The novel phosphoramidate derivatives of NSAID 3-hydroxypropylamides: synthesis, cytostatic and antiviral activity evaluations.

The target phosphoramidates 5a-e were prepared in one step from 3-hydroxypropyl derivatives 3a-e of nonsteroidal anti-inflammatory drugs (fenoprofen, ketoprofen, ibuprofen, indomethacin, diclofenac). The products 3a-e and 5a-e were evaluated for their cytostatic and antiviral activity against malignant tumour cell lines and normal human fibroblasts (WI 38). All phosphoramidate derivatives 5a-e possess significantly greater inhibitory activities than the corresponding 3-hydroxypropyl derivatives 3a-e, whereby compound 5a showed the most potent inhibitory activities against cervical, pancreatic and colon carcinoma cell lines (IC(50)=5-7 microM).

Neutropenic enterocolitis in acute myeloid leukemia.

In this report we focus on the importance of an accurate diagnosis of gastrointestinal complications during chemotherapy for acute myeloid leukemia. The leukemic infiltrtion of the digestive system may cause mucosal ulcers which can lead to bleeding or perforation. The immune system deficiency in this cohort of patients may result in necrotic enterocolitis (leukemic typhlitis), perianal inflammation, abscesses, and peritonitis. We describe a 37-year old male who presented in June 2004 with 2-month history of fever, weakness and sore throat, treated with antibiotic therapy. Physical examination demonstrated palor. The peripheral blood count at admittance was as follow: Hemoglobin 87 g/l, WBC 63 x 10(9)/l, and platelets 56 x 10(9)/l. The peripheral blood differential count showed: myeloblasts 4%, polymorphonuclear neutrophils (PMN) 20%, monocytes 60%, lymphocytes 16%. The diagnosis of acute myeloid leukemia (AML) was confirmed by bone marrow aspirate, which presented an almost total infiltration by monocytoid blasts, AML type M5 according to FAB classification. Immunophenotypic evaluation by flow cytometry showed that the blast cells reacted with antibodies to CD33, CD13, CD14, CD64, CD15, cytogenetics showed normal karyotype. Induction treatment consisting of cytarabine 2 x 200 mg intravenously in push on days 1-8, vepeside 200 mg i.v. on days 1-5, adriblastine 90 mgon days 1,3 and 5. On day 15 of chemotherapy the patient got fever 38.5 degrees C, abdominal pain and diarrhea (10 stools daily). Broad-spectrum antibiotic therapy with ceftriaxone and amikacin was promptly instituted but condition worsened, abdominal pain extended to all abdomen while the fever and diarrhea persisted. Ultrasonography on day 18 documented bowel wall thickness of colic tract, part of duodenum and jejunum. Owing to suspicion of neutropenic enterocolitis, antibiotic therapy intensified with teicoplanin, fluconazole, metronidazole and pipril. Patient was neutropenic and thrombocytopenic, although daily platelet transfusion from a single donor were given. We started with granulocyte colony stimulating factor (G-CSF) 5 g/kg, which was adiminstered for 7 days. After 7 days neutrophil value reached 1 x 10(9)/l, but fever persisted, abdominal distension and diarrhea progressively improved. The fever peristed and central venous catheter was removed on day 30. After removal of the catheter the patient was getting better: the fever disappeared. The blood count showed Hb 91 g/l, WBC 3,4 x 10(9)/l, platelet 114 x 10(9)/l and normal leukocyte differential count. We emphesize the importance of collaboration between the hematologist and the surgeon in monitoring gastrointestinal complications during and after chemotherapy for acute leukemias and value of abdominal ultrasonography evaluation.

Clinical, Immunophenotypic and Cytogenetic Features of Megakaryocytic Blast Crisis of Chronic Myeloid Leukemia: A Single Institution Study.

We present 15 patients with megakaryocytic (Mk) blast crisis (BC) of a Philadelphia (Ph) chromosome positive CML confirmed by immunophenotype analysis between 1989-2000. The primary aim of this study is to define clinical, immunological, cytogenetic and laboratory characteristics of Mk BC in Ph positive CML. We have done retrospective analysis regarding basic clinical findings, immunologic phenotype, cytogenetic studies and platelet functions. All patients had significant expression of CD61 (14/14) and CD34 (13/13) antigens, and a high frequency of expression of CD13 (9/12), CD33 (10/12) and CD11b (9/11). The BC in 6/15 patients was presented with thrombocytosis, 7/15 had a normal platelet count and two patients had thrombocytopenia. A grade IV myelofibrosis was present in 8/10 patients. Six patients evolved additional karyotypic abnormalities. Two patients had extramedullary BC. The serum activity of LDH (med. 1095.6) was elevated in all patients. A platelet dysfunction was documented in 4/5 patient tested. There are no clinical and hematological characteristics specific for Mk BC of CML. Normal or elevated platelet count (med. 427.4 x 109/L) in BC of CML with prominent expression of CD34 and CD61 antigens, and significant myelofibrosis (grade IV) are the most consistent clinical findings.

