Total quality management: the challenge for hospitals in the 1990s.
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Australia↗
Biomedical subjects
C J Eastman
Publications and source records attributed to C J Eastman.
The neurology of endemic cretinism. A study of two endemias.
Endemic cretinism is the most severe manifestation of dietary iodine deficiency. Two forms of the syndrome are traditionally described: neurological and myxoedematous. Although this classification highlights the important neurological sequelae of the disorder it implies that myxoedematous cretins have an alternative mechanism. Further, the nature of the neurological deficit associated with both types of endemic cretinism has received scant attention in recent times considering that it remains a common disorder in many parts of the world. The nature and extent of the neurological deficit found in endemic cretinism was investigated in 104 cretins from a predominantly myxoedematous endemia in western China and in 35 cretins from central Java, Indonesia, a predominantly neurological endemia. We found a similar pattern of neurological involvement in nearly all cretins from both endemias, regardless of type (myxoedematous or neurological), and of current thyroid function. Hallmarks of the neurological features included mental retardation, pyramidal signs in a proximal distribution and extrapyramidal signs. Many patients exhibited a characteristic gait. This probably reflected pyramidal and extrapyramidal dysfunction, although joint laxity and deformity were important contributing factors. Other frequently encountered clinical features were squint, deafness, and primitive reflexes. Cerebral computerized tomography (CT) revealed basal ganglia calcification in 15 of 50 subjects. The presence of basal ganglia calcification was confined to cretins with severe hypothyroidism. Otherwise, cerebral CT scanning demonstrated only minor abnormalities which did not contribute to the localization of the clinical deficits. We conclude that the same neurological disorder is present in both types of endemic cretinism reflecting a diffuse insult to the developing fetal nervous system. These clinical findings support the concept of maternal and fetal hypothyroxinaemia, arising from severe iodine deficiency, as the primary pathophysiological event in endemic cretinism. Differences between the two types of cretinism may be explained by continuing postnatal thyroid hormone deficiency in the myxoedematous type, which results in impaired growth, skeletal retardation and sexual immaturity.
Adult↗
Ontogeny of insulin binding in different regions of the rat brain.
Insulin binding was measured on crude mitochondrial or plasma membranes prepared from different rat brain regions during postnatal development. In the cerebral cortex and brainstem, insulin binding decreased 60-70% between birth and the adult period. In the cerebellum, insulin binding doubled in the first 10 postnatal days and then decreased 40% in the adult, while in the olfactory bulb, insulin binding changed little during postnatal development. Postnatal reductions of insulin binding in cerebral cortex and brainstem were from a loss of binding sites and not from a change in binding affinity. Of the major postnatal developmental processes, maximal insulin binding was most closely associated with neuronogenesis, less closely with gliogenesis and not with synaptogenesis, neural process formation or myelination.
Aging↗
Supplementary iodine fails to reverse hypothyroidism in adolescents and adults with endemic cretinism.
The efficacy of supplemental iodine in correcting hypothyroidism in adults and older children with endemic myxedematous cretinism is not known. To investigate this issue we administered im iodized oil (1.5 mL) to 28 hypothyroid endemic cretins (TSH, greater than 5 mIU/L) from western China, aged 14-52 yr (mean = 29 SD = 11 yr). Clinical examination, intelligence testing (Hiskey Nebraska Test of Learning Aptitude and the Griffiths Mental Development Scales), and thyroid function tests were performed before and 6 months after iodine supplementation. We found that signs of thyroid hormone deficiency, dwarfism, and delayed sexual maturity persisted after iodine supplementation. Further, mental disability and other clinical features of neurological damage were not altered by treatment. The mean serum concentration of total T4 before treatment was 75 nmol/L (SD = 40) and fell after iodized oil administration to 56 nmol/L (SD = 29; P less than 0.001). Mean serum levels of TSH before and after iodine showed a paradoxical fall [85 mIU/L (SD = 102) and 46 mIU/L (SD = 46), respectively]. Serum TSH levels decreased into the normal range (less than 5 mIU/L) in only 1 of 28 patients (4%). We conclude that iodine supplementation does not reverse thyroid hormone deficiency or its sequelae in adolescents and adults with endemic myxedematous cretinism. Iodized oil in this age group of patients with endemic cretinism does not appear to be beneficial and should be used with caution.
