Removal of DNA adducts.

DNA adducts are associated with a number of diseases, including cancer. Based on a recent report by our group, the aim of this study was to test the hypothesis that DNA adducts can be removed by means of one or more of the following three intervention programmes: intermittent whole-body hyperthermia; detoxification; and cell repair. The number of DNA adducts and total DNA adduct concentrations were measured in 104 patients who underwent one or more of the three intervention programmes. DNA adduct assessments were carried out on extracted genomic DNA by gas-liquid chromatography, with any DNA adducts found being localised using DNA microarrays. The baseline median number of DNA adducts was 2. The follow-up median number of adducts was highly significantly lower at 0 (p < 0.000000000000003). The mean total DNA adduct concentration at baseline was 9.308 ng/mL, and highly significantly lower at follow-up at 1.553 ng/mL (p < 0.000000000000006). Of the three intervention programmes, only the intermittent whole-body hyperthermia was associated with a significant reduction in DNA adducts. This study offers support for the hypothesis that DNA adducts can be removed by intermittent whole-body hyperthermia. The intermittent hyperthermia used involved infrared-A (wavelength 700-1400 nm, or, equivalently, a frequency of 215-430 THz) being preferentially delivered to the whole body, apart from the head, for up to one hour per session, with gradual core body temperature elevation usually occurring during the first 20-30 min. These results may offer an explanation at the molecular level for other reported clinical benefits of intermittent whole-body hyperthermia.

Fructose-associated hepatotoxicity indexed by the lactate dehydrogenase isoenzyme LDH-5.

Modern diets have become increasingly rich in fructose, for example through the addition of high-fructose corn syrup to many foods and drinks. It has been suggested that this might lead to hepatotoxicity, including the development of non-alcoholic fatty liver disease. After entering hepatocytes via insulin-independent glucose transporter 2 transmembrane carrier proteins, fructose is phosphorylated to fructose-1-phosphate in a reaction catalysed by fructokinase (ketohexokinase). In turn, fructose-1-phosphate is hydrolysed by aldolase B to glyceraldehydes. Glyceraldehydes may enter gluconeogenesis via fructose-1,6-bisphosphate and fructose-6-phosphate; glyceraldehydes may also enter glycogenolysis via pyruvate. The last pathway involves conversion of pyruvate to acetyl-CoA. Alternatively, pyruvate may be converted, via the action of the hepatic lactate dehydrogenase isoenzyme LDH-5, into lactate. In liver damage, the LDH-5 isoenzyme becomes elevated, predominantly in serum/plasma. We therefore hypothesised that if dietary fructose is associated with hepatotoxicity, there should be a positive correlation between erythrocyte fructose-6-phosphate and plasma LDH-5. This hypothesis was tested by assaying venous blood samples taken from 39 patients at rest, three hours after eating. Quantitative Fourier transform infrared spectrometry following gel electrophoresis was used to assay erythrocyte fructose-6-phosphate levels. Similarly, plasma LDH-5 concentrations were spectrophotometrically analysed, using the pyruvate-lactate reaction, following electrophoretic separation of the LDH isoenzymes. A significant positive correlation was found between the two variables (r = 0.44, p = 0.0047). This result, which supports our hypothesis, is evidence in favour of the possibility that dietary fructose is associated with hepatotoxicity. In addition to being a marker of hepatic damage, LDH-5 may play a more direct epigenetic role in causing liver damage; acute hepatic injury is associated with nuclear translocation of LDH, causing the production of lactate from pyruvate in the nucleus; in turn, the lactate inhibits histone deacetylase and is associated with upregulation of genes associated with the damage response, leading to cell death.

Inverse relationship between human erythrocyte fructose-6-phosphate and short-chain fatty acid levels.

