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Biomedical subjects

K North

Publications and source records attributed to K North.

At least 19 recordsLinked to original sources
PubMed2004

Blood pressure and pulse responses to three stressors: associations with sociodemographic characteristics and cardiovascular risk factors.

Cardiovascular reactivity is hypothesized to increase the risk of hypertension and other CVD-related conditions. However, studies to date are inconclusive. We compared the association of blood pressure and pulse responses to three stressors (postural challenge, handgrip test, mental arithmetic) with sociodemographic characteristics and CVD risk factors. We included 782 participants from the Hypertension Genetic Epidemiology Study. Blood pressure and pulse responses to stressors were defined as the difference between post- and pre-stress measurements. Stepwise regression analyses examined change in SBP and pulse in response to stressors as a function of sociodemographic and CVD risk factors. Age, race, and gender were forced into models and other variables (education, BMI, waist circumference, resting SBP and DBP, cigarette smoking, LDL and HDL cholesterol, glucose, and antihypertensive medications (beta-blockers, calcium channel blockers, diuretics, ace inhibitors)) were retained if P<0.10. Age was a significant predictor of SBP response to all stressors. The SBP response to a change in posture was not related to other variables. The SBP response to mental arithmetic was significantly higher among men, those with larger waists, higher SBP, beta-blocker users, and lower among smokers. SBP response to the handgrip was significantly higher among those with higher SBP and beta-blocker users. Similarly, the association of the pulse response to the risk factors varied considerably across the stressors. Overall, the socio-demographic and CVD risk factors accounted for between 9 and 14% of the variance in the SBP response to the stressors and from between 4 and 12% of the variance in the pulse response to the three stressors. The associations between sociodemographic and CVD risk factors and the SBP and pulse response to stress were modest and inconsistent across stressors. The findings suggest that cardiovascular reactivity is a concept that needs to be defined in reference to specific stressors so that mechanisms leading to responses can be better understood.

Adult↗
PubMed2004

Evaluation of primary haemostasis in people with neurofibromatosis type 1.

Assessment of haemostasis in people with neurofibromatosis type 1 (NF-1) is essentially lacking, despite case reports of an association with von Willebrand disorder (VWD) and reported excessive bleeding post-surgery. We assessed routine blood haematology, routine coagulation parameters [prothrombin time (PT), activated partial thromboplastin time (APTT), thrombin time (TT) and fibrinogen], coagulation factors II, V, VII, VIII, IX, X, XI and XII, von Willebrand (VWF) factor antigen and activity, and platelet function [using the platelet function analyser (PFA-100)] in a group of individuals with NF-1 (n = 30). Their perceived haemorrhagic bleeding risk was also graded by means of a structured clinical assessment and physical examination. Routine blood assessments including platelet counts were generally normal, as were the routine coagulation tests PT, TT and fibrinogen, and most coagulation factors. Elevated APTTs were detected in 11 individuals, reduced factor XII levels in three, reduced VWF levels in four, and elevated PFA closure times (CTs) in 13. Laboratory results correlated with each other in some but not all cases. For example, elevated APTTs were identified in two of three individuals with a reduced factor XII level and prolonged CTs were identified in three individuals who also showed reduced aggregation responses in classical platelet function studies. Moreover, all individuals with VWF results below the normal reference range showed elevated CTs with both PFA test cartridges, and those with VWF results identified as borderline normal (i.e. 50-65%) also showed elevated CTs with both PFA test cartridges in three of five cases. The relationship between VWF and CTs was also identified by linear regression analysis (P-values of <0.05, for all comparisons). However, as clinically perceived bleeding risk did not appear to be correlated with laboratory test results in most cases, blanket screening of NF-1 individuals for evaluation of laboratory haemostasis may not be warranted.

Adolescent↗
PubMed2004

Outcome of children with neuromuscular disease admitted to paediatric intensive care.

