Physiological response to Vibro-Acoustic stimulation in healthy subjects: a preliminary study.

Over the last decade Vibro-Acoustic Therapy (VAT) was used for several clinical applications. This paper investigates the use of AcusticA®, an innovative VAT solution represented by a wooden chaise longue that follows the construction principles of a "musical instrument that stimulates the whole body" in relation to the sound frequencies produced by the music tracks. Ten healthy young subjects were enrolled for this study. Wearable sensors were used to monitor the human physiological response during the VAT session but also during a traditional acoustic therapy (AT) to highlight similarity and differences of those stimulations. Signals from heart activity, brain activity and electrodermal activity were analyzed to investigate the response during the non-stimulated and the stimulated phases. Additionally, two supervised classification algorithms were used to investigate whether the extracted instances could be grouped into two different groups. The results identify a trend of the attention and meditation features extracted from brain activity, which pointed out the relax efficacy of the VAT.Clinical Relevance - There are not significant differences (p<0.05) in the physiological response between the VAT and the AT stimulation, but during the VAT the alpha coefficients were significant different during the stimulated phase. Finally, the classification algorithms were able to classify the groups with an accuracy equal to 100% in the best case.

[Hairy cell leukemia and pregnancy]. / Volosatokletochnyi leikoz i beremennost'.

The paper presents experience in following up and treating hairy cell leukemia (HCL) during pregnancy. The combination of HCL and pregnancy was observed in 5 patients. The patients' median age was 35 years (range, 28-42 years). The diagnosis of HCL was based on a conventional examination protocol: clinical blood analysis with the morphological assessment of lymphocytes, a myelogram and trepanobiopsy, immunophenotypic analysis of lymphocytes or bone marrow (in all the patients), cytochemical determination of tartrate-resistant acid phosphatase in 3 patients, and identification of BRAFV600E mutation in 3 patients. Three pregnant women were treated for HCL in the postpartum period. In one patient with HCL, pregnancy was seen in remission after treatment with cladribine. In one patient with HCL detected at 11 weeks' gestation, interferon-α therapy during the second trimester of pregnancy was performed for increased cytopenia, which was followed by cladribine therapy after delivery. Pregnancy and delivery were uncomplicated in all the patients; 3 patients had vaginal delivery and 2 patients underwent cesarean section. All infants were healthy, with no developmental abnormalities during a follow-up period of 6-140 months (median 30 months). All the patients with HCL are currently in remission: 4 patients in first remission at a follow-up of 10 to 48 months (median 15 months) and one patient in second remission at a follow-up of 88 months. Possible observational tactics is possible when HCL is detected during pregnancy. Treatment of HCL during pregnancy is necessary in cases of deep or progressive cytopenia and/or splenomegaly. The use of interferon-α or splenectomy is preferable.

A Single-center Experience in Splenic Diffuse Red Pulp Lymphoma Diagnosis.

The World Health Organization 2008 classification highlighted a new nosology-splenic diffuse red pulp lymphoma (SDRPL) with clinical and laboratory features similar to both splenic marginal zone lymphoma and hairy cell leukemia (HCL) and variant form of HCL. Experience of hematologists on the diagnosis and differential diagnosis of SDRPL is extremely limited. The aim of our report was to characterize the clinical and immunomorphologic features of SDRPL on our own observations. During 2013-2014, in National Research Center for Hematology, 87 spleen specimens removed from various B-cell lymphomas were analyzed. In four (4.6%) cases, the diagnosis SDRPL was made based on morphologic, immunohistochemical, immunophenotypic, molecular examination of spleen biopsies, blood and bone marrow samples. In all cases of SDRPL were observed significant splenomegaly, lymphocytosis from 56% to 94% (in two cases with leukocytosis 55.000 and 75.000 109/l). The circulating "villous" lymphocytes phenotype was CD20+ (bright), CD11c+/±, CD103 (weakly)+/±, LAIR-1+, CD25-, CD5-, CD10-, and CD23-. Mutation BRAFV600E was not detected. Bone marrow with minor lymphoid CD20+, CD25-, Annexin1-, Cyclin D1- cell infiltration. The average weight of the spleen was 3900 g (1450-9500 g), and morphologically, there was revealed lymphoid infiltration of red pulp with phenotype CD20+, DBA.44+, CD25-, Annexin1-, Cyclin D1-, CD103-, CD123-, CD27-, focal SD11c± and TRAP±. Now patients are observed in remission: two patients after splenectomy, two after splenectomy and cladribine+rituximab chemotherapy. SRDPL-a rare lymphoma that is suspected in the cases with significant splenomegaly and lymphocytosis with villous lymphocytes forms that have only a part of the classic markers HCL, with minor bone marrow infiltration. The standard diagnosis and treatment is splenectomy. Differential diagnosis of SMZL and HCL has clear criteria, but criteria of differentiation with variant HCL are still unknown.