In muscle cells, fructose is initially metabolised to fructose-6-phosphate. In the liver, fructose is metabolised to fructose-1-phosphate and thence to glyceraldehydes, which in turn can either enter glycogenolysis via pyruvate or gluconeogenesis via fructose-1,6-bisphosphate and fructose-6-phosphate. High levels of fructose-1-phosphate inhibit both glycogenolysis and gluconeogenesis. We hypothesised that, if systemically absorbed short-chain fatty acids constitute a major metabolic fate of unabsorbed dietary fructose, then levels of erythrocyte fructose-6-phosphate would be inversely correlated with plasma levels of short-chain fatty acids. The aim of this study was to test this hypothesis in respect of the three main short-chain fatty acids acetate, propionate and butyrate. Venous blood samples from 39 patients (16 male, 23 female, mean (standard error) age 42.4 (3.3) years) were analysed. Erythrocyte fructose-6-phosphate was measured using quantitative Fourier transform infrared spectrometry following gel electrophoresis, while plasma acetate, propionate and butyrate levels were measured using gas-liquid chromatography. The erythrocyte fructose-6-phosphate level was inversely correlated with the plasma acetate (r = -0.30, p = 0.06), propionate (r = -0.31, p = 0.05) and butyrate (r = -0.40, p = 0.01). These results support our hypothesis. The conversion of unabsorbed dietary fructose into short-chain fatty acids may represent a protective mechanism against the adverse effects of hypoglycaemia.

Neuromuscular taping reduces blood pressure in systemic arterial hypertension.

Systemic arterial hypertension, a well-known cause of morbidity, is associated with dysfunction of the autonomic nervous system. Neuromuscular taping (also known as kinesio taping, medical taping and Vendje neuromuscular) allows movement and muscle activity to treat pain, muscle disorders and lymphoedema, in which its mode of action may involve muscular stimulation leading to increased local blood circulation or stimulating dermatological, muscular and fascial structures with a form of passive massage. We hypothesised that neuromuscular taping may reduce blood pressure in systemic arterial hypertension. This hypothesis was tested by carrying out the first pilot study of its kind to determine whether the non-invasive technique of neuromuscular taping can reduce blood pressure in patients suffering from systemic arterial hypertension. Neuromuscular taping was symmetrically applied to the back, between C1 and T2, of seven hypertensive patients for 5-7 days. Cardiovascular autonomic parameters were assessed at baseline and at the end of the study. Taping was associated with falls in mean arterial blood pressure (p = .001), mean systolic blood pressure (p < .01), mean diastolic pressure (p < .01) and cardiac vagal tone at rest (p = .063). The beneficial effects on blood pressure appeared to last for at least five days post-neuromuscular taping. There is an indication, given the reduction in cardiac vagal tone at rest, that the mechanism of action of this intervention involves modulation of the brainstem parasympathetic system during cardiovascular control. Further studies are indicated to replicate the present findings, further investigate the effects of taping on autonomic functioning, and establish the optimum time-period and taping positioning.

The relationship between plasma vascular endothelial growth factor and erythrocyte 2,3-bisphosphoglycerate: The putative role of chronic hypoxia.

The non-invasive assessment of chronic tissue hypoxia is difficult. Pulse oximetry only allows the peripheral oxygen saturation to be measured, while the detection of hyperlactataemia needs to take into account the fact that the accumulation of lactic acid may result from several causes other than prolonged tissue hypoxia. Arterial blood oxygen measurement is invasive and often does not give a good indication of the level of tissue hypoxia. Other suggested methods include the use of positron emission tomography, magnetic resonance T2∗ relaxation time measurement, photoacoustics and high-frequency ultrasound. Tissue hypoxia leads to increased levels of hypoxia-inducible factor-1α, which in turn upregulates VEGFA, leading to increased levels of vascular endothelial growth factor (VEGF), which promote angiogenesis. Hypoxia lasting for more than a few hours is associated with increased synthesis in erythrocytes of 2,3-bisphosphoglycerate (BPG), a powerful regulator of the allosteric properties of haemoglobin, via the Rapoport-Luebering phosphoglycerate cycle. We therefore hypothesised that plasma VEGF and erythrocyte BPG levels should be positively correlated. Venous blood samples from 34 patients (18 male, mean age (standard error) 43.4 (3.2) y) were analysed; plasma VEGF was measured using an enzyme-linked immunosorbent assay while the erythrocyte BPG was assessed by quantitative Fourier transform infrared spectrometry following gel electrophoresis. The Pearson product-moment correlation between the two variables was 0.622 (p < 0.0001). Based on our findings, we suggest that it may be useful to measure both erythrocyte BPG and plasma VEGF, together, when assessing chronic hypoxia; elevated levels of both are likely to indicate hypoxia.

Carbon dioxide therapy in hypocapnic respiratory failure.

