Increased upper airway cytokines and oxidative stress in severe obstructive sleep apnoea.

Inflammation may contribute to upper airway pathophysiology in obstructive sleep apnoea (OSA). Our objective was to compare upper airway pro-inflammatory cytokine expression, oxidative stress and connective tissue deposition in severe (n = 25) versus mild (n = 17) OSA patients. Upper airway surgical specimens were separated by predominance of either mucosal or muscle tissue. Expression levels of interleukin (IL)-1α, IL-6, interferon-γ, RANTES (regulated on activation, normal T-cell expressed and secreted), transforming growth factor (TGF)-ß and l-selectin were measured by ribonuclease protection assay. Oxidative stress was assessed via protein carbonyl group detection by immunoblotting. Histochemistry was employed for immunolocalisation of selected cytokines and connective tissue morphometry. In the severe OSA group, expression of IL-1α, IL-6 and TGF-ß was significantly higher in mucosa-predominant tissues, whereas in muscle-predominant specimens, RANTES expression was greater in severe OSA. Increased protein carbonylation was observed in severe OSA within both mucosal and muscle compartments. Immunohistochemistry localised TGF-ß to submucosal and perimuscular inflammatory cells, while IL-6 was primarily localised to myocytes. Consistent with the pro-fibrotic cytokine profile observed in mucosa-predominant tissue, morphometric analysis revealed greater submucosal and perimuscular connective tissue in severe OSA subjects. There is increased pro-inflammatory and pro-fibrotic cytokine expression, oxidative stress, and connective tissue deposition in upper airway tissues from severe versus mild OSA patients.

Comparative outcome study between triplet and singleton preterm newborns.

AIM: To evaluate the outcome of triplet versus singleton preterm newborns. METHODS: The study population included 64 sets of preterm triplet (gestational age 25-34 wk) and 64 singleton controls. Data on prenatal and perinatal findings, neonatal complications, duration of hospitalization, and neonatal mortality were collected by chart review. RESULTS: Mothers of triplets were more likely to receive prenatal tocolytic treatment and more antenatal steroids for foetal lung maturation, and to be delivered by caesarean section. No differences were found between the groups in perinatal parameters (cord pH, Apgar score, respiratory support after birth), respiratory parameters (severity of acute and chronic lung disease, use and duration of oxygen treatment and assisted ventilation), or neonatal complications (patent ductus arteriosus, intraventricular haemorrhage, periventricular leukomalacia, necrotizing enterocolitis, retinopathy of prematurity, meningitis, sepsis and jaundice). This was also true for duration of hospitalization and neonatal mortality. No differences were recorded by birth order among the triplets for any of these parameters. CONCLUSION: The study indicates that good prenatal care can lead to a good outcome for preterm triplets, close to that of preterm singleton infants. Families and physicians should consider this information when foetal reduction is offered.

Early postnatal dexamethasone treatment and increased incidence of cerebral palsy.

OBJECTIVE: To study the long term neurodevelopmental outcome of children who participated in a randomised, double blind, placebo controlled study of early postnatal dexamethasone treatment for prevention of chronic lung disease. METHODS: The original study compared a three day course of dexamethasone (n = 132) with a saline placebo (n = 116) administered from before 12 hours of age in preterm infants, who were ventilated for respiratory distress syndrome and had received surfactant treatment. Dexamethasone treatment was associated with an increased incidence of hypertension, hyperglycaemia, and gastrointestinal haemorrhage and no reduction in either the incidence or severity of chronic lung disease or mortality. A total of 195 infants survived to discharge and five died later. Follow up data were obtained on 159 of 190 survivors at a mean (SD) age of 53 (18) months. RESULTS: No differences were found between the groups in terms of perinatal or neonatal course, antenatal steroid administration, severity of initial disease, or major neonatal morbidity. Dexamethasone treated children had a significantly higher incidence of cerebral palsy than those receiving placebo (39/80 (49%) v. 12/79 (15%) respectively; odds ratio (OR) 4.62, 95% confidence interval (95% CI) 2.38 to 8.98). The most common form of cerebral palsy was spastic diplegia (incidence 22/80 (28%) v. 5/79 (6%) in dexamethasone and placebo treated infants respectively; OR 4.45, 95% CI 1.95 to 10.15). Developmental delay was significantly more common in the dexamethasone treated group (44/80 (55%)) than in the placebo treated group (23/79 (29%); OR 2. 87, 95% CI 1.53 to 5.38). Dexamethasone treated infants had more periventricular leucomalacia and less intraventricular haemorrhage in the neonatal period than those in the placebo group, although these differences were not statistically significant. Eleven children with cerebral palsy had normal ultrasound scans in the neonatal period; all 11 had received dexamethasone. Logistic regression analysis showed both periventricular leucomalacia and drug assignment to dexamethasone to be highly significant predictors of abnormal neurological outcome. CONCLUSIONS: A three day course of dexamethasone administered shortly after birth in preterm infants with respiratory distress syndrome is associated with a significantly increased incidence of cerebral palsy and developmental delay.

