[Traumatic arteriovenous fistulas].
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Arteriovenous Fistula↗
Biomedical subjects
S Radulović
Publications and source records attributed to S Radulović.
Survival advantage for carboplatin substituting cisplatin in combination with vindesine and mitomycin C for stage IIIB and IV squamous-cell bronchogenic carcinoma: a randomized phase III study.
This communication represents the definitive report of a randomized phase III study comparing cisplatin and carboplatin, in combination with vindesine and mitomycin C in stage IIIB and IV squamous-cell bronchogenic carcinoma. A total of 221 patients entered the study and were randomized into two arms. Of these, 114 patients (109 evaluable for activity) were randomized to arm A, receiving cisplatin 120 mg/m(2), mitomycin C 8 mg/m(2) and vindesine 3 mg/m(2) per cycle; 107 patients (101 evaluable for activity) were randomized to arm B receiving carboplatin 500 mg/m(2) with the same doses of mitomycin C and vindesine per cycle. Patients with progressive disease (PD) were excluded from the study after the 2nd cycle, and those with stable disease (SD), partial response (PR) and complete response (CR) received six cycles of chemotherapy (or less in case of early progression). Patients were stratified according to the clinical stage (IIIB vs. IV), performance status (0+1 vs. 2+3) and tumor histological grade (I+II vs. III). In the cisplatin arm two patients (1.9%) achieved a CR, 38 (34.9%) a PR, 45 (41.2%) a SD and 24 (22.0%) had PD; the overall response rate was 40/109 (36.8%). In the carboplatin arm five patients (5.0%) achieved a CR, 31 (30.7%) a PR, 40 (39.6%) a SD, and 25 (24.7%) had PD; the overall response rate was 36/101 (35.7%). No statistically significant difference in response rate was present between the two arms, and the response rate was not influenced by performance status, histological grade or clinical stage. The Kaplan-Meyers curves displayed a significant advantage both for time to progression (P=0.005) and overall survival (P=0.008) for patients in the carboplatin arm. The advantage for patients receiving carboplatin instead of cisplatin appeared evident in univariate setting for patients with a good performance status and clinical stage IV, and occurred irrespectively of tumor histological grade; response duration and survival of responders was identical in the two arms. Patients achieving a stable disease survived longer in the carboplatin than in the cisplatin arm (P=0.012). Thus, substitution of cisplatin by carboplatin in the combination chemotherapy regimen, although more hematologically toxic (but less emetogenic) resulted in a similar response rate, but a significantly longer time to progression and overall survival.
Adult↗
Therapeutic implications of the kinetics of immunomodulation during single or combined treatment of melanoma patients with dacarbazine and interferon-alpha.
The therapy of metastatic melanoma has not given satisfactory results. Single chemo- or immunotherapeutic agents in the adjuvant setting or combined chemoimmunotherapy for metastatic disease have generally been evaluated only in terms of clinical benefit. Considering that dacarbazine (DTIC) and interferon-alpha (IFN-alpha) are among the most frequently used agents in the treatment of melanoma, the aim of this study was to evaluate the kinetics of immunological changes during adjuvant treatment of melanoma patients with DTIC or with IFN-alpha monotherapy, as well as by their combination in metastatic disease. The evaluated immunological parameters showed significant early increase in the activity of NK (natural killer) cells, CD4/CD8 ratio, CD4+ T cell number in patients treated with combined chemoimmunotherapy and an increase in expression of the early activation antigen CD38 on CD8+ cytotoxic T cells, both, in patients treated with combined chemoimmunotherapy and with IFN-alpha alone, while, no significant change in any one parameter was detected in the group of patients receiving DTIC. The kinetics of the observed immunological changes, restricted to combined chemoimmunotherapy, indicate that the engagement of antitumor immune response appears early but is short-lived and that this favorable effect should be augmented and prolonged by the timely introduction of additional immunomodulating agents.
ADP-ribosyl Cyclase↗
[War injuries of blood vessels of the extremities].
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Blood Vessels↗
Eight-hour infusion versus bolus injection of doxorubicin in the EAP regimen in patients with advanced gastric cancer: a prospective randomised trial.
