Endothelin-1 levels in infants with pulmonary hypertension receiving extracorporeal membrane oxygenation.

We studied the possibility of an etiological role for endothelin-1 (ET-1) in the development of persistent pulmonary hypertension of the newborn (PPHN). Ten infants with severe PPHN requiring extracorporeal membrane oxygenation (ECMO) were studied. Pre and post pulmonary blood samples were obtained on commencing ECMO and on recovery. The samples were analyzed by radio-immunoassay. The infants with PPHN requiring ECMO had a significantly higher mean ET-1 concentration (21.1 pmol/l, S. D. 3.59) than a group of healthy controls (16.6 pmol/l, S. D. 4.44); however 8 of our 10 infants had individual ET-1 levels within our reference range for healthy newborns. Pre and post pulmonary ET-1 levels did not differ significantly and there was no evidence of a decline in ET-1 levels with resolution of PPHN. Pulmonary overproduction of ET-1 does not appear to be the cause of PPHN, although the endothelin system may still play a role in the pathophysiology of PPHN, probably mediated through changes in receptor expression.

Salicylate toxicity masquerading as malignant hyperthermia.

We report a case of hyperpyrexia presumed due to topical salicylate toxicity occurring immediately following general anaesthesia for appendicectomy in an eleven year old boy. Some of the features strongly suggested the diagnosis of malignant hyperpyrexia.

Acute-phase responses to cardiopulmonary bypass in children weighing less than 10 kilograms.

BACKGROUND: Cardiopulmonary bypass induces a systemic inflammatory response. This study investigated, in a pediatric population, cytokine-induced responses and their potential modification by intraoperative steroid administration. METHODS: Markers of the acute-phase response were measured perioperatively in 24 children weighing less than 10 kg undergoing cardiac operations. Those having operations with cardiopulmonary bypass were randomized to receive either no steroid (group I, n = 8) or 10 mg/kg methylprednisolone in the pump prime (group II, n = 10); patients undergoing nonbypass procedures were controls (group III, n = 6). RESULTS: In all groups, plasma interleukin-6 level was elevated (p < 0.01) above baseline throughout the post-operative period, peaking earlier in group I. Levels of C-reactive protein peaked at 48 hours, and postoperative core temperature was raised in all groups. Levels of interleukin-6 from 2 to 6 hours and C-reactive protein at 24 hours postoperatively were greater (p < 0.05) in group I than in group II. Maximum interleukin-6 level, C-reactive protein level, and temperature were all significantly greater in group I than in group III. Maximum interleukin-6 level correlated with maximum C-reactive protein level in group I only (rs = 0.76; p < 0.05) and showed no association with temperature. Duration of bypass did not correlate with levels of interleukin-6. CONCLUSIONS: This study demonstrated a marked acute-phase response to operation; the greater response to procedures with cardiopulmonary bypass was abrogated by intraoperative steroid administration. The importance of interleukin-6 as an inducer of acute phase proteins after bypass is supported by its association with C-reactive protein levels, but other factors must be important in the induction of pyrexia.

Hypomagnesaemic tetany.

Hypomagnesaemic tetany (hypomagnesaemic tetany with secondary hypocalcaemia) is a rare inherited form of hypomagnesaemia. Initial reports involved affected males only; however, affected females have also been reported. The case of a child with hypomagnesaemic tetany is described, the biochemical and genetic aspects of this condition are reviewed and the importance of the assessment of renal magnesium excretion in patients presenting with hypomagnesaemia is highlighted.

Neonatal endothelin-1 concentrations in term infants.

Endothelin-1 concentrations were studied in 30 term infants during the first week of life using a radioimmunoassay kit. A neonatal reference range was established (7.5-25.7 pmol/l). No significant relation with age, sex, gestation, or birth weight was found.

EEG burst suppression with propofol during cardiopulmonary bypass in children: a study of the haemodynamic, metabolic and endocrine effects.

We have studied the effects of propofol, given to maintain EEG suppression throughout cardiopulmonary bypass (CPB), in 20 children aged 1-15 yr, in a parallel group comparison. Anaesthesia was produced by fentanyl 50 micrograms kg-1, enflurane or halothane and midazolam 0.1 mg kg-1 at the start of CPB. After randomization, 50% of the children also received propofol during CPB. All children were cooled during CPB (25-28 degrees C) and pump flows (non-pulsatile) were 2.4 litre min-1 m-2, reducing to 1.2-1.6 litre min-1 m-2 during hypothermia. Large rates of infusion of propofol were required to maintain EEG suppression, particularly during rewarming. Compared with control, the propofol group showed significant increases in mixed venous oxygen saturation and significant reductions in systemic oxygen uptake and glucose and cortisol concentrations. There were no differences in triiodothyronine and lactate concentrations, mean arterial pressure during CPB and inotrope requirement after CPB, or in recovery times.

The effects of cardiopulmonary bypass on thyroid function in infants weighing less than five kilograms.

Triiodothyronine is an important regulator of cellular metabolism and may have potential use as an inotropic agent. The aim of this study was to determine the effects of cardiopulmonary bypass on thyroid function in infants weighing less than 5 kg. Serial measurements of triiodothyronine, thyroxine, and thyroid-stimulating hormone were made in 10 infants and corrected for the effects of hemodilution. We demonstrated a fall in triiodothyronine and thyroxine levels, with some recovery after 3 to 6 hours. An additional decrease then occurred, reaching a trough at 48 hours (representing a fall of 78% for triiodothyronine and 57% for thyroxine) before hormone levels returned to normal at 5 to 7 days. Thyroid-stimulating hormone concentrations increased and decreased, predating and complementing exactly the changes in triiodothyronine and thyroxine. These results are quantitatively and, for thyroid-stimulating hormone, qualitatively different from those previously reported in adults. In two patients who died, however, and in one who had a particularly difficult postoperative course, no increase in triiodothyronine, thyroxine, or thyroid-stimulating hormone concentrations was found after a trough had been reached at 48 to 72 hours, which suggests abnormal function at the hypothalamopituitary level.