Interferometry in the assessment of biomechanical features of the masticatory system hard segments.

Biomechanical studies have found wide application and solved many problems in dental medicine. An interdisciplinary approach has allowed an ever-faster progress in the field. The aim of this study was to point out the advantages of holographic interferometry. With the use of this method, the study object is observed as a whole rather than as a substrate, thus providing a three-dimensional holographic image visualizing the load transmission from one jaw to another, tooth pressure against the alveolus, and strain of Sharpey's fibers, and yielding precise data on deformities, dislocations and force distribution.

Mandibular border positions in eugnathic subjects during the second bite lifting.

This research was aimed at performing a clinical functional analysis during the second bite lifting, in order to define mandibular border positions and possible differences by sex and/or age. Out of a total of 9680 examined children from the region of Medimurje, Croatia, 103 were found to be eugnathic, with dentition in occlusion during the phase of the second bite lifting. All the eugnathic patients belonged to the class I by Angle, without any caries, fillings or extracted teeth. They were divided into three predefined groups for the sake of comparison. The obtained values of mandibular border positions in eugnathic subjects during the second bite-lifting phase vary with age and with the number of present permanent teeth in occlusion. Generally, all the values are higher in girls than in boys, which speaks in favour of the assumption that mandibular border positions are determined by sex, hormonal activity, growth and intercuspidation. Also, girls show a higher TMJ flexibility as well as a higher mandibular mobility. The knowledge of these facts will contribute to a more precise treatment in child prosthetics and pedodontics.

Model for computer simulation of bone tissue.

The paper deals with the dependence of the torsional moment on the angle of the compact bone torsion in laboratory animals and humans. Based on the data for laboratory animals obtained by measurements, the data on dependence of the torsional moment and the angle of torsion were predicted for humans. The measurements were carried out in four groups of laboratory animals. One was the control group, and the other three groups were treated by various vitamin D3 metabolites. The same measurements were performed also in only one group of humans, due to the impossibility to treat humans with vitamin D3 metabolites. The functional relationship between the angle of torsion and the torsional moment for all the groups of animal bone tissue were determined by measurements, and results were used to predict the reaction of the human compact bone tissue if treated by vitamin D3 metabolites.

Trends in dental caries in 12-year old children in Croatia.

In this epidemiological study the caries status of 12-year-old children was compared over time for the years 1968, 1973, 1980, 1985, 1990, 1991 and 1999. The mean number of decayed, missing and filled teeth (DMFT) decreased from 7.0 in 1968 to 2.6 in 1991. From 1991 to 1999 and increase of DMFT 2.6 in 1991, to 3.5 in 1999) has been seen which is result of war in Croatia and reorganisation of health care delivery system. With the expected continuing decline in the prevalence and severity of oral diseases, one of the main problems in the future seems to be the transition of the oral health care delivery system from a disease-oriented system to a health-oriented one.

The patient's and the therapist's evaluation of bridges of different materials and age.

The aim of this study was to find out patients' satisfaction with their bridges made of different materials (metal-ceramics, Au/resin, Ag-Pd/resin). One hundred and sixty four patients were examined at the Dental School, University of Zagreb, Croatia. They assessed their bridges--the overall quality, aesthetics, speech, chewing and the health of the gingiva by the scale from 1-5. The same categories were also assessed by a trained prosthodontist. The majority of the patients was really satisfied and gave the highest grades (quality, aesthetics, speech, etc.) and therefore the results were skewed and asymmetrical towards the biggest scores (biggest grades). The best gingival health was evaluated by the group of patients with ceramic crowns and bridges (p < 0.05) and the worst by the patients with Ag-Pd bridges. Speech was scored higher for the lateral than for the frontal bridges. Patients evaluated the health of the tissue surrounding their bridges, overall quality of fixed prosthodontic appliance and aesthetics with significantly higher scores than the prosthodontist (p < 0.01). The results point at a difference between the patient's and the therapist's evaluations and to the patient's insufficient care about the gingiva around the bridge abutments.

Evaluation of craniometric methods for determination of vertical dimension of occlusion.

