Biomedical subjects
Publications and source records attributed to M Popović.
We report the case of a littoral-cell angioma of the spleen, a recently described benign vascular tumour, whose imaging and pathological characteristics have been discussed only by a few authors. The diagnosis was made after elective splenectomy. The CT images, scintigraphy and histological specimens are presented, and differential diagnoses discussed.
Alkali hydrolysis of 2,4,6-trinitrotoluene (TNT) was studied using batch experiments with starting pH values 11 and 12 in glass conical flasks covered with aluminum foil. Isothermal (25 and 40 degrees C) as well as non-isothermal experiments were conducted. Experiments starting at pH 12 resulted in >95% reduction in the concentration of TNT; those starting at pH 11 had a maximum reduction of 20-25% in TNT concentration. In all the experiments, one major stable intermediate was produced but it could not be identified. The experimental data were used to determine the overall stoichiometry of TNT and hydroxyl ions. Approximately 100 M (standard deviation 11.4) of hydroxyl ions were consistently consumed per mole of TNT. However, control experiments showed that all but 13 M (standard deviation 2) of hydroxyl ions were consumed in reactions not related to TNT. A simple kinetic model involving formation of the intermediate was proposed to account for changes in concentrations of TNT and hydroxyl ions. The rate constants and activation energies of the reactions were identified using isothermal data and the kinetic model was then used to predict the experimental data in the non-isothermal experiments reasonably well.
Felbamate (2-phenyl-1,3-propanediol dicarbamate, FBM) can cause aplastic anemia and hepatotoxicity. The mechanism of FBM-induced toxicities is unknown; however, it has been proposed that 2-phenylpropenal, a reactive metabolite of FBM, is responsible. The pathway leading to this metabolite involves hydrolysis of FBM to 2-phenyl-1,3-propandiol monocarbamate (MCF), oxidation to 3-carbamoyl-2-phenylpropionaldehyde (CBMA), and spontaneous loss of carbon dioxide and ammonia. We made a polyclonal antibody against 2-phenylpropenal bound to protein and confirmed its specificity using ELISA. We attempted to develop an animal model of FBM-induced aplastic anemia and/or hepatotoxicity, and we also used the antibody to try to detect covalent binding of 2-phenylpropenal using immunoblotting. However, none of the animals developed evidence of bone marrow or liver toxicity, and we were unable to detect covalent binding, possibly because significantly less 2-phenylpropenal is formed in rodents than in humans. As this type of idiosyncratic drug reaction is believed to be immune-mediated, we also studied the potential of FBM and its metabolites to stimulate an immune response using the reporter antigen popliteal lymph node assay in female Balb/c mice. We found that neither FBM nor MCF induced an immune response in popliteal lymph nodes (PLNs). However, CBMA treatment appeared immunogenic, causing footpad inflammation, hardening, scab formation, and an increase in thickness. The PLN cell count in CBMA-treated mice increased 8-fold as compared to control, FBM-, or MCF-treated mice. Immunohistochemical analysis of the CBMA-exposed PLNs revealed germinal center formation, indicating B cell proliferation, later confirmed by flow cytometry. Most of the cells expressing the activation surface marker CD54 were B cells. We also found that CBMA treatment caused an increase in the production of IgM and IgG1 antibodies as well as IL-4 and IFN-gamma cytokines. Our findings indicate that 2-phenylpropenal is a very potent immunogen, supporting its possible involvement in the FBM-induced hepatotoxicity and aplastic anemia.
