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Biomedical subjects

B Jeremić

Publications and source records attributed to B Jeremić.

15 recordsLinked to original sources

[Quantitative analysis of gallbladder function using quantitative dynamic radionuclide cholecystography].

The aim of the study is to demonstrate general function of the cholecyst through selected quantitative parameters derived from the quantitative radionuclide cholecystography method, using our own computer software HIDATA, and to evaluate values of specific quantitative parameters in 15 patients presenting with chronic calculous and 15 with chronic acalculous cholecystitis. A control group comprised 10 subjects with no changes on the cholecyst. Of four quantitative parameters calculated during cholecyst filling, the only significant one was the ascending segment slope of the curve from specific ROI, that is, K1 derived from it, because it shows its functional status, depending on the changes in its wall and the lumen content. The most significant parameters which maintain motor function of the cholecyst are ejection fraction (EF) and ejection rate (ER) which are always decreased in chronic cholecystitis, regardless of the presence of calculosis and the number of calculi in the lumen. The ejection fraction is especially decreased in the multiple sclerosis group; it is significantly decreased when compared with acalculous chronic cholecystitis. Our results indicate that a selection of parameters used in clinical practice for the assessment of the cholecyst function is necessary. Our program HIDATA included a large number of parameters of which three were classified as important for the assessment of the cholecyst function (K1, EF, ER), reflecting the process of filling and emptying of the cholecyst and offering reliable and valuable data for the treatment.

Cholecystitis

Acute toxicity from BOPP (BCNU, vincristine, procarbazine, cisplatinum) chemotherapy for glioblastoma multiforme.

Between January 1988 and October 1988, we treated 12 patients with glioblastoma multiforme with BOPP chemotherapy after surgery and radiotherapy. The protocol consisted of BCNU 50 mg/m2 days 1-3, vincristine 1.4 mg/m2 (maximum 2 mg) day 1, procarbazine 50 mg/m2, days 1-7 and cisplatinum 20 mg/m2, days 1-3. All patients had at least three courses of chemotherapy ECOG toxicity criteria were used. We observed 9/12 changes in WBC, 7/12 in Hgb. All patients had nausea and vomiting. We also observed 2/12 neuropathies related to CNS. Other toxicities were not observed.

Antineoplastic Combined Chemotherapy Protocols

[Single-fraction radiotherapy of painful bone metastases].

We analyzed first results obtained in 92 patients treated with single-dose fraction radiotherapy for painful bone metastases. Tumour doses was 10 Gy in a single fraction. Response was obtained in 59/92 (64%) patients. Thirty nine patients had complete response and 20 had partial response. Pain recurred in 18/39 patients who initially responded. Toxicity of this radiotherapeutic treatment is acceptable, and can easily be managed with standard therapy.

Adult

[Radiotherapy of metastatic brain tumors].

On the basis of data from literature, the authors present the role of radiotherapy in the treatment of brain metastases. This role has been considered as a sole treatment or as a combined treatment, especially with surgery. New techniques of radiotherapy which could enable better results in the treatment of brain metastases in the future, are presented.

Brain Neoplasms

[Radiotherapy of primary spinal cord tumors in adults].

Between 1980 and 1985 we treated 21 patients with primary spinal cord tumors. There were two diffuse and ten localized ependymoma, six low grade astrocytoma and three malignant glioma. Surgery consisted of total resection in six patients, subtotal resection in three and biopsy in twelve patients. Radiation doses ranged 45-55 Gy. Median age was 55 years (34-70 years), and median follow-up after therapy was 5 years (1-9 years). For patients with localized ependymoma, overall survival and 5-year recurrence-free survival are 80%. Of two patients with diffuse ependymoma, one is alive with no evidence of disease 6 years after the initial diagnosis, while the other is dead. Overall survival and 5 years recurrence-free survival for patients with low grade astrocytoma are 83% and 67%, respectively. All three patients with malignant glioma died of local recurrence (one had diffuse craniospinal metastases, too) one year after the initial diagnosis. Radiotherapy is therapy of choice after surgery in primary spinal cord tumors in adults, although local recurrences remain the major problem.

