hypertension in an infant following heart surgery for septum defect].

A 5-month-old female infant with Down syndrome underwent surgical repair of a complete atrioventricular septal defect and a patent ductus arteriosus. The postoperative course was complicated by life-threatening pulmonary hypertensive crises which did not respond to conventional vasodilating therapy. Nitric oxide inhalation resulted in rapid decrease in pulmonary artery pressure and improvement of haemodynamics and oxygenation without causing any untoward side effects. Inhalation of NO was continued over the next 4 days, with a maximum NO concentration of 20 ppm during a period of 12 hours. The subsequent postoperative course was uneventful and the patient was discharged from the hospital in good health on the 23rd postoperative day.

Down Syndrome↗

Quantitative sensory examination in diabetic children: assessment of thermal discrimination.

Vibration perception thresholds (VPTs) and thermal discrimination thresholds (TDTs) were investigated in 55 insulin-dependent diabetic children aged 11.3 +/- 3.9 years (mean +/- SD) and in 81 controls. There was no significant difference in VPTs between the two groups. TDTs were significantly higher in the group of diabetic children (p less than 0.03). Eight diabetic children had abnormal thermal sensation and one child had abnormal vibratory sensation. TDT correlated positively with duration of diabetes mellitus (r = 0.25; p less than 0.05). Both investigations can be carried out easily and are unobtrusive, which is an important advantage in the examination of children.

Adolescent↗