[New knowledge in the heredity of autoimmune diabetes. 1st part--Monogenetically determined types of autoimmune diabetes]. / Nové poznatky v genetice autoimunitního diabetu (1): Monogenne podmínené typy autoimunitního diabetu.

The incidence of type 1 diabetes (DM1) varies greatly among different nations and ethnic groups. Precise mapping of DM1 incidence and its trends is useful in the study of the interaction of genetic and non-genetic factors which influence the manifestation and course of the disease. Important progress has been made in the understanding of the mechanisms of autoimmune diabetes by the study of genes and autoimmune forms of monogenetic diabetes.

Longitudinal observation of enterovirus and adenovirus in stool samples from Norwegian infants with the highest genetic risk of type 1 diabetes.

BACKGROUND: Enterovirus and adenovirus are common in infancy, causing mostly asymptomatic infections. However, even an asymptomatic infection may be associated with increased risk of development of certain chronic non-infectious diseases, as has been suggested for enterovirus and type 1 diabetes. Data on occurrence and course of the infections in infancy are therefore important for designing effective approaches towards study of the association. OBJECTIVES: To estimate the frequency of enterovirus and adenovirus infections in Norwegian infants, to evaluate the duration of the infections, to investigate their association with symptoms, and to establish a robust procedure that will be used to study the association between these viruses and the development of auto-immunity leading to type 1 diabetes. STUDY DESIGN: Parents of infants, recruited for a study on environmental triggers of type 1 diabetes, submitted monthly samples of infant faeces, as well as information on symptoms of infection. The samples were analysed for enterovirus and adenovirus using quantitative real-time PCR, and enterovirus-positive samples were sequenced. RESULTS: Enteroviruses were found in 142/1,255 (11.3%), and adenoviruses in 138/1,255 (11.0%) of stool samples. Approximately half of the infants were exposed to these viruses at least once during the first year of observation (period 3-14 months of age). The presence of adenovirus was associated with fever and with symptoms of cold but not with diarrhoea and vomiting. The enterovirus positivity was not associated with any symptoms. CONCLUSIONS: The prevalence of enterovirus and adenovirus in longitudinally obtained faecal samples from infants is sufficiently high to enable studies of their association with chronic diseases. The present protocol for evaluating exposure to these viruses is well suited for large-scale efforts aimed at assessing possible long-term consequences, particularly in relation to type 1 diabetes.

Glucose evaluation trial for remission (GETREM) in type 1 diabetes: a European multicentre study.

OBJECTIVE: Strict metabolic control during the 1st year of type 1 diabetes is thought to be a key factor for achieving clinical remission. The aims of this study were two-fold: (i) to evaluate the frequency and duration of spontaneous remission (defined according to the parameters issued by the International Diabetic Immunotherapy Group (IDIG)) in a European population of consecutive recent onset type 1 diabetes patients (aged 5-35 years), followed-up for a period of 36 months with a common protocol of intensive insulin therapy and without adjunct immune-intervention; and (ii) to identify the predictive factors for clinical remission. RESEARCH DESIGN AND METHOD: A total of 189 consecutive patients with newly diagnosed type 1 diabetes according to ADA criteria were recruited in participating centres (Belgium, Czech Republic, Estonia, France, Germany, Hungary, Italy, Poland, Romania, Sweden and Turkey) and followed-up for a period of up to 36 months. In all patients, intensive insulin therapy was implemented consisting of three or four injections of regular insulin daily with NPH insulin at bedtime. Adjustment of insulin dose was made according to a common protocol. Various clinical characteristics (age, gender, severity of presentation, etc.), history (presence of diabetic siblings in the family, etc.) and integrated parameters of metabolic control (HbA(1c), blood glucose, the total insulin dose at hospital discharge adjusted for body weight) were collected. RESULTS: Twenty-two patients (11.6%) experienced remission. The median duration of remission was 9.6 months and the range was 31 months. There was a wide variation among centres. Logistic regression analysis focused on the centre as the main variable in achieving remission. CONCLUSION: Remission was shown to be very heterogeneous between centres depending on 'other factors' such as patient care and family awareness of the disease rather than on 'measurable factors' such as sex, age, HbA(1c) and severity of presentation at diagnosis. Using intensive insulin therapy and optimisation of metabolic control, remission occurred in nearly one out of eight patients.

