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Biomedical subjects

S Jelić

Publications and source records attributed to S Jelić.

107 records · Page 6Linked to original sources
PubMedDate not supplied

[Serum antithyroid antibodies in patients with pernicious anemia].

We investigated the incidence of thyroid auto-antibodies and their relationship to antigastric antibodies in 20 euthyroid patients with pernicious anaemia. To evaluate possible thyroid dysfunction we also measured total level of thyroid hormones (TT3 and TT4) and TSH in our patients. Histologic evidence of autoimmune atrophic gastritis and intestinal metaplasia was obtained in 15 patients. We found that it was surprisingly high incidence of thyroid auto-antibodies in patients with pernicious anaemia, particularly in the group with intestinal metaplasia (antithyreoglobulin antibodies 71% and antimicrosomal antibodies 100%). The incidence of antigastric antibodies in these patients was similar to that of those with significant antithyroid antibodies (16/18). Total triiodo thyronine and TSH were significantly higher in the patients with pernicious anaemia than in the control group (p less than 0.05), in the normal range. The results of our study suggest that this upset in immunological physiology is due to a more generalized defect in immune tolerance.

Aged↗
PubMedDate not supplied

[Serum gastrin in patients with diabetes].

We evaluated the basal and postprandial circulating levels of gastrin in 20 diabetic patients and in 20 normal subject. The basal gastrin concentrations were not statistically different in comparison to controls. The blood tests provoked increased circulating levels of gastrin. In our study diabetes significantly enhanced that response, particularly in diabetics with severe disease, peripheral neuropathy and in untreated patients. Histologic evidence of antral hyperplasia was obtained in 7 patients; atrophic gastritis and intestinal metaplasia were found in 3 diabetics. We postulate that postprandial gastrin levels raised secondary to achlorhydria, common in diabetics.

Diabetes Mellitus↗
PubMedDate not supplied

[Adrenocortical "incidentalomas" as a diagnostic and therapeutic problem].

P. Carpenter (1986) used the term "incidentalomas" in connection with all incidentally discovered adrenal masses. Previously these masses were frequent incidental discoveries at autopsies, but now, with the increasing use of abdominal computed tomography. In the last 10 years 5 patients with incidentally diseases, significant number of them have been detected. In the last 10 years 5 patients with incidentally discovered adrenal masses (4 males and 1 female, aged from 37 to 66 years) were examined and treated in our Department. Long-lasting arterial hypertension was found in all of them, and in one patient here was impaired glucose tolerance with further evolution of diabetes. A possible excessive secretion of glucocorticoids, mineralocorticoids, androgenes and catecholamines was excluded. However, markedly elevated urinary excretion of pregnanediol, proved in all patients, indicated to a possible preservation of the first reaction in the biosynthesis of cortisol, at least synthesis of pregnenolone from cholesterol. One patient, submitted to a regular functional and morphological evaluation of previously discovered 'incidentaloma', showed no sign of expansion or pathological hormonal activity. Four patients were operated because of the suspected expansion and malignant alteration of the adrenal nodus. The histological proof of adrenocortical adenoma or hyperplasia, composed of the 'fasciculata-like' cells, postoperatively maintained elevated values of steroid precursors in urine, and also a finding of adrenocortical noduses in remained adrenal noduses, confirmed the presumption that such masses could be the non-essential finding in long-lasting arterial hypertension and degenerative changes during aging.

Adrenal Cortex↗
PubMedDate not supplied

[Anti-pain effect of salmon calcitonin in bone metastases of malignant tumors with the exception of breast and prostatic carcinoma].

In 16 patients with pain caused by diffuse osteolytic or osteoplastic-osteolytic metastases, salmon calcitonin was used as pain relieving treatment. All patients were pretreated with opiate type analgesics without a satisfactory effect. In 2 patients it was possible to withdraw completely previous opiate intake. In most of the patients the analgesic effect of salmon calcitonin consisted in decrease of pain with identical or decreased intake of opiate type analgesics. In 3 patients the pain relieving treatment with salmon calcitonin completely failed. Our investigation seems to demonstrate that there is a subpopulation of patients with bone metastases, resistant to opiate type analgesics, in which salmon calcitonin can be administered as an additional useful pain relieving drug.

Analgesics↗
PubMedDate not supplied

[Levels of certain immunologic parameters in patients with carcinoma of the epipharynx].

