Biomedical subjects

N Milanović

Publications and source records attributed to N Milanović.

At least 19 recordsLinked to original sources

PubMed2003

Croatia has reached iodine sufficiency.

This study was performed in 2002, 6 yr after the introduction of a new regulation on salt iodination with 25 mg KI/kg of salt. The aim of the study was to evaluate whether further significant positive results of improved iodine intake could be observed among schoolchildren in Croatia. A total of 927 schoolchildren of both sexes, aged 6-12 yr, were included in the study. In Croatia, with a population of 4,437,460 the research was implemented in four major geographical regions: the Northwestern, Slavonia, Northern Adriatic and Dalmatian regions. Investigations included randomly selected pupils from regional centers and neighboring smaller towns or villages. The results have revealed that thyroid volumes were within the normal range according to the provisional WHO/ICCIDD reference values for sonographic thyroid volume in iodine-replete school-age children, updated in 2001. A significant improvement in medians of urinary iodine excretion was detected in 2002: from 9 microg/dl in 1991 to 14.6 microg/dl in Zagreb, from 4.3 microg/dl in 1995 to 13.1 microg/dl in Split, from 9.4 microg/dl in 1997 to 14.2 microg/dl in Rijeka and from 13.4 microg/dl in 1997 to 14.7 microg/dl in Osijek. An overall median of 14.0 microg/dl of urinary iodine excretion was detected in Croatian schoolchildren. The control of salt at different levels, from production to consumption, including salt produced in all three Croatian salt plants and imported salt, revealed that Croatian salt is adequately iodized. From severe iodine deficiency before the 1950s, through mild-to-moderate iodine deficiency in the 1990s, Croatia has now reached iodine sufficiency.

Chemical Industry↗

PubMed1999

Comparison of two non-anthracycline-containing regimens for elderly patients with diffuse large-cell non Hodgkin's lymphoma--possible pitfalls in results reporting and interpretation.

Age over 65 years is a risk factor per se for doxorubicin administration, and coexisting diseases pose additional problems. There is still controversy whether chemotherapy regimens for elderly patients with aggressive NHL should be full-dose doxorubicin containing or whether development of non-anthracycline containing regimens is warranted. In this prospective study, 47 patients aged over 65 years with diffuse large cell NHL clinical Stage I/IE bulky-IV and no other initial exclusion criteria were randomized to receive either BCNU 120 mg/m2 d. l, VP 16 60 mg/in2 d.2-4, procarbazine 85 mg/m2 d. 2-8 (arm A, 27 patients) or mitoxantrone 6 mg/m2 d. l. with VP16 and procarbazine in the same dosage and schedule (Arm B, 20 patients). Partial responders received additional irradiation treatment if feasible. Arms were well balanced according to age, sex, clinical stage and performance status. Ten patients from arm A and 13 from arm B had PS 2 or 3; 14 patients from arm A and 8 from arm B had clinically significant antecedent and/or concomitant disease (SACD: cardiac, vascular, cerebrovascular, neurological, renal or other). On the intent-to-treat basis, the results were the following. ARM A: median number of cycles 3 (range 1--6); early death 3 patients; 16/27 responses (59%), 7 complete (30%). ARM B: median number of cycles 3 (range 1-6); early death 4 patients; 12/20 responses (60%), 3 complete (15%). There was no difference either in response rate or survival between the two arms, and pooled results from the two arms displayed a plateau on the survival curve from the 20-th month onwards on the probability level of 0.40. Clinical stage of NHL, bulky disease, age and sex did not influence survival. Initial performance status did influence survival at the significance level of p = 0.045. Although presence of SACD did not influence initial performance status, it had a strong negative impact on survival p = 0.0004). The results point to the existence of two prognostic categories of elderly patients with large cell NHL, one with a poor survival, the other achieving a significant response rate and relapse free survival. Comorbidity (SACD) apparently accounts for the poor survival in a subpopulation of elderly patients. Clinical trials with elderly patients with NHL with PS 0 or 1 and no serious coexisting disease as inclusion criteria, analyzed on an evaluable patients basis, target only to a prognostically better subpopulation among these patients.