[Hormonal suppression and sexual development in children with central precocious puberty in the first treatment cycle 12 weeks after injection of triptoreline 11.25 mg (Diphereline S. R. 11.25 mg): a pilot study]. / Hormonální suprese a pohlavní vývoj detí s centrální predcasnou pubertou v prvním lécebném cyklu 12 týdnu po injekci triptorelinu 11.25 mg (Diphereline S. R. 11.25 mg): pilotní studie.

OBJECTIVE: To evaluate hormonal suppression and pubertal development in children with central precocious puberty (CPP) after injection of triptoreline 11.25 mg (Diphereline S. R. 11.25 mg; Ipsen) in the first treatment cycle of 12 weeks. DESIGN: Pilot study. SETTING: Paediatric department, University Hospital Motol-Prague. METHODS: Serum levels of FSHmax and LHmax and basal levels of estradiol/testosterone were monitored in GnRH test before, 4, 8 and 12 weeks after triptoreline 11.25 mg injection in 3 girls and 2 boys with CPP (age 3.9-10.6 years) previously treated by triptoreline 3 mg every 4 weeks. Uterine and ovarian volume, hormonal cytology (vaginal smear), breast development and testicular volume were evaluated before and 12 weeks after triptoreline 11.25 mg injection. RESULTS: 8 weeks after triptoreline 11.25 mg, FSHmax in girls increased (2.3 IU/l vs. 1.7 IU/l before injection; median) without any other change in 12th week. In boys after initial decrease LHmax 12 weeks after injection rose to 1.7 IU/l (identical as LHmax before injection). Estradiol and testosterone levels were in prepubertal range. Pubertal development in girls did not progress, and testicular volume decreased in both boys (treated for CPP 0.3 and 0.7 years). CONCLUSIONS: Triptoreline 11.25 mg injection in 12 weeks interval can be considered as effective, useful and safe for therapy of CPP. The long-term follow-up will be necessary.

[Childhood diabetes in the Czech Republic: a steady increase in incidence]. / Detský diabetes mellitus v Ceské republice: stale více a cím dál drive.

BACKGROUND: The aim of the study was to assess the incidence and prevalence of type 1 diabetes in Czech children aged 0-15 years over the period 1989-2003. METHODS AND RESULTS: The cases were ascertained using two independent sources, the population-wide Czech Childhood Diabetes Register and the Association of Parents and Friends of Diabetic Children, and the completeness was calculated using the capture-recapture method. The background population size was obtained from annual reports of the Czech Statistic Bureau. Trends in incidence were estimated using Poisson regression. A total of 3 454 cases was ascertained, with an estimated deficit of 28 (95% CI 16-41) individuals. The average age-standardized incidence was 12.0 (95% CI 11.6-12.4) / 100,000/year, and its average relative increase was 6.8% / year. The incidence has risen from 6.8 (95% CI 5.7-7.9) in 1989 to 18.3 (95% CI 16.2-20.4) in 2003. The prevalence in 2003 was 1.01 (95% CI 0.96-0.06) cases per 1000, and its projection into the coming decade expects a rise to approximately 1.7/1000 in 2013. CONCLUSIONS: The present work shows that the Czech population has an intermediate childhood type 1 diabetes incidence compared to other European countries, and although its continuous rise may be expected, the prevalence is very unlikely to reach dramatically high figures.

Use of a skin explant model for predicting GVHD in HLA-matched bone marrow transplants - effect of GVHD prophylaxis.

