Applicability of the Demirjian, Willems and Haavikko methods in Croatian children.

Age estimation is an inescapable part of every identification process. During growth and development, it is possible to estimate age based on the developmental stages of teeth. The aim of this study was to evaluate three frequently used methods for dental age estimation on a broad sample of Croatian children. The sample comprised 1996 digital, standardized orthopantomograms of children (1121 boys and 875 girls) aged 5 to 16, collected in four major Croatian cities. Age was estimated according to the Demirjian, Willems and Haavikko methods and the accuracy of the estimation was evaluated. The Kappa for intra-examiner agreement was 0.83 for the Haavikko stages and 0.92 for the Demirjian stages. Using the Demirjian method, the average overestimation of age was 0.80 years for boys and 0.84 years for girls. The Willems method overestimated the mean age by 0.41 years in boys and 0.22 years in girls. The Haavikko method underestimated the mean age by 0.60 years in boys and 0.80 years in girls. The Willems method proved to be the most accurate and can be used for dental age estimation among Croatian children. The Demirjian and Haavikko methods showed greater deviation between dental and chronological age and require adaptation when used in the Croatian population.

One year treatment of Barrett's oesophagus with proton pump inhibitors (a multi-center study).

OBJECTIVES: Aim of the study was to investigate the effects of 1-year therapy by different proton pump inhibitors (PPIs) on epithelial tissue and surrounding inflammatory changes in Barrett's oesophagus, in patients who have abandoned invasive therapy. METHODS: A group of 120 patients (sampled in 60-month period, from 61201 upper gastrointestinal endoscopies) who were diagnosed both, endoscopically and pathohistologically with Barrett's oesophagus, and who have abandoned invasive therapeutic approach were enrolled in study. Treatment with different PPIs was initiated and continued for a year. At the end of treatment, patients were reassessed by endoscopy with tissue biopsy and pathohistological analysis. RESULTS: No difference in regenerating squamous epithelium or degree of dysplasia was seen between different treatment groups. Interestingly, most patients receiving pantoprazole (94%) ended up with thinner squamous epithel (P<0.0001). The squamous epithel was consider thinner only if its total thickness, measured on histological specimen, was smaller for more than 50% of the thickness before therapy. Significantly less of difference (P<0.0014) was seen with patients receiving lansoprazole (65%) and (P<0.003) omeprazole (50%). CONCLUSION: Regeneration of the squamous epithel was the same for all PPIs but not good enough to stop the progression of the disease.

Appointment of statistical editor and quality of statistics in a small medical journal.

AIM: To test if the appointment of a statistical editor improves the quality of manuscripts published in a small general medical journal. METHODS: Retrospective review of all manuscripts containing statistical data published in the Croatian Medical Journal between 1992 and 2000 (n=241). Statistical analysis and its presentation were assessed by a single observer. RESULTS: Before the appointment of statistical editor in 1996, 97 manuscripts with statistical data were published. Statistics was not satisfactory in 52 (54%) of them, including 26 definite errors in analysis and 43 in presentation. After the appointment of statistical editor, 144 manuscripts containing statistical data were published. Statistics was not satisfactory in 91 (63%) of them, with 51 definite errors in analysis and 69 in presentation. Out of 144 manuscripts, the editor-in-chief sent out 30 (21%) for statistical review. Statistics was not satisfactory in 25 of them, including 11 definite errors in analysis and 17 in presentation. Statistical editors comments improved three manuscripts. If the authors had acknowledged all statistical editors suggestions, 9 more manuscripts would have been improved. Statistical editor had a total of 195 comments on 30 published manuscripts. Most numerous were the comments concerning the presentation of the statistical analysis (51%), followed by the general comments (26%), comments on analysis (11%), study design (8%), and interpretation (4%). CONCLUSION: Appointment of a statistical editor is not a guarantee of improvement of statistics in small journals. Other measures are necessary, including strict editorial policy on statistical review, monitoring of revised manuscript versions, and enrollment of formally trained biostatisticians.

Staging in untreated patients with small cell lung cancer.

