Association of angiotensin-converting enzyme DD genotype with 24-h blood pressure abnormalities in normoalbuminuric children and adolescents with Type 1 diabetes.

AIMS: To assess the distribution of the insertion/deletion (I/D) polymorphism of the angiotensin-converting enzyme (ACE) gene in children and adolescents with Type 1 diabetes and to evaluate the association between ACE genotype and blood pressure (BP). METHODS: ACE genotypes were assessed in 124 normoalbuminuric, clinically normotensive Type 1 diabetic children and adolescents and 120 non-diabetic controls using polymerase chain reaction. Twenty-four-hour ambulatory BP monitoring was undertaken in all patients. RESULTS: ACE genotypes distributed in patients as follows: 34 (27%) DD, 57 (46%) ID, 33 (27%) II. The distribution was similar in the control group: DD in 28% (33), ID in 45% (54), and II in 27% (33). Patients with DD genotype had higher mean 24-h diastolic BP (73.8 +/- 6.2 vs. 70.2 +/- 5.0 and 69.7 +/- 6.3 mmHg; P = 0.005) and lower diurnal variation in BP (11.8 +/- 4.6 vs. 14.2 +/- 4.2 and 14.8 +/- 4.3%; P = 0.011) compared with ID and II groups. Four patients in the DD group proved to be non-dipper compared with one in the ID and none in the II group (P = 0.026). Twenty-four-hour diastolic blood pressure was independently predictive for AER as dependent variable in the DD genotype patient group (r(2) = 0.12, P = 0.03). CONCLUSIONS: Children and adolescents with Type 1 diabetes do not differ from the non-diabetic population regarding the I/D polymorphism of the ACE gene. ACE gene polymorphism is associated with BP abnormalities in normotensive and normoalbuminuric children and adolescents with Type 1 diabetes.

Multicentric Castleman disease and systemic lupus erythematosus phenotype in a boy with Klinefelter syndrome: long-term disease stabilization with interferon therapy.

An 11-year-old boy with Klinefelter syndrome had Castleman disease (CD) of plasma cell type develop. Nonregulated antibody production mimicked systemic lupus erythematosus (SLE). Hepatitis C virus (HCV) infection caused significant disease worsening. The patient was treated with a daily dosage of 2 million units/m2 of IFN-alpha. Dramatic clinical improvement and decreasing autoimmune phenomenon were observed. HCV RNA were cleared. Hypergammaglobulinemia did not change. The boy has been living for 8 years with his disease. Plasma cell type CD can mimic collagenosis. Disease worsening is caused by HCV, though it can be reversed with IFN-alpha. Klinefelter syndrome may be a genetic susceptibility factor for CD in some cases.

[Glucose metabolism and insulin sensitivity in patients with Turner syndrome treated with growth hormone]. / A glükózanyagcsere és inzulinszenzitivitás vizsgálata a növekedési hormonkezelt Turner-szindrómás betegeknél.

The authors investigated the effect of growth hormone treatment on 20 Turner syndrome patients. The aim was to assess glucose and insulin responses to oral glucose loading in 9 prepubertal and 11 pubertal patients with Turner syndrome. Thirty eight healthy subjects matched for chronological age and BMI were selected as controls. Similar glucose responses were observed in the prepubertal and postpubertal patients groups and no difference was found between patients and controls. No correlation was observed between glycaemic control of insulin sensitivity and growth hormone treatment. Although the supraphysiological doses of growth hormone did not result in substantial impairement in glucose tolerance, it is concluded that hyperinsulinaemia could be a consequence of the treatment and regular check up for glycaemic control is needed in these patients.

Prospective assessment of severe hypoglycaemia in diabetic children and adolescents with impaired and normal awareness of hypoglycaemia.

