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Biomedical subjects

S K Hall

Publications and source records attributed to S K Hall.

At least 19 recordsLinked to original sources
PubMed2003

Free use of fruits and vegetables in phenylketonuria.

This study aimed to evaluate systematically the effect of the free use of fruits and vegetables containing an intermediate amount of phenylalanine (51-100 mg/100 g) on the biochemical control in children with phenylketonuria (PKU). Fifteen subjects with PKU, with a median age of 6 years (range 1-24 years) were studied. In a three-part prospective 15-week study, subjects sequentially ate fruits and vegetables containing phenylalanine 0-50 mg/100 g for weeks 1 to 3; 51-75 mg/100 g for weeks 4 to 8; and 76-100 mg/100 g for weeks 9 to 15. Plasma phenylalanine concentrations were measured twice daily for three consecutive days in weeks 1, 3, 6, 8, 11, 13 and 15. A standard menu was followed on the blood sampling days. Daily dietary records of fruits and vegetables under study were kept throughout the trial. Control of phenylalanine concentrations was not adversely affected by the free use of fruits and vegetables containing 51-100 mg/100 g. Pre-breakfast median plasma concentrations were: weeks 1 to 3, 260 micromol/L (range 90-890); weeks 4 to 8, 255 micromol/L (range 130-920); and weeks 9 to 15, 278 micromol/L (range 30-880). Pre-evening meal median plasma phenylalanine concentrations were: weeks 1 to 3, 240 micromol/L (range 30-820); weeks 4 to 8, 210 micromol/L (40-880); and weeks 9 to 15, 238 micromol/L (range 20-880). These data suggest that free use of fruits and vegetables containing 51-75 mg/100 g poses no problem for children with PKU.

Adolescent↗
PubMed2003

Administration of protein substitute and quality of control in phenylketonuria: a randomized study.

Uneven administration of an L-amino acid protein substitute is an important contributing factor in variability in plasma phenylalanine concentrations over the 24-hour period in patients with phenylketonuria under treatment. The aim of this study was to determine whether manipulating the timing of protein substitution would reduce variability in plasma phenylalanine over 24 h. Sixteen children (aged 1-11 years) with well-controlled phenylketonuria were entered into a randomized crossover study in which four protocols of the same daily dose of protein substitute administration were compared. In protocol A, three equal, divided doses were given with meals over 10 h; in protocol B, three equal doses over 14 h; in protocol C, four equal doses over 14 h; and in protocol D, six equal doses over 24 h (3 subjects only). Four-hourly skin puncture blood specimens were collected for 48 h in each study protocol. In protocols A, B and C, but not in protocol D, there was wide variability in 24 h plasma phenylalanine. The median daily differences (micromol/L) between highest and lowest phenylalanine concentrations were: for protocol A, 140; for protocol B, 100; for protocol C, 120; and for protocol D, 40. In protocol D, 97% of all phenylalanine concentrations were below 120 micromol/L and no concentration fell below 40 micromol/L. Administration of protein substitute overnight as well as during daytime produces stable and lower plasma phenylalanine concentrations and may lead to improved dietary phenylalanine tolerance.

Amino Acids↗
PubMed2003

Are tablets a practical source of protein substitute in phenylketonuria?

BACKGROUND: A phenylalanine-free amino acid based protein substitute is necessary to provide the major source of protein in phenylketonuria (PKU). Protein substitutes in PKU are usually given as drinks. These are unpalatable and compliance is often poor. Tablets containing a suitable mixture of phenylalanine-free amino acids (Aminogran Food Supplement, UCB) are now available. AIMS: To compare the effectiveness and acceptability of these tablets with conventional protein substitute drinks. METHODS: Twenty one subjects with PKU, aged 8-25 years, participated in a randomised crossover study. During one phase, subjects received at least 40% of their protein substitute requirements from the amino acid tablets and the rest from their usual protein substitute tablets. During the other phase, they received their usual protein substitute. Each period lasted 12 weeks. Blood phenylalanine concentrations were measured at least once every two weeks and other plasma amino acids were measured at the beginning, at crossover, and at the end of the study. The subjects kept a diary of all protein substitute taken. RESULTS: Compliance appeared to be better with the new tablets than with patients' usual protein substitutes. Ninety per cent (18/20) recorded that they took the tablets as prescribed, compared with 65% (13/20) fully compliant with their usual protein substitute. Moreover, plasma phenyalanine was lower on the amino acid tablets, and the median difference in blood concentrations between the two groups was 46 micro mol/l (95% CI 14.8 to 89.0, p = 0.02). Tyrosine increased by a median of 16 micro mol/l daily on the amino acid tablets (95% CI 7.1 to 40.5, p = 0.01). Most subjects (70%) preferred incorporating the new tablets into their usual protein substitute regimen. CONCLUSIONS: Amino acid tablets are an effective and relatively popular protein substitute in older children, teenagers, and adults with PKU.

