Contemporary drug discovery and development (DDD)process is extremely complex from scientific, technical,legal and economic point of view, and its final outcomeis determined in very costly and sometimes inconclusiveclinical trials. Overview of the process is presentedfrom chemical angle, with focus on molecular structureas determinant of substance properties, and ever increasingrole of chemo- and bioinformatics in designsegment. In development part, evolution of manufacturingprocess towards total quality management byon-line analytical control is pointed out, in view of currentregulatory guidances.

Analgesia and sedation are important components ofpostoperative care in children. This paper describespostoperative analgesia and sedation practice in PediatricIntensive Care Unit II (PICU II) of Childrens’ MemorialHealth Institute in Warsaw and analgesia/sedationprotocols based on assessment of patients’ conditionand predicted postoperative course. The mainstay ofdeveloped protocols is analgesia-based sedation.

Acute liver failure (ALF) in infants is rare but severe conditionwith poor prognosis. Causes of ALF in infants andadults differ a lot. Additionally, clinical encephalopathymay not be present in young children. Authors analyzedthe main causes of ALF in infants such as acuteviral hepatitis, inherited metabolic disorders (includingmitochondrial respiratory chain disorders, tyrosinemiatype I, neonatal hemochromatosis, galactosemia,hereditary fructose intolerance, fatty acid oxidationdefects, urea cycle disorders and haemophagocyticsyndrome).Infants with ALF should only be treated in specializedpediatric centers with access to liver transplantation.Orthotropic liver transplantation provides no survivaladvantage in children with multisystem illness due tomitochondrial DNA depletion syndrome, but it may beconsidered in children with isolated liver disease. Livertransplantation is contraindicated in primary haemophagocyticsyndrome.

The use of probiotics is receiving increased attentionin many areas of medicine. However, currently, thereis both true and misleading information surroundingprobiotics that is widely believed by both parents ofchildren and the health care professionals who carefor them. The consequences of these misconceptionsinclude the use of inappropriate probiotics and/or theuse of probiotics in the wrong clinical situation. In orderto help caregivers make informed decisions, this articlesummarizes evidence from randomized controlled trialsand meta-analyses on the effectiveness of probioticspublished in 2010. The availability of the probiotic microorganismsand preparations in Poland and/or themagnitude of the problem guided the choice of datafor presentation here.

Superficial fungal infections in children are mostlycaused by dermatophytes and yeasts. Dermatophytemycoses in children manifest in the majority as scalpand glabrous skin infections, however more common(comparing to adults) fungal infections of nails are observedin these patients. Infections caused by yeaststhe most often occur as intertrigo lesions in skin foldsand as characteristic changes on oral mucous membranes.The clinical diagnosis of mycosis requiresa laboratory confirmation, because its symptoms aresimilar to other dermatological disorders. In the studyepidemiological and clinical aspects of the most commondermatophyte and yeast mycoses in children werediscussed. A brief outline of epidemiological conditioningsand modern treatment capabilities of superficialmycoses in children were also presented.

Molds are multicellular fungi that are ubiquitous inoutdoor and indoor environments. Exposure to moldscan occur through inhalation, ingestion, and touchingmoldy surfaces. Alternaria alternata is the most allergenicfungus, despite the fact that is not the mostintensive. Allergenic activity of fungus depends onspores appearance in the air and other fungus parts(moved to dust). The molds are known to play the rolein asthma, allergic rhinitis, allergic bronchopulmonaryaspergillosis, sinusitis, and hypersensitivity pneumonitis.Sensitization to fungi has been linked to the presence,persistence, and severity of asthma. In this reportwe examine all allergenic aspects of mold exposure tochildren.

Background. Urea Breath Test (UBT) is a simple, noninvasivetest assuming status of H. pylori infection. Verylimited data concerning its specifity and sensivity inpolish pediatric population is currently available.Aim. The aim of the study was to evaluate specifity,sensivity, positive predictive value (PPV) and negativepredictive value (NPV) of UBT in children.Material and Methods. 83 children aged 12,1 ±3,8[mean ±SD], 43F, 40M were involved to the study andhad UBT performed. Patients had also gastroscopy withrapid urea test and sampling for culture and histologicalexamination for H. pylori. Patient was regarded asH. pylori positive if:nn culture was positiveand/ornn rapid urea test and histological examination wereboth positive.The UBT results were compared to patient H. pyloristatus.Results. 48 out of 83 (58%) patients had H. pylori infection.UBT sensivity was 0,92 (0,80 to 0,98) (95% CI),specifity 0,91 (0,77 to 0,98), PPV 0,94 (0,82 to 0,99), NPV0,89 (0,74 to 0,97). Conclusion. UBT is senitive and specific test to diagnoseH. pylori infection in children.