In clinical practice, fully precise method for exact determination of vertical relation of occlusion still does not exist. This study examines the relationship between different craniofacial distances and the distance subnasale-gnathion (Sn-Gn), which represents the lower third of the face in vertical relation determination. The highest coefficient of correlation was (r = 0.8678, p < 0.05) between the distance eye-ear (E-E = lateral border of the ocular orbit-medial opening of the meatus of the external auditory canal) and Sn-Gn. The prediction of the distance Sn-Gn could be determined through the formula: Sn-Gn = E-E/1.08 or through the regression analysis: Sn-Gn = 1.9197 + 0.6449 x E-E. None of the calculated coefficients of correlation was 1, but was < 1, so that the prediction of the distance Sn-Gn by craniometric distances is not absolutely reliable, although it is considerably helpful. Our results point at the variations of craniofacial distances in the Croatian population. Yet, craniometry could still be recommended in everyday clinical practice for prediction of vertical relation of occlusion, as it is a simple, economic and non-invasive method, however in combination with some other methods, which have proved to be helpful.

Chronology, dynamics and period of permanent tooth eruption in Zagreb children (Part II).

The aim of the present paper is to determine the beginning, order, median time, termination, dynamics, continuity and intensity of the permanent tooth eruption, as well as its calendar, in a sample of Zagreb children. The study included 2768 children (1398 boys and 1370 girls). All subjects were classified in one-year age groups. The continuity of tooth eruption occurs from 5.1 years to 14.97 years, i.e., for a period of 9.87 years. Each particular tooth has its own dynamics of eruption (V5-V95) which on the average amounts to 4.25 years. The continuity of eruption is 10.1 years in boys and 9.8 years in girls. The dynamics of eruption is 4.15 years in boys and 4.35 years in girls. A certain asymmetry in eruption has been described.

Preventive sealing of dental fissures with Heliosil: a two-year follow-up.

Due to their shape and configuration of dental crown, especially its biting surface with numerous pits and fissures permanent molars are suitable sites for retaining food remnants and bacteria. For this reason, preventive efforts and early prophylactic procedures should prevent the development of caries at these critical sites. Deciduous and permanent teeth of 300 children aged 6-7 years with healthy parallel teeth were included in the study. Fissure sealing was performed on one side, whereas contralateral teeth served as controls. During a two-year period, control examinations with finding recording were performed every six months. During the two-year follow-up period, the sealed teeth remained free of caries as long as the coating persisted. In deciduous teeth, the sealant was first observed to be missing at 18 months in 5%, and at 24 months in 8% of the teeth. None of these teeth was affected by caries, suggesting that a part of the sealant was retained in the fissures. In permanent teeth, caries developed in 18% of the sealed teeth at 24 months.

Multiple karyotypic aberrations in a polymorphous variant of Waldenström macroglobulinemia.

A 71-year-old woman presented with malaise, skin bruising, epistaxis, and gingival bleeding of recent and prompt onset. There was no adenopathy. The liver and spleen were not enlarged. Bone marrow aspirate showed a polymorphous infiltration with lymphocytes (22%), typical Marschalko plasma cells (16%), plasmacytoid lymphocytes (29%), lymphoblasts (8%), and immunoblasts (13%). The immunoblasts morphologically resembled lymphosarcoma cells with a frequent "clover-leaf" appearance. An IgM paraprotein concentration in serum was 38.5 g/L. The bone marrow histopathology confirmed the presence of heterogenous cell infiltration, with 30% of the population being comprised of lymphoblasts and immunoblasts. In order to differentiate a polymorphous variant of Waldenström macroglobulinemia (WM) from the more common small cell lymphocytic lymphoma (SLL) in anaplastic metamorphosis, flow cytometric studies were performed on marrow specimens. A typically bright surface IgM (lambda) was demonstrated with a less bright CD38. Further immunophenotype was HLA-DR+, CD19+, CD20+ and CD10-, CD22-, T-Ag- and kappa light chain- expression. This corroborated the diagnosis of an extremely rare, polymorphous variant of WM. The marrow cytogenetics disclosed 50% (10/20) pathologic metaphases 48,X,dup(X)(p21p22),der(2), +5,del(6)(q11q21), +12,inv(16)(p13q22), del(17) (p12), and 50% normal metaphases. The patient was treated with a LOPP protocol. She failed to respond and died 5 months after the diagnosis with myocardial and renal insufficiency complicating a pronounced pancytopenia in the peripheral blood.

Chronology, dynamics and period of primary tooth eruption in children from Zagreb, Croatia.

