How practical are recommendations for dietary control in phenylketonuria?

In patients with phenylketonuria, blood phenylalanine concentration during childhood is the major determinant of cognitive outcome. Guidelines provide age-related recommendations for treatment. To ascertain the extent to which these aims are achievable, we audited results from four centres for the years 1994-2000. The median proportion of samples with phenylalanine concentrations above those recommended was less than 30% for those younger than age 10 years but almost 80% for those aged 15 years and older. Similarly, the median frequency of blood sampling, expressed as a proportion of that recommended, was more than 80% for patients younger than 10 years but less than 50% by age 15 years. Our results indicate the difficulty of maintaining control in phenylketonuria, especially in older rather than younger children.

Non-hepatic hyperammonaemia: an important, potentially reversible cause of encephalopathy.

The clinical syndrome of encephalopathy is most often encountered in the context of decompensated liver disease and the diagnosis is usually clear cut. Non-hepatic causes of encephalopathy are rarer and tend to present to a wide range of medical specialties with variable and episodic symptoms. Delay can result in the development of potentially life threatening complications, such as seizures and coma. Early recognition is vital. A history of similar episodes or clinical risk factors and early assessment of blood ammonia levels help establish the diagnosis. In addition to adequate supportive care, investigation of the underlying cause of the hyperammonaemia is essential and its reversal, where possible, will often result in complete recovery. Detection of an unborn error of metabolism should lead to the initiation of appropriate maintenance therapy and genetic counselling.

Toxic shock syndrome secondary to a dental abscess.

A 9-year-old girl presented with arthralgia and myalgia which progressed to developing renal failure and overwhelming septic shock. The underlying cause was assumed to be a periodontal abscess from an upper right deciduous canine tooth. The pus from the abscess grew a toxic shock syndrome toxin 1-producing Staphylococcus aureus. This case illustrates the importance of an oral surgical review of patients presenting with features of toxic shock syndrome if the source of the infection is not immediately obvious.

Randomised controlled trial of L-carnitine as a nutritional supplement in preterm infants.

AIMS: To evaluate the effect of L-carnitine supplementation (25 mg/kg/d) on the growth and incidence of hypoglycaemia in preterm infants. METHODS: A double blind, placebo controlled randomised trial, stratified for gestational age, was conducted of 86 preterm infants between 28 and 34 gestational weeks. The median gestational ages in the carnitine group and placebo groups were 30.7 weeks (range 28.0 to 33.6) and 31.4 weeks (range 28.0 to 33.9), respectively. The median birthweights were 1.557 kg (range 0.944 to 2.275) and 1.645 kg (range 0.885 to 2.545), respectively. RESULTS: Mean plasma free carnitine concentrations were below values for normal term infants in both groups on day 1 (carnitine group 44.8 mumol/l, placebo group 25.5 mumol/l) in the placebo group on day 7 (50.7 mumol/l), but in neither group on days 14 and 28. Total, free, and acylcarnitine concentrations were significantly increased in both urine and blood in the L-carnitine group. There was no significant difference between the placebo and carnitine supplemented groups in growth rate, as assessed by weight, length, skinfold thickness and head circumference measurements, or in the incidence of episodes of hypoglycaemia. CONCLUSION: The addition of carnitine as a nutritional supplement at a dose of 25 mg/kg/day did not improve growth in our group of preterm infants nor protect them from episodes of hypoglycaemia.

Photosensitivity associated with the Smith-Lemli-Opitz syndrome.

A case of severe photosensitivity in a girl with the Smith-Lemli-Opitz syndrome is reported. Children with this recessively inherited metabolic disorder of cholesterol metabolism present with a variety of congenital abnormalities of the nervous system and internal organs in association with varying degrees of mental retardation. Photosensitivity is a feature which has previously only briefly been mentioned in the literature in association with this syndrome. However, more recently, it has become apparent that photosensitivity is not uncommon among children with the Smith-Lemli-Opitz syndrome, although the nature of the photosensitivity in these patients has remained undefined. Our patient has suffered from sunlight intolerance since early infancy, with redness and pruritus of sun-exposed skin developing within minutes of sun exposure. Monochromator ultraviolet (UV) radiation and visible light testing revealed an immediate and persistent reaction to low-dose UVA at 350 nm, and an abnormal erythemal response to visible light at 400 nm.

Peripheral gangrene associated with fulminating meningococcal septicaemia. Is early escharotomy indicated?

We present a case of a 3-month-old boy presenting with fulminating meningococcal septicaemia associated with extensive peripheral gangrene requiring amputation of three limbs. The surgical management options and the role of early fasciotomy are discussed.

Audit of medical students' experiences of paediatric teaching: a tool to monitor and improve clinical teaching.