In order to describe the real biological behavior of the small-cell lung cancer we have analyzed survival rates of 66 patients with small-cell lung cancer who did not receive any specific anti cancer therapy. Also, objective of this study was to evaluate the staging system of the small-cell lung cancer. Untreated small-cell lung cancer patients with limited stage disease had statistically significant (p < 0.05) better survival rates in comparison to patients with extensive stage disease. T and N factor of the TNM classification did not influence the survival in untreated small-cell lung cancer patients. It appears that the TNM staging system is not predicting survival probabilities of untreated patients with small-cell lung cancer, while the two-stage system appeared very well based on survival probabilities of these patients.

The effect of the zeolite clinoptilolite on serum chemistry and hematopoiesis in mice.

Zeolites are natural or synthetic crystalline alumosilicates with ion exchanging properties. Supplied in fodder, they promote biomass production and animal health. Our aim was to assess the effects of the natural zeolite, clinoptilolite, on hematopoiesis, serum electrolytes and essential biochemical indicators of kidney and liver function in mice. Two preparations differing in particle size were tested: a powderized form obtained by countercurrent mechanical treatment of the clinoptilolite (MTCp) and normally ground clinoptilolite (NGCp). Young adult mice were supplied with food containing 12.5, 25 or 50% clinoptilolite powder. Control animals received the same food ration without the clinoptilolite. After 10, 20, 30 and 40 days, six animals from each group were exsanguinated to obtain blood for hematological and serum for biochemical measurements as well as to collect femoral bone marrow for determination of hematopoietic activity. Clinoptilolite ingestion was well tolerated, as judged by comparable body masses of treated and control animals. A 20% increase of the potassium level was detected in mice receiving the zeolite-rich diet, without other changes in serum chemistry. Erythrocyte, hemoglobin and platelet levels in peripheral blood were not materially affected. NGCp caused leukocytosis, with concomitant decline of the GM-CFU content in the bone marrow, which was attributed to intestinal irritation by rough zeolite particles. The mechanically treated clinoptilolite preparation caused similar, albeit less pronounced, changes. In a limited experiment, mice having transplanted mammary carcinoma in the terminal stage showed increased potassium and decreased sodium and chloride levels, severe anemia and leukocytosis, decreased bone marrow cellularity and diminished content of hematopoietic progenitor cells in the marrow. The clinoptilolite preparations ameliorated the sodium and chloride decline, whereas the effects on hematopoiesis were erratic.

Good editorial practice: editors as educators.

There may be valuable research going on in the developing and financially less-privileged countries, but it usually does not reach international visibility, in spite of a large number of scientific journals in these countries. Such journals are not only invisible but, by perpetuating a vicious circle of inadequacy, may be directly damaging to the local science and research culture. We call for an international action to help journal editors in less privileged countries. International associations of editors may be leaders of these activities by defining, promoting, and perhaps controlling good editorial practice, as a main criterion for international recognition of a journal. However, the editors of small journals have the power and moral obligation to become a stronghold of quality and advancement in their scientific community. Their educational "tools" are editorial integrity and author-friendly policy. Editors can teach the authors study design, statistical analysis, precision, punctuality, research integrity, style and format of writing, and other aspects of scientific communication. The editors of "big", mainstream scientific journals can act as global educators, teaching and providing guidance to editors of small journals. The editors from developed countries as leaders, and editors from less advantageous environments as teachers are the key figures in shaping research communication in less privileged scientific communities.

Curricular and extracurricular activities of medical students during war, Zagreb University School of Medicine, 1991-1995.

War, as a major human disaster, affects many aspects of life, including medical education. This report describes curricular and extracurricular activities of the students at the Zagreb University School of Medicine during the wars in Croatia and neighboring Bosnia and Herzegovina. Although condensed versions of the curricula were prepared in case of a major breakdown in civilian life, the school maintained the continuity and quality of its curriculum throughout the war. Students engaged in extracurricular activities related to medical aspects of the war, including organization of resuscitation and first aid courses, collecting medical documentation on war victims, humanitarian help to refugees, and peace-promoting activities. Some students joined mobile surgical teams on the battlefronts. After army service, most of them returned to the school and successfully continued with their studies. The school also accepted guest-students from other new states emerged from former Yugoslavia. The authors found that the students' engagement in extracurricular activities related to medicine was enormously beneficial both to the psychological well-being of the students and to the region's peace-building efforts.

Croatian Medical Journal at the turn of the millennium.