To establish whether impaired hypoglycaemic awareness is associated with increased rate of severe hypoglycaemia and to assess clinical predictors of severe episodes without warning symptoms a prospective study of 130 insulin-dependent diabetic children and adolescents was undertaken for 1 year. Using a structured questionnaire, 48 patients reported impaired awareness and 82 reported normal awareness of hypoglycaemia at baseline of the study. The two groups did not differ regarding clinical and metabolic characteristics. Episodes of severe hypoglycaemia were recorded for 1 year. The rate of severe hypoglycaemia was higher in the group with impaired awareness than in the group with normal awareness (p < 0.0001). Of the severe hypoglycaemic episodes, 34.0% developed without warning symptoms. Patients with impaired awareness experienced more severe episodes without warning symptoms than those with normal awareness (p = 0.0054). Severe hypoglycaemia occurred more frequently in patients with impaired awareness aged 6 years and less (p = 0.0041) than in older counterparts. Impaired awareness reported at baseline [adjusted odds ratio (OR): 5.8; p =0.0021], age 6 years or less (3.4; p = 0.0121), previous severe episode (4.8; p = 0.0043) and more than 5 % of home blood glucose readings 3.3 mmol/l or less in the preceding month (4.2; p = 0.0211) proved to be independently predictive of severe hypoglycaemic events without warning symptoms. In conclusion, impaired hypoglycaemic awareness is associated with an increased rate of severe hypoglycaemia in diabetic children and adolescents. One third of severe episodes developed without warning symptoms. Impaired awareness, young age and recent biochemical or severe hypoglycaemias are independent risk factors for such episodes. Avoidance of hypoglycaemia should be a priority in preschool children with diabetes.

Enhanced progression of urinary albumin excretion in IDDM during puberty.

OBJECTIVE: To determine whether the progression of urinary albumin excretion rate (AER) is higher during puberty than before or after this period. RESEARCH DESIGN AND METHODS: A prospective study was conducted in which normoalbuminuric prepubertal (n = 20), pubertal (n = 28), and postpubertal (n = 26) IDDM groups matched for diabetes duration and long-term metabolic control were followed for 3 years. At 6-month intervals, 24-h urine collection was used to determine AER. RESULTS: AER increased significantly over a period of 3 years in the pubertal (P = 0.001) and postpubertal (P = 0.003) subjects but not in prepubertal subjects. The annual progression of AER was significantly higher in the pubertal group than in the prepubertal (P = 0.001) or postpubertal (P = 0.001) groups. Six pubertal, two postpubertal, and none of the prepubertal subjects developed microalbuminuria (AER > or = 20 micrograms/min on two consecutive occasions) over a 3-year period (P = 0.047). Multiple logistic regression analysis showed that the risk of development of microalbuminuria was increased in pubertal subjects compared with the prepubertal and postpubertal subjects (adjusted relative risk [95% CI]: 4.3 [1.5-9.3], P = 0.012, and 2.1 [1.1-5.0], P = 0.023, respectively). CONCLUSIONS: Puberty represents an independent risk of the development of microalbuminuria in diabetes. This findings suggests that the endocrine changes of puberty lead to an accelerated process of early kidney damage in diabetes. In pediatric diabetes care, screening for microalbuminuria is needed soon after the onset of puberty.

Peripheral sensory nerve dysfunction in children and adolescents with type 1 diabetes mellitus.

The aim of the present study was to investigate peripheral sensory nerve function in diabetic children and adolescents without neurological symptoms. Ninety-two children and adolescents with Type 1 (insulin-dependent) diabetes mellitus (mean +/- SD age: 14.2 +/- 2.1 years, diabetes duration: 5.8 +/- 3.0 years) and 80 healthy control subjects (age: 13.8 +/- 2.2 years) matched for age, sex, body mass index, and height standard deviation score were involved in the study. Using a sine-wave transcutaneous stimulator, current perception threshold (CPT) testing at 2000, 250 and 5 Hz was performed on the left median and peroneal nerves. Diabetic children had increased CPT at 2000 Hz on both nerves as compared to the control group (median (interquartile range), median nerve: 2.43 (2.20-3.43) vs 1.80 (1.51-2.60) mA, p = 0.02; peroneal nerve: 3.51 (2.81-4.82) vs 2.70 (2.04-3.70) mA, p = 0.01). Twenty-one (23%) of patients had CPT values higher than that of any healthy individual. Of these, elevated CPT was observed in 9 (9.8%) patients on the median nerve, in 8 (8.7%) patients on the peroneal nerve, and in 4 (4.3%) patients on both median and peroneal nerves. Using multiple logistic regression analysis, worse long-term metabolic control and advanced puberty were independently predictive of peripheral sensory nerve dysfunction as the dependent variable (adjusted OR (95% CI): 3.4 (1.2-6.2), p = 0.01, and 2.8 (1.1-5.6), p = 0.03, respectively). In conclusion, evidence of peripheral sensory nerve dysfunction is not rare in children and adolescents with diabetes and can be demonstrated by CPT testing in asymptomatic patients. Poor metabolic control is a risk factor for such subclinical neuropathy, and pubertal development may be involved in the pathogenesis of diabetic peripheral neuropathy.