Late diagnosis of Down syndrome due to incorrect cytogenetic diagnosis and extreme prematurity.

A 26-week gestation, premature neonate who developed a transient myeloproliferative disorder is presented. The morphological features of Down syndrome were not obvious at this gestational age, and the cytogenetic studies gave a misleading normal karyotype after the infant received non-irradiated blood. The diagnosis of Down syndrome was not made until 27 weeks after delivery. The problem of misleading cytogenetic results is discussed in particular in premature infants receiving transfusions with non-irradiated blood products. Although the possibility of uniparental diosomy due to loss of one chromosome 21 was not excluded, this seems to be the first report of a false-normal cytogenetic study after non-irradiated blood.

Are bilirubin and plasma lipid profiles of premature infants dependent on the lipid emulsion infused?

The effect of a lipid emulsion containing long-chain triglycerides (LCT) and supplemented with L-carnitine on plasma lipids and bilirubin in premature neonates on total parenteral nutrition was compared to that of lipid emulsions containing either LCT or a mixture of LCT and medium-chain triglycerides (MCT). In a double-blind randomized study 49 premature neonates received one of the three fat emulsions, given intravenously, over 16-20 h daily for 6 days. Plasma carnitine levels increased significantly in the supplemented group only; the addition of carnitine did not seem to affect any of the parameters studied. Mean plasma triglycerides rose by 193 and 199% in the carnitine-supplemented and the LCT groups, respectively, and by 314% in the MCT/LCT group. On the sixth day of the study free fatty acids were significantly higher in the MCT/LCT group than in the other two groups. Plasma phospholipids and free cholesterol increased (p < 0.05) progressively in all groups and were correlated (r = 0.74, p < 0.001). At the end of the 6-day study all groups showed a similar decline in free and total bilirubin levels despite the significant increase in plasma lipids and free fatty acids resulting from the stepwise increase in lipid load. No correlation was found between free fatty acids and free bilirubin. Since hyperbilirubinemia and hypertriglyceridemia appear to be clinically independent factors, the infusion of lipids should not be withheld from jaundiced infants on total parenteral nutrition.

Effect of three intravenously administered fat emulsions containing different concentrations of fatty acids on the plasma fatty acid composition of premature infants.

The effects of an intravenously administered lipid emulsion supplemented with gamma-linolenic acid on the fatty acid profile of premature infants were compared with those of two conventional lipid emulsions. Fifty-nine premature neonates receiving total parenteral nutrition were randomly assigned to receive either fat emulsion containing gamma-linolenic acid and long-chain triglycerides (LCT), an LCT emulsion, or a 50% (wt/wt) mixture of medium-chain triglycerides and LCT emulsion. Forty-nine infants completed the study. During the 6-day study there was a significant tenfold increase in the plasma levels of gamma-linoleic acid in the supplemented group versus the other two groups. A significant threefold to fivefold increase in the omega 6 long-chain polyunsaturated fatty acids was observed in all groups. These changes seemed to be attributable mostly to linoleic acid from the lipid emulsion, despite the 50% lower dose in the medium- and long-chain triglycerides group. The increase in the omega 3 long-chain polyunsaturated fatty acids also was mainly caused by a similar increase in the level of alpha-linolenic acid. No differences were recorded in the linoleic/alpha-linolenic acid ratio among the groups. Plasma levels of some of the semiessential fatty acids were significantly higher in the medium- and long-chain triglycerides group than in the LCT group. This may be related to slower elimination of LCT, to the difference between emulsions, or to less substrate inhibition on delta-6-desaturase, which seems to be less of a rate-limiting enzyme than previously considered. Further intravenous feeding trials are needed to identify the optimal balance of fatty acids for nutrition of these premature infants.