The turn of the millennium coincided with the inclusion of the Croatian Medical Journal into the bibliographic databases MEDLINE (1998), and Current Contents/Clinical Medicine (1999), which greatly increased the number of submitted manuscripts. The increased pressure on the editorial office prompted us to modify the editorial procedure and sharpen our acceptance criteria. At the same time, we extended our author-friendly policy to all for global medicine and (2) medicine in translational and emerging countries. The Editorial Board and the Advisory Board were critical in developing and improving the Journal and setting the highest standards in all aspects of publication, especially in manuscript selection by high-quality peer review. In this editorial, we finally meet the members of the two Boards in person, or rather, in photographs and short biographies.

Joining together to combat poverty.

The International Poverty and Health Network (IPHN) was created in December 1997 following a series of conferences organized by the World Health Organization, with the aim of integrating health into plans to eradicate poverty. Around 1.3 billion people live on less than US$1 per day. Of the 4.4 billion people in developing countries nearly 60% lack access to sanitation, 30% do not have clean water, 20% have no health care, and 20% do not have enough dietary energy and protein. Even among rich nations there are gross socioeconomic inequalities. Many children are robbed of their physical and mental potential through poverty. Expressed in constant 1963 US dollars, an average Croatian family needed the annual income of US$894 to meet the poverty line in 1960 and US$9,027 in 1995. Accordingly, 9-25% of Croatian households were below the poverty line between 1960 and 1995. The increase in the poverty rate after 1991 was compounded by the war that destroyed almost a third of industrial capacity and infrastructure. Dissipation of the communist economy and inadequate privatization have contributed to the increase in unemployment rate, corruption, and other social ills. IPHN invited Croatian Medical Journal to publish this editorial to help push the issue of poverty up political and medical agendas on a global level. We argue that a factor contributing to the failure of most large-scale programs against poverty to date is the excessive emphasis on material and infrastructure assistance at the expense of spiritual, moral, and intellectual development.

Clinical, histopathological and flow-cytometric properties of incidental renal cell carcinomas.

Medical records of 63 patients operated on for renal cell carcinoma (RCC) between 1986 and 1996 in the Karlovac General Hospital were studied retrospectively. In 23 (36.5%) patients, the tumor was incidentally detected. The median patient age was 62 in the incidental group and 64 years in the symptomatic group (P > 0.05). Ultrasonography was the leading technique for incidental detection of RCC. The median tumor diameter was 6 cm in the incidental group and 9 cm in the symptomatic group (P < 0.001). Incidental carcinomas had a lower stage (P = 0.022) and a lower nuclear grade (P < 0.001) than the symptomatic ones. The incidental cases were associated with a more favorable ploidy status (P = 0.027) and a lower proliferative activity (P = 0.005). The 5-year survival rate was significantly higher in incidental (81.4%) than in symptomatic cases (44.3%) (P = 0.020). Univariate analysis showed that tumor stage, ploidy status, and proliferative activity were good prognostic parameters, while patient age, tumor size, and nuclear grade were not. Tumor stage was the only independent prognostic parameter in multivariate analysis. In conclusion, the incidentally detected RCC show more favorable clinical, histopathological, and flow-cytometric characteristics and their prognosis is significantly better than in symptomatic cases.

Small scientific journals from small countries: breaking from a vicious circle of inadequacy.

In this editorial we describe the confounding factors that contribute to the poor international recognition of small journals: author pool, review process, finances, language, and visibility. These factors originate from relative scientific inadequacy of the local environment and close a positive feedback loop (vicious circle) of journal inadequacy. We argue that small journals may provide important information and outline the ways in which they can be assisted.

[The curriculum plan for the Split University Medical School--a modern concept for a new school]. / Nastavni plan Medicinskog fakulteta Sveucilista u Splitu--suvremena koncepcija za novi fakultet.

The transformation of the Zagreb University Medical School into an independent medical school, i.e., Split University Medical School prompted us to develop a new curriculum which had to adapt Zagreb curriculum to the new circumstances and to overcome its weaknesses. Additional reasons for new curriculum were the need for implementation of the current trends in medical education and adaptation to the Split Faculty. Principles according which the curriculum was developed took into account the current international recommendations on medical education, equal treatment of all teaching subjects, flexible curriculum and vertical integration of the elective subjects. New curriculum requires substantial changes in the organization of the undergraduate teaching. Because of the differences between Croatian medical schools, it is impossible and unnecessary to have a unique curriculum. Joint effort of medical schools has to be directed to the development of a common curriculum core and corresponding computer base of questions for examinations, enhancing state examination development, standard for the evaluation of the medical schools' quality.