[Experience in investigating splenic red pulp lymphoma]. / Opyt izucheniya limfomy krasnoi pul'py selezenki.

AIM: To generalize hematologists' experience of the diagnosis and differential diagnosis of splenic red pulp lymphoma (SRPL). MATERIAL AND METHODS: Eighty-seven splenic biopsy specimens taken from patients with different B-cell lymphoproliferative diseases were examined in the Hematology Research Center in 2013-2014. The diagnosis of SRPL was based on the morphological, immunohistochemical, immunophenotypic, and molecular examinations of the splenic biopsy specimens, blood and bone marrow (BM) tests in 4 (4.6%) cases. RESULTS: There was significant splenomegaly in all SRPL cases, lymphocytosis in 56 to 94% (leukocytes, 55 and 75·109/l in 2 cases), circulation of hairy lymphocytes with the phenotypes CD20+ (markedly), CD11c+/±, CD103+/± (weakly), LAIR-1+, CD25-, CD5-, CD10-, and CD23-, which did not contain tartate-resistant acid phosphatase, without BRAFV600E mutation, BM with insignificant lymphoid infiltration of CD20+, CD25-, Annexin 1-, and Cyclin D1-. The weight of the spleen averaged 3900 g (1450-9500 g); its tissue exhibited lymphoid infiltration of the red pulp with the phenotypes CD20+, DBA.44+, CD25-, Annexin1-, Cyclin D1-, CD103-, CD123-, CD27-, focal СD11c±, and TRAP±. Four patients (2 after splenectomy (SE) and 2 after SE and chemotherapy with cladribine and rituximab) are being followed up in remission. CONCLUSION: SRPL is a rare disease that should be presumed to be in significant splenomegaly and lymphocytosis with hairy lymphocytes, which have only some markers for classical hairy cell leukemia (HCL), in minor BM lesion. SE is the standard for diagnosis and treatment. The differential diagnosis of SRPL with HCL has clear criteria and that with HCL-v is undetected.

[Isolated sacral injury in hairy cell leukemia: A case report and analysis of literature data].

Hairy cell leukemia (HCL), a chronic B-cell lymphoproliferative disease with special villous morphology and immunophenotypic markers of lymphoid cells, is characterized by the involvement of bone marrow and spleen. The paper describes a case of a 29-year-old female patient without abnormal clinical blood tests and myelograms, with normal spleen sizes, in whom the only manifestation of HCL was massive scrotal injury with a soft tissue component in the small pelvic cavity.

[Nodular lymphocyte-predominant Hodgkin's lymphoma: Principles of diagnosis and treatment].