According to several histological and immunological features undifferentiated carcinoma of the nasopharynx (UCNT) is different from other ORL carcinomas (abundant lymphocytic infiltrate and frequent positive serology to EBV). Thus, immunological and virusological investigations were frequently performed in order to determine their diagnostic and prognostic significance. This study mainly concerned EBV serology and related immunological parameters. There are less data about immunological profile in those patients. In the present study, several standard immunological parameters were tested (number of different rosette-forming cells in peripheral blood, immunoglobulins serum levels and blastic transformation in the presence of PHA) in 17 patients with UCNT, 16 males and 1 female, aged 20 to 79 years. The aim of this study was to find out whether these patients were different from healthy controls, and if any of these parameters could be of prognostic value. Results point to the following disturbances in our group of patients: absolute lymphopenia caused by T-lymphopenia and significant decrease in ability of blastic transformation. Contrary to the registered suppression of cellular immunity there was a certain degree of stimulation of humoral response detected by hypergamaglobulinaemia and appearance of monoclonal immunoglobulin components in sera of few patients. All these immunological disturbances have no prognostic value in predicting the treatment response to chemotherapy.

Adult↗
PubMedDate not supplied

[High-dose medroxyprogesterone acetate in the treatment of metastatic carcinoma of renal parenchyma].

In animals it was found that the growth of oestrogen induced renal cell carcinoma can be inhibited by progesterone derivatives. In human clinical studies of metastatic renal cell carcinoma treated with MPA doses of 500 mg/24 h the overall response was about or below 10%. However, it has been noted that there is a dose effect relationship in MPA in breast cancer. As the level of hormonal receptors in renal cell carcinoma tissue is low, it could be expected that dose escalation of MPA might influence the therapeutic response. Thirteen patients with metastatic renal cell carcinoma with progressive disease treated with MPA doses of 500 mg/24 h were treated with escalated doses of MPA 2000 mg/24 h for 10-15 consecutive days, the drug free interval being 3-4 weeks. Twelve patients were evaluated for response. Partial response was registered in 3/12 patients with median survival-time of 15 months, 4/12 patients had stable disease and 5/12 patients had progressive disease. All patients with a partial response have been previously nephrectomised, and had lung metastases. The type of the response was also noted in interferon treated patients. During the high-dose MPA treatment several patients displayed thrombocytopenia, a phenomenon difficult to interpret. One patient, previously nephrectomised, developed fatal renal vein thrombosis of the remaining kidney. Other toxic effects (weight gain, transitory psychotic episodes) did not require treatment interruption. There seems to be a dose response relationship of MPA in a sub-category of patients with metastatic renal cell carcinoma, and additional treatment responses may be observed in patients treated with escalated MPA doses.

Adult↗
PubMedDate not supplied

[Malignant mesothelioma--therapeutic response to various combinations of anthracyclines].

This report deals with results of chemotherapy with different antracycline combination in advanced malignant mesothelioma. Two patients were treated with CYVADIC combination including Adriamycin 40 mg/m2. There was no treatment response and both patients were evaluated as stable disease with median survival 5.5 months and median time to progression 4 months. Four patients were treated with Adriamycin 75 mg/m2 and Cisplatin 120 mg/m2. Two patients achieved a partial response with median survival 8 months and median time to progression 6.5 months. Combination treatment with Epirubicin 180 mg/m2 and Cisplatin 120 mg/m2 was applied to 5 patients, 4 being evaluable for activity. There was one partial response, median survival in this group was 5 months and median time to progression 3.5 months. The Adriamycin dose of 75 mg/m2 and the Epirubicin dose of 180 mg/m2, which were used in our patients are the highest escalated doses, not reported in literature data. Using the meta-analysis of both literature data and our study, which can be considered as a pilot study for dose escalation, there seems to be dose-effect relationship for antracyclin activity in malignant mesothelioma. The meta-analysis registers also slightly better treatment results (response rate 12.6% in 277 patients) with antracyclin containing regimens as compared to combination chemotherapy which does not include antracyclines (response rate 10.3% in 175 patients).

Antibiotics, Antineoplastic↗
PubMedDate not supplied

[Evaluation of quality of life in oncology].

Studies of quality of life are more and more becoming an integral part of cancer care in situations when treatment of cancer patients is burdened with significant toxicity, and results of survival of these patients are unsatisfactory. Modern concept of health-related quality of life measurement means consensus about its two basic features: multidimensionality of concept, and essentially subjective experience in a treated person. As a minimum, domains of physical, psychological and social are assessed, and the patient is considered to be the primary source of information. The most widely used instruments for quality of life assessment are questionnaires, especially developed for cancer patients, with supplemental items for particular diagnosis. These instruments must satisfy the basic psychometric properties-validity and reliability. Quality of life studies are focused mostly on phase III trials, where differences between treatment arms for tumour response and survival are expected to be small. Another approach is developed in parallel which, based upon quality of life measurement, initiates decisions for the treatment of a set of patients up to health policy level. In these "cost-utility" studies, efficacy and cost of the treatment, and improvement of patients' quality of life are independently estimated, and then integrated in medical decision making.

