Evaluation of the SIOPEN semi-quantitative scoring system in planar simpatico-adrenal MIBG scintigraphy in children with neuroblastoma.

Neuroblastoma is the most common malignancy in children comprising 7.6% of all infantile cancers. MIBG scintigraphy is a mandatory neuroblastoma diagnostic test, which is among others methods, semi-quantified by the SIOPEN method. The aim of this study was to test both the skeletal and the soft tissue segments of the SIOPEN scoring method in the diagnostic milieu and to correlate them with the Curie score. Since there is little knowledge of their diagnostic power, the following variables were tested: VMA, HVA, LDH, and MYCN, ferritin, bone marrow infiltration, the INSS and the INPC classification. The cross-sectional study with repeated measurements of 143 scintigrams was performed on 76 pediatric patients with suspected or proven neuroblastoma, who had been referred to the Center for Nuclear Medicine of the Clinical Center of Serbia in the period 2007-2012. The range of the SIOPEN soft tissue scores was 0-5. The range of the SIOPEN skeletal scores was 0-57. The range of the Curie scores was 0-26. The skeletal SIOPEN scores were significantly higher in bone marrow positive children, in children with pathologically elevated urinary VMA levels and in children having a more advanced clinical stage. There was no difference in the SIOPEN soft tissue score due to higher VMA levels, or depending on the clinical stage and positive bone marrow assessment. There was no difference between the SIOPEN skeletal and soft tissue scores on one hand and the histological grade of the tumor; elevated or normal levels of HVA, LDH, NSE and ferritin, or the presence or absence of MYNC amplification in the neuroblastoma cell line, on the other hand. The results of both SIOPEN scores showed a high linear correlation with the Curie score. The conclusion is that the soft tissue segment of the SIOPEN score needs further elucidation in a more controlled milieu. Excellent correlation between all segments of the two semi-quantitative scoring methods speaks in favor of the application of the complete SIOPEN scoring system in every day mIBG scanning.

The role of the psychologist in the preparation of young children for radiotherapy: short review.

Psychooncology is now recognized as an important part of the holistic approach to therapy of very young cancer patients. When the psychologist is included in a multidisciplinary team, his/her duty is to prepare the child for several procedures he/she is scheduled for. If the very young child has to be treated by radiotherapy, adequate preparation of the child before the start of radiotherapy may enable the child to undergo the whole procedure without sedation or repeated anesthesia. Such practice has started in Serbia in 2002, at the Department of Pediatric Oncology of the Institute for Radiology and Oncology of Serbia, Belgrade. In this article, we discuss the model we currently use, and we present how this approach has been successfully applied in a 5-year-old girl treated by radiotherapy.

Diagnosis of Fanconi's Anemia by Diepoxybutane Analysis in Children from Serbia.

The high sensitivity of Fanconi's anemia (FA) cells to drug induced DNA interstrand crosslinks (ICL) such as diepoxybutane (DEB) was used as a part of FA screening in the children with clinical suspicion of FA. The study considered a total of 66 children with the hematological and/or congenital phenotypic symptoms reminiscent of FA. Blood samples from patients with clinical suspicion of FA and controls were collected for chromosome fragility evaluation by the DEB test. According to the results of DEB test, the patients were divided into two subgroups: FA displaying typical DEB sensitive cellular response and non FA. In this study, 10 out of 66 patients were found to have a FA cellular phenotype. The percentage of DEB-induced aberrant cells was increased more than 26 times in FA patients (range 22.00-82.00% with a mean of 48.32%) when compared to non FA patients (range 0.00-12.00% with a mean of 1.84%). The number of DEB-induced breaks/cells was more than 68 times higher in FA patients (range 0.26-4.39 with a mean of 1.37 breaks/cell) when compared to non FA patients (range 0.00-0.20 with a mean of 0.02 breaks/cell). The spontaneous chromosome fragility values in FA patients were overlapping those in non FA patients. Our results indicate that the DEB sensitivity test is the most reliable in vitro method for verification of the FA cellular phenotype.

