Myasthenia gravis as an unusual non-hematological autoimmune manifestation of a relapsed chronic lymphocytic leukemia - clinical case and review of literature.

BACKGROUND: Autoimmune phenomena are well known to complicate chronic lymphocytic leukemia (CLL) and occur in 10% to 25% of the cases. Although less common, non-hematological autoimmune manifestations have been reported. Myasthenia gravis (MG) is an autoimmune disease of the neuromuscular junction, characterized by fatigable weakness of the extraocular, bulbar, and limb musculature. The co-existence of MG and CLL is exceedingly rare and there are very few cases reported in literature. CASE PRESENTATION: We present a case of a 63-year-old female patient with a severe form of MG which is likely related to a relapse of CLL. Treatment with combined targeted and immunotherapy was initiated with acceptable tolerability. CONCLUSIONS: Targeted agents and monoclonal antibodies exert complex activities on the patient's immune system. It will be of interest to assess their role in managing autoimmune complications, accompanying CLL.

[Can we do therapy without a therapist? Active components of computer-based CBT for depression]. / Peut-on faire une TCC sans thérapeute ? Composantes actives des TCC informatisées pour la dépression.

OBJECTIVES: Computer-delivered Cognitive Behavioral Therapies (C-CBT) are emerging as therapeutic techniques which contribute to overcome the barriers of health care access in adult populations with depression. The C-CBTs provide CBT techniques in a highly structured format comprising a number of educational lessons, homework, multimedia illustrations and supplementary materials via interactive computer interfaces. Programs are often administrated with a minimal or regular support provided by a clinician or a technician via email, telephone, online forums, or during face-to-face consultations. However, a lot of C-CBT is provided without any therapeutic support. Several reports showed that C-CBTs, both guided or unguided by a therapist, may be reliable and effective for patients with depression, and their use was recommended as part of the first step of the clinical care. The aim of the present qualitative review is to describe the operational format and functioning of five of the most cited unguided C-CBT programs for depression, to analyze their characteristics according to the CBT's principles, and to discuss the results of the randomized clinical trials (RCT) conducted to evaluate its effectiveness, adherence and user's experience. METHODS: We analyzed five C-CBTs: Beating The Blues (BTB), MoodGYM, Sadness, Deprexis and Overcoming Depression on the Internet (ODIN) and 22 randomized controlled studies according to 5 dimensions: General characteristics; Methodology, structure and organization; Specific modules, themes and techniques: Clinical indications, recruitment mode, type of users with depression, type and mode of therapist's support, overall therapeutic effects, adherence and user's experience. RESULTS: The C-CBT have a secured free or pay-to-use access in different languages (English, German, Dutch, and Chinese) but not in French. The programs may be accessed at a medical center or at home via a CD-ROM or via an Internet connection. Some C-CBTs are very close to textual self-helps provided via an E-learning mode (Sadness, MoodGYM, ODIN), others adopt interactive software technologies (Deprexis, BTB), but their interactivity and the possibility of personalization is low. The C-CBTs use similar principles and techniques as in face-to -face CBT (e.g. self-evaluation, psychoeducation, cognitive restructuring, cognitive restructuring of schema, behavioral activation and agenda setting, problem solving techniques, communication and crisis management techniques, relaxation, principles of positive psychology and relapse prevention, positive reinforcement methods, motivational feedbacks, social learning, homework assignments and progress monitoring). The results of the 22 RCSs showed that both the effectiveness and the adherence of the unguided C-CBT is high with self-referred active help-seekers with major depression, but the latter is low with users who are depressed out-patients referred by general practitioners or clinicians. The presence of therapist support improves the effectiveness and the adherence of the C-CBT, especially in clinical out-patients. CONCLUSIONS: In light of the existing insight of the advantages and the inconvenient of the C-CBT, the actual challenge is to find its optimal clinical indication and the modality of its effective use in clinical populations.

[Individual responses of arterial pressure to geomagnetic activity in practically healthy subjects].