Oxygen therapy, usually administered by a facemask or nasal cannulae, is the current default treatment of respiratory failure. Since respiration entails intake of oxygen and release of carbon dioxide from tissues as waste product, the notion of administering carbon dioxide in respiratory failure appears counter-intuitive. However, carbon dioxide stimulates the chemosensitive area of the medulla, known as the central respiratory chemoreceptor, which activates the respiratory groups of neurones in the brainstem and stimulates inspiration thereby initiating oxygen intake during normal breathing. This vital initiation of normal breathing is via a reduction in the pH of the cerebrospinal fluid and the medullary interstitial fluid. We hypothesise that in cases of type I respiratory failure in which the PaCO2 is low, administration of carbon dioxide by inhalation would stimulate the respiratory groups of brainstem neurones and facilitate breathing, which would be of therapeutic value. Preliminary clinical evidence in favour of this hypothesis is presented and we recommend that a formal randomised study be carried out.

The effect of artesunate on short-term memory in Lyme borreliosis.

Lyme borreliosis is associated with memory deficits. While this may be related to cerebral infection by Borrelia bacteria, it may also be caused by concomitant co-infection by Babesia protozoa. The anti-malarial artemisinin-derivative artesunate has been shown to be effective against a number of Babesia species and to have efficacy against human cerebral malaria. We hypothesised that concomitant administration of artesunate in Lyme borreliosis patients would help alleviate the severity of self-reported short-term memory impairment. This hypothesis was tested in a small pilot study in which patients were treated with both an intravenous antibiotic and oral artesunate (20mg four times per day); treatment was associated with a reduction in the severity of short-term memory difficulties (P≃0.08). In light of these findings, we recommend that a formal randomised, placebo-controlled study be carried out.

The risk of lead contamination in bone broth diets.

The preparation and consumption of bone broth is being increasingly recommended to patients, for example as part of the gut and psychology syndrome (GAPS) diet for autism, attention-deficit hyperactivity disorder, dyslexia, dyspraxia, depression and schizophrenia, and as part of the paleolithic diet. However, bones are known to sequester the heavy metal lead, contamination with which is widespread throughout the modern environment. Such sequestered lead can then be mobilised from the bones. We therefore hypothesised that bone broth might carry a risk of being contaminated with lead. A small, blinded, controlled study of lead concentrations in three different types of organic chicken broth showed that such broths do indeed contain several times the lead concentration of the water with which the broth is made. In particular, broth made from skin and cartilage taken off the bone once the chicken had been cooked with the bones in situ, and chicken-bone broth, were both found to have markedly high lead concentrations, of 9.5 and 7.01 µg L(-1), respectively (compared with a control value for tap water treated in the same way of 0.89 µg L(-1)). In view of the dangers of lead consumption to the human body, we recommend that doctors and nutritionists take the risk of lead contamination into consideration when advising patients about bone broth diets.

Effect of incorporating legume flour into semolina spaghetti on its cooking quality and glycaemic impact measured in vitro.

Spaghetti is a favoured carbohydrate source because of its low glycaemic impact. The protein quality of semolina spaghetti is not ideal, however, and could be improved by including legume flour. We investigated whether incorporating legume flour in spaghetti, to improve its nutritional value, would affect its cooking quality and glycaemic impact. Four types of spaghetti containing 10% of either mung bean, soya bean, red lentil or chickpea flour were made and compared with a spaghetti control made only of durum semolina. Cooking quality was determined as the optimal cooking time (OCT), cooking loss (CL), dry matter (DM), swelling index, colour, hardness and adhesiveness. The spaghetti samples with legume flour were similar to one another and to the control in values of OCT, DM, swelling index, colour, CL, hardness and adhesiveness. Glycaemic impact of the samples was measured in vitro as release of rapidly available carbohydrate and slowly available carbohydrate during pancreatic digestion. The glycaemic index (GI) of the spaghetti samples was estimated by calculation, using data obtained for a reference food of known GI (shredded wheat horizontal line an extrusion-cooked wheat-only product). The shredded wheat underwent rapid parabolic digestion, and the near linear phase during which most of the starch was digested was completed between 20 and 60 min digestion. In contrast, the digestion of spaghetti was much slower and progressed almost linearly to completion. All spaghetti samples, moreover, were similarly susceptible to digestion, and compared with the wheat reference were all significantly lower in terms of relative glycaemic impact. We conclude that the incorporation of 10% legume flour in spaghetti to improve its nutritional value does not affect its cooking quality or increase its glycaemic impact.

The changing state of surgery for adult congenital heart disease.

The number of patients with adult congenital heart disease is expected to increase by 25% during this decade, so that by 2010 there will be more patients undergoing surgery for congenital heart disease over 16 years of age than under.

The failing Fontan circulation: successful conversion of atriopulmonary connections.

