Experience with high-dose immunosuppressive therapy followed by transplantation of autologous stem hematopoietic cells in patients with multiple sclerosis

AIM: To assess efficiency of immunosuppressive therapy and subsequent autologous transplantation of stem blood cells (SBC) in patients with multiple sclerosis. MATERIAL AND METHODS: The trial enrolled 23 patients (4 men and 19 women) with multiple sclerosis (MS) lasting for 3 to 12 years. The age of the patients ranged from 18 to 44 years. The index of the progression was above 1 in all the patients. A remitting, primary-progredient, secondary-progredient course was diagnosed in 3, 3 and 17 patients, respectively. Posttransplantation follow-up was 1 to 1.5 years. The degree of the neurological deficiency (0-6 scores) was estimated by the scale of functional systems damage. Lymphocyte subpopulations were evaluated by enzyme immunoassay according to expression of membrane antigens CD3, CD4, CD8, CD16, CD20, CD25, CD56, CD95 using monoclonal antibodies ICO (Biomedspectr), humoral immunity--by serum levels of IgA, IgM and IgG. SBC mobilization was conducted for 5 days by subcutaneous introduction of neipogen (Roche) in a dose 8.7-10 mcg/kg. Preparation of SBC was made on Haemonetics blood separator on mobilization day 4-5. Cryopreservation was carried out in programmed freezer (Cryomed) with 7% dimethylsulphoxide as a cryoprotector. Pretransplantation conditioning was conducted according to the schemes BEAM + antilymphocytic globulin (protocol N 1) and fludar + melfalan + ALG (protocol N 2). RESULTS: In posttransplantation period most of the patients achieved a fall in intensity of motor and coordination disorders. No recovery of cranial nerve function was observed. The protocols of pretransplantation preparation were compared by efficiency and organic toxicity. CONCLUSION: Indications to immunosuppressive therapy in MS patients were defined, pathogenetic validation of the immunosuppressive therapy was attempted.     

Population ageing in the Balkan countries

INTRODUCTION: As we enter the third millennium, we are witnessing an unprecedented rapid expansion of the population of older persons in both the developed and developing world. The total worldwide aged population (aged 60 and older) is projected to rise from 605 million in 2000 to 1.2 billion in 2025 and to nearly 2 billion in 2050. AIM: To study the process of population ageing in Bulgaria and Balkan countries and to reveal its main characteristics, similarities and differences as compared to other European countries. MATERIAL AND METHODS: Primary information was obtained from the European Database "Health for all", the European Public Health Information Network for Eastern Europe and the US Census Bureau International Database. Total, male and female old and youth dependency ratios and ratio of people over 65 to 0-14 years were calculated and trends were followed for 30 years. Countries were ranked and compared with Europe and East European countries. RESULTS: From 1970 to 1999 the old dependency ratio increased dramatically in Bulgaria (14.2-23.6%), Greece (17.2-24.7%), Romania and Slovenia. The ratio of old to young people surpassed 100% in Greece (107.3%, for female 122.6%) and in Bulgaria (99.7% and 116.8%, respectively). Albanian and Turkish populations differ substantially from the other Balkan countries. DiSCUSSION: Population ageing creates great socio-economic and health problems--slower economic growth, lack of young labour force, higher tax charges on working-age population, etc. The process in Balkan countries is aggravated by the rise of inflation, unemployment and other socio-economic factors. CONCLUSION: All Balkan countries face multiple challenges posed by population ageing. Most of them experience the same demographic tendencies as for market economy countries even though their economic development is far worse. This is especially true for Bulgaria.     

双链断裂修复蛋白hKu70缺陷细胞株的建立及其生物学特性

目的 建立并鉴定DNA双链断裂(DSB)修复蛋白hKu70缺陷细胞株,并观察该缺陷细胞的某些生物学效应,用于AKu70基因功能及职业有害因素对DNA双链断裂修复影响的研究。方法 用构建的AKu70基因反义RNA绿色荧光蛋白真核表达载体(pEGFP—CI—K)转染人胚肺成纤维细胞(HLF),用蛋白兔疫印迹法鉴定转染细胞中AKu70基因的表达水平。同时观察转染细胞生长形态,绘制生长曲线,软琼脂培养法鉴定恶性程度。结果 pEGFP—CI—K载体在转染细胞内可较稳定表达,hKu70蛋白缺陷细胞株AKu70基因的蛋白表达水平下降了42％,转染后hKu70蛋白缺陷细胞生长形态、生长速度无明显变化,软琼脂培养未见细胞集落。结论 成功建立和鉴定了hKu70蛋白缺陷细胞株,该缺陷不足以单独引起可观察的某些生物学效应。     

Euthyroid Graves' disease (problems of diagnosis and treatment)

Twenty-six patients with endocrine ophthalmopathy without signs of thyroid disease (according to ultrasonic scanning, measurements of free thyroxin and thyrotropic hormone-TTH) were examined. Edematous exophthalmos in the compensated stage was diagnosed in 13 patients, subclinical stage of this condition in 10, and endocrine myopathy in 3 patients. Russian drug thyroliberin was used for accurate diagnosis of thyroid dysfunction; injection of this drugs to normal subjects leads to a drastic (3.5-5-fold) increase of TTH level. After measurement of TTH, the drug was infused intravenously by jet injection in a dose of 500 micrograms. Ten normal subjects were controls. 30 min after thyroliberin injection, TTH was measured. It was sharply increased in half of patients and in the control group. In one-third of cases (mainly with edematous exophthalmos) TTH level increased negligibly or even decreased after the test. After 1.5-2 years, signs of hyperthyrosis manifested in one-third of this group of patients. The authors consider that patients with the so-called Graves' disease are at a high risk of thyroid abnormalities and should be regularly consulted by both ophthalmologist and endocrinologist.     

Thyroid-stimulating autoantibodies in the blood of patients with diffuse toxic goiter

The level of thyrostimulating autoantibodies (TSA) in IgG fraction isolated from the blood serum by precipitation of (NH4)2SO4 was determined in 36 patients with diffuse toxic goiter (DTG) and in 8 healthy donors. TCA which were assessed by a rise of the level of cAMP in human thyroid sections (obtained at operation from extranodal tissue of patients with nodal euthyroid goiter) after 2 h-incubation at 37 degrees C with IgG, were determined in 32 DTG patients (89%). The patients were divided into 2 groups with respect to their clinical and thyroid status: with a high and normal or subnormal content of the blood thyroid hormones. In the 1st group the frequency of detection (96%) and the level of TSA (570.64 +/- 109.63%) were much higher than in the 2nd group of patients (70 and 186.29 +/- 23.06%, respectively). The highest levels of TSA (1085.25 +/- 551.27%) were found in 4 of 26 patients (the 1st group) who had not received specific therapy.     

A comparison of the effect of tranquilizers in experiments and clinical practice]

Experimental and clinical study of the analgesic effects of mebicar and benzodiazepine series tranquilizers (sibazon and chlozepid) and their combinations with non-narcotic analgesics (amidopyrin, pyranal) or local anesthetic lidocaine has demonstrated a more marked effect of benzodiazepine derivatives on pain sensitivity thresholds as against mebicar. Tranquilizer combinations with other analgesics helped define the optimal premedication variants: benzodiazepine derivative augment analgesic activity whereas mebicar potentiates lidocaine effect.