[The effect of captopril therapy on the degree of microalbuminuria in diabetic children and adolescents with incipient nephropathy]. / Captopril kezelés hatása a microalbuminuria mértékére incipiens nephropathiás gyermek-és serdülókorú cukorbetegekben.

In the present study the effect of angiotensin converting enzyme inhibitor captopril was studied in normotensive diabetic children and adolescents with persistent microalbuminuria (repeated albumin excretion rate higher than 30 mg/24 h). In 1993/1994, 15 microalbuminuric patients (age: 10-17 yrs, diabetes duration: 6.5 +/- 3.0 yrs) had been treated with captopril (0.9 mg/kg/day for a period of 13.1 +/- 4.4 months). In 1992/1993, 13 patients (age: 11-17 yrs, diabetes duration: 5.8 +/- 2.7 yrs, study period: 12.3 +/- 4.0 months) had not received captopril. Same restriction of the dietary protein intake was recommended in both groups (less than 10% of the total calorie intake). Timed 24-h urine samples were used to determine albumin excretion by an immunonephelometric method. Significant increase in microalbuminuria was observed in patients who had not received captopril during the study period (56.2 +/- 16.0 mg/24 h vs. 77.8 +/- 20.1 mg/24 h, p = 0.045). There was no change in microalbuminuria in the captopril treated group during the study period (60.6 +/- 19.5 mg/24 h vs. 60.4 +/- 25 mg/24 h, n. s.). No change in metabolic control and blood pressure was observed in the two groups during the study period. These results support that captopril treatment may prevent or delay the progression of incipient nephropathy in normotensive children and adolescents in diabetes.

Physical work capacity in diabetic children and adolescents with and without cardiovascular autonomic dysfunction.

The aim of the present study was to evaluate the influence of autonomic nervous system dysfunction on work capacity in children and adolescents with Type 1 (insulin-dependent) diabetes. Fifteen patients with autonomic dysfunction (abnormal autonomic tests, age: 14.9 +/- 2.3 years), 35 patients without autonomic dysfunction (normal autonomic tests, age: 15.2 +/- 2.5 years), and 25 non-diabetic subjects (age:15.0 +/- 2.3 years) were investigated. Resting heart rate, deep breathing heart rate variation, standing/lying heart rate ratio, decrease in blood pressure during orthostasis, and increase in blood pressure during sustained handgrip were used to assess cardiovascular autonomic dysfunction. Physical work capacity at heart rate of 170 min-1 was determined by bicycle ergometry. Glycated haemoglobin level was higher in patients with than without autonomic dysfunction (12.3 +/- 3.1 vs 9.4 +/- 2.9%, p = 0.04). Patients with autonomic dysfunction had significantly lower physical work capacity at heart rate of 170 min-1 than those with normal autonomic function or non-diabetic subjects (0.81 +/- 0.12 vs 1.49 +/- 0.16 and 1.54 +/- 0.20 W kg-1 p = 0.01). Physical work capacity at heart rate of 170 min-1 was related to glycated haemoglobin level (r = -0.55, p = 0.01), to resting heart rate (r = 0.57, p = 0.01), and to deep breathing heart rate variation (r = 0.51, p = 0.02). In conclusion, impaired work capacity is associated with poor blood glucose control and cardiovascular autonomic dysfunction. Autonomic tests can help to identify those patients who may need special consideration during exercise.

[Polycytemia vera in an 11-year old girl]. / Valódi polycythaemia 11 éves leányban.

The case of an 11 year old girl with three line type of polycythaemia vera, with 4 cm splenomegaly and a plethoric complexion is presented. Peripheral blood values were as follows: RBC: 7.75 x 10(12)/l, Hb: 18.8 g/l, WBC: 15.2 x 10(9)/l, platelets: 920 x 10(9)/l. Serum erythropoietin level: < 1 mU/ml. In vitro, erythroid colonies developed from the bone marrow in the absence of added erythropoetin. For three years the haematocrit value has been controlled by regular venesections. Since extreme thrombocytosis developed, the treatment was continued with interferon alpha. Different treatment protocols are discussed.

Severe hypoglycaemia and cardiovascular autonomic dysfunction in type I diabetic children treated with intensified conventional insulin therapy.

