[Familial aggregation of insulin-dependent diabetes mellitus in Denmark. A nation-wide population study]. / Den familiaere ophobning af insulinkraevende diabetes mellitus i Danmark. Et landsdoekkende populationsbaseret studium.

This study aimed to assess the prevalence of familial aggregation of insulin-dependent diabetes mellitus (IDDM), among Danish families with a diabetic child and to compare epidemiological data for familial and sporadic cases of IDDM children. All IDDM patients aged 19 years or less treated at paediatric departments or departments of internal medicine were identified and asked to complete a questionnaire regarding diabetes onset and family history. Of 1574 probands identified, 1419 participated (90.2%). Additional cases of IDDM were found in 12.8% of the families. Among these families, in 6.8% the father and in 2.1% the mother were diabetics and in 5.0% at least one of the siblings were diabetics. In familial cases the proband was significantly younger at diabetes onset, the parents were younger at birth of the IDDM child and no differences in gender were observed in contrast to sporadic cases, where more males were found. Thus, heterogeneity in epidemiological characteristics was observed between familial and sporadic cases.

[Cryptorchism. Treatment with human chorionic gonadotropin or gonadotropin-releasing hormone?]. / Kryptorkisme. Behandling med human chorion gonadotropin eller gonadotropinfrigørende hormon?

In a modified double-blind study on the effect of human chorionic gonadotrophin (hCG), gonadotrophin releasing hormone (GnRH) and placebo, 163 prepubertal boys (aged 1.8-13.0) with bilateral and 94 (aged 1.5-13.1 years) with unilateral cryptorchidism fulfilled the inclusion criteria and completed the treatment protocol. hCG was administered as intramuscular injections twice weekly for three weeks. GnRH and placebo were given intranasally. hCG was superior to GnRH and placebo in the treatment of both bilateral (p < 0.0016) and unilateral (p < 0.013) cryptorchidism with success rates of respectively 23% and 19%. Linear and logistic regression analysis on the results obtained by treatment of bilateral disease showed that all treatments were more successful the younger the age of the boys. The data indicated that bilateral and unilateral cryptorchidism respond differently to hormonal treatment. We conclude that the success rates obtained in this study justify the use of hCG in prepubertal boys with cryptorchidism.

A nationwide population-based study of the familial aggregation of type 1 (insulin-dependent) diabetes mellitus in Denmark. Danish Study Group of Diabetes in Childhood.

The objective of the present study was to assess the prevalence of familial aggregation of Type 1 (insulin-dependent) diabetes mellitus among Danish families with a diabetic child aged 20 years or less and to compare epidemiological data for familial and sporadic cases. We attempted to identify all patients with Type 1 diabetes aged 0-19 years in Denmark treated at paediatric departments or at departments of internal medicine. This comprises more than 98% of all patients with Type 1 diabetes in this age group. Patients were identified through the local diabetic out-patient registry and asked to complete a questionnaire regarding data on diabetes onset and family history. Of 1574 probands 1419 agreed to participate (90.2%). Additional cases of Type 1 diabetes were found in 171 families (12.8%). Of these 115 were parent-offspring affected families, and in 56 families at least two siblings had Type 1 diabetes and healthy parents. Significant correlation in age at onset of Type 1 diabetes in concordant siblings was observed (r = 0.5, p = 0.0004). Significantly more probands had an affected father with Type 1 diabetes than a mother affected (p < 0.0001). Heterogeneity in epidemiological characteristics was observed between familial and sporadic cases, i.e. familial index cases were younger at onset of the disease, their parents were younger at birth of the index case, and there was no difference in gender of familial cases in contrast to sporadic cases where significantly more males were found. Over a 4-year period (1986-1989) an increasing trend in incidence was observed.(ABSTRACT TRUNCATED AT 250 WORDS)

Hormonal treatment of cryptorchidism--hCG or GnRH--a multicentre study.

In a modified, double-blind controlled study, 163 prepubertal boys (aged 1.8-13.0 years) with bilateral and 94 (aged 1.5-13.1 years) with unilateral cryptorchidism were allocated to treatment with either human chorionic gonadotrophin (im), gonadotrophin releasing hormone (intranasally) or placebo (intranasally). In individuals with the bilateral condition treatment with human chorionic gonadotrophin resulted in complete descent of both testes in 23% of patients. Treatment with human chorionic gonadotrophin in unilateral cryptorchidism resulted in complete descent in 19% of patients; all results were significantly better than those obtained with gonadotrophin releasing hormone or placebo. Linear and logistic regression analysis of the results obtained by treatment of bilateral disease showed that all treatments were more successful the younger the age of the boys. The data indicated that bilateral and unilateral cryptorchidism respond differently to hormonal treatment. We suggest that human chorionic gonadotrophin should be the first choice of treatment for prepubertal boys older than one year.