BACKGROUND: Doxorubicin (40 mg/m2/cycle), etoposide (360 mg/m2/cycle) and cisplatin (80 mg/m2/cycle) comprise an efficient regimen in patients with advanced gastric cancer (AGC). However, its excessive hematological toxicity led doctors to avoid using the combination. Doxorubicin is the main cause of myelotoxicity in the EAP regimen. The aim of this study was to compare an eight-hour infusion of doxorubicin (arm A) with intravenous injection of doxorubicin (arm B) in the EAP regimen with respect to toxicity, objective responses, time to progression (TTP) and survival in patients with AGC. PATIENTS AND METHODS: One-hundred twenty chemotherapy-naïve patients with measurable AGC were randomised between September 1994 and August 1998. Sixty patients in arm A and sixty patients in arm B were considered as fully evaluable. The arms were well balanced for age, sex distribution, previous therapy, histological grade and performance status. One-hundred eighty cycles were applied in arm A (median 2) and 201 in arm B (median 4). RESULTS: No difference was detected (P = 0.28) in the response rate of arm A 20% (CR 3; PR 9; 95% CI: 10-30) and B 28% (CR 3; PR 14; 95% CI: 17-40). But there was a significant difference in PD (P = 0.005) between arm A (51%) and arm B (36%). TTP (P = 0.01) and survival (P = 0.02) analyses detected an advantage for arm B vs. arm A. Grades 3-4 toxicity were as follows (arms A%/B%): anemia 8/10, leukopenia 24/26, thrombocytopenia 6/16 (significance, P = 0.05), nausea/vomiting 5/8, diarrhea 6/2, mucositis 8/5. Apart from the trombocytopenia, there was no significant difference in toxicity grades 3-4 between the two arms. Four treatment-related deaths occurred, two in each arm. CONCLUSIONS: Bolus injection of doxorubicin is superior to eight-hour doxorubicin infusion in the EAP regimen in terms of survival, TTP and PD without being significantly more toxic.
Adult↗
Patient statement of satisfaction with antiemetic treatment is related to quality of life.
The aim of our study was to explore the possible relationship between patient satisfaction with antiemetic treatment and quality of life (QoL). The study sample consisted of 136 chemotherapy-naive patients with breast cancer, with Karnofsky index 90% to 100%, scheduled to receive their first cycle of, mainly adjuvant, 5-fluorouracil/doxorubicin/cyclophosphamide chemotherapy. Two antiemetic regimens were used for the prevention of acute emesis. No antiemetic prophylaxis was given for delayed emesis. QoL was assessed using the Rotterdam Symptom Checklist (RSCL). The RSCL was completed before chemotherapy (day 1) and on day 5. Statement of satisfaction was given on day 5. The change in RSCL scores between day 5 and day 1 was calculated and compared in three subgroups of patients: those very satisfied (n = 55), satisfied (n = 65), and unsatisfied with antiemetic treatment (n = 16). Patient statement of satisfaction was related to psychological distress (p = 0.002), physical symptom distress (p = 0.002), and activity level (p = 0.002). It was also related to the control of nausea (p < 0.01) and vomiting (p < 0.0001). We suggest that patient statement of satisfaction with antiemetic treatment could be an outcome measure for response assessment in antiemetic trials.
Adult↗
[Occurrence of atrial fibrillation and cerebrovascular insult in patients at the Emergency Center of the General Hospital in Konjic].
Atrial fibrillation (AF) presents disorganized activity of atrium with irregular ventricular striking. It is observed in paroxysmal and persisting form. Paroxysmal form is more risky for embolism (about 6 times). Aim of this research was to determine frequency of atrial fibrillation as increased risk for cerebrovascular insult (CVI). We conducted our research in general hospital Konjic and all patients who were treated in the period 1998-1999 are included. The results of the research are the following: 1. Total number of CVI patients was 126 what compared with total number of hospitalized patients indicates increased prevalence of 8.8% in relation to world parameters (2-5%). 2. 55.7% CVI patients had verified persistent AF what also represents increased percentage compared to the world parameters. 3. The following cardiovascular diseases are involved in the etiology of AF where CVI was a result: *atherosclerosis of heart 84.9%, *coronary disease 15.6%, *heart malformations, 4.76%, *other diseases (hyperthyroidism 1.5%, idiopathic AF). 4. Incidence of other risk factors at the patients with CVI and AF: *hypertension 63.4%, *diabetes mellitus 23.8%, *smoking 9.5%, *hyperlipoproteinemia 5.5%, *2 and more risk factors 97.8%. 5. Patients with CVI and AF are more often women and more than 60 years old. According to the results of this research, an incidence of AF in CVI is lager in comparison to the world parameters. AF in persisting form occurs mostly at arteriosclerosis of heart. Women more than 60 years old are the most jeopardized category. Concerning that CVI is in the first place as a cause of invalidity and in the third place as a cause of death, AF as a risk for CVI has important place in the prevention and treatment together with other risk factors.
