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Biomedical subjects

J Mulligan

Publications and source records attributed to J Mulligan.

At least 37 records · Page 2Linked to original sources
PubMed1998

Randomised trial of growth hormone in short normal girls.

BACKGROUND: There are few data on the long-term outcome of growth-hormone treatment in short normal children. We assessed the impact of growth-hormone treatment on pubertal development and near-final height in girls. METHODS: In a randomised controlled trial, we studied ten girls, with a mean age of 8.07 years and height 2 SDs or more below the mean for their age, and eight short untreated controls matched for age, and 20 short untreated girls who did not give consent for randomisation. The girls received either 30 IU/m2 somatropin per week as daily subcutaneous injections or no treatment. We assessed pubertal staging and height gain every 6 months. FINDINGS: Eight treated girls completed a mean of 6.2 years' therapy. By a mean age of 16.4 years, their mean height SD score had changed significantly from -2.42 to -1.14 (p=0.008) and they were, on average, 7.5 cm taller than the girls in the control group (height SD scores did not change significantly from -2.55) and 6.0 cm taller than the non-consent group. The timing of each pubertal stage, and the age and amplitude of peak height velocity were similar for all groups. INTERPRETATION: Growth-hormone therapy effectively increased height SD score among short normal girls started on treatment in early to mid childhood, with no untoward effect on pubertal progression.

Body Height↗
PubMed1998

Short stature at school entry--an index of social deprivation? (The Wessex Growth Study).

This study was carried out to examine the biological and environmental variables associated with non-organic short stature. We observed an unselected population of very short normal children (SN) and their age- and sex-matched controls (C) within the community. All 14,346 children in two health districts entering school during 2 consecutive years were screened for short stature, and those whose height lay below the 3rd centile, according to Tanner and Whitehouse standards (n = 180) were identified. Excluding 32 with pathology, five from ethnic minorities and three who refused to take part, the remaining SN children (mean height SDS-2.26) were matched with 140 age- and sex-matched controls (C) of average height (mean height SDs 0.14). Birth weight, target height and predicted adult height (based on parental height and bone age respectively), medical and social background (obtained from parental interviews), and school performance (assessed by class teachers) were the main outcome measures. Mean birth weight of the SN children was significantly lower than C (SN = 2845 g, C = 3337 g, P < 0.001). Mean mid-parental target height was also very different (SN = 162.0 cm, C = 170.9 cm, P < 0.001). Thirty-five per cent of SN children (C = 6%) had height SD scores below parental target range, though only 10% had predicted heights below target range (mean delay in bone age 0.68 years). There was a significant difference between SN children and C in the number of children in the household (SN = 2.8, C = 2.4 (P = 0.007) and in socio-economic status (P < 0.002). Many more SN children were in social classes IV and V (SN = 31%, C = 13%, P < 0.002), and had an unemployed father (SN = 22%, C = 10%, P < 0.010), highlighting the importance of environmental influences on growth. One in four SN children was judged to have serious psychosocial problems. However, the lower the socio-economic class, the less likely the SN children were to be inappropriately short for parents. Significantly more SN children were reported to have asthma (SN = 18%, C = 7%, P < 0.007) and eczema (SN = 19%, C = 5%, P < 0.001), though only the latter was significantly associated with stature below target height for both SN and C groups. Biological variables are often insufficient to explain short stature. No child, whatever the parental height, should be dismissed as normal without careful evaluation, as poor growth in the early years may be an important pointer to an adverse but potentially remediable environment.

Adult↗
PubMed1998

Growth monitoring: testing the new guidelines.

OBJECTIVE: To assess the impact of recent guidelines from the UK joint working party of child health surveillance recommending that all children be measured at age 5 and again between 7 and 9 years of age to determine how many normal school age children are likely to be referred for specialist assessment. METHODS: The longitudinal data of 486 children measured by school nurses in a community setting were examined and compared with measurements made in a research setting by a single, skilled observer. MAIN OUTCOME MEASURES: Number of children identified as having abnormal stature (< 0.4th or > 99.6th centile) and abnormal growth rate height standard deviation score (HSDS) change > 0.67). RESULTS: The community survey identified seven (1.4%) children as having abnormal stature (four short, three tall), 11 (2.3%) were identified as "slow growing", and nine (1.9%) increased their HSDS by more than 0.67. These results were comparable to data collected in ideal research conditions. CONCLUSIONS: Following the recommendations would not result in an excess number of inappropriate referrals. However, this study highlights several unresolved issues such as interobserver variability and time interval between measurements. A large scale prospective study should be considered to establish realistic and cost-effective criteria before implementation of a national screening programme.

