Features of carnitine palmitoyltransferase type I deficiency.

Carnitine palmitoyltransferase type I (CPT I) is unique among long-chain fatty acid oxidation enzymes in that there are two tissue-specific isoforms, 'hepatic' and 'muscle', which are encoded by two separate genes. The 'hepatic' isoform is expressed in liver, kidney and fibroblasts and at low levels in the heart, while the other isoform occurs in skeletal muscle and is the predominant form in heart. Reported patients with CPT I deficiency lack activity of the hepatic isoform and present before 30 months of age with hypoketotic hypoglycaemia, hepatomegaly with raised transaminases, seizures and coma. We discuss four new cases in three families showing, variously, renal tubular acidosis, transient hyperlipidaemia and, paradoxically, myopathy with elevated creatinine kinase or cardiac involvement in the neonatal period as additional features that deserve wider recognition.

Serum S100B and hypothermic circulatory arrest in adults.

BACKGROUND: Cerebral injury is the most important complication of cardiac operations with cardiopulmonary bypass. Prolonged total circulatory arrest (TCA) can expose patients to an even greater risk of cerebral injury. We sought to detect the degree of cerebral injury in adults who had thoracic aortic operations with TCA by measuring S100B protein, which is released into the circulation after cerebral injury. METHODS: Serial measurements of S100B protein, a highly specific serum marker of astroglial damage, were performed in 26 patients who had complex aortic operations, of whom 13 required cardiopulmonary bypass alone (for aortic root replacement), and in 13 patients who required an additional period of TCA (for type A aortic dissections and arch aneurysms). Blood samples were taken preoperatively, at skin closure, and 5 and 24 hours postoperatively. RESULTS: There were significant increases in serum S100B concentrations in all patients, and peak levels occurred at skin closure. The magnitude of the increase in S100B was significantly greater at all postoperative time points and persisted longer in the TCA group. There was a significant correlation between the duration of the TCA and S100B concentration at 5 hours (r = 0.66, p = 0.01) and 24 hours (r = 0.63, p = 0.02) postoperatively. CONCLUSIONS: S100B levels were higher in all patients who had complex aortic operations and were significantly greater in patients requiring a period of TCA. The duration of the TCA period correlated with S100B levels 5 hours and at 24 hours postoperatively. Circumstantial evidence, in accordance with other studies, suggests that S100B protein is a marker for cerebral injury during cardiac operations.

Serum S-100 protein concentration after cardiac surgery: a randomized trial of arterial line filtration.

INTRODUCTION: Embolization of gaseous and particulate matter is incriminated in the neuropsychological morbidity of CPB and can be reduced by membrane oxygenators and arterial line filtration. It is not known if the use of arterial line filtration in conjunction with membrane oxygenators might have an additive effect in reducing cerebral injury. METHODS: Forty patients undergoing elective coronary artery surgery were prospectively randomized to a 43 microns heparin coated arterial line filter (Cobe Sentry) or to no filtration (control group). All operations were performed by one surgeon (DPT) using intermittent ischaemia with nonpulsatile CPB, a COBE CML membrane oxygenator and alpha-stat paCO2 management. Flow rates were maintained between 2.0 and 2.4 l-1 m2 per min with a perfusion pressure of 50-80 mmHg and a systemic temperature of 34 degrees C. Cerebral injury was defined by careful neurological examination and serial measurement of the serum concentration of S-100 protein (a highly specific astroglial cell derivative, elevated serum levels of which correlate with proven cerebral injury). RESULTS: There was no difference [mean (S.D.)] in the control and filter groups with respect to age [61(9) vs. 62(9) years], ejection fraction, number of grafts [2.8(0.6) vs. 2.6(0.7)] or CPB times [55(19) vs. 57(18) min]. Preoperatively, no patient had detectable S-100. In the postoperative period 23 of 40 patients (58%) showed elevated S-100 levels. At 1, 5 and 24 h the respective number of patients in the control and filter groups with elevated S-100 was (14 vs. 9), (4 vs. 0), (4 vs. 0)) (P < 0.05). No patient had overt cerebral injury. CONCLUSIONS: This study suggests that (i) subclinical cerebral injury is common (58% of patients in this study) even after apparently uncomplicated surgery with short CPB times; (ii) serum S-100 protein is a valuable marker for investigating potentially cerebral protective innovations during CPB; and (iii) arterial line filtration significantly reduces but does not eliminate cerebral injury.