Atrial Fibrillation↗
Antiproliferative action of isatine-beta-thiocarbohydrazone and N-ethylisatine-beta-thiocarbohydrazone on human PBMC and on two neoplastic cell lines.
The antiproliferative action of two synthetic compounds, isatine-b-thiocarbohydrazone (IsTCH) and N-ethyl isatine-beta-thiocarbohydrazone (N-Et-IsTCH), towards healthy human peripheral blood mononuclear cells (PBMC) and two neoplastic cell lines in vitro, was investigated. IsTCH and N-Et-IsTCH were dissolved in DMSO and then diluted with nutrient medium to desired final concentration. Target cells were PBMC, as well as human cervix carcinoma - HeLa cells, and murine melanoma B16 cells. Five different concentrations (3 microM to 50 microM) of investigated agents were applied on target cells. Cell survival was determined 72 h after the agent's action using MTT test. Results obtained showed that both investigated compounds exerted a dose dependent antiproliferative action to neoplastic cell lines. Their action was only cytostatic; trypan blue exclusion test did not show any sign of direct drug cytotoxicity when drugs concentration were less than 50 microM. ICs50 +/- SD for IsTCH antiproliferative action were 61.69 +/- 4.25 microM for HeLa cells; 34.1 +/- 7.15 microM for B16 cells: 17.62 +/- 7.11 microM for nonstimulated and 30.0 +/- 9.46 microM for stimulated (by 5 mg/ml PHA) PBMC. ICs50 +/- SD for the action of N-Et-IsTCH were 21.86 +/- 1.77 microM for HeLa cells; 10.37 +/- 1.55 microM for B16 cells; >47 microM for both, nonstimulated and for stimulated, PBMC. Nonstimulated human PBMC appeared to be the most sensitive to the cytostatic IsTCH action; while HeLa cells were the most resistant. N-Et-IsTCH showed more than two or five fold stronger antiproliferative effect toward B16 cells than on HeLa or PBMC cells, respectively, and more than three times intensive activity compared to IsTCH, indicating specificity of N-Et-IsTCH towards inhibition of melanoma cell growth. While increasing concentrations of IsTCH led to decrease in the the PBMC induced suppression of HeLa cell survival; N-Et-Is-TCH in the difference from IsTCH, in dose dependent way contributed to the PBMC induced suppression of HeLa cell survival. In conclusion, the activity of N-Et-Istch on malignant melanoma cells deserves further investigation.
Adult↗
Lyophilized whole human melanoma cells stimulate human PBMC proliferation and enhance suppressive action of PBMC toward survival of the same malignant cell line in vitro.
The goal of this work was to determine: a) do lyophilized human melanoma BG or Fem-X cells affect the proliferative capacity of normal human peripheral blood mononuclear cells (PBMC) and b) does the PBMC six-days preincubation in nutrient medium with FBS with, or without lyophilized human melanoma BG or Fem-x cells, affect their suppressive action on the survival of the same malignant cell line in vitro. In the aim to avoid any stimulating effect of FBS, other group of experiments were done in nutrient medium with human AB serum in order to determine: c) does the PBMC six-day-preincubation with lyophilized human melanoma BG or Fem-x cells affect their antiproliferative action on the corresponding malignant cell line in vitro and d) does the PBMC six-day preincubation with lyophilized normal PBMC, obtained from healthy volunteer (as a source of allogenous, but not of tumor antigens), affect their suppressive action on the survival of both melanoma BG and Fern-x cell lines in vitro. Results obtained in the presence of FBS in nutrient medium, showed that lyophilized BG cells induced a proliferation of the healthy PBMC, depending on the number of stimulating lyophilized cells. Lyophilized Fem-x cells induced healthy PBMC proliferation in lesser degree than lyophilized BG cells. This stimulation was almost constant, not dependent on the number of stimulating lyophilized Fem-x cells. Six-day stimulation in vitro by both lyophilized melanoma cells enhanced the suppressive action of PBMC on the survival of the corresponding malignant cell line. Experiments done in nutrient medium with normal human AB serum showed that six-day stimulation with lyophilized melanoma cells enhanced, again, the suppressive action of PBMC on the survival of the corresponding malignant cell line. Contrary, six day preincubation of normal PBMC with the lyophilized healthy PBMC (obtained from other healthy person) inhibited their suppressive action on the survival of both malignant cell lines in vitro.