Pre-treatment of transplant bone marrow cells with hydrocortisone and cyclosporin A alleviates graft-versus-host reaction in a murine allogeneic host-donor combination.

The aim of the study was to alleviate graft-versus-host reaction (GVHR) by pre-treatment of the bone marrow (BM) transplant with hydrocortisone (HC) and cyclosporin A (CsA) in C57BL/6J (donor) --> CBA/J (recipient) mouse combination. BM cells were exposed to HC and CsA for 1 h at 37 degrees C and then injected into lethally irradiated (9.5 Gy) mice at a dose of 2 x 10(6) BM cells/mouse. Haematopoietic recovery was assessed on day 12, and survival was followed for 100 days. Combinations of 1000 microg/ml HC and 100 microg/ml CsA, and 100 microg/ml HC and 10 microg/ml CsA significantly reduced MLR and additively mitigated GVHR in vivo, achieving 40% and 26% survival rates, respectively. However, HC and CsA altered neither the peripheral blood cell counts nor in vitro and in vivo BM cell clonogenic potential. Additional studies have shown that HC and CsA blocked con A-driven differentiation of CD8+ and CD4+ CD8+ lymph node cells (LNC) and progression of LNC to S + G2/M cell cycle phases, and inhibited IL-1, IL-2 and TGF-beta while enhancing GM-CSF gene expression in BM cells. Taken together, these data indicate that the pre-treatment of the BM transplant with HC and CsA results in inactivation of GVHR effector cells and mitigation of GVHR while sparing BM repopulating capacity.

Effects of tamoxifen on steroid hormone receptors and hormone concentration and the results of DNA analysis by flow cytometry in endometrial carcinoma.

OBJECTIVES: Tamoxifen is a nonsteroidal triphenylethylene derivate with a predominant antiestrogen activity, used in the endocrine treatment of breast and endometrial cancer. It is not known which endometrial carcinomas will respond favorably to tamoxifen and which ones will not. The aim of this study was to find out whether tamoxifen has an effect on hormone steroid receptors, hormone concentration, DNA content, and proliferative activity in endometrial cancer and to correlate the tamoxifen-induced changes with pathologic parameters such as clinical stage, tumor differentiation, depth of invasion, and histologic type. METHODS: Thirty postmenopausal women with endometrial carcinoma were treated with 30 mg of tamoxifen daily for 7-10 days after curettage. Steroid hormone receptors (estrogen and progesterone receptors), levels of follicle-stimulating hormone, luteinizing hormone, prolactin, estradiol, progesterone, testosterone, dehydroepiandrosterone sulfate, sex hormone binding globulin, and DNA ploidy and proliferative activity were determined before and after therapy. The patients were also divided into favorable and unfavorable prognosis groups according to classical histological parameters. The patients in the favorable group consisted of patients with stage I disease, well and moderately differentiated tumors, favorable histologic type, and a depth of myometrial invasion of less than (1/3). The patients with only one of the unfavorable parameters (clinical stage II or III, poorly differentiated tumors, unfavorable histologic types, and deeper invasion of myometrium) were included in the unfavorable prognosis group. RESULTS: After the treatment, there was a net increase in the progesterone receptors and sex hormone binding globulin and a significant decrease in the estrogen receptors. The increase in progesterone receptors and decrease in estrogen receptors occurred in the patient group with favorable prognosis regarding histologic type, degree of differentiation, and clinical stage, but also in the unfavorable prognosis group regarding the depth of myometrial invasion. Statistically significant decrease in the follicle-stimulating hormone concentration was observed in the groups with favorable prognosis regarding histologic type, depth of myometrial invasion, and grade of differentiation. Concentration of sex hormone binding globulin was significantly increased in groups with favorable prognosis if histologic type and grade of differentiation were taken into account. On the other hand, there was a significant decrease in the concentration of luteinizing hormone in the group with unfavorable histologic type and also a decrease in progesterone concentration in patients with unfavorable prognosis regarding the grade of differentiation. There was no statistical significance either in the concentrations of other hormones measured or in the DNA analysis by flow cytometry. CONCLUSIONS: Our results revealed that tamoxifen can increase progesterone receptors and decrease estrogen receptors in endometrial cancer. The effect was most pronounced in tumors with favorable clinicopathologic parameters. We conclude that tamoxifen therapy can induce progesterone receptor synthesis even in tumors with low initial progesterone receptor levels, making such tumors potentially responsive to additional hormonal therapy with progesterone.