Comparison of serum S-100 beta levels during CABG and intracardiac operations.

BACKGROUND: The risk of overt and subtle cerebral injury may be higher in intracardiac operation (ICO) rather than coronary artery bypass grafting (CABG). S-100 protein is a specific astroglial protein whose serum level increases after cerebral injury. Elevated serum levels of S-100 have been detected after adult cardiac operations and correlated with neurologic injury. METHODS: The level of S-100 protein was measured serially over 24 hours in 40 patients (27 undergoing aortic valve replacement, 9 mitral valve replacement, 4 closure of atrial septal defect) undergoing ICO and 20 patients undergoing CABG. RESULTS: The groups were similar with respect to age and cardiopulmonary bypass times. The S-100 level was not elevated before operation in any patient. Peak S-100 levels were reached at skin closure, when 35 of the ICO patients (88%) and 13 of the CABG patients (65%) had elevated S-100 levels. At skin closure peak S-100 levels were significantly greater in the ICO group (median [interquartile range], 0.76 [0.44-1.16] versus 0.3 [0-0.55] microgram/L; p < 0.01). At 5 hours S-100 levels were still elevated in 22 patients in the ICO group compared with 1 patient in the CABG group (p < 0.01), and at 24 hours 17 ICO patients had persistently elevated S-100 levels in comparison with 2 in the CABG group (p < 0.01). One valve patient had a stroke 24 hours after operation accompanied by a secondary increase in the S-100 level. There was no significant difference in postoperative S-100 levels between 5 patients in the ICO group with a prior history of stroke and those without. The peak S-100 level correlated with patient age (r = 0.59; p < 0.001) but not with the duration of cardiopulmonary bypass or core temperature during the operation. CONCLUSIONS: Intracardiac operation results in a significantly greater elevation in S-100 levels than CABG. Elevated S-100 levels correlate with increasing patient age but not with the duration of cardiopulmonary bypass or intraoperative core temperature. These findings raise the possibility that ICO patients may be more vulnerable to even subtle levels of cerebral injury than CABG patients.

Oral phosphate supplements reverse skeletal muscle abnormalities in a case of chronic fatigue with idiopathic renal hypophosphatemia.

A 57-yr-old man presented with a long history of undiagnosed fatigue but no evidence of bone disease. He was noted to have hypophosphatemia due to an idiopathic phosphaturia. Marked abnormalities of exercising skeletal muscle detected by phosphorus magnetic resonance spectroscopy and by plasma metabolite measurements were consistent with mitochondrial dysfunction. Oral phosphate supplements restored plasma phosphate concentration and muscle biochemistry to normal and produced considerable improvement in symptoms and exercise tolerance, although the phosphate concentration in muscle was only marginally low and increased little by treatment. We conclude that hypophosphatemia should be excluded in unexplained fatigue.

Glycated haemoglobin: an assessment of high capacity liquid chromatographic and immunoassay methods.

We have assessed five high-throughput systems for the measurement of glycated haemoglobin and have reviewed published evaluations of individual analysers. All systems offered better precision than a widely used electroendosmosis method. The low pressure chromatography and immunoassay systems demonstrated greater between-batch imprecision than the high performance liquid chromatography analysers, the latter achieving the proposed analytical goal of between-batch coefficients of variation less than 5%. Agreement between all systems measuring HbA1 was good but there was variability amongst observed HbA1c values. The systems were also assessed for their quality of chromatographic separation, simplicity of operation, flexibility, cost and potential for interference by other haemoglobins.

Maternal alpha-fetoprotein screening: two years' experience in a low-risk district.

Over a two-year period, 3479 pregnant women in the Kings' Lynn Health District were screened for neural tube defects by estimation of maternal serum alpha-fetoprotein. Most pregnancies were scanned by sonar for fetal maturity. Eight women had fetuses with open neural tube defects; four with anencephaly were associated with very high alpha-fetoprotein values. Of the four with open neural tube defects without anencephaly, only one was detected by screening and confirmed after amniocentesis. One other had a raised serum alpha-fetoprotein but a normal amniotic fluid value. The other two affected fetuses were missed. This disappointing outcome was attributed to the poor predictive value of alpha-fetoprotein in detecting open neural tube defects (anencephaly apart) rather than to errors in its estimation or in assessment of fetal maturity by sonar scan. We question the validity of screening, particularly in areas of intermediate or low incidence.