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My Research


My Research Publications


1. Secular trend of growth in pre-school children in Singapore.

Mabel A Yap, Kwok Chan Lun, Kenneth R Lyen and Sian Lian Lam

Asia Pacific J Clin Nutr (1994) 3, 61-64.

An anthropometric study was conducted in 1988 on 13,500 children from 0 to 4 years of age. Percentile charts were plotted for height for age, weight for age, weight for height and head circumference for age. When compared to an earlier study done in 1972, it was found that Singapore pre-school children had increased in height by 4.4%; weight by 10.9%; and head circumference by 4.1%. When the median height for age, weight for age and head circumference for age were plotted against those of the NCHS charts (1978), Singapore's pre-school children were generally shorter, lighter and had smaller head circumferences than their American counterparts of the same age. But, the median weight-for-height for each age group was comparable to the Americans. The results indicate the secular trend of growth in Singapore children and a trend towards reaching their full genetic potential for growth.


2. Mass poisoning in Perak, Malaysia or the Tale of the Nine Emperor Gods and rat tail noodles.

Chao TC, Maxwell SM, Lyen KR, Wang D, Chia HK.

J Forensic Sci Soc. 1991 Apr-Jun;31(2):283-8.


3. Normal standard of pubertal development in Singapore school children.

Loke KY, Lee BW, Tan SH, Lun KC, Lee WK, Lyen KR.

J Singapore Paediatr Soc. 1991;33(3-4):126-32.

A cross-sectional study of the pubertal status of normal school children in Singapore was performed in 1987. The results of the data analysis are presented as an update from the last survey performed in 1977. The norms of pubertal development in boys and girls are thus defined.


4. Rett syndrome.

Choong CT, Lyen KR.

J Singapore Paediatr Soc. 1990;32(3-4):169-76.

Five girls, aged 2.5 years to 10 years, with Rett Syndrome are presented. The girls (four Chinese and one Indian) demonstrate the classic features of developmental regression with dementia, loss of hand function and stereotyped hand movements. There are as yet no pathognomonic laboratory markers and diagnosis can be difficult especially in the early stages before evolution of the full clinical spectrum. Adherence to current diagnostic criteria is essential. Rett Syndrome is probably not an uncommon cause of severe progressive neurological disability in girls.


5. Prevention of intellectual and other disabilities: the Singapore experience.

Lyen KR.

Asia Pacific J Public Health. 1989;3(4):278-84.

In Singapore, first level prevention, aimed at reducing the occurrence of disabilities, has included neonatal screening for glucose-6-phosphate dehydrogenase deficiency, a programme of universal vaccination, screening for congenital hypothyroidism, and improvements in obstetric and neonatal care. Non-specific measures, such as improved housing, better nutrition and higher standards of education, have also contributed to the reduction in serious illnesses that can potentially cause disabilities. Second level prevention, designed to limit or reverse a disability, has included a developmental screening programme carried out in the primary health care sector. Centralised multi-disciplinary developmental assessment clinics have been established to define better the disabilities and to advise on rehabilitation. An early intervention programme has been started, and special schools are being upgraded. Third level prevention, aimed at preventing a disability from becoming a handicap, has included the setting up of comprehensive rehabilitation programmes, provision of aids and appliances, vocational training, and job opportunities. The integration of the handicapped back into society is currently being promoted.


6. Growth disorders.
Lyen KR.

J Singapore Paediatr Soc. 1985;27(3-4):146-57.


7. Hypoglycaemia in infancy and childhood.
Lyen KR.

J Singapore Paediatr Soc. 1984;26(1-2):73-82.


8. The insulin receptor.

Lyen KR.

Annals Acad Med Singapore. 1985 Apr;14(2):364-73.

The insulin receptor is a glycoprotein with a molecular weight in the order of 300,000. There are probably two pairs of subunits joined together by disulphide bonds. The distribution of receptors appears to be tissue-specific. On liver plasma membranes they are found predominantly as singletons, whereas on adipocytes they occur mainly in groups. The groups of receptors are held together by disulphide bonds, but these are different from the bonds holding the subunits together. When insulin binds to the receptor, the hormone-receptor complex is internalised in pinocytotic invaginations in the adipocyte, and in coated pits in fibroblasts. Half the receptors are transported to lysosomes where they are degraded, and the other half are recycled to the cell surface presumably for further re-utilisation. Obese patients and those with type II diabetes have in common both a reduced number of insulin receptors and a post-receptor defect. However the degree of insulin resistance in type II diabetes cannot be accounted for on the basis of obesity alone. Moreover many type II diabetics are not obese. The insulin receptor is also altered in certain physiological states. Fasting and exercise lead to increased binding of insulin to its receptor. Pregnancy, on the other hand, may either increase or reduce binding. The effects of glucocorticoids are heterogeneous, and it is probable that the insulin resistance they induce is post-receptor in nature. Auto-antibodies to the insulin receptor is a rare cause of severe insulin-resistant diabetes, but the condition has given considerable insight into the nature of the insulin receptor.