Preoperative radiotherapy with (CRT) or without chemotherapy (RT) in the management of patients with locally advanced rectal carcinoma is increasingly accepted as therapeutic modality to reduce local recurrence and improve survival, decrease tumor size and/or stage, has less toxicity compared to postoperative therapy, improves sphincter preservation and the ability to perform a curative resection. In a brief review of literature we discussed the possible prognostic role of most important pathologic parameters and their clinical implications. At present, predictive value of tumor response to neoadjuvant therapy remains uncertain, whether evaluated as five-point histological tumor regression grade (TRG) or recently proposed three-point rectal cancer regression grade (RCRG). However, most reports emphasize reduced local reccurence rates and disease-free survival advantage in patients with complete tumour regression or tumour down-staging, occuring in up to 20% and 60% of cases, respectively. Patients with advanced post-treatment tumour stage (ypT3/4), positive lymph nodes (ypN1/2), vascular invasion, positive circumferential resection margin, clearance < 2mm, or absence of tumor regression are shown to have poor clinical outcome. Among CRT-induced morphological features, only "fibrotic-type" stromal response with minimal inflammatory infiltrates and absence of surface ulceration are correlated to recurrence-free survival. Preliminary unpublished results of a pilot study from our multidisciplinary prospective trial relate to correlation of histopathologic parameters and morphologic changes to rectal cancer regression grade (RCRG). Therefore, we studied 22 consecutive patients, mean age 56 (range 23-69) years, with transmural cT3/4 stage and were subgrouped as follows: RCRG-1 (7 patients, 31.8%), RCRG-2 (9 patients, 40.,9%) and RCRG-3 (6 patients, 27,2%). In addition, 14 patients (63%) showed tumour downstaging and only 1 patient (4.5%) nodal down-staging after ypTNM restaging. There was the predominance of fibrotic-type stroma (16 patients, 72.8%) versus fibro-inflammatory response (6 patients, 27.2%), frequent tumoral necrosis (13 patients, 59%) but infrequent surface ulceration (5 patients, 22.7%) and peritumoural eosinophylic infiltration as well as endocrine cell differentiation (4 patients, 18%). The second aim of our study was to investigate determinants of radiosensitivity, i.e. the relationship between proliferative activity indices (Ki-67 and PCNA) as well as the induction of apoptosis (p53) and the tumour regression (RCRG) after neoadjuvant CRT. The interaction between Ki-67 and PCNA immunoexpression levels and the benefit of CRT was significant for Ki-67 (p = 0.03), but not for PCNA (p = 0.08) and p53 levels (p = 0.4). In a conclusion, high percentage of Ki-67-positive tumor cells in the preoperative biopsy predicts an decreased treatment response after preoperative CRT of rectal cancer. However, long-term follow-up and large studies are necessary to establish the value of regression grade and the need for its prediction by reliable biological markers.
Gastrointestinal stromal tumor is a form of mesenchimal neoplasm that may be present in all parts of gastrointestinal system. We are reviewing diagnostic and therapeutic algorithms for patient with diagnosed gastrointestinal neoplasm of small intestine, experiencing repeated episodes of painful bleeding from gastrointestinal trackt.
The aims of the study were to review the patients with choroid plexus tumor (CPT) treated in Slovenia between 1972-1999, to calculate the incidence of CPTs, and to evaluate treatment results in respect to tumor histology and mode of therapy. Cancer Registry of Slovenia database was used for patientś identification. Histological specimens and medical records were reviewed. Twelve patients (7 females, 5 males), 0.8-43 years old (median 6.1 years; <15 years: 10/12,83%) with CPT, representing 0.36% of all intracranial tumors registered during the period under study, were identified. Considering children less than 15 years old only, the corresponding percentage was 3.69. There were eight papillomas (CPPs) and four carcinomas (CPCs) with no difference in age distribution between the groups. Of seven patients with gross tumor resection in CPP group, one patient died of postoperative meningitis and one had local recurrence 1.6 years after surgery; the latter is disease-free 17.9 years after re-operation. One patient with macroscopic residue after surgery is alive and asymptomatic after 16.5 years. In the CPC-group, only the patient who received adjuvant BEP chemotherapy and craniospinal irradiation following incomplete surgery is alive with no signs of disease after 6.5 years. Ten-year disease-specific survival for all CPTs and for CPP subgroup was 73% and 100%, respectively. In Slovenia, CPTs represent 0.36% of intracranial tumors. In children, the incidence is 3.69%. CPPs are twice as frequent as CPCs. In CPPs, the treatment of choice is surgery alone. After incomplete surgery, wait-and-see policy seems to be justified. For CPCs, adjuvant multiagent chemotherapy and craniospinal radiotherapy following surgery should be considered.
The case of a healthy 31-year-old woman in the 40th week of second pregnancy is presented. During preparation for an emergency caesarean section, she developed an amniotic fluid embolism (AFE) with unusual and unique features. The acute onset of disease with cardiorespiratory failure with hypotension, tachycardia, cyanosis, respiratory disturbances and loss of consciousness, suggested at first a pulmonary thromboembolism, but the appearance of convulsions led to the diagnosis of AFE. The patient died after 5 days due to an untreatable brain edema. At autopsy, AFE with the usually associated disseminated intravascular coagulation was found in the lungs, brain, left adrenal gland, kidneys, liver and heart. Eosinophilic inflammatory infiltrates were found in the lungs, hepatic portal fields and especially in the heart, suggesting a specific hypersensitivity reaction to fetal antigens. Moreover, intravascular accumulation of macrophages in the lungs also favored a non-specific immune reaction to amniotic fluid constituents.