[The characteristics of mediastinal neuroblastoma and perspectives on surgical excision]. / Osobine neuroblastoma medijastinuma i perspektive hirurskog lecenja.

Thoracic (mediastinal) neuroblastomas (NB) have been reported to differ from abdominal (suprarenal and retroperitoneal) NB and to be associated with better prognosis. The comparison between them is rarely published. In this retrospective study, the characteristics of thoracic NB (17 cases) are investigated and compared with abdominal NB (51 cases). Regarding the diagnosis, thoracic NB presented in lower clinical stages I and II in 35.3% of cases, compared to 11.7% of abdominal NB in stages I and II (p<0.001). The disease was initially diagnosed at less than one year of age in 7/17 (41.2%) of thoracic NB and in 12/51 (23.5%) in abdominal cases (p<0.001). The median age at the time of initial diagnosis was 15.3 months for thoracic NB and 27.6 months for abdominal neuroblastoma (p<0.05). The cases with an elevated vanillylmandelic acid (VMA) and homovanyillic acid (HVA) excretion were 9/17 (52.9%) in the mediastinal NB, and 43/51 (84.3%) in the abdominal NB, respectively (p<0.05). The quantitative values of tumour markers were significantly lower in thoracic NB (0.85 vs. 2.14, p<0.001). Regarding surgery, complete tumour resection was achieved in 15/17 thoracic NB (88.2%) compared to 36/51 (70.6%) radicality in abdominal NB. Surgical complications developed in 5/17 thoracic procedures (29.4%) without a lethal outcome. The mean tumour mass of thoracic NB was 56.5 g vs. 106.3 g of abdominal neuroblastoma (p<0.001). The incidence of ganglioneuroblastoma in mediastinal tumours was 3/17 (17.6%) compared to 8/51 (15.7%) in abdominal NB (non significant). A favorable histology based on Shimada classification was found in 37% of the mediastinal neuroblastoma cases and in 22% in the abdominal NB cases (p<0.05). Regarding the biological properties, genetic malformations associated with NB were identified in 2 thoracic cases (1p deletion and polyploidy). Genetic changes were identified in 12 cases of abdominal NB (1p deletion in 4 cases, DNA ploidy in 6 cases, N-myc amplification in 1 case). One additional abdominal NB had 1p deletion, DNA ploidy and N-myc amplification. This study supports results of other investigations that thoracic NB differs significantly in many aspects from abdominal NB. Important differences in favorable histology and biological properties of thoracic NB have changed the concept of surgical treatment, although unnecessary attempts of surgical radicality still lead to serious complications. Complete excision remains the mainstay of therapy of localised thoracic NB, while in most abdominal tumours the aim of an initial operation should be sampling of tumour tissue for histology and molecular biological examination, with complete excision of the mass as the second priority.

Isotropic versus anisotropic modeling of photorefractive solitons.

The question of the isotropic versus anisotropic modeling of incoherent spatial screening solitons in photorefractive crystals is addressed by a careful theoretical and numerical analysis. Isotropic, or local, models allow for an extended spiraling of two interacting scalar solitons, and for a prolonged propagation of vortex vector solitons, whereas anisotropic, nonlocal, models prevent such phenomena. In the context of Kukhtarev's material equations, the difference in behavior is traced to the continuity equation for the current density. We further show that neither an indefinite spiraling of two solitons nor stable propagation of vortex vector solitons is generally possible in both isotropic and anisotropic models. Such systems do not conserve angular momentum, even in the case of an isotropic change in the index of refraction.

The mutational spectrum of human malignant autosomal recessive osteopetrosis.