Adolescent↗
PubMed2003

Transient neonatal hypothyroidism due to a maternal vegan diet.

Iodine is an important constituent of thyroid hormones and deficiency can lead to a range of problems depending on the degree and at what stage of life the deficiency occurs. We report a 10 day-old infant with a goitre, who presented with raised TSH on dried blood spot screening. It was observed that her mother also had a goitre. The mother was a vegan and, on dietary assessment, her iodine intake was extremely low. Both mother and infant had abnormal thyroid function tests. Mother was given Lugol's iodine and her thyroid function tests normalised. Her baby was initially prescribed thyroxine on the basis of the raised screening TSH. This was subsequently withdrawn at the age of 2 weeks, following a normal plasma TSH. Thyroid function tests remained normal and the goitre disappeared by the age of 2 months. Iodine deficiency is uncommon in the Western World. However the incidence may be rising in otherwise iodine replete areas, particularly in those who adhere to restrictive and unusual diets. In the case of pregnant mothers their unborn child's health is in danger. This report demonstrates the need to ascertain maternal diets early in antenatal care, and supplement if necessary to avoid risk to their own health and that of their offspring.

Diet, Vegetarian↗
PubMed2002

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.

Adolescent↗
PubMed2002

Quantitative determination of plasma phenylalanine and tyrosine by electrospray ionization tandem mass spectrometry.

BACKGROUND: Phenylketonuria patients on protein-restricted diets require monitoring of their blood phenylalanine concentrations. Small sample volumes are essential for neonates and infants, with the need for results to be generated in a timely manner by robust methods. We present a tandem mass spectrometry assay for phenylalanine (and tyrosine) which fulfils these criteria. METHODS: Plasma samples were deproteinized using a methanolic solution of phenylalanine-d5 and tyrosine-d4 that served as the internal standards for the assay. Following centrifugation each liquid phase was dried in a well of a microtitre plate and the amino acids converted to butyl esters using butanolic hydrogen chloride. After drying again and reconstituting in 80% acetonitrile in water, the samples were analysed using electrospray ionization tandem mass spectrometry. RESULTS: For both phenylalanine and tyrosine the limit of detection was 1 micromol/L and the carry-over less than 1%. The assay was linear to 3000 micromol/L in both amino acids (phenylalanine: r= 0.999; tyrosine: r= 0.992). Inter-sample precision varied with concentration but was 3.4-5.2% for phenylalanine and 4.3-7.6% for tyrosine. Between-batch precision was more variable, being 4.1-12.9% for phenylalanine and 8.4%-10.5% for tyrosine. CONCLUSIONS: Good agreement was found between the assay and results from existing ion-exchange chromatography and high performance liquid chromatographic assays in this department. Carry-over and precision were acceptable for monitoring work and the linearity allowed most specimens to be analysed without dilution. Where available, tandem mass spectrometry offers a convenient means of transferring the routine work for both neonatal screening and monitoring to one instrument.

Humans↗
PubMed2001

Concordance between DSM-III-R and DSM-IV diagnoses of substance use disorders in adolescents.

Except for cannabis and alcohol, concordance between DSM-III-R and DSM-IV substance use disorder diagnoses has not been reported in adolescents. We assessed a clinical sample of 102 adolescents using CIDI-SAM. Prevalence of either an abuse or dependence diagnosis was lower with DSM-IV than DSM-III-R except for cannabis and alcohol, and concordance rates were better for dependence than for abuse. For most substances, rates of DSM-IV withdrawal were lower than in DSM-III-R, but rates of DSM-IV physiological dependence remained high. Changes in DSM-IV criteria appear to have impacted diagnoses in these adolescents, particularly for the substances they use most--i.e. alcohol, tobacco, and cannabis.

Adolescent↗
PubMed2000

Conditional and unconditional inhibition of calcium-activated potassium channels by reversible protein phosphorylation.