AIM: To describe the clinical and morphological features of the rare Hodgkin's lymphoma (HL) subtype--nodular lymphocyte-predominant HL (NLPHL). SUBJECTS AND METHODS: Forty-two patients were diagnosed with NLPHL in 2010 to 2014. The male to female ratio was 2.2:1; the median age was 37 years (range 17-68 years). NLPHL was diagnosed on the basis of the histological and immunohistochemical examinations of tumor biopsy specimens; disease stages were determined by standard HL studies. RESULTS: Before NLPHL was detected, 23 (55%) patients were diagnosed as having HL in 13 cases, follicular lymphoma in 2, lymphofollicular hyperplasia in 3, angioimmunoblastic lymphoma in 1, diffuse large B-cell lymphoma in 3, and B-cell lymphoma (non-HL) in 1. Long-term (3-21-year; median 8 years) persistent lymphadenopathy was observed in 16 (38%) patients. Seventeen (40.5%) patients had early (I-II) stages of the disease and 25 (59.5%) had advanced stages. B symptoms were noted in 24% of cases. There was involvement of extranodal sites (salivary gland, tonsil) in 2 patients, spleen in 14 (33%), bone marrow in 8, and bulky disease in 2. Cycles of ABVD ± rituximab ± radiotherapy (RT) were used in early-stage NLPHL; those of R-BEACOPP-14 ± RT were performed in the advanced stages of the disease or its transformation to diffuse large B-cell lymphoma with excessive T cells. CONCLUSION: When patients have a history of long-term asymptomatic lymphadenopathy, it is necessary to rule out NLPHL, for which purpose an immunohistochemical examination of a biopsy specimen and its reexamination in a laboratory having experience in diagnosing NLPHL must necessarily be done. Lower RT doses and rituximab incorporated into the cycle of treatment are indicated to reduce its toxicity and to preserve therapeutic efficiency.

[Thrombosis of the sinus durae matris as a complication of therapy in patients with Hodgkin lymphoma].

AIM: To describe thrombosis of the sinus durae matris (TSDM) in lymphomas. SUBJECTS AND METHODS: 402 patients with Hodgkin lymphoma were treated using the BEACOPP-14 protocol in 2006 to 2013. Thrombotic events occurred in 6% of the patients, including 3 (0.8%) who developed brain magnetic resonance imaging-verified TSDM. RESULTS: TSDM developed in 3 women aged 17, 18, and 25 years during 3-6 chemotherapy cycles involving glucocorticosteroids in a dose of 80 mg/m2 on days 1-7 and an oral contraceptive used continuously for 1.5-3 months. The symptoms of thrombosis were severe headache; 2 patients had convulsive syndrome with short-term loss of consciousness. Anticoagulant therapy with intravenous heparin 20,000--24,000 U/day led to thrombus recanalization within 4-10 days. No rethromoboses were observed during a subsequent follow-up. CONCLUSION: The BEACOPP-14 treatment in young women with Hodgkin lymphoma who continuously take oral contraceptives should be combined with anticoagulant therapy, by monitoring their coagulogram.

[Viral mucosal lesions of the gastrointestinal tract organs in patients with lymphoma].

Infectious complications are one of the main causes of the lower efficiency of chemotherapy in hematologic oncology. The common infectious pathogens are herpes group viruses. The manifestations of herpesvirus infection or reactivation may be extremely diverse; just the same, digestive tract injury is rarely associated with herpesvirus infection in clinical practice. Viral mucosal injury of the intestine and pharynx is described in 2 patients with lymphomas during agranulocytosis. Virus-specific DNA was absent in blood; however, it was detected at high titers (the number of copies of 10(3) 10(5) genome-equivalent/mI) in feces and mucosal biopsy specimens. Addition of antiviral therapy could rapidly abolish infectious complications in both cases. Virological examination of material from the injury focus makes it possible to reveal a pathogenic virus even though the latter is undetectable in blood.

[Tuberculosis in patients with lymphoproliferative diseases].

AIM: To study the clinical manifestations, diagnosis, and treatment of lymphoproliferative diseases (LPD) concurrent with tuberculosis. SUBJECTS AND METHODS: In 1990 to 2013, the Hematology Research Center, Ministry of Health of Russia, followed up 4422 patients with LPD. Lymphomas and leukemias were diagnosed using the universally protocols. Tuberculosis was verified by the results of a comprehensive examination involving the histological study of biopsy specimens. RESULTS: Tuberculosis was identified in 85 (2%) patients with LPD. According to the nosological entity, the tuberculosis detection rates were 3% (40/1350) in Hodgkin lymphoma (HL), 1.2% (20/1627) in aggressive lymphomas, 1.4% (16/1136) in mature cell lymphomas and chronic lymphocytic leukemia, and 2.9% (9/309) in hairy cell leukemia. In accordance with its site, pulmonary tuberculosis was 73%; extrapulmonary tuberculosis, 14%; generalized tuberculosis, 12%. In pulmonary tuberculosis, its disseminated and focal involvements were found in 71 and 18% of cases, respectively. Tuberculosis was detected in 43% of the patients with HL in remission; it occurred only in other hemoblastoses in its active phase. When tuberculosis and LPD were simultaneously found, both diseases were concurrently treated. If the chemotherapy of LPD was effective, tuberculosis was cured in all the patients. CONCLUSION: Patients with LPD are a group at increased risk for tuberculosis. The diagnosis of recurrent LPD must be histologically proven. When tuberculosis and LPD are simultaneously found, both diseases should be concurrently treated.