Adult

[Acute signs and symptoms of toxicity due to the BOPP regimen (BCNU, vincristine, procarbazine, cisplatin) during treatment of high-grade astrocytoma].

BOPP chemotherapy regimen was introduced in patients with high-grade astrocytoma after surgery and radiotherapy. There were 10 anaplastic astrocytomas and 19 multiforme glioblastomas. Protocol consisted of BCNU 50 mg/m2, days 1-3, Vincristine 1,4 mg/m2 (max 2 mg), day 1, Procarbazine 50 mg/m2, days 1-7 and Cisplatin 20 mg/m2, days 1-3. All patients received at least three cycles of BOPP chemotherapy. The used toxicity criteria corresponded to ECOG. We observed 12 changes in WBC, 29 changes in haemoglobin, 18 changes in platelets and 11 changes in hematocrite. All patients had nausea and vomiting. We also observed 4 neurologic toxicities. Toxicities we observed responded favourably to standard means of therapy which can suggest either shortening of the interval between the cycles or increasing the dose per cycle.

Acute Disease

[Use of chemotherapy in brain tumors in children--possibilities and perspectives].

In the past two decades a huge progress was achieved in the treatment of malignant diseases in children. The cyclical chemotherapy combined with surgery and radiotherapy gave very good results. However, the contribution of chemotherapy to paediatric neuro-oncology was not as great is it was to other branches of paediatric oncology (acute leukaemia, malignant lymphoma, Wilms' tumour). One of the reasons is that although brain tumours are usually solid in children the existence of different histological types contributes to the fact that they are not very frequent or are rare. Consequently, for many types the necessary number of representative controlled studies is lacking. On the other hand, the leading paediatric oncology associations in the world (Children's Cancer Study Group (CCSG), International Society of Paediatric Oncology (SIOP) and Paediatric Oncology Group (POG)) have applied the prospective clinical programmes of treatment of these tumours later than in other malignant diseases. On the basis of the analysis of these programmes and experience of individual oncological centres a certain experience was acquired in present-day possibilities of chemotherapy in children suffering from brain tumours.

Brain Neoplasms

[Long-term oral administration of etoposide in the treatment of patients with advanced non-small-cell carcinoma of the lung. The second phase of a clinical study].

Over the period from May 1989 to May 1992 thirty-four patients with advanced non-small cell lung cancer (NSCLC) were treated with prolonged administration of oral etoposide. Etoposide was administered in a dose of 50 mg/m2 a day for 21 days. Nine (26%) patients partially responded to the treatment that lasted 2-7 months (median 5 months). Median survival time was 6 months, and 1-year survival was 32%. The most common toxic events were alopecia and myelosuppression. No patient died of treatment-related toxicity. Results of this study demonstrate moderate efficiency of the prolonged administration of oral etoposide to patients with advanced NSCLC.

Administration, Oral

[Ondansetron in the prevention of radiation-induced nausea and emesis in patients treated with single-fraction irradiation].