Prognostic significance of cell cycle parameters in infiltrative ductal breast carcinoma.

Flow-cytometric DNA analysis was performed retrospectively from paraffin-embedded blocks in 158 consecutive ductal infiltrative breast carcinoma patients grades I-III. Normal breast tissue was used as control. Tumor proliferative activity, cell ploidy, and DNA index (DI) were related to age of patients, histological grade of tumor, tumor size, axillary lymph node status, estrogen and progesterone receptor status, menopausal status,TNM clinical classification, and survival. There was a significant association between DNA aneuploidy and a high cellular proliferative activity, increased DI, poor differentiation of tumor, primary tumor size, number of positive lymph nodes, and postmenopausal state. Increased proportion of cells in S-phase was associated with positive lymph node status and higher number of positive lymph nodes. The cell cycle parameters had no prognostic value either for overall survival of disease-free survival of the patients.

Peer review in the Croatian Medical Journal from 1992 to 1996.

We analyzed the peer review process in the Croatian Medical Journal (CMJ) from 1992 to 1996 by a retrospective analysis of review forms for 319 manuscripts. The forms asked about manuscript's structure (7 questions), its scientific value (7-item scale), clarity and length, and final recommendation (5-item scale). An international manuscript had at least one author affiliated with a non-Croatian institution. The overall rejection rate of manuscripts was 23.5%. National and international manuscripts had similar rejection rates except for original research manuscripts in clinical sciences (34.7% vs. 18.9%, p=0.046). Out-door peer review was asked for 77.4% of the manuscripts; other manuscripts were commissioned and passed an in-house review. Over the years, the number of international reviewers increased, and that of national reviewers decreased. National reviewers more often did not fill in the review form, and international reviewers more often asked for a major revision. The agreement between reviewers ranged from 34.1% (scientific value) to 90.7% (reference citations). Kappa for inter-rater agreement was poor to fair, without difference between national and international manuscripts. International manuscripts had shorter median review time (from receipt to decision) and publishing time (from acceptance to publication) than national manuscripts: 58 vs. 112 days (p<0.001), and 116 vs. 140 days (p<0.009), respectively. Our analysis shows that peer review can be introduced and sustained in a small journal from the scientific periphery. It can be fair both to national and international manuscripts, although work with the authors of national manuscripts may be needed to improve the quality of data presentation.

Indirect demonstration of the lifetime function of human thymus.

The aim of this study was to test the hypothesis that human thymus maintains its function as the site of early T cell development throughout life, but to a progressively diminishing extent. Mononuclear cell suspensions prepared from the samples of 39 human thymuses were analysed for the total number of cells per gram of thymus tissue, percentage of single marker-positive CD2, CD4 and CD8 cells, percentages of double-positive CD4CD8 and CD2CD8 cells, double-negative CD4CD8 cells, absolute numbers of these cells per gram of tissue, and extent of the in vitro proliferation upon stimulation with concanavalin A (Con A), phytohaemagglutinin (PHA) and pokeweed mitogen (PWM) mitogens. The main outcome measures were flow cytometric data on thymus lymphoid cell composition (according to CD classification), expressed as percentages and numbers of cells per gram of thymus tissue. The total number of mononuclear cells expressed per gram of thymus tissue exponentially decreased with age. The slope of none of the analysed cell subpopulations differed from the slope of the line constructed for age-related decline of the total number of mononuclear cells (-0.024 on a semilogarithmic scale). The thymuses of all ages contained all analysed cell subpopulations in approximately the same proportions: percentages of these cell subpopulations did not change with age, except for all CD4+ (P=0.017) and double-positive CD4+CD8+ (P=0.016) cells, which tended to decrease with age. The extent of proliferation of thymus cells upon stimulation with T and B cell mitogens was unrelated to age. We conclude that the thymus retains its function as the site of differentiation of T lymphocytes throughout life. With respect to the number of involved lymphoid cells, the function exponentially decreases with age.