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In the dynamic realm of business, ethics serves as a critical compass, guiding the delineation between right and wrong actions. Gaining momentum as a focal point within organisational discourse, the concept of ethics has burgeoned into a cornerstone element of corporate identity and operations.

Purpose: We investigated the impact of anthracycline-based chemotherapy on methylation status of RB1 gene in peripheral blood leukocytes together with parameters of oxidative stress and inflammation in sarcoma patients., Patients/methods: Blood samples were collected from 51 consecutive newly diagnosed sarcoma patients admitted to University Hospital Center Zagreb (Zagreb, Croatia) for first-line chemotherapy before the first cycle and post-chemotherapy. Methylation and copy number variation (CNV) of leukocyte RB1 gene were assessed using MS-MLPA probes. In addition, in blood samples, parameters of oxidative stress (ROS, MDA, SOD, and GSH) and inflammation (CRP, WBC, and NBC) were followed., Results: In pre-chemotherapy samples, no CNVs and aberrant methylation of CpG106 promoter region of RB1 gene were detected; however, one patient had hypermethylation (by approximately 10%) of imprinted locus CpG85 in intron 2 of RB1 gene. In addition, a very good correlation of the tumor burden and CRP and tumor burden and GSH was found. The anthracycline-based chemotherapy reverts methylation of RB1 gene-imprinted locus CpG85 to normal level. Moreover, inflammation and oxidative stress parameters such as CRP, WBC, ROS, and MDA were significantly decreased in post-chemotherapy samples., Conclusion: This single-centered study on a cohort of consecutive sarcoma patients indicates that sarcoma patients can have aberrant germline DNA methylation and confirms the relationship of tumor burden with inflammation and oxidative stress. The applied chemotherapy protocols reverted RB1 gene methylation to normal level and decreased the level of inflammation and oxidative damage, thus indicating chemotherapy benefit to the patient's health status., (© 2024. The Author(s), under exclusive licence to Federación de Sociedades Españolas de Oncología (FESEO).)

The virus SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus 2) is capable of attacking the nervous system in several ways and leading to neurological diseases such as GBS (Guillain-Barré syndrome) through the resulting neurotropism and immune response. The aim of this study is to show the relationship between Coronavirus disease (COVID-19) and GBS and to better understand the clinical symptoms to prevent poor outcomes. Data from 15 patients were extracted from the Department of Neurology, University Hospital of Split, Croatia, for the year 2021. The age of the patients ranged from 26 to 89 years, of whom 27% were women. Sixty seven percent of all GBS patients recovered from COVID-19 infection, whereas post-vaccinal polyradiculoneuritis was detected in 6%. Forty four percent of the patients who developed GBS had a severe form of COVID-19 infection. Forty percent of patients were treated with intravenous immunoglobulins (IVIG), followed by therapeutic plasma exchange (PLEX) in 27%. After the therapy, improvement was observed in 13 patients, while two patients died. The results suggest that SARS-CoV-2 triggers GBS because it follows a similar pattern of infection as the other viral and bacterial agents that contribute to the onset of GBS. There is no evidence that prior infection with COVID-19 worsens the clinical presentation of GBS.

Fluoropyrimidines (FPs) are antineoplastic drugs widely used in the treatment of various solid tumors. Nearly 30% of patients treated with FP chemotherapy experience severe FP-related toxicity, and in some cases, toxicity can be fatal. Patients with reduced activity of DPD, the main enzyme responsible for the breakdown of FP, are at an increased risk of experiencing severe FP-related toxicity. While European regulatory agencies and clinical societies recommend pre-treatment DPD deficiency screening for patients starting treatment with FPs, this is not the case with American ones. Pharmacogenomic guidelines issued by several pharmacogenetic organizations worldwide recommend testing four DPD gene ( DPYD ) risk variants, but these can predict only a proportion of toxicity cases. New evidence on additional common DPYD polymorphisms, as well as identification and functional characterization of rare DPYD variants, could partially address the missing heritability of DPD deficiency and FP-related toxicity.