Aged↗

PubMed1999

Epirubicin 150 mg/m2-cisplatin versus epirubicin 180 mg/m2-cisplatin for advanced soft tissue sarcoma.

We have previously reported the superiority of the epirubicin 180 mg/m2-cisplatin combination over single drug epirubicin 180 mg/m2 for advanced soft tissue sarcoma both in terms of response (54% vs. 29%, p = 0.025) and survival (p = 0.001). The aim of the present study was to establish whether decreasing the dosage of epirubicin to 150 mg/m2 would result in the same activity but with less hematological toxicity. One hundred fifty-nine patients with advanced soft tissue sarcoma were randomized for either epirubicin 150 mg/m2-cisplatin 120 mg/m2 (group A) or epirubicin 180 mg/m2-cisplatin 120 mg/m2 (group B). The results were as follows: group A: 79 patients were evaluated. Overall response rate was 24/79 (30%) (95% CI 21-41%). Median survival was 11 months and probability of survival at 1 year was 0.46. Grade IV granulocytopenia was present in 111/274 cycles and febrile neutropenia in 22/274. Group B: 73 patients were evaluated. The overall response rate was 39/73 (53%), (95% CI 42-64%). Median survival was 14 months and probability of survival at 1 year was 0.58. Grade IV granulocytopenia was present in 136/295 cycles and febrile neutropenia in 30/295. The differences were as follows: for overall response rate p = 0.004; power (for p = 0.05) 85%; for survival p = 0.09; for grade IV granulocytopenia p = 0.3; and for febrile neutropenia p = 0.61. A survival advantage (p = 0.043) was evident for patients randomized to group B and with performance status 0 or 1 compared with similar patients from group A. A plateau-like formation on the probability level of 0.26 on the survival curve started from month 26 onwards. In conclusion, both regimens share the same toxicity but epirubicin 180 mg/m2-cisplatin seems more active in soft tissue sarcoma, possibly indicating a breakthrough for activity between an epirubicin dosage of 150 mg/m2 and 180 mg/m2 in combination with cisplatin. The superiority of the epirubicin 180 mg/m2-cisplatin regimen appears evident both in terms of response and survival.

Adolescent↗

PubMed1997

Randomised study of high-dose epirubicin versus high-dose epirubicin-cisplatin chemotherapy for advanced soft tissue sarcoma.

A randomised study was started in chemotherapy-naive patients with advanced soft tissue sarcomas who received either epirubicin 60 mg/m2/24 h (total dose for cycle 180 mg/m2) days 1, 2 and 3, (group A) or epirubicin 60 mg/m2/24 h days 1, 2 and 3 and cisplatin 30 mg/m2/24 h days 2, 3, 4 and 5 (group B). The maximal number of cycles foreseen in both groups was eight. Cardiotoxicity of the regimens was monitored by serial LVEF determinations. 106 patients entered this study, 50 (45 evaluable for activity) randomised to group A, and 56 (54 evaluable for activity) to group B. The groups were well balanced for age, sex, performance status and histological type. In group A, there was 1 complete response (CR) and 12 partial responses (PR), the overall response being 13/45 (29%); in group B, there were 7 CRs and 22 PRs, the overall response being 29/54 (54%). The difference between the overall response was statistically significant (chi 2 = 6.19, P < 0.025). The epirubicin-cisplatin regimen was found to be more toxic for platelets and more emetogenic, but cardiotoxicity, either acute or cumulative, was not found to be a major problem in both groups. However, a complete responder receiving a cumulative epirubicin dose of 1440 mg/m2 died from congestive heart failure after a disease-free interval of 27 months. The high response in group B could be the result of the synergism between high-dose epirubicin and cisplatin in patients with advanced soft tissue sarcomas.

