Eighteen years of heart transplantation--a single center experience

The best option for the treatment of a failing heart is heart transplantation. The transplantation program at the University Hospital Center Rebro Zagreb started in 1988. To the best of our knowledge this is the first retrospective study on cardiac transplantation in Croatia looking into survival following heart transplantation. Between 1988 and 2006, we performed 81 heart transplantations at the University Hospital Center Rebro Zagreb. Our study focused on the last ten years after establishment of the Department of cardiac surgery as a separate institution. There were thirteen different hospitals throughout Croatia, which contributed to the donor network. Average age of the heart recipient was 48+/-11.8 years (range 14-72), and average age of the heart donor was 34+/-10.7 years (range 14-56). There were more women among the heart donors (34%) then among the heart recipients (18%). During the first ten years, from 1988-1998, the average number of cardiac transplantations was 3 per year In the period from 1998-2006, average number of cardiac transplantations increased to 6 per year. The average thirty-day mortality for the last nine years was 27%. It declined from 30% and 40% in 1998 and 1999, respectively down to 0% in the last two years. Average age of the patients who died was 50+/-6.5years (range 44-62) and did not significantly differ from those who survived. The donor network has grown up to fourteen different hospitals throughout Croatia. The limiting factor in cardiac transplant surgery is the number of available donors. Therefore in attempt to form a good transplant program it is crucial to form an efficient donor network. The number of performed cardiac transplantations is expected to rise until it reaches the number of available donors. With advances in operative technique and postoperative management--immunosuppressive therapy we have observed a remarkable drop in the early operative mortality in the studied period.     

Do parathyroid glands from individuals of different age and gender contain lymph vessels?

Whereas lymph vessels in some endocrine glands have been thoroughly investigated, data on these vessels in human parathyroid glands are often contradictory and deficient in available literature. Therefore, the aim of this study was to histomorphologically investigate whether lymph vessels could be found in human parathyroid glands postnatally and, if so, whether their presence was age- and gender-dependent. A total of 44 parathyroid glands from subjects of both genders, aged 4-90 years, were studied. The glands were divided into three groups. Those from the 1st and the 2nd age group demonstrated similar morphological structure of parenchyma with predominant chief cells with pale-staining cytoplasm, while the frequency of lymph vessels was lower in the 2nd group. Unlike in these groups, chief cells with dark- staining cytoplasm predominated in the glandular parenchyma of the 3rd age group where lymph vessels were not found in any of the examined glands. The frequency of lymph vessels in parathyroid glands was almost the same for both genders. Histomorphologic occurrence of lymph vessels coincided with the presence of endocrine cells with pale-staining cytoplasm, which allowed the assumption that lymph vessels were also one of the signs of functional activity of human parathyroid glands.     

Do we need the "adolescent crisis" diagnosis?

The aim of the study was to examine patients in adolescent crisis at the beginning of treatment and after a period of 12 months in order to evaluate the relative diagnostic and therapeutic validity. The study included 153 Split University students in adolescent crisis; 90 of them were treated by counseling and 63 served as controls. For diagnosis, Hampstead index and Diagnostic and Statistical Manual of Mental Disorders Fourth Edition (DSM-IV) multiaxial evaluation were used, allowing a wider insight into personal functioning. The study sample was split in 7 significantly different diagnostic subgroups. The counseling-treated examinees had better personality functioning after 12 months, but did not differ significantly from the control group. Some of their single functions were more severely disturbed at the very beginning. Counseling is a valuable therapeutic and diagnostic tool for adolescent crisis. The assessment must evaluate the entire person, because looking at only one aspect, due to different development and its place, a wrong conclusion may be reached. The "adolescents crisis" entity is clinically relevant.     

Quantification model for muscular forces and momentums in human lower extremities

The possibility of calculating muscular forces and momentums and their influence on skeleton was evaluated in this study by means of computerized tomography performed on a living person. Through this, the surface and corrected surface for each muscle cross section area were obtained, the distance from muscular centroide to the neutral bone axis was measured, and muscular force and muscular momentum on the bone were determined. Muscular momentum on the bone was obtained by multiplication of the muscular force and the distance between muscular centroide and neutral bone axis. The use of computerized tomography, as a method for creating a model for quantification of muscular forces and momentum, was proven to be reliable according to exactness in evaluation of all human lower extremity structures which is the basis for muscular biomechanical characteristic calculations.     

Pregnancy outcome after treatment with radioiodine for differentiated thyroid carcinoma

The aim of the study was to investigate the influence of radioiodine (RAI) therapy on pregnancies and the health status of children born to mothers who had received therapeutic doses of I-131 for differentiated thyroid carcinoma (DTC). Gestational histories of 76 women treated for DTC from 1971-2005 were retrospectively analyzed. The outcome of 49 pregnancies after RAI was: 35 children (72%), 5 (10%) miscarriages and 9 (18%) induced abortions. RAI did not adversely affect the rate of successful delivery and live birth demographics. Congenital malformation and first year mortality were not observed. The children's ages range from 1 month to 29 years (chi+/-SD=8.0+/-8.4). A higher therapeutic dose (>100 mCi) did not significantly alter the pregnancy outcome. There is no reason to discourage females treated with 1-131 from becoming pregnant. Patients should avoid pregnancy after RAI administration for 1 year.     