We provide clear aims and objectives for our students during their attachment in child health. To assess how well these are being met we reviewed their experience over the 3-year period 1991-1994. The audit was based on a questionnaire and was anonymous and voluntary; 45.4% of the students completed the questionnaire. These students' experiences were generally satisfactory and covered a wide variety of common childhood disorders. Of concern was that 32% of them received less than 1 hour per week of teaching in protected time and that they seemed reluctant to avail themselves of the opportunity of attending casualty; 54% did not visit the casualty department at all during their attachment. We have identified several areas where improvements in our teaching can be made and we are confident that our system of regular audit constitutes a valuable tool to monitor and improve clinical teaching.

Assessing undergraduates' practical clinical skills.

A list of practical skills to observe or learn was included in an undergraduate child health core curriculum. The ability of students to perform these tasks was assessed in a short objective test. This testing has encouraged them to become more proficient in these important skills.

Phenylalanine kinetics in sick preterm neonates with respiratory distress syndrome.

The cause of hyperphenylalaninemia in sick preterm infants has yet to be determined; one reason may be reduced tolerance to phenylalanine as a consequence of immaturity of phenylalanine hydroxylase. Phenylalanine metabolism was studied in vivo in 23 ventilated preterm infants of gestational age 23 to 36 wk within the first 6 d of life using a continuous i.v. infusion of the stable isotope-labeled amino acids [2H5]phenylalanine, [2H4]tyrosine, and [2H2]tyrosine. Phenylalanine hydroxylation was calculated from two different methods. In the first method, used in all 23 infants receiving glucose and in seven of these infants who subsequently received parenteral nutrition, phenylalanine hydroxylation was calculated from the plasma enrichments of [2H5]phenylalanine and [2H4]tyrosine and from the molar ratio of tyrosine to phenylalanine in mammalian tissue protein. In this instance, the mean hydroxylation was 16.0 (SD 10.9) and 48.4 (SD 14.9) mumol/kg/h, which was 17.3% (SD 8.4%) and 33.2% (SD 9.8% of the total phenylalanine flux for infants receiving glucose and parenteral nutrition, respectively. Additionally, in six infants receiving glucose, hydroxylation was calculated from the measured phenylalanine (2H5), independent tyrosine (2H2) fluxes, and the plasma enrichments of (2H5) phenylalanine and its hydroxylation product [2H4]tyrosine. In this case, hydroxylation was 20.5 (SD 13.0) mumol/kg/h, which represented 22.3% (SD 9.8%) of the phenylalanine flux. In the same six infants, phenylalanine hydroxylation derived using the first method was 22.2 (SD 13.1) mumol/kg/h, 23.6% (SD 9.9%) of the total phenylalanine flux.(ABSTRACT TRUNCATED AT 250 WORDS)

Validation of a croup score and its use in triaging children with croup.

The Syracuse croup scoring system was validated in 165 children with croup who were admitted to an intensive therapy unit for assessment over a one year period. The unit served as a croup triage point for Cardiff and its environs. A score of > 5 was taken as an indication that a patient was at risk of upper airway obstruction and was used to support a triage decision by the junior hospital doctor to admit a patient to the intensive therapy unit. All patients with an initial score < or = 5 were considered safe for transfer to a general paediatric ward and none of these required subsequent admission to intensive care. This score was then tested on a further 134 children with croup, in order to identify those patients who required specialised monitoring, observation or treatment in intensive care. A score of > 5 gave a specificity of 100% and a sensitivity of 80%. Croup scoring continued after admission on the general paediatric wards. Two patients who were originally admitted to the intensive therapy unit with a score > 5 improved within 6 h and were transferred to the general ward with a score < or = 5. These children subsequently required readmission to the intensive therapy unit. Our tracheal intubation rate of 2% was low and may relate to the routine use of regular adrenaline nebulisation. We recommend this scoring system to other paediatric departments for initial triaging decisions and for documenting progress on the wards.

Are medical students missing out?

Increasing discontent, even boredom, shown by many clinical medical students is in marked contrast to the enthusiasm of school children interviewed for a place at medical school. The roots of the problem are sown in the pre-clinical years with too much teaching that is of little relevance to clinical practice and insufficient contact with clinical problems that are needed to keep the youthful flame of idealism alive. In clinical years disillusion continues with less time available for teaching by NHS colleagues because of clinical directorates and other administrative chores and a far from ideal balance between teaching and research activities amongst academic staff. To help enthusiasm return we recommend greater clinical involvement in the pre-clinical years, teaching to be better valued and teaching and examination methods reassessed. More self-directed learning, though desirable, will be difficult unless adequate resources are made available. At a time of increased pressure on all sides if we cannot meet the challenge of modern undergraduate clinical education disillusion amongst our students will continue with serious implications for the whole continuum of medical education.