Focal laryngeal dystonia (LD) is a rare, idiopathic disease affecting the laryngeal musculature with an unknown cause and clinically presented as adductor LD or rarely as abductor LD. The most effective treatment options include the injection of botulinum toxin (BoNT) into the affected laryngeal muscle. The aim of this narrative review is to summarize the patho-neuro-physiological and genetic background of LD, as well as the standard recommended therapy (BoNT) and pharmacological treatment options, and to discuss possible treatment perspectives using neuro-modulation techniques such as repetitive transcranial magnetic stimulation (rTMS) and vibrotactile stimulation. The review will present two LD cases, patients with adductor and abductor LD, standard diagnostic procedure, treatments and achievement, and the results of cortical excitability mapping the primary motor cortex for the representation of the laryngeal muscles in the assessment of corticospinal and corticobulbar excitability.

Aims: Cancer patients with reduced dihydropyrimidine dehydrogenase (DPD) activity are at increased risk of severe fluoropyrimidine (FP)-related adverse events (AE). Guidelines recommend FP dosing adjusted to genotype-predicted DPD activity based on four DPYD variants (rs3918290, rs55886062, rs67376798 and rs56038477). We evaluated the relationship between three further DPYD polymorphisms: c.496A>G (rs2297595), *6 c.2194G>A (rs1801160) and *9A c.85T>C (rs1801265) and the risk of severe AEs., Methods: Consecutive FP-treated adult patients were genotyped for "standard" and tested DPYD variants, and for UGT1A1*28 if irinotecan was included, and were monitored for the occurrence of grade ≥3 (National Cancer Institute Common Terminology Criteria) vs. grade 0-2 AEs. For each of the tested polymorphisms, variant allele carriers were matched to respective wild type controls (optimal full matching combined with exact matching, in respect to: age, sex, type of cancer, type of FP, DPYD activity score, use of irinotecan/UGT1A1, adjuvant therapy, radiotherapy, biological therapy and genotype on the remaining two tested polymorphisms)., Results: Of the 503 included patients (82.3% colorectal cancer), 283 (56.3%) developed grade ≥3 AEs, mostly diarrhoea and neutropenia. Odds of grade ≥3 AEs were higher in c.496A>G variant carriers (n = 127) than in controls (n = 376) [OR = 5.20 (95% CI 1.88-14.3), Bayesian OR = 5.24 (95% CrI 3.06-9.12)]. Odds tended to be higher in c.2194G>A variant carriers (n = 58) than in controls (n = 432) [OR = 1.88 (0.95-3.73), Bayesian OR = 1.90 (1.03-3.56)]. c.85T>C did not appear associated with grade ≥3 AEs (206 variant carriers vs. 284 controls)., Conclusion: DPYD c.496A>G and possibly c.2194G>A variants might need to be considered for inclusion in the DPYD genotyping panel., (© 2021 British Pharmacological Society.)

DNA accessibility of cis -regulatory elements (CREs) dictates transcriptional activity and drives cell differentiation during development. While many genes regulating embryonic development have been identified, the underlying CRE dynamics controlling their expression remain largely uncharacterized. To address this, we produced a multimodal resource and genomic regulatory map for the zebrafish community, which integrates single-cell combinatorial indexing assay for transposase-accessible chromatin with high-throughput sequencing (sci-ATAC-seq) with bulk histone PTMs and Hi-C data to achieve a genome-wide classification of the regulatory architecture determining transcriptional activity in the 24-h post-fertilization (hpf) embryo. We characterized the genome-wide chromatin architecture at bulk and single-cell resolution, applying sci-ATAC-seq on whole 24-hpf stage zebrafish embryos, generating accessibility profiles for ∼23,000 single nuclei. We developed a genome segmentation method, ScregSeg (single-cell regulatory landscape segmentation), for defining regulatory programs, and candidate CREs, specific to one or more cell types. We integrated the ScregSeg output with bulk measurements for histone post-translational modifications and 3D genome organization and identified new regulatory principles between chromatin modalities prevalent during zebrafish development. Sci-ATAC-seq profiling of npas4l / cloche mutant embryos identified novel cellular roles for this hematovascular transcriptional master regulator and suggests an intricate mechanism regulating its expression. Our work defines regulatory architecture and principles in the zebrafish embryo and establishes a resource of cell-type-specific genome-wide regulatory annotations and candidate CREs, providing a valuable open resource for genomics, developmental, molecular, and computational biology., Competing Interests: The authors declare no competing interests., (© 2021 The Authors.)

