Biomedical subjects
Publications and source records attributed to A V Pivnik.
The authors present their own observation of a patient suffering from drug-induced agranulocytosis, cured with filgastrim-neupogen, a recombinant colony-stimulating human granulocyte factor.
AIM: To determine the role of histological diagnosis of lymphadenopathy (LAP) associated with clinico-laboratory picture in patients with HIV infection/AIDS. MATERIAL AND METHODS: Target biopsy of the peripheral lymph node was made in 80 HIV-infected patients from 2002 to 2005. Histological diagnosis was made in all the patients with light microscopy, in some patients at immunohistological examination. RESULTS: Most of the patients had peripheral blood CD4 lymphocytes under 200 cell/mcl. Viral load was hundred thousands copies in mcl. Tuberculosis was diagnosed in 33 (41%) patients, lymphomas--in 23(29%), lymphogranulomatosis--in 5 (6%), reactive lymphadenopathy--in 15 (19%), germinogenic tumors--in 3 (4%), sarcoidosis--in 1 (1%). Histologically, LAP was represented by follicular hyperplasia (n = 9), involution (n = 2), bacterial lymphadenitis with necrosis (n = 4). CONCLUSION: Biopsy of peripheral lymph nodes is an early, safe, reliable and cost-effective method of LAP diagnosis in patients with AIDS.
AIM: To analyse overall recurrence-free survival of lymphogranulomatosis (LGM) patients given polychemotherapy (PCT) MOPP (mustargen-caryolisin, vincristine, natulan, prednisolone) - ABVD (adriamycin, bleomycin, vinblastin, dacarbasin) in combination with radiotherapy (RT) for 10 years. MATERIAL AND METHODS: The trial included 211 LGM patients admitted to Hematological Research Center in 1990-1996 from other hospitals without random selection. The patients were examined by the standard program including biopsy of the affected organ or lymph node, bilateral trephine biopsy. Splenectomy was performed in 17 patients, 83 patients received PCT in other hospitals, 128 untreated patients received MOPP-ABVD therapy (3 courses of MOPP and 3 courses of ABVD). Forty one patients had defects in PCT, 16 of them rejected PCT and RT. The latter was performed 4 weeks after the 6th course, contraceptives were not prescribed to women. At LGM stage II-III RT was performed by the subradical program (no radiation to ilioinguinal lymph nodes) in doses 40-44 Gy on the foci and 32-36 Gy preventively, on massive and residual foci after PCT - 5-10 Gy additionally. RESULTS: Ten-year overall and recurrence-free survival in the untreated group reached 83 and 80%, respectively, for pretreated patients - 46 and 36%, respectively. Causes of death of 26 patients were LGM progression, infection (tuberculosis, as a rule), secondary tumors and acute myeloblastic leukemia (AML). After remission 25 women gave birth to a healthy child and 12 healthy children were born to 9 males. CONCLUSION: MOPP-ABVD plus radiotherapy program according to subradical and radical variants was in the past effective but invalidating rescue therapy. Present-day programs consider the histological variant, stage and prognostic factors allowing an individual therapeutic approach with step-by-step reduction of RT in the treatment of LGM patients. Involvement of the bone marrow in primary patients had no influence on the treatment results. This refers this affection not to a generalized stage IV, but to stage III along with involvement of the lymph nodes and the spleen.
AIM: To study clinical symptoms, course and diagnosis of tuberculosis in patients with hemoblastosis (HB). MATERIAL AND METHODS: 79 patients with tuberculosis and HB were examined. HB was represented by lymphoproliferative diseases (n = 61), acute leukemia (n = 4), chronic myeloproliferative diseases (n = 14). RESULTS: Pulmonary tuberculosis was in 61 (77.2%) patients: in 46 with lymphoproliferative disease (LPD), 4 with acute leukemia (AL) and 11 with myeloproliferative disease(MPD). Generalized tuberculosis was detected in 8 (10.1%) patients (7 with LPD and 1 with MPD) and extrapulmonary tuberculosis was in 10 (12.7%) patients (8 with LPD and 2 with MPD). Infiltrative, disseminated and military tuberculosis of the lungs developed in 55.7, 6.6 and 1.6% HB patients. CONCLUSION: Persistent fever in HB patients may point to developing tuberculosis infection. Fever syndrome and intoxication in patients with HB remission may serve a diagnostic marker of tuberculosis.
