Cranial computed tomographic findings in children with newly diagnosed acute lymphoblastic leukemia: A prospective follow-up study during treatment

Cranial computed tomography (CT) was performed on 40 consecutive children with newly diagnosed acute lymphoblastic leukemia (ALL) on admission before any chemotherapy, 5 months after CNS therapy (n = 39) and after 2 to 3 years of therapy (n = 31). Changes related to leukemia were found in only 10% of the patients at the time of diagnosis (4/40). These initial changes, two intracranial hemorrhages, one dural thickening and one contrast enhancement, all disappeared during therapy. The findings which persisted unchanged in the next two CT scans were thought to be normal variations or caused by earlier disorders. CNS therapy consisted of intrathecally and intravenously administered methotrexate in 20 standard risk (SR) patients and cranial irradiation in addition to chemotherapy in 19 intermediate risk (IR) or high risk (HR) patients. Four SR patients developed changes during therapy. Three had enlarged cerebrospinal fluid (CSF) spaces and one developed a focal low density area suggesting disturbances in brain blood circulation and also experienced disturbances in level of consciousness. Of the 19 IR or HR patients, eight developed changes related to the therapy, including four with white matter hypodensity areas, of whom three also had enlarged CSF spaces, and four others who developed enlarged CSF spaces. The medians of the widths of the cortical sulci (P < .001), insular cisterns (P < .01), third ventricles (P < .01), and frontal horns (P < .05), and also of Evans' ratios (P < .05) increased significantly after CNS therapy as compared with the findings at diagnosis in the patients who had received cranial irradiation. Most of these changes persisted during the follow-up. We conclude that the clinical value of CT scanning during therapy for ALL is restricted to patients with neurological symptoms or those who have undergone CNS irradiation. © 1992 Wiley-Liss, Inc.     

Effect of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on tryptophan and glucose homeostasis in the most TCDD-susceptible and the most TCDD-resistant species,guinea pigs and hamsters

 We have previously reported that in rats 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) lethality is associated (although not necessarily causally) with changes in brain serotonin (5-HT) metabolism. In the present study, we have examined whether this holds for other species by comparing the effect of TCDD in the most TCDD-susceptible and the most TCDD-resistant species, guinea pigs and hamsters, respectively. Body weight gain of guinea pigs exposed to TCDD (0.3–2.7 μg/kg) diminished dose dependently, while the effect was marginal in hamsters (900–4600 μg/kg). Brain 5-hydroxyindoleacetic acid (the main metabolite of brain 5-HT), brain tryptophan (the precursor amino acid of 5-HT), and plasma free and total tryptophan were not affected at any dose in guinea pigs. In contrast, 4 days after exposure, the levels of plasma free and total tryptophan were consistently increased in hamsters. These, as well as brain tryptophan, were still elevated 10 days after exposure. TCDD did not affect plasma glucose level in either species. Liver glycogen was decreased in a dose-dependent manner in TCDD-treated guinea pigs as well as in their pair-fed controls on day 10. There was no change in liver glycogen in hamsters. The activity of the gluconeogenic enzyme, phosphoenolpyruvate carboxykinase was only depressed in hamsters by all doses of TCDD. We conclude that changes in tryptophan metabolism or in carbohydrate homeostasis cannot explain the wide interspecies differences in susceptibility to the acute lethality of TCDD, although they may correlate with some aspects of its toxicity in certain species. Received: 12 January 1995 / Accepted: 27 February 1995     

Chemotaxis in yersinia arthritis.

Chemotactic and chemokinetic migration of polymorphonuclear leukocytes in sera from patients with previous yersinia arthritis and from healthy subjects with or without HLA–B27 were studied by the leading front method. Irrespective of yersinia arthritis, zymosan-activated sera from subjects who were HLA–B27 positive were significantly more chemokinetic than were HLA–B27 negative zymosan-activated sera from healthy control subjects. The chemotactic activities of zymosan-activated sera that were HLA–B27 positive or negative, as determined by chemotactic increments, were much the same. The results suggest that zymosan-activated serum that is HLA–B27 positive stimulates random migration of polymorphonuclear leukocytes, but not their directional migration, more than does HLA–B27 negative serum that has been zymosan activated. This may contribute to accumulation of polymorphonuclear leukocytes at the site of inflammation in vivo and thereby to inflammatory symptoms in yersinia arthritis patients with HLA–B27.     