Melatonin state in Mendenhall's syndrome.

We report a case of Mendenhall's syndrome that presented as hypoglycaemia. The clinical and biochemical features of the case are described including, for the first time, studies of melatonin state showing raised melatonin metabolite excretion in the urine as might be expected with disordered pineal function.

Quantitative determination of phosphatidylglycerol in amniotic fluid by enzymatic assay.

Phosphatidylglycerol (PG) was extracted from 54 human amniotic fluids for the assessment of fetal lung maturity. The PG values were derived from an enzymatic assay involving initial conversion of PG to glycerol by phospholipase C and alkaline phosphatase with subsequent analysis of the glycerol formed. This method proved to be reliable when compared with a method for two-dimensional thin layer chromatographic (2D TLC) analysis of amniotic fluid phospholipids. The results revealed that in all but one of 27 amniotic fluids in which no PG was detected by 2D TLC, enzymatic PG concentrations were less than or equal to 1.5 mumol/l and out of these, from 10 newborn infants delivered within 72 h of sampling, 4 developed respiratory distress syndrome (RDS). Conversely, in all but one of 27 amniotic fluids found to contain PG by 2D TLC, enzymatic PG concentrations were greater than 1.5 mumol/l and except for one subject from non-identical twins, no infants developed RDS.

Renal vein renin measurement and arteriography in the investigation and management of severe childhood hypertension.

Forty-two children aged one to sixteen years with persistent and severe hypertension were investigated by renal vein renin measurements. There were no serious complications in the 49 procedures performed and technical failure occurred on three occasions. Arteriography was performed in 35. Asymmetrical renin release was found in 22 patients and of these 15 underwent surgery. This was successful in 12 patients (80%) who became normotensive. Ten had unilateral disease (100% cure rate) but only 2 (40%) with bilateral disease became normotensive. Renal vein renin studies combined with arteriography have a useful role in the investigation and management of childhood hypertension.

HPLC of phospholipids in biological fluids -- application to amniotic fluid for the prediction of fetal lung maturity.

Because of both the advantage of speed compared with thin layer chromatography (TLC) and the dearth of high pressure liquid chromatography (HPLC) methods for phospholipid separation, it was decided to investigate the use of HPLC with a differential refractometer as detector for the separation and quantitation of amniotic fluid phospholipids required for the prediction of fetal lung maturity. A method was devised which gave results which compared well with those from TLC both in terms of quantitation and predictive value. Despite this, the method was found to lack sufficient reliability for application to the routine clinical assessment of fetal lung maturity. The method does, however, offer a good alternative to two dimensional TLC with phosphate analysis in research work involving quantitation of phosphatidyl inositol, phosphatidyl glycerol and particularly lecithin.

Amniotic fluid phosphatidylglycerol and the lecithin/sphingomyelin ratio in the assessment of fetal lung maturity.

Based on the analysis of 561 amniotic fluid samples obtained within 72 h of delivery, including 288 samples collected from the vagina, the detection of phosphatidylglycerol (PG) in the fluid together with the determination of the lecithin/sphingomyelin (L/S) ratio gave an accurate prediction of the risk of the newborn infant developing respiratory distress syndrome (RDS). In the presence of PG, regardless of the L/S ratio, only 0.6% of the babies developed RDS, while absent PG was associated with an 82.8% incidence of RDS. The predictive ability was improved by knowing the L/S ratio since in the presence of both PG and a mature L/S ratio (greater than 2.0), no baby developed RDS whereas 3.4% of them did when the ratio was immature despite the presence of PG. The test appears to be a useful determinant of the risk of RDS in babies born to diabetic mothers and it seems particularly effective in assessing amniotic fluid collected vaginally. It is recommended that laboratories dealing with amniotic fluid from high-risk pregnancies should detect PG as well as measuring the L/S ratio.

Amniotic fluid phospholipid profile determined by two-dimensional thin-layer chromatography as index of fetal lung maturation.

A phospholipid profile, the main features of which were the lecithin/sphingomyelin (L/S) ratio and the presence or absence of phosphatidylglycerol (PG), was determined in amniotic fluid from 188 patients. There was a mature profile (L/S ratio of at least 2 . 0 and detectable PG) in 145 patients, including seven insulin-dependent diabetics, and noe of their babies developed respiratory distress syndrome (RDS). The L/S ratio was less than 2 . 0 and PG absent in 12 patients, nine of whose babies developed RDS, whereas only three small babies (delivered between 28 and 35 weeks because of fulminant pre-eclampsia or severe abruptio placentae) out of 31 developed RDS when the L/S ratio was less than 2 . 0 but PG was present. When amniotic fluid was collected from the vagina only one out of 69 babies developed RDS when PG was present (regardless of the L/S ratio), while all of seven babies developed RDS when PG was absent. It is concluded that the amniotic fluid phospholipid profile, particularly the presence or absence of PG, gives an accurate assessment of fetal lung maturation. The profile may prove a useful adjunct to the management of high-risk pregnancies, especially after premature membrane rupture and perhaps also when the mother is diabetic.