AIM: To distinguish T-cell lymphomas and reactive T-cell proliferation it is important to confirm the ability of T-cells to be cloned. Conventional histological and immunophenotypic methods fail to determine the ability of T-cells to be cloned. An experience in the use of detection of T-cell receptor gene gamma-chain (TCRy) rearrangement for determining T-cellular clonality is described. MATERIAL AND METHODS: Polymerase chain reaction (PCR) and single strand conformational polymorphism (SSCP) were used to determine T-cell clonality. Twenty healthy donors, 28 patients with T-lymphomas, and 26 patients with various non-T-cell lymphoproliferative disorders or reactive processes were studied. RESULTS: T-cell monoclonality was detected in 23/28 (82%) T-cell lymphoma cases, whereas in all the samples from normal subjects a polyclonal pattern of rearrangements TCRy was found. The sensitivity of the method was estimated as 2.5%, 7%, and 10% was demonstrated for bone marrow, spleen, and peripheral blood, respectively. CONCLUSION: PCR-SSCP for TCRy was found to be a useful supplement to routine histological and immunophenotypic methods in the diagnosis of T-cell lymphomas.
AIM: To characterize patients with various nosological unities [symbol: see text] of porphyria in accordance with their age, clinical symptoms, provoking factors, therapy and outcome. MATERIAL AND METHODS: Patients with acute intermittent porphyria (43), hereditary coproporphyria (8), variegate porphyria (3), porphyria cutanea tarda (7), hepatoerythropoietic porphyria (1), and hereditary erythropoietic porphyria (2) were studied. One patient was suspected of porphyria caused by deficiency of delta-aminolevulenic acid dehydrogenase. RESULTS: The patients were from the CIS. The overwhelming majority of them were young and middle-aged subjects. Rapid development of the disease and severe neurological symptoms were predominantly observed in patients with acute forms of porphyria. CONCLUSION: Early diagnosis of porphyrin metabolism disorders makes it possible to decrease abruptly the number of cases leading to severe complications, disability, and fatal outcome. The use of inexpensive methods of screening of porphyrin metabolism disorders provides a promising approach to solving this problem. These methods should be used in municipal hospitals. In addition, asymptomatic carriers of defective gene should be revealed at the preclinical stage using various methods of molecular genetic assay.
AIM: To characterize diagnosis of tuberculosis in hemoblastosis patients. MATERIAL AND METHODS: Diagnosis of active tuberculosis in 2.6% from 2123 hemoblastosis patients admitted to Hematological Research Center in 1990-1999 shows that such patients can be referred to high risk group in relation to tuberculosis infection. Methods and terms of tuberculosis diagnosis in hemoblastosis patients are analysed. RESULTS: Bacteriological and histological tests were positive in 27.8% examinees with hemoblastosis. In extrapulmonary tuberculosis location, histological diagnosis was positive in 60%. Especially helpful is a complex of clinical and x-ray examinations in high tuberculosis alertness. This allowed to suspect the infection in 51.9% patients (63.9% had pulmonary location). A marked positive response to antituberculosis treatment proved tuberculosis diagnosis. CONCLUSION: Difficulties of tuberculosis diagnosis in hemoblastosis patients are explained by low informative effectiveness of most common methods of this infection verification. Therefore, in addition to bacteriological and histological examinations, clinical diagnostic techniques should be employed keeping alert in relation of tuberculosis in hemoblastosis patients who are at risk to catch this infection.
