Further delineation of the 22q13 deletion syndrome.

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.

Selection of women at high risk of breast cancer using two lifestyle markers: a case control study.

OBJECTIVE: To select a population of women with high risk of invasive breast cancer by using two markers of high risk lifestyle--age at first delivery > = 25 and daily alcohol intake > = 7 g. DESIGN: Case control study based on a structural interview. SETTING: Two general practices in Copenhagen, Denmark. PARTICIPANTS: 30 patients with invasive breast cancer and 30 age-matched controls. MAIN OUTCOME MEASURE: The combined selection power of the two markers of high risk lifestyle. RESULTS: The combined selection power of the two markers was significant (P < 0.025, odds ratio 4.3, 95% CI 1.2-15.6). CONCLUSION: Using these markers it may be possible to select about 80% of all cases of invasive breast cancer in a high risk group comprising only 49% of the female population. This could be of importance for mammography screening; rather than unselectively screening all women in a given age bracket, it might be preferable selectively to screen only the high risk group.

Glucose tolerance in cystic fibrosis.

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 less than 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 (HbA1c) (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.

Simultaneous meningeal and testicular lymphoblastic transformation of Ph1-positive chronic myelocytic leukaemia in a three-year-old boy.

A three-and-a-half-year-old boy presented in the blastic phase of chronic myelocytic leukaemia (CML) with lymphoblastic infiltration of CNS and testes. The clinical signs and symptoms and also blood and bone marrow findings were otherwise compatible with the chronic phase of the disease, and none of the factors predictive of early transformation were present. Cytogenetic analysis revealed that the Ph1 chromosome, with no additional chromosomal abnormalities, was present in 85% of the bone marrow cells. Meningeal leukaemia is almost unknown in the chronic phase of CML. However, the incidence in the blastic phase may resemble the incidence of CNS leukaemia at diagnosis in children with acute leukaemias. Testicular involvement appears to be extremely rare even in the blastic phase of CML; the "true" incidence may, however, also resemble that of acute leukaemias. This raises the question of the need for testicular and meningeal surveillance and prophylaxis, at least during the blastic phase of CML. One should consider whether the simultaneous meningeal and testicular lymphoblastic leukaemia in this patient was the result of blastic transformation at two independent sites, or whether the testes were seeded from the meninges without identifiable spread to blood and bone marrow.

[Mammographic screening for breast cancer--a cost-benefit analysis]. / Mammeografisk screening for cancer mammae--en cost-benefit analyse.

A cost-benefit analysis of the Swedish model for screening for neoplasma malignum mammae revealed scientific shortcomings in the basis for decision. It was not possible to determine whether the screening model involved a net loss or a net profit for the individual woman. Since false confidence seems to increase the mortality in breast cancer a new dimension was introduced, a sensitivity index as an expression of revealed fractions of the incidence in the participant population. This sensitivity index estimated some two thirds of the malignant neoplasms which are normally diagnosed in a two year period.

[Diagnosis in low prevalence of disease. Significance of specificity rather than sensitivity in sequencing of diagnostic tests]. / Diagnostik ved lave sygdomspraevalenser. Betydningen af specificitet fremfor sensitivitet for raekkefølgen af diagnostiske tests.

The significance of specificity rather than sensitivity for the sequence of diagnostic tests is discussed. The rule of thumb states that when the prevalence of disease is low it is advisable to save time and money by eliminating as many healthy individuals as possible from the test system.

[EEG in general practice to demonstrate primary intracranial tumors. Field of applications and limitations]. / Eeg til påvisning af primaere intrakraniale svulster i almen praksis. Anvendelseområde og begraensning.

In Denmark, the annual death rate due to primary intracranial tumours is 320, an unsatisfactory result of treatment that stresses the need of earlier diagnosis. This entails investigation on a wide range of indications. In a population with a low prevalence of a given disease, but with a high prevalence symptom which might be due to the disease in question, is required a highly accurate diagnostic test. Is EEG sufficiently reliable?

Prognostic factors in neuroblastomas treated in Denmark from 1943 to 1980. A statistical estimate of prognosis based on 253 cases.

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.

Neuroblastomas treated at the four major child oncologic clinics in Denmark 1943-1980: an evaluation of 180 cases.

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.

Transcutaneous PO2 monitoring during treatment with continuous positive airway pressure in infants with idiopathic respiratory distress syndrome.

During a 20-month period, 20 infants with idiopathic respiratory distress syndrome (IRDS) were treated with continuous positive airway pressure (CPAP) when they required at least 40% inspired oxygen. The infants were allocated to monitoring with either repeated blood-gas determinations according to the usual practice or continuous transcutaneous PO2 measurements supplemented by blood-gas measurements only when judged necessary. The groups were comparable with regard to birth weight and gestational age, and did not differ significantly with regard to effectiveness or duration of the CPAP treatment, survival rates (90 versus 80%) or number of complications. None developed retrolental fibroplasia. However, PtcO2 monitoring resulted in significantly less hypo- and hyperoxaemia and the number of blood-gas analyses performed during CPAP therapy amounted to only 0.6 per infant per day in the transcutaneously monitored group as against 5.3 in the other group. We propose that PtcO2 monitoring should now be the method of choice and that the use of umbilical artery catheterization should be restricted to selected groups of very low birth-weight infants and to infants in need of ventilator therapy.