Over the last decade we have successfully evaluated the use of a human skin explant assay for predicting acute GVHD in HLA-matched sibling transplants. In the present study, we modified GVHD prophylaxis on an individual patient basis depending on the GVHD outcome predicted by the skin explant model. We have summarised our previous data describing how the skin explant assay results correctly predict GVHD occurrence and severity in 45/56 patients (80%); P< 0.0001, chi2 19.97, df = 1. In a further cohort of 19 patients, all were predicted to develop grade II or above GVHD. These patients were given increased GVHD prophylaxis with the addition of methotrexate and a significant reduction in the expected incidence of GVHD was observed (P = 0.02; chi2 7.7, df = 1; Fisher exact test P = 0.04). The results from these studies suggest that modifying GVHD prophylaxis, based on skin explant assay results, may reduce the expected incidence and severity of GVHD. We suggest that the technique might be used for selective GVHD prophylaxis in T cell non-depleted HLA matched sibling transplants.

Higher maternal age at delivery, and lower birth orders are associated with increased risk of childhood type 1 diabetes mellitus.

In several populations, maternal age at delivery and birth order have been demonstrated to variously affect the risk of Type 1 diabetes mellitus in the offspring. The aim of the present study was to investigate this relation in the Czech population. Questionnaire data on 640 children with childhood-onset Type 1 DM and data on 50 random controls to each case, obtained from the national Birth Registry and matched for the calendar year of birth, were analysed using multivariate logistic regression. The risk of Type 1 DM increases with higher maternal age at birth of the child (OR = 1.07, CI 95 % 1.05 - 1.09 per one year increment), and decreases with higher birth order (OR = 0.70, CI 95 % 0.62 - 0.79 per increment in birth order). There was no significant difference in these effects across the five-years bands of age at diabetes onset. We detected no independent effect of maternal education, either. Our study provides further evidence that the risk of Type 1 diabetes in the offspring increases with higher maternal age at delivery and lower birth order.

Pregnancy in a woman suffering from type 1 diabetes associated with Addison's disease and Hashimoto's thyroiditis (fully developed Autoimmune Polyglandular Syndrome Type 2).

In this article the pregnancy of a woman suffering from the complete triad typical of Autoimmune Polyglandular Syndrome Type 2 (Addison's disease + type 1 diabetes + Hashimoto's thyroiditis) is reported. By using insulin pump therapy with insulin lispro, it was possible to balance diabetes control with changes of steroid replacement therapy. Pregnancy was uneventful until week 27, when signs of preeclampsia occurred. The boy was born without difficulty at gestational age 37 weeks by planned cesarean section but signs of diabetic fetopathy (macrosomia, hypoglycaemia and hypocalcaemia) were expressed. He required a short course of hydrocortisone therapy. He made a good and rapid recovery. The mother made a good post-operative recovery too, but 4 months after the delivery microalbuminuria as well as mild hyperuricemia are still present. Interdisciplinary approach and very careful observation of the mother as well as of the child enabled successful outcome of this highly risky pregnancy.

HLA-DQ polymorphisms modify the risk of thyroid autoimmunity in children with type 1 diabetes mellitus.

OBJECTIVE: Type 1 diabetes mellitus (DM1) is frequently accompanied by thyroid autoimmunity (TAI). The aims of the present study were to estimate the prevalence of TAI and to determine the contribution of HLA-DQA1 and -DQB1 polymorphisms to TAI susceptibility among children with DM1. PATIENTS AND METLHODS: Screening for TAI was performed in 285 children with DM1 by measuring autoantibodies against thyroid peroxidase (anti-TPO) and thyroglobulin (anti-Tg). HLA-DQA1 and -DQB1 were genotyped using PCR-SSP. RESULTS: Repeated positivity of anti-TPO and/or anti-Tg was found in 45/285 children with DM1 (15.8%). The prevalence was significantly higher in girls than in boys (26.7% vs 6.7%; p<10(-5)). The HLA-DQB1*0302 allele conferred susceptibility to TAI in children with DM1 (OR 2.7, 95% CI 1.1-6.4), while the DQB1*05 alleles acted protectively (OR 0.2, CI 95% 0.08-0.7). CONCLUSIONS: HLA-DQ polymorphisms significantly modify the risk of TAI in children with DM1.

[Prediction of type 1 diabetes in the neonates of diabetic mothers or fathers]. / Predikce diabetu 1. typu u novorozencu diabetických matek nebo otcu.