To assess the relationship between severe hypoglycaemias and autonomic dysfunction, five cardiovascular tests (resting heart rate, hyperventilatory arrhythmia, standing/lying heart rate ratio, orthostatic decrease in blood pressure, and increase in blood pressure during sustained handgrip) were performed in a 1-yr prospective study of 34 insulin-dependent diabetic children treated with intensified conventional insulin therapy (ICIT). There were twelve severe episodes in 7 diabetic children, and the remaining 27 patients had no severe hypoglycaemia. The hypoglycaemic group had a longer duration of diabetes than the nonhypoglycaemic group (5.4 SD 2.5 years vs. 2.8 SD 2.2 years, p less than 0.02). The hyperventilatory arrhythmia in the hypoglycaemic group in comparison with the nonhypoglycaemic group was significantly decreased (before ICIT: 16.1 SD 3/min vs. 24.4 SD 5/min, p less than 0.01; 1 yr thereafter: 17.3 SD 3/min vs. 26.0 SD 5/min, p less than 0.01). The hypoglycaemic group showed a pronounced orthostatic decrease in blood pressure compared to the nonhypoglycaemic group (before ICIT: 13.2 SD 4 mmHg vs. 6.0 SD 4 mmHg, p less than 0.01; 1 yr thereafter: 12.3 SD 4 mmHg vs. 5.6 SD 4 mmHg, p less than 0.01). Three or more abnormal cardiovascular test results were found in patients of the hypoglycaemic group who showed abnormal hyperventilatory arrhythmia and abnormal orthostatic decrease in blood pressure simultaneously, whereas such a coexistence was not found in the nonhypoglycaemic group. These observations may support the view that diabetic children and adolescents with autonomic dysfunction are susceptible to severe hypoglycaemia during ICIT.

Association of microalbuminuria with slow acetylator phenotype in type 1 diabetes mellitus.

The genetically determined acetylator phenotype in diabetic children with and without increased urinary albumin excretion was investigated. Acetylator phenotype was determined according to Evans, and 24-hour albumin excretion rate (AER) was measured by immunoturbidometry in 86 children and adolescents with type 1 (insulin-dependent) diabetes mellitus and in 100 age-matched healthy controls. In diabetics, the fast acetylator phenotype was found in 36 (41.9%) patients and the slow one in 50 (58.1%); the control group had 52 (52%) fast and 48 (48%) slow acetylators. There were no significant differences in acetylator phenotypes between diabetic patients and control subjects (chi 2 = 1.0, NS). Among patients with normal albumin excretion (n = 70, mean age: 12.9 +/- 3.5 years, mean diabetes duration: 5.3 +/- 3.8 years, AER < 20 micrograms/min), 35 (50%) fast acetylators and 35 (50%) slow acetylators were found. In patients with elevated albumin excretion (n = 16, mean age: 14.0 +/- 3.2 years, mean diabetes duration: 4.9 +/- 3.0 years, AER > 20 micrograms/min), 1 (6.3%) patient was a fast acetylator and 15 (93.7%) were slow acetylators. A significant difference has been found between the two groups in the rate of fast/slow acetylators (chi 2 = 8.79, p < 0.01). The strong correlation between the slow acetylator phenotype and microalbuminuria in diabetics suggests that: (a) genetic factors may play a role in the development of diabetic nephropathy; (b) the acetylator status could be a useful tool to detect patients 'at risk' of nephropathy.

[Connection between microalbuminuria and subclinical cardiovascular autonomic neuropathy in diabetic children]. / A microalbuminuria és a szubklinikai cardiovascularis autonom neuropathia összefüggésének vizsgálata diabeteses gyermekekben.