9. Insulin antibodies in insulin-dependent diabetics before insulin treatment.

Palmer JP, Asplin CM, Clemons P, Lyen KR, Tatpati O, Raghu PK, Paquette TL.

Science. 1983 Dec 23;222(4630):1337-9.

A sensitive assay was used to measure the binding of iodine-125-labeled insulin in serum obtained from 112 newly diagnosed insulin-dependent diabetics before insulin treatment was initiated. Two groups of nondiabetics served as controls: children with a variety of diseases other than diabetes and nondiabetic siblings of insulin-dependent diabetics. Eighteen of the diabetics were found to have elevated binding and 36 were above the 95th percentile of control values. The insulin-binding protein is precipitated by antibody to human immunoglobulin G, has a displacement curve that is parallel and over the same concentration range as serum from long-standing insulin-dependent diabetics, and elutes from a Sephacryl S-300 column at the position of gamma globulin. These insulin antibodies are present in a large percentage of newly diagnosed, untreated diabetics and may be an immune marker of B-cell damage.


10. Randomized prospective trial of pure porcine and conventional bovine/porcine insulin.

Asplin C, Raghu P, Clemons P, Lyen KR, Tatpati O, McKnight B, Baker L, Guthrie R, Sperling M, Palmer J.

Diabetes Care. 1987 May-Jun;10(3):337-42.

Use of pure porcine insulin versus partially purified insulin of bovine/porcine origin might be expected to have certain clinical benefits, e.g., a lower incidence of skin reactions, a lower insulin dosage, better diabetes regulation, and greater preservation of endogenous insulin secretion. To test this hypothesis, we randomly assigned 112 newly diagnosed, untreated, insulin-dependent diabetic children to therapy with either pure porcine or partially purified bovine/porcine insulin. They were followed for 1 yr, data being available on at least 90 subjects at each visit. More skin reactions were found in the group treated with the bovine/porcine insulin. This insulin was of higher antigenicity, and binding of radiolabeled insulin (mean +/- SE) by serum from bovine/porcine insulin treatment was 35.5 +/- 2.6 versus 16.8 +/- 1.4% (P less than .001) for pure porcine insulin treatment 12 mo after initiation of insulin therapy. However, throughout the 12 mo of observation the levels of glycosylated hemoglobin, insulin dosage, fasting plasma glucose, and C-peptide concentration were similar for the groups. Reported incidences of hypoglycemia and nocturia were also similar. Thus, insulin-antibody formation and skin reactions were minimized by the use of pure porcine versus partially purified bovine/porcine insulin, but no other clinical advantages were apparent.


11. Insulin autoantibodies at diagnosis of insulin-dependent diabetes: effect on the antibody response to insulin treatment.

Sutton M, Klaff LJ, Asplin CM, Clemons P, Tatpati O, Lyen KR, Raghu P, Baker L, Guthrie R, Sperling M, et al.

Metabolism. 1988 Nov;37(11):1005-7.

Insulin autoantibodies (IAA) are frequently found in newly diagnosed untreated insulin-dependent diabetics. We evaluated whether the insulin antibody response over the first year of treatment with insulin was different in individuals with IAA v those without IAA. One hundred five previously untreated type I diabetics were randomly assigned to treatment with either pure porcine or mixed bovine/porcine insulin. Twenty-one in each group had detectable IAA at diagnosis. Percent binding rose in all patients after commencing insulin therapy and was significantly greater in those with IAA at diagnosis irrespective of the type of insulin administered. The elevated binding in the IAA positive patients at all time points was equivalent to the binding that could be attributed to the insulin autoantibodies. Two different mechanisms could explain this greater insulin antibody binding during insulin therapy in the IAA positive patients. First, there may be summation of binding due to insulin autoantibodies and binding due to insulin antibodies formed in response to the exogenous insulin. Alternatively, the insulin antibodies formed in response to exogenous insulin could replace the IAA, with those individuals positive for IAA at diagnosis having a proportionately greater antibody response to injected insulin. Irrespective of the mechanism, patients with IAA at diagnosis develop higher insulin antibody measurements when subsequently treated with exogenous insulin.


12. Aggregation of monomeric ferritin-insulin occupied receptor sites on liver plasma membranes caused by anti-insulin antibody.

Lyen KR, Smith RM, Jarett L. J Recept Res. 1981-82;2(5-6):523-30.


13. Differences in the ability of anti-insulin antibody to aggregate monomeric ferritin-insulin occupied receptor sites on liver and adipocyte plasma membranes.

Lyen KR, Smith RM, Jarett L.

Diabetes. 1983 Jul;32(7):648-53.


14. Insulin does not aggregate its own receptor.

Lyen KR.

Diabetologia. 1983 Apr;24(4):304-5.


15. Cold stress and congenital adrenal hyperplasia heterozygotes.

Lyen KR.

