Polymorphism in factor VII gene modifies phenotype of severe haemophilia

Summary.  The basis for 10–15% of patients with severe haemophilia having clinically mild disease is not fully understood. We hypothesized that polymorphisms in various coagulant factors may affect frequency of bleeding while functionally significant polymorphisms in inflammatory and immunoregulatory genes may also contribute to variations in the extent of joint damage. These variables were studied in patients with severe haemophilia, who were categorized as 'mild' (<5 bleeds in the preceding year, <10 World Federation of Haemophilia clinical and <10 Pettersson scores, n  = 14) or 'severe' (all others, n  = 100). A total of 53 parameters were studied in each individual for their association with the clinical severity. Age, F8:c activity and the incidence of thrombotic markers were comparable between the groups while the median number of bleeds, number of affected joints, clinical, radiological and functional joint scores ( P  ≤ 0.001) and life-time clotting factor use ( P  ≤ 0.007) were different. Patients with severe molecular defects had a 4.1-fold increased risk for a severe phenotype (95% CI: 1.18–14.42, P  = 0.026) compared with other mutations. Of the polymorphisms studied, the FVII353Q (RR = 3.5, 95% CI: 1.04–12.05, P  = 0.044) allele was associated with a severe phenotype. This data shows that apart from the F8/F9 genotype, functional polymorphisms in FVII gene affect the phenotype of patients with severe haemophilia.     

Oxidative stress in non‐small cell lung cancer patients after chemotherapy: Association with treatment response

Background and objective: The aim of this study was to assess the level of oxidative stress after chemotherapy in non‐small cell lung cancer patients, and its association with treatment response and survival. Methods: Two hundred and three previously untreated non‐small cell lung cancer patients and 150 healthy subjects were selected for the study. Patients received cisplatin + etoposide, and were followed for up to six cycles, for evaluation of oxidative stress. Blood levels of lipid peroxidation products (LPO), glutathione (GSH) and nitric oxide (NO), and superoxide dismutase (SOD) activity were measured at day 0 and after the third and sixth cycles of chemotherapy. Response and survival were measured at the end of follow up. Survival was estimated by the Kaplan–Meier method using the log–rank test. Results: In the patients, pretreatment levels of LPO and NO were low, while GSH and SOD levels were high compared with those after the third and sixth cycles of chemotherapy. Among the 203 patients, there were 51 deaths, 82 non‐responders and 70 responders at the end of the sixth cycle. Overall mean survival was higher among responders than non‐responders (24.6 vs 21.2 weeks, P < 0.01). The hazard ratio was 2.4 (95% CI: 1.3–3.77). Pretreatment levels of oxidative stress were similar among responders and non‐responders (P > 0.05). After the third and sixth cycles of chemotherapy, LPO and NO levels were low (P < 0.05 or P < 0.01) and GSH levels and SOD activity were high (P < 0.05 or P < 0.01) in responders as compared with non‐responders. Conclusions: In lung cancer patients, oxidative stress increased and anti‐oxidant enzymes decreased as the disease progressed. Chemotherapy may suppress oxidative stress and decreased anti‐oxidant enzyme activity in responders as compared with non‐responders. These effects may contribute to improved survival among responders.     