[Pneumocystis pneumonia in patients with Hodgkin lymphoma].

AIM: To assess the results of diagnosing and treating Pneumocystis pneumonia (PP) in patients with Hodgkin lymphoma (HL) over 15 years. SUBJECTS AND METHODS: In 1999 to 2013, PP occurred in 22 (3%) of 741 HL patients receiving programmed polychemotherapy (PCT). The male/female ratio was 1:1.1; median age was 32 (18-65) years. Advanced stages (IIB-IV) of the disease were seen in 82% of the patients. The diagnosis of PP was established when Pneumocystis (more than 5 cysts in the specimen) was detected in the lavage fluid by indirect immunofluorescence assay. RESULTS: PP developed after 4 or more cycles of PCT. Along with Pneumocystis, all the cases were found to have additional pathogens: herpes virus in 72% and bacteria and fungi in 33%. All the patients received combined antimicrobial therapy using high doses of intravenous trimethoprim-sulfamethoxazole. Ten (45%) patients required mechanical ventilation (MV). The total mortality in PP was 32% (7 patients died); moreover, none of the patients without MV died whereas the mortality among those who had MV was 70% (7 of the 10 patients died). High death rates (80%) were noted among the patients with recurrent and resistant HL. CONCLUSION: PP should be prevented with trimethoprim-sulfamethoxazole in patients with LH during PCT. If respiratory failure and X-ray signs of interstitial pneumonia appear, there is a need for fibrobronchoscopy with bronchoalveolar lavage and comprehensive microbiological testing of lavage fluid.

[Successful use of vemurafenib in a patient with resistant hairy cell leukemia].

The paper describes a case of a patient with refractory hairy cell leukemia. In spite of the absence of CD25 expression, the disease was classified as a classical form according to the WHO classification (2008), as also confirmed by the detection of BRAFV600E mutation. The disease was characterized by resistance to all lines of therapy (interferon-a, splenectomy, cladribin). Clinical and hematological remission was achieved within 2 months of administration of the BRAF kinase inhibitor vemurafenib.

[Treatment for recurrent hairy cell leukemia].

AIM: To give data on the frequency of recurrent hairy cell leukemia (HCL) and to characterize the immediate and late results of its treatment in this group of patients. MATERIALS AND METHODS: The data on the frequency of recurrences were analyzed in 165 patients with HCL after remission achieved by the purine analogue cladribin in the period 1995 to 2011. The treatment of recurrent HCL included splenectomy, interferon-a, cladribin, and rituximab. RESULTS: After a course of cladribin therapy, the total frequency of recurrent HCL was 22%. The high (47%) frequency of recurrences was found in young patients (less than 45 years) as compared to that (9%) in older patients. A combination of cladribin and rituximab showed a high efficacy in treating the early recurrence of HCL. CONCLUSION: The differences found in the frequency of recurrences give grounds to incorporate rituximab into the standard therapy regimen for HCL in young patients and in patients with early disease recurrence.

[The silicone spleen (description of a clinical case)].

The paper describes a rare case of verified foreign body (silicone) migration into the spleen. The specific feature of this clinical case is a rare clinical finding through histological study and the use of inductively coupled plasma-mass spectrometry for the determination of silicone in splenic tissues.

[Differential diagnosis of thymic hyperplasia and mediastinal tumor in patients with lymphogranulomatosis after chemotherapy].

AIM: To make differential diagnosis of thymic hyperplasia and mediastinal tumor after chemotherapy (CT) in patients with Hodgkin's disease (HD). MATERIAL AND METHODS: The examination of 182 HD patients aged 16-71 years (median 28 years) included chest x-ray computed tomography (XCT) at baseline, during treatment, each 3 months, ultrasound investigation of the chest and abdominal cavity. All the patients received 6-8 courses of the treatment according to the program BEACOPP-14 followed by radiotherapy on the residual tumor in 137 patients, or not followed in 45patients. RESULTS: Soft tissue tumor in the anterior mediastinum was detected in 14 (31%) from 45 unirradiated patients (age 19-31 years, median 24 years) 1 to 10 months (median 3.5 months) after chemotherapy. The analysis of the data of ultrasound investigation and tomography identified a mediastinal lesion as thymic hyperplasia. The patients are now in remission with follow-up median 21 months (13-36 months). No recurrence was registered. CONCLUSION: Young HD patients with unirradiated mediastinum develop thymic hyperplasia in 31% cases within one year after chemotherapy. In view of this, detection of the lesion in the anterior mediastinum after CT demands complex examination for differential diagnosis of thymic hyperplasia with tumor recurrence to avoid unwanted intensification of the treatment.

[Hairy cell leukemia in young patients].

AIM: To characterize clinical symptoms, course, immediate and long-term treatment results in young patients with hair cell leukemia (HCL). MATERIAL AND METHODS: The data on 41 HCL patients were analysed. The diagnosis was made by standard diagnostic protocol for HCL detection. RESULTS: The analysis of the age of 160 HCL patients studied demonstrated high (26%) incidence of HCL at young age. Young patients with HCL had special clinical manifestations and specific long-term outcomes of treatment with standard schemes. CONCLUSION: Differences in occurrence of recurrences after standard therapy make it necessary to consider young HCL patients as a separate group who need adjuvant treatment to prolong remission.

[Determination of T-cell clonicity by a T-cell receptor gamma-chain: final data].

AIM: To test diagnostic efficacy of T-cell clonicity determination by a gamma-chain of T-cell receptor (TCR). MATERIAL AND METHODS: The examination covered 426 patients (458 tests). T-cell tumors were detected in 132 patients. The samples from 294 patients in whom T-cell tumors were not found were referred to the laboratory for a differential diagnosis. Clonicity was determined by gamma-chain of TCR in the test for conformation polymorphism of one-chain DNA fragments. All the tests were made in one laboratory. RESULTS: Sensitivity of the method, found by analysis of different delusions of the cell line Jurkat in selected polyclonal CD3+ cells is 10%. The results were of 3 kinds: clonal, doubtful and polyclonal. In patients free of T-cell tumors there were 15 (5%), 34 (11%) and 258 (84%) false positive, doubtful and true negative results. False positive results were most frequent in an acute phase of infectious mononucleosis--in 8 (33%) of 24 patients. 127 (84%) true positive, 5 (3%) doubtful and 19 (13% 0 false negative results were documented in patients with T-cell lymphoma. The occurrence of false negative results was the highest in anaplastic CD30+ T-cell lymphomas--in 6 (46%) of 13 cases. CONCLUSION: Diagnostic efficacy of the method is 92%, but in 10% the result is doubtful. Main reason of false negative results is a small number of tumor cells in tissue samples. The main reason of false positive results is prevalence of one or some T-cell clones in the presence of immune response caused by viruses, autoimmune diseases and, possibly, depletion of bone marrow in aplastic syndromes.

[Lymphocytoma of the spleen--a separate nosological form requiring a specific management procedure]. / Limfotsitoma selezenki--otdel'naia nozologicheskaia forma, trebuiushchaia spetsificheskoi taktiki vedeniia.

The paper presents new findings in favor of recognition of splenic lymphocytoma (SLC). This disease was characterized by A. I. Vorob'ev and M. D. Brilliant in 1982 in terms of detailed clinicomorphological features, prognosis and optimal treatment policy. The study included 52 patients (mean age 53 years) of which 36 were females and 16 males. They were followed up for 5.7 years, on the average. SLC manifested clinically by splenomegaly with minimally enlarged lymph nodes, morphologically by nodular lymphocytic proliferates in the spleen, bone marrow and liver, diffuse or diffuse-nodular proliferation in the lymph node. Peripheral blood contained middle-size lymphoid cells with round nuclei. SLC immunophenotype exhibits moderate or marked expression of CD22 and membrane immunoglobulins, the absence of CD5, CD23 and EM receptor, combination of CR1-/ CR2+. Paraprotein secretion was recorded in 49% of cases. There were frequent autoimmune reactions, especially against erythroid cells and platelets (42%). Optimal therapeutic policy is expectation and eventual splenectomy producing a persistent clinical effect in 94% of patients. In progressive disease long-term therapy with cyclophosphamide is recommended. Thus, SLC is a mature-cell lymphatic tumor growing as a rule in the spleen. Its prognosis in valid therapy is favourable.

[The clinico-hematological indices of the participants in the cleanup of the aftermath of the Chernobyl accident]. / Kliniko-gematologicheskie pokazateli uchastnikov likvidatsii posledstvii Chernobyl'skoi avarii.

Clinicohematological investigations and cytogenetic analysis of blood lymphocytes were made 5-7 years after the Chernobyl accident in 201 liquidators who had worked in the radionuclide-contaminated zone. Among the somatic diseases found in the examinees statistically more prevalent were cardiovascular and gastrointestinal affections, asthenic syndrome, thyroid disorders. Hemograms presented a rise in hemoglobin, red cell and eosinophil content, a drop in the number of neutrophils. A tendency to erythrocytosis was observed in 20.3% of the wreckers. Dicenters and rings were abundant in the lymphocytes of 69% of the cytogenetically examined examinees 5-7 years after the exposure to radiation.

Major difference in the hepatocarcinogenicity and DNA adduct forming ability between toremifene and tamoxifen in female Crl:CD(BR) rats.

The hepatoproliferative effects of 2 antiestrogens, tamoxifen and toremifene, were compared in a sequential 15-month study in which 2 doses of each compound were administered by daily gavage to female Sprague-Dawley rats for up to 12 months. The doses were 11.3 and 22.6 mg/kg for tamoxifen and 12 and 24 mg/kg for toremifene. There were scheduled sacrifices at 3, 6, 12, and 15 months, the latter including a 3-month recovery period from the 12th through the 14th month. In the chronic toxicity study, tamoxifen at 22.6 mg/kg produced 100% incidence of hepatocellular carcinoma at the 12- and 15-month sacrifice intervals and 67% and 71% incidences at the 11.3-mg/kg dose. Sequential observations showed an increased incidence of glutathione S-transferase-positive foci of hepatocellular alteration by 3 months with tamoxifen in the absence of hepatotoxicity, with the first liver carcinoma appearing by 6 months of treatment. Unscheduled deaths occurring beyond 7.5 months in the tamoxifen treated groups were due in almost all cases to liver cancer. In striking contrast, toremifene did not produce any hepatoproliferative effects at 12- and 24-mg/kg dose levels, nor in a pilot study at 48 mg/kg. The 24-mg/kg dose of toremifene exerted an inhibiting effect on foci of hepatocellular alteration in rat liver detectable by glutathione S-transferase immunohistochemistry at 3 months and by conventional histology at 12 months. An antiproliferative effect was also evident in mammary gland and anterior pituitary where both toremifene and tamoxifen suppressed tumor incidence in comparison to the control group. The ability of these drugs to modify rat liver DNA after p.o. administration was investigated using the 32P-postlabeling assay. Administration of tamoxifen at 45 mg/kg for 7 days produced liver DNA nucleoside modifications represented by 7 spots on the autoradiogram. Unlike tamoxifen, toremifene did not produce any modified bases in rat liver DNA detectable by the 32P-postlabeling technique. The dose levels of tamoxifen that are strongly hepatocarcinogenic in the rat are compared with doses used in humans in various applications. Taking internal drug exposure into account, we conclude that the margin of safety for use of tamoxifen as an endocrine prophylactic agent for healthy, but breast cancer prone, women is questionable.