Adolescent↗
Topical iodine-containing antiseptics and neonatal hypothyroidism in very-low-birthweight infants.
The thyroid function of very-low-birthweight (VLBW; below 1500 g) infants admitted to neonatal intensive-care units was studied at two hospitals; one routinely used topical iodinated antiseptic agents and the other used chlorhexidine-containing antiseptics. Serial monitoring of urinary iodine excretion and serum thyrotropin and thyroxine levels was undertaken from birth for the first 4 weeks of life. Urinary iodine excretion rose dramatically in the 54 iodine-exposed infants and was up to fifty times greater than in the 29 non-exposed infants. Within 14 days, 25% (9 of 36) of the infants exposed to iodine had serum thyrotropin levels above 20 mIU/l, compared with none of the control group. The mean serum thyroxine level in these 9 infants (44.1 nmol/l) was significantly lower than that in exposed infants with normal thyrotropin levels (83.1 nmol/l) and in the non-exposed control group (83.0 nmol/l); thyroxine levels fell before serum thyrotropin rose. These disturbances in thyroid function correlated positively with urinary iodine excretion and hence iodine absorption. Thyroid function had returned to normal by the time of discharge from hospital. It is concluded that iodine absorption, from topical iodine-containing antiseptics, may cause hypothyroidism during a critical period of neurological development in the newborn infant. The routine use of iodine antisepsis in VLBW infants should be avoided because of this effect.
Administration, Topical↗
Endemic cretinism: possible role for thyroid autoimmunity.
Thyroid atrophy, rather than goitre, is a characteristic feature of myxoedematous cretinism but its cause and nature are unknown. In this study, purified IgG fractions of serum from patients with myxoedematous endemic cretinism inhibited thyrotropin-induced DNA synthesis in guineapig thyroid segments in a sensitive cytochemical bioassay. IgG from patients with euthyroid neurological endemic cretinism or from normal subjects did not inhibit thyroid growth. Furthermore, in myxoedematous subjects, the presence of the thyroid-growth-blocking immunoglobulins showed a positive relation with thyroid atrophy found on ultrasound. These findings provide a pathogenic basis for the variable clinical expression of endemic cretinism.
Adolescent↗
Iodine deficiency impairs intellectual and neuromotor development in apparently-normal persons. A study of rural inhabitants of north-central China.
Intelligence was measured by means of the Hiskey-Nebraska Test of Learning Aptitude or the Griffiths Mental Development Scales in a sample of 369 patients from iodine-deficient rural villages (Baihuyao), iodine-sufficient rural villages (Huanglo) and urban populations to test for the damaging effects of iodine deficiency on the development of the nervous system in the presumed healthy section of a community. In urban school-children who were aged seven to 14 years (n = 78), a normal range of measured intelligence was found (mean +/- SD intelligence-quotient score, 107.0 +/- 18.3). By comparison, intelligence-quotient scores were lower in all rural cohorts (a rural suppression effect) but the distribution of intelligence-quotient scores showed a further shift to the left in the iodine-deficient township. In Baihuyaon villagers who were aged 30-35 years (n = 50), who were born during the period of severe iodine deficiency, 72% of villagers had an intelligence-quotient score of less than 70 compared with 41% (P less than 0.05) of villagers who were aged 28-35 years from Huanglo, a rural iodine-sufficient control group (n = 49). Although measured intelligence was higher in Baihuyaon children whose mothers had received iodized salt - 44% of seven- to 14-year-old children had intelligence-quotient scores of less than 70 (n = 141)--it remained significantly depressed compared with rural (n = 51) and urban (n = 78) control subjects (18% and 4%, respectively). These findings were consistent with other parameters (that is, the persistently-high rate of goitre), which indicated that the salt-iodization programme was inadequate. In the iodine-deficient village, lower intelligence-quotient scores showed a relationship with the detection by audiometry of nerve deafness and with the presence of abnormal neurological signs. The latter included spasticity and pyramidal signs which were of a similar pattern to the neurological deficits that have been demonstrated in overt neurological cretins. We conclude that iodine deficiency imposes a further suppressive effect on the intellectual performance of rural inhabitants, and results in a shift of the entire population distribution of cognitive skills to a lower level.