Body Height↗
PubMed1998

Normal growth in the short normal prepubertal child: the Wessex Growth Study.

OBJECTIVE: The study aimed at defining the normal rate of growth for short, prepubertal children, and comparing their pattern of growth with those of average stature. SETTING: Community based. DESIGN: Observation of an unselected population of 109 very short, normal prepubertal children (< 3rd height centile) and 107 controls matched for age and sex (10th to 90th centile). MAIN OUTCOME MEASURES: Height, velocity, change in height standard deviation score, from 6 to 9 years of age. RESULTS: The absolute mean rate of growth was significantly different between groups--short normal 5.3 cm/year, controls 5.9 cm/year--corresponding to velocities on the 25th and 50th centiles, respectively. The relative growth rates, however, as shown by the changes in height standard deviation score (short normal 0.10 (SD 0.22), controls 0.10 (SD 0.24) did not differ, and each group remained close to its original 3rd and 50th centiles. Two short children showed "catch up" growth after adoption, but, otherwise, the divergence from their original height centile was the same for short normal and control children. No social or biological factors were found to predict growth rate in the short normal children, and only target height in controls. "Normal" velocity is conditional on height. Short normal children do grow more slowly than children of average stature, but they do not necessarily grow more poorly. From 6 to 9 years of age they are no more likely to fall off their height centiles than children of average stature. The value of height monitoring at this age is questioned.

Body Height↗
PubMed1997

The nucleotide sequence of Saccharomyces cerevisiae chromosome V.

Here we report the sequence of 569,202 base pairs of Saccharomyces cerevisiae chromosome V. Analysis of the sequence revealed a centromere, two telomeres and 271 open reading frames (ORFs) plus 13 tRNAs and four small nuclear RNAs. There are two Tyl transposable elements, each of which contains an ORF (included in the count of 271). Of the ORFs, 78 (29%) are new, 81 (30%) have potential homologues in the public databases, and 112 (41%) are previously characterized yeast genes.

Base Sequence↗
PubMed1997

Are short normal children at a disadvantage? The Wessex growth study.

OBJECTIVE: To examine whether short stature through childhood represents a disadvantage at around 12 years. DESIGN: Longitudinal non-intervention study of the physical and psychological development of children recruited from the community in 1986-7 after entry into primary school at age 5-6 years; this is the second psychometric assessment made in 1994-5 after entry into secondary school at age 11-13 years. SETTING: Southampton and Winchester health districts. SUBJECTS: 106 short normal children (< 3rd centile for height when recruited) and 119 controls of average stature (10th-90th centile). MAIN OUTCOME MEASURES: Psychometric measures of cognitive development, self concept development, behaviour, and locus of control. RESULTS: The short children did not differ significantly from the control children on measures of self esteem (19.4 v 20.2), self perception (104.2 v 102.4), parents' perception (46.9 v 47.0), or behaviour (6.8 v 5.3). The short children achieved significantly lower scores on measures of intelligence quotient (IQ) (102.6 v 108.6; P < 0.005), reading attainment (44.3 v 47.9; P < 0.002), and basic number skills (40.2 v 43.5; P < 0.003) and displayed less internalisation of control (16.6 v 14.3; P < 0.001) and less satisfaction with their height (P < 0.0001). More short than control children, however, came from working class homes (P < 0.05). Social class was a better predictor than height of all measures except that of body satisfaction. Attainment scores were predicted by class and IQ together rather than by height. Height accounted for some of the variance in IQ and locus of control scores. CONCLUSIONS: These results provide only limited support for the hypothesis that short children are disadvantaged, at least up until 11-13 years old. Social class seems to have more influence than height on children's psychological development.

Adolescent↗
PubMed1997

Mutations in the consensus helicase domains of the Werner syndrome gene. Werner's Syndrome Collaborative Group.