Humans↗
PubMedDate not supplied

Assessment of early epirubicin cardiotoxicity in women with breast cancer.

BACKGROUND: Anthracycline-containing chemotherapy has been the most frequently observed cause of iatrogenic cardiac damage in patients with breast cancer. The purpose of this study was to evaluate by radionuclide ventriculography whether a mean cumulative dose of epirubicin (MCDE) induced left ventricular (LV) systolic or/and diastolic dysfunction in 32 patients treated for breast cancer. MATERIALS AND METHODS: Thirty-two patients with breast cancer according to chemotherapeutical trials received MCDE of 360 m/m2. All patients were studied before and after they completed chemotherapy with radionuclide ventriculography at rest. Systolic and diastolic left ventricular parameters were assessed. RESULTS: Diastolic left ventricular parameters and R-R intervals significantly differed before and after completed chemotherapy in our patients: peak filling rate (PFR: 2.8 +/- 0.6 vs. 2.2 +/- 0.7 EDV/sec) and time to filling rate (TPFR: 182 +/- 48 vs. 2.25 +/- 50 msec), R-R: 723 +/- 51 vs. 620 +/- 45 msec, p < 0.01. Ejection fraction, as a systolic parameter/did not significantly differ before and after completed chemotherapy (EF: 59 +/- 7 vs. 58 +/- 6%), p > 0.05. CONCLUSION: Our results indicate that left ventricular diastolic dysfunction even at an MCDE of 360 mg/m2 may be an early sign of epirubicin cardiotoxicity.

Antibiotics, Antineoplastic↗
PubMedDate not supplied

[Chronotherapy with high dose carboplatin, 5-fluorouracil and leucovorin in advanced colorectal carcinoma].

INTRODUCTION: Fluorouracil (5-FU) has remained the mainstay of treatment of advanced colorectal cancer disease for nearly 40 years, and despite the implementation of various strategies to increase response rates no substantial improvement in survival has been achieved. 5-FU efficacy has been enhanced by modulating its cytotoxicity with leucovorin (LV) or by administering it as a continuous intravenous infusion. These regimens resulted in a few-fold improvement of tumour response rate in patients with metastatic disease compared with standard 5-FU treatment. The figures are still low (25%), and survival is affected only modestly [1, 2]. Cisplatin and carboplatin are also able to modulate 5-FU cytotoxicity in experimental systems [3]. Recent results of experimental studies suggested that high doses of carboplatin were necessary to achieve biochemical modulation of 5-FU cytotoxicity in vivo [6]. The use of chronobiologically determined drug over a 24-hour period may allow an increase in antitumour effect and a decrease in side effects. Experiments in animals revealed large changes in the toxic effects of 5-FU and platinum analogues, depending on the circadian rhythm of drug administration [9, 10]. The aim of the study was to investigate the toxicity and efficacy of combination of high dose carboplatin, fluorouracil and leucovorin in patients with advanced colorectal adenocarcinoma. Carboplatin and 5-FU were administered in circadian-dependent rhythm regimen in a 4-h infusion. PATIENTS AND METHODS: An open, prospective study was carried out in 99 patients enrolled in the study. The following treatment schedule was used: carboplatin 150 mg, a 4-hour-infusion, start at 8 a.m., day 1-7; 5-FU 750 mg/m2, a 4-hour-infusion, start at 6 p.m., day 1-5; leucovorin 100 mg/m2, bolus i.v. at 8 p.m., day 1-5. The cycles were repeated every 28 days. Dose modifications were not planned. Treatment response and toxicity were evaluated according to WHO criteria [11]. Time to progression was calculated from the beginning of chemotherapy. Survival was calculated from start of chemotherapy using the Kaplan-Meier method [12]. RESULTS: We treated 99 patients (27 colon and 72 rectal cancers) with metastatic diseases. There were 52 males and 47 females, average age 58 years (range 34-72). There were 82 patients (pts) with previous surgical treatment, 30 pts. with previous radiotherapy and 19 pts. with previous adjuvant chemotherapy. Performance status was 0 for 9 pts., 1 for 53 pts., 2 for 33 pts. and 3 for 4 pts. We carried out 469 cycles (mean 4/pts.). Ninety seven pts. were evaluated. The response rate was 28% (95% CI: 19.9-37.9) with 4/97CR, 23/97PR, 48/975D and 22/97PD. Mean time to progression was 5.5 months (range 2-18). The mean survival time was 7 months (range 4-27). The mean survival time was 11 months for responders and 6 months for non-responders. WHO grades 3 and 4 leukopenia were observed in 19 pts (19.2%). WHO grades 3 and 4 thrombocytopenia occurred in 21 (21.2%) pts. The main nonhaematologic toxicity were diarrhea, nausea/vomiting and mucositis. No grades 4 of nonhaematological toxicity were seen, except diarrhea grade 4 was observed in one patient. There was no life-threatening toxicity. DISCUSSION: Carboplatin is able to modulate 5-FU cytotoxicities [3]. A high dose of carboplatin is necessary to achieve biochemical modulation of 5-FU cytotoxicities in vivo [6]. The studies of colon tumour cell lines demonstrated sensitivities to carboplatin when used at clinically achievable dose level [4]. Clinical studies of carboplatin, as a single agent or in combination, in the treatment of colorectal cancer, reported controversial results [19, 20]. Animal studies indicated large and predictable changes in the toxic effects of carboplatin and 5-FU, depending on the circadian rhythm of drug administration. Mechanisms included 24 h changes in the activities of several enzymes involved in 5-FU and carboplatin catabolism or in the anabolism of its cyt