OBJECTIVES: Symptoms from low cardiac output or refractory atrial arrhythmias are complicating atriopulmonary (classical) Fontan connections. We present our experience of converting such patients to total cavopulmonary connections with and without arrhythmia surgery. METHODS: Between 1997 and 2002, 15 patients (mean age, 19.7 +/- 7.0 years) underwent conversion operations 12.7 +/- 3.5 years after atriopulmonary Fontan operations. Preoperative New York Heart Association functional class was I in 2 patients, II in 2 patients, III in 6 patients, and IV in 5 patients. Four patients underwent intracardiac lateral tunnel conversion alone, and 11 received extracardiac total cavopulmonary connection, right atrial reduction, and cryoablation. RESULTS: No mortality occurred. One patient had conduit obstruction in the immediate postoperative period requiring replacement, and another required a redo operation for endocarditis. Average hospitalization was 17.9 +/- 9.38 days; chest drains were removed on median day 4 (range, 1-29; mean, 7.4 +/- 7.58 days). At follow-up (mean, 42.6 +/- 22.1 months), late atrial arrhythmias had recurred in 3 of 4 patients with intracardiac total cavopulmonary connections (without ablation) and 1 of 11 patients with extracardiac total cavopulmonary connections with ablation. All patients are in New York Heart Association class I or II. Exercise ability (Bruce protocol) improved 69% from a mean of 6.18 +/- 4.01 minutes to 10.45 +/- 2.11 minutes (P <.05). Need for antiarrhythmic agents decreased postoperatively (patients receiving < or =1 antiarrhythmic: 9 preoperatively vs 15 at long-term follow-up, P <.05). No patient has required transplantation. Protein-losing enteropathy, which was present in 1 patient, improved transiently with conversion. There was 1 late death from gastrointestinal hemorrhage. CONCLUSIONS: Fontan conversion can be achieved with low mortality and improvement in New York Heart Association class and exercise ability. Concomitant arrhythmia surgery reduces the incidence of late arrhythmias.

Virtual food components: functional food effects expressed as food components.

BACKGROUND: The ability to communicate food benefits is essential for the successful development of functional foods and their role in improving public health. However, the functional efficacy of foods often cannot be represented by food composition. The concept of virtual food components (VFCs)-food data that express health-related effects, properties or functions of foods in the format of food components-is therefore proposed. OBJECTIVE: To develop protocols for designing VFC data sets that communicate functional efficacies of foods to end users, in order to facilitate evidence-based food choice, and allow data management systems to provide a more complete description of nutritional effects of foods than has been possible with values for actual food components alone. METHOD: A framework within which to develop VFCs was constructed, linking food choice to health end points. It involves scientific validation, generation of relative indices, their translation into a meaningful language based on equivalents to known and understood reference foods, followed by data consolidation and ecological validation. Criteria used to evaluate VFCs were importance, independence, validity, accuracy, robustness, sensitivity, linearity/additivity, relevance, comprehensiveness, acquirability, completeness, meaningfulness, acceptability and safety. The developmental framework and evaluative criteria were applied to glycaemic glucose equivalents (GGE), a VFC representing postprandial glycaemia, and to wheat bran equivalents for faecal bulk (WBE(fb)), a VFC representing faecal bulking efficacy. RESULTS: VFCs were used to identify foods according to health-related effects that cannot be accurately predicted from food composition data, and were used in a nutrition management system to concurrently show nutrient intake and physiological effects in the same units. The proposed evaluative criteria identified points requiring further research, and showed that lack of integrity-tested VFC data is an immediate challenge. CONCLUSION: VFCs are a means of communicating relative functional efficacy of foods as a continuous variable, and provide end users with a more accurate and complete view of the health effects of foods than can be provided by health claims or food composition data alone.

Adequate intake values for dietary fibre based on faecal bulking indexes of 66 foods.

