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Biomedical subjects

M Marinković

Publications and source records attributed to M Marinković.

At least 19 recordsLinked to original sources

Extranodal marginal zone B-cell lymphoma most probably of MALT type appearing in CNS as parasagittal extracerebral tumor.

A 63 years old male patient with systemic extranodal marginal zone lymphoma, most probably originating from mucosa associated lymphoid tissue (MALT) involving central nervous system (CNS) is presented. The usual site of origin of this type of lymphoma was not identified. The diagnosis was stated after neurosurgery according to histopathology, immunohistochemistry and additional haematologic examination. Postoperative therapy included local irradiation (30Gy) of rest tumor, combined by Rituximab-CHOP (R-CHOP) protocol, which resulted in complete remission lasting three years up to now.

Antibodies, Monoclonal↗

The absence of correlation between immunoregulatory T cells and induced lymphoproliferative response in treated B-chronic lymphocytic leukemia patients.

BACKGROUND: Many data suggest T cell functional impairment in B-cell chronic lymphocytic leukemia (B-CLL). The mechanism responsible for this phenomenon is still unresolved. METHODS: In 88 B-CLL patients (RAI II-IV) the relationship between immunoregulatory T cells and PHA induced lymphoproliferative response (LPR) was analysed before and after the therapy. The number of peripheral blood CD3+, CD4+ and CD8+ T lymphocytes was determined by indirect immunofluorescence assay using monoclonal antibodies. LPR was estimated in whole blood culture method. RESULTS: The absolute number of CD3+, CD4+ and CD8+ cells in untreated CLL patients was much higher than in healthy controls (n = 26), but the percentages of these subpopulations, CD4/CD8 ratio and LPR to PHA were significantly (p < 0.00001) decreased. The chemotherapy induced a significant rise of CD3+ and CD4+ percentages (p < 0.006 < p < 0.022 respectively) in comparison to baseline levels, but their levels remained significantly (p < 0.00001) lower than the controls. The CD4/CD8 ratio was also elevated after the therapy (p < 0.048) but remained below the normal value as well. The absolute number of CD3+ and CD4+ T cells were normalized after treatment, while the CD8+ cells were still higher (p < 0.044) than controls. The increase of LPR has been registered after treatment, but it failed to reach the control values. We could not find any correlation between the number of immunoregulatory T cells and induced LPR (r = 0.07, for CD4+; r = 0.09 for CD8+ cells). CONCLUSIONS: These data indicate some profound lymphoid cell defect in CLL patients affecting CD8+ proliferation as well as LPR.

Adolescent↗

Bone marrow involvement and the prognosis of low grade non-Hodgkin's lymphoma.

AIM: To analyze the bone marrow (BM) infiltration in low-grade non-Hodgkin's lymphomas (LGNHL) and assess its association with the histopathology type, clinical behavior, and disease prognosis. METHOD: BM smears obtained by needle biopsy and stained by standard methods were analyzed in 60 patients with LGNHL using the Working Formulation. RESULTS: BM infiltration was observed in 57% of the lymphocytic lymphomas (A), in 48% of lymphoplasmocytic/ plasmocytoid lymphomas (AI), and in 31% of follicular lymphomas (follicular small cleaved cell and follicular mixed B and C). The difference was not significant. The 5-year survival rates for patients with and without bone marrow infiltration were 53% and 56% respectively, and 10-year survival rates were 31% and 45% (p>0.05). CONCLUSION: The presence of bone marrow infiltration at diagnosis did not significantly affect the prognosis of LGNHL.

Adult↗

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↗

Reactivity of monoclonal antibodies OK-CLL (anti-CD5) with peripheral blood cells of patients with B cell lymphoproliferative disorders.