Human malignant infantile osteopetrosis (arOP; MIM 259700) is a genetically heterogeneous autosomal recessive disorder of bone metabolism, which, if untreated, has a fatal outcome. Our group, as well as others, have recently identified mutations in the ATP6i (TCIRG1) gene, encoding the a3 subunit of the vacuolar proton pump, which mediates the acidification of the bone/osteoclast interface, are responsible for a subset of this condition. By sequencing the ATP6i gene in arOP patients from 44 unrelated families with a worldwide distribution we have now established that ATP6i mutations are responsible for approximately 50% of patients affected by this disease. The vast majority of these mutations (40 out of 42 alleles, including seven deletions, two insertions, 10 nonsense substitutions and 21 mutations in splice sites) are predicted to cause severe abnormalities in the protein product and are likely to represent null alleles. In addition, we have also analysed nine unrelated arOP patients from Costa Rica, where this disease is apparently much more frequent than elsewhere. All nine Costa Rican patients bore either or both of two missense mutations (G405R and R444L) in amino acid residues which are evolutionarily conserved from yeast to humans. The identification of ATP6i gene mutations in two families allowed us for the first time to perform prenatal diagnosis: both fetuses were predicted not to be affected and two healthy babies were born. This study contributes to the determination of genetic heterogeneity of arOP and allows further delineation of the other genetic defects causing this severe condition.

[Primary myelodysplastic syndrome in children]. / Sindrom primarne mijelodisplazije kod dece.

Primary MDS is a group of heterogenous clonal haematopoetic disorders. In a third of patients MDS terminates as acute myeloid leukaemia, usually resisitant to treatment, while the others succumb due to infections and haemorrhage. Conservative managements of MDS (chemotherapy, haematopoetic growth factors, modulation of cytokine network) are unsuccessful, while the bone marrow transplantation is the only definite treatment. We reviewed clinical and haematological presentations, frequency of dysplastic features, histological and cytogenetic findings in 29 children with primary MDS. Indications for haematological evaluation in our patients were symptoms and signs of isolated or combined cytopenias, fever of unknown origin and frequent infections. Hepatosplenomegaly was found in 19 (65%) patients, while this pattern was found in 10% of adult patients. Normochromic anaemia was found in 25 (86%) patients and thrombocytopenia in 23 (76%). Patients presenting pancytopenia had the lowest probability of survival. Degree of dysplasia, histology and kariotype of bone marrow had no influence on survival rates. Prognostic factors in paediatric MDS are of limited significance, as MDS in children is an absolute indication for bone marrow transplantation.

[Molecular characteristics of the thalassemia syndrome and prenatal diagnosis in a high risk family]. / Molekularna osnova sindroma talasemije i dijagnostika kod deteta pre rodjenja u porodici s visokim rizikom.

The diagnosis of thalassaemia maior has been established in a 6 months old infant by screenig tests. The sick child and his parents were included in the study. Reverse dote blot and allelle-specific PCR confirmed that the mother was heterozygous for mutation in the first intone of beta-globin chain at position 110-beta-IVSI-110. By gap-PCR it was established that the father was heterozygous for haemoglobinopathy Lepore. The child was double heterozygous for both mutations. During the next pregnancy, in the 11th week, faetal DNA was extracted from chorion villous. Fetus was heterozygous for haemoglobinopathy Lepore and carried the same mutation as the father. The parents the accepted information that the second child will be a silent carrier of mutation.

Non-Hodgkin's lymphoma of the uterus and CNS.

We report a case of a non-Hodgkin's lymphoma of the uterus and central nervous system in an 8-year-old female. The neurologic signs included blurred vision, neck stiffness, and walking difficulties but no abdominal problems. She deteriorated further, and repeated lumbar punctures revealed the presence of malignant cells in the cerebrospinal fluid. A repeated ultrasound scan of the abdomen demonstrated a markedly enlarged uterus. Biopsy revealed B-cell non-Hodgkin's lymphoma. Treatment according to the Berlin-Frankfurt-Münster protocol was initiated, but she developed hyperventilation syndrome and required mechanical ventilation. Her condition improved after 1 week but then deteriorated again, and despite additional chemotherapy she developed myelosuppression and septicemia with multiresistant Klebsiella pneumoniae and eventually died 13 months after her first admission to the hospital. No clinical or laboratory signs of relapse were evident at the time of death.

Unusual cases of suicide among health care workers.

We describe three unusual cases of suicide committed by health care workers. The aim of this paper was to analyze and evaluate the evidence of general diagnostic elements of poisoning in these cases.

Haploidentical bone marrow transplantation in leukemia and genetic diseases.