Alleviation of Nickel-Induced Biochemical Alterations by Chelating Agents

Alleviation of Nickel-Induced Biochemical Alterations by ChelatingAgents. Misra, M., Athar, M., Hasan, S. K., and Srivastava,R. C. (1988). Fundam. Appl. Toxicol 11, 285–292. The effectof 1,4,8,11-tetraazacyclotetradecane (Cyclam), triethylenetetramine(TETA), reduced glutathione (GSH), ethylenediamine tetraaceticacid (EDTA), cyclohexanediamine tet-raacetic acid (CDTA), diethylenetriamine pentaacetic acid (DTPA), and hydroxyethylenedia-minetriacetic acid (HEDTA) on the alleviation of nickel-inducedbiochemical and trace-metal alterations in serum, liver, andkidney of nickel-treated rats was studied. The lipophilic chelatingagents Cyclam and TETA exhibited a higher order of effectivenessin alleviating nickel-induced alterations compared to EDTA,CDTA, DTPA, and HEDTA, the hydrophilic chelating agents. Thehigher efficacy of lipophilic agents may be due to their abilityto bind to nickel present in extracellular fluid as well asin intracellular fluid, while the hydrophilic agents may bindonly to nickel present in extracellular fluid. Our data alsosuggest that the efficacy of Cyclam to ameliorate nickel-inducedalterations is exceptionally high.     

Health education perspectives in Latin America

While health education and health promotion are acknowledgedas vital by Latin American health leaders, few systematic effortshave been made to promote these fields and few human resourceshave been allocated to them. This article provides a frameworkfor a collaborative effort to design health education strategiesfor health promotion in Latin America. The framework is basedon the theoretical work of leading Latin American public healthscholars, on selected data on the health status of people inLatin American countries, and on the results of a needs assessmentstudy done in five Latin American countries over the last twoyears. First is a review of the concepts of epidemiologicaltransition and the stages of development in public health inLatin America. Current health data are then presented to illustratethe state of Latin American epidemiological transition. Theconcept of epidemiological transition characterizes a set ofcircumstances in which various stages of development in healthstatus coexist within countries, regions or population groups.These circumstances have significant implications for healtheducation. Finally there is an analysis of the public healthand health education priorities for Latin America identifiedby a sample of 130 key health experts from 5 Latin Americancountries. The experts' recommendations for strategies are designedto help overcome the wide regional gaps in health educationcharacteristic of an epidemiological transition and to furtherdevelop this area of public health. The recommendations emphasizethe need for the establishment of networks of mutual collaborationfor training, research, and the exchange of information, publicationsand experts.     

THE SYNTHESIS OF PROSTAGLANDINS IN PLATELETS FROM PATIENTS WITH MULTIPLE SCLEROSIS

As a continuation of our previous studies on the synthesis of prostaglandins (PGs) in human thrombocytes, the present study concerns the biosynthesis of PGs in thrombocytes from patients with multiple sclerosis, as this condition has been suggested to be linked to thrombotic and/or thrombocyte abnormalities. It was found that in these patients a statistically decreased synthesis of PGE1, PGE2 and PGF took place compared to the corresponding values in normal subjects. The ratio between PGE1 and PGE2 was, however, unchanged.     

PERSONALITY FACTOR CORRELATES OF GROWTH HORMONE AND HYPOTHERMIC RESPONSE TO BUSPIRONE CHALLENGE IN SUICIDAL SOLDIERS

The biological underpinnings of suicidal behaviour and possible rational pharmacotherapy of persons exhibiting such behaviour is the focus of this study. The study was conducted on 25 male Armed Forces personnel who attempted suicide and 25 matched healthy controls. Hypothermic and Growth Hormone response to Buspirone challenge was measured serially. 11 cases of attempted suicide had subsensitive postsynaptic 5 HT-1A receptors as indicated by blunted Growth Hormone response, while in other suicidal soldiers hypothermic response was markedly blunted indicating subsensitive presynaptic 5HT-IA receptors in the latter. Personality factor assessment carried out by 16 personality factor test, indicated overt extraversion marks for subsensitive postsynaptic 5 HT-IA receptors, while overt intraversion marks for subsensitive presynaptic 5 HT-IA receptors, in suicidal soldiers. In the light of the above, therapeutic options of Serotonin reuptake inhibition, agonist load at presynaptic 5 HT-IA and reciprocal stimulation of postsynatpic 5 HT-IA receptors for prevention of future attempts and completed suicides is discussed.KEY WORDS: Attempted suicide, Buspirone, Personality factors, Serotonin receptors, Soldiers