Gamma-irradiated RecD overproducers become permanent recB-/C- phenocopies for extrachromosomal DNA processing due to prolonged titration of RecBCD enzyme on damaged Escherichia coli chromosome

The RecBCD enzyme of Escherichia coli consists of three subunits RecB, RecC and RecD. RecBCD enzyme activities are regulated by its interaction with recombination hotspot Chi. Biochemical and genetic evidence suggest that interaction with Chi affects RecD subunit, and that RecD polypeptide overproduction antagonizes this interaction, suggesting that intact RecD replaces a Chi-modified one. We used bacteria with fragmented chromosomes due to double-strand breaks inflicted by UV and gamma-irradiation to explore in which way increased concentrations of RecBCD's individual subunits affect DNA metabolism. We confirmed that RecD overproduction alters RecBCD-dependent DNA repair and degradation in E. coli. Also, we found that RecB and RecC overproduction did not affect these processes. To determine the basis for the effects of RecD polypeptide overproduction, we monitored activities of RecBCD enzyme on gamma-damaged chromosomal DNA and, in parallel, on lambda and T4 2 phage DNA duplexes provided at intervals. We found that gamma-irradiated wild-type bacteria became transient, and RecD overproducers permanent recB(-)/C(-) phenocopies for processing phage DNA that is provided in parallel. Since this inability of irradiated bacteria to process extrachromosomal DNA substrates coincided in both cases with ongoing degradation of chromosomal DNA, which lasted much longer in RecD overproducers, we were led to conclude that the RecB(-)/C(-) phenotype is acquired as a consequence of RecBCD enzyme titration on damaged chromosomal DNA. This conclusion was corroborated by our observation that no inhibition of RecBCD activity occurs in gamma-irradiated RecBCD overproducers. Together, these results strongly indicate that RecD overproduction prevents dissociation of RecBCD enzyme from DNA substrate and thus increases its processivity.     

Transgene insertion in intronic sequences of Mdga2 gene shows methylation in an imprinted manner in an Acrodysplasia (Adp) mouse line

The Acrodysplasia (Adp) mutation arises from the insertion of a transgene containing a mouse metallothionein-promoted bovine papilloma virus and human growth hormone-releasing factor gene. Although the transgene is not expressed, mice that are hemizygous for the transgene show skull and paw deformities when the progeny receive the transgene paternally. To elucidate the molecular mechanisms underlying the mutant phenotype and the modified transmission pattern of the Adp phenotype, a junctional fragment around the transgene integration site was cloned. The transgene was inserted into the intronic sequences between exon 3 and exon 4 of the Mdga2 gene and the degree of methylation of the transgene and the severity of the phenotype were reciprocally related in that the transgene was highly or under methylated in normal and deformed mice, respectively. Thus, methylation of the transgene appears to regulate phenotypic expression and imprinting of Adp.     

Real-time expression of hTERT in primary melanoma biopsies

Skin melanoma is by far the most lethal skin cancer, it is unpredictable by nature and presents a severe diagnostic problem. One of the major issues in melanoma diagnostics is to differentiate it with confidence from a dysplastic nevus. Thus, the aim of this study was to evaluate hTERT expression on a spectrum of dermal lesions (from normal skin toprimary melanoma) in order to examine its possible role as a diagnostic marker in melanoma diagnostics. In this study we analyzed the expression of hTERT by real-time PCR on 58 freshly obtained biopsy samples (4 samples of normal skin, 12 dermal nevi, 23 dysplastic nevi, 19 primary melanomas). Our results showed slightly greater hTERT expression in dysplastic nevi than melanomas with major data overlap. Considering the given results, hTERT does not seem to be a reliable diagnostic marker for melanoma.     

Quality of life after cardiac surgery

The aim of this study was to determine a health-related quality of life two or more years after a cardiac surgery using the MOS-36 item short-form health survey questionnaire. 330 members of "Croatian society of patients who underwent cardiac surgery" were asked and 196 responders, 122 men and 74 women, were included in survey, all of them more than two years after surgery and older than fifty years of age. The answers were collected by phone. Women gained better results for Physical Functioning (p < 0.003) and men estimated better scores for psychical health (p < 0.001). Our patients gained some different results in respect to the Croatian sample of healthy people of the same age. They declared better General Health (p < 0.001), less Bodily Pain (p < 0.001), but inferior Role-Emotion (p < 0.001) and Social Functioning (p < 0.001). The estimations of QOL improving were comparable with the results of numerous shorter follow-ups.     

WRN mutations in Werner syndrome patients: genomic rearrangements, unusual intronic mutations and ethnic-specific alterations

Werner syndrome (WS) is an autosomal recessive segmental progeroid syndrome caused by null mutations at the WRN locus, which codes for a member of the RecQ family of DNA helicases. Since 1988, the International Registry of Werner syndrome had enrolled 130 molecularly confirmed WS cases from among 110 worldwide pedigrees. We now report 18 new mutations, including two genomic rearrangements, a deep intronic mutation resulting in a novel exon, a splice consensus mutation leading to utilization of the nearby splice site, and two rare missense mutations. We also review evidence for founder mutations among various ethnic/geographic groups. Founder WRN mutations had been previously reported in Japan and Northern Sardinia. Our Registry now suggests characteristic mutations originated in Morocco, Turkey, The Netherlands and elsewhere.