Adult↗
PubMedDate not supplied

[Chemotherapy of colorectal carcinoma].

The benefit of adjuvant therapy in colorectal cancer (CRC) has been provided in clinical studies that have demonstrated reduction of up to 30% in a 5-year overall mortality in patients (pts.) with TNM stage III (Dukes' stage C) carcinoma. Patients with metastatic CRC are usually in a relatively good condition despite their advanced disease. Therefore, some clinicians wished to withheld the toxicity of chemotherapy until the disease became symptomatic. Others, however, felt it appropriate to treat patients early in the course of the disease. Four clinical trials may be cited addressing this clinical uncertainty (Table 1). Patients receiving chemotherapy had a significantly longer median survival in comparison with only best supportive care. The delay of the carrying out of systemic chemotherapy in patients with metastatic disease decreases the symptom free interval (2 vs. 10 months, p < 0.001), time to disease progression (3 vs. 8 months, p < 0.001) and median survival (14 versus 9 months, p < 0.02) compared to an early start of therapy [7C. Patients with metastatic colorectal cancer benefit from early chemotherapy in terms of survival and quality of life. It is clear that survival is determined by prognostic factors, mainly the performance status, which is a highly significant predictor of therapeutic response and overall survival in advanced colorectal cancer patients. Some authors suggests that the response is a potent and independent prognostic factor of survival, and that response can be used as surrogate marker of survival. Stable disease is a category in therapy response evaluation which is not included in the overall response rate. In many studies with a response rate below 20%, chemotherapy almost doubles the survival of patients. In most chemotherapy trials in advanced colorectal cancer patients, about 30-50% had stable disease. One of the possible reasons may be that in colorectal cancer stabilization of disease is a clinically relevant effect of chemotherapy. If we accept that disease stabilization is a clinically relevant effect of chemotherapy, should we continue with chemotherapy after 3 or 4 courses, and for how long, or should we stop treatment according to rules for stable disease, i.e. following 4 courses? The results of on study, which we performed in 99 patients with advanced colorectal cancer, indicate that under category of "stable disease" there are two different subpopulations of patients with quite different symptom responses as an effect of chemotherapy, different time to progression and possible different survival (Graph 1 and Graph 2). It seems that stable disease patients with clinical benefit could be a target group for policy "to treat until disease progression". The tumour response is likely to be positively correlated with improvement in quality of life when a patient is a symptomatic from cancer before the treatment. Stable disease patients without symptom improvement have no benefit from further chemotherapy and in these patients treatment should be stopped. Such selection would spare from toxicity stable disease patients without clinical benefit. We have no data whether different number of chemotherapy cycles in the groups of patients with and without clinical benefit could lead to a bias in survival estimation. Patients who achieved also a stable disease, but who were asymptomatic from the beginning of chemotherapy, and who are still asymptomatic after 4 chemotherapy courses, make a group for which is hard to make decision either to continue or to stop chemotherapy. We have treated and followed-up these stable disease patients as patients without clinical benefit. We have no answer if they could reach better time to progression and/or survival if they had been treated for more than 4 courses. Careful studies in the evaluation of the quality of life in connection with treatment effects for all stable disease subpopulations of patients are warranted. (ABSTRACT TRUNCATED)

Colorectal Neoplasms↗