Dynamic analysis of arterial blood pressure in relation to the Earth's magnetic field perturbations was performed in 77 practically healthy volunteers (staff of Bulgarian Academy of Sciences). Almost half of them proved magneto-sensitive, i.e. experienced AP elevation with increased geomagnetic activity. The probability of development of magnetic sensitivity was independent of age and gender but increased in volunteers having even mild cardiovascular pathology. These subjects complained of worsened health condition upon a rise in geomagnetic activity. However, some volunteers reported deteriorated well-being without AD elevation. It means that AD measurement may be insufficient for reliable monitoring magnetic sensitivity.

Exact solution of the isovector neutron-proton pairing Hamiltonian.

The complete exact solution of the T = 1 neutron-proton pairing Hamiltonian is presented in the context of the SO(5) Richardson-Gaudin model with nondegenerate single-particle levels and including isospin symmetry-breaking terms. The power of the method is illustrated with a numerical calculation for for 64Ge for a pf + g9/2 model space which is out of reach of modern shell-model codes.

Influence of local geomagnetic storms on arterial blood pressure.

This study attempts to assess the influence of local geomagnetic storms at middle latitudes on some human physiological parameters. The blood pressure (bp), heart rate and general well-being of 86 volunteers were measured, the latter by means of a standardised questionnaire, on work days in autumn, 2001 (1 Oct to 9 Nov), and in spring, 2002 (8 April to 28 May). These timespans were chosen as periods of maximal expected geomagnetic activity (GMA). Altogether, 2799 recordings were obtained and analysed. A four factor analysis of variance (MANOVA) was employed to check the significance of the influence of four factors (local GMA level; sequence of the days of measurements covering up to 3 days before and after geomagnetic storms; sex and the presence of medication) on the physiological parameters under consideration. Post hoc analysis was performed to elicit the significance of differences in the factors' levels. Arterial bp was found to increase with the increase of the GMA level, and systolic and diastolic bp were found to increase significantly from the day before till the second day after the geomagnetic storm. These effects were present irrespective of sex and medication.

The epidemiology of hepatitis C virus infection. An update for clinicians.

Since the advent of sensitive diagnostic blood tests for the detection of antibody to hepatitis C virus (HCV) in donors, there has been a large decline in the incidence of transfusion-related hepatitis. Globally, the infection has an estimated prevalence of 3%, with a prevailing 1% in Europe while varying geographically within a North-South gradient, ranging from around 0.5% in Northern countries to 2% in Mediterranean area. The incidence is very difficult to estimate accurately as many patients with acute HCV infection are asymptomatic and, thus, do not present for diagnosis. Data from the US report a fall in the annual occurrence of new cases per year from 230,000 in the late 1980s to approximately 35,000 in the 1990s. Therefore, a reduction in incident cases might eventually lead to lower prevalence of HCV infection. Although the incidence of viral infection may be decreasing, the prevalence of liver disease caused by HCV is on the rise. This is due to the significant lag, often 20 years or longer, between the onset of infection and clinical manifestation of liver disease. HCV can be transmitted by a variety of routes. It is most efficiently passed on by large or repeated percutaneous exposures such as through transfusions, transplantation from an infected donor or intravenous drug use. Transmission may also occur from contacts with infected subjects in the household, through perinatal and parenteral exposures in the health care setting. The risk of sexual transmission of HCV is low. Despite this knowledge, nearly half of infected patients do not have a history suggesting a parenteral route of acquisition. Since a prophylactic vaccine is hitherto not available, prevention becomes extremely important: identification of infected persons and of risk factors associated with acquiring HCV allow to develop strategies for preventing the spread of infection as well as its complications, and for planning appropriate care and support services.

Early events in the life cycle of JC virus as potential therapeutic targets for the treatment of progressive multifocal leukoencephalopathy.

The human polyomavirus, JC virus (JCV), is the etiological agent of progressive multifocal leukoencephalopathy (PML). PML occurs almost exclusively in the setting of severe and prolonged immunosuppression and it remains an important and life-threatening complication in the acquired immunodeficiency syndrome (AIDS) population. Several drugs that target DNA replication have shown efficacy at inhibiting JCV replication in vitro but none to date have shown in vivo efficacy. The authors' laboratory has been studying early events that contribute to infection of susceptible cells by JCV. They previously demonstrated that infection of glial cells by JCV requires clathrin-dependent endocytosis and that this early step in the viral life cycle can be blocked by the antipsychotic drug, chlorpromazine. As chlorpromazine is associated with the development of extrapyramidal symptoms that may be heightened in AIDS patients, the authors sought to test the atypical antipsychotic, clozapine, for antiviral activity against JCV. In this report, the authors show that clozapine is as effective as chlorpromazine at inhibiting infection. They further demonstrate that low-dose combinations of both drugs synergistically inhibit infection.

