摘要:

AbstractGeneralized resistance to thyroid hormone (GRTH) is an inherited syndrome characterized by hyposensitivity of target tissues to thyroid hormone. The clinical presentation is variable. The syndrome is usually suspected when elevated serum thyroid hormone levels are associated with a non‐suppressed thyroid‐stimulating hormone (TSH). While goiter and thyroid test abnormalities have more often led to the suspicion of thyroid gland dysfunction, short stature, hyperactivity, learning disability and goiter in children or adolescents and recalcitrant goiter in adults, should raise the suspicion of GRTH. Hypothyroidism has been considered when growth or mental retardation was the presenting symptom and thyrotoxicosis when confronted with attention deficit, hyperactivity or tachycardia. Failure to recognize the inappropriate persistence of TSH secretion in spite of elevated thyroid hormone levels has commonly resulted in erroneous diagnosis leading to antithyroid treatment. More than 300 subjects with this syndrome have been identified. The mode of inheritance in the majority of families is autosomal dominant. Recessive transmission has been found in only one family.It has long been speculated that this defect is likely to be caused by an abnormal thyroid hormone receptor (TR), but this hypothesis could not be directly tested until the isolation of two TR genes, TRα and TRβ. Mutations in the TRβ gene have been identified in 42 families with GRTH. All are located in the T3‐binding domain straddling the putative dimerization region and exhibit various degrees of hormone‐binding impairment. This finding, and the fact that heterozygous subjects with complete TR deletion are not affected while those with point mutations are, indicates that interactions of a mutant TR with normal TR and with other factors are responsible for the dominant inheritance of GRTH and its heterogeneity. Elucidation of the etiology of GRTH has not only added a new means for the early diagnosis of the syndrome but provided new insights in the understanding of the mechanism of horm

ISSN:1328-8067    

DOI:10.1111/j.1442-200X.1994.tb03121.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

摘要:

AbstractThe activity of porphobilinogen deaminase (PBGD), an enzyme whose partial deficiency is associated with acute intermittent porphyria (AIP), changes during development. Little is known about the postnatal change of PBGD activity and the prevalence of its electrophoretic variant in the Japanese population.The activity of PBGD was measured fluorometrically in 194 infants aged 0–12 months, while isoelectric focusing of PBGD was performed in 400 healthy Japanese adults aged 20–45 years and 30 children with various hematological disorders aged 1–15 years.The PBGD level was 1.9 times higher in the neonates than in the adults, decreased abruptly during the first month of life, and reached the adult level at the age of 9 months. None of the 400 healthy Japanese adults and the 30 children with hematological disorders showed any electrophoretic variant.These results suggest that there is no need to consider any polymorphism in the gene dose study of PBGD and that the biochemical screening of AIP is applicable to since the late in

ISSN:1328-8067    

DOI:10.1111/j.1442-200X.1994.tb03122.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

摘要:

AbstractThe effects of peroxovanadate or tungstate on 3‐O‐methylglucose uptake were characterized using isolated rat adipocytes to elucidate the mechanism(s) of their actions. The stimulatory effect of peroxovanadate was observed from 1 μmol/L and reached the maximum at about 100 μmol/L. The concentration showing the half‐maximal effect was approximately 16 μmol/L. The maximal response of peroxovanadate was 1.19 times higher than that of insulin significantly(P<0.01). On the other hand, the stimulatory effect of tungstate was seen only at the higher concentrations of 10–30 mmol/L Judging from the experiments using different tungsten compounds, tungstic acid (WO42‐) appeared responsible for the effect. The effects of 20 mmol/L tungstate and 20 nmol/L insulin were not additive. The stimulatory effects of 1 mmol/L peroxovanadate, 20 mmol/L tungstate or 20 nmol/L insulin were not seen in the adipocytes deprived of ATP by exposure to 2 mmol/L KCN. The adipocytes which had been stimulated with insulin and further exposed to 2 mmol/L KCN were used to test whether or not peroxovanadate works directly on the function of glucose transporters. In such cells on which GLUT4‐rich transporters were rendered immobile, the effect of peroxovanadate was not observed. These results indicate that the effects of peroxovanadate or tungstate are ATP or energy dependent and may be exerted through the mechanism analogous to that of insulin action, and suggest that peroxovanadate does not directly activate the fun