Adolescent↗
Effect of starvation on insulin receptors in rat brain.
To determine the effect of starvation on brain insulin receptors, rats were fed 4 g of chow/day for 14 days and then P2 fraction membranes were prepared from different brain regions. Compared to the fed state, there was an 18% reduction of insulin binding in olfactory bulbs from starved animals, but no change in the cerebellum, frontal cortex, amygdala, medial hypothalamus or lateral hypothalamus. A 15% reduction of olfactory bulb insulin binding was obtained by totally starving animals for four days. When membrane content was measured using the plasma membrane marker Na/K ATPase, insulin binding decreased by 26% and 14% in olfactory bulb membranes from starved and totally starved animals, respectively. The starvation-induced change in olfactory bulb binding was due to a loss of binding sites and not a decrease in binding affinity. Non-specific catabolism of protein and a change in the composition of membranes following starvation were excluded as causes for this effect. As streptozotocin induced diabetes had no effect on brain insulin binding, it was concluded that hypoinsulinaemia associated with starvation had not caused the reduction in olfactory bulb binding. Under similar conditions of starvation and diabetes, insulin binding in liver plasma membranes increased 26% and 38%, respectively. At 8 and 14 days of starvation, the reductions in olfactory bulb insulin binding and body weight were similar. On refeeding for three days, there was no increase in insulin binding, although body weight increased 7%. On refeeding for eight days, olfactory bulb insulin and body weight had returned to near normal.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
Thyroid autoimmunity in endemic goitre caused by excessive iodine intake.
The pathophysiology of endemic goitre caused by excessive iodine intake is not well defined. By interacting with the immune system, iodine excess may trigger the development of autoimmune thyroid disease such as lymphocytic Hashimoto's thyroiditis (LT). In an attempt to examine this further, we compared the presence of thyroid autoantibodies in 29 goitrous children, from an iodine excess area, and in 26 healthy children, from an iodine sufficient area, of north central China. Serum was tested for antimicrosomal (MAb), anti-thyroglobulin (TgAb), second colloid antigen antibodies (CA2-Ab) and TSH binding inhibitory immunoglobulins (TBII). Affinity chromatographically purified IgG was tested for thyroid growth-stimulating activity (TGI) by two different methods: a sensitive cytochemical bioassay (CBA) using guinea-pig thyroid explants and a mitotic arrest assay (MAA) employing a continuous rat thyroid cell line (FRTL-5). We found no increased prevalence of LT in patients with endemic iodine goitre. The levels of MAb, TgAb and CA2-Ab did not differ significantly between the two groups of children. Further, TBII were not present in either group. Thyroid growth-stimulating immunoglobulins (TGI) were the major autoantibodies found in children with goitres caused by iodine excess. In the CBA, 12 of 20 (60%) goitrous children and 0 of 12 (0% P less than 0.05) healthy children were positive for TGI. Similar results were found in the MAA, and a good correlation between results of the CBA and MAA was found (P = 0.003). Maximal TGI activity in dose-response CBA showed a good relation with clinical goitre size (r = 0.63; P less than 0.05) indicating a possible pathophysiological role for these antibodies. We conclude that endemic iodine goitre is not associated with Hashimoto's lymphocytic thyroiditis. Nevertheless, autoimmune growth factors such as TGI may play a primary role in the pathogenesis of thyroid growth in this condition.
Adolescent↗
Effects of protracted hypothyroidism on pituitary function and structure in endemic cretinism.