OBJECTIVE: To determine an adequate daily intake value for dietary fibre (AIdf) based on faecal bulking indexes (FBIs) for 66 foods of known total dietary fibre (TDF) content. DESIGN: FBIs of 66 foods were measured and expressed as wheat bran equivalents (WBEfb) per 100 g of food. A daily WBEfb requirement for humans was calculated from faecal bulk generated per gram of wheat bran TDF in humans, using a critical faecal mass of 200 g/day for protection against large bowel disease. TDF content was regressed against WBEfb content for all 66 foods assayed, and an AIdf value obtained by substituting the calculated human WBEfb requirement into the regression equation. METHOD: FBI was measured using a validated rat assay, with eight large (400+/-50 g) rats per group, preadapted to dietary fibre, and fed adequate restricted diets containing test foods at inclusion rates consistent with human intakes. The critical faecal mass was based on epidemiological studies, and the faecal bulk generated per gram of wheat bran TDF was the mean of 27 published values. RESULTS: WBEfb requirements for humans were calculated to be 90 g/day, corresponding to a faecal output of 200 g/day. The regression equation relating WBEfb measured in the FBI assay to TDF in all 66 foods was TDF=0.491WBEfb + 3.19, R2=0.81 Substituting the human WBEfb requirement of 90 g into the regression equation gave an AIdf value of 40.9 g TDF/day. CONCLUSION: The AIdf value of 40.9 g TDF/day based on faecal bulking supports the AIdf of 38 g TDF/day recently set by the Institute of Medicine (USA), for young men, based on protection against heart disease. The AIdf value is obtained from the relation between the effects of foods and their content of mixed function, plant cell wall dietary fibres within the food matrices, and should not be used to guide intakes of extrinsic functional polysaccharides.

Glycaemic glucose equivalent: validation as a predictor of the relative glycaemic effect of foods.

BACKGROUND: Glycaemic glucose equivalent (GGE) content of a quantity of a food, based on glycaemic index, food composition and food quantity, is the theoretical weight of glucose that would induce a glycaemic response equivalent to that induced by the given amount of food. OBJECTIVES: To test whether GGE content predicts glycaemic response to foods differing in glycaemic index, carbohydrate content and intake, over a practical range of carbohydrate intakes. DESIGN: : Controlled randomised study. SETTING: Clinical trials unit at the Department of Human Nutrition, University of Otago, Dunedin, New Zealand. SUBJECTS: In all, 12 volunteers with and 12 without type II diabetes were recruited. All but one subject completed the trial. METHOD: Yams, biscuits, white rice and porridge were consumed at 10 and 20 GGE doses, and 2-minute noodles at 24 and 48 GGE, following an overnight fast. Incremental areas under the blood glucose response curves (IAUC) over 3 h were calculated for each individual for all foods, and individual glycaemic responsiveness was determined as IAUC/GGE. RESULTS: Within GGE dose, blood glucose responses to all foods, except rice, were similar. Doubling GGE dose approximately doubled glycaemic response. Relative glycaemic effects were accurately predicted by GGE intake after adjusting for individual glycaemic sensitivity (individual average IAUC/GGE). The accuracy of prediction of relative glycaemic effect from GGE intake was affected little by carbohydrate dose. CONCLUSION: GGE content predicted glycaemic impact of foods over a practical range of carbohydrate intakes, and may therefore be useful for accurate dietary management of glycaemia in diabetes mellitus. The predictive validity of GGE in mixed meals now needs to be tested. SPONSORSHIP: Health Research Council of New Zealand contract 00/453.

Aortic root replacement in patients with Marfan's syndrome: the Southampton experience.

BACKGROUND: The purpose of this study was to evaluate the early and late clinical outcome after aortic root replacement (ARR) in patients with Marfan's syndrome. METHODS: A total of 65 consecutive patients with Marfan's syndrome (mean age 41.7 +/- 10.7 years, range 15 to 76 years) undergoing ARR between 1972 and 1998 in Southampton were studied. Of the patients, 45 had a chronic aneurysm of the ascending aorta and 20 had a type A dissection (16 acute and 4 chronic). The operations were elective in 38 and nonelective in 27 cases (emergency in 22 and urgent in 5). Mean size of the ascending aorta was 6.3 +/- 1.4 cm (3.8 to 12 cm). A Bentall procedure was performed in 62 and a homograft root replacement in 3 patients. Mean follow-up was 8 +/- 4.1 years (0 to 22.9 years). RESULTS: Operative mortality was 6.1% (4 deaths) (for the elective vs nonelective procedures it was 2.6% vs 11%, p = 0.2). The 10-year freedom from thromboembolism, hemorrhage, and endocarditis was 88%, 89.8%, and 98.4% (0.9%, 0.9%, and 0.2% per patient-year) and from late aortic events it was 86.3% (1.3% per patient-year). Aortic root replacement for dissection was an independent predictor of occurrence of late aortic events (p = 0.01). Five patients had a reoperation with one early death. The 10-year freedom from reoperation was 89.2% (1.1% per patient year) (for elective and nonelective procedures, 90.8% vs 84.6%, p = 0.6). The 10-year survival, including operative mortality, was 72.7% (for elective and nonelective procedures, 78% vs 66.5%, p = 0.6). Late aortic events was an independent adverse predictor of survival (p = 0.02). CONCLUSIONS: In patients with Marfan's syndrome, elective ARR, usually for chronic aneurysm, is associated with a low mortality, low rate of aortic complications, and good late survival. Nonelective ARR, mostly for dissection, has a greater operative risk and a significantly higher incidence of late catastrophic aortic events. Early prophylactic surgery in these patients is therefore recommended. Long-term clinical and radiologic follow-up to prevent or to treat late aortic events is highly desirable.