Metastatic involvement of the breast is far less common than primary breast carcinoma, comprising 0.5%-6.6% of all breast malignancies. Malignant pleural mesothelioma (MPM) is a rare and aggressive tumor with higher incidence among men, particularly smokers, strongly associated with asbestos exposure. The epithelioid type of MPM can represent a diagnostic pitfall in this setting, as it shows similar histologic features to primary breast carcinoma as well as other metastatic epithelioid malignancies. We report a rare case of breast metastasis of malignant pleural mesothelioma in a 61-year-old female., (© 2020 Wiley Periodicals LLC.)

Background: Histomonosis, caused by the protozoan parasite Histomonas meleagridis, is a severe disease especially in turkeys where it can cause high mortalities. Recently, outbreaks were described in which turkey hens showed no clinical signs despite high mortalities in toms, from which they were separated only by a wire fence. The present study investigated three similar outbreaks of histomonosis whereby in two of them only a few hens were being affected and none in the third. Hens from all flocks were kept until end of production and slaughtered as scheduled. However, in all three cases, the disease progressed in toms reaching nearly 100% within two weeks., Methods: Following diagnosis of the disease, tissue samples were obtained from toms and hens at necropsy. Environmental dust, cloacal swabs and blood were taken on three successive farm visits within compartments of hens and toms and tested by real-time PCR or ELISA. The DNA from a total of 18 samples positive for H. meleagridis was further subjected to conventional PCR utilizing the 18S rRNA primers and sequenced for phylogenetic analysis., Results: All tissue samples and some cloacal swabs were tested positive. Dust samples confirmed the presence of H. meleagridis DNA that spread within entire houses up to 6 weeks after the first clinical signs of histomonosis. Sequence analysis of the 18S rRNA locus demonstrated the presence of the same strain in birds of both sexes within each of the turkey houses. Investigation of serum samples two weeks post-initial diagnosis and prior to euthanasia resulted in antibody detection in 73% of toms and 70% of hens. Until the end of the investigation the number of positive hens per farm increased up to 100% with mean OD-values approaching those noticed in toms prior to euthanasia., Conclusions: For the first time it could be demonstrated that turkey hens kept in the same house as toms became infected during fatal outbreaks in toms. This highlights the value of different diagnostics methods in order to trace the parasite in connection with the host response. The strange phenomenon that only single hens succumb to the diseases despite being infected requires further investigations.

