Treatment of homozygous protein C deficiency and neonatal purpura fulminans with a purified protein C concentrate.
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Biomedical subjects
Publications and source records attributed to M Dehan.
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The effectiveness of intravenously administered immunoglobulin (Ig) therapy for prophylaxis of infection was evaluated in high-risk preterm infants. Two hundred thirty-five premature newborns were randomly assigned, in a double-blind controlled trial, to treatment and placebo groups. Thirty-five infants (29%) of the Ig group and 29 (25%) of the placebo group had one or more episodes of certain infection. Thirty infants (25%) of the Ig group and 18 (16%) of the placebo group had one or more episodes of probable infection. No significant differences were observed in the incidence of certain or probable infection in treated and control infants. Nevertheless, among the infants who had one or more certain or probable episodes of infection, more of them belonged to the Ig group than to the placebo group. The possible deleterious effect of the administration of large amounts of polyspecific Ig is discussed.
Bronchopulmonary dysplasia (BPD) is one of the most serious complications of neonatal intensive care. This chronic lung disease usually follows early pulmonary injuries. Surfactant defect, oxygen toxicity and barotrauma are three major factors leading to diffuse alveolar and bronchiolar damage, first step of BPD. BPD usually appears in preterm infants and correlates with degree of prematurity and the severity of neonatal distress syndrome. Infants with BPD frequently have poor outcome; the mortality rate is near 30%. The long-term survival prognosis is uncertain with a risk of bronchopathy in adulthood. Until date, current management of BDP is unsuccessful. New strategies are required to prevent neonatal respiratory distress syndrome and decrease its severity.
One peculiarity of pulmonary surfactant, which is the tensioactive material physiologically present at the surface of alveoli, lies in its very quick localization at in the air-water interface. This being one of the limiting factors of artificial exogenous surfactants for the treatment of patients suffering of respiratory distress syndromes, we have studied the mechanisms which are intervening in the adsorption kinetics of a pure liquid--phase phospholipid, the dioleylphosphatidylcholine (DOPC), and of mixtures of dipalmitoylphosphatidylcholine (DPPC) and phosphatidic acid (PA) in presence of divalent cations (Ca++ and Mg++). The adsorption kinetics of liposomal suspensions of DOPC, which were studied by the Wilhelmy plate method, are determined by the existence of a barrier potential which height depends on the temperature and medium osmolarity, and on the deformability of vesicules. The study of PA-DPPC liposomes was performed with the help of a pulsating bubble surfactometer, a physicochemical instrumentation which mimics the pulmonary alveoli. To obtain performant responses with this model, high concentrations of PA and of divalent cations Ca++ and Mg++ are needed. These results, which are similar to those observed during the study of liposomal fusion, allow to propose a model, according to which adsorption of liposomes at the air-water interface is comparable to liposomal fusion and may be related to the presence of a thin aqueous film.
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Phospholipid analysis of tracheal aspirates obtained from 37 newborn infants, all intubated for respiratory diseases, was performed in order to compare infants having hyaline membrane disease (HMD) (n = 11), to those presenting with transient tachypnoea (TT) (n = 16) or another respiratory disorder (n = 10) and to determine if distinguishing features could be discovered for HMD or TT. In the HMD group, a significantly lower amount (about 20%) of recoverable phospholipid material was observed. Furthermore, the groups differed in their phospholipid profile: infants with HMD presented with a deficiency in saturated phosphatidylcholine, but had a related increase in unsaturated phosphatidylcholine, and an increased proportion of phosphatidylethanolamine (about 2.5 times more) as compared with both other groups. In infants suffering HMD and TT, phosphatidylglycerol was lower and phosphatidylinositol was higher than in infants with other diseases. This change was the only one displayed in infants with TT. We speculate that the observed changes reflect changes in amount and composition of surfactant and are involved in the etiology of HMD and TT.
