The effect of metabolic and hormonal parameters on microalbuminuria in adolescents with type 1 diabetes mellitus.

INTRODUCTION: The prevalence of microalbuminuria (MA), the most important early marker of incipient nephropathy in patients with type 1 diabetes mellitus (T1DM), increases during puberty, the period of exaggerated physiological insulin resistance. OBJECTIVE: To assess the prevalence of MA and the relationship between MA and metabolic risk factors and pubertal hormones in adolescents with T1DM. METHODS: In a cross-section study involving a group of 100 adolescents of both sexes of mean age 14.90+/-2.18 years and with mean duration ofT1DM 5.99+/-73.64 years, we assessed the presence of MA. In all patients, we determined albumin-to-creatinine ratio (ACR) in two or three morning first-void urine samples in the period up to 6 months. Persistent MA was confirmed in the patients with the finding of ACR rating 2.5-25 mg/mmol in males and 3.5-25 mg/mmol in females in two out of three first morning urine samples. RESULTS: MA developed in 16 (16.0%) patients. Predictors of MA determined by using multiple logistic regression were high HbA1c (OR 4.6; 95% CI 2.1-10.0), higher night-time SBP (OR 1.9; 95% CI 0.8-1.3) and higher insulin dose (OR 62.6; 95% CI 2.3-1678.5). Markers of insulin resistance such as higher body mass index (BMI) which was statistically significantly related to MA (p= 0.241, p<0.05) and higher dehydroepiandrosterone sulfate (DHEA-S) which was significantly higher in patients with MA (7.82 micromol/L vs. 5.02 micromol/L, p<0.01), were also identified as predictors but did not remain significant by multivariate analysis, possibly because of a small sample of subjects with persistent MA. CONCLUSION: In addition to poor glycemic control and higher night-time systolic blood pressure, markers of insulin resistance (higher insulin dose, higher BMI and higher DHEA-S) contribute to the increased risk of MA.

Successful sulfonylurea treatment of a neonate with neonatal diabetes mellitus due to a new KCNJ11 mutation.

Mutations in the KCNJ11 gene, which encodes the Kir6.2 subunit of the ATP-sensitive potassium channel, often result in neonatal diabetes. We describe a female neonate who is a heterozygous for a new missense mutation, V252L, in the KCNJ11 gene and who has been successfully transitioned from insulin to sulfonylurea therapy.

Reference values of capillary blood saturation in neonates and its difference from pulse oximetry.

INTRODUCTION: Haemoglobin saturation is an obligatory oxygen parameter in the assessment of neonatal oxygenation. Although, pulse oximetry is currently one of the major methods in the determination of haemoglobin saturation, capillary blood saturation is still present in the diagnostic process. As well known, haemoglobin saturation value of capillary blood is insufficiently accurate, but not as much as the difference in relation to the values determined by pulse oximetry. Until now published studies have reported that capillary samples are obtained according to a protocol by the principle of free blood outflow, which is practically almost unachievable in the neonate. OBJECTIVE: Determination of the reference values of oxygen saturation (SCO2) and partial pressure (pcO2) of capillary blood by squeezing of the foot. The determination of difference between ScO2 and pulse oximetry (SpO2). METHODS: In 134 term newborns, we determined SpO2. Subsequently, we measured the values of ScO2 and pcO2 from the same extremity. While withdrawing a capillary sample, we exerted multiple squeezing of the foot. The mean value of ScO2, pcO2, SpO2 and the difference between ScO2 and SpO2 were determined. RESULTS: Mean ScO2 value was 80.5 +/- 8.5%, pcO2 was 48.2 +/- 11.4 mm Hg and SpO2 was 98 +/- 1.9%. The difference between ScO2 and SpO2 values was 17.5 +/- 8.6% (t = 23.568; p = 0.000). CONCLUSION: There is a statistically highly significant difference between the values of ScO2 and SpO2. Having the knowledge of this difference can increase the accuracy of clinical evaluation and further diagnostics. Comparison in up-to-now conducted studies suggests that the squeezing of the foot for obtaining a capillary sample in relation to free blood outflow does not bear any significant influence on the resultant values of haemoglobin saturation.

Possible interactions of genetic and immuno-neuro-endocrine regulatory mechanisms in pathogenesis of congenital anomalies.

The process of organogenesis depends on genetic and environmental factors. Besides genetic background, congenital anomalies can also be influenced by micro environmental changes, which are related to maternal-foetal interactions followed by the production of cytokines, hormones, neurotransmitters, growth factors and biochemical mediators, and stress proteins. Pre-natal maternal stress, including infections, psychological stress and other teratogens, can influence a disregulation of maternal immune, endocrine and nervous systems, during pregnancy. This is a crucial condition for the abnormal growth and development of the foetus. Activated maternal immune system can alter the cytokine network and make it inadequate for normal embryogenesis and organogenesis. Heat-shock proteins play an important role in stress physiology repairing DNA errors or activating pro-inflammatory response. Regarded from this aspect, the altered cytokine network suggests aetiopathogenetic basis of congenital anomalies in neonates. It is our wish to point out our potentially harmful conditions in the development of congenital anomalies, as well as their control by using pre-natal and pre-conceptional diagnostics and treatment.