Pituitary function and structure were assessed in 69 endemic cretins from western China. In hypothyroid cretins (TSH greater than 10 mIU/l), CT imaging of the pituitary revealed adenoma in five of 20 (25%) and partially empty sella (PES) in a further eight of 20 (40%). The majority of tumours were microadenomas and showed a relation with higher levels of serum TSH but not with duration of hypothyroidism. Dynamic pituitary testing with TRH and GnRH in four patients with adenoma on CT gave a flat TSH response but significant rises in serum PRL, GH, LH and FSH concentrations. Hyperprolactinaemia (greater than 350 mIU/l) was present in hypothyroid cretins only (13 of 26; 50%) and serum PRL showed a curvilinear relation with serum TSH levels (r = 0.7, P less than 0.0001). Hypogonadism was seen in approximately half the cretins with high PRL levels. Our data suggest that severe protracted thyroid hormone deficiency may result in thyrotrophin adenomas of the pituitary gland. Disturbances of growth, puberty, and sexual function in endemic cretins are explained by the secondary effects of thyroid hormone deficiency on pituitary function.
Adenoma↗
Endemic goitre and iodine deficiency disorders--aetiology, epidemiology and treatment.
Disorders caused by iodine deficiency continue to be a major health problem in many underdeveloped areas of the world. The most significant is the impaired mental and physical development which occurs as a result of iodine deprivation early in life. Individuals in affected communities show a spectrum of abnormalities which can be attributed to two interacting pathological processes. Fetal hypothyroidism in the first and early second trimester predominantly affects the developing nervous system causing deaf-mutism and mental retardation. If hypothyroidism occurs in the early postnatal period the main abnormalities are growth stunting and related somatic abnormalities. Subclinical deficits of intellectual and motor development may also be found in apparently normal individuals living in affected areas. Although dietary iodine deficiency is clearly the major aetiological factor in both endemic goitre and cretinism, cofactors such as goitrogens, other trace element deficiencies and immunological mechanisms may greatly modify the expression of these disorders. Iodine supplementation programmes form the basis of the public health strategy in combatting these disorders. Where the iodization of foodstuffs is not feasible, an alternative is the use of iodine containing oil which can be given orally or intramuscularly to provide a long-lasting supply of iodine.
Goiter, Endemic↗
Long-term canine duct-occluded segmental pancreatic autografts: endocrine function.
This study examines the endocrine function of duct-obliterated canine segmental autografts for periods up to 5 years posttransplant. Overall the response profile of autografted animals was subnormal. After intravenous glucose tolerance tests K-values in transplanted animals (2.8 +/- 0.9%/min) were significantly lower than normal (4.6 +/- 1.2% min, p less than 0.001). After oral glucose stimulation, blood glucose in the autografted dogs reached a mean peak of 10.6 +/- 2.8 mmol/L whereas in normal dogs the peak value was 6.0 +/- 1.0 mmol/L (p less than 0.002). The mean insulin response in autografted dogs showed lower insulin concentrations in the early stages of the test, whereas insulin secretion after glucagon stimulation was significantly reduced in autografted dogs. Intravenous glucose tolerance tests were analyzed by calculating K value or measuring a single blood glucose concentration 40 min after glucose injection. This value had a high correlation with the K value (r = 0.967). No progressive deterioration of graft function up to 5 years was found. Glycosylated hemoglobin levels were measured in autografted (646 +/- 59 pmol/mg) and normal dogs (620 +/- 85 pmol/mg) and no significant difference was found. In conclusion, duct-occluded segmental pancreatic autografts were shown to have a reduced functional capacity but there was no deterioration of function up to 5 years after duct-occlusion and grafting. The degree of metabolic control may be sufficient to prevent diabetic complications.
Animals↗
Subcellular localization of rat brain insulin binding sites.
Fractions and subcellular structures were prepared from rat brain homogenate and their purity was assessed using enzyme markers, gamma-aminobutyric acid binding, DNA content, and electron microscopy. Insulin binding was highest on the plasma membrane preparations and approximately 50% less so on brain homogenate crude mitochondrial (P2), myelinated axon, and synaptosome preparations. Very low levels of binding were found on mitochondria and nuclei. Differences in binding between fractions were due to numbers of binding sites, and not variable binding affinity. There was a close relationship between insulin binding and the activity of Na/K ATPase (E.C. 3.6.1.4) in all fractions (r = 0.98). Insulin binding to the P2 was compared with plasma membrane fractions in seven brain regions, and the results demonstrated the same close relationship between insulin binding and plasma membrane content in all regions except hypothalamus. Plasma membrane insulin binding was well represented by the binding on P2 membranes in all regions except hypothalamus and brainstem. It was concluded that insulin binding is distributed evenly over the surface of brain cells and is not increased on nerve endings.