Skeletal muscle has been recognized as an endocrineorgan able to produce, express and release myokines(cytokines produced by muscles). The discovery ofmyokines shed a light on the role of regular physicalactivity as the non-pharmacological intervention orprophylaxis for several chronic disorders. To date thelist of myokines includes IL-6, IL-8, IL-15, BDNF. Recentdata have revealed that myokines are able to reduceinflammation, increase lipolysis, increase glucose uptake,stimulate angiogenesis. Myokines are involved inmediating the health beneficial effects of exercise andplay important role in the protection against chronicdisorders associated with metabolic or neurodegenerativechanges.

Neutrophil gelatinase-associated lipocalin (NGAL) isa 25 kDa protein from the lipocalin superfamily, thatis involved in many biochemical processes in humanbody. Low expression of the NGAL can be observed inhealthy human tissues (e.g. digestive tract, kidney etc.),however in the injured epithelial cells NGAL expressionincreases, that results in significant rise of the proteinconcentration in blood and urine of the patients. Basedon the recent literature, this paper aims to presentNGAL as a new and early marker in kidney and heartdiseases, cancer, metabolic syndrome and diabetes.

In the article we focused on clinical utility of total parathormone(total PTH) and its subfractions PTH 1-84(CAP) and PTH 7-84 (CIP) determination, basing on currentliterature and our own experience. CIP subfractionacts like an antagonist against CAP subfraction inthe target tissues. Also we discussed available laboratorymethods of PTH assaying and special situationsin which PTH results require particular caution fromthe clinician.

Background. Utilization of unregistered medicinalproducts in pediatric population (off-label drug use)is related with increased incidence and severity of theadverse drug reactions. It was indicated in the guidelinespublished by American Academy of Pediatrics thatit is unethical to limit children’s access to the existingand new medicinal products and that it is shared responsibilityof pediatricians, pharmaceutical industryand regulatory authorities to conduct relevant studieswhich also should be supported by the general public.Following these recommendations, during past two decadesseveral new law regulations were developed topromote clinical studies in pediatric population.Aim of the study. The aim of the study was to presentthe review of international law regulations pertainingconducting clinical studies in children, with special considerationof European Union regulations.Discussion. The first regulations promoting clinicalstudies in children were published in the United Statesin the 90-ies of the past century. They were followedby the Regulation (EC) No 1901/2006 (as called as PaediatricRegulation) which is fully implemented since Jan2009. The key elements of Paediatric Regulation includeobligation of pharma companies to develop and implementPaediatric Investigational Plans (PIP), setting upPaediatric Committee (PDCO) and European PaediatricResearch Network (EnprEMA)Conclusions. During past years several internationallaw regulations have been implemented to promoteclinical studies of medical products for children by defining both formal requirements and system of incentivesfor pharma companies investigating pediatricproducts. Waiting for positive long term effectsof Paediatric Regulations it is necessary to monitorthe efficacy of the new procedures and the way theyare followed by the pharmaceutical industry and competentauthorities. Further development of EuropeanPaediatricResearch Network (EnprEMA) and local pediatricnetworks should be supported by active participationof pediatric environment.

Causes of upper gastrointestinal bleeding in childrenare analyzed in concern of clinical course and therapeuticapproach. 352 children (150 girls) aged 1 month to 17years admitted to the Department of Gastroenterology,Hepatology and Immunology of the Children’s MemorialHealth Institute for upper gastrointestinal bleedingfrom 1980 to 2000 were included into the study.The assessment was based on retrospective analysisof patients’ documentation.The majority of patients presenting with gastrointestinalbleeding were school children (31.8%), infants(8.8%) and teenagers (10%) presented rarely to theclinic. The most common cause of bleeding were oesophagealvarices (71.8%). Recurrent bleeding wasvery common (50%). Most of the children were in intermediategeneral condition (56.8%) at the momentof admission. In older children (preschool, school andteenagers) bleeding was successfully managed within24h. In younger ages treatment had to be continuedfor several days.

Objectives: Cryosurgery (derived from the Greek wordkry’os – cold, ice) is a method of local therapy whichdepends on the targeted destruction of diseased tissueby applying low temperatures. Use of cold have beenused for many years in dermatology in the treatmentof numerous skin diseases, such as cutaneous carcinomas,precancerous states, viral skin and oral mucosadiseases. The article presents results of treatment ofthe chosen skin conditions by means of cryosurgeryin patients treated at the Dermatological OutpatientDepartment.Material and Methods: Cryosurgery was performedin 501 patients in whom a total number of 1212 procedureswithin the pathological foci were carried out. Thepatients had common warts, foot warts, flat and seborrhoeicwarts, solar keratosis, and other dermatoses.Results: Very good results of the treatment wereachieved. Regression of pathological lesions was observedin 90% of patients. Only in 10% another methodof therapy had to be applied and concerned the casesof the basal cell epithelioma and foot warts.Conclusions: Cryosurgery with the use of liquid nitrogenis a valuable method of treatment of differentdermatological diseases; adverse effects are transientand occur only scarcely. Low treatment costs and the possibility of applying cryosurgery in ambulatory conditionsare a big advantage of the method, which is ofimportance especially to the elderly patients.