Wheat bran equivalents based on faecal bulking indices for dietary management of faecal bulk.

Wheat bran equivalents for faecal bulking (WBEfb) are defined as the gram quantity of wheat bran that would augment faecal bulk to the same extent as a given quantity of a specified food, and its development as a food datum for the dietary management of distal colonic bulk is discussed in this paper. The WBEfb content of a food is derived from the faecal bulking index (FBI), which is a standardised physiological measure of the relative faecal bulking efficacy of foods on an equal edible weight basis. The FBI is defined as the increment in hydrated faecal matter per gram of a food consumed as a percentage of the increment due to the same weight of reference food (1 mm hard red wheat bran; FBI = 100). The FBI values allow the contribution of hydrated solids to the distal colon to be related to that of any reference of known FBI such as wheat bran, the suitability of which as a reference material is discussed. By expressing the increment in bulk as WBEfb, the relative impact of any quantity of an individual food on faecal bulk may be determined, and the effect of foods in mixed diets approximated by summation. Examples are given of the dietary management of distal colonic bulk using WBEfb, with one cup of wheat bran containing 27.5 g of dietary fibre - about the mean recommended daily fibre intake for adults--used as theoretical adequate daily intake of potential faecal bulk. The FBI and WBEfb are proposed as examples of the types of evidence-based data sets that may complement food composition data in selecting foods for physiological function.

Is there still a place for open surgical valvotomy in the management of aortic stenosis in children? The view from Southampton.

OBJECTIVE: The most appropriate management of aortic stenosis (AS) in children remains controversial. The purpose of this study was to determine the outcome following open valvotomy for AS in children. METHODS: Ninety-seven consecutive, unselected, children (mean age 3.2 +/- 3.6 years, 1 day--15 years) underwent an open valvotomy for critical (n=36) or severe (n=61) AS between 1979 and 2000 in Southampton. Twenty-six were neonates (1--31 days), 27 were infants (1--12 months) and 44 were older children (1--15 years). Mean follow-up was 10 +/- 5.4 years, 1 month--21.9 years. RESULTS: Two neonates died early giving an overall operative mortality of 2.1% (7.7% for the neonates and 0% for infants and older children). The mean aortic gradient was reduced from 76 to 24.5 mmHg (P < 0.0001). Residual or recurrent AS occurred in 17 patients and severe aortic regurgitation in eight patients. Kaplan--Meier 10-year freedom from residual or recurrent AS was 83.1 +/- 4.7% and from severe aortic regurgitation was 95.3 +/- 2.7%. Twenty-five patients required an aortic re-operation or re-intervention, 18 of whom had an aortic valve replacement (AVR) (mean valve size 21.8 +/- 0.9 mm, range 21--25 mm). Ten-year freedom from any aortic re-operation or re-intervention was 78.4 +/- 5.2% and from AVR was 85.1 +/- 4.6%. There were ten late deaths. Overall 10-year survival, including hospital mortality, was 90.2 +/- 3.1% (69.7 +/- 9.7% for the neonates, 92 +/- 5.4% for the infants and 100% for older children, (P < 0.0001). Ten-year survival for children with isolated AS (n = 69) was 100% and for those with associated cardiovascular problems (n = 28) was 67.3 +/- 8.9% (P < 0.0001). All survivors are in New York Heart Association functional class I. CONCLUSIONS: Open valvotomy remains the gold standard in the management of AS in neonates, infants and older children. It is associated with low operative mortality and provides lengthy freedom from recurrent AS and regurgitation. Re-operations are common but if AVR is required, implantation of an adult-sized prosthesis is usually possible. There is a late death-hazard for those with severe associated lesions, but the survival prospects for the patients with isolated AS are excellent.