Validation of a portable indirect calorimetry system for measurement of energy expenditure in sick preterm infants.

A portable indirect calorimeter adapted from adult use was validated for use in preterm infants. Oxygen consumption (VO2) and carbon dioxide production (VCO2) were subsequently measured in 16 preterm infants breathing spontaneously in room air (canopy mode) and in nine preterm infants receiving intermittent positive pressure ventilation (ventilator mode). Validation of the system was performed using a gas injection technique with nitrogen to simulate VO2 and carbon dioxide for VCO2. Mean errors in validation of the canopy mode were 1.4% and 0.2% for VO2 and VCO2 with limits of agreement of 0.6 (+2SD) ml/min and -1.3 (-2SD) ml/min, and 0.9 (+2SD) ml/min and -2.3 (-2SD) ml/min respectively. In validation of the ventilator mode mean errors were -1.8% and -5.05% for VO2 and VCO2 with limits of agreement of 1.02 (+2SD) ml/min and -0.74 (-2SD) ml/min, and 0.93 (+2SD) ml/min and -1.45 (-2SD) ml/min respectively. Values of VO2 and VCO2 in 16 preterm infants in the canopy mode were 6.2 ml/kg/min (0.5 1SD) and 6.7 ml/kg/min (0.6 1SD) and in nine preterm infants in the ventilator mode 4.98 ml/kg/min (1.09 1SD) and 4.74 ml/min/kg (1.08 1SD) respectively. Mean energy expenditure was 45.5 kcal (191 kJ)kg/day for infants measured in the canopy mode and 35.5 kcal (149 kJ)/kg/day for ventilated infants. This metabolic system can be adapted for use in the newborn but accuracy is reduced when it is used in those weighing less than 1000 g.

Serum immunoglobulins to endotoxin core glycolipid: acute leukaemia and other cancers.

Circulating antibody to endotoxin core glycolipid and total serum immunoglobulin concentrations were measured in 86 children with cancer (54 with acute lymphoblastic leukaemia, four with acute myeloid leukaemia, and 28 with various solid tumours). Measurements were made before treatment in the group with acute lymphoblastic leukaemia as well as when patients were both on and off chemotherapy. In the other two groups measurements were made when patients were both on and off treatment. Significant reductions in endotoxin antibody and serum immunoglobulin concentrations were found only in patients with acute lymphoblastic leukaemia. In addition, there was a significant correlation between febrile episodes and the concentration of antibody to core glycolipid in the children with acute lymphoblastic leukaemia. These findings suggest that the use of prophylactic high titre endotoxin antibody may be of benefit to children with life threatening Gram negative infections who are receiving cytotoxic chemotherapy.

Serum immunoglobulins to endotoxin core glycolipid: establishment of normal concentrations.

Serum antibody to lipopolysaccharide core glycolipid was measured in normal children and in full term and premature (less than or equal to 1500 g) infants. Antilipopolysaccharide core glycolipid antibody was present in term infants and normal children, and reached adult titres by 15 years of age. The specific anti core glycolipid antibody was predominately of the IgG class. Preterm infants (less than 32 weeks' gestation) had significantly lower titres of antilipopolysaccharide core glycolipid than more mature preterm or term infants. The results suggest that administration of anticore glycolipid immunoglobulin may be beneficial in the treatment or prevention of Gram negative septicaemia in preterm and very young infants.

Decline of passively acquired antibodies in young and adult rats.

The rate of decline (half-life) of passively acquired antibodies was studied in young and adult rats. There was a wide variation in half-life when varying concentrations of diphtheria or tetanus antibody were administered by intraperitoneal injection; half-lives ranged from 1-2 to 12-0 days in both age groups. When different concentrations of diphtheria and tetanus antibody were administered together by the same route, significant differences in half-lives were demonstrated in individuals of each group. Each of the curves describing the relationship between initial antibody titre and half-life took the shape of a rectangular hyperbola; individuals with high initial titres had short half-lifes, whereas in animals with low initial titres antibody declined at a slower rate. The results are in agreement with those previously reported for the decline of maternally acquired antibodies in infants and young rats and for the catabolism of IgG.

Postnatal decline of maternally acquired antibodies in the rat.

The decline (half-life) of maternally acquired antibodies of two different specificities (diphtheria and tetanus) was studied in rats. Essentially similar half-lives for antibody of each specificity were found in young rats from the same litter. In contrast, half-lives varied from 2 to 10 days in individuals of different litters. Significant differences in half-lives were demonstrated in young rats possessing markedly different initial titres of antibodies of the two specificities. It was established that there was a relationship between the half-life and the initial titre of antibody of each specificity which could be described by a rectangular hyperbola. These findings are in close aggreement with previous studies in human infants.