Examining 2321 patients admitted for various forms of hemoblastoses (HB) to the Hematology Research Center, Russian Academy of Medical Sciences, in 1990-1999 revealed active forms tuberculosis in 60 (2.6%) patients. Among them generalized tuberculosis and predominantly extrapulmonary tuberculosis were detected in 8 (10.1%) and 10 (12.7%) patients, respectively. Bacteriological and morphological studies confirmed the diagnosis only in 22 (27.8%) patients, including in 15 (22.9%) patients with pulmonary tuberculosis. In the bulk of patients [n = 51 (64.6%)], the diagnosis of tuberculosis was suspected on the basis of a complex of clinical and X-ray data and evidenced by the beneficial effect of antituberculous chemotherapy. The clinical and X-ray manifestations of tuberculosis were similar in patients with different forms of HB. They are characterized by an aptness to hematogenous dissemination of the process, by the incidence of generalized and extrapulmonary lesions involving blood-forming organs, and by the significant extent of infiltrative changes in the lung with a relatively formation of single and small decay cavities. Antituberculous chemotherapy according to the standard regimen recommended by the WHO yielded a prompt and significant effect by improving the patients' status, eliminating fever, and ceasing bacterial isolation. Deaths occurred in 6 (7.6%) patients with lifetime undiagnosed generalized tuberculosis untreated with antituberculous drugs.
AIM: To clarify the potential of delayed densitometry of late (fixed) contrast in differentiation between tumor and fibrosis in residual mediastinal lesion (RML). MATERIAL AND METHODS: Computed tomography (computed tomograph of the third generation COMATOM CR-3 made in Germany, SIEMENS) has examined 12 patients with mediastinal lymphosarcomas after polychemotherapy. All of them had a RML 3 to 6 cm in diameter. RESULTS: CT has detected 8 cases of the tumor and 4 cases of fibrosis. The criteria of the tumor were the following: increased RML density shortly after the contrast medium introduction and 30 min after urographine introduction (p < 0.01); RML density 30 min after introduction of contrast medium was higher than above the aorta (p < 0.01). Fibrosis in RML was stated if RML density before, at the high of concentration and after introduction of the contrast medium was the same (p > 0.01); aortic density was significantly higher of RML density at the height of the contrast (p < 0.01). CONCLUSION: The above method differentiates the tumor with fibrosis in RML with maximal probability. This facilitates further choice of therapeutic policy in secondary resistant form of primary mediastinal lymphosarcoma.
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AIM: To study the cardiovascular system in patients with lymphogranulomatosis (LGM) at prolonged remission. MATERIALS AND MATERIALS: 78 patients received radiation and chemotherapy for lymphogranulomatosis in 1973 to 1995. All the patients underwent electro- and echocardiography (EchoCG), 40 patients had radioisotopic ventriculography (RVG). RESULTS: EchoCG revealed nonspecific changes in the ST segment in 19 (24.3%) patients. Systolic function was decreased vto 46% only in 1 patient. RVG showed a significant reduction in ejection fraction in the experimental group as compared to the control one (55.5 +/- 9.5 and 68.4 +/- 8.0, respectively; p < 0.05). CONCLUSION: Cardiac disorders revealed in patients with LGM at prolonged remission are mainly insignificant. The risk for cardiac events is not a guide for reducing radiation doses and the intensity of chemotherapy.
Porphobilinogen deaminase (PBGD) is a key enzyme of the heme biosynthetic pathway. Defects in the PBGD gene lead to an autosomal dominant disease, acute intermittent porphyria (AIP). Almost all AIP patients with rare exceptions are heterozygous for the defective gene. To date, at least 160 different mutations causing AIP are identified. Extensive investigations along this line are conducted in many countries of the world. In Russia these studies had not been hitherto performed. Here we report the results of molecular genetic examination of four Russian patients with AIP diagnosed from clinical symptoms. By direct sequencing of the PBGD gene or the corresponding cDNA, we have detected four mutations, three of which were not previously encountered in the world population. These are TAAG deletion in intron 7 between positions +2 and (IVS7 2-5 delTAAG); T deletion in the initiation codon ATG of exon 3, and the G for C replacement at position -1 of intron 5 (IVS5 as -1 G:C), which disrupts splicing. In addition, in one female patient, a known deletion CT in codon 68 was revealed. In two patients, expression of PBGD gene alleles was significantly disproportional, so that normal mRNA prevailed in one case and mRNA of nonerythroid type in the other. Deletion in intron 7 was easily detectable due to the formation of a heteroduplex fragment with abnormal electrophoretic mobility directly in PCR. This simple heteroduplex analysis allowed us to exclude AIP carriage in son and daughter of a female patient with the genetic defect.
