About one half of medical products licensed in EuropeanUnion have not been clinically tested in pediatricpopulation. It causes frequent use of unlicensedmedicines or “off-label” use of medicines, especially inneonates and children under 2 years of age. This situationleads to increase risk of adverse events, and manymedical, ethical and legal problems. In case of vaccines,“off-label” use involves age, number of doses, timing ofvaccination, and utilisation of vaccines in specific riskgroups, such as preterm infants, immunocompromisedand chronicaly ill children. New initiatives on Europeanlevel are directed to change the current situation andto extend the area of clinical evaluation of medicinalproducts in pediatric population.

Over the last decades rapid and global increaseof the incidence of type 1 diabetes, mainly in children,was noticed in most European countries. Multiplemechanisms of β-cell destruction were considered asa reason. Despite of the known genetic predispositiononly environmental factors can explain such a rapidchange “The burden of diabetes”, as well in Poland,requires fast solutions in public health, social and economicprograms.

Monogenic diabetes are a heterogenic group of diseaseswith varied phenotypes. It is assumed that theymay total up to 10% of all cases of diabetes. Diagnosisof these clinical conditions by an efficient selection ofpatients for genetic diagnostics may be problematiceven for experienced diabetologists. This paper focuseson key aspects of these guidelines and elucidatescrucial features of the clinical picture which canbe used for differential diagnosis of diabetes. Amongfactors suggesting monogenic background of diabetesthe most notable are: low daily insulin requirement(<0,5 U/kg), moderate hyperglycemia (5,5–8,5 mmol/l),positive familial history with a dominant pattern ofinheritance, lack of immunologic markers typical fortype 1 diabetes and presence of structural or functionalabnormalities within other organs and systems. Theseincongruities have been resolved by the authors of thispaper with added suggestions of how to implement relevant solutions in clinical practice. In this article currentguidelines on the treatment of monogenic diabetesin children were also presented. Current therapeuticstandards were taken into consideration as well asprospects for causal treatment of selected forms ofmonogenic diabetes in children.

Diabetic ketoacidosis (DKA) is a main cause of death intype 1 diabetic children and adolescents. DKA resultsfrom absolute or relative deficiency of circulating insulin.The risk of DKA is increased at the onset of diabetes,in children with poor metabolic control and in patientswith acute infections. The diagnostic and therapeuticguidelines were elaborated by the group of internationalexperts and published in ISPAD Clinical PracticeConsensus Guidelines 2009 Compendium.The mortality rate from DKA in children is from 0.15% to0.30%. The death is mainly caused by cerebral edema.DKA prevention is essential. Children and adolescentswith DKA should be managed in centers experiencedin its treatment.

The aim of the treatment is to achieve and maintainblood glucose levels as close as possible to the normalrange to prevent long-term complications and to minimizethe risk of acute complications in type 1 diabeticchildren and adolescents. The substitution of insulinshould be based on the methods of intensive insulintherapy. Continuous subcutaneous insulin infusion(CSII) by external insulin pumps has been used in clinicalpractice for several years. CSII is the most physiologicalmethod of insulin delivery currently available.This review briefly summarizes the guidelines of insulinpump therapy in type 1 diabetic children. The initiatingof therapy and its complications were presented.The pediatric team experienced in CSII is required toinitiate pump therapy and to supervise the ongoingmanagement of children on pump therapy. The patientsand theirs families should be carefully educated on theprinciples of CSII. The cooperation between pediatricdiabetes team and patients and theirs caregivers isnecessary to achieve the benefits of CSII.

Hypoglycemia is one of the most common complicationsof the management of type 1 diabetes. Mostdiabetic patients and their caregivers fear hypoglycemiamore than they care about potentially disablingchronic complications of the disease. Therefore, despitedevelopment of new insulin preparations, progress intechnologies of blood glucose measurement and monitoringand in insulin injection and continuous insulindelivery systems, hypoglycemia is still the critical limitingfactor preventing type 1 diabetic patients fromachieving good glycemic control. In this paper we presentcurrent opinion on: 1) assessment and classificationof hypoglycemia in children and adolescents with type1 diabetes, 2) factors associated with increased risk ofsevere hypoglycemia, 3) treatment of hypoglycemia and4) principal rules of hypoglycemia prevention.

In 1999 a new classification for diabetes mellitus-basedon etiology- was suggested. According to the classification,type 1 diabetes was subclassified as type 1A (autoimmune)and type 1B (idiopathic). Both forms resultfrom the destruction of b cells leading to impairmentof insulin synthesis, however in type 1A the process isimmune-mediated but in type 1B the origin of the bcells impairment is still unknown. Besides subtype Bis considered to be very heterogeneous and diagnosticcriteria are still not clear. The purpose of this articlewas to review studies of pathogenesis of idiopathicType 1 diabetes.

Surgical procedure in diabetic patient disturbs endocrinehomeostasis and could result in acute hyperglycemiaand its metabolic consequences. Moreover,perioperative hyperglycemia is connected with excessiverisk of wound infection and problems with woundhealing. The best method to maintain normoglycemiais continuous intravenous insulin therapy but in somecases other methods of treatment may be useful. Toachieve the best possible metabolic control in diabeticpatients in perioperative period international guidelinesare being established. The aim of this article is to gathercurrent recommendations in this subject.

Obesity is one of the most important problems of publichealth. The succeeding years bring evidence for increasingrole of genetic factors in the development ofobesity. The review of current information on ways ofinheritance of obesity was presented in this study. Themonogenic and polygenic disturbances that lead to theobesity development were presented. Possible epigeneticdisturbances were described that can contribute tothe pathogenesis of obesity and also probable furthertrends in research on genetic background of obesity.