The aim of the present paper is to determine the beginning, order, median time, termination, dynamics, continuity and intensity of the primary tooth eruption, as well as its calendar, in a sample of children from Zagreb, Croatia. The study included 1288 children. All subjects were classified in one-year age groups. In the examined group, the continuity of tooth eruption occurs from 4.2 months to 41.5 months, i.e., for a period of 37.3 months. Each particular tooth has its own dynamics of eruption (V5-V95) which on the average amounts to 14.35 months (14.92 months in boys and 13.79 months in girls). The continuity of eruption is 35.6 months in boys and 38.9 months in girls. The dynamics of eruption is 14.82 months in boys and 13.79 in girls. The termination of tooth eruption is similar for both sexes.

Taurodontism in Down's syndrome.

Forty-three pantograms of the subjects with Down's syndrome were examined for the diagnosis of taurodontic teeth, grade of taurodontism, sex distribution and individual tooth involvement. Taurodontic teeth were found in 55.8% of the subjects, 32.6% females and 23.2% males. Second molars were most frequently affected (53.2%), followed by first molars (40%) and third molars (6.5%). The mesotaurodontic form was the most frequent form of the anomalia (72.5%). Hyypotaurodontic teeth were observed in 9.7% and pyramidal teeth in 17.7% of the cases. Hypertaurodontic teeth were not found.

Hypodontia in patients with Down's syndrome.

The aim of this study was to assess the prevalence of hypodontia in subjects with Down's syndrome. A group of 112 subjects with cytogenetically confirmed diagnosis of Down's syndrome, aged 12-36 years were examined. Hypodontia of the permanent teeth has been established on the basis of dental examination and orthopantomogram analysis in all cases. Hypodontia was present in 38.6% patients. Upper lateral incisors were most commonly missing. In patients with Angle class I, hypodontia most frequently referred to upper left lateral incisors, upper left first premolars and lower left second premolars. In patients with Angle class II, lower second premolars and upper incisors were most commonly affected by hypodontia. In patients with Angle class III, hypodontic findings more frequently referred to the maxilla as compared to mandible.

Basic amino acid in the pathogenesis of caries.

Amino acid pattern in total saliva was studied in 43 children with caries, aged 12-15 years, using the method of ion exchange chromatography. The results were compared to those obtained in a control group of 39 children without caries. In saliva from the children with caries, a significantly lower level of arginine (22.02 mumol/l), and a complete lack of histidine and its derivatives were observed when compared to the control group, where the concentrations of arginine and 1-methylhistidine were 28.36 and 26.34 mumol/l, respectively. The results obtained suggested that a decreased concentration of arginine, and a lack of histidine and its derivatives might imply an increased risk of caries.

[Principles in medical ethics and duties in working with dental patients]. / Nacela etike i duznosti lijecnika u radu sa stomatoloskim bolesnikom.

Dental deontology is a branch of medical deontology which defines the relationship of a dentist with his patient and other medical workers. The purpose of medical deontology is to prevent and eliminate psychic harms, as well as to put more self-confidence in a patient, so important for his good health and treatment. The proper relationship of a dentist with a dental patient is based upon two main principles, namely psychoprophylaxis and psychotherapy. The dentist (with his improper conduct and words) should not pose additional psychic harm to a patient, so he should mind his behaviour. At the same time, the dentist should be active and have to know how to dismiss too high an emotional tension of a patient. Preparation to a dental treatment should be adjusted to age and particularities of each patient. This is where one most often makes a mistake, since the patient is usually approached too habitually, with no understanding at all of his personal problems. Should one show compassion and interest in a patient, his worries and preoccupations, the patient will surely bear, although painful and not at all comfortable, the treatment much better. Finally, it is highly important to educate individuals, groups and the community on the whole how to take care of their own teeth and mouth, and the medical education should be paid much more attention in this field.

Oral health in SFR Yugoslavia in 1986.

A pilot oral health epidemiological survey using WHO assessment forms was conducted in Yugoslavia in the year 1986. The study population consisted of 2600 persons aged 6, 12, 15, 18, 35-44, and over 65 yr. The survey included 22 towns (11 developed and 11 underdeveloped) in the six Republics and two Provinces of Yugoslavia. The results showed the prevalence of dental caries in the Yugoslav population to be very high (98.7% in 12-yr-olds). The mean decayed, missing, and filled teeth (DMF) scores were as follows: 6.1 at age 12 yr, 9.6 at age 15, 10.9 at age 18, 18.0 at age 35-44, and 28.0 in persons aged over 65 yr. Assessment of the periodontal status showed calculus to be the predominant disorder in the age groups 18 and 35-44 yr, while loss of sextants prevailed in persons aged over 65 yr.