Dear Editor, Inhibition of the epidermal growth factor receptor (EGFR) is a new strategy in treatment of a variety of solid tumors, such as colorectal carcinoma, non-small cell lung cancer, squamous cell carcinoma of the head and neck, and pancreatic cancer (1). Cetuximab is a chimeric human-murine monoclonal antibody against EGFR. Cutaneous side effects are the most common adverse reactions occurring during epidermal growth factor receptor inhibitors (EGFRI) therapy. Papulopustular rash (acne like rash) develop with 80-86% patients receiving cetuximab, while xerosis, eczema, fissures, teleangiectasiae, hyperpigmentations, and nail and hair changes occur less frequently (2). The mechanism underlying these skin changes has not been established and understood. It seems EGFRI alter cell growth and differentiation, leading to impaired stratum corneum and cell apoptosis (3-5). An abdominoperineal resection of the rectal adenocarcinoma (Dukes C) was performed on a 43-year-old female patient. Following surgery, adjuvant chemo-radiotherapy was applied. After two years, the patient suffered a metastatic relapse. Abdominal lymphadenopathy was detected on multi-slice computer tomography (MSCT) images, with an increased value of the carcinoembryonic antigen (CEA) tumor marker (maximal value 57 ng/mL). Hematological and biochemical tests were within normal limits, so first-line chemotherapy with oxaliplatin and a 5-fluorouracil (FOLFOX4) protocol was introduced. A wild type of the KRAS gene was confirmed in tumor tissue (diagnostic prerequisite for the introduction of EGFRI) and cetuximab (250 mg per m2 of body surface) was added to the treatment protocol. The patient responded well to the treatment with confirmed partial regression of the tumor formations. Three months after the patient started using cetuximab, an anti-EGFR monoclonal antibody, the patient presented with a papulopustular eruption in the seborrhoeic areas (Figure 1) and eczematoid reactions on the extremities with dry, scaly, itchy skin (Figure 2). Furthermore, hair and nail changes gradually developed, culminating with trichomegaly (Figure 3) and paronychia (Figure 4). The patient was treated with oral antibiotics (tetracycline) and a combination of topical steroids with moisturizing emollients due to xerosis, without reduction of EGFRI therapy and with a very good response. Trichomegaly was regularly sniped with scissors. Nail fungal infection was ruled out by native examination and cultivation, so antiseptics and corticosteroid ointments were introduced for paronychia treatment. During the above-mentioned therapy, apart from skin manifestations, iatrogenic neutropenia grade IV occurred, with one febrile episode, and because of this, the dose of cytostatic drugs was reduced. After 10 months of therapy, progression of the disease occurred with lung metastases, so EGFRI therapy was discontinued and the patient was given second-line chemotherapy for metastatic colorectal carcinoma. This led to gradual resolution of all aforementioned cutaneous manifestations. Since the pathogenesis of skin side-effects due to EGFRI is not yet fully understood, there are no strict therapy protocols. Therapy is mainly based on clinical experience and follows the standard treatments for acne, rosacea, xerosis, paronychia, and effluvium. The therapeutic approach for papulopustular exanthema includes topical and systemic antibiotics for their antimicrobial as well as anti-inflammatory effect, sometimes in combination with topical steroids. Topical application of urea cream with K1 vitamin yielded positive results in skin-changes prevention during EGFRI therapy, especially with xerosis, eczema, and pruritus (6). Hair alterations in the form of effluvium are usually tolerable, and if needed a 2% minoxidil solution may be applied. Trichomegaly or abnormal eyelash growth can lead to serious complications, so ophthalmologic examination is needed. At the beginning of the growth, regular lash clipping may reduce possibility of corneal abrasion (7,8). Nail changes can just be a cosmetic problem (pigmentary changes, brittle nails), and in the occurrence of paronychia or onycholysis (of several or all nails) they result in high morbidity and impair daily activities. Nail management should be started as soon as possible because of slow nail growth and the relatively long half-life of EGFRI. Combination of topical iodide, corticosteroids, antibiotics, and antifungals with avoidance of nail traumatization will yield the best results (9). EGFRI are potentially life prolonging therapies, and our goal as dermatovenereologists is to provide optimal patient care and improve their quality of life in a multidisciplinary collaboration with oncologists, radiotherapists, and ophthalmologists.

Interindividual variability in drug metabolism is an important cause of adverse drug reactions and variability in drug efficiency. Polymorphisms of cytochrome P450 (CYPs) genes have a significant effect on drug metabolism and toxicity. This review brings an update about how genetic polymorphisms of CYP2C8 and CYP2C9 enzymes affect the disposition and clinical outcomes of ibuprofen and diclofenac, two of the most common pain relievers. The most common side effects associated with the influence of CYP2C8*3 and CYP2C9*2*3 variants on ibuprofen and diclofenac pharmacokinetics are hepatotoxicity and gastrointestinal bleeding. CYP genotyping may therefore identify patients at increased risk of these adverse reactions, and these patients could have their doses adjusted or start receiving another NSAID that does not share the same metabolic pathways with ibuprofen or diclofenac. However, before genotyping is introduced into regular clinical practice, more research is needed to evaluate the effectiveness of this strategy in improving treatment with ibuprofen and diclofenac.

The use of epidermal growth factor receptor inhibitors (EGFRI) for the treatment of solid tumors is increasing due to elevated expression of epidermal growth factor receptors (EGFR) in the stimulation of tumor development. EGFR inhibitors have shown to be effective in the treatment of neoplasms of the head, neck, colon, and lung. Inhibition of EGFR may cause cutaneous reactions in more than 50% of patients. The most common skin manifestations are papulopustular lesions in the seborrhoeic areas (upper torso, face, neck, and scalp). Other cutaneous side effects include xerosis and hair and nail changes. The onset of eruption is usually within one to three weeks after starting therapy, although in some cases it may occur much later. All dermatologic side effects are reversible and generally resolve after adequate therapy. However, for a minority of patients side effects are severe and intolerable, demanding dose reduction or even interruption of therapy. A positive correlation has been demonstrated between the degree of cutaneous toxicity and the antitumor response. For dermatologists the goal is to provide treatment of symptoms, so that the patient may continue to benefit from the EGFRI therapy. However, frequent cutaneous manifestations, even though related to a better antitumor response, may limit use of the therapy considering the interference with patient quality of life. Early management of cutaneous side effects of EGFRI may prevent severe, extensive symptoms, the need for dose reduction, or antitumor therapy interruption. This indicates a dermatologist should play a role in early stages of treatment.