ISSN:1328-8067    

DOI:10.1111/j.1442-200X.1994.tb03123.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

摘要:

AbstractThis study investigates the dose‐dependent effect of administration of commercially available intravenous immunoglobulins (IVIG) on the survival of newborn rats experimentally infected with group B streptococci (GBS). The opsonic activity of various concentrations of IVIGin vitrowas determined by examination of opsonophagocytosis of GBS by peritoneal macrophages and bacterial killing by blood neutrophils.The best survival was observed in newborn rats who received immunoglobulins at doses of 250, 500 and 1000 mg/kg of bodyweight. The survival of animals that received either 125 mg/kg or 2.5 g/kg of immunoglobulins was no better than that of animals who received no immunoglobulins. The maximal phagocytosis and bacterial killing were observed atin vitroimmunoglobulin concentrations ranging from 32 to 250 mg/dL (thesein vitroconcentrations may correspond roughly toin vivoadministration doses ranging from 150 to 1200 mg/kg). These doses are comparable to the doses of IVIG currently administered to neonates. However use of very high doses may be harmful to babies since the high concentration of non‐specific immunoglobulins inhibitedin vitrophagocytosis and bacterial killing by phagocy

ISSN:1328-8067    

DOI:10.1111/j.1442-200X.1994.tb03124.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

摘要:

AbstractLong‐term effects of bone marrow transplantation (BMT) were evaluated in patients with I‐cell disease, metachromatic leukodystrophy (MLD), Maroteaux‐Lamy syndrome or Hunter syndrome (mild form). Donors were human leukocyte antigen (HLA)‐matched siblings, and the follow‐up periods were 24–71 months after BMT. The enzyme activities were increased in leukocytes, plasma or liver tissues compared with pre‐BMT levels. A patient with I‐cell disease acquired development of 4–8 month old infants and showed no further progression in cardiac dysfunctions. A patient with MLD showed a decelerated disease progression and an improved peripheral neuropathy, but progressive brain atrophy was not prevented. Patients with Maroteaux‐Lamy syndrome or Hunter syndrome showed improvements in hepatomegaly, joint contractures, short stature and tight skin, and this greatly increased their quality of life. These results indicated that the long‐term therapeutic effects achieved by BMT were subject to multiple factors including biochemical improvements, a reversibility of affected tissues, or advanced states of disease and central nervous system impairments in inborn

ISSN:1328-8067    

DOI:10.1111/j.1442-200X.1994.tb03125.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

摘要:

AbstractPatients who undergo bone marrow transplantation (BMT) frequently experience impaired pituitary function, but precise assessment using repeated provocative tests has not been described. We studied 32 children (16 boys) who had BMT after receiving preparative irradiation. Assessment of pituitary function was performed by infusing insulin, luteinizing hormone‐releasing hormone (LHRH), and thyrotropin‐releasing hormone (TRH) on several occasions at various intervals during the follow‐up period.Serum free thyroxine (FT4) and thyrotropin (TSH) levels tended to be low during the early period following BMT. Serum FT4 concentrations reverted to the low‐normal range 1 year after transplant, and eight of 29 patients had subnormal and delayed TSH response to TRH consecutively. No children showed overt hypothyroidism. Basal and peak serum gonadotropin levels in response to LHRH were elevated in the patients who had received transplant around the time of puberty. Leydig cell function assessed by human chorionic gonadotropin test was normal. Three girls experienced menarche, and one male patient fathered a normal boy 7 years after BMT. Pituitary‐adrenal function and prolactin secretion were not affected.A high incidence of transient hypothyroidism which did not require replacement therapy and gonadal failure among pubertal children were observed. Shielding of gonads should be attempted, if possible, at the time of preparative irradiation to prevent resultant hyp

ISSN:1328-8067    

DOI:10.1111/j.1442-200X.1994.tb03126.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

摘要:

