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.

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 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.

Effect of dihydroergosine (DHESN) on the serotoninergic system and behaviour: is DHESN a new antidepressive agent?

Acute (50.0 mg/kg) and repeated (0.1-10.0 mg/kg) administration of dihydroergosine (DHESN) to rats over 5 days lowered the concentration of 5-HIAA in the brain. DHESN given acutely increased the brain 5-HT in p-CPA-treated animals and diminished the probenecid-induced increase in brain 5-HIAA. In pargyline-treated rats DHESN enhanced the 5-HT/5-HIAA ratio. DHESN administered to rats repeatedly over 5 days decreased the level of 5-HT in blood platelets, and in vitro at concentrations of 10(-4) M and 10(-3) M inhibited the uptake of [14C]-5-HT in platelets. DHESN (10.0-100.0 mg/kg) potentiated the 5-HT syndrome produced in rats by pargyline and 5-HTP. This potentiation was blocked with cyproheptadine but not with haloperidol. DHESN (1.0 and 10.0 mg/kg) lowered the locomotor activity of rats and 10.0 mg/kg DHESN also reduced the duration of immobility in rats forced to swim in a restricted space. The results indicate that DHESN, like antidepressants, decreases the turnover of serotonin in the brain and potentiates the 5-HT-mediated behaviour. This might suggest that the drug should be further investigated for its potential antidepressive properties.

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.

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.

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.

Involution of bursa of fabricius in male and female chickens: a light microscopic histoquantitative study.

A histoquantitative study of the bursa of Fabricius in 3- and 6-month-old male Prelux Bro chickens (domestic selection) was made. All compartments of normal bursal tissue were examined. At 3 months of age, there were no significant differences in bursal weight and structure between males and females. The only difference observed was the higher volume density of follicular cortex and the lower proportion of follicular medulla in males compared to females. In 6-month-old male and female chickens, a different degree of bursal involution was observed. In the bursa of males, an advanced stage of involution was observed, whereas only the initial signs of bursal involution were found in females.

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.

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.

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.

[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.

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.

[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.

[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.

[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.

[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.