Hemophilia B in a neonate: unusual early spontaneous gastrointestinal bleeding.

A full-term male, healthy newborn infant suddenly developed melena and rectal fresh blood oozing at age of 4 days. He is the second patient described in the literature presenting a spontaneous gastrointestinal bleeding in the neonatal period as the first clinical manifestation of hemophilia B. The early appearance and severity of the hemorrhage, its short duration, and good response to Factor IX (inefficiency of vitamin K) was the characteristics of the affected neonate. Whenever a newborn presents early spontaneous gastrointestinal bleeding, hemophilia B should be considered a possible etiology and blood coagulation studies should be performed accordingly.

A rare coexistence of a multicentric hepatic hemangioendothelioma with a large brain hemangioma in a preterm infant.

A preterm infant with a rare association of a multicentric hepatic hemangioendothelioma (MHH) and a large brain hemangioma is described. The imaging investigations and their findings are discussed. It is recommended that whole-body radionuclide imaging with 99mTc-labeled red blood cells is employed immediately following ultrasonography to confirm the suspected diagnosis of MHH and to detect other unsuspected hemangiomas.

An outbreak of multiresistant Klebsiella in a neonatal intensive care unit.

An outbreak of multiresistant Klebsiella pneumoniae occurring in a neonatal intensive care unit is described. All infections developed at least 5 days after admission to the unit (range, 5-40 days). Four infants had septicaemia and one had urinary tract infection. Three of the infected infants died. All klebsiella isolates were resistant to ampicillin, cefotaxime, cefuroxime, co-amoxiclav, mezlocillin, chloramphenicol, gentamicin, and ceftazidime (except in two); all were susceptible to imipenem, amikacin and quinolones. An extensive case-control study identified the following significant risk factors for colonization: prematurity; presence of indwelling catheters; previous antibiotic treatment; and parenteral nutrition. The outbreak was controlled with re-emphasis on strict handwashing practices, cohorting, closure of the unit to outborn admissions, and changing the regimen of empirical antibiotic therapy. Physicians should be aware of multiresistant Klebsiella spp. and change treatment whenever clinically indicated, even before culture results are available.

Ranitidine-induced bradycardia in a neonate--a first report.

Bradycardia, an extremely rare side-effect of ranitidine therapy is described in a 4-day-old full-term male neonate, who was admitted because of massive gastro-intestinal bleeding. Two hours after the intravenous injection of 1 mg/kg body weight per day, ECG showed sinus bradycardia of 60 beats/min with normal axis and QRS complex. The bradycardia gradually resolved in the next 24 h.

Analysis of the anti-p53 antibody response in cancer patients.

Mutations in the p53 tumor suppressor gene giving rise to mutant p53 proteins are among the most common genetic alterations associated with tumor cells. Mutant p53 gene products lose the wild type ability to suppress transformation in vitro or regulate cellular gene transcription. Mutant and wild type p53 protein conformations differ and mutant p53 is often present at high levels in the tumor cell relative to the low levels found in normal cells. Despite the major advances made to characterize the structure and biology of mutant and wild type p53, the humoral immune response against mutant p53s remains to be clearly defined. In the present study we have examined the anti-p53 response from cancer patients against the native and denatured state of mutant and wild type p53. Western blot analysis, immunoprecipitation analysis, and dilution analysis demonstrate that the anti-p53 sera recognize both wild type and mutant p53 conformational and denaturation resistant epitopes. There was no evidence that the mutant p53 molecules contain dominant antigenic epitopes which are not present on the wild type p53 protein. We also demonstrate that patients with ovarian cancer are also among those which can produce anti-p53 antibodies.