Walking limitation assessment in multiple sclerosis patients (MSPs) is a demanding task, especially in the clinical setting. The aim of this study is to correlate the visual analogue scale (VAS), a simple method for measuring subjective experience, with measures of walking ability used in clinical research of MS. The study included 82 ambulatory MSPs who have resided in the local community. The applied measures of walking ability were the following: the single-item and patient-rated Walking Ability Visual Analogue Scale (WA-VAS), the Expanded Disability Status Scale (EDSS), the 25-foot walk test (25FWT), the Six Spot Step Test (SSST), the 2 min timed walk (2 min TW), the Multiple Sclerosis Walking Scale-12 (MSWS-12), and step activity monitor accelerometer (SAM) during 7 day period. The SAM analysis included the average daily step count, the average steps/min of the highest 1 min of a day, and the average steps/min of the highest continuous 60 min of a day. The WA-VAS scores significantly and strongly correlated with EDSS (ρ = 0.679, P < 0.001), 25FWT (ρ = 0.606, P < 0.001), SSST (ρ = 0.729, P < 0.001), 2 min TW (ρ = -0.643, P < 0.001), MSWS-12 (ρ = 0.746, P < 0.001), average daily step count (ρ = -0.507, P < 0.001), average steps/min of the highest 1 min of a day (ρ = -0.544, P < 0.001), and average steps/min of the highest continuous 60 min of a day (ρ = -0.473, P < 0.001). Correlations between WA-VAS and measures of walking ability used in clinical research of MS were satisfactory. The results obtained in this research indicate that the WA-VAS could be an instrument for simple measurement of walking limitations in MSPs in the clinical setting.

Chronic recurrent multifocal osteomyelitis (CRMO) is an extremely rare and most severe form of chronic nonbacterial osteomyelitis of unknown etiology. Here we present the first case of a six-year-old girl in which was observed that the stress fracture mimic osteomyelitic foci in the course of CRMO.

Background: The aims of this paper are: 1) to present the data of systemic thrombolysis for ischemic stroke in five Croatian centers from July 2008 till January 2010; 2) to compare the results between centers and; 3) to compare data with previously published results from 2006 to 2008 period from our center, and with the data from SITS (Safe Implementation of Treatments in Stroke)., Methods: We retrospectively reviewed the medical data of thrombolysed patients in following hospitals: University Hospital Center Zagreb (91 patients), University Hospital Split (25 patients), University Hospital Osijek (22 patients), General Hospital Varaždin (21 patient), and General Hospital Zadar (7 patients)., Results: The "time to door" for all centers was 79.71±38.63 min, the "door to needle" period was 64.39±24.18 min. Systolic and diastolic blood pressures at admission were 158.65±27.72 and 90.18±15.03 mm Hg, respectively. Systolic and diastolic blood pressures measured immediately prior to administering rt-PA were 152.19±23.17 and 85.40±15.27 mm Hg, respectively. Initial median NIHSS score was 12, median NIHSS 2h post thrombolysis was 8, and 7th day after rt-PA treatment 4. Intracerebral hemorrhages or secondary hemorrhagic transformations occurred in 21 (12.65%) patients, among which nine were symptomatic. In a 4.5h time window total of 17 patients were thrombolysed. We did not find any differences in outcome between this group and group of patients thrombolysed in the 3h time-window. The group of patients older than 80 years had a worse outcome., Conclusions: According to our data, treatment with rt-PA is safe, feasible and effective for stroke patients in both university as well as regional hospitals having stroke units established. Organization of stroke units in regional hospitals, as well as systematic education of public health workers and neurologists, leads to the possibility for each patient to reach the nearest stroke unit and gets the thrombolytic therapy in the therapeutic time window., (Copyright © 2011 Elsevier B.V. All rights reserved.)