Werner syndrome (WS) is an autosomal recessive disease with a complex phenotype that is suggestive of accelerated aging. WS is caused by mutations in a gene, WRN, that encodes a predicted 1,432-amino-acid protein with homology to DNA and RNA helicases. Previous work identified four WS mutations in the 3' end of the gene, which resulted in predicted truncated protein products of 1,060-1,247 amino acids but did not disrupt the helicase domain region (amino acids 569-859). Here, additional WS subjects were screened for mutations, and the intron-exon structure of the gene was determined. A total of 35 exons were defined, with the coding sequences beginning in the second exon. Five new WS mutations were identified: two nonsense mutations at codons 369 and 889; a mutation at a splice-junction site, resulting in a predicted truncated protein of 760 amino acids; a 1-bp deletion causing a frameshift; and a predicted truncated protein of 391 amino acids. Another deletion is >15 kb of genomic DNA, including exons 19-23; the predicted protein is 1,186 amino acids long. Four of these new mutations either partially disrupt the helicase domain region or result in predicted protein products completely missing the helicase region. These results confirm that mutations in the WRN gene are responsible for WS. Also, the location of the mutations indicates that the presence or absence of the helicase domain does not influence the WS phenotype and suggests that WS is the result of complete loss of function of the WRN gene product.

Asian People↗
PubMed1996

Efficient random subcloning of DNA sheared in a recirculating point-sink flow system.

Based on a high-performance liquid chromatographic pump, we have built a device that allows recirculation of DNA through a 63-microm orifice with ensuing fractionation to a minimum fragment size of approximately 300 base pairs. Residence time of the DNA fragments in the converging flow created by a sudden contraction was found to be sufficiently long to allow extension of the DNA molecules into a highly extended conformation and, hence, breakage to occur at midpoint. In most instances, 30 passages sufficed to obtain a narrow size distribution, with >90% of the fragments lying within a 2-fold size distribution. The shear rate required to achieve breakage was found to be inversely proportional to the 1.0 power of the molecular weight. Compared with a restriction digest, up to 40% of all fragments could be cloned directly, with only marginal improvements in cloning efficiency having been observed upon prior end repair with Klenow, T4 polymerase or T4 polynucleotide kinase. Sequencing revealed a fairly random distribution of the fragments.

Bacteriophage M13↗
PubMed1996

Genomic structure and expression of STM2, the chromosome 1 familial Alzheimer disease gene.

Mutations in the gene STM2 result in autosomal dominant familial Alzheimer disease. To screen for mutations and to identify regulatory elements for this gene, the genomic DNA sequence and intron-exon structure were determined. Twelve exons including 10 coding exons were identified in a genomic region spanning 23,737 bp. The first 2 exons encode the 5'-untranslated region. Expression analysis of STM2 indicates that two transcripts of 2.4 and 2.8 kb are found in skeletal muscle, pancreas, and heart. In addition, a splice variant of the 2.4-kb transcript was identified that is the result of the use of an alternative splice acceptor site located in exon 10. The use of this site results in a transcript lacking a single glutamate. The promotor for this gene and the alternatively spliced exons leading to the 2.8-kb form of the gene remain to be identified. Expression of STM2 was high in skeletal muscle and pancreas, with comparatively low levels observed in brain. This expression pattern is intriguing since in Alzheimer disease, pathology and degeneration are observed only in the central nervous system.

Alternative Splicing↗
PubMed1996

Positional cloning of the Werner's syndrome gene.

Werner's syndrome (WS) is an inherited disease with clinical symptoms resembling premature aging. Early susceptibility to a number of major age-related diseases is a key feature of this disorder. The gene responsible for WS (known as WRN) was identified by positional cloning. The predicted protein is 1432 amino acids in length and shows significant similarity to DNA helicases. Four mutations in WS patients were identified. Two of the mutations are splice-junction mutations, with the predicted result being the exclusion of exons from the final messenger RNA. One of the these mutations, which results in a frameshift and a predicted truncated protein, was found in the homozygous state in 60 percent of Japanese WS patients examined. The other two mutations are nonsense mutations. The identification of a mutated putative helicase as the gene product of the WS gene suggests that defective DNA metabolism is involved in the complex process of aging in WS patients.

Aging↗
PubMed1996

Psychological response to growth hormone treatment in short normal children.

This study provides a controlled assessment of the psychological (and physical) effects of growth hormone treatment. Fifteen short 'normal' children (height SD score < -2) have been treated with growth hormone since the age of 7/8 years. They, together with untreated short controls and average controls (10th-90th centiles), were assessed at recruitment, after three years, and after five years. Only the treated group showed a significant height increase (SD score -2.44 to -1.21 over five years). No significant differences were found at recruitment, three years, or five years in IQ, attainment, behaviour, or self esteem. Also at five years, there were no significant differences in locus of control, self perception, or parental perceptions of competence. Both short groups displayed less satisfaction with their height than the controls (p < 0.01), though all groups were optimistic of being tall adults. The treated children were no more unrealistic over final height than the untreated children. To date, no psychological benefits of treatment have been demonstrated; but nor have there been any discernible ill effects for either the treated or the untreated children.