Lactic acid as a predictor for erythrocyte transfusion in healthy preterm infants with anemia of prematurity.

Elevated blood lactate levels that declined to normal after erythrocyte transfusion were observed in 17 of 37 otherwise healthy infants with anemia of prematurity (26.1 +/- 2.1 mg/dl vs 12.3 +/- 0.9 mg/dl; p < 0.001). Posttransfusion heart rate in this group decreased from 155 +/- 1 beats/min to 150 +/- 2 beats/min (p = 0.01). Blood lactate concentration may be a predictor of the need for transfusion in anemia of prematurity.

Systemic candidiasis in babies with retinopathy of prematurity.

Fifteen premature babies developed systemic candidiasis during the administration of intravenous hyperalimentation in the Beilinson Neonatal Intensive Care Unit. Candida albicans was found in the blood cultures of all the babies and in the urine cultures of 66.7% of them. Repeated funduscopic examinations revealed no evidence of septic embolization in the retinal or choroidal circulation. It should be noted that acute retinopathy of prematurity (ROP) grade 2 or 3 was found in all the babies.

Lipid infusion with different triglyceride cores (long-chain vs medium-chain/long-chain triglycerides): effect on plasma lipids and bilirubin binding in premature infants.

The possible beneficial effects of infusing a lipid emulsion containing 50% by weight of medium-chain triglycerides (MCT) compared with a standard long-chain triglyceride (LCT) emulsion were studied in 18 premature neonates (gestational age less than 34 weeks) requiring parenteral nutrition. The infants were assigned in a double-blind manner to receive one of the two lipid emulsions over 17 hours a day as a supplemental regimen for total parenteral nutrition. A lipid load of 1 g/kg per day was initiated on the third day of life and was increased at the rate of 1 g/kg per day until a maximal dose of 3 g/kg per day was obtained on the fifth day of life and maintained thereafter. Both bound and unbound bilirubin decreased with both infusion regimens during the study period. Despite a marked increase in plasma free fatty acid levels (260% in the MCT/LCT group compared with 210% in the LCT group), the fraction of unbound (free) bilirubin was significantly lower in the MCT/LCT group (34% vs 13%). Free fatty acid levels, corrected to albumin, were positively correlated to the percentage of free bilirubin only for the LCT lipid infusion. The finding of a significant elevation of plasma cholesterol levels only in the MCT/LCT group is now under investigation. Use of the MCT-containing emulsion was not associated with a higher frequency of adverse effects than the commonly used LCT-containing emulsion.(ABSTRACT TRUNCATED AT 250 WORDS)

Normal ranges of hip motion of preterm infants.

The hip motion of 158 preterm infants with gestational ages between 25 and 36 weeks was measured. The results of this study, compared with those of previous studies of term infants, show that hip motion changes with increasing gestational age above 25 to 27 weeks.

Evaluation of bilirubin as possible protective factor in the prevention of retinopathy of prematurity.

Retinopathy of prematurity (ROP) appears to be a multifactorial disease, the prevention of which is probably impossible even with the most accurate methods of blood-gas monitoring and oxygen restrictions. The oxidative processes and consequent formation of free radicals are probably influenced by the availability of various antioxidants in the immature retina. Bilirubin, the end product of haem catabolism, has recently been regarded as a potential physiological antioxidant. In order to test the suggestion as to the possible effect of bilirubin in reducing the incidence of ROP a retrospective study was undertaken of the medical records of 151 neonates born between 1984 to 1988 who weighed less than 1500 g. Of these, 78 had various degrees of ROP, whereas 73 had no ROP and served as a control group. The daily mean bilirubin values were analysed in accordance with gestational age and birth weight as well as the severity of ROP, and the results were compared with those obtained for the control group. The results showed no correlation between bilirubin levels and severity of ROP in all subgroups of gestational age and birth weight. These findings indicate that there is no apparent protective effect of bilirubin on the development of ROP.