The primary goals of this study were to adapt the Quality of Life in Epilepsy Inventory-31 items (QOLIE-31) questionnaire to the Croatian language and to assess the translated questionnaire's psychometric properties. Translation/retranslation of the English version of the QOLIE-31 was done, and all steps for cross-cultural adaptation process were performed properly by an expert committee. Later, QOLIE-31 questionnaires and previously validated Short Form-36 (SF-36) outcome instruments were given to 200 patients with epilepsy. 172 patients (86%) responded to the first set of questionnaires, and 114 of the first time respondents (66%) returned their second survey. The two measures of reliability as internal consistency and reproducibility were determined by Cronbach alpha statistics and intraclass correlation coefficient, respectively. Concurrent validity was measured by comparing with a SF-36 questionnaire, and measurement was made using the Pearson correlation coefficient (r). The study demonstrated satisfactory internal consistency with high Cronbach a values for all of the corresponding domains (seizure worry 0.84, medication effects 0.80, emotional well-being 0.73, energy/fatigue 0.76, cognitive functioning 0.71, social functioning 0.77, overall quality of life 0.65). The intraclass correlation coefficient for six domains of QOLIE-31 questionnaire demonstrated excellent test/retest reproducibility (ICC > or = 0.75), and good test/retest reproducibility (ICC 0.71) in one domain (cognitive functioning). Considering concurrent validity, three domains had excellent correlation (r = 0.75-1), while 11 had good correlation (r = 0.50 to 0.75), and 3 had moderate correlation (r = 0.25-0.50). This study demonstrated that, if measures are to be used across cultures, the items must not only be translated well linguistically but also must be culturally adapted to maintain the content validity of the instrument at a conceptual level across different cultures. Croatian version of QOLIE-31 will be a valuable contribution to outcome measurement in epilepsy patients, particularly in the context of treatment trials, but als in a wider research context.

The objective of this study was to compare noncontrast computed tomography (NCCT) and computed tomography perfusion (CTP) in early diagnosis of acute ischemic stroke and to define influence of these diagnostic procedures on early outcome of thrombolytic therapy (TLTH). The study included 45 patients, 35 patients submitted to NCCT and CTP and 10 patients who underwent only NCCT, before CTP was introduced. Based on the National Institute of Health Stroke Scale (NIHSS) score we compared early outcome of patients who received TLTH after NCCT only (group 1) with the early outcome of patients who received TLTH following NCCT and CTP (group 2). Statistically significant difference was found in acute stroke diagnosing between CTP and NCCT (p = 0.002). There were no statistically significant differences in TLTH early outcome between group 1 and group 2. In conclusion, CTP should be done regulary in patients presenting with acute ischemic stroke symptoms. More research needs to be done in defining exact influence of CTP implementation on the TLTH outcome.

The aim of the study was to justify the hypothesis that risk factors do not differ between ischemic and hemorrhagic stroke. This retrospective study included 1066 stroke patients. The prevalence of risk factors and hospital-based survival were compared between patients with ischemic and hemorrhagic stroke. Data were retrieved from patient records. Statistical analysis was done by use of chi2-test and t-test for dependent samples. The group of hemorrhagic stroke consisted of 70 (47.9%) female and 76 (52.1%) male patients. The group of ischemic stroke included 450 (48.9%) female and 470 (51.1%) male patients. Ischemic stroke patients had a higher prevalence of hypertension (79% vs. 72%), atherosclerotic diseases (50% vs. 34%) and atrial fibrillation (15.5% vs. 4.2%), and were statistically significantly older (72.5 +/-10.4 vs. 65.7 +/- 12.8) than those with hemorrhagic stroke, however, fatal outcome was more common in the latter (26% vs. 17%). In conclusion, data analysis pointed to differences between hemorrhagic and ischemic stroke according to both risk factors and stroke outcome.

The aim of this study was to determine the level of dental health condition in children with disabilities and to find out weather dental health status might be used as a quality control parameter regarding overall health care for disabled children. Disabled and healthy children from 3 to 17 years old were examined. There were 86 boys and 34 girls in each group. Dental health status was evaluated using the World Health Organization diagnostic criteria for decayed, missing and filled teeth. The relations between mean decayed, missing and filled teeth index for primary, mixed and permanent dentition showed no statistically significant differences among groups. Our results showed that disabled children have evenly level of dental caries as their healthy peers. One can conclude that organized health care for disabled children have positive influence on dental care, too. Furthermore, dental status as an indicator of dental care level might be used as a parameter for quality control regarding overall health care for disabled children.