From 1986 to June 2000, sixty children suffering from acute and chronic leukemia (n = 42, 33 of which in resistant relapse), genetic diseases (n = 11), aplastic anemia (n = 2, one of which with platelet refractoriness and bleeding), myelodysplasia (n = 5) received an haploidentical bone marrow, mismatched for 2-3 HLA loci. The donor's marrow was treated in vitro with vincristine and methylprednisolone to obtain a functional T depletion (MLC and CTL inhibition, functional blockade of Th1 and Th2). The prevalence of infectious complications and GVHD was similar to that recorded in matched unrelated donor (MUD) transplants. In situations of high risk of rejection (chronic leukemia, genetic diseases) we infused immediately one half of the harvest and then frozen aliquots from the second week. Of the 25 ALL and 8 AML in resistant relapse, 3 survived, disease-free at 14, 8 and 1 years respectively. Of the 3 ALL, transplanted during remission, 1 is surviving at 18 months. Of the 6 CML, 1 had fractionated bone marrow and is surviving at 3 years, and 5 had standard single dose infusion and died of progression of their disease after rejection of the graft (4) or blast crisis after complete engraftment (1). The 2 patients with aplastic anemia, those with myelodysplasia, and 6 of the 10 with genetic disorders died of transplant-related complications or disease progression. 4 patients with osteopetrosis (n = 2), MLD (n = 1), Wiskott Aldrich dis. (n = 1) survive at 8, 2, 5 and 1.5 years respectively. In patients transplanted with fractionated marrow GVHD > 2nd grade occurred in 15%. Only one patient rejected the graft. Compared with MUD transplantation, mismatched BMT whenever performed in patients in good conditions provides similar outcome and widens the donor availability.

Microprocessor-controlled freezing device for cryopreservation of cell samples.

A freezing device for cryopreservation of blood mononuclear cells has been developed. The device is microcontroller operated, allowing cell freezing by a fully automatic, unattended process. To ensure optimum preservation, the temperature in the cell suspension uniformly decreases from room temperature to -100 degrees C and then the samples are transferred to long-term storage. The performance of the device has been tested using both physiological solution and a sample of cell suspension. The control of temperature variation of cell suspension in the entire temperature range has been realised with an accuracy better than +/- 0.1%. The viability of cells recovered from the frozen samples was 95%. The nitrogen consumption for one cycle of cryopreservation was 1.51. In addition to the fully automatic mode, the manual and semi-automatic modes are available for research purposes. The device has been designed using low cost and widely used electronic components and materials, it is compact and simple to operate.

A comparison of remifentanil and morphine sulfate for acute postoperative analgesia after total intravenous anesthesia with remifentanil and propofol.