Age at Onset of Type 1 Diabetes in Parents and Recurrence Risk in Offspring

OBJECTIVE

Our aim was to study the recurrence risk of type 1 diabetes in the offspring of parents with adult-onset (15–39 years) type 1 diabetes and to evaluate the transmission of diabetes within a continuum of parental age at onset of diabetes from childhood to adulthood.

RESEARCH DESIGN AND METHODS

Diabetes status of all offspring (n = 9,636) in two Finnish cohorts of parents with type 1 diabetes was defined until the end of year 2007. Cumulative incidences of type 1 diabetes among the offspring were estimated, and several factors contributing to the risk were assessed.

RESULTS

During 137,455 person-years, a total of 413 offspring were diagnosed with type 1 diabetes. The cumulative incidence by 20 years was 4.0% (95% CI 3.1–4.8) for the offspring of parents with adult-onset diabetes. The risk was equal according to the sex of the parents. The cumulative incidence decreased in parallel with the increase in age at onset of diabetes in the fathers. In the offspring of diabetic mothers, the risk was equal regardless of the age at onset of diabetes. However, the reduced risk in the maternal offspring was most pronounced in the daughters of the mothers with a diagnosis age <10 years.

CONCLUSIONS

Type 1 diabetes transmission ratio distortion is strongly related to the sex and age at onset of diabetes in the diabetic parents.Type 1 diabetes can occur at any age, although it is predominantly seen in children and young adults. Therefore, the majority of studies have been conducted in children aged <15 years. The recurrence risk in the offspring ranges from 3 to 6% depending on the study design, follow-up time, and the population where the study was conducted (1–3). Little is known about the recurrence risk in first-degree relatives of subjects diagnosed with type 1 diabetes, aged >15 years. The incidence of type 1 diabetes is much lower in young adults than in children (4–6). Consequently, the risk of family members may also be different among the diabetic subjects affected after childhood.Sex-related factors seem to be involved in the transmission of diabetes from one generation to the next (7). By 20 years of age, 5–8% of the offspring of diabetic men and only 2–5% of the offspring of diabetic women have been found to be affected (1–3,8). We have previously shown that the recurrence risk of diabetes in the offspring of parents diagnosed between 0–17 years of age was higher the younger the father was when diagnosed with type 1 diabetes. This pattern was not present in the offspring of the mothers (8). However, it is not known whether the sex-related factors play a role in the transmission of diabetes in adult-onset type 1 diabetes. We have now enlarged our study to also include the offspring of parents diagnosed with diabetes between 15 and 39 years of age. This gives us an opportunity to determine the risk in the offspring of parents with a broad age span at diagnosis and to elucidate whether there are differences in the risk between the offspring of diabetic mothers and fathers.     

Visual fields at school-age in children treated with vigabatrin in infancy

Purpose:   The use of vigabatrin (VGB) as an antiepileptic drug (AED) has been limited by evidence showing that it causes vigabatrin-attributed visual field loss (VAVFL) in at least 20–40% of patients exposed at school age or later. VGB is an effective drug for infantile spasms, but there are no reports on later visual field testing after such treatment. Our aim was to investigate the risk of VAVFL in school-age children who had received VGB in infancy.
Methods:   Visual fields of 16 children treated with VGB for infantile spasms were examined by Goldmann kinetic perimetry at age 6–12 years. Normal fields were defined as the temporal meridian extending to more than 70°, and mild VAVFL between 50 and 70°. Abnormal findings were always confirmed by repeating the test. Exposure data were collected from hospital charts.
Results:   Vigabatrin was started at a mean age of 7.6 (range, 3.2–20.3) months. The mean duration of therapy was 21.0 (9.3–29.8) months and cumulative dose 655 g (209–1,109 g). Eight children were never treated with other AEDs, five received only adrenocorticotropic hormone (ACTH) in addition to VGB, and three children had been treated with other AEDs. Fifteen children had normal visual fields. Mild VAVFL was observed in one child (6%) who had been treated with VGB for 19 months and who received a cumulative dose of 572 g.
Conclusions:   The risk of VAVFL may be lower in children who are treated with VGB in infancy compared to patients who receive VGB at a later age.     