In the present study the antioxidative properties of the bulbs, leaves and stalks of Allium psekemense B. Fedtsch were investigated. The activities of antioxidant enzymes (superoxide dismutase, catalase, peroxidase, glutathione peroxidase), quantities of malonyldialdehyde, superoxide and hydroxyl radicals and reduced glutathione and also the content of total flavonoids, chlorophylls a and b, carotenoids, vitamin C and soluble proteins were determined. The results indicate that extracts from all plant organs exhibited antioxidant activity. The highest antioxidant activity was observed in the leaves. Furthermore, the ESR signal of DMPO-OH radical adducts in the presence of the leaf phosphate buffer (pH 7) extract was reduced by 54.3%.
Crohn's disease is pandigestive disease of unknown aethiology, with tendency to reccurrences. Until now it is impossible to heal this disease either by medical or surgical treatment. All unfavourable consequences of this disease are result of inadequate treatment of complications which are leading to systemic weakening, with further progression of morbid process. Therefore, the principle of timely and minimal invasive surgical procedure has been generally adopted. Introduced in eighties, strictureplasty is a procedure of such characteristics. During the period 1980-2001 this method was used in 1/3 of 126 patients with Crohn's disease. There were 79 strictureplaties performed, 9 long and 70 short. Out of these 42, 12(28.6%) were postoperative recurrences, and there was one case of duodenal strictureplatsty. Postoperative small bowel fistulae were not observed, and there was no mortality in this group. During the follow up period of at least 5 years, in only two cases (4.76%) some functional disturbances of digestive functions were observed, without indications for reoperation. In this article indications and details of operative technique are discussed.
In the period 01.01.1991-12.31.1996, 523 operations due to rectal carcinoma were performed on the First Surgical Clinic, the Third Department for Colorectal Surgery. Most common localization of tumor was in the distal third of the rectum 65.2%. In the middle third, there were 28.9% and in the upper, intraperitoneal third 5.9%. We performed 286 low anterior stapled resections, 93 anterior resections with hand-sewn anastomosis and 144 Abdominoperineal excisions of rectum (Miles procedure). Pathohistological examination revealed adenocarcinoma in all cases. In this study we analyzed local recurrence and five-year survival after long-term follow-up in the group where Miles procedure was carried out as a potentially curative procedure (except 4.9% cased with Dukes D stage). There were 74.3% males and 23.7% females median age 59.2 years. According to Dukes classification there were 4.9% in stage A, 47.2% in stage B, 43.1% stage C, and 4.9% stage D. There were 4(2.7%) postoperative deaths. Recurrence of the disease was registered in 44 (30.5%) patients. Local recurrence alone was found in 14 (9.7%) patients, while distant spread was registered in 30 (20.8%) patients. At present, the median follow-up is at 72.9 months. Analysis by the Kaplan-Meier's test shows cumulative survival of 61%, and disease free survival of 63.4% at 60 months of the follow-up. Dukes C is associated with a very poor prognosis; survival after 60 months of follow up shows cumulative Survival of 0.35 while Dukes B has far better prognosis (0.86). Analysis of disease free survival by Dukes stage shows that Dukes C has the worst prognosis (disease free survival 0.36 after 60 months), while stage B has much better prognosis (0.84). Local recurrence analysis by the Kaplan-Meier's test shows disease free survival of 84.9% at 60 months of follow-up. Analysis of local recurrence by Dukes stage shows 1.00% disease free survival for cases in stage A, 0.94 for Dukes B and 0.66 for Dukes C, while overall comparison between groups regarding local recurrence using the Wilcoxon (Gehan) statistic shows statistically significant difference (p-0.005). There is no statistical difference between Dukes A and Dukes B cases in distribution of local recurrence.