Department of Neurology, Split University Hospital has 77 contracted hospital beds. 70 health professionals were employed in the Department; 17 medical doctors and 53 nurses. Aim was to evaluate work results in the one-year period with emphasis on the number of employed health professionals compared to the standards defined by the Ministry of Health. Age median of medical doctors specialists was 42.0 years. Length of stay median was 8.0 days. Average bed occupation rate in the Department of Neurology in 2005 was 88%. Shortage of nurses in the Department was determined as the result of analyses of required number of nurses for the Department compared with national standards. Despite the shortage of medical professionals in the Department, work results were better than national, displayed with average bed occupation rate and average length of stay. Neurological diseases have growing share in the human pathology, and adequate organization and implementation of out-of-clinic and clinic health services is a priority in the national health strategy.

Aim: To examine the association of counties' urbanization level and gross domestic product (GDP) per capita on the access to health care., Methods: Counties were divided in two groups according to the urbanization level and GDP per capita in purchasing power standards. The number of physicians per 100,000 inhabitants, the number of physicians in hospitals in four basic specialties, physicians' workload, average duration of working week, the average number of insurants per general practice (GP) team, and the number of inhabitants covered by one internal medicine outpatient clinic were compared between predominantly urban and predominantly rural counties and between richer and poorer counties. Our study included only GP teams and outpatient clinics under the contract with the Croatian Institute for Health Insurance. Data on physicians were collected from the Ministry of Health and Social Welfare, the Croatian Institute for Health Insurance, the Croatian Institute for Public Health, and the Croatian Medical Chamber. Data on the contracts with the Croatian Institute for Health Insurance and health care services provided under these contracts were obtained from the database of the Institute, while population and gross domestic product data were obtained from the Database of the Croatian Institute for Statistics. World Health Organization Health for All Database was used for the international comparison of physician's data., Results: There was no significant difference in the total number of physicians per 100,000 inhabitants between predominantly urban and predominantly rural counties (206.9+/-41.0 vs 175.4+/-30.3; P=0.067, t test) nor between richer and poorer counties (194.5+/-49.8 vs 187.7+/-25.3; P=0.703, t test). However, there were significantly fewer GPs per 100,000 inhabitants in rural than urban counties (49.0+/-5.5 vs 56.7+/-4.6; P=0.003, t test). GPs in rural counties had more insurants than those working in urban counties (1.749.8+/-172.8 vs 1.540.7+/-106.3; P=0.004, t test). The working week of specialists in the four observed specialties in hospitals was longer than the recommended 48 hours a week., Conclusion: The lack of physicians, especially in primary health care can lead to a reduced access to health care and increased workload of physicians, predominantly in rural counties, regardless of the counties' GDP.

Introducing serotonin 5-HT1B/1D agonists in the migraine treatment in the early 1990s had for the first time set guidelines for targeting a hypothetic physiologic source of the sequence of events in migraine, and results thus achieved were considerably better than those accomplished with earlier nonselective pharmacological approach. Triptans have revolutionized migraine management and inspired many epidemiological and public health surveys, strengthened efforts in understanding pathophysiology of migraine and initiated synthesis of many similar drugs in the triptan group, the first being sumatriptan. Triptans have risen to a therapeutic challenge posed by migraine, successfully thwarting the cycle of pain. In treating migraine sufferers, physicians can choose among seven triptans with different attributes. Each patient merits individualized approach in the treatment of migraine with triptans. Choosing the right triptan for a given patient is a matter of first matching the appropriate formulation to the patient, then deciding which agent will best meet the patient's needs. This process requires thorough understanding of the patient, careful and accurate assessment of the efficacy of previous medications used in acute care, and analysis of the individual features of the triptans being considered.