Adult↗
T-2 toxin affects proliferation of three different neoplastic cell lines.
The antiproliferative effect of T-2 toxin (T-2) towards mouse melanoma B16 cells, human myelogenous leukemia K562 cells, and human cervix carcinoma, HeLa cells, was studied. For the first four days of T-2 presence B16 cell survival was decreased in dose dependent fashion. However, cell survival after eleven days T-2 action may be dual: some stimulation of cell growth that was direct function of the number of seeded cells per well was observed and cell survival (for the highest number of seeded cells) six times greater than control, was noticed at 20 nM T-2 toxin concentration. A smaller cell growth stimulation (cell survival more than 3 times higher than control) was observed with a lower cell number seeded per well. Nevertheless, by eleventh day concentrations of T-2 higher than 35 nM completely inhibited B16 cell proliferation. The same trend was noticed for T-2 action towards K562 cells. Treatment of HeLa cells with various T-2 concentrations led to a marked inhibition of cell survival that was more pronounced at the end of 44th or 72nd hour, than after the 20th hour of agent's action. ICs50 values obtained in the present work, suggest that B16 cells were the most sensitive to T-2 antiproliferative action, while HeLa cells were the most resistant. When PBMC were cultured with HeLa cells the antagonism against various T-2 concentrations was observed; cell survival determined after 44, or 72 hours of cells incubation, was less decreased compared to cultures treated with T-2, or with PBMC only. In addition, it was shown that T-2 and cis-DDP had an antagonist effect on HeLa cells survival.
Cell Division↗
Adenosine contributes to the amine oxidase-mediated spermine cytotoxicity to human myelogenous leukemia K562 cells.
The effects of adenosine, aminophylline, dipyridamole and salbutamol on the amine oxidase-mediated spermine cytotoxicity to KS62 human myelogenous leukemia cells without Ph-chromosome, spontaneously enriched with mildly adherent cells, were studied. In the absence of spermine, adenosine expressed very mild inhibitory action on K562 cell survival, while in combination with the polyamine an almost additive increase in spermine-FBS cytotoxicity was observed. Aminophylline and salbutamol attenuated both spermine-FBS and spermine-FBS-adenosine suppression of cell survival and viability when equimolar concentration of these agents and the adenosine were applied. Pre-treatment of the cells with higher adenosine levels, in the presence of either aminophylline or dipyridamole, or salbutamol, was associated with decreased K562 cell survival, with the appearance of morphological changes in 10-20% of cells. Additional spermine-FBS cytotoxic effect was not observed in cells pre-treated with adenosine-aminophylline, or adenosine-salbutamole, but morphological changes in 10-20% of cells, even in the presence of spermine, was observed again. Dipyridamole alone suppressed very weakly K562 cell survival. In cells pretreated with dipyridamole, in the presence of spermine-FBS, an additive decrease in cell survival was observed. Pre-treatment of cells with dipyridamole and adenosine in presence of spermine-FBS did not result in a decrease of cell survival compared to the one obtained in dipyridamole-spermine-FBS treated cells.
Adenosine↗
The mechanism of 8-Cl-cAMP action.