Animals↗
A comparative study of neurological and myxedematous endemic cretinism in western China.
Endemic cretinism occurs in areas of severe iodine deficiency and is manifested by two major clinical patterns, myxedematous and neurological. The relationship between these types and the factors responsible for the clinical variability are not clear. We examined 69 endemic cretins, aged 4-52 yr, categorized clinically at the beginning of the study into the three traditional types of endemic cretins, myxedematous (n = 25), neurological (n = 15), and the mixed form (n = 29), from a previously unreported endemia in Qinghai Province, China. These patients underwent detailed endocrine and neurological examination, including intelligence assessment using the Hiskey-Nebraska Test of Learning Aptitude or the Griffiths Mental Development Scales, audiometry (in a subset of 37 patients); thyroid function testing and thyroid ultrasonography; and radiology of the skull, hand, and hip. We found that categorization of the cretins into the conventional types did not reflect the pathophysiology of the condition, since an identical pattern and intensity of neurological, intellectual, and audiometric deficits were common to and equally present in all three types of endemic cretins regardless of their thyroid function. Gait disorder (in 99%) and pyramidal signs such as patellar hyper-reflexia (in 91%) were the most common neurological abnormalities. There was no difference in mean intelligence test scores among the three groups [overall mean intelligence score (Hiskey or Griffiths tests), 28.8 +/- 12.8 (SD)]. The differing clinical manifestations of cretinism could be explained by the length and severity of thyroid hormone deficiency. Myxedematous cretins were severely thyroid hormone deficient, and as a result sexually immature, dwarfed, and had retarded skeletal maturity. They had clinical and sonographic thyroid atrophy, rather than goiter. Although neurological cretins were euthyroid, linear growth arrest lines (demonstrated radiologically) in the long bones of these cretins suggested previous hypothyroidism. Furthermore, all cretins were growth retarded when compared with peers of similar age and race. Our data therefore suggest that the different clinical types of endemic cretinism are in fact the same disorder phenotypically modified by the length and severity of postnatal hypothyroidism. The neurological manifestations are interpreted as reflecting the effects of maternal and fetal hypothyroxinemia, secondary to severe iodine deficiency, on the developing nervous system.
Adolescent↗
Cyclosporin-induced dysmorphic changes in the BB/W rat.
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Alopecia↗
Endemic goitre in central China caused by excessive iodine intake.
Thyroid status was examined in children from two villages in central China where the iodine concentrations in drinking water were 462.5 and 54 micrograms/l. Goitres were present in 65% (n = 120) and 15.4% (n = 51), respectively. All children in both groups were clinically euthyroid and neurologically normal. Growth measurements and intellectual performance were similar in the two groups. Children from the high-iodine village had a lower mean serum triiodothyronine and higher serum free thyroxine and serum thyroid-stimulating hormone concentrations than the children from the control village. 2 cases of overt hypothyroidism were detected in the high-iodine village.
Adolescent↗
Thyroid hormone response to thyrotrophin releasing hormone stimulation in subjects from endemic goitre regions of Sarawak, Malaysia.
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Adolescent↗
Prolactin secretion during prolonged lactational amenorrhoea.
Basal serum prolactin levels were elevated up to 66 weeks postpartum in lactating amenorrhoeic women. The serum prolactin level in fully breast-feeding women was significantly higher than in women who were partially breast-feeding. The mean basal serum prolactin level in menstruating, lactating women was significantly higher than the mean level in women who had weaned and had normal menstrual cycles. The rise in prolactin due to suckling was seen up to 66 weeks postpartum. The marked variability and lack of reproducibility of individual suckling responses may obscure the importance of prolactin secretion in the postpartum period. Nevertheless, this study confirms that prolactin secretion is increased in women with prolonged lactational amenorrhoea.
Amenorrhea↗