In the last decades a constant increase in an incidenceof inflammatory bowel disease in children has beenobserved. Many factors participate in the etiopathogenesisof the disease. The key role is played by geneticpredisposition, which leads to overreaction of immunesystem of mucosa of the alimentary tract against saprophyticbacterial flora or other environmental factors.Disturbed immune response against an unknown antigencauses the disturbance of the balance betweenpro- and anti-inflammatory factors in intestinal mucosaor in the whole intestinal wall. Many studies emphasizethe role of cytokines in regulation, induction and suppressionof inflammation as well as in reparation ofthe intestinal mucosa. Constant progress in the understandingof etiopathogenesis of inflammatory boweldisease leads to the change the modes of treatmentand to introduction of new therapeutic methods in thetreatment of inflammatory bowel disease. Among thesemethods there is a biological treatment which includesmonoclonal antibodies against TNF-α, neutralizationof anti-adhesive molecules and recombined cytokines.In spite of a significant progress, the treatment of inflammatorybowel disease is still difficult. The presentpossibility of the use of biological treatment showsa significant progress. It is expected that in the futurethe early prevention of the disease in genetically predisposedsubjects could be achieved by the application ofgenetic therapy and modulation of intestine ecosystem.

Symptoms of depression are present in 40 to 60 percentof patients with epilepsy. Prior research indicatedsignificant correlation between the prevalence of focalseizures and clinical depression, especially in patientswith temporal lobe epilepsy. Anticonvulsive drugs andpsychosocial factors contribute to the occurrence ofdepression as well. Moreover, some less specific factorswere found to act upon mood of patients with epilepsy,like those typical for chronic diseases in general (i.e.feeling of isolation and social withdrawal) and individualsusceptibility to depression. There is substantialevidence that some basic mechanisms are similar indepression and epilepsy. Emotional states of high intensityevoke changes in neurotransmission and inversely,changes in neurotransmission evoked by seizures, localizedin specific brain regions predispose and intensifyemotional disturbances. It seems to be correlated withcertain types of epileptic seizures with high frequencyof seizures, sub-optimal pharmacologic treatment andlack of occupational and social activity. Depression inpatients with epilepsy is a serious medical and socialproblem since it afflicts almost a half of all patientstreated in the epilepsy referral centers.

Tick-borne encephalitis (TBE) is a disease of centralnervous system caused by tick-borne virus, belongingto Flavoviridae family. During last years in majorityof European countries the increased incidence of thedisease has been observed. In Poland the greatestnumber of disease cases are reported seasonally fromeastern-north part. Following unspecific flu like symptomsof the first phase, potentially fatal neurologicalsecond phase appears. There is no specific treatmentof infection. Vaccination campaign against tick-borneencephalitis in Austria resulted with decreased incidence.

Background. Long lasting safety and efficacy studiesare necessary before the new medication is registeredand become commercially available. These studies involveinvestigators – physicians and general practitioners.Aim of the study. The aim of the study is to describethe medication development process and to discussdifferent types of clinical trials conducted to assessefficacy and safety of drugs.Discussion. The time from the discovery of the substancewith possible therapeutic potency to its registrationas a medication with proven safety and efficacyvaries from 12 to 15 years. The medication developmentprocess includes: the basic studies which determine thesubstance characteristic; animal model preclinical studieswhich determine basic pharmacokinetics and toxicityand four phases of the human studies evaluatingsafety and efficacy. The paper describes the differencesamong particular phases and types of clinical studies.The following types of the studies were discussed: interventionaland noniterventional, single center and multicenterstudies, retrospective and prospective trials,randomized, controlled and open studies, blinded trials,kohort, cross-sectional, and case-control studies, etc.Conclusions. The knowledge about the medication developmentprocess and different types of clinical studiesis necessary for proper understanding of medicationevaluation methodology and for proper interpretationof the data published in medical literature.

Hypersensitivity on hymenoptera is a worldwide problemnot only for sensitized patients, but also for theirphysicians. Knowledge about proper medical interventionafter stinging and guidelines of qualification forimmunotherapy has influence on number of deathsin children. Authors described medical and diagnosticintervention in case of suspected sensitization on hymenopteravenom.

The article focuses on diagnostic difficulties of vitaminD-dependent rickets type I.Authors present case report, describe the clinical, biochemical,radiological aspects, differential diagnosis ofgenetic rickets, which is characterized by no response toa dose of vitamin D that would cure vitamin D deficiency.

Measurement of serum immunoglobulin levels ( IgG,IgA and IgM ) is one of the basic method in the assessementof the immune status of healthy and sickpeople. Low levels of immunoglobulins are observed inprimary and secondary immunodeficiencies. High immunoglobulinlevels are observed in infections, chronicallergic and inflammatory disorders, some immunodeficiencyand haematological diseases. In contrast toIgG, IgA and IgM, measurement of IgD serum level inclinical practice should be limited to specific indicationsas diagnosis of periodic fever syndromes and IgDmyeloma. Determining of the age-specific referencerange for immunoglobulins is essential for correct interpretationof individual results. Within last decadessignificant changes in environment, better social andeconomic conditions and improvement of health care potentially could influence the immunological status ofhealthy population, particularly of children. The aim ofthe study was to determine the actual reference valuesfor immunoglobulins in healthy children and adults.In total, we analysed IgG, IgA, IgM and IgD levels in285 individuals including 242 children, 18 adults and25 cord blood samples obtained from inhabitants ofMazovia district. The results were analysed in twelveage-dependent groups. The geometric means accompaniedby 5 and 95 percentile for each immunoglobulinwere calculated.