INTRODUCTION: Intensity and severity of radiation-induced nausea and emesis depend on a number of factors including irradiation site, irradiation dose, treatment field (width and length), and age of the patients. Although less intensive than that induced by chemotherapy, during protracted courses of fractionated radiotherapy discomfort can be substantial. As early as 1953, Court-Brown [2] described characteristic symptoms after a single-fraction radiotherapy as "acute irradiation syndrome": irradiation was followed by asymptomatic period of 40-90 minutes, after that the patient experienced an acute episode of emesis, usually without preceding nausea. After a period of relative stabilization, additional episodes of emesis occurred for six hours after irradiation, decreasing its intensity with time. Danjoux et al. [5] noted a higher incidence of radiation-induced emesis after the upper half-body irradiation (UHBI) than after the lower half-body irradiation (LHBI), lack of efficacy of antiemetics administered, and similar response to emesis after the lower or the upper half-body irradiation. These results suggested that critical area was the upper abdomen. Although the exact mechanism of occurrence of radiation-induced emesis is still unknown, recent studies revealed that serotonin released from the gastrointestinal tract also produced emesis through mechanisms of involvement of 5-hydroxytriptamines (5-HT3) receptors, visceral afferent fibers and chemoreceptor trigger zone. We have, therefore, used a new 5-HT3 antagonist, ondansetron, in prevention of radiation-induced emesis in patients treated with single-fraction radiotherapy. MATERIAL AND METHODS: All patients included in the study had bone metastases treated for pain relief and in all of them, the entire or a part of the upper abdomen was enclosed in the treatment field. The patients' characteristics are given in Table 1. Patients in group I had vertebral lesions that required the central radiation field at Th8-L3 level. Patients in group II were treated with LHBI-the upper field border at crista illiaca; those in group III with UHBI-the lower field border at umbilicus, while those treated with mid-half-body irradiation had the lower field border at the floor of the pelvis. Patients in group I received 8 mg of ondansetron orally, three times a day, for 3-5 days after irradiation. Those in groups II-IV received 0.15 mg/kg of ondansetron intravenously 15 minutes before HBI, just on the day of irradiation. To verify patients' data we used a special questionnaire. Emetic episodes were defined as every emetic episode with minimal interval of 1 minute between separate episodes. Response to therapy was considered complete (no episodes within 24 hours), major response (with only 1-2 episodes), minor (3-5 episodes) and no response (more than 5 episodes of emesis or administration of additional new antiemetics). RESULTS: In group I, 93% of patients had complete response within 24 hours, while 7% had major response of emesis. Regarding nausea, 89% had complete lack of nausea, while 11% had moderate nausea. In the next 5 days, 96-100% of patients had complete response or major response. At the same time, nausea was controlled in more than 80% of patients. In group II, there was a 100% response rate regarding nausea and emesis lasting for 5 days after radiation therapy. Patients in groups III and IV had also a 100% response rate regarding both nausea and vomiting. Side-effects of ondansetron administration were not observed. DISCUSSION: The results of this pilot study showed the excellent effect of the new 5-HT3 antagonist, ondansteron, in prevention of radiation-induced nausea and emesis. They confirmed results of the other authors [9, 10, 11] that used this antiemetic in the control of radiation-induced emesis. These studies included a variety of radiotherapeutic time-dose fractionation schedules, and some of them [11] included results of the total body irradiation. (ABSTRACT TRUN

Antiemetics

[Significance of formation of micronuclei in SCC VII murine cells treated with various chemotherapeutic agents].