AIMS: To determine the outcome of children with neuromuscular disease (NMD) following admission to a tertiary referral paediatric intensive care (PICU). METHODS: All children with chronic NMD whose first PICU admission was between July 1986 and June 2001 were followed up from their first PICU admission to time of study. The outcomes recorded were death in or outside of PICU, duration of PICU admission, artificial ventilation during admission and following discharge from PICU, and readmission to PICU. RESULTS: Over 15 years, 28 children were admitted on 69 occasions. Sixteen (57%) children had more than one admission. The median duration of PICU admission was 4 days (range 0.5-42). Twenty three per cent of unplanned admissions resulted in the commencement of respiratory support that was continued after discharge from the PICU. Severity of functional impairment was not associated with longer duration of stay or higher PRISM scores. Ten children (36%) died, with four (14%) deaths in the PICU. A higher proportion of children with severe limitation of function were among children that died compared to survivors. CONCLUSION: Most children with NMD admitted to the PICU recover and are discharged without the need for prolonged invasive ventilation. However, in this group of children, the use of non-invasive home based ventilation is common and they are likely to require further PICU admission.

Adolescent↗
PubMed2003

Principal mutation hotspot for central core disease and related myopathies in the C-terminal transmembrane region of the RYR1 gene.

The congenital myopathies are a group of disorders characterised by the predominance of specific histological features observed in biopsied muscle. Central core disease and nemaline myopathy are examples of congenital myopathies that have specific histological characteristics but significantly overlapping clinical pictures. Central core disease is an autosomal dominant disorder with variable penetrance which has been linked principally to the gene for the skeletal muscle calcium release channel (RYR1). Two recent reports have identified the 3' transmembrane domain of this gene as a common site for mutations. Two other studies have reported single families that have features of both central core disease and nemaline myopathy (core/rod disease) caused by mutations in RYR1. Screening of the 3' region (exons 93-105) of the RYR1 gene for mutations in 27 apparently unrelated patients with either central core disease or core/rod disease by single strand conformation polymorphism analysis and DNA sequencing identified three described and nine novel mutations in 15 patients.

DNA Mutational Analysis↗
PubMed2003

Aberrant monocyte prostaglandin synthase 2 (PGS2) expression in type 1 diabetes before and after disease onset.

METHODS: We examined monocyte prostaglandin synthase 2 (PGS2/COX2) expression in individuals at risk for or with type 1 diabetes including: (i) 58 established type 1 and 2 diabetic patients; (ii) 34 autoantibody positive (AA+) children and adults; (iii) 164 infants and young children with insulin-dependent diabetes mellitus (IDDM) susceptibility human leukocyte antigen (HLA) alleles; and (iv) 37 healthy control individuals, over a 5-yr period. RESULTS: Established type 1 diabetic patients (1 month to 30+ yr post-disease onset) had significantly higher PGS2 expression than healthy controls; by contrast, insulin-treated type 2 diabetic patients had significantly lower PGS2 expression than healthy controls. Longitudinal studies of AA+ subjects at risk for type 1 diabetes indicated that 73% (11/15) of individuals who developed this disease during the study period expressed high levels of PGS2 prior to or after onset. We also found high level PGS2 expression in genetically at-risk infants and young children that correlated with having a first-degree relative with type 1 diabetes, but not with age, gender, or HLA genotype. In this population, high level PGS2 expression coincided with or preceded autoantibody detection in 30% (3/10) of subjects. CONCLUSIONS: These findings suggest that high level monocyte PGS2 expression, although subject to fluctuation, is present in at-risk subjects at an early age and is maintained during progression to and after type 1 diabetes onset.

Adult↗
PubMed2001

Differential expression of the actin-binding proteins, alpha-actinin-2 and -3, in different species: implications for the evolution of functional redundancy.

The alpha-actinins are a multigene family of four actin-binding proteins related to dystrophin. The two skeletal muscle isoforms of alpha-actinin (ACTN2 and ACTN3) are major structural components of the Z-line involved in anchoring the actin-containing thin filaments. In humans, ACTN2 is expressed in all muscle fibres, while ACTN3 expression is restricted to a subset of type 2 fibres. We have recently demonstrated that alpha-actinin-3 is absent in approximately 18% of individuals in a range of human populations, and that homozygosity for a premature stop codon (577X) accounts for most cases of true alpha-actinin-3 deficiency. Absence of alpha-actinin-3 is not associated with an obvious disease phenotype, raising the possibility that ACTN3 is functionally redundant in humans, and that alpha-actinin-2 is able to compensate for alpha-actinin-3 deficiency. We now present data concerning the expression of ACTN3 in other species. Genotyping of non-human primates indicates that the 577X null mutation has likely arisen in humans. The mouse genome contains four orthologues which all map to evolutionarily conserved syntenic regions for the four human genes. Murine Actn2 and Actn3 are differentially expressed, spatially and temporally, during embryonic development and, in contrast to humans, alpha-actinin-2 expression does not completely overlap alpha-actinin-3 in postnatal skeletal muscle, suggesting independent function. Furthermore, sequence comparison of human, mouse and chicken alpha-actinin genes demonstrates that ACTN3 has been conserved over a long period of evolutionary time, implying a constraint on evolutionary rate imposed by continued function of the gene. These observations provide a real framework in which to test theoretical models of genetic redundancy as they apply to human populations. In addition we highlight the need for caution in making conclusions about gene function from the phenotypic consequences of loss-of-function mutations in animal knockout models.