Splenectomy is definitive treatment for idiopathic thrombocytopenic purpura (ITP) because it removes both the sites of autoantibody producing cells and also the major site of platelet destruction. The purpose of this study was to evaluate long term results of splenectomised patients with ITP and to determine predictor factors for good response. A 167 patients with chronic ITP (136 females, 31 males), median aged 35 years (17-74) was splenectomised after 2 to 160 months (Median 12) from diagnosis of ITP. Indications for splenectomy were: 6 weeks of steroid therapy with platelet count below 10 x 10(9)/l or 3 months with platelet count under 30 x 10(9)/l, or treatment with prednisone above 30 mg more of 6 months to increase platelet count over 30 x 10(9)/l, or repeated relapses. Postoperative complications developed in 16 patients (9.5%), 3 of them died (1.8%) due to thromboembolism and 17 patients discontinued later controls. During follow up to 172 months (Median 62) 111/147 splenectomised patients were in remission (75.5%), 99 in complete (above 100 x 10(9)/l), 12 in partial (50-100 x 10(9)/l) and 36 patients (24.5%) were relapsed (below 50 x 10(9)/l). Remission was achieved in 79/88 patients (89.8%) with good response to prednisone before splenectomy toward 32/62 patients (51.6%) with poor response to prednisone (p < 0.01). Remission was obtained in 9/11 patients (81.8%) who responded well to intravenous immune globulin (0.4 g/kg x 5 d) and only in 1/8 who did not (p < 0.05). Higher response rate was achieved in patients under 40 years of age (81.6%) than in older ones (63.4%) (p < 0.05). No difference was shown between sex and time intervals (3, 6, 12, 24, 36 or over 36 months) from diagnosis to splenectomy. Splenectomy is an effective treatment of refractory ITP with response rate of 75.5% after median follow up of 62 months. In our patients better results on splenectomy were associated with age less than 40 years, good responses to steroid, and intravenous immune globulin.
Explore the source record for details and available documents.
Idiopathic thrombocytopenic purpura is an autoimmune disease in which macrophages of reticuloendothelial system, mainly in the spleen, remove platelets covered by autoantibodies from circulation. By removing the spleen 60-80% of patients are cured. Partial remission is achieved in 10-20% cases. Very few patients do not react on splenectomy. Recurrency of idiopathic thrombocytopenic purpura in a splenectomized patient after already achieved complete remission, may be caused by hypertrophy of one or more of the retained accessory spleens. We present 3 patients, 41, 23 and 44 year old, in whom splenectomy for ITP had been performed 10, 3 and 11 years earlier. After full remission which lasted 10, 2.5 and 10.5 years a full recurrency of ITP took place with signs of severe thrombocytopenia and haemorrhagic syndrome. Using ultrasonography, computed tomography and scintigraphy accessory spleen/s, were discovered. By their removal, a full remission was achieved in all 3 patients, but full favorable effect appeared approximately three months after surgery during which period additional steroid therapy was necessary.
Immune thrombocytopenic purpura (ITP) associated with pregnancy often involves considerable risk both for mother and child, and usually worsens in the third trimester of gestation. Pregnancy and delivery are especially difficult in patients with severe ITP (platelet count below 20 x 10(9)/L), who are resistant to prednisone and high dose intravenous immunoglobulin (IVIgG). In those cases we applied cesarean section (CS), to prevent intracranial haemorrhage due to fetal/neonatal ITP, and splenectomy at the same time as an effective therapeutic strategy for ITP. We present 5 patients (4 with chronic ITP and 1 with ITP associated with HIV infection), aged 21-35 years, with severe ITP (platelet count 2-10 x 109/L), resistant to prednisone (1-2 mg/kg), and 2/3 were resistant to IVIgG (0.4 g/kg x 5 d). Four patients with severe resistant ITP were supported with 1-2 doses of platelets from cell separator before CS and 1-3 dose during splenectomy. One patient increased platelet count to 55 x 109/L after treatment with IVIgG and splenectomy following CS were done without platelet transfusion. Splenectomy was performed immediately after CS in all patients, and two of them were hysterectomised (one with HIV infection). After splenectomy, platelet count was normalised in all patients, and they had no haemorrhage, wound haematoma formation or any adverse events. But ITP relapsed in 2/5 patients after 1-2 months. Two newborns had severe thrombocytopenia, which solved spontaneously after 3 days in one or after treatment with IVIgG in other. We propose that splenectomy following cesarean section should be considered as approach for delivery and treatment option for mothers with severe resistant ITP.
Splenectomy--the surgical removal of spleen is being performed in cases of: traumatic spleen rupture, as part of other surgical procedures, number of hematological, infectious and metabolic disorders. During the years 1988.-2001., there were 396 splenectomies performed at the First surgical clinic, for the cause of: autoimmune disorders 187 (47.34%), lymphoproliferative diseases 89 (22.59%). Hodgkin disease 35(8.94%), myeloproliferative disease 39 (9.95%), as part a of "staging" laparotomy 37(9.34%), other hematological disorders 7(2.20%). The spleen of [table: see text] 244 patients weighted 500-1500 g(61.62%), in 56 patients (14.14%) weighted less than 500 g, and in 96 patients (24.24%) spleen weighted more than 1500 g. Patients with thrombocytes less than 40,000/l 16 (4.04%) were perioperativly treated with fresh thrombocytes. Postoperative morbidity and mortality were registered in 54 (13.64%), i.e. 8 (2.02%) patients. Delayed results depended on primary disorder, comorbidities and supportive therapy. In this article, the particularities of the operative procedure were discussed, as well as importance of cooperation of surgeon and hematologist in perioperative treatment.