Adult↗

PubMed1997

Randomized study of zorubicin versus zorubicin-cisplatin in undifferentiated carcinoma of the nasopharynx (UCNT)

BACKGROUND: The most active chemotherapy regimens in UCNT were those combining anthracyclines (doxorubicin or epirubicin) and cisplatin. Our previous pilot study on 37 patients treated with the zorubicin-cisplatin combination with a RR of 67% and literature data about other anthracyclines such as epirubicin achieving a response rate of over 50% were the basis of this randomized study comparing efficacy and toxicity of the combination vs. zorubicin as monotherapy. PATIENTS AND METHODS: A total of 80 patients entered the study. The diagnosis of UCNT was confirmed by two independent pathologists. All patients had their primary tumors in the nasopharynx. The patients were randomized in two groups: group A (zorubicin 325 mg/m2, day 1), and group B (zorubicin 250 mg/m2, day 1 and cisplatin 30 mg/m2, days 2-5). The inter-cycle interval was four weeks. The two groups were well balanced according to sex, age, stage Ho and TNM stage. RESULTS: Group A: 40 patients included, 34/40 evaluable for activity. Activity on evaluable patient basis: CR 4/34 (11.75%), PR 4/34, SD 14/34, PD 12/34, response rate 8/34 (23.5%); response rate on intent to treat basis 8/40 (20%). TOXICITY: granulocytopenia grade 3-4 6/40, thrombocytopenia grade 3-4 2/40, no febrile neutropenias, nausea/vomiting any grade 3/40, cardiac toxicity any grade (rhythm) 3/40 other toxicities minor or absent. Group B: 40 patients included, 36/40 evaluable for activity. Activity on evaluable patient basis: CR 10/36 (27.78%), PR 17/36, SD 3/36, PD 6/36, response rate 27/36 (75%); response rate on intent to treat basis 27/40 (67.5%). TOXICITY: granulocytopenia grade 3-4 10/40, thrombocytopenia grade 3-4 8/40, two febrile neutropenias, nausea/vomiting any grade 13/40, other toxicities mild or absent. Of the group of patients achieving a CR, four relapsed following 7, 11, 22 and 23 months, one was lost to follow-up, one died after six months from fulminant hepatitis B and eight are in complete remission lasting for 30+ to 66+ months. Following CR achievement none received any consolidation radiotherapy, and the projected five years of freedom from relapse for complete responders is about 60%. CONCLUSION: Zorubicin is an effective drug in UCNT and its combination with cisplatin has a significant activity and an acceptable toxicity.

Adolescent↗

PubMed1997

Richter syndrome with emphasis on large-cell non-Hodgkin lymphoma in previously unrecognized subclinical chronic lymphocytic leukemia.

The authors report seven cases of Richter's syndrome, i.e. of large-cell non-Hodgkin's lymphoma (NHL) arising in association with chronic lymphocytic leukemia (CLL). Six patients had the recently recognized variant of this syndrome, occurring in patients with previously undiagnosed subclinical CLL. All patients were treated with aggressive chemotherapy and a complete response of large cell NHL was achieved in 4/7. A complete response of NHL was observed in 3 out of 6, and a partial response in 2/6 patients with simultaneous occurrence of subclinical CLL and large cell NHL (response rate 5/6). Our findings might suggest that patients with Richter syndrome occurring in previously undiagnosed subclinical CLL could represent a better prognostic group in the overall population of patients with large cell NHL transformation of CLL.

Aged↗

PubMed1995

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↗

PubMed1994

[Therapeutic possibilities of recombinant interferon alfa-2b (Intron A) in non-AIDS Kaposi sarcomas and angiosarcomas].