Actinin↗
PubMed2000

Neurofibromatosis type 1.

Neurofibromatosis 1 (NF1) is an autosomal dominant neurocutaneous disorder with an incidence of approximately 1 in 4000. Cognitive deficits and academic learning difficulties are the most common neurological 'complication' of NF1 in childhood and can be responsible for significant lifetime morbidity. The NF1 gene is usually classified as a tumor suppressor gene, but it is not yet known how NF1 gene mutations cause many of the non-tumor manifestations of the disorder. The NF1 protein, neurofibromin is expressed early during embryonic development with high levels of expression in the brain, suggesting that it plays an important role in regulating the orderly differentiation of central nervous system neurons. The mouse model for NF1 demonstrates behavioral abnormalities which bear striking similarity to the cognitive phenotype observed in humans with NF1. This review summarises our current understanding of the function of the NF1 gene, the nature of cognitive deficits in this disorder and correlations between neuroradiological, pathological and neuropsychological findings and animal studies which provide an insight into the pathogenesis.

Animals↗
PubMed2000

Delayed conception and active and passive smoking. The Avon Longitudinal Study of Pregnancy and Childhood Study Team.

OBJECTIVE: To determine whether passive as well as active smoking by women or smoking by men is associated with delayed conception, after adjustment for confounding factors. DESIGN: Population study of couples expecting a baby. Logistic regression was performed to identify factors associated with delayed conception. SETTING: The Avon Health Authority area, United Kingdom. PATIENT(S): All couples expected to deliver between April 1991 and December 1992. INTERVENTION(S): Questionnaires administered early in pregnancy. MAIN OUTCOME MEASURE(S): Time taken to conceive, categorized as <6 months, 6-11 months, 1-3 years, and >3 years. RESULT(S): After correction for confounding factors, delayed conception was statistically significantly associated with both active smoking by the woman (odds ratio [OR] 1.23 [95% CI 0.98-1.49] for > 6 months and 1.54 [95% CI 1.19-2.01] for >12 months) and her exposure to passive smoking (OR 1.17 [95% CI 1.02-1.37] and 1.14 [95% CI 0.92-1.42]) compared with women with no exposure to tobacco smoke (referent). Heavy smoking by men was independently associated with delayed conception. In active smokers, the effect increased with the number of cigarettes. CONCLUSION(S): Smoking by men and passive and active smoking by women are associated with delayed conception.

Adult↗
PubMed2000

Types of drinks consumed by infants at 4 and 8 months of age: a descriptive study. The ALSPAC Study Team.

OBJECTIVE: To document the type and volume of drinks given to infants and investigate whether giving supplementary drinks leads to reduced milk consumption. DESIGN: Carers were asked to record all drinks consumed by the infants in a 24-hour period at two ages, detailing the types and volume taken. SETTING: The Avon Longitudinal Study of Pregnancy and Childhood (ALSPAC). SUBJECTS: A randomly chosen population sample of over 1000 infants at 4 and 8 months of age. RESULTS: The different types of milk feed were used to group infants, compare volumes consumed and look at the use of non-milk drinks. The average volume of drinks consumed over 24 hours at 4 months was 861 ml and at 8 months was 662 ml. At 4 months 69.7% consumed infant formula and 43.0% breast milk. The mean volume of milk consumed by those having only formula was 802 ml and for those having only breast milk was estimated at 850 ml. The volumes of milks consumed were slightly lower in the groups who also had supplementary drinks. A quarter of infants were given fruit drinks and 14.6% herbal drinks. Supplementary drinks and solids were more likely to be given to formula-fed than breast-fed infants. At 8 months, formula milk was consumed by 71.4% and breast milk use had decreased (22.9%) but fruit drink use had increased (squash/cordial: 55.8%, fruit juice: 14.9%), with 13.9% of infants having no infant milk at all. More infants were fed formula milk and less were fed cows' milk compared with a nationally representative British study conducted 5 years earlier. CONCLUSIONS: Many infants were given supplementary drinks by 4 months; there is some evidence that this led to a small reduction in milk intake. A minority were not being given infant milks at all by 8 months, contrary to British infant feeding recommendations.