BACKGROUND: The transition from remifentanil intraoperative anesthesia to postoperative analgesia must be planned carefully due to the short duration of action (3-10 min) of remifentanil hydrochloride, a potent, esterase-metabolized mu-opioid agonist. This study compared the efficacy and safety of transition regimens using remifentanil or morphine sulfate for immediate postoperative pain relief in patients who had surgery under general anesthesia with remifentanil/propofol. METHODS: One hundred fifty patients who had received open-label remifentanil and propofol for intraoperative anesthesia participated in this multicenter, double-blind, double-dummy study and were randomly assigned to either the remifentanil (R) group or the morphine sulfate (M) group. Twenty minutes before the anticipated end of surgery, the propofol infusion was decreased by 50%, and patients received either a placebo bolus (R group) or a bolus of 0.15 mg/kg morphine (M group). At the end of surgery, the propofol and remifentanil maintenance infusions were discontinued and the analgesic infusion was started: either 0.1 microg x kg(-1) x min(-1) remifentanil (R group) or placebo analgesic infusion (M group). During the 25 min after tracheal extubation, remifentanil titrations in increments of 0.025 microg x kg(-1) x min(-1) and placebo boluses (R group), or 2 mg intravenous morphine boluses and placebo rate increases (M group) were administered as necessary at 5-min intervals to control pain. Patients received the 0.075 mg/kg intravenous morphine bolus (R group) or placebo (M group) at 25 and 30 min after extubation, and the analgesic infusion was discontinued at 35 min. From 35 to 65 minutes after extubation, both groups received 2-6 mg open-label morphine analgesia every 5 min as needed. RESULTS: Successful analgesia, defined as no or mild pain with adequate respiration (respiratory rate [RR] > or =8 breaths/min and pulse oximetry > or = 90%), was achieved in more patients in the R group than in the M group (58% vs. 33%, respectively) at 25 min after extubation (P < 0.05). The median remifentanil rate for successful analgesia was 0.125 microg x kg(-1) x min(-1) (range, 0.05-0.23 microg x kg(-1) x min(-1)), and the median number of 2-mg morphine boluses used was 2 (range, 0-5 boluses). At 35 min after extubation, > or = 74% of patients in both groups experienced moderate to severe pain. Median recovery times from the end of surgery were similar between groups. Transient respiratory depression, apnea, or both were the most frequent adverse events (14% for the R group vs. 6% for the M group; P > 0.05). CONCLUSIONS: Remifentanil provided safe and effective postoperative analgesia when administered at a final rate of 0.05-0.23 microg x kg(-1) x min(-1) in the immediate postextubation period. Remifentanil provided more effective postoperative analgesia than did intraoperative treatment with morphine (0.15 mg/kg) followed by morphine boluses (< or = five 2-mg boluses). The effects of remifentanil dissipated rapidly after ending the infusion, and alternate analgesia was required. Further studies are underway to define transition regimens that will improve postoperative analgesia in patients receiving anesthesia with remifentanil.

[The effect of subtotal parathyroidectomy in patients on haemodialysis]. / Rezultati suptotalne paratireoidectomije kod bolesnika na hemodijalizi.

Secondary hyperparathyroidism is one of the main and most consistent clinical manifestations of chronic renal failure. It develops in the early stage of chronic renal failure, and its severity increases with further deterioration of renal function. Renal osteodystrophy is the most frequent form of secondary hyperparathyroidism. The management of secondary hyperparathyroidism leads to improvement of calcium and phosphorus homeostasis and suppression of parathyroid secretion. Such treatment with medicament may be unsuccessful, and certain features of secondary hyperparathyroidism may necessitate parathyroid surgery. The aim of this article is to present our experience in the treatment of secondary hyperparathyroidism with subtotal parathyroidectomy. Twenty two patients on haemodialysis after subtotal parathyroidectomy were followed for about 2 years (x +/- SD: 2.0 +/- 1.5) after the operation. During this time the effect of operation on biochemical and clinical signs, and radiographical features of secondary hyperparathyroidism was evaluated. According to our results the subtotal parathyroidectomy stopped in most cases, the progression of secondary hyperparathyroidism. In two patients the reappearance of overt secondary hyperparathyroidism was observed 2.5 and 3.5 years after the operation.

[Arterial hypertension in patients with primary glomerulonephritis]. / Arterijska hipertenzija kod bolesnika s primarnim glomerulonefritisom.

Arterial hypertension is a state of blood pressure permanently higher than 160/90 mm Hg (21.3/12.6 kPa). The renal cause of hypertension occurs in about 10% of all cases. The aim of this article was to establish the frequency, the level, and the connection of the hypertension in different types of primary glomerulonephritis. In this study 90 patients with primary glomerulonephritis were observed. Hypertension was present in 45 patients (50%) and different frequency were noticed in different types of glomerulonephritis. The smallest frequency was recorded in the group with minimal changes and IgA nephritis. In the group with mesangioproliferative glomerulonephritis 52% of patients had hypertension and in the group with focal segmental sclerosis 78%. The most frequent hypertension was observed in the group with rapidly progressive glomerulonephritis. Renal failure was more frequent in patients with hypertension. Different frequencies of hypertension was established in different types of glomerulonephritis. It was not severe and was well controlled by remedies. In most cases it suggest a severe glomerular lesions and fast progression of the disease.

[Acute pancreatitis in a patient treated with hemodialysis]. / Akutni pankreatitis kod bolesnika lecenih hemodijalizom.