Adolescent↗
PubMed1994

Growth and metabolic consequences of growth hormone treatment in prepubertal short normal children.

Growth and the metabolic effects of growth hormone were monitored in a randomised, controlled group of 41 short, normal, prepubertal children. The treated group received daily injections of growth hormone as Genotropin (Kabi Pharmacia) 30 IU/m2/week. Fifteen children in the treated group (21 children) have completed three years of treatment, have grown significantly more than 14 (of 20) untreated children, and have a significantly greater adult height prediction. They do, however, remain leaner (body fat 13.5% in the treated group, 18% in the untreated group) and relatively hyperinsulinaemic (insulin 66.7 pmol/l in the treated group, 44.5 in the untreated group) after three years compared with untreated children. Although growth hormone appears to improve the height potential of prepubertal short normal children, the long term outcome is still uncertain.

Body Composition↗
PubMed1992

Poor growth in school entrants as an index of organic disease: the Wessex growth study.

OBJECTIVE: To establish whether poor height or height velocity, assessed during the year of school entry, might identify children with previously undiagnosed organic disease. DESIGN: Observation of a total population and their case controls. SETTING: Community base. SUBJECTS: All 14,346 children in two health districts entering school during two consecutive years were screened for height by school nurses, and those whose height lay below the 3rd centile according to Tanner and Whitehouse standards (n = 180) were identified. After excluding 32 with known organic disease, five from ethnic minorities, and three who refused to take part, the remaining 140 short normal children were matched with 140 age and sex matched controls of average height (10th-90th centile) and their height velocities over 12 months measured. MAIN OUTCOME MEASURES: Height, height velocity, previously diagnosed organic disease, and organic disease diagnosed as a result of blood tests and specialist examination. RESULTS: Twenty five of the 180 short children (14%) were already known to have chronic organic disease which could explain their poor growth. Blood tests and specialist examination revealed a further seven with organic disease, which was acquired rather than congenital in three, and a second cause of short stature in one with known organic disease. These eight conditions had been missed at the school entry medical examination. The shorter the child, the more likely an underlying organic disorder, with seven of the 12 children whose heights were more than 3 standard deviations below the mean having some organic disease. Height velocity measured over 12 months, however, did not distinguish short normal children from those with disease or from their matched controls. CONCLUSIONS: Height, but not height velocity, is a useful index for identifying unrecognised organic disease at school entry. The shorter the stature the greater the prevalence of organic disease. The frequency of newly diagnosed remediable disease in this study (1 in 3-4000) is similar to that of neonatal hypothyroidism, which is routinely screened for. Routine investigation of all very short school entrants is recommended.

Body Height↗
PubMed1991

Communication problems between doctors and nurses.

Communication difficulties between hospital doctors and nurses are well documented. A survey undertaken jointly by medical and nursing administration at Sir Charles Gairdner Hospital in Perth, Western Australia, verified difficulties in doctor-nurse communication as perceived by doctors and nurses, as well as by ward clerks as impartial observers. Questionnaire responses revealed some impediments in the flow of communication. Both nurses and doctors perceived less frequency of difficulties in communicating with members of their own professional group than with members of the other group. Nurses with university preparation and other special clinical qualifications perceived significantly fewer communication problems with doctors than nurses with less education. Interns perceived greater frequency in difficulty communicating with nurses than did more highly qualified doctors, and female doctors who were not interns claimed fewer problems than their male counterparts. Moreover, more highly qualified male doctors who had a previous occupation acknowledged fewer doctor-nurse communication problems.

Attitude of Health Personnel↗
PubMed1991

Short stature and school performance--the Wessex Growth Study.

The relationship between short stature and school performance was examined by comparing an unselected cohort of 140 'normal' short children (below 3rd centile) aged between 7 and 9 years with 140 control children of normal height (10th-90th centiles). The short children had unimpaired self-esteem and normal patterns of behaviour, but a tendency towards hyperactivity and poor concentration. Their IQ scores were normal, but attainment, especially in reading, was low. The underachievement observed in the short children is largely due to the low socio-economic status of this group. All the children in the study were prepubertal and these data will serve as a baseline for further follow-up during and after puberty.

Body Height↗