Animals↗
PubMed2000

Multivariate analysis of diet among three-year-old children and associations with socio-demographic characteristics. The Avon Longitudinal Study of Pregnancy and Childhood (ALSPAC) Study Team.

STUDY OBJECTIVE: The study of the whole diet in combination rather than the consumption of individual food items or the intake of specific nutrients could be enlightening. This has been previously performed using principal components analysis (PCA) on adult diets but not on those of children. DESIGN: The frequency of consumption of a range of food items was recorded for 10,139 3-y-old children by their mothers using self-completion postal questionnaires. These children form part of the Avon Longitudinal Study of Pregnancy and Childhood (ALSPAC). METHODS: PCA was performed to identify individual dietary types which were then related to various socio-economic and demographic characteristics. RESULTS: Four distinct dietary components were obtained explaining 23.5% of the total variation in the sample, and the socio-demographic characteristics of the sample were related to them. The first represented a diet based on convenience foods and was associated with younger, less educated mothers and the presence of older siblings. The second was associated with a high consumption of foods currently considered to be healthy and was particularly related to vegetarian mothers and higher education levels. The third component described the established British 'meat and two veg' diet and was associated with girls and children with no older siblings, while the fourth had high loadings for snack and finger foods and was related to socially advantaged conditions and the presence of older siblings. CONCLUSIONS: Identifiable groups of mothers were associated with feeding their child each of the four dietary types, supporting the hypothesis that social, demographic and lifestyle factors relating to the mother have an influence on the early eating patterns of children. This analysis will form a basis for the future study of various childhood outcomes including growth, health and development. SPONSORSHIP: University of Bristol European Journal of Clinical Nutrition (2000) 54, 73-80

Adult↗
PubMed2000

A maternal vegetarian diet in pregnancy is associated with hypospadias. The ALSPAC Study Team. Avon Longitudinal Study of Pregnancy and Childhood.

OBJECTIVE: To investigate the possible role of the maternal diet, particularly vegetarianism and consumption of phytoestrogens, in the origin of hypospadias, which is reported to be increasing in prevalence. SUBJECTS AND METHODS: Detailed information was obtained prospectively from mothers, including previous obstetric history, lifestyle and dietary practices, using structured self-completed questionnaires during pregnancy. Previously recognized associations with environmental and parental factors were examined, focusing particularly on the hypothesized hormonal link. Multivariate logistic regression was used to identify independent associations. RESULTS: Of 7928 boys born to mothers taking part in the Avon Longitudinal Study of Pregnancy and Childhood, 51 hypospadias cases were identified. There were no significant differences in the proportion of hypospadias cases among mothers who smoked, consumed alcohol or for any aspect of their previous reproductive history (including the number of previous pregnancies, number of miscarriages, use of the contraceptive pill, time to conception and age at menarche). Significant differences were detected for some aspects of the maternal diet, i.e. vegetarianism and iron supplementation in the first half of pregnancy. Mothers who were vegetarian in pregnancy had an adjusted odds ratio (OR) of 4.99 (95% confidence interval, CI, 2.10-11.88) of giving birth to a boy with hypospadias, compared with omnivores who did not supplement their diet with iron. Omnivores who supplemented their diet with iron had an adjusted OR of 2.07 (95% CI, 1.00-4.32). The only other statistically significant association for hypospadias was with influenza in the first 3 months of pregnancy (adjusted OR 3.19, 95% CI 1.50-6.78). CONCLUSION: As vegetarians have a greater exposure to phytoestrogens than do omnivores, these results support the possibility that phytoestrogens have a deleterious effect on the developing male reproductive system.

Diet, Vegetarian↗
PubMed2000

Increasing paternal age is associated with delayed conception in a large population of fertile couples: evidence for declining fecundity in older men. The ALSPAC Study Team (Avon Longitudinal Study of Pregnancy and Childhood).