Large conductance, calcium-activated potassium channels (BK(Ca) or maxi-K) are important determinants of membrane excitability in many cell types. We used patch clamp techniques to study the biochemical regulation of native BK(Ca) channel proteins by endogenous Ser/Thr-directed protein kinases and phosphatases in cell-free membrane patches from rat pituitary tumor cells (GH(4)C(1)). When protein kinase activity was blocked by removing ATP, endogenous protein phosphatases slowly increased BK(Ca) channel activity approximately 3-fold. Dephosphorylated channels could be activated fully by physiological increases in cytoplasmic calcium or membrane depolarization. In contrast, endogenous protein kinases inhibited BK(Ca) channel activity at two functionally distinct sites. A closely associated, cAMP-dependent protein kinase rapidly reduced channel activity in a conditional manner that could be overcome completely by increasing cytoplasmic free calcium 3-fold or 20 mV further depolarization. Phosphorylation at a pharmacologically distinct site inhibited channel activity unconditionally by reducing availability to approximately half that of maximum at all physiological calcium and voltages. Conditional versus unconditional inhibition of BK(Ca) channel activity through different protein kinases provides cells with a powerful computational mechanism for regulating membrane excitability.

Adenosine Triphosphate↗
PubMed1999

ATP inhibition of a mouse brain large-conductance K+ (mslo) channel variant by a mechanism independent of protein phosphorylation.

1. We investigated the effect of ATP in the regulation of two closely related cloned mouse brain large conductance calcium- and voltage-activated potassium (BK) channel alpha-subunit variants, expressed in human embryonic kidney (HEK 293) cells, using the excised inside-out configuration of the patch-clamp technique. 2. The mB2 BK channel alpha-subunit variant expressed alone was potently inhibited by application of ATP to the intracellular surface of the patch with an IC50 of 30 microM. The effect of ATP was largely independent of protein phosphorylation events as the effect of ATP was mimicked by the non-hydrolysable analogue 5'-adenylylimidodiphosphate (AMP-PNP) and the inhibitory effect of ATPgammaS was reversible. 3. In contrast, under identical conditions, direct nucleotide inhibition was not observed in the closely related mouse brain BK channel alpha-subunit variant mbr5. Furthermore, direct nucleotide regulation was not observed when mB2 was functionally coupled to regulatory beta-subunits. 4. These data suggest that the mB2 alpha-subunit splice variant could provide a dynamic link between cellular metabolism and cell excitability.

Adenosine Diphosphate↗
PubMed1999

Congenital hypothyroidism, seasonality and consanguinity in the West Midlands, England.

Seasonal variation in the incidence of congenital hypothyroidism (CHT) is reported by some centres. Also, the incidence of CHT varies with ethnic origin. We report our experience in the West Midlands, England. The overall incidence of CHT among 1128 632 neonates screened over 16 years in the West Midlands was 1:2924 live births, but was increased (1:2323; p<0.05) between October and December. In the city of Birmingham between 1981 and 1991, the incidence of CHT was 1:781, 1:5540 and 1:2257 in Pakistani, Indian and North-West European children, respectively; no cases were seen in those from other ethnic groups. Consanguinity among those of Pakistani descent could account for the increased incidence within this population. Identification of the cause of seasonal variation may aid development of preventative strategies.

Catchment Area, Health↗
PubMed1998

The origin of red blood cell biopterin.

Data are presented to support the hypothesis that the biopterin content of red blood cells arises during erythropoiesis. Only when the plasma concentration rises above the erythrocyte concentration of biopterin is there likely to be diffusion into the cell.

Adult↗
PubMed1998

Does a single plasma phenylalanine predict quality of control in phenylketonuria?

A 1993 MRC working group on phenylketonuria suggested standardising blood phenylalanine measurements by taking blood samples at the same time each day. Since it is not known how representative of a 24 hour period a single phenylalanine concentration is, the aim of this study was to investigate the 24 hour variability of plasma phenylalanine in well controlled children with phenylketonuria. Sixteen subjects, 12 girls and four boys aged 1 to 18 years, had hourly venous blood samples collected for 13 hours between 09.00 and 21.00 on one day. Serial skin puncture blood specimens were then collected at 24.00, 03.00, and 06.00 within the same 24 hour period. All food and drink was weighed. The median variation in plasma phenylalanine concentration was 155 mumol/l/day, with a minimum of 80 and a maximum of 280. The highest concentration occurred in the morning between 6.00 and 9.00 in 63% of subjects; the lowest occurred between midday and midnight in 94%. Concentrations < 100 mumol/l occurred in 46% of children below 11 years, three having concentrations < 30 mumol/l for two, six, and seven hours respectively. Three of five subjects had concentrations above the MRC guidelines for 24% of the period studied. Except in two subjects, the blood concentrations did not rise in response to phenylalanine consumption. However, the greater the quantity of protein substitute taken between waking and the 16.00 specimen, the larger the decrease in daytime phenylalanine concentration (r = -0.7030) (p < 0.005). There is therefore wide variability in phenylalanine concentrations in a 24 hour period in children with phenylketonuria which is not reflected in a single observation. Further study is needed to investigate the effects of timing of protein substitute on the stability of phenylalanine concentrations.