[Surfactant treatment of newborn infants with respiratory distress syndrome primarily treated with nasal continuous positive air pressure. A pilot study]. / Surfaktantbehandling af nyfødte med respiratorisk distress-syndrom primaert behandlet med nasalt kontinuerligt positivt luftvejstryk. En pilotundersøgelse.

In this pilot study, Curosurf (200 mg/kg) was administrated to 34 patients with the respiratory distress syndrome in nasal-CPAP therapy with FiO2 requirements greater than 0.60 and/or TcPCO2 greater than 8 kPa. The surfactant was instilled during a short period of intubation or in a few cases via an intratracheal catheter (Ch. 6). The age of the patients on surfactant treatment ranged from two to 72 hours. Eighteen patients could be maintained on nasal-CPAP after treatment with Curosurf and only a few complications were seen in these infants. The other 16 patients subsequently required artificial ventilation and had a higher incidence of pulmonary and extrapulmonary complications. On the basis of these observations, we plan a randomized trial to investigate whether, administration of surfactant reduces the need for ventilator treatment and improves the odds for uneventful recovery in this category of patients.

[Liver transplantation undertaken on Danes abroad]. / Levertransplantation af danskere i udlandet.

The indication for liver transplantation is the end stage of liver disease. Liver transplantations are not carried out in Denmark at present, one of the reasons being that it requires introduction of the brain death criterion, because the donor liver must be removed during maintained circulation. To date (November 1988), liver transplantations have been carried out abroad on seven Danes. One of these died after operation, one has chronic rejection and is to have retransplantation while the remaining five patients are well. In Europe (including Sweden, Norway and Finland) and USA, more than 5,000 patients have been liver transplanted. The one-year survival is approximately 75%. After this, only few liver-related deaths occur and the majority of patients can resume their previous activities. A total of 18 Danes have been assessed in transplantation centres abroad: Two are waiting for transplantation in the near future and seven have been accepted for transplantation at a later date, depending on the course of the disease. In a number of Danes, liver transplantation has been considered indicated but has not been effectuated because the disease was so advanced at the time of referral, that the patient died before transfer or the patient did not desire operation abroad.

Treatment of cryptorchidism with human chorionic gonadotropin or gonadotropin releasing hormone. A double-blind controlled study of 243 boys.

We have conducted a modified double-blind study on the effect of human chorionic gonadotropin (hCG), gonadotropin releasing hormone (GnRH) and placebo on bilateral and unilateral maldescended testes. One hundred and fifty-five boys with bilateral and 88 boys with unilateral cryptorchidism fulfilled the inclusion criteria and completed the treatment protocol. The boys were between 1 and 13 years of age. hCG was administered as intramuscular injections twice weekly for 3 weeks. GnRH and placebo were given intranasally. hCG was superior to GnRH and placebo in the treatment of bilateral maldescended testes (p = 0.0009). Both testes descended in 25% of the boys following treatment with hCG, and improvement in the position of the testes was obtained in a further 25% of the cases. hCG administration resulted in complete testicular descent in 14% of boys with unilateral cryptorchidism compared with 3 and 0% after placebo and GnRH, respectively (p = 0.07). The testis had moved to a more distal position in 46% of the boys treated with hCG. There was no significant difference between the treatment groups with regard to age or initial position of the testes. We conclude that a success rate of 25% justifies the use of hCG in the treatment of maldescended testes, whereas the study did not support a general use of GnRH administered intranasally.

Normal excretion of urinary acid mucopolysaccharides in a boy with iduronate sulphatase deficiency, Hunter phenotype and alpha 1-antitrypsin deficiency.

The chance coincidence of an X-linked disorder with an autosomal recessive disorder in one child is described. The child had the clinical phenotype of a mucopolysaccharidosis and the activity of iduronate sulphatase was almost absent. Furthermore, fibroblasts from a typical Hunter patient were unable to correct the patient's fibroblasts. However, three 24 h urine samples collected at 18-36 months of age showed a nearly normal excretion of acid mucopolysaccharides. The boy died in liver coma at 3 years of age. Autopsy showed cirrhosis of the liver and changes in liver tissue consistent with alpha 1-antitrypsin deficiency.

