Therapeutic drug monitoring and the conservative management of chronic tuberculous empyema: case report and review of the literature.

BACKGROUND: Chronic tuberculous empyema (CTE) is a rare and unusual, low grade and protracted, infection of the pleural space resulting in marked thickening, even calcification of the visceral and parietal pleura. Historically its management has been extraordinarily challenging. Differential penetration of anti-TB drugs into the pleural space has resulted in acquired drug resistance and surgery to remove the empyema or close a complicating bronchopleural fistula (BPF) has been technically difficult or unacceptably hazardous. On the basis of limited experience, the combination of tube thoracostomy or catheter drainage and high-end dosing of anti-TB drugs has been recommended as an initial approach to these lesions. Herein we report the first well documented case of closure of a BPF and cure of a CTE using this approach. The chances of a favorable outcome are improved, we suggest, by using therapeutic drug monitoring (TDM) to guide high-end drug dosing. CASE PRESENTATION: An 84 year old male immigrant to Canada from Croatia was diagnosed with a CTE after he developed a BPF. The diagnosis was made 62 years after what was, in retrospect, an episode of tuberculous pleurisy. He was treated with computed tomography-guided catheter drainage and TDM-guided high-end dosed anti-TB drugs (serum and pleural fluid drug concentrations) over a 10 month period. Sustained closure of the BPF and mycobacteriologic cure of the CTE was achieved. Drug concentrations in the present case and all other reported cases are summarized and interpreted. CONCLUSION: When serum concentrations of the anti-TB drugs isoniazid, pyrazinamide and ethambutol at the high end of the normal range are achieved, pleural fluid concentrations at the low end of the normal range may be anticipated in CTE. Though highly protein bound drugs such as rifampin and moxifloxacin appear to penetrate CTEs less well, their free concentrations in the pleural space may be proportionately higher on account of lower protein concentrations. Interventional radiology and TDM increase the chances that conservative management of CTE will be successful.

Validation of the Croatian and Lebanese Revised Illness Perception Questionnaires for Healthy People (IPQ-RH).

The absence of Croatian- and Arabic-language measures to assess illness representations has contributed to lack of research among Croatian and Lebanese populations. Utilising the robust confirmatory factor analysis (CFA) approach, this study aimed to validate Croatian and Arabic versions of the Revised Illness Perception Questionnaire for Healthy People (IPQ-RH) in the breast and cervical cancer contexts, and compared these illness perceptions among Croatian and Lebanese women living in Australia. Forward and back-translated versions of the IPQ-RH were administered in Croatian to Croatian-born (n = 238), and Arabic to Lebanese-born (n = 240) women. The IPQ-RH illness perceptions were assessed for each cancer type, and the Negative Affect (NA) subscale of the Positive and Negative Affect Schedule (PANAS) assessed discriminant validity. The CFA method demonstrated acceptable models across the Croatian and Lebanese IPQ-RH measures. The internal reliabilities for the IPQ-RH subscales were adequate and the subscales had low correlations with the NA subscale of the PANAS, indicating that the IPQ-RH measures are largely distinguishable from negative affective dispositions. These findings demonstrate that the Croatian and Lebanese IPQ-RH breast and cervical cancer measures have a factor structure similar to the originally developed IPQ-RH scale and provide further support for the theoretically developed illness representations.

Water consumption in Iron Age, Roman, and Early Medieval Croatia.

Patterns of water consumption by past human populations are rarely considered, yet drinking behavior is socially mediated and access to water sources is often socially controlled. Oxygen isotope analysis of archeological human remains is commonly used to identify migrants in the archeological record, but it can also be used to consider water itself, as this technique documents water consumption rather than migration directly. Here, we report an oxygen isotope study of humans and animals from coastal regions of Croatia in the Iron Age, Roman, and Early Medieval periods. The results show that while faunal values have little diachronic variation, the human data vary through time, and there are wide ranges of values within each period. Our interpretation is that this is not solely a result of mobility, but that human behavior can and did lead to human oxygen isotope ratios that are different from that expected from consumption of local precipitation.

Recent trends of cancer mortality in Romanian adults: mortality is still increasing, although young adults do better than the middle-aged and elderly population.