Adolescent↗
PubMed1998

A comparison of disease and gene frequencies of inborn errors of metabolism among different ethnic groups in the West Midlands, UK.

OBJECTIVE: To assess birth and gene frequencies of specific autosomal recessively inborn errors of metabolism (IEM) within different ethnic groups. DESIGN: Retrospective study in a regional centre for investigation and treatment of IEM. SUBJECTS: All children born within the West Midlands NHS Region, UK, during the decade immediately preceding the 1991 National Census. METHODS: Birth frequencies for individual IEM were calculated separately for the main ethnic groups in the West Midlands using data from the West Midlands Neonatal Screening Programme, the regional register of IEM patients, and population frequencies from the National Census. Gene frequencies were calculated using previously documented observations on parental consanguinity rates and inbreeding coefficients. RESULTS: The overall incidence of recorded IEM was tenfold higher among Pakistanis compared to white children (1:318 v 1:3760), whereas only one AfroCaribbean child was identified (incidence 1:16 887). Tyrosinaemia type 1, cystinosis, mucopolysaccharidosis type 1, non-ketotic hyperglycinaemia, and hyperchylomicronaemia all occurred more frequently among Pakistanis. An increased gene frequency was only confirmed for tyrosinaemia. The incidence of phenylketonuria was similar in Pakistani and white children (1:14 452 v 1:12 611), but the gene frequency was significantly lower in Pakistanis (1:713 v 1:112). These results illustrate the interplay between gene frequency and parental consanguinity in determining disease frequencies in different populations, and indicate anticipated disease frequencies in the absence of consanguineous marriage. These figures have implications for the organisation of services for management of inborn errors, for genetic counselling, and for the assessment of gene flow in world populations.

Ethnicity↗
PubMed1997

An early transient current is associated with hyposmotic swelling and volume regulation in embryonic chick cardiac myocytes.

Hyposmotically induced changes in membrane conductance were measured in embryonic chick cardiac myocytes using conventional and perforated patch-clamp recording techniques; simultaneous measurements of cell volume were made from the video image of the voltage-clamped cell. Hyposmotic challenge was associated with a rapid, transient current coincident with the onset of cell swelling; cell volume subsequently recovered towards control values (regulatory volume decrease; RVD). The transient swelling-induced current (I(swell)) reversed at +15 mV, and was not found to be carried exclusively by any single ion in the physiological solutions. I(swell) was abolished by gadolinium (Gd3+), a blocker of stretch-activated ion channels, and was absent when the cytoskeleton was disrupted by treatment with cytochalasin B. I(swell) was also prevented when intracellular [Ca2+] was buffered with BAPTA AM. Under those experimental conditions which prevented the generation of I(swell), cell volume regulation failed so that the cells remained swollen in hyposmotic solution. Our data reveal a functional relationship between I(swell) and RVD, whereby I(swell) is a necessary prerequisite, although not exclusively sufficient, for volume recovery following cell swelling. We propose that I(swell) is an important early signalling event which activates subsequent mechanisms to regulate cell volume.

Animals↗
PubMed1996

Factors affecting the variation in plasma phenylalanine in patients with phenylketonuria on diet.

The optimal dietary management of children with phenylketonuria (PKU) has rarely been rigorously explored. The aim of this study was to assess longitudinally the effects of three factors thought to influence plasma phenylalanine concentrations in PKU: total energy intake; protein intake from natural foods allowed freely in addition to allocated phenylalanine exchanges; and the distribution of protein substitute throughout the day. Nineteen subjects, 15 girls and four boys aged 1-16 years, were enrolled. Food intake was weighed, and twice daily plasma phenylalanine concentrations measured during either 3-day or 4-day periods, for a total of 21 days throughout six months. There was a negative correlation between the percentage of protein substitute eaten by the time of the evening meal and the fall in plasma phenylalanine concentration during the day (r = -0.941; p < 0.0001). On average, 49% of pre-evening meal plasma phenylalanine concentrations were less than 100 mumol/l in children who had taken at least 65% of their protein substitute by the time of their evening meal. There was no correlation between excess natural protein intake from freely allowed foods and (a) pre-breakfast or pre-evening meal plasma phenylalanine concentrations or (b) the daily change between pre-breakfast and pre-evening meal concentrations. Nor was there any correlation between excess natural protein intake on the previous day and plasma phenylalanine concentration on the following morning. Energy intake was not correlated with plasma phenylalanine concentrations. It is therefore preferable to distribute the protein substitute evenly through the day in order to achieve stable phenylalanine concentrations, rather than to carry out further fine manipulation of the phenylalanine intake, which would make management of the diet even more difficult.

Adolescent↗