Forty-one preterm and fullterm infants (26.5-40.5 weeks gestational age and 31.5-50 weeks postconceptional age) free from neurologic and cardiopulmonary disease at the time of testing underwent a standardized esophageal dilatation test (EDT) during polygraphically controlled REM sleep. RR interval and total duration of the respiratory cycle (TTOT) were measured (1) during the 60 s preceding the EDT, i.e. mean control RR and mean control TTOT; (2) during EDT. Percent RR (%RR) was defined as the longest RR interval in milliseconds during EDT divided by mean control RR in milliseconds multiplied by 100, and percent TTOT (%TTOT) as the longest TTOT in seconds during EDT divided by mean control TTOT in seconds multiplied by 100. EDT provoked prolongation of both RR interval and TTOT. %RR decreased significantly with advancing gestational age (p less than 0.003), and %TTOT with advancing postconceptional age (p less than 0.003), indicating that both cardiac and respiratory responses to an EDT challenge are blunted with maturation.
Thirty-three premature and full-term infants (PCA, 31.5 to 50 weeks) who were free from neurologic and cardiopulmonary disease at the time of testing underwent a standardized TAS test during polygraphically controlled REM sleep. The R-R interval and the TTOT were measured before and during TAS. The R-R interval and TTOT changes during TAS were compared to the preceding 60-second mean R-R interval and TTOT in each infant and expressed as a percentage of mean control values (ie, % RR and % TTOT). During TAS, there was a significant negative correlation between cardiac and respiratory responses and postconceptional age (p less than 0.001 and p less than 0.0001, respectively). Prolongation of both the R-R interval and the TTOT elicited by TAS was significantly blunted by maturation.
Bronchopulmonary dysplasia (BPD) has become a frequent and worrying issue in neonatal intensive care units (NICU). The aim of this retrospective study was to define more precisely the incidence of BPD within a population of 2,216 newborns admitted at less than 24 hrs of life. 138 cases of BPD were diagnosed. The BPD rates decrease exponentially with regard to gestational ages (GA) [67% at less than 28 weeks (w), 37% at 28-29 w, 22% at 30 w, 9% at 31-32 w, 3% at 33-34 w and 0.4% at greater than or equal to 35 w]. The presence of hyaline membrane disease (HMD) increases the GA related risks by 1.5, 2, 3, 10, 20 and 40 times at less than 28 w, 28-29 w, 30 w, 31-32 w, 33-34 w and greater than or equal to 35 w, respectively. Other factors such as interstitial emphysema, refractory hypoxemia and hypotrophy associated with HMD, have been found associated with increased risks. A chart taking into account all these parameters has been constructed allowing the determination of individual risks of developing BPD during the first days of life.
Assessing the short-term prognosis of bronchopulmonary dysplasia (BPD) (duration of mechanical ventilation, of O2 therapy, and risk of death) is often uncertain at the early stages of the disease. From a retrospective study of 124 cases of BPD, we made a search for factors of poor prognosis which could be recognized early. Among the 124 BPD, 56 (45%) had a severe disease (mechanical ventilation for greater than 3 months and/or O2 for greater than 4 months), and 24 of them (20%) died. Two types of factors have been identified as linked to a poor prognosis (risk of evolution towards a severe disease in a proportion of 70 to 90%): some respiratory events (refractory hypoxemia, recurrent pneumothorax, interstitial emphysema, no improvement of hyaline membrane disease at 3-4 days of life in babies less than 32 weeks gestational age) and hemodynamic failures (cardiac failure due to persistent ductus arteriosus, collapse following infection or anoxia). We have also defined different values of a ventilatory index (I = mean airway pressure x FiO2) which allows the neonatologists to estimate the final prognosis of BPD during the first two months of life.