OBJECTIVE: Verification of the possibility to predict diabetes in the neonates of mothers and fathers with Type 1 diabetes. DESIGN: Prospective clinical study. SETTING: Mother and Child Care Institute, Prague. Paediatric Clinic of the 2nd Faculty of Medicine at the Charles University, Prague. METHODS: In 31 neonates of mothers and fathers with Type 1 diabetes, the long-term and short-term risk of the occurrence of Type 1 diabetes was established. The genotypification of HLA, DQB1, HLA DQA1 and DRB1 *04 was carried out by using the PCR method to establish the long-term risk and according to the result of the examination, the examined child was included into one of the five categories of genetic risk. In all the monitored persons, the levels of antibodies against GAD65, IA-2 and IRA insulin were repeatedly identified by means of the methods, which are the markers of autoimmune insulitis and show the short-term risk of the occurrence of diabetes. The function-related examination of secretion of beta cells was carried out by using the intravenous glucose tolerance test (i.v. GTT) in children with significant titres of one or more antibodies. RESULTS: A very high risk of the occurrence of Type 1 diabetes was identified in 1 child with the genotype DQA1*03-DQB1*0201/DQA1*05-DQB1*0302 (3.23%); an increased risk was identified in 12 children (38.71%); a medium risk was identified in 11 children (35.48%); a relatively low risk was identified in 3 child (9,68%) and a low risk was identified in 4 children (12,90%). In 4 children (12.9%), a strongly protective alelle DQB1*0602 was found. In 4 children, positivity for one of the antibodies was identified. In 1 child of a diabetic father with an increased genetic risk, there was a decrease in the titre of antibodies in the case of repeated check and function-related examination of the insulin secretion (FPIR) will be carried out. In another child, disappearance of antibodies was identified when samples were taken for verification; function-related examination of insulin secretion produced normal results, and the child has remained without clinical manifestation of diabetes. In a third child, the positivity of the antibodies from the umbilical blood was only temporary and was probably caused by a passive transfer from the mother; now, when repeated checks were made, the antibodies have remained negative. In a fourth child, the parents refused further examinations after antibody positivity was observed; the child has been without clinical manifestation of diabetes up until now. CONCLUSION: This scheme for predicting diabetes by means of immunogenetic and immunological examination of risk individuals is a rational measure aimed at timely identification of autoimmune insulitis, which precedes the occurrence of Type 1 diabetes, and it should become a standard part of diabetological care.

[Association of insulin gene variants with type 1 diabetes mellitus in Czech population]. / Asociace variant inzulínového genu s diabetes mellitus 1. typu v ceské detské populaci.

BACKGROUND: The objective of the study was to quantify the association of insulin gene variants with type 1 diabetes mellitus (TIDM) in the Czech population. METHODS AND RESULTS: In an association study, we compared genotypes of 332 T1DM patients (age at T1DM onset was 8.1 +/- 4.4 yrs) with 292 healthy nondiabetic controls of similar age. All subjects were previously genotyped for HLA-DQB1, -DQA1 polymorphisms and DRB1*04 subtypes. The insulin gene was typed using the -23 HphI single nucleotide polymorphism after we had demonstrated a nearly complete linkage disequilibrium between this polymorphism, and the etiological VNTR in the Czech population. The protective variant of the insulin gene was present in 24% T1DM patients, and in 48% controls (OR=0.34, CI 95% 0.24-0.48), a risk comparable to weaker-associated HLA-DQ alleles. The association was independent of the HLA-conferred T1DM risk. The insulin gene polymorphism had no influence on the age at T1DM onset. CONCLUSIONS: We conclude that the insulin gene genotyping confers important information on T1DM risk in our population, and should be used in determining the disease risk along with the HLA-DQ typing.

[Autoantibodies to GAD65, IA2 and insulin in Czech children with type 1 diabetes]. / Autoprotilátky proti GAD65, IA2 a inzulinu u ceských detí pri manifestaci diabetu 1. typu.