8-Chloroadenosine 3',5'-monophosphate (8-Cl-cAMP) is a potential new anticancer agent, but its mechanism of action is not clearly defined. In this work we have studied the effect of various heat inactivated and heat untreated human sera in the absence or in the presence of a nonspecific phosphodiesterase (PDE) inhibitor, IBMX, or of nucleoside transport inhibitor and cGMP-specific PDE inhibitor dipiridamole (DP), or of inosine-monophosphatedehydrogenase (IMPDH) inhibitor, tiazofurin, (T), on the antiproliferative 8-Cl-cAMP action towards two human malignant cell lines, K562 and HeLa cells, in vitro. Cell survival was determined 72 hrs after the agents action, using MTT assay. The results obtained, indicated the similar inhibitory effect of 8-Cl-cAMP on HeLa cell survival in the presence of four different heat untreated human sera (IC50 = 4-4.8 microM). Serum heat inactivation caused decrease in 8-Cl-cAMP antiproliferative action depending on the blood donor (IC50 = 23 microM, 15 microM, 19 microM, and 9 microM) and suggesting that some thermolabile ingredient(s) present in sera is involved, at least partially, in the induction or permittance of antiproliferative 8-Cl-cAMP action. K562 Cells were not as much resistant to 8-Cl-cAMP as HeLa cells, or mouse melanoma B16 cells; in the presence of heat untreated FBS, IC50 = 16 microM, while for B16 cells IC50 was 8 microM. Different human sera show different effect on 8-Cl-cAMP action on K562 cells: IC50 = 7.5 microM and 16.5 microM. In the presence of heat inactivated human sera 8-Cl-cAMP IC50 concentrations were higher, with relevant mutual differences. The effect of different sera on 8-Cl-cAMP action was only partly abrogated in the presence of a nonspecific PDE inhibitor, IBMX, suggesting that the serum PDE action is one of the various factors contributing to the induction of 8-Cl-cAMP antiproliferative action. Nucleoside transport inhibitor and cGMP-specific PDE inhibitor dipiridamole inhibited the antiproliferative 8-Cl-cAMP action to HeLa and K562 cells. Tiazofurin and 8-Cl-cAMP acted as antagonists on HeLa, but not on K562 cells.
1-Methyl-3-isobutylxanthine↗
Tumour-induced hypercalcaemia, resistant to systemic anti-hypercalcaemic and chemo-endocrine treatments, but responding to radiotherapy in a breast cancer patient.
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Antineoplastic Agents, Hormonal↗
Pilot study of enhancement of cisplatin activity by high dose cytarabine in advanced gastric and colorectal (G3/G4) cancer.
The response rate of advanced gastric cancer to cisplatin monotherapy averages 20% and in colorectal cancer no activity of cisplatin monotherapy has been detected in initial studies. Cytarabine is ineffective in gastric cancer and displays borderline activity in colorectal cancer. In vitro studies on cell lines from human digestive cancers have demonstrated a dose and timing dependent enhancing effect of cytarabine on cisplatin antitumor activity. The aim of the present study was to investigate whether this enhancing activity can also be demonstrated in vivo. We have treated 37 patients with advanced gastrointestinal cancer (21 gastric and 16 colorectal), poorly differentiated G3-G4. The treatment included-Day 1: cytarabine 500 mg/m2 0 h and 12 h, cisplatin 15 mg/m2 6 h and 18 h. Day 2-4:cisplatin 30 mg/m2. Cycles were repeated every 4 weeks. Thirty four patients were evaluable for objective response. The overall response rate was 16.7% (CR 2/18, PR 1/18, SD 5/18, PD 10/18) for patients with gastric cancer and 25% (CR 1/16, PR 3/16, SD 7/16, PD 5/16) for patients with colorectal cancer. Grade 4 anemia (WHO criteria) occurred in 1/37 and thrombocytopenia in 1/37 patients. These patients had previous adjuvant chemotherapy. Vomiting grade 3 occurred in 4/37 and hepatotoxicity grade 3 in 1/37 patients. There were no toxic deaths. Our study did not demonstrate any enhancement of cisplatin activity by high dose cytarabine in advanced gastric cancer. There appears to be an enhancing activity on colorectal cancer although true synergism can not be ruled out since cytarabine has a borderline activity in this type of human cancer.
Aged↗
Cardioprotection with ICRF-187 (Cardioxane) in patients with advanced breast cancer having cardiac risk factors for doxorubicin cardiotoxicity, treated with the FDC regimen.