Data concerning treatment of vascular neoplasia with biological response modifiers are still scanty, but encouraging results have been observed with alpha-2b interferon in AIDS related Kaposi sarcoma. In this study five treatment naive patients with Kaposi sarcoma and four heavily pretreated patients with angiosarcoma with still evolutive disease were treated with Etopozid 120 mg/m2/24h, days 1, 3 and 5, and recombinant alpha-2b interferon 6.000.000 U/24h, days 1-15, the intercycle interval being 21-28 days. All patients were negative for anti-HIV 1, anti-HIV 2 and anti-HTLV 1 antibodies; one patient had a high titer of IgG anti-chlamydia antibodies amounting to 1/4.194.304. This group differed from similar HIV 1 positive patients by having a normal CD4/CD8 ratio. In the Kaposi sarcoma group 1/5 achieved a complete response lasting 24+ months and 3/5 achieved a good partial response lasting 5+, 12+ and 35+ months. In the angiosarcoma group 1/4 patient achieved a complete response but relapsed after 18 months and one patient experienced stable disease lasting for 15+ months. These findings could be understood in two different ways. Since an infective etiology has been proposed for Kaposi sarcoma, the positive effect of alpha-2b interferon could be related to its "antiinfective" effects observed in viral disorders. However, similar activity in angiosarcoma points to the possibility that the positive effect of alpha-2b interferon in this group of disorders is related to interfering effects of the drug with factors implicated in neoplastic angiogenesis.

Adult↗

PubMed1994

Non-IPSID small intestinal lymphoma: evidence for disseminated disease at presentation.

During the period 1984-1989 the authors have observed 20 patients with non-IPSID small intestinal lymphomas, 11 males and 9 females. In 11 patients the first symptoms were abdominal cramps requiring laparotomy, in 4 ileus, and in 5 perforation with peritonitis. Resection of the involved part of the intestine was performed in 17 patients. Lymphoma tissue was present in 4 of 5 retrogradely examined resection lines on macroscopically normal small intestine. According to Working Formulation, 3 patients had low grade, 3 intermediate grade and 14 high grade histology. Affection of extra intestinal/mesenteric structures was found in 18 of 20 patients, with a total of 36 other lymphoma localizations. 8 of 20 had affection of the nasopharynx and/or Waldeyer's ring. According to the Crowther's classification 55% of patients were in Stage IV, 35% in Stage III and 10% in Stage Ib. All patients were treated with chemotherapy, 13 with ProMACE regimen and 7 with CHOP-type regimens. Ten of twenty patients are alive and in complete remission for over 5 years (7 of 11 of Stage IV and 3 of 9 of Stage Ib/III; 8 of 14 with high grade and 2 of 6 with intermediate/low grade histology). Our results point to the fact that in non-IPSID lymphoma of the small intestine, lymphoma involvement of the intestinal wall might be present beyond obvious lymphoma lesions. Most patients with apparently primary small intestinal lymphoma have a widespread disease. Thus, local forms of treatment such as surgery, and/or radiotherapy can not be expected to be curative in the majority of patients. Data from this study suggest that following initial surgery the chemotherapy is the treatment of choice for these patients.

Adult↗

PubMed1990

High-dose epirubicin-cisplatin chemotherapy for advanced soft tissue sarcoma.

A chemotherapy regimen with epirubicin (60 mg/m2, days 1, 2 and 3) and cisplatin (30 mg/m2, days 2, 3, 4 and 5) was started for 35 patients with advanced soft tissue sarcoma (28 males and 7 females; median age, 50 years). All patients were chemotherapy-naive and with an expected survival of more than 2 months. All patients were evaluable for activity and toxicity. The intercycle interval was 4 weeks. Median number of cycles applied was 4 (range, 2-8). The overall response rate was 20/35 (57.1%). A complete response (CR) was achieved in 7/35 patients (20%), lasting for 26+, 26+, 13+, 13+, 9+, 9+ and 5 months; 13/35 patients (37.1%) entered a partial remission (PR), 9/35 patients (25.7%) had stable disease (SD), and 6/35 (17.1%) had progressive disease (PD). In non-responders (SD + PD), the median survival was 4 months; the median survival of responders (CR + PR) was 9+ months (the median has not yet been reached). Hematologic toxicity of grade 4 was present at least in one cycle for hemoglobin in 6/35 patients, for leukocytes in 22/35, and for platelets in 13/35. No hemorrhagic syndrome was observed. The leukopenia was usually of short duration (nadir on days 10-12). Febrile episodes were present in 18 patients during the nadir of leukopenia. No other significant toxicity was noted (apart from grade III alopecia in all patients), and specifically, there was neither acute nor cumulative cardiotoxicity.