Objective: Universal hearing screening at the delivery centers enable early detection of hearing impairment. Since the 2002, hearing screening in neonates is performed in all Croatian delivery centers. The aim of this study was to propose the retest after 3 weeks period to those neonates with presumably hearing impairment demonstrated by evoked otoacoustic emission (E-OAE) method. Second aim was to asses the prevalence of hearing impairment in the Northern Adriatic region of Croatia., Patients and Methods: Investigation has been conducted at the Department of Gynecology and Obstetrics, University Hospital in Rijeka, Croatia, in the period from 16 October 2002 to 31 December 2006. The hearing screening was performed in all newborns immediately before their discharge from the hospital, using the E-OAE method. Newborns with a possibility of hearing impairment were invited for retesting after 3 weeks, using the same method. Those newborns, whose repeated screening suggested a possible hearing impairment, were sent to an audiologist., Results: The hearing screening was performed by E-OAE method in 11.746 (98.9%) out of 11.869 newborns. The positive result indicating hearing impairment had 5.7% (676) children. These children where retested 3 weeks later using same method and only 128 (1.1%) of them still had positive results. Definite bilateral hearing impairment was confirmed by audiologists in seven children, which accounts for the total incidence of hearing impairment of 0.6 per thousand., Conclusions: Universal newborn hearing screening provides early detection of hearing loss. Retesting after 3 weeks with the same-E-OAE method we raised the specificity of E-OAE method, eliminating false-positive results (4.2%), decreased the attendance of healthy children to the audiologist center and most likely lowering the total costs and eventual parental and/or children stress.

Macromolecular oxidative alterations have been analysed in vitro in anisotonic suspensions of mouse splenocytes. Both hypertonicity and hypotonicity induced the generation of thiobarbituric acid reactive species (TBARS) and carbonylation of the proteins, which took place along with cell death. Addition of antioxidants partially inhibited oxidative changes in isotonic and hypotonic suspensions. Anisotonic shock of mouse splenocytes proved to be an inducer of oxidative stress. The oxidative macromolecular alterations might contribute to pathogenesis of cell death caused by osmotic stress., (Copyright (c) 2005 John Wiley & Sons, Ltd.)

Reperfusion of ischaemic tissue provides oxygen and substrates that are necessary for tissue recovery and concurrently removes toxic metabolites. However, reperfusion may induce various detrimental processes that may cause further tissue damage. Such deterioration of tissue function after reperfusion is defined as ischaemia-reperfusion injury. The consequences of ischemia-reperfusion injury vary from reversible cell dysfunction to local and remote tissue destruction, multiple organ failure and death. The pathogenesis of ischaemia-reperfusion injury is complex and includes excessive production of reactive oxygen species, activation of neutrophils, activation of complement, involvement of cytokines and other inflammatory mediators, vasoactive substances NO and endothelin. This review discusses the pathophysiology of ischaemia-reperfusion injury, the mechanisms of reactive oxygen species production, and the role of other factors in the pathogenesis of such injury. Several approaches and procedures used in pre-clinical and clinical studies in order to limit ischaemia-reperfusion injury are also presented.

The paper reviews diagnostic evaluation of a military recruit who was accidentally found positive on hepatitis C virus test during blood donation drive. Because of its high tendency of transferring to a chronic disease, acute hepatitis C is one of the major problems in public health. Since in a number of cases chronic hepatitis C may lead to cirrhosis of the liver and hepatocellular carcinoma, it is clear that early identification of the infection and early treatment in young people, as military recruits are, is essential. Diagnostic and therapeutic evaluation of the military recruit positive on hepatitis C virus test must be conducted with maximum thoughtfulness and dedication. It is obligatory to inform and include in the treatment recruit himself and more specialists of various branches of medicine. Inclusion of a military psychologist and commanding officer in evaluation and treatment is desirable. Popular health education and preventive medicine measures must be taken by troop physician in such case.

This paper describes the work of a military physician in an army healthcare institution and the scope and aim of activity of medical corps. The analysis includes data collected over one year and shows that officers and non-commissioned officers are more frequent users of medical services than conscripts. The consumption of medical products is high in both populations. The military physician has to face a number of organisational difficulties in everyday practice which diminish the quality of health services. Resolving these difficulties is a priority, especially in view of high healthcare and organisational standards set by NATO, which are eventually to be adopted and maintained by the Croatian medical corps in the process of joining. One of the tasks with that aim is to provide a continued medical training for military healthcare personnel.

The paper reviews morbidity of recruits during basic military training in Military training center in Sinj. The analysis comprised one generation of recruits (1/2000). Data had been collected from the protocol of health-care institution in Military training Center in Sinj. Acute respiratory infections make 50% of all reasons for contacting health-care professionals in Military training center. The importance of acute respiratory infections is ambiguous. They are the most frequent reason for absence from military training and they appear often and spread easily. Implementation of preventive measures is an unavoidable and obligatory part of job of every military unit physician, as well as of the commander of the unit.