Growing intracranial arteriovenous malformation in a newborn.

A case is reported of a growing arteriovenous malformation in a newborn, premature baby. The reason for early operative intervention is emphasized, based on histological investigation of the malformation. The literature is reviewed.

General (medium-chain) acyl-CoA dehydrogenase deficiency (non-ketotic dicarboxylic aciduria): quantitative urinary excretion pattern of 23 biologically significant organic acids in three cases.

Urinary analysis of the pattern of 23 organic acid metabolites derived from fatty acids in three patients with general (medium-chain) acyl-CoA dehydrogenase deficiency was performed. Although there exist quantitative differences in the excreted amounts of the different metabolites in the three patients the qualitative picture was the same. The excretion of adipic, suberic and sebacic acids was substantial, whereas that of dodecanedioic acid was within or just above control limit. The monounsaturated C6-C10-dicarboxylic acid excretion was only marginally or not increased. 5-OH-hexanoic acid and hexanoylglycine were excreted in excessive amounts, whereas 7-OH-octanoic acid, 9-OH-decanoic acid, octanoylglycine and decanoylglycine were excreted in limited amounts. The excreted amounts of 6-OH-hexanoic, 8-OH-octanoic and 10-OH-decanoic acids were not or only marginally elevated compared to controls. In one of the patients the excretion of ethylmalonic and methylsuccinic acids was enhanced, whereas the excretion of these two acids in the two other patients was comparable to that in controls. The urinary excretion of hexanoic, octanoic, decanoic and dodecanoic acids was just a little above the control limit, whereas the esterified hexanoic and octanoic acids were excreted in appreciable amounts. It is argued that the microsomal omega- and omega-1-oxidation systems are involved in the dicarboxylic and omega-1-OH-monocarboxylic acids formation at C10 and C12 level and that the C8-C6-dicarboxylic and omega-1-OH-monocarboxylic acids are formed from higher chained acids by beta-oxidation in both mitochondria and peroxisomes.

Non-ketotic C6-C10-dicarboxylic aciduria: biochemical investigations of two cases.

Two boys, who are not related, with hypoglycemia and C6-C10-dicarboxylic aciduria were investigated. Besides substantial amounts of adipic, suberic and sebacic acids, the urinary metabolic profile of organic acids contained 5-OH-caproic acid and caproylglycine. During acute attacks the concentrations of adipic, suberic and sebacic acids were 300--530, 160--200 and 35--200 micrograms/mg creatinine, respectively, and the excretions of 5-OH-caproic acid and caproylglycine were 75--330 and 41--260 micrograms/mg creatinine, respectively. It is argued that the biosynthesis of adipic acid passes through an omega-oxidation, that the production of 5-OH-caproic acid is caused by an omega-1-oxidation, and that caproylglycine formation passes through a glycine-N-acylase catalysed conjugation of accumulated caproic acid in the patients. Suberic acid and sebacic acid are in the same way omega-oxidation products of accumulated caprylic acid and capric acid, respectively. From the excretion pattern presented it is hypothesized that the patients suffer from a defect in the dehydrogenation of fatty acids in the beta-oxidation pathway. The biological significance of the findings is discussed.

Studies on the required analytical quality of TSH measurements in screening for congenital hypothyroidism.

In the present study analytical reliability has been evaluated from the point of view of medical practice. The data were obtained from a screening program for congenital hypothyroidism in newborns using measurements of TSH. The aim of the investigation has been to evaluate the optimal analytical quality of the TSH determinations in the classification of children into two groups, with and without hypothyroidism. Evaluation of analytical quality was attempted at four different levels: (i) the numbers of misclassifications at a certain fixed value of the cutoff point, (ii) the numbers of false positives when the percentage of false negatives is fixed, (iii) the total costs of the screening program, and (iv) the social costs. When the evaluations are performed at level (i) and (ii) the results indicate a need for a high analytical quality. At level (iii) a lower analytical quality is acceptable from consideration of costs only. When social costs (iv) are considered, the acceptable analytical quality will depend on the weights given to the different factors. Finally the results point to a close relationship between the imprecision and the cutoff point chosen.