Auto transplantation of the spleen can be performed in the patients with traumatic rupture of the spleen, in whom spleen could not be conserved in the other way. The right indication for this method is isolated rupture of the spleen (concvasation or complete devascularisation). This method is not recommended in the endangered patients, patients with previous disease of the spleen as well as in the patients with the perforation of the other abdominal organs at the same time. Auto transplantation was performed in 12 patients with isolated splenic rupture and hematoperitoneum, 11 men and one woman. The majority of patients are younger. In 8 patients, autotransplant was placed into big omentum, in three into lipomatous tissue surrounding left kidney, and in one into anterior abdominal wall. In all the patients from this group, following analysis were taken: MCV (middle volume of erythrocytes), HTC, Hb, Le, Glucose, urea, creatinin, sodium, potassium, alkali phosphatasis, target cells, Howell Jolly's bodies, Heinz's bodies, IgG, IgA, IgM, C3, C4, T3, T4, T8, B, segmentated, eosinophiles, lymphocytes, reticulocytes, thrombocytes, fibrinogen, PT, APTT, aggregation of thrombocytes and aggregation of thrombocytes on collagen. The same parameters were taken in 12 patients with surgery similar to splenectomy and in 12 after splenectomy. After splenectomy, there was decrease of the immunologic defending abilities of the organism because of the loss of the childrens function of the spleen, decreased level of the opsonines and tutsin, which leads to the impaired phagocytosis, decreased concentration of IgM and T and B lymphocytes, while in patients after auto transplantation the results were physiological. The most important thing in the assessment of the function of the autotransplanted spleen is scintigraphic investigation using 99mTc-denaturated red blood cells. In our study, auto transplant function was assessed in 10/12 patients by scintigraphy. Five years after surgery, no one patient was proved to have postsplenectomic sepsis.
The stability of homeostasis is important to keep a balance between coagulation and fibrinolysis. A disorder of homeostasis leads to different physiological changes and causes different diseases such as cardiopathies and malignant tumors. Cardiopathies is characterized by a hypercoagulation. In the malignant tumors, besides the hypercoagulation due to plasminogen activators (PA) formed inside the tumor, a disorder of homeostasis leads also to acceleration of the fibrinolysis. The variety of internal and external factors in both cases determine the deviation of time for the clots formation, as well as the lyses of blood and fibrin clots. In this study the venous blood as well as the blood and the fibrin clots, derived from healthy dogs, the dogs with cardiopathies and with malignant tumors, were examined for the time of coagulation and fibrinolysis by adding different substances. In these experiments we used a glycolipoprotein extract from earthworm tissue homogenate (G-90) and the proteolytic enzymes P I and P II, isolated from G-90. The efficacy of the tested substances was comparable with the clinically administered anticoagulants. The most significant differences in clotting time among the three tested groups of dogs were obtained by application of the original G-90. The results suggest a possibility that G-90, along with the fibrinolytic enzymes and other biologically active factors, also contains a factor that decelerates the formation of clot in a specific medium, such as the blood from the dogs with malignant tumors.
Improving the control of artificial arms remains a considerable challenge. It may be possible to graft remaining peripheral nerves in an amputated limb to spare muscles in or near the residual limb and use these nerve-muscle grafts as additional myoelectric control signals. This would allow simultaneous control of multiple, degrees of freedom (DOF) and could greatly improve the control of artificial limbs. For this technique to be successful, the electromyography (EMG) signals from the nerve-muscle grafts would need to be independent of each other with minimal crosstalk. To study EMG signal propagation and quantify crosstalk, finite element (FE) models were developed in a phantom-arm model. The models were validated with experimental data collected by applying sinusoidal excitations to a phantom-arm model and recording the surface electric potential distribution. There was a very high correlation (r > 0.99) between the FEM data and the experimental data, with the error in signal magnitude generally less than 5%. Simulations were then performed using muscle dielectric properties with static, complex, and full electromagnetic solvers. The results indicate that significant displacement currents can develop (> 50% of total current) and that the fall-off of surface signal power varies with how the signal source is modeled. Index Terms-Control, electromyography (EMG), finite element (FE), modeling, prosthesis.