The impact of male age on fecundity remains controversial. Here, a large population study was used to investigate the effect of paternal age on time to conception. All couples in the Avon Health district expecting a baby between 1 April 1991 and 31 December 1992 were eligible. Questionnaires completed by both the man and the woman at 18 weeks gestation covered specific fertility factors, e.g. parity, paternity, cohabitation and oral contraception; and non-specific factors, e.g. educational achievement, housing, cigarette smoking, alcohol consumption, obesity. Logistic regression was used to identify factors independently related to conception in < or =6 or < or =12 months. Of 8515 planned pregnancies, 74% were conceived in < or =6 months, 14% in the second 6 months and 12% after more than a year. Nine variables, including the age of the woman, were independently related to time to conception. After adjustment for these, the likelihood of conception within 6 or 12 months was lower in older men. Compared to men <25 years old, the adjusted odds ratios (95% confidence interval) for conception in < or =12 months were 0.62 (0.40, 0.98), 0.50 (0.31, 0.81) and 0.51 (0.31, 0.86) in men aged 30-34, 35-39 and > or =40 years respectively.

Adult↗
PubMed1999

Pertussis vaccination and wheezing illnesses in young children: prospective cohort study. The Longitudinal Study of Pregnancy and Childhood Team.

OBJECTIVES: To examine the relation between pertussis vaccination and the prevalence of wheezing illnesses in young children. DESIGN: Prospective cohort study. SETTING: Three former health districts comprising Avon Health Authority. SUBJECTS: 9444 of 14 138 children enrolled in the Avon longitudinal study of pregnancy and childhood and for whom data on wheezing symptoms, vaccination status, and 15 environmental and biological variables were available. MAIN OUTCOME MEASURES: Episodes of wheezing from birth to 6 months, 7-18 months, 19-30 months, and 31-42 months. These time periods were used to derive five categories of wheezing illness: early wheezing (not after 18 months); late onset wheezing (after 18 months); persistent wheezing (at every time period); recurrent wheezing (any combination of two or more episodes for each period); and intermittent wheezing (any combination of single episodes of reported wheezing). These categories were stratified according to parental self reported asthma or allergy. RESULTS: Unadjusted comparisons of the defined wheezing illnesses in vaccinated and non-vaccinated children showed no significant association between pertussis vaccination and any of the wheezing outcomes regardless of stratification for parental asthma or allergy. Wheeze was more common in non-vaccinated children at 18 months, and there was a tendency for late onset wheezing to be associated with non-vaccination in children whose parents did not have asthma, but this was not significant. After adjustment for environmental and biological variables, logistic regression analyses showed no significant increased relative risk for any of the wheezing outcomes in vaccinated children: early wheezing (0.99, 95% confidence interval 0.80 to 1.23), late onset wheezing (0.85, 0.69 to 1.05), persistent wheezing (0.91, 0.47 to 1.79), recurrent wheezing (0.96, 0.72 to 1.26), and intermittent wheezing (1.06, 0.81 to 1.37). CONCLUSIONS: No evidence was found that pertussis vaccination increases the risk of wheezing illnesses in young children. Further follow up of this population with objective measurement of allergy and bronchial responsiveness is planned to confirm these observations.

Cohort Studies↗
PubMed1999

Does employment improve the health of lone mothers? The ALSPAC Study Team. Avon Longitudinal Study of Pregnancy and Childhood.