Transoesophageal echocardiography should be considered in patients with ischaemic stroke or transient ischaemic attack

BACKGROUND AND PURPOSE: In this present study, we tried to find out if there is a subgroup of patients that should not undergo transoesophageal echocardiography (TEE) after an ischaemic stroke or transient ischaemic attack (TIA). METHODS: A total of 441 consecutive unselected patients with ischaemic stroke or TIA suitable for anticoagulation were examined with TEE in the acute phase. The patients were divided into five subcategories according to their rhythm, age and the findings in carotid sonography, and into two groups according to the presence of clinical risk factors for ischaemic stroke or TIA. RESULTS: From the 441 studied patients, 60 (14%) had chronic or paroxysmal atrial fibrillation (AF) and 381 (86%) were in sinus rhythm (SR). Of the patients in SR, 46 (12%) were below 50 years old. The carotid sonography was conducted in 240 patients above 50 years old and in SR, and <50% internal carotid artery (ICA) stenosis was found in 194 (81%) patients and > or =50% ICA in 46 (19%) patients. Potential cardiac sources of embolism were found in patients both with AF or in SR (70% versus 46%), both below and above 50-year-old patients in SR (37% versus 47%), both in over 50-year-old patients in SR with <50% ICA stenosis and > or =50% ICA stenosis (41% versus 61%) and in patients in SR either without or with clinical risk factors for ischaemic stroke or TIA (43% versus 51%). On the basis of the TEE study, oral anticoagulation was started in 36 (9%) patients in SR. CONCLUSION: These results support TEE in patients with ischaemic stroke or TIA who are candidates for receiving oral anticoagulation.     

Osteonecrosis in children treated for acute lymphoblastic leukemia

The purpose of the study was to find out the prevalence of osteonecrosis in children with acute lymphoblastic leukemia (ALL) in complete bone marrow remission at the end of the treatment. Twenty-eight children with ALL underwent MRI of the upper and/or lower extremities. Bone marrow signal intensity was analyzed on T1-weighted images, where cir-cumscribed lesions with a rim of low signal intensity were considered typical of osteonecrosis. Osteonecrosis was found in 9 of the 28 children (32%, 95% CI 16% to 52%). Five of them were asymptomatic. They had been treated with high risk and intermediate risk protocols, both of which include a delayed intensification phase with dexamethasone. None of the patients with standard risk ALL were found to have developed osteonecrosis. Osteonecroses occurred unexpectedly in symptomless patients and in patients with mild transient symptoms treated with high risk and intermediate risk protocols. Our study suggests that the intensification phase of the treatment protocols with intensive dexamethasone medication might be responsible for the development of osteonecrosis. Med. Pediatr. Oncol. 29:260–265, 1997. © 1997 Wiley-Liss, Inc.     

Dental maturity in Finns and the problem of missing teeth

Development of teeth was studied from 2483 dental panoramic tomograms of 1651 healthy Finns ranging in age from 2 to 25 years. Dental maturity was assessed using a method based on developmental stages of 7 left mandibular teeth. We give sex-specific tables of maturity scores as a function of ages and of ages as a function of maturity scores. Also generated are percentile graphs for visual evaluations of dental maturity in children and adolescents. Since maturity scales do not tolerate any missing data, a great limitation for their use, we have developed linear regression models for predicting the formation stages of each of the 7 mandibular teeth. It was easiest to predict the formation stage of the mandibular first molars (correct in 87% within the study material) and most difficult to predict second molars and second premolars (correct in 69% and 70%, respectively). We expect the data and formulae presented in this study to prove useful in research and in clinical and forensic dentistry.