INTRODUCTION: The in vitro chemosensitivity testing aims at predicting the response of an individual tumour to chemotherapy choosing optimal agents for a particular patient. Among many chemosensitivity tests developed over the years [1-6], special emphasis was made on clonogenic assays that showed good use and correlation between laboratory and clinical data [7-9]. One of the assays used to predict the response to various anti-cancer modalities is the micronucleus assay using the cytokinesis-block [12-14]. This block is achieved by administration of Cytochalasin-B in order to prevent cytoplasmic, but not the nuclear, division. This leads to micronucleus formation which are counted in binuclear cells. Since there are only a few reports of the use of this assay in predicting chemosensitivity [13, 16], we explored the possibility of using this assay to predict chemosensitivity to various anti-cancer agents. MATERIAL AND METHODS: Exponentially growing SCC VII cells were treated with various concentrations of 11 anti-cancer agents: Mitomycin C, Doxorubicin (ADR), Epirubicin (EPI), Cisplatin, Carboplatin (CBDCA), Etoposide (VP-16), Vincristine, 5-fluorouracil, Methotrexate, Nimustine, and Dacarbazine for 1 hour. After that, Cytochalasin-B was added and dishes were incubated. After various time intervals, cells were fixed in situ and dried. Electron microscope was used to count the number of micronuclei (MN) in binucleate cells as well as multinucleate cells (MNC) in the total cell population. Cell survival was also evaluated by using the colony formation assay [18]. RESULTS: Maximal % of binucleate cells (BNC) was usually reached at 24-30 hours of culture, except for cells treated with ADR and EPI, in which it was reached at 30-72 hours (Figures 1 and 2). All drugs induced formation of micronuclei and dose-response curves for micronucleus frequency were obtained using the data at peak % BNC times. For all drugs, micronucleus frequency increased with concentration (Figure 3), but at the highest concentration used (considered to be overly toxic-Figure 4), the micronucleus frequency was rather lower. This decrease in micronucleus frequency was largely attributed to the decrease in % BNC. When the data at the highest concentrations of all drugs were excluded, a correlation was found between micronucleus frequency and surviving fraction (r = 0.85; p < 0,001) (Figure 5). DISCUSSION: Since micronucleus formation is a sign of chromosome damage that leads to cell death, we used this assay to evaluate chemosensitivity in 11 widely used anticancer agents. Although they can be classified according to mechanism of action as different class agents, they have in common the formation of micronuclei as a sign of cytotoxicity. Cell cycle arrest observed in some agents might be evaluated by assessing the delay in increase of BNC and MNC. The difference observed regarding cell cycle arrest suggested different mechanisms of its action. MN frequency was almost dose-dependent at lower concentrations, but at the highest concentrations, it obviously decreased, showing, therefore, some discrepancies with the data obtained when radiosensitivity was tested that way [14], probably due to extreme toxicity of agents. The optimal concentrations seem to be those providing a 20-80% surviving fraction. Another slight difference, when compared with similar radiosensitivity studies is a decrease with longer duration of culture observed in chemosensitivity testings. The reason for this difference is still unknown, but it emphasized the necessity for choosing the optimal duration of culture, probably that necessary for reaching maximal % BNC. This assay seems useful in predicting chemosensitivity of at least some tumour cells to various (appropriate) concentrations of various anti-cancer agents. However, new studies are warranted to further use of this assay, before testing it in clinical practice.

Animals

[The effect of extent of tumor resection on the outcome of combined therapy in patients with glioblastoma multiforme].

INTRODUCTION: The importance of the extent of surgery as a prognostic factor in multiform glioblastoma has been investigated for years. Some studies could not establish its influence on survival of patients treated with surgery, postoperative radiotherapy, with or without chemotherapy. On the other hand, there are data suggesting benefit for patients treated with more aggressive surgical approach. The aim of this study was to investigate the influence of the extent of surgery on survival/progression-free survival of patients with multiform glioblastoma treated with two consecutive protocols of a combined approach. MATERIAL AND METHODS: Of 86 patients that entered this study, thirty-seven were treated with surgery, postoperative hyperfractionated radiotherapy using 1.2 Gy b.i.d. to a total tumour dose of 72 Gy in 60 fractions in 30 treatment days and adjuvant chemotherapy consisting of BCNU, vincristine, procarbazine and cisplatin for up to 6 cycles or until tumour progression. Forty-nine patients were treated with surgery and postoperative accelerated hyperfractionated radiotherapy using 1.5 Gy b.i.d. fractions to a total tumour dose of 66 Gy in 44 fractions during 22 treatment days. BCNU and hydroxyurea were given once weekly during the irradiation period. Surgery consisted of biopsy in 25 patients and subtotal or gross total tumour resection in 61 patients. Patients treated with a more radical surgery had longer median survival time and higher 1- and 2-year survival rates than those treated with biopsy (56 v.s. 29 weeks, respectively; 62% and 23% v.s. 16% and 0%, respectively; long rank, p = 0.0000) (Figure 1). They also had longer median time to tumour progression and higher 1-year progression-free survival rate than those treated with biopsy only (33 v.s. 21 weeks, respectively; 20% v.s. 0%, respectively; log rank, p = 0.00000) (Figure 2). Multivariate analyses using both survival and progression-free survival as endpoints confirmed that the extent of surgery was an independent prognostic factor, together with the age, tumour location, and interfraction interval (Tables 3 and 4). DISCUSSION: The benefit of a more radical surgery remains controversial in patients with multiform glioblastoma, although maximal tumour reduction should be supported from the cytokinetic point of view. Findings of various authors support this view. Results of this study add further evidence that the aggressive surgical approach carries significant benefit for patients with multiform glioblastoma regarding the survival and progression-free survival. These observations are confirmed with multivariate analyses that showed independent influence of this prognostic factor.