Adult↗

PubMed1982

Nutritional status and physical working capacity.

In a population of schoolchildren aged 12-15 years in which biochemical deficiencies of vitamin C, riboflavin and pyridoxine affected 30.0, 33.9 and 17.2 per cent of subjects respectively, a small but statistically significant correlation was found between VO2max and vitamin C, riboflavin, vitamin A, and parameters of iron nutrition status. The administration of tablets containing 70.0 mg ascorbic acid, 2.0 mg riboflavin and 2.0 mg pyridoxine resulted in a statistically significant reduction in prevalence of vitamin deficiency, and in a small but statistically significant increase in VO2max. No such changes were observed in the untreated control groups. When data from both the experimental and control groups were pooled and analysed together, the results showed that the increase in VO2max was associated with an increase in plasma vitamin C level, in erythrocyte riboflavin content and in blood haemoglobin level. On the basis of presented data, it is not possible to conclude whether the increase in VO2max was the result of correction of vitamin deficiency per se or was due to its effect on resorption and utilization of dietary iron.

Adolescent↗

PubMed1982

Blood pressure and blood lipids in adolescent obesity.

The relationship of relative body weight (RBW) and adiposity to blood pressure and blood lipids was studied in a selected group of adolescents aged 15-17 years with RBW between 95 and 140 per cent and body fat tissue between 10 and 45 per cent. The increase in RBW and percentage of body fat was positively associated with systolic blood pressure in boys and girls and with diastolic blood pressure in girls. In boys, the RBW and percentage of body fat were also positively associated with total lipids, VLDL and negatively associated with HDL. In girls, there was a positive association of RBW and body fat with blood cholesterol, total lipids and LDL-cholesterol. These associations, though statistically significant, were of a rather low order when the entire range of body mass and percentage of body fat distribution were considered, but became more significant in more extreme distribution categories. The results indicate that the increase of RBW over 25 per cent of standard in both boys and girls as well as the increase in percentage of body fat over 25 per cent in boys and over 35 per cent in girls may be associated with elevated blood pressure and changes in blood lipid values in adolescents.

Adolescent↗

PubMed1980

Zinc nutrition and taste acuity in school children with impaired growth.

A study on the relationship between zinc nutrition status and the parameters of growth and physical development was carried out in a group of school children aged 9 to 12 years, selected from a population showing a higher prevalence of "below average" hair zinc concentrations. The growth of the children was assessed as the attained height for age in comparison with the reference population median, whereas the physical development was assessed on the basis of the weight for height and upper arm circumference. Taste acuity was also examined. The results showed an increased prevalence of the "below average" and "low" zinc values in hair and plasma in children of shorter stature and poorer nutrition status. The examination of taste acuity has shown that the occurrence of moderate to severe hypogeusia was statistically significantly associated with the reduction of hair zinc content. The children with moderate and more severe hypogeusia also belonged to the most poorly nourished in the examined population.

Anthropometry↗

PubMed1979

The effects of riboflavin administration on iron metabolism parameters in a school-going population.

The effect of riboflavin administration on iron metabolism was studied in a group of riboflavin-deficient children with Erythrocyte Glutathione Reductase (EC 1.6.4.2) reactivation above 1.20. The results have shown that the administration of riboflavin has resulted in a decrease of serum iron as well as in transferrin saturation which was accompanied by an increase in blood hemoglobin in subjects with initially lower hemoglobin values (less than or equal to 13.5 g/100 ml). There was, however, no change in blood hemoglobin in the group with initially higher hemoglobin values (greater than or equal to 14.0 g/100 ml). The results suggest that inadequate riboflavin intake may affect the iron utilization. The possible mechanism of riboflavin action on iron utilization is discussed.

Child↗

PubMed1979