This study was designed to determine the effects of a mild increase in body temperature within the physiological range (0.8 degrees C) in healthy premature infants. Seven unsedated premature infants (38.4 wk +/- 1.5 postconceptional age) were monitored polygraphically during "morning naps" in an incubator under two different environmental temperatures: (1) normothermia with the incubator temperature set at 25 degrees C and the rectal temperature equal to 36.9 degrees C +/- 0.1; (2) hyperthermia with the incubator temperature set at 35 degrees C and the rectal temperature equal to 37.7 degrees C +/- 0.15. Respiratory frequency and heart rate, respiratory events, i.e., central and obstructive apnea, and periodic breathing with and without apneic oscillations were tabulated. Results for respiratory events were expressed as (1) indices of the total number of respiratory events, and of specific respiratory events per hour of total, quiet and active sleep times; (2) duration of total and specific respiratory events expressed as a percentage of total sleep, quiet and active sleep times. Respiratory frequency and heart rate were significantly increased by hyperthermia (P less than 0.05). Hyperthermia did not significantly modify the indices or the duration of central and obstructive apnea. But the indices and the duration of periodic breathing with and without apneic oscillations were significantly increased by hyperthermia during active sleep (P less than 0.05) but not during quiet sleep. The present study shows that a mild increase in body temperature within the physiological range in premature infants enhances the instability of the breathing pattern during active sleep.
The hyaline membrane disease (HMD) is a respiratory distress occurring at birth of some premature infants, attributed to an endogenous pulmonary surfactant deficiency. The present treatments are iatrogenic and inefficient for the most diseased infants. The exogenous surfactant supplementation intends to give to the baby formulations playing in vivo the role of the natural surfactant. The research developed for the formulation and the diffusion of these exogenous surfactants have to solve physicochemical problems but also of industrial production and of safety use. In spite of their adequate physicochemical and pharmacological properties, surfactants of natural sources, for industrial grounds, are not still distributed at a large scale. The efficiency of artificial surfactants is variable, and the use of non-biodegradable molecules in several preparations let to safety problems. The development of new types of artificial surfactants, more efficient and safe, implies a better knowledge of the physico-chemical mechanisms intervening in the pulmonary surfactant dynamics.
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Improvements in combining obstetrics and neonatology led to a trend to intervene earlier in premature babies born before the 33rd week of gestational age. The enquiry that was carried out in 1985 in the Paris geographical region had as its objective to assess on the one part how many premature deliveries occurred between the 25th and 33rd week of amenorrhea and on the other hand what happened in the short term to the infants born from these pregnancies, i.e., their mortality; and for those who survived, their quality of life. The study was carried out on a representative sample of the deliveries in 1985 in the four departments of the Paris region--Paris and the three departments of the Petite Couronne--where half of all deliveries were assessed. The enquiry covered 53,430 deliveries for which the overall prematurity rate was 4.5%, and those deliveries that occurred before 33 weeks of gestational age constituted 1.0% (539 babies). Twenty children were lost for follow-up after a year. This was 4.9% of the live births and 6.3% of the live children who left the neonatology centres. At 2 years of age, the numbers that were not followed up were eventually 24, which was 5.8% of live births and 7.6% of those that left the centres of neonatology. The results show a very high rate of antepartum mortality but also of mortality during and after labour. Only 379 infants out of the 539 (70%) were transferred into special care baby units. By 1 year of age, the survivors were 57% of the total number of deliveries and 75% of the live births and 82% of those transferred to the special units. As far as concerned those that were live born, the survival rate at the age of 1 year varied considerably according to the duration of the pregnancy. The number of those that survived a pregnancy of less than 27 weeks was low (31%). It was, at 28 weeks, 53%. This is the age where births have to be registered. It reached 87% of the live births that occurred at 32 weeks. One has to point out that there is no statistically significant difference between 27 and 28 weeks of gestation. Whereas there is a significant difference (p less than 0.05) with those delivered at 29 weeks (75%). 80% of those 291 infants that were examined at 1 year of age were considered to be normal as far as psychomotor and sensorial behaviour was concerned.(ABSTRACT TRUNCATED AT 400 WORDS)
The authors report the case of a newborn whose mother presented with pre-eclampsia. Intrauterine growth retardation, peripheral edema, ascitis and pleural effusion were present at birth. The authors suggest that placental vascular abnormalities could be responsible for fetal heart failure and edema syndrome.