Acute pancreatitis presents about 1% of all acute abdominal diseases. Its mortality is about 20-50%. The main etiological causes are diseases of the biliary tract and alcoholism. In 10-20% of cases the cause is still unknown. Chronic renal failure is also mentioned as a possible cause of acute pancreatitis. The purpose of this article was to show the frequency and course of acute pancreatitis in patients on haemodialysis during the last 15 years with a case report. From 1976, to 1991, in our Centre about 600 patients have been observed. The diagnosis of acute pancreatitis has been posed in 5 patients (0.8%). In 2 of them the course was easy, 2 died and 1 survived despite a number of complications and two surgical operations. Acute pancreatitis is a rare disease in patients on dialysis, but it is more frequent in them than in persons with healthy kidneys. The mortality in those patients is also high. With adequate care and treatment there is a possibility to survive even heavy type of acute pancreatitis.

Bromocriptine (Bromergon, Lek) in the management of premenstrual syndrome.

The efficacy of bromocriptine (Bromergon, Lek) was studied in a group of 21 women with premenstrual syndrome (PMS). To qualify for inclusion, the patients had to have a score of 20 or more on Casper's Analog Self-Rating Scale for Premenstrual Tension Syndrome completed during the last premenstrual week. The study was designed as a double-blind, randomized, cross-over trial introduced by a wash-out cycle. Patients received Bromergon in a daily dose of 5 mg from cycle day 10 to the onset of menstruation for two consecutive menstrual cycles, followed by two placebo cycles or vice versa. The subjects were instructed to complete the scale every three days from cycle day 3 to the onset of menstruation. A statistically significant improvement due to the administration of Bromergon was observed in symptoms associated with overreactiveness to normal prolactin levels, i.e. abdominal tension, edema, weight gain and breast tenderness. Scores on the linear analog scale and physician's assessments differed regarding psychological symptoms. The investigators observed no difference in the presence of psychic symptoms in the treatment-free period, on Bromergon therapy and during the administration of placebo. On the other hand, self-rating scores reflected an improvement in the presence of depression and irritability during Bromergon treatment. The results obtained suggest that Bromergon may be a useful agent for the treatment of somatic symptoms associated with PMS, while it seems somewhat less effective in PMS cases where psychic symptoms are the major complaint.

[IgA nephropathy]. / IgA-nefropatija.

A great interest in IgA nephropathy was demonstrated in the last few years. Unfortunately, a complete picture of this chronic disease should not yet been made. The article deals with 7 patients with IgA nephropathy treated in our Institute. The following characteristics were examined during a long period of time (1-17 years): clinical picture, course of the disease, clinical and morphologic correlations. The disease is characterised by micro-and macro-haematuria. In 6 patients a moderate proteinuria and slow progression of the disease were noted. Hypertension, massive proteinuria and azothemia in IgA nephropathy suggested a bad prognosis of the disease. This was confirmed in one patient who developed terminal renal insufficiency within 4 months. The pathological finding by optic microscope revealed a wide spectrum of changes. The role of immunofluorescent microscopy is crucial in the diagnosis of this disease.

Amino acid supplemented diet vs. selective low protein diet in chronic renal failure.

Two groups of patients with chronic renal failure (creatinine clearance 13 ml/min) were treated with two different low protein diets: unselected protein diet with 0.35 g of protein/kg/day supplemented with amino acids (first group; 10 patients) and selective protein restricted diet with 0.6 g/kg/day of high biologically valuable proteins (second group; 9 patients). Both diets showed a good patient compliance. The serum urea level decreased significantly only in the first group of patients with a simultaneous disappearance of uremic gastrointestinal side effects. Progression of renal failure, shown by plotting the reciprocal of the serum creatinine concentration against the time, was significantly slower in the first group of patients and therefore their survival without dialysis was longer than that in the second group. The nutritional state was well maintained in both groups. Comparison of two low protein diets showed that the unselected protein diet supplemented with amino acids is more effective in delaying the progression of renal failure. The clinical state of patients is improved and their protein nutrition maintained.