Med Hypotheses. 1983 Sep;12(1):77-83.

Congenital adrenal hyperplasia due to 21-hydroxylase deficiency is common in certain regions of the world characterised by cold winters. The persistence of this potentially lethal recessively inherited disease suggests that an evolutionary advantage is conferred upon the partially affected heterozygotes. Profound hypothermia following acute cold exposure in normal subjects carries a considerable mortality especially from cardiac arrhythmias and dehydration. A hypothesis is proposed to suggest that the incomplete block at the 21-hydroxylase step of steroid biosynthesis decreases stress-induced steroid responses, especially in the younger heterozygote and clinically non-salt-losing homozygote; glucocorticoid and mineralocorticoid insufficiency reduces the severity of cold-induced water diuresis; prevention of severe dehydration contributes towards the ability to survive profound hypothermia. Studies into the salt and water metabolism of the congenital adrenal hyperplasia heterozygote at various ages as well as examination of antidiuretic hormone and steroid hormone interactions upon the renal tubule in cold-exposed normal individuals are merited.


17. Transient thyroid suppression associated with topically applied povidone-iodine.

Lyen KR, Finegold D, Orsini R, Herd JE, Parks JS.

Am J Dis Child. 1982 Apr;136(4):369-70.


18. In search of the Somogyi effect.

Lyen KR, Finegold D, Baker L.

Lancet. 1980 Sep 27;2(8196):700-1.


19. Anorexia nervosa.

Baker L, Lyen KR.

Curr Concepts Nutr. 1982;11:139-49.


20. Anorexia nervosa.

Lyen KR.

J Singapore Paediatr Soc. 1985;27(3-4):158-65.


21. Endocrine function, morbidity, and mortality after surgery for craniopharyngioma.

Lyen KR, Grant DB.

Arch Dis Child. 1982 Nov;57(11):837-41.

The records of 59 children with craniopharyngioma first treated between 1960 and 1980 were reviewed. There was a high incidence of postoperative growth hormone deficiency (43 of 43), andrenocorticortopin deficiency (26 of 36), thyrotrophin deficiency (13 of 20), gonadotrophin deficiency (15 of 16), and diabetes insipidus (44 of 58). Fifteen patients have died: diabetes insipidus was a contributory factor in 5 patients who died within the first 4 months of surgery; and 8 further children died unexpectedly after the postoperative period, probably as a result of anterior pituitary insufficiency. In addition, hypopituitarism led to medical emergencies in 12, 9 of whom had symptomatic hypoglycaemia. These findings illustrate the high incidence of pituitary deficits which follow current methods for treating childhood craniopharyngioma, and the long-term risks associated with these deficits.;57/11/837


22. Hypopituitarism after surgery for craniopharyngioma.

Grant DB, Lyen K.

Childs Brain. 1982;9(3-4):201-4.


23. Early diagnosis of herpes simplex encephalitis in childhood. Clinical, neurophysiological and neuroradiological studies.

Schauseil-Zipf U, Harden A, Hoare RD, Lyen KR, Lingam S, Marshall WC, Pampiglione G.

Eur J Pediatr. 1982 Mar;138(2):154-61.

In the initial phase of HSE the clinical symptomatology is more variable and insidious in babies and young children than in older children and adults. Combined clinical, neurophysiological and neuroradiological studies have been carried out in 12 children with proven HSE. Ten patients had the first EEGs taken during the acute phase of the illness and all showed large amplitude irregular slow activity, sharp waves and often spikes with variable distribution; in 7 cases periodic phenomena were recognisable. At a later stage localised low amplitude EEG activities were found in children with focal neurological symptoms. Areas of low attenuation were seen in the CT scans of the 7 children who had this investigation done at an early stage of their illness. Such low density regions persisted at follow-up and eventually cerebral atrophy with irregular features became obvious. Prompt EEG investigations combined with CT scans provide an early diagnostic clue for treatment. Follow-up EEG studies (including VEP) and CT scans may help assess the severity of residual cerebral damage in the survivors.


24. Reversible cerebral atrophy in infantile spasms caused by corticotrophin.

Lyen KR, Holland IM, Lyen YC.

Lancet. 1979 Jul 7;2(8132):37-8.


25. Mucocutaneous lymph node syndrome in two siblings.

Lyen KR, Brook CG.

Br Med J. 1978 May 6;1(6121):1187.


26. The effects of hypoxia in the reflex respiratory response to induced oscillations of alveolar PCO2 in man.

Cunningham DJ, Lyen KR, McPherson GA, Marsh RH, Pearson SB.

J Physiol. 1973 Jun;231(2):104P-105P.


27. Breath-by-breath effects of imposed alternate-breath oscillations of alveolar CO2.

Marsh RH, Lyen KR, McPherson GA, Pearson SB, Cunningham DJ.

Respir Physiol. 1973 Jun;18(1):80-91.