We analysed the mortality trends (1986-2009) for all cancers combined and selected cancers in adult Romanians by three age groups (15-49, 50-69 and older than 70 years of age) in comparison with 11 other European countries. We extracted mortality data from the WHO database and grouped the countries into four regions: central and eastern Europe (Romania, Bulgaria, the Czech Republic, Hungary), Baltic countries (Estonia, Latvia and Lithuania), western and northern Europe (Austria, the Netherlands and Finland), and southern Europe (Croatia and Slovenia). Mortality rates were age-standardized against the standard European population. Significant changes in mortality trends were identified by Joinpoint regression and annual percentage changes (APCs) were calculated for periods with uniform trends. Cancer mortality in Romania was among the lowest in Europe in 1986, but was higher than most countries by 2009. Despite the declining mortality (APC) in younger Romanians for all cancers combined (men-1.5% from 1997, women-1.2% 1997-2004 and -3.8% 2004-2009), male lung cancer (-2.8% from 1997), female breast (-3.5% from 1999) and cervical (-5.4% from 2004) cancers, mortality has increased in middle-aged and elderly patients for most cancers analysed. The exception was declining stomach cancer mortality in most Romanians, except elderly men. For most cancers analysed, mortality declined in the Baltic countries in young and middle-aged patients, and in western and northern countries for all ages. Lung cancer mortality in women increased in all countries except Latvia. We urge immediate steps to reverse the alarming increase in cancer mortality among middle-aged and elderly Romanians.

High-resolution HLA haplotype frequencies of stem cell donors in Germany with foreign parentage: how can they be used to improve unrelated donor searches?

In hematopoietic stem cell transplantation, human leukocyte antigens (HLA), usually HLA loci A, B, C, DRB1 and DQB1, are required to check histocompatibility between a potential donor and the recipient suffering from a malignant or non-malignant blood disease. As databases of potential unrelated donors are very heterogeneous with respect to typing resolution and number of typed loci, donor registries make use of haplotype frequency-based algorithms to provide matching probabilities for each potentially matching recipient/donor pair. However, it is well known that HLA allele and haplotype frequencies differ significantly between populations. We estimated high-resolution HLA-A, -B, -C, -DRB1 haplotype and allele frequencies of donors within DKMS German Bone Marrow Donor Center with parentage from 17 different countries: Turkey, Poland, Italy, Russian Federation, Croatia, Greece, Austria, Kazakhstan, France, The Netherlands, Republic of China, Romania, Portugal, USA, Spain, United Kingdom and Bosnia and Herzegovina. 5-locus haplotypes including HLA-DQB1 are presented for Turkey, Poland, Italy and Russian Federation. We calculated linkage disequilibria for each sample. Genetic distances between included countries could be shown to reflect geography. We further demonstrate how genetic differences between populations are reflected in matching probabilities of recipient/donor pairs and how they influence the search for unrelated donors as well as strategic donor center typings.

Changing cultures, changing cuisines: Cultural transitions and dietary change in Iron Age, Roman, and Early Medieval Croatia.

Food is well-known to encode social and cultural values, for example different social groups use different consumption patterns to act as social boundaries. When societies and cultures change, whether through drift, through population replacement or other factors, diet may also alter despite unchanging resource availability within a region. This study investigates the extent to which dietary change coincides with cultural change, to understand the effects of large-scale migrations on the populations' diets. Through stable carbon and nitrogen isotope analysis of Iron Age, Roman, and Early Medieval human bone collagen, we show that in Croatia large-scale cultural change led to significant changes in diet. The isotopic evidence indicates that Iron Age diet consisted of C(3) foodstuffs with no isotopic evidence for the consumption of C(4) or marine resources. With the Roman conquest, marine resources were added to the diet, although C(3) foodstuffs continued to play an important role. In the Early Medieval period, this marine component was lost and varying amounts of C(4) foodstuffs, probably millet, were added to the otherwise C(3) diet. In both of these transitions it is likely that the changes in diet are related to the arrival of a new people into the area.

Identification of a novel CRYBB2 missense mutation causing congenital autosomal dominant cataract.