AIM: Determination of the importance of serum cytokines (sCD30, sIL-2R, IL-10, IL-6) for diagnosis, response to chemotherapy and remission in patients with lymphogranulomatosis and lymphosarcoma. MATERIAL AND METHODS: Cytokine concentrations were measured in 87 samples of serum (plasma) from 54 patients by ELISA. Diagnosis of Hodgkin's disease (HD) and non-Hodgkin's lymphoma (NHL) was made histologically in 24 and 30 patients, respectively. RESULTS: The threshold concentrations of sCD30 (and less specific sIL-2R) for HD and NHL patients allowed to estimate sensitivity to chemotherapy after the second course. The threshold concentration of IL-10 can distinguish HD from NHL. Changes in IL-6 concentrations were nonspecific. CONCLUSION: On the basis of the threshold concentrations of sCD30 and IL-10 we offer the scheme of lymphoma diagnosis and prediction of the disease sensitivity to chemotherapy which reduce the duration of lymphoma restaging.
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AIM: To assess diagnosis of parvovirus B19 infection (PI) in patients with aplastic crises by combined use of polymerase chain reaction (PCR) and enzyme immunoassay (EIA) of specific IgM and IgG. MATERIAL AND METHODS: A total of 159 serum samples from 77 PI suspects were examined. The examination for virus DNA was conducted with modified "net" PCR in 108 samples, for specific IgM and IgG with EIA in 110 samples. RESULTS: The percentage of patients infected with parvovirus detected by PCR or EIA reached 60%. 21 of 77 patients with hemolytic anemias were infected with parvovirus B19, the virus persisting in 8 cases (40%). persistence of the virus was registered if viremia occurred in immunodeficiency due to the disease or immunosuppressive therapy. Immunity to parvovirus has not developed: IgM expression was the same as in patients without hemopoietic abnormalities, while IgG was not detected. The absence of specific immunity to parvovirus B19 occurred in patients treated with immunosuppressive drugs early after the end of viremia period in high IgM level and at the initial phase of IgG synthesis. IgM levels also remained unchanged; the level of IgG declined and was not identified furthermore. There were cases of reinfection. CONCLUSION: Combined use of PCR and EIA is optimal for diagnosis of parvovirus B19 infection in patients with hemolytic anemias. It was found that there are correlations between defects in specific immunity, persistence and immunodeficiency onset regarding viremia. Abnormal for the disease course levels of IgM and IgG indicate the persisting virus, the condition of specific immune response to parvovirus B19 and feasibility of reinfection. Reliable diagnosis of parvovirus infection is possible only in simultaneous use of PCR and EIA.
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AIM: To evaluate toxicity and efficacy of CDxOP regimen in the treatment of primary non-Hodgkin's lymphoma (PNHL). MATERIAL AND METHODS: The study included 8 males and 6 females who had large B-cell lymphoma (n = 11), follicular lymphoma, predominantly large cell (n = 1), mantle cell lymphoma (n = 1) and peripheral T-cell lymphoma (n = 1). Seven patients were over 60. PNHL stage IV, III and II was diagnosed in 7, 5 and 2 patients, respectively. Daunoxome dose was 80 mg/m2 with an increase up to 100 mg/m2 in case of slow response and good tolerance. The other drugs were used in standard doses. RESULTS: 6 patients achieved complete remission (43%) and 5 patients--partial response (36%), the overall response was 79%. Three patients did not respond to therapy and died. Six patients are still in complete and two in partial remission, median follow-up being 22 months. The rest 3 patients were treated with other modalities, one of them died of infection. As to complications that might be related to daunoxome, there was myelodepression (6% of profound neutropenia < 1000 microl). No patients had deterioration of the left ventricular ejection fraction (ultrasound measurements) or clinical signs of congestive heart failure (median follow-up for 10 patients was 22 months) including those in whom high cumulative doses were used (640-840 mg/m2). One patient with compromised heart function had frequent ventricular extrasystole immediately after daunoxome infusion. CONCLUSION: Tolerance of CDxOP is acceptable. The results of the treatment are comparable with those of standard chemotherapy. Further comparative studies are needed for determination of efficacy and maximal tolerated dose of daunoxome in combination with other drugs and irradiation, of long-term side effects. This drug may be beneficial for elderly patients.