Cardiovascular tests were investigated in 16 microalbuminuric, in 20 normoalbuminuric diabetic children and a control group of 20 healthy children. Comparing to the control group, in both of two diabetic groups a similar increase in resting heart rate (74.5 +/- 2.5/min vs. 87.8 +/- 3.5/min, p less than 0.01, and 83.6 +/- 3.2/min, p less than 0.05) and a decrease in hyperventilatory arrhythmia (32.3 +/- 1.2/min vs. 20.1 +/- 0.8/min, p less than 0.01, and 17.2 +/- 0.8/min, p less than 0.01) was observed. In the diabetic group with microalbuminuria in comparison with both the control group and the normoalbuminuric group there was a lower standing/lying heart rate ratio (1.02 +/- 0.03 vs. 1.30 +/- 0.05, p less than 0.01, and 1.22 +/- 0.05, p less than 0.05), a pronounced orthostatic decrease in blood pressure (15.1 +/- 0.3 mmHg vs. 2.0 +/- 0.1 mmHg, p less than 0.001, and 5.0 +/- 0.2 mmHg, p less than 0.01) and a diminished increase in blood pressure during sustained handgrip (6.3 +/- 0.2 mmHg vs. 14.0 +/- 0.3 mmHg, p less than 0.01, and 12.2 +/- 0.3 mmHg, p less than 0.05). The occurrence of cases with distinct autonomic dysfunction (3 or more abnormal cardiovascular tests) proved to be more frequent in the group with microalbuminuria than in the diabetic group with normal albumin excretion (6/16 vs. 1/20, p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Autonomic dysfunction and severe hypoglycaemia in insulin dependent diabetes mellitus.

The aims of the present study were to investigate the relationship between severe hypoglycaemia and autonomic dysfunction in diabetic children, and to assess the glycaemic response to an insulin infusion test. In a one year period, 12 of 69 diabetic patients (17%) experienced at least one severe episode of hypoglycaemia, defined as an event which required outside assistance. All patients underwent five cardiovascular autonomic tests. Seven of the hypoglycaemic patients showed three or more abnormal autonomic tests. Among the 57 non-hypoglycaemic diabetics, there was no patient with three or more abnormal tests. In hypoglycaemic diabetics with and without autonomic dysfunction, and in eight healthy age matched subjects an insulin infusion test was performed. A pronounced blood glucose decline and a subnormal increase in heart rate during insulin infusion were obtained in patients with autonomic dysfunction. Thus, severe hypoglycaemia may be due to impaired defence mechanisms against blood glucose decline in diabetic children with autonomic dysfunction.

Decreased urinary excretion of dopamine and sodium in diabetic children with incipient nephropathy.

It has been suggested previously that a decrease in urinary dopamine output might be related to a decrease in the urinary sodium excretion in subjects with diabetic nephropathy suffering from type 2 diabetes. To investigate the renal dopamine status in children with type 1 (insulin-dependent) diabetes mellitus, we measured the 24-hour urinary excretion of dopamine, norepinephrine and sodium in 12 patients with incipient nephropathy (group A, 24-hour albumin excretion rate 70-200 micrograms/min), in 20 age matched patients with normal microalbuminuria (group B, AER less than 20 micrograms/min) and in 8 healthy controls (group C). The mean values for urinary excretion of dopamine and norepinephrine were significantly lower in group A compared to groups B and C (25.6 +/- 14.8 vs. 65.9 +/- 25.5 and 73.3 +/- 18.0 micrograms/day, p less than 0.001 and 11.8 +/- 4.6 vs. 25.1 +/- 12.1 and 28.4 +/- 8.9 micrograms/day, p less than 0.01, respectively). The mean value for the urinary excretion of sodium was also significantly lower in group A than in groups B and C (98.4 +/- 24.1 vs. 206.2 +/- 59.5 and 198.1 +/- 42.8 mEq/day, p less than 0.01). The 24-hour urinary excretion of dopamine correlated significantly with the sodium excretion (r = 0.65, p less than 0.001). Arterial blood pressure was elevated in group A compared to group C (p less than 0.01). Our results suggest that a decrease in endogenous dopamine could play a role in the low urinary sodium excretion thereby resulting in sodium retention which may in turn lead to the development of higher blood pressure in diabetic children with incipient nephropathy.

Application of aluminium ammonium-sulphate solution in treating massive haemorrhage of bladder origin.

The effect of the 1% aluminium ammonium-sulphate solution has been studied. As revealed by animal experiments and clinical examination, the new method can effectively be used without side-effects in the symptomatic treatment of the massive vesical haemorrhages of different origin.

Purulent cholangitis and hepatic abscess after choledochoduodenostomy diagnosed by ERCP.

The authors report on a case of purulent cholangitis and hepatic abscess developing 5 years after choledochoduodenostomy, diagnosed by means of ERCP. They believe viscous pus adhering to the wall of the bile ducts to be responsible, as a mechanical factor, for causing the inhibiting bile discharge. After the ERCP examination, the patient became free from complaints, and could be discharged.