In Britain the government is currently proposing legislation that will encourage welfare recipients to gain employment. A central tenet of this 'welfare to work' policy is that employment will not only reduce the poverty of welfare recipients, but also improve their health. This research assessed the extent to which the movement from 'welfare to work' is likely to benefit the mental and physical health of lone mothers with preschool children. The sample was 719 lone mothers and a comparison group of 8779 women with partners drawn from the Avon Longitudinal Study of Pregnancy and Childhood (ALSPAC). Data collected by self completion questionnaire at 33 months postpartum provided information about average weekly take home family income and the mother's employment status. The health outcomes measured were general well being, both minor and major depression (using the Edinburgh Postnatal Depression Scale), self report of respiratory symptoms (cough/cold, wheeze, influenza) from 18-33 months postpartum and self report of symptoms common in the childbearing years (backache, haemorrhoids) also from 18-33 months postpartum. Lone mothers who were not employed were the poorest group in the sample; 94% of this group (402) had a family income of less than pound sterling 200 per week, compared with 72% (188) of lone mothers who were employed, 25% (905) of partnered women who were not employed and 12% (466) of partnered women who were employed. Lone mothers were significantly more likely than women with partners to report poorer well being (chi2 = 11.7, df = 3, P = 0.01), to have a major depressive disorder (chi2 = 92.6, df = 1, P = 0.0001) and to report wheeze (chi2 = 31.1, df = 1, P = 0.0001), but significantly less likely to report cough/cold (chi2 = 9.9, df = 1, P = 0.0001) or haemorrhoids (chi2 = 16.6, df = 1, P = 0.0001). Lone mothers who were unemployed and living on less than pound sterling 100 per week were significantly more likely to be depressed (chi2 = 3.9, df = 1, P = 0.05) than those who were employed and living on pound sterling 200 or more per week, and significantly less likely to report cough/cold (chi2 = 3.8, df = 1, P = 0.05). Logistic regression analyses showed no significant independent association between employment and better health for lone mothers. Rather, when compared with lone mothers who were not working, those who were employed were more likely to report minor respiratory symptoms such as cough/cold (OR = 1.51, 95% CI = 1.00,2.31). Overall, the results suggested that the movement from 'welfare to work' is unlikely to improve the health of lone mothers.

Adult↗
PubMed1999

Homozygosity for a nonsense mutation in the alpha-tropomyosin slow gene TPM3 in a patient with severe infantile nemaline myopathy.

The nemaline myopathies are muscle disorders of variable severity and age of onset, with characteristic nemaline bodies in the sarcoplasm. Genes for dominant (NEM1) and recessive (NEM2A) nemaline myopathy have been localised to chromosomes one and two, respectively. A missense mutation in the alpha-tropomyosin gene (TPM3) has been associated with NEM1 in one family. Probands from 76 other nemaline myopathy families have now been screened for TPM3 mutations. One proband, who was not noted to have any weakness neonatally, but who died at 21 months of age, was shown to be homozygous for a single strand conformation polymorphism (SSCP) in skeletal-muscle-specific exon 1 of TPM3. Sequencing revealed homozygosity for a nonsense mutation at codon 31 (CAG to TAG). The patient should have no functioning alpha-tropomyosin slow protein. The nemaline bodies in this patient were exclusively in type one fibres, consistent with the expression of TPM3 only in type one fibres.

Fatal Outcome↗
PubMed1999

Pacifier use and morbidity in the first six months of life.

OBJECTIVE: To assess the prevalence of pacifier use and whether this habit adversely affects the health of 6-month-old infants. DESIGN: Data collected via self-completion questionnaires from mothers forming part of the prospective, population-based Avon Longitudinal Study of Pregnancy and Childhood. METHODS: The mothers of 10 950 infants gave information on their child's use of a pacifier at 4 weeks and 6 months of age and the presence of specific health symptoms. Adjusted logistic regression was performed to identify any associations between pacifier use and ill health. RESULTS: Two thirds of the sample had been given a pacifier at some point, with 42% being reported as having one at both ages. Younger, lower educated mothers, mothers who smoked, those living in council and overcrowded accommodation, and those reporting financial difficulties were significantly more likely to give their infant a pacifier. Pacifier use was associated significantly with a higher risk of symptoms such as wheezing, earache, vomiting, fever, diarrhea, and colic as well as with the general practitioner being called to the home and hospital admission. CONCLUSIONS: Although significant differences exist in the risk of experiencing several health symptoms between infants who do and infants who do not use a pacifier, stronger and more detailed evidence is required before recommendations can be made to discourage the use of pacifiers based purely on reducing occurrences of these symptoms.

England↗
PubMed1997

Neurofibromatosis of the small intestine mesentery in a child with neurofibromatosis type 1.

The authors present a case of mesenteric neurofibromatosis in a child, which is a rare complication of neurofibromatosis type 1 (NF1). This case is presented to illustrate the clinical features and the radiological appearance of mesenteric neurofibromatosis, which, in the appropriate clinical setting of NF1, are diagnostic. The authors also discuss the long-term complications of this condition, which includes the potential risk of malignant degeneration.

Child↗