Glucose tolerance was evaluated in 356 living and dead patients with cystic fibrosis who were recorded at the Danish Cystic Fibrosis Centre. Twenty two patients (6%) were treated elsewhere, 25 (7%) were unable, unwilling or too young (age <2 years) to participate; 309 patients (87%) were therefore eligible for the study of whom 99 (32%) were dead and 210 (68%) were alive. Of the dead patients, 13 also had diabetes mellitus (13%). Of the living patients (median age 14 years, range 2-40), nine (4%) were known to have diabetes and all were being treated with insulin. In the remaining 201 patients an oral glucose tolerance test (1-75 g/kg body weight, maximum 75 g) was carried out. A total of 155 patients (74%) had normal glucose tolerance, 31 (15%) had impaired glucose tolerance, and 15 (7%) had diabetes mellitus according to the WHO criteria. The percentage of glycated haemoglobin (HbA1j) (reference range 4.1-6-4%) increased significantly as glucose tolerance decreased: when glucose tolerance was normal the median was 5-2%; when it was impaired the figure was 5-5%; in patients whose diabetes was diagnosed by the oral glucose tolerance test it was 5-9%; and in patients already known to have diabetes mellitus it was 8-6%. The incidence and prevalence of impaired glucose tolerance and diabetes mellitus increased with age. From the age of 15 to 30 years the decrease in the prevalence of normal glucose tolerance was almost linear. Within this age span the proportion of patients with cystic fibrosis with normal glucose tolerance was reduced by roughly 5%/ year. Only 35% (95% confidence interval (CI) 22 to 48%) of the patients with cystic fibrosis who were alive at the age of 25 years had normal glucose tolerance; 32% (95% CI 14 to 49%) were diabetic.The prevalence of glucose intolerance in cystic fibrosis is rapidly increasing with age; its potentially harmful effect on the prognosis of cystic fibrosis is of increasing importance as the length of survival of these patients increases.Cystic fibrosis is an autosomal recessive disorder that affects many organs including the pancreas. In addition to insufficiency of pancreatic exocrine function, there is a high incidence of pancreatic endocrine dysfunction. October 1989, 99 patients (50 men) had died, and 22 (12 men) had been treated elsewhere. From the records of the dead patients, information was obtained about sex, age at death, family history of diabetes, presence or absence of diabetes mellitus (diagnosed by raised blood glucose concentration or glycosuria, or both), and, if they were diabetic, the age at the time of diagnosis of the diabetes.Of the 235 patients (119 men) currently attending the clinic regularly, 210 (89%) patients (104 men) were willing to participate in the study. Reasons given for not taking part were: unwillingness (n=9), inability because of mental disease (n= 3), and age less than 2 years (n= 13), which was the minimal age for inclusion. The median age of the 210 patients was 14 years (range 2-40), median height 152 cm (range 81-190), and...

A chromosomal deletion syndrome associated with a 22q13 microdeletion has previously been reported in approximately 75 children. We report six cases from Denmark with a deletion of 22q13. One was cytogenetically visible by conventional karyotyping, one was diagnosed by high resolution karyotyping after the demonstration of low arylsulfatase A activity. Two were diagnosed by high resolution CGH analysis, one was diagnosed by multisubtelomeric FISH analysis and one was diagnosed serendipitously as lack of the control signal in a FISH analysis for 22q11 deletion. One of the cases was a mosaic with 16% of cells showing two signals. The phenotype of the children included: generalized developmental delay, compromised language development, hypotonia, normal or accelerated growth and minor facial dysmorphism. Other features were partial agenesis of the corpus callosum, bilateral ureteropelvic stricture, gastroesophageal reflux and hearing loss. One case had a different phenotype, and showed a deletion as well as a duplication. The extent of the deletion was studied by quantitative PCR analysis of a number of DNA markers in the 22q13 region. The deletions varied in size, extending from 4.0 to 9.0 Mb. The clinical phenotype seemed rather similar although some specific features might be attributable to differences in deletions.

Multivariate analysis on an unselected patient population consisting of all 253 children treated for neuroblastoma in Denmark during 1943 to 1980 shows that stage, age, and treatment given are independent prognostic variables. Calendar year of diagnosis, sex of the patient, and site of primary tumor were not significant prognostic factors. Further analysis shows that multimodal treatment with surgery, irradiation, and chemotherapy, especially in patients older than 1 year of age with Stage II disease, has influenced the survival significantly. The fact that age at diagnosis and the administration of chemotherapy have independent prognostic significance can be explained by the theory that all neuroblastomas are virtually congenital; therefore, the difference in age at diagnosis largely reflects the difference in growth rates of the tumor. Thus, according to this theory, age may be a measure of the probability of micrometastases in addition to the clinical extent or stage of the disease, as it represents the duration of the disease. Additional chemotherapy may thus have eradicated these micrometastases in the older children, since the age influence on Stage II disease disappeared when multimodal treatment was given in this study. The implications for treatment policy are discussed in view of this theory.

One hundred and eighty cases of neuroblastomas from the four child oncology clinics are reviewed. The overall cure rate was 24%. During the 38-year period, there was a significant increase in survival from 0% during the period of 1943-1950 to 32% during the period of 1971-1980. This improved survival rate is most likely a result of adjuvant chemotherapy. Forty percent of the patients appear chronically ill, which reflects the fact that nearly 60% have metastases when they are first seen. In localized disease (stages I-II), the prognosis was favourable (cure rate 69%), while the prognosis for disseminated disease (stage III-IV) was poor (cure rate 5%). A favourable outcome was seen in patients under 1 year (survival rate 46%), and in patients with primary tumours located in the neck or mediastinum (survival rate 48%). When related to stage, however, the survival rates for the former tumours were not significantly better in patients below 1 year or in patients with cervical or thoracic tumours. As is the case in other studies, we found that survival is significantly poorer in males.

No abstract