PURPOSE: To identify the genetic defect in a four-generation Croatian family presenting with autosomal dominant cataract. METHODS: Genome-wide linkage analysis with 250K single nucleotide polymorphism (SNP) arrays was performed using DNA from one unaffected and seven affected individuals. Mutation screening of candidate genes was performed by bidirectional Sanger sequencing. RESULTS: Evidence for linkage was observed for eight genomic regions. Among these was a locus on chromosome 22 which encompasses the ß-crystallin gene cluster. This cluster includes four genes, namely beta-crystallin B1 (CRYBB1), beta-crystallin B2 (CRYBB2), beta-crystallin B3 (CRYBB3), and beta-crystallin A4 (CRYBA4). A novel sequence variant was found in the CRYBB2 gene (p.Arg188His). This variant cosegregated with the disease phenotype in all affected individuals but was not present in the unaffected family members and 100 healthy control subjects. CONCLUSIONS: We report a novel missense mutation, p.Arg188His, in CRYBB2 associated with congenital cataract in a family of Croatian origin. This variant is the most COOH-terminal missense mutation in CRYBB2 that has been identified so far.

Moyamoya disease in Europeans.

BACKGROUND AND PURPOSE: We describe the clinical, diagnostic, and outcome features of a cohort of white patients with idiopathic moyamoya disease treated in a German institution. METHODS: Our cohort included 21 white patients with moyamoya disease. Clinical and diagnostic features were obtained by retrospective chart review; follow-up information and outcome were obtained prospectively. We used the Kaplan-Meier methods to estimate stroke risk by treatment status. RESULTS: The mean age at onset of symptoms was 31 years. The female predominance was 4.25:1. In our cohort, the initial symptom was a cerebral ischemic event in all patients. There was no patient with a hemorrhage at onset; only one patient experienced subarachnoidal hemorrhage in the further course of disease. The Kaplan-Meier risk for recurrent stroke was very high after the first ischemic event and smaller after angiographic diagnosis. The 5-year-Kaplan-Meier risk of recurrent stroke was 80.95% after the first ischemic event for all patients. Most subsequent ischemic events appeared in the first 2 years after symptom onset. Eleven patients (52.3%) underwent neurosurgical revascularizing procedures. After surgery, the Kaplan-Meier risk of perioperative or subsequent stroke was 27.27% within the first month and was stable thereafter. CONCLUSIONS: Clinical features and course of moyamoya disease of whites analyzed in this German study are comparable to American results. Moyamoya disease in whites differs clearly from Asian moyamoya disease in timing of onset of vasculopathy and lower rate of hemorrhages.

NOD2/CARD15 mutations in Croatian patients with Crohn's disease: prevalence and genotype-phenotype relationship.

BACKGROUND: Crohn's disease (CD) is a chronic inflammatory disorder of the gastrointestinal tract with variations in localization and behaviour. Mutations in the NOD2/CARD15 gene on chromosome 16q have been implicated in the pathogenesis of the disease and three main sequence variants, all single nucleotide polymorphisms (SNPs), have been identified in North American and European populations. AIMS AND METHODS: As no data exist in the Croatian population, we consecutively collected a cohort of 136 CD patients and 91 healthy controls to determine the prevalence of NOD2/CARD15 mutations and their association with phenotypic expression of the disease. All patients and controls were genotyped for Arg702Trp (Hugot SNP8), Gly908Arg (Hugot SNP12), and Leu1007fsinsC (Hugot SNP13) and allele frequencies were compared between the Crohn's patients and controls. The correlation of NOD2/CARD15 genotypes with the phenotypic expression of Crohn's disease was further assessed by logistic regression analysis. RESULTS: NOD2/CARD15 variants were found in 38/136 CD patients (27.9%) compared to 10/91 (10.9%) healthy controls (P = 0.0022). Allele frequencies in patients with CD were 13.97%, 4.4% and 11.76%, respectively, for SNP8, 12 and 13, compared to 5.49%, 1.12% and 4.40% in controls (P = 0.041, P = 0.162, P = 0.055). Six CD patients carried double mutations and, remarkably, we identified two homozygous mutants amongst the healthy control group. Surgery over the course of the disease and a younger age at onset of the disease were significantly more frequent in patients who were carriers of NOD2/CARD15 mutations. CONCLUSIONS: This report on NOD2/CARD15 mutations in Croatian patients with CD demonstrates that this gene is also implicated in susceptibility to CD in the Croatian population. Phenotypic association showed a younger age at diagnosis and a higher need for surgery in patients carrying NOD2/CARD15 mutations. However, the prevalence is somewhat lower compared to other reports, likely due to a more prominent colonic inflammation.