Reactivity of OK-CLL monoclonal antibodies that can identify CD5 antigen on peripheral blood mononuclear cells, was investigated in 172 patients with B cell chronic lymphocytic leukemia (B-CLL) in clinical stages RAI O-I and RAI II-IV and in patients with non-Hodgkin's lymphomas, classified according to the Working formulation into high and low grade histologic type. The OK-CLL reactivity with B-CLLs in the initial (RAI O-I), as well as in advanced stages of disease (RAI II-IV) was significantly higher than in controls. Peripheral blood cells of lymphoma patients, regardless of histological type, showed a much lower values of the CD5 positive population than chronic lymphocytic leukemia (CLL) patients, and a non significant discrepancy between the number of cells stained with anti-CD5 and those stained with other T cell markers. In spite of the showed considerable decrease of CD5 positive cells in CLL patients during therapy, elevated number of this population compared to normal individuals, after chemotherapy, was found. However, in lymphoma patients of both types of malignancies, CD5 positive population increased concomitantly with therapy. These results may suggest that analysis of CD5 antigen expression on peripheral blood cells of patients with B cell lymphoproliferative malignancies may have diagnostic, or, in correlation with some relevant clinical parameters, a potential predictive value in the treatment of those patients.

Adult↗

[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↗

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↗

Controlled multicentre comparison of captopril versus lisinopril in the treatment of mild-to-moderate arterial hypertension.

The antihypertensive efficacy and safety of lisinopril (L), a novel ACE inhibitor, were compared to those of captopril (C), the familiar drug of the same class, in a multicentre controlled trial. The study included 91 mild-to-moderate, middle-aged hypertensives of both genders, 46 of which were randomized to C and 45 to L. After a two-week placebo period the examinees were receiving either L o.d. in increasing dosage of 10, 20, or 40 mg per day (amount necessary to achieve normotension), or C b.i.d. in a corresponding daily dose of 25, 50, or 100 mg. During the eight-week formal part of the trial, L decreased the systolic blood pressure from the initial values by an average of 14.9%, and the diastolic pressure by some 15.2%. The same parameters were lowered on C by 11.2%, and 11.7%, respectively. The mean arterial pressure from an initial average of 125.5 mmHg was lowered to 110.9 mmHg on C (11.6% reduction, p < 0.01), and from 125.3 mmHg to 108.2 mmHg on L (13.6% reduction, p < 0.01). Although the L effects were more pronounced, the observed between-group differences did not reach the level of statistical significance, except for the achievement of normotension, which disclosed the superiority of L (p < 0.05). The tolerability of both drugs was good and only one examinee had to be excluded because of side-effects (proteinuria). It is concluded that both ACEIs under study showed comparable efficacy and safety, L being marginally more potent and longer acting.

Adolescent↗

[Determination of T lymphocyte subpopulations in malignant lymphoproliferative diseases].

The aim of this work was to investigate T cell subset composition of peripheral blood cells in patients with acute myeloid leukaemia, acute lymphoblastic and chronic lymphocytic leukaemia, by enumerating T cells positive for receptors for sheep erythrocytes (E-RFC, A-RFC) using the method of E-rosette, and for CD3, CD4 and CD8 antigens, by indirect immunofluorescence technique, using the monoclonal antibodies of the OK series. The study was performed on 57 patients without therapy and 46 healthy persons. The results of enumeration of T cells and their subsets obtained in the stage of the disease when the total leukocyte count was below 20 x 10(9)/L, were markedly decreased in all three types of leukaemias. The most significant decrease of relative count of T cells and their subpopulations was obtained in CLL patients. Analysis of T cells subsets and their ratio in CLL patient in the stage of disease when the total leukocyte count as higher than 20 x 10(9)/L, demonstrated the most pronounced decrease of total T lymphocytes and CD4+ cells. The relative count of the "active" (A-RFC)T cells and CD8+ cells did not change, and was the same as in the patients suffering from CLL with a lower leukocyte count.

Humans↗

[Renin levels in renal veins in patients with essential arterial hypertension].

The data on plasma renin activity (PRA) obtained by catheterization of renal veins in 272 patients with essential arterial hypertension (EH) are reported. In order to exclude a secondary nature of hypertension, all patients were hospitalized and submitted to the extensive clinical and laboratory examinations (according to the protocol) including renal angiography. The aim of the work was to get evidence whether in the apparently homogeneous group of patients with EH there are differences in renin activity between the renal veins giving the quotient (Q) higher than 1.5, and possibly to recognize the clinical meaning of the differences of Q found. In the examined patients as a whole regardless of PRA, 50 of them (18.3%) showed Q greater than or equal to 1.5 and among them in 16 (5.8%) patients Q greater than or equal to 2 was found. The patients were divided according to PRA into those with low, normal and high PRA. In the hyperreninemic group of patients no Q greater than or equal to 2.0 has been found. In the hyporeninemic group 9 patients (9.9%) exhibited Q greater than or equal to 2.0. Although, one does not expect in EH to find differences in PRA between left and right renal vein, we have found the values of Q greater than or equal to 1.5 in nearly 1/5 of our patients. These differences found could be resulting from the existence of asymmetrical angiosclerotic or other renal pathological changes that can not be examined by the available clinical methods.(ABSTRACT TRUNCATED AT 250 WORDS)

Humans↗

Enalapril versus captopril: a double-blind multicentre comparison in essential hypertension.