Brain Neoplasms

[Modern diagnostic and therapeutic methods in bronchiolo-alveolar carcinoma].

In this article is described problems of bronchioloalveolar carcinoma, with respect to increased incidence of adenocarcinoma and bronchioloalveolar carcinoma. It was observed that bronchioloalveolar carcinoma occurs more frequently in younger persons and in women. Etiology of bronchioloalveolar carcinoma is still unknown. There is not an obvious connection with smoking but connection with previous damage of lung parenchyma. Bronchioloalveolar carcinoma can be defined as neoplasm which is not of central origin , but is peripherally located; therefore the term "bronchiolo-" but not "broncho-alveolar" carcinoma. It grows along alveolar septa and lung parenchyma remains intact. There is three pathohistological subtypes of bronchioloalveolar carcinoma: mucinous, non-mucinous and sclerotic form and three radiological patterns: solitar, pneumonia-like and diffuse. Clinical features depend of the stage and patient are most frequently asymptomatic. They later present with chest pain, dyspnea, cough, hemoptysis and weight loss. Complications include bronchorrhoea and intrapulmonal shunts. These findings, together with laboratory analysis, radiological tests (including CT scans) and cytological or hystological proof of malignancy, make definite diagnosis. Therapy depends on the stage of disease and is identical with that of other subtypes of non-small-cell lung cancer.

Adenocarcinoma, Bronchiolo-Alveolar

[Modern approach to malignant pleural mesothelioma. 1) Pretherapeutic evaluation].

In this review we outlined the basis of current concepts of pretreatment evaluation in patients with malignant pleural mesothelioma. This tumour, rarely reported until sixties, is mostly connected with exposure to asbestos. Its increased incidence of approximately 50% is noted in last decades. Various histological types of this tumour are well known, but its biology is not well understood. Recent TNM classification and modern diagnostic approach such as computerized tomography and thoracoscopy, as well as standard means of diagnosis are aimed at obtaining early diagnosis and staging in order to undertake the adequate therapy.

Humans

[Modern aspects of antiemetic therapy].

We summarized the current knowledge about chemotherapy and radiotherapy-induced nausea and vomiting. Nausea and vomiting are among the most frequent side effects in the treatment of malignancies, and they are very unpleasant for the patient. We reviewed basic aetiological and physiological mechanisms (except that of delayed emesis, which is not enough explored), particularly the role of serotonin in acute chemotherapy and radiotherapy-induced nausea and vomiting. An oncologist cannot make many changes in the treatment of malignancies and patient-related prognostic factors, but he (she) can make changes in the treatment of nausea and vomiting in order to improve the quality of life of patients with malignancies. We also listed some of the most widely used antiemetic drugs with their most important pharmacological properties. Important progress in the control of nausea and vomiting was obtained by the use of selective antagonists of 5-HT3-receptors such as ondansetron, granisetron, tropisetron and dolasetron. Usually ondasetron and granisetron were used. Their clinical activity is similar but better results were obtained with the combination of 5-HT3-antagonists and corticosteroids (complete response was approximately 90%) than by their individual use (complete response was approximately 50%). The problem of delayed emesis has not yet been solved, and best results were obtained with the combination of metoclopramide and corticosteroids. For the control of nausea and vomiting caused by radiotherapy, orally given ondansetron is effective.

Antiemetics

[Malignant pleural mesothelioma. II. Modern therapeutic concepts].

In the second part of our review of malignant pleural mesothelioma, we reviewed current concepts of the treatment of this highly malignant disease. Although there are still advocates for the use of best supportive care to the treatment of these patients, the accumulated evidence favorizes the combined modality approach. Surgery, followed by postoperative external beam radiotherapy (or intraoperative radiotherapy), offers increased response rates and median survival as well as a higher percentage of patients surviving a two-year period. Although widely tested, both single-agent and multiple-agent chemotherapy did not succeed in transmitting high response rates into an improved survival. New treatment approaches are needed to improve poor survival in patients with malignant pleural mesothelioma.

Humans