BACKGROUND: Autoimmune insulitis leading to insulin dependent diabetes mellitus (IDDM, Type 1 Diabetes) is accompanied by autoantibodies as its invaluable markers. The aim of the study was to determine the frequency of autoantibodies against GAD65, IA2 and insulin in Czech diabetic children at the disease onset. METHODS AND RESULTS: Sera of 105 newly diagnosed children with IDDM drawn within 24 hours after the first insulin dose were investigated for anti-GAD65, anti-IA2 and insulin autoantibodies (IAA) using RIA methods. The cut-off normal levels were determined as the 99th percentile of 105 non-diabetic children. At given 99% specificity, the sensitivity was 71% for anti-GAD65, 73% for anti-IA2, and 46% for IAA. 29% diabetic children were positive for all three autoantibodies, 25% had anti-GAD65 and anti-IA2 (IAA negative), 5.7% anti-GAD65 and IAA (anti-IA2 negative), 7.6% anti-IA2 and IAA (anti-GAD65 negative). As the only positive autoantibody, anti-GAD65 was found in 12%, anti-IA2 in 11%, and IAA in 3.8% children. In 5.7% children, none of the investigated autoantibodies was positive. Diabetic children diagnosed before the age of 5 years had significantly higher prevalence of IAA than the older ones. CONCLUSIONS: We have determined normal levels in healthy children, and prevalence at childhood IDDM onset of autoantibodies against three main molecular-defined autoantigens.

[Type I diabetes mellitus and associated autoimmune diseases in the first-degree relatives of diabetic children: questionnaire based study]. / Diabetes mellitus 1. typu a sdruzená autoimunitní onemocnení u prvostupnových príbuzných diabetických deti: výsledky dotazníkové studie.

BACKGROUND: Type 1 diabetes mellitus (T1DM) is associated with increased incidence of other autoimmune diseases. The shared genetic background may play a role in the disease pathogenesis. The aim of our study was to assess the prevalence of T1DM and other autoimmune disorders in the first-degree relatives of diabetic children. METHODS AND RESULTS: Data were retrospectively obtained using structured questionnaires from 868 diabetic children younger than 18 years (434 girls and 434 boys, age 12.5 +/- 4.0, mean +/- SD) and their 2704 relatives. The control group included 1466 non-diabetic schoolmates and friends (796 girls, 670 boys, age 11.9 +/- 4.5) and their 4510 first-degree relatives. In the questionnaire we asked about occurrence of thyroid and celiac disease in cases and controls, and about occurrence of T1DM, thyroid and celiac disease in their first-degree relatives. We observed significantly higher prevalence of T1DM in fathers (4.4% vs. 0.8%), mothers (2.0% vs. 0.5%) and siblings (2.5% vs. 0%) of diabetic children compared to controls. Thyroid disease was found significantly more in diabetic children (10.0% vs. 1.9%) and their siblings (3.1% vs. 1.7%). Prevalence of celiac disease was also higher in diabetic children than in controls (3.2% vs. 0.5%), but it does not differ in their first-degree relatives. CONCLUSIONS: We found significantly higher prevalence of thyroid and celiac disease in T1DM children than in controls. Targeted screening and early detection of thyroid and celiac diseases in T1DM patients are likely to be necessary. We observed an increased prevalence of T1DM and thyroid disease in first-degree relatives of diabetic children, however screening of autoimmune diseases associated with T1DM in the first-degree relatives remain controversial.

[Prediction of insulin-dependent diabetes mellitus in children of first-degree relatives of diabetic patients]. / Predikce inzulin dependentního diabetes mellitus u detských prvostupnových príbuzných diabetických pacientu.

BACKGROUND: Individuals at risk for insulin dependent diabetes mellitus (IDDM) can be identified using a combination of genetic, immunological and metabolic markers. Our study was aimed at prediction of IDDM in a cohort of children having a first-degree relative with IDDM. METHODS AND RESULTS: In the period of three years, we investigated 208 non-diabetic children and adolescents, aged 10.0 +/- 5.3 (mean +/- SD), mostly siblings of diabetic children. The genetic risk was determined by the HLA-DQB1, -DQA1 genotyping and subtyping of the DRB1*04 alleles carried on the DQB1*0302 haplotypes. Insulitis was detected using a combination of autoantibody tests against three molecular-defined antigens (insulin, GAD65, IA-2). Prevalence of insulitis (defined as confirmed positivity of at least one autoantibody) was 9/208 (4.3%). In children carrying the IDDM highest-risk genotype (HLA-DQB1*0201-DQA1*05/DQB1*0302-DQA1*03), insulitis was almost 10 times more frequent (5/24, 21%) than in children with other genotypes (4/184, 2.2%, P = 0.003). In all subjects with insulitis, the first phase insulin response (FPIR) was determined by the intravenous glucose tolerance test. Three of the nine children had decreased FPIR, of whom two were later diagnosed with IDDM. None of the remaining children developed IDDM. CONCLUSIONS: We present the first IDDM prediction study in the Czech population, emphasising the utility of genetic risk investigation in the prediction scheme.