[Initial antibiotic therapy of neonatal sepsis]. / Inicijalna antibiotska terapija neonatusne sepse.

It is certain that in the past the types of bacterial agents responsible for neonatal sepsis and their sensitivity to antibiotics were not the same in all historical periods. However, the reports confirming the conclusion have been published only in the last three years. According to these facts, the bacterial causes of neonatal sepsis were analyzed in patients treated at the University children's hospital in Belgrade (S&M) as well as their sensitivity to antibiotics to determine the most effective initial therapy. Between January 2001 and June 2004, 35 neonates, aged from 1-30 days, with positive blood culture were treated. Gram-negative bacteria were the cause of sepsis in 57% of patients (Pseudomonas--20%, Klebsiella--20%, E. coli--8.5%, Acinetobacter--8.5%), gram-positive in 43% (coagulase-negative Staphylococci--14%, Staphylococcus epidermidis--14%, Staphylococcus aureus--9%, Streptococcus group B--3%, Listeria monocytogenes--3%). The bacteria were the most sensitive to carbapenems (85-89%), amikacin (68%), third-generation cephalosporins (47-50%), while the sensitivity to gentamicin was less than expected (48.5%). Sensitivity to ampicillin (8%) confirmed a high level of resistance to this antibiotic. All isolated Staphylococci were sensitive to vancomycin, and the overall methicillin resistance was 46%. Combined cefotaxime and amikacin therapy was the most effective of all suggested initial combinations of antibiotics (74%). The sensitivity to all other combinations of antibiotics was 51-71%. The most adequate initial combination of antibiotics for the treatment of neonatal sepsis is cefotaxime plus amikacin. The most adequate antibiotic for the treatment of nosocomial neonatal sepsis is carbapenem.

[Persistent hyperinsulinemic hypoglycemia of the neonate]. / Perzistentna hiperinsulinemijska hipoglikemija novorodjenceta.

Persistent hyperinsulinemic hypoglicemia of the neonate is a rare heterogenous disease (clinically, histologically, metabolically and genetically), which is characterized by inadequatly high insuline rates in the presence of severe hypoglicemia. Hyperinsulinism, rather a syndrome than a disease, of which the main metabolic feature is hypoglicemia and decreased concentration of free fatty acids and ketones in serum (insulin inhibits lypolisis and synthesizes ketonic bodies), presents a major diagnostic and therapeutic chalenge. The disease is often followed by brain atrophy contributed by the attacks of hypoglicemia. It is inherited as an autosomally recessive and autosomally dominant disease. The genetic defects is located on the short arm of the chromosome 11. The authors report a successfully applied conservative treatment in a neonate with persistent hyperinsulinemic hypoglicemia.

[Nonclassic congenital adrenal hyperplasia resulting from 21-hydroxylase deficiency]. / Neklasicna kongenitalna adrenalna hiperplazija uzrokovana deficitom 21-hidrosilaze.

Nonclassic CAH, also termed as late onset of CAH, is a very mild form of 21-hydroxylase deficiency. The incidence of disease is estimated at 0.1% of population. Nonclassic CAH is usually diagnosed in the childhood before the age of 6 to 8 years as premature pubarche. The disease is not common in the infants and usually not before 6 to 8 months. This is a case report of 7-month female infant who was suspected of mild hyperandrogenism because of premature pubarche. The diagnosis was confirmed by mild basal elevation of 17-OHP (5.55 ng/ml) and characteristic hyper-response to ACTH, reaching values of 21 ng/ml, as well as accelerated bone maturation. The conventional treatment of NCAH was initiated, with glucocorticoid therapy (hydrocortisone) for one year and a half. After that period, our decision was to discontinue the hormonal therapy because of the impression that hyperandrogenism was mild (mild deficiency of the enzymes for steroid hormone synthesis). Child's growth, development and maturation are under constant control.

[Rubinstein-Taybi syndrome]. / Rubinstajn-Tejbijev sindrom.

Rubinstein-Taybi syndrome is a malformation occurring with approximate incidence of 1 per 10,000 live-born children. The diagnosis is usually based on specific facial dysmorphism in neonatal period, as well as on characteristic deformities of the hands and feet. Our study presents a male child who was diagnosed to have Rubinstein-Taybi syndrome when he was one month old. The child had all characteristic clinical features. In further follow-up period, corrective surgery and control of his psychomotor development are being planned.