A study of cardioprotection with ICRF-187 (Cardioxane, Eurocetus) has been performed in 35 patients with metastatic breast cancer treated with the FDC regimen (5-fluorouracil 500 mg/m2 i.v., day 1; doxorubicin 50 mg/m2 i.v., day 1; cyclophosphamide 500 mg/m2 i.v., day 1). All patients had one or more cardiac risk factors for doxorubicin cardiotoxicity including 24 who had previously received left-chest-wall irradiation. Cardioxane was applied at a dosage of 1000 mg/m2 as a 15-min infusion in Ringer lactate solution 30 min before doxorubicin administration. Cardiological monitoring included left-ventricular ejection fraction (LVEF) determination by echocardiography before treatment and before each cycle following the cumulative doxorubicin dose of 200 mg/m2. Of the 35 patients, 34 were evaluable fore response, and the overall response rate was 19/34 (56%) with 3/34 complete responses and 16/34 partial responses. Statistical analysis of LVEF values in relation to increasing cumulative doxorubicin doses with Wilcoxon's test of equivalent pairs and Friedman's test has demonstrated that no cardiotoxicity was detected up to a cumulative doxorubicin dose of between 800 mg/m2 and 1000 mg/m2, except for 2 patients in whom a decrease of 20% in relation to the LVEF pretreatment level was demonstrated following a cumulative drug dose of 250 mg/m2. Thus Cardioxane provides an effective cardioprotection even in breast cancer patients with cardiac risk factors for doxorubicin cardiotoxicity treated with the FDC regimen.
Adult↗
[Diagnosis of placenta praevia using ultrasound].
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Female↗
The effect of ergot alkaloids ergosinine, dihydroergosine and dihydroergotamine on neurotransmission and contractility of the isolated ileum of the guinea-pig.
The effects of ergosinine (ESNN), dihydroergosine (DHESN) and dihydroergotamine (DHE) on contractions of the isolated terminal and middle segments of the guinea-pig ileum were studied in-vitro. Responses to cholinergic (3 Hz) and adrenergic stimulation (30 Hz in the presence of atropine) were inhibited, albeit at high concentrations of all three alkaloids (1-30 micrograms ml-1). Cholinergic neurotransmission was surprisingly more affected than adrenergic transmission. Noradrenaline (NA) contractions, however, were inhibited at very low concentrations (1-30 ng ml-1) with the following order of potency: DHESN = DHE greater than ESNN. Prazosin was equally as potent as DHESN in inhibiting NA contractions and similarly potent in inhibiting responses to adrenergic stimulation. ESNN, DHESN and DHE when used at concentrations from 1-30 micrograms ml-1 were also found to inhibit 5-hydroxytryptamine greater than histamine greater than acetylcholine greater than KCl contractions. The results suggest that the principal pharmacological action of ESNN, DHESN and DHE on the guinea-pig isolated ileum is the antagonism to NA on the postsynaptic and extrajunctional population of alpha-adrenoceptors. The neurotransmission, adrenergic as well as cholinergic, appeared to be inhibited via a non-specific presynaptic mechanism presumably regulating the transmitter release. Anti-5-hydroxytryptamine, anti-acetylcholine and antihistamine actions were obtained at similar and relatively high concentrations, thus pointing to a non-specific depressant action upon a common mechanism regulating the contractility of the smooth muscle.(ABSTRACT TRUNCATED AT 250 WORDS)
Acetylcholine↗
Calcium antagonistic action of pentobarbitone on the isolated terminal ileum of the guinea-pig.
Action of pentobarbitone was studied on isolated segments of the terminal and middle ileum of the guinea-pig and compared with the effects of verapamil. Pentobarbitone (10(-4)-10(-3) M) was found to almost equally inhibit responses produced by ES at 3 Hz and ACH, and those elicited by ES at 30 Hz and NA. Increase in the extracellular calcium did not antagonize the effects of pentobarbitone on both types of ES. These results are an indication of a postsynaptic site of action. The concentration-response curves to calcium-induced contractions (3-300 microM) were displaced to the right by both drugs; however, unlike verapamil, pentobarbitone markedly reduced the maximum response to calcium. Calcium-induced contractions after reaching the plateau level were relaxed both by pentobarbitone and verapamil. Pentobarbitone lowered the resting tone even in the high-KCl depolarizing solution, while verapamil produced no change in this series of experiments. It could be concluded that pentobarbitone when used in anesthetic concentrations might affect contractility of the intestinal smooth muscle by an action located at the postsynaptic membrane or beyond it. The antagonism between pentobarbitone and calcium appeared to be noncompetitive and is presumed to be effected via an indirect action on the functioning of calcium channels.
Acetylcholine↗