[A method for modeling skin explants--an in vitro predictive test for graft vs host disease in allogenic hematopoietic cell transplantation]. / Metoda modelu kozního explantátu--in vitro graft versus host disease prediktivní test pro alogenní transplantace hematopoetických bunek.

BACKGROUND: Acute graft versus host disease (GvHD) remains a severe complication of allogeneic haematopoietic stem cell transplantation (HSCT). Our study summaries results of skin explant assay (SEA) as a pretransplant GvHD predictive test in a cohort of paediatric (n = 33) and adult (a = 8) patients receiving grafts from their HLA identical siblings (n = 28), haploidentical relatives (n = 3) and unrelated donors (n = 10). Results GvHD prediction are correlated with the occurrence and severity of acute GvHD posttransplant and effect of GvHD prophylaxis on GvHD clinical outcome is evaluated. METHODS AND RESULTS: SEA utilises responding lymphocytes of the donor, which are sensitized firstly in vitro by mononuclears cells of patient in allogeneic mixed lymphocyte culture (MLC) and subsequently co-cultured with recipient's skin. Histopathological changes found in patients' skin explants are evaluated according to standard Lerner classification for acute GvHD. In general, GvHD predictive results in SEA correlated with GvHd clinical outcome in 28 out of 41 tested patients (68%, p = 0.015). In a cohort of HLA identical sibling transplants GvHD predictive results correlated with clinical manifestation of acute GvHD only in 15 out of 28 patients on individual GvHD prophylaxis. GvHD prophylaxis in the form of cyclosporine A (CsA) combined with short-term methotrexate (MTX) reduced the risk of acute GvHD in 10 out of 14 transplanted patients (71%) meanwhile CsA alone prophylaxis only in 1 out of 5 patients (20%). In a cohort of unrelated pairs on CsA/MTX prophylaxis combined with horse anti-lymphocyte globuline (ALG) correlated the GvHD prediction with GvHD clinical outcome (100%, p = 0.003). In all patients transplanted with the grafts from their haploidentical relatives the occurrence of severe GvHD was predicted. CONCLUSION: Skin explant assay helps identify pretransplant patients at higher risk of severe acute GvHD. GvHD predictive results enable the transplantation team to individualise GvHD prophylaxis and to optimise selection of the donor.

[Relation between retinopathy and glucose compensation in diabetic children and adolescents]. / Závislost retinopatie na glukózové kompenzaci diabetu u detí a mladistvých.

The fundus of the eye was examined in 302 children and adolescents with insulin dependent diabetes (mean age 14.2 years, SD 3.60, mean duration of diabetes 6.4 years, SD 3.83) by prolonged chromato-ophthalmoscopy and the finding was classified according to the authors' own extended classification of diabetic retinopathy. In 295 patients the authors assessed the mean value of glycosylated protein during the period of 3-6 months before assessment of the retina. When these values were compared with the retinal findings, a statistically highly significant relationship of retinopathy and the glucose compensation of diabetes was found (p < 0.001). The increase of the mean glycoprotein value during adolescence, as compared with the prepubertal period, was also statistically significant, while adolescents without retinopathy had lower mean glycoprotein values as compared with the group as a whole.

[Relation of retinopathy to puberty and sex in insulin-dependent diabetics]. / Vztah retinopatie k puberte a pohlaví u inzulíndependentních diabetiku.