Use of granular slag columns for lead removal.

The use of granular blast furnace slag (GBFS)-packed columns to treat lead-containing solutions has been investigated. The results obtained indicated that the slag usage rate decreased with increasing flow velocity, particle size, initial lead concentration and decreasing with bed height. Lead removed selectively in the presence of other heavy metal ions. High concentrations of sodium and especially calcium in the solutions impeded the uptake of lead. For 20 mg l(-1) lead concentration an empty bed contact time greater of 4 min provided to efficient use of the slag bed. Column pH was an important parameter to lead removal under dynamic conditions and reflected the influence of the investigated factors. During all runs lead breakthrough coincided with an abrupt drop in effluent pH. The apparent mechanisms of lead removal in GBFS column are sorption (ion exchange and adsorption) on the slag surface and precipitation.

Possibilities for restoration of severely destroyed dental crowns with inlays.

In everyday dentistry practice cases with diffuse destruction of masticatory teeth are common. In the study presented the possibilities of their restoration with metal or metal-ceramic inlays are reviewed. Twenty-one inlays were fabricated, 16 from metal and 5 from metal-ceramic. The quality of the fabricated obturations were assessed immediately after they were cemented and one year later. The results showed that this is a reliable method. During the studied period there were no changes in the inlays, the teeth tissues and marginal adaptation.

Study of asbestos exposure in some applications of asbestos materials in the chemical industry.

This study is designed to determine the effects of short-term asbestos exposure on workers in the production of asbestos gaskets and filter materials for technological equipment in the chemical industry. The workers from the "Cathode workshop", "Diaphragm electrolysis", "Polymers" Co., Devnja (12 operators) who operate the installation of asbestos diaphragms manufacture and installation of electrolysis cells, and the staff of the "Mechanical" shop of "Nephtochim" Co., Burgas, engaged in the cutting of gaskets made of pressed asbestos-polymer boards (6 workers), were studied. The hygienic normative standards and methodology for measuring and assessment of the asbestos exposure, used all over the world were applied: mean shift count concentration of respirable asbestos fibres; entire shift personal sampling (BSS 2200-85), PCOM light microscopy (BSS 16909-89). The level of asbestos exposure registered was in the range 0.04 to 0.38 f/cm3 for the operators in the "Diaphragm electrolysis" shop and for the staff in the "Mechanical" shop of "Nephtochim" Co. from 0.04 to 0.43 f/cm3. The established concentrations are acceptable according to the requirements of the official hygienic threshold limit value (TLV) in Bulgaria (1 f/cm3), but because asbestos is a human cancerogen and there is tendency for regular revision with the intention of decreasing the hygienic TLV, the asbestos occupational exposure of these groups of workers cannot be accepted as safe. The statements made increase the necessity of dust control by technical preventive means and the medical control of the workers exposed to asbestos-related injuries.

L-deprenyl-induced increase in IL-2 and NK cell activity accompanies restoration of noradrenergic nerve fibers in the spleens of old F344 rats.