A collective, multicentre (Ljubljana, Split, Zagreb) comparison of the antihypertensive effects between two angiotensin converting enzyme inhibitors (ACEI) captopril and enalapril was made in 69 hypertensives of both sexes, having a diastolic blood pressure (DBP), following two weeks on a placebo, of between 110 and 130 mm Hg (14.7 and 17.3 kPa). There were 35 patients on enalapril (20-40 mg), and 34 on captopril (50-100 mg). Both drugs under study decreased significantly the mean DBP already after the first week of ACEI treatment (p less than 0.001). By the end of the trial (9th week) captopril had decreased the DBP in the supine position from the initial 180.3 +/- 15.3/117.7 +/- 6.4 mm Hg to 151.6 +/- 11.1/96.8 +/- 7.2 mm Hg. Enalapril had lowered the DBP more efficiently: from 182.7 +/- 16.7/118.7 +/- 7.7 to 145.6 +/- 12.8/92.2 +/- 6.4 mm Hg (p less than 0.05). The average reduction in mean DBP was 16.9% on captopril, and 20.9% on enalapril. Low dose ACEI monotherapy (i.e. 50 mg and 20 mg) achieved DBP normalization in 11.8% on captopril and in 26.4% on enalapril (p less than 0.01). There were no significant heart rate changes. The laboratory results did not change appreciably and there were no relevant side-effects, although particular attention was paid to the expected adverse reactions, such as cough, ageusia or proteinuria. It is concluded that the ACEIs under study showed comparable effectiveness within the used dose range, enalapril being more potent, longer acting, and possibly safer.

Blood Pressure↗

Nicardipine versus nifedipine: multicentre controlled trial in essential hypertension.

Ninety-five hypertensive outpatients of both sexes, aged 23 to 65 years with diastolic blood pressures above 105 but below 120 mmHg (greater than 14.0 but less than 16.0 kPa), after one week on a placebo were randomly assigned either to nicardipine plus a placebo (40 mg/day - 48 patients) or nifedipine sustained-release plus a placebo (20 mg/day - 47 patients) for an additional six weeks. The study groups were homogeneous and comparable. After the run-in period the average blood pressure was 181 +/- 17/116 +/- 9 mmHg (24.1 +/- 2.3/15.5 +/- 1.2 kPa) in the nicardipine and 177 +/- 22/116 +/- 9 mmHg (23.6 +/- 2.9/15.5 +/- 1.2 kPa) in the nifedipine group (p greater than 0.10). In the acute oral test (nicardipine 40 mg to all the subjects; blood pressure measured at 30 min intervals during two hours) almost identical hypotensive effects within and between groups were observed (mean arterial pressure decrease of 11%, after 120 min; p less than 0.05). At the end of this trial blood pressure decreased further to 152 +/- 12/94 +/- 11 mgHg (20.3 +/- 1.6/12.5 +/- 1.5 kPa) (mean decrease of 20%; p less than 0.01) on nicardipine and to 145 +/- 12/94 +/- 11 mmHg (19.3 +/- 1.6/12.5 +/- 1.5 kPa) (mean decrease of 20%; p less than 0.01) on nifedipine. There were no significant changes in pulse rate. The observed between-group differences were trivial (p greater than 0.10). The laboratory data did not alter appreciably during this study. Three patients on nicardipine and four on nifedipine reported headache, palpitations and flushing: one patient on nicardipine and two on nifedipine were as a result excluded from the trial. It was concluded that nicardipine and nifedipine sustained-release were comparably effective and well-tolerated drugs suitable as the first-line agents for the management of mild to moderate hypertension.

Administration, Oral↗