Psychometric properties of the eating attitudes test and children's eating attitudes test in Croatia.

The factor structure of the children's version of the Eating Attitudes Test (ChEAT) and Eating Attitudes Test (EAT-26) were examined in Croatian girls of different ages. A self-report survey was given to 225 girls (Grades 5 to 8), 525 high school girls (Grades 9 to 12), and 646 female university students. Factor analysis revealed the existence of four factors for ChEAT, and three interpretable factors for EAT-26. Internal consistency of both instruments was satisfactory. 10.3% of school girls scored 20 or higher on ChEAT, when 7.6% of high school girls and 11.3% of university students had elevated EAT-26 scores. The ChEAT and EAT-26 were useful for screening large non-clinical groups and measuring disturbed eating behaviours. Those with elevated ChEAT and EAT-26 scores were more likely than those with lower scores to be engaged in extreme weight control methods (e.g. vomiting, binging).

[Echinococcosis--case report and review of the literature]. / Die Echinokokkose--Fallbeschreibung und Literaturübersicht.

Echinococcosis is a rare disease in central Europe. But with the increasing numbers of foreign citizens, this disease becomes more important in cases of cystic processes of unknown origin. It is still very difficult to achieve a diagnosis and a subsequent therapy, particularly in cases of multiple cysts, means a long lasting process containing certain risks. We report on a 20 years old female patient, suspected to have a severe inflammatory pelvic disease. We found multiple abdominal cysts, not originating from or involving ovaries, tubes, bowel, liver or kidneys. The serologic investigations proved our clinical suspicion on an echinococcosis. But neither serology nor clinical investigations could provide any indication on which kind of echinococcosis we found. We started a therapy with high doses of mebendazole to achieve a shrinkage of the multiple cysts to enable a surgery.

[Hepatic echinococcosis with gallstones of the echinococcal cavity]. / Leberechinokokkose mit Gallensteinbefall der Echinococcus-Höhle.

HISTORY AND CLINICAL FINDINGS: A 65-year-old woman was hospitalized with suspected cholelithiasis. The only contributory item in the history was jaundice of uncertain cause 15 years previously. Physical examination elicited pain in the right upper abdomen on deep palpation. INVESTIGATIONS: Alkaline phosphatase and gamma-GT activities were raised (324 and 407 U/ml, respectively). Ultrasound revealed cholecystolithiasis; the bile duct was 5 mm in diameter. Intravenous contrast-medium cholangiography showed choledocholithiasis and circular flat calcification in the bifurcation of the hepatic duct. Computed tomography revealed this structure to be a space-occupying mass (10 x 6 x 5 cm), with a calcified border (density of 27 Hounsfield units), raising the suspicion of a blood-containing hydatid cyst. Additionally there were two calculi in the left hepatic duct. But the echinococcus test (by indirect haemagglutination and enzyme-linked immunosorbent assay) was negative. TREATMENT AND COURSE: Endoscopic retrograde cholangiography (ERC) with papillotomy was performed and two choledochal concrements removed. Concrements within the mass were also visualized. Obstructive jaundice developed 3 days after the ERC and a laparotomy was performed. Excision of the hydatid was not possible because the stone-filled hydatid cavity could not be punctured. Choledochal exploration discovered membranes which histologically were chitin-like structures and corresponded to scolices. Under chemical litholysis the hydatid became smaller. In addition, albendazole was given in two four-week cycles (400 mg twice daily). The patient quickly recovered and 5 months later was symptom-free.

[Neurocysticercosis]. / Neurozystizerkose.

A 49-year-old woman from Croatia, resident in Switzerland for 22 years, had a history of headaches and arterial hypertension for 8 years. While in hospital for assessment and treatment she developed focal seizures. She had an eosinophilia (10%) and computed tomography of the skull demonstrated cysts and multiple calcified foci in the left cerebral hemisphere. Antibodies against Taenia solium antigen were found in both serum and cerebrospinal fluid. Anthelminthic treatment with albendazole (15 mg/kg daily for 25 days) and anticonvulsive treatment with phenytoin (serum levels between 10 and 20 mg/l) markedly improved the symptoms and the cysts regressed. Neurocysticercosis, caused by the larvae of the pork tapeworm, is occurring even more frequently because of the migration of people from countries where the disease is endemic.