Previously, we have hypothesized a causal relationship between some measures of immunosenescence and the age-related decline in sympathetic noradrenergic (NA) nerve fibers in spleen and lymph nodes of F344 rats. In the present study, we investigated this interrelationship further by measuring NK cell activity, Con A-induced IL-2 production, norepinephrine (NE) concentration, and morphological localization of NA and neuropeptide-Y (NPY) nerve fibers in the spleens of old (21 months old) male F344 rats after 10 weeks of daily treatment with low doses of L-deprenyl, an irreversible monoamine oxidase-B inhibitor, followed by a 9-day wash-out period. NK cell activity and Con A-induced IL-2 production were increased in deprenyl-treated old rats in comparison to untreated and saline-treated old rats. Deprenyl treatment did not alter the percentage of CD5+ T-cells, but moderately increased the percentage of sIgM+ B-cells in the spleens of old rats. In addition to changes in immune responses, NE content and the volume density of NA and NPY nerve fibers were partially augmented in the spleens of deprenyl-treated old rats. In a separate study, various concentrations of deprenyl were added in vitro to spleen cells from young and old F344 rats to examine the direct effects of the drug on Con A-induced IL-2 production. In contrast to in vivo treatment, in vitro addition of deprenyl did not alter the Con A-induced IL-2 production by splenocytes from old rats. Together, these results suggest that the ability of deprenyl to enhance certain immune responses are interlinked to the restoration of sympathetic NA and NPY nerve fibers in the spleens of old rats.

Inhibitory action of extracts of Maclura aurantiaca and Epilobium hirsutum on tumour models in mice.

Primary screening of alcohol extracts of fruits of Maclura aurantiaca (Moraceae) and the overground part of Epilobium hirsutum (Onagraceae) was conducted in order to test the anti-tumour action on models in mice. Applied in doses of 100 mg/kg and 90 mg/kg, Maclura extract increased the life span of the mice by 158 and 152% accordingly in leucosis P-388 and ascitic tumour of Ehrich. In doses of 1 mg/kg and 3 mg/kg the Epilobium extract prolonged the life span of the mice by 156 and 158% accordingly in leucosis P-388 and ascitic tumour of Ehrlich.

[Carcinoembryonic antigen, its clinical and prognostic significance in malignant tumors of the gastrointestinal system]. / Rakovo-émbrional'nyi antigen, ego klinicheskoe i prognosticheskoe znachenie pri zlokachestvennykh opukholiakh zheludochno-kishechnogo trakta.

A radioimmunoassay to determine the CEA level in 100 patients with GIT malignant tumors was performed. The test was shown to be of particular value for making a preoperative prognosis of the disease. In operated on patients it could be used for early diagnosis of recurrences and metastases. The dynamic performance of the test made it possible to evaluate therapeutic efficacy.

[Complex radioisotope diagnosis of thyroid gland diseases in vivo and in vitro]. / Kompleksnaia radioizotopnaia diagnostika zabolevanii shchitovidnoi zhelezy in vivo i in vitro.

A variety of in vivo and in vitro methods: radioactive iodine accumulation, thyroid suppression and stimulation test, a scintigraphic study and a radioimmunoassay to determine triiodothyronine-binding capacity (free T3), thyroxine (T4) concentration and the effective thyroxine ratio (ETR), was used for diagnostic specification and accurate planning of therapy of patients with thyroid diseases. The suppression test combined with the results of the in vitro analysis (free T3, T4 and ETR) was decisive for establishing diagnosis.

[Clinical and prognostic significance of determining the carcinoembryonic antigen in patients with gastrointestinal cancer]. / Klinicheskoe i prognosticheskoe znachenie opredeleniia rakovo-émbrional'nogo antigena u bol'nykh rakom zheludochno-kishechnogo trakta.

The paper discusses the results of a radioimmunologic assay of carcinoembryonic antigen (CEA) levels in 100 cases of gastrointestinal cancer. CEA--PRIST kits (Phadebas, Sweden) and NGR-603 automatic gamma-unit (Tesla, Czechoslovakia) were employed. The test proved to be highly instrumental in the preoperative evaluation of prognosis and early detection of recurrence and metastasis. CEA concentrations within 30-50 ng/ml are highly suggestive of recurrence or metastases, whereas 50-100 ng/ml should serve an indicator of organ dissemination. The test is useful in assessing the effectiveness of treatment in the course of follow-up.

Investigations of serum testosterone levels in patients with laryngeal cancers.

Serum testosterone levels were determined by a radioimmunological method in 102 patients with laryngeal carcinoma and in a control group of 10 healthy men. All patients were examined before the initiation of any operative or radiation therapy and after termination of treatment. The testosterone levels in the cancer patients showed a tendency toward higher values when compared with a control group of healthy men. These results indicate that hormone preparations could be considered as part of the therapy of laryngeal carcinomas.