AbstractNine children, aged 2.5 months to 16 years, presenting with tachyarrhythmias were treated with intravenous (i.v.) flecainide, a type 1C antiarrhythmic drug. There were four boys and five girls; seven were supraventricular and two ventricular tachycardias and three had structural cardiac abnormalities. The i.v. dose required to terminate the arrhythmias ranged from 1.0 to 2.4 mg/kg (mean 1.55 mg/kg) although a mean of 1.94 mg/kg per dose was required to maintain sustained sinus rhythm after a single i.v. dose. Eight of the patients — six supraventricular and two ventricular tachyarrhythmias, required maintenance oral flecainide. Oral dosages of 6.7–9.5 mg/kg per day (mean of 7.97 mg/kg per day in three divided doses) were required to effectively prevent the tachyarrhythmias. Intravenous and oral flecainide are safe and effective in terminating supraventricular and ventricular tachyarrhythmias. No evidence of proarrhythmia was found in the patients during follow up of between 5 and 9 months. The present limitation of performing radiofrequency ablation on infants and small children justifies the important place of medical therapy for re‐entrant supraventricular tachyarrhyt

ISSN:1328-8067    

DOI:10.1111/j.1442-200X.1994.tb03127.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

摘要:

AbstractThe levels of soluble interleukin‐2 receptors (sIL‐2R) and tumor necrosis factor (TNF) were determined in the serum of 61 children with hematological malignancy, including 20 patients with leukemia and 16 with lymphoma in active state of malignancy, and 20 patients with leukemia and 5 with lymphoma in complete remission. In addition, serum samples from 15 healthy children were used as controls. It was found that the mean serum levels of sIL‐2R and TNF were significantly increased in active malignancy (207.0±17.1 pmol/L for sIL‐2R; 209.7±35.0 pg/mL for TNF) compared to the remission status and normal controls (P<0.001). No such difference was observed between leukemia and lymphoma groups.It was concluded that serum sIL‐2R and TNF are of potential value in the diagnosis and follow up of patients with neoplast

ISSN:1328-8067    

DOI:10.1111/j.1442-200X.1994.tb03128.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

摘要:

AbstractTo eliminate the role of natural killer (NK), antibody‐dependent cell‐mediated cytotoxicity (ADCC), and polymorphonuclear leukocyte (PMN)‐mediated cytotoxicity in Varicella zoster virus (VZV) infections, peripheral blood mononuclear cell (PBMC)‐mediated NK and ADCC, and phorbol myristate acetate‐stimulated PMN‐mediated cytotoxicity against VZV‐infected targets were studied in children with leukemia.Natural killer and PMN‐mediated cytotoxic activity was depressed for 6 months after complete remission and ADCC activity was depressed for 1 year after complete remission. The magnitude of three cytotoxic mechanisms in leukemic children gradually increased while they continued in complete remission.These results suggested that decreased cytotoxic activities of PBMC and PMN might contribute to serious VZV infections and susceptibility to herpes zoster in le

ISSN:1328-8067    

DOI:10.1111/j.1442-200X.1994.tb03129.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

摘要:

AbstractThe peritoneal equilibration test (PET) is generally accepted as a valuable tool in individualizing continuous ambulatory peritoneal dialysis (CAPD) treatment schedules in adults. However, the classification of peritoneal permeability as described by Twardowski is not available for children due to differences in peritoneal transport abilities. In this paper, we report the results of the PET for 20 patients aged from 1.5 to 24 years (mean 10.3 years), who started CAPD therapy at age 0–15 years, using Twardowski's standardized technique. D/P creatinine (dialysate to plasma ratio of creatinine at 4 h), D/D0glucose (the ratio of dialysate glucose at 4 h dwell time to dialysate glucose at 0 dwell time), and the residual volume (RV) in the abdominal cavity were calculated. The mean and standard deviation values for D/P creatinine and D/D0glucose were of a higher permeability level than those reported in Twardowski's data. Furthermore, a significant correlation of creatinine and glucose with fluid drainage ability of the peritoneum were observed. A large amount of RV (425±125 mL/m2) was detected in the patients' peritoneal cavity and this had a significant correlation with dialysate leak occurrences. The authors suggest that the RV would be an indicator for leaks and especially latent leaks. The cause of a large RV is unknown, but there is a probability that drainage volume and transport rates of metabolites decrease because the concentration of the instilled dialysate is immediately diluted by a large RV within the peritone

ISSN:1328-8067    

DOI:10.1111/j.1442-200X.1994.tb03130.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY