Amplification of c-MYC and MLL Genes as a Marker of Clonal Cell Progression in Patients with Myeloid Malignancy and Trisomy of Chromosomes 8 or 11.

Gene amplification (amp) is one of the basic mechanisms connected with overexpression of oncogenes. The c-MYC (located in 8q24) and MLL (located in 11q23) are the most often over represented genes that lead to a rapid proliferation of the affected cell clone in patients with myeloid neoplasms. Assessment of the level of amp c-MYC or amp MLL in the cases with trisomy 8 (+8) or trisomy 11 (+11) and myeloid malignances is necessary for a more precise estimation of the disease progression. A total of 26 patients with acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS) were included in the study: 18 with +8, six with +11 and two with complex karyotypes suspected of the partial trisomy. Routine cytogenetic analysis and fluorescent in situ hybridization (FISH) were applied to indicate the chromosome alterations and genes amp in the bone marrow cells. Amp c-MYC was observed in 12 from 18 (66.7%) patients with +8. All the patients with +11 demonstrated a different level of amp MLL. In most of the cases with MDS (9/10), the coincidence of the +8 or +11 with amp c-MYC or amp MLL, respectively, leads to transformation to AML and/or short overall survival. Our data suggest that amp c-MYC and amp MLL develop in conformity with +8 and +11, especially in cases with progressive deviations in the karyotype as an aggressive expansion of an aberrant cell clone and appearance of additional chromosome anomalies.

Effects of carbon monoxide-modified atmosphere packaging and irradiation on E. coli K12 survival and raw beef quality.

The objective of this study was to evaluate the combined effects of irradiation and carbon monoxide in modified atmosphere packaging (CO-MAP) on total plate counts, Escherichia coli K12, color, and odor of fresh beef during refrigerated storage. Beef was packaged aerobically or in CO-MAP, and irradiated at 0, 0.5, 1.0, 1.5 or 2.0kGy then held at 4°C for 28days. Raw beef odor decreased and acid/sour, rancid and grassy odors increased starting on day 14. Initially, no difference existed for visual green color scores due to gas atmosphere. After 14days of storage, aerobically packaged beef was greener and less red than CO-MAP packaged beef. The a∗ value of CO-MAP packaged beef was higher than that of aerobically packaged beef. Red color of CO-MAP packaged samples decreased slightly in some irradiated samples after 14days of storage. On day 0 and thereafter, no coliforms were detect after irradiation at 1.5 or 2.0kGy regardless of packaging format. These findings suggest that CO-MAP could be used to preserve beef color irradiated at doses sufficient to reduce microbial loads to safe levels during 28days of storage.

Intact neurogenesis is required for benefits of exercise on spatial memory but not motor performance or contextual fear conditioning in C57BL/6J mice.

The mammalian hippocampus continues to generate new neurons throughout life. Experiences such as exercise, anti-depressants, and stress regulate levels of neurogenesis. Exercise increases adult hippocampal neurogenesis and enhances behavioral performance on rotarod, contextual fear and water maze in rodents. To directly test whether intact neurogenesis is required for gains in behavioral performance from exercise in C57BL/6J mice, neurogenesis was reduced using focal gamma irradiation (3 sessions of 5 Gy). Two months after treatment, mice (total n=42 males and 42 females) (Irradiated or Sham), were placed with or without running wheels (Runner or Sedentary) for 54 days. The first 10 days mice received daily injections of bromodeoxyuridine (BrdU) to label dividing cells. The last 14 days mice were tested on water maze (two trials per day for 5 days, then 1 h later probe test), rotarod (four trials per day for 3 days), and contextual fear conditioning (2 days), then measured for neurogenesis using immunohistochemical detection of BrdU and neuronal nuclear protein (NeuN) mature neuronal marker. Consistent with previous studies, in Sham animals, running increased neurogenesis fourfold and gains in performance were observed for the water maze (spatial learning and memory), rotarod (motor performance), and contextual fear (conditioning). These positive results provided the reference to determine whether gains in performance were blocked by irradiation. Irradiation reduced neurogenesis by 50% in both groups, Runner and Sedentary. Irradiation did not affect running or baseline performance on any task. Minimal changes in microglia associated with inflammation (using immunohistochemical detection of cd68) were detected at the time of behavioral testing. Irradiation did not reduce gains in performance on rotarod or contextual fear, however it eliminated gain in performance on the water maze. Results support the hypothesis that intact exercise-induced hippocampal neurogenesis is required for improved spatial memory, but not motor performance or contextual fear in C57BL/6J mice.

Secondary acute myeloid leukemia early after therapy for Hodgkin's disease--a case report.

A case of acute myeloid leukemia (AML) after successful therapy for Hodgkin's disease (HD) is reported. The patient was diagnosed with stage IIB HD at the age of 25. She was treated with chemotherapy and radiotherapy (RT), and complete remission (CR) was achieved. Seven months after the CR was obtained the patient developed AML. Knowing that the prognosis of patients with secondary AML (sAML) after primary HD is poor we decided to perform autologous peripheral stem cells' transplantation.

Acute megakaryoblastic leukaemia with extreme thrombocytosis and p190(bcr/abl)rearrangement.

Acute megakaryoblastic leukaemia (AML-M7) is an uncommon disease, composing 0.5-1.2% of newly diagnosed adult acute myeloid leukaemias (AML). It is characterised by higher incidence and complexity of cytogenetic abnormalities. We report a rare case of Philadelphia (Ph) chromosome-positive AML-M7, presenting with extreme thrombocytosis and having a poor outcome. The diagnosis was established on the basis of morphological and flow cytometry data for megakaryoblastic proliferation in the bone marrow. Cytogenetics revealed 47,XX,+8,t(9;22)(q34;q11), and p190(BCR-ABL)-rearrangement was detected. MDR1-gene overexpression was not demonstrated; however, the patient was resistant to therapy and died in 6 months. The reported case contributes to the overt heterogeneity of Ph-positive AMLs, which warrants further investigation and understanding.

Application of reverse transcription polymerase chain reaction for analysis of multidrug resistance in patients with acute myeloblastic leukemia.

PURPOSE: To test the multidrug resistance 1 (MDR1) gene expression in acute myeloid leukemia (AML) patients using the reverse transcription polymerase chain reaction (RT-PCR) in order to assess the application of the method for routine screening. MATERIALS AND METHODS: 39 AML patients (mean age 43.9-/+18.2 years) and 10 healthy volunteers were studied by simultaneous amplification of the MDR1 and beta2-microglobulin (beta2-M) mRNA, as an internal control. Semi-quantitative characterization of MDR1 expression was done using a 4-grade scoring system: negative (-/+), weakly positive(-/+), moderately positive (+), strongly positive(++), according to the intensity of the MDR1 and beta2-M bands. RESULTS: The amplification of the MDR1 in healthy individuals yielded no products in 9 samples and in 1 case a (-/+) reaction was observed. In AML patients, RT-PCR revealed no MDR1 product (normal level) in 19 (48.7%) and (+)/(++) reaction (overexpression) in 15 (38.5%) patients. In the remaining 5 (12.8%) patients a (-/+) reaction was found, comparable to that of the (-/+) healthy individual (the level of MDR1 expression could not be defined). MDR1 overexpression was seen in 73.3% of the M1/M2 patients, and only in 14.3% of the M3 and M4/M5 patients. Besides, the MDR1(- )/(-/+)patients were significantly younger than MDR1(+)/ (++) patients (mean age 38.4-/+19.5/43.0-/+8.7 years, versus 51.1-/+16.7/65.0-/+4.3 years). CONCLUSION: RT-PCR allows for the identification of patients with moderate and higher levels of MDR1 overexpression, while the weak positive reactions require additional testing. Besides, our data support the observation that the level of expression might be associated with the French-American-British (FAB) subtype of AML and with the age of the patients.

[The communal hygiene problems of hospital institutions]. / Niakoi komunalnokhigienni problemi na statsionarnite zdravni zavedeniia.

The study covers 17 hospitals on the territory of the Capital Community, including their clinics, departments and rooms for treating of social significant and other diseases. The analysis reveals a number of negative aspects: inappropriate situation, insufficiency or lack of green areas, unfavourable aspect of the rooms, overcrowding, insufficient area of the windows, irrational heating regime, lack of ventilation regime, etc. Undesirable parameters of the microclimate are observed in the patients' rooms and this leads to discomfort to the patients and prolonging of the convalescent period. A study on a large scale for the town of Sofia is presented which aims at revision of the current building norms and requirements in respect of their correction and the improving the future building of hospitals in our country.

[The microclimate conditions of the environment for treating patients in hospital clinics and wards (a review)]. / Mikroklimatichni usloviia na sredata za lechenie na bolnite v niakoi kliniki i otdeleniia na statsionarite (obzor).

The problem of the microclimatic parameters of the environment in some clinics and hospital departments is discussed as well as their significance in the general therapeutic course. The impact of the air environment as a potent therapeutic factor is outlined. It is stated that the temperature regime in the rooms must be differentiated in accordance to the climatic conditions, seasons, patient's age, the nosologic group. Discussing the problem with regard to the balance "man-environment" it is outlined that the adaptive capabilities, which are narrowed and altered in the patient, can not compensate for the unfavourable conditions of the environment. The authors point at differentiated values of the microclimatic parameters for the rooms in some clinics and departments.

[The hygienic characteristics of the hospital environment in a cardiovascular pathology ward during the heating season]. / Khigienna kharakteristika na vutrebolnichnata sreda v otdelenie za surdechno-sudova patologiia prez otoplitelniia sezon.

A study is carried out on the microclimate, physiological reaction of patients, chemical and bacteriological composition of the air in rooms of different location in the ward for cardiovascular pathology during the heating period of the year, according to some basic and integral indices. The characteristics of the interhospital environment in the rooms of the investigated ward is determined mainly by the irrational regime of heating, location, size of the glazed transparent area. In the hospital rooms are formed unsatisfactory hygienic norm parameters of the microclimate and the chemical composition of the air. The specific thermal environment affects the physiological reactions of the patients and leads to creation of conditions of discomfort and loading of the thermoregulation in direction of overheating.

[Sanitary chemical research on the atmosphere in wards for cardiac patients]. / Sanitarno-khimicheski izsledvaniia na vuzdushnata sreda v otdeleniia za surdechno bolni.

Man passes a greater part of the day-and-night in closed premises. The pollutants of the inside air, in quantity and quality are more various than that of the atmospheric air, which is due to the additional sources of pollution. The investigation performed is part of a complex study and hygienic assessment of the environment in the hospital rooms of two cardiological wards in view of the prevailing contingent of patients with heart diseases and their specific sensitivity to its qualities. The chemical state of the aerial environment was traced according to several basic indices: concentration of CO2, ammonia, total content of organic substances (oxidizable) and some pollutants, migrating from the polymeric materials, used for furnishing of the hospital rooms. The results received show the necessity for strictly following the regime of ventilation, ensuring the indispensable area for each patient and high light for the rooms. In view of economy of time, labour and means it is recommended the determination of oxidizability and content of ammonia in the air to be carried out one daily. It is also recommended to use synthetic polymer materials in the hospital premises subject to enforced sanitary protection, as little as possible.

[Intrahospital communal and hygienic problems and the construction of health institutions]. / Komunalno-khigienni vuprosy na v'trebolnichnata sreda i stroitelstvoto na zdravni zavedeniia.

A number of requirements, tendencies and trends in the building of health establishments are given in brief, as well as their location in the settlement. The complex of intrahospital factors is pointed out, which appear with slight intensity, but have a constant influence on the patients. In two cardiological wards a complex study of the patients' environment is performed. The study includes the microclimate in the hospital rooms, the physiological state of the patients according to some basic criteria indices, the indoor air with its chemical and bacteriological pollution. The quality of the environment do not respond to the hygienic requirements. There is a considerable impairment of the microclimate parameters and the chemical status of the indoor air and in individual cases, to a slight degree those of the bacteriological status. The air temperature in the hospital rooms for patients with cardio-vascular diseases is standardized. Specific recommendations are given for the new hospital building and the investigation of the intrahospital environment.

[Hygiene research in solving the health aspects of urban development]. / Khigiennite prouchvaniia v reshavaneto na zdravnite aspekti na urbanistichnoto razvitie.

The urban development and the problems it raises at present, are in direct relation with the conditions, which affect considerably the health of the population. The territorial and settlement system, the urban planning on ecological basis, the new methods of building in applying polymeric materials, the conditions of the environment in health establishments, the regulations of the physical factors, noise and electromagnetic energy are subject to the hygienic studies, in which the Institute of Hygiene and Occupational Health is engaged. The connective unit in the variety of the mentioned fields of investigation is the health of the inhabitants and finding the right way in its protection and keeping. The attitudes of prophylaxis, the creation and establishing of urban environment, corresponding to the conflict-free existence and potentiation of the health development of the inhabitants, are clarified, as they are related to the basic trends of the world Health Organization, whose targets are "Health for All by the year 2000".

[Determination of the economic effect of optimizing the hospital environment]. / Vurkhu opredelianeto na ikonomicheskiia efekt ot optimiziraneto na bolnichnata sreda.

The effect of hospital environment on the course and effectiveness of the curative process has its economic expression. Besides the health and social importance, human health, working capacity and welfare have also definite material interests which if given a correct meaning, could result in improving the quality and the material and technical equipment of our curative and preventive activity. The formula given in the present work for defining the economic effect for implementing the planning and operation of the cardiological departments on differentiated approach and hygienic norms and requirements for the formation of favourable environment for the patients is the first attempt in the field of economic approach for solving the problems for improving the patient's environment in our health establishments.

[The hospital environment as a hygienic problem]. / Bolnichnata sreda kato khigienen problem.

The hospital environment, studied according to the parameters of microclimate, natural and artificial lighting and acoustic regime, is a factor with an effect on the disposition and healing process. Concrete data are presented, suggesting some failures in the micro-climate kept in the hospital premises studied and substantial unfavourable discrepancies in the existing standardization and the present conditions of stay. The artificial illumination is considerably diminished--20-70 lx, at a norm of 300 lx. The windows proved to be unnecessarily large, guaranteeing increased penetration of natural light but hence - creating conditions for overheating (cooling resp.) - at at a norm 1:5 to 1:4, the established light coefficient is 1:3 up to 1:2. The acoustic regime showed also some great deviations towards the increase of noise levels - at a norm of 35 dB A, the established levels are within the limits of 38 to 72 dB A. The hospital environment is obvious to need some changes that would have a favourable effect only with a strict adherence to the hygienic standardization in the course of design and building.

[Air environment conditions in the patients' rooms of multistory hospitals]. / Prouchvane usloviiata na vuzdushnata sreda v bolnichnite stai v mnogoetazhni bolnitsi.

Air conditions, in winter and summer, were studied in 4 hospital rooms of the multistorey Institute of Obstetrics and Gynaecology, Medical Academy - Sofia. The studies were carried out in the following principal directions: I) Chemical pollution of air; 2) Microbic contamination; 3)Physical state of the environment; 4) Physiological examinations of 52 afebrile patients. The air in the hospital rooms depends on season, storey, cubage, heating regime, airing and maintaining, expressed by various indices. The state of the patients examined according to some principal physiological indices is adequate to the physical components of the environment.

[Hygienic evaluation of the effectiveness of short-term suburban recreation from the viewpoint of natural climatic and demographic factors]. / Khigienna otsenka na efektivnostta na kratkovremenniia kraigradski otdikh s ogled na prirodoklimatichnite i demografskite faktori.

The importance of recreation grew considerably with the increase of leisure time and cultural level of the workers. In our country, on the other hand, there are no complete hygienic studies on the problems of organization and necessary equipment for recreation. In that connection, hygienic-urbanization, hygienic-sociological, microclimatic and physiological studies, as well as investigations on ultraviolet radiation, level of noise and extent of air pollution in some typical recreation places (Sofia and Varna) were carried out. Better conditions were established in nature - town ourskirts environment (as regard ultraviolet radiation, noise level, degree of air pollution, temperature-humidity and radiation microclimate) and their favourable effect on the physiological functions of organism (particularly as regards thermoregulation and cardiovascular system). A dependence was also established between the population recreation needs and social-demographic and nature - climatic factors. Tangible recommendations for the improvement of the state of short-term town outskirts recreation in Sofia and Varna are proposed on the base of the results.