The authors examined by chromatoophtalmoscopy the optic fundus in 302 children and adolescents with insulin dependent diabetes. They classified the findings according to their own classification and selected from the entire number two groups of patients where the common sign was persistence of diabetes for a period of 5-8 years. Group A (n = 32) was, however, formed only by children under 11 years, while group B (n = 35) comprised adolescents aged 16-20 years. In group A the authors found incipient retinopathy in 12.5% children, in group B in 48.6% of the patients (p < 0.005). The degree of retinopathy was also more severe in older subjects. Comparison of the whole group by sex did not reveal a significant relationship (p > 0.05). In the conclusion the authors draw attention to the necessity of careful follow up of the optic finding in child diabetics, in particular during adolescence.

[Extended classification of diabetic retinopathy in children and adolescents]. / Rozsirená klasifikace diabetické retinopatie u deti a mladistvých.

The authors submit their own modification of the classification of diabetic retinopathy elaborated on the background of several years experience with the examination of children and adolescents with insulin dependent diabetes. The extended classification pattern makes it possible to differentiate and classify more accurately even slight incipient changes detected by chromatooophthalmoscopy. The presence of microaneurysms reflects well the degree of retinal damage in early stages. Special attention must be paid to intraretinal microvascular abnormalities (IRMA). The classification pattern is presented in a table included in the text.

[Occurrence of diabetic retinopathy in children and adolescents and its relation to the duration of diabetes and patient age]. / Výskyt diabetické retinopatie u deti a mladistvých a jeji závislost na trváni diabetu a veku nemocných.

In a retrospective investigation the authors give an account of a group of 302 children and adolescents with insulin dependent diabetes (mean age 14.2 years, mean duration of diabetes 6.4 years) whom they examine regularly by chromatoophtalmoscopy and evaluate the findings according to their own extended classification of diabetic retinopathy. In 29% of the patients the finding was positive and in 25% the finding was suspect. The most frequent pathological change were microaneurysms; intraretinal microvascular abnormalities (IRMA) were detected in 13 patients. The trend towards proliferative changes is apparent in some patients surprisingly soon. The authors emphasize the sensitivity of the method which along with the extended classification of retinopathy makes its monitoring possible. The authors discuss the value of fluorescent angiography in the initial stages of retinal damage. They provide evidence of a statistically significant relationship of diabetic retinopathy and the duration of diabetes (p < 0.001) and age (p < 0.001).

[The effect of heart surgery during extracorporeal circulation and deep hypothermia on glucose metabolism in infants and young children]. / Vliv operace srdce v mimotelním obehu a v hluboké hypotermii na metabolismus glukózy u kojencu a malých detí.

Authors examined levels of glucose, insulin, and C-peptide in the plasma of 6 infants and small children with the isolated transposition of the great arteries (3 pts) and ventricular septal defect (3 pts) in the course of open-heart surgery in deep hypothermia. The mean age of the patients was 7.2 months (6 to 15) and weight 5.6 kg (5.2-7.5). Exogenous intake of glucose during the operation was excluded. Methods of anaesthesia, operation technique, and conduction of extracorporeal circulation (ECC) were constant in all patients. Fresh ACD blood diluted with Hartman solution approximately 1:1 was used for the prime of ECC circuit (content 800 ml) to get the hematocrit 0.27 +/- 0.2 after mixing the prime with the patient's blood volume. Glycemia was determined by Beckman ERA 2001 analyzor, and levels of insulin and C-peptide by radioimmunoassay kits MJ-96 (Poland) and Novo (Denmark). Significant hyperglycemia was found in all patients during the period of hypothermia, and was overlasting to the rewarming period until the end of the operation and 1 hour postoperatively. Then level of glycemia was decreasing to the normal values which were found in the last sample (17 hours post-op). The raise of glycemia was not a stimulus to the proportional increase of insulin and C-peptide levels in plasma. It proved transitional suppress of insulin secretion in the beta cells of the pancreas in the cooling period. Levels of insulin and C-peptide significantly and concordantly increased after 20 min. of rewarming (r = 0.83). However, hyperglycemia overlasted during the course of rewarming, too.(ABSTRACT TRUNCATED AT 250 WORDS)