Our experience in the treatment of acute Amanita phalloides poisoning

INTRODUCTION: The present study aimed at investigating phalloid mushroom poisoning and the toxicological aid services in Plovdiv region as this pathology shows in this country high mortality rate (40-100%) and increasing incidence; it is difficult to diagnose and is far from featuring adequately in the literature in our country. MATERIAL AND METHODS: A caseload of 270 patients with mushroom poisoning from Plovdiv region, Bulgaria, admitted for treatment to the Clinic of Toxicology, Higher Medical Institute, Plovdiv, for the period 1991-1998 was studied. Of these 270 patients 25 (9.26%) had an acute phalloid poisoning. The following indicators were registered: gender, age, reported type of consumed mushrooms, time of appearance of the first complaints after the mushroom consumption, time of medical aid, disease outcome. The diagnosis and the applied treatment was based on our own diagnostic-therapeutic protocol for phalloid intoxication. RESULTS: All phalloid poisoning cases were accidental by character. The most frequently reported type of ingested mushroom was unidentified wild edible mushrooms. Of all the patients males were 56%, females--44% with mean age of 47.71 years (SD = 17.53). From 25 phalloid poisoning cases 15 survived (60%), 10 died (40%). The summer-fall seasonal pattern of phalloid poisoning occurrence was apparent. The mean duration of the latency period was 12 hours (SD--6.66). In 4 (16%) patients the disease exhibited an unusually early onset--up to 2 hours after the mushroom ingestion. The mean time period from the mushroom ingestion to the presentation in a medical institution for first medical aid was 32 hours (SD--21.69), for men--27.59 hours, for women--43.75 hours. Almost one third (32%) of the diseased presented for medical help more than 36 hours after the poisoning. CONCLUSIONS: The acute mushroom poisoning cases in adults comprise 7.01% of the total acute poisoning caseload. The phalloid poisoning accounts for 9.26% of the total number of patients with mushroom poisoning admitted for treatment. The application of contemporary diagnostic-therapeutic protocol lowers the hospital lethality rate from phalloid poisoning to 40%. There were no statistically significant differences in the compared parameters between the subgroups of patients with favorable and lethal outcome and between the subgroups of men and women--most probably due to the small sample. In order to lower the incidence and mortality rate from phalloid mushroom poisoning the authors recommend preventive health education on the problem, targeting the population at risk and the introduction of contemporary diagnostic and treatment methods--determining the amatoxins, intravenous application of Silibinin and liver transplantation.     

Relationship between absolute and relative hematocrit changes and bone marrow response in rats

The object of the present study was to evaluate the physiologic mechanisms regulating erythropoiesis by monitoring the changes in reticulocyte count in the circulation and the formation of erythroblastic islands in the bone marrow following hypertransfusion and dehydration. Forty-eight male Wistar rats (110-130 grams) were transfused with 70% isogenic suspension of washed and packed red cells at a dose of 2.5 ml/100 g body weight intravenously on two consecutive days (absolute erythrocytosis) or deprived of water for three days to produce relative erythrocytosis and then injected i.v. with saline at a dose of 2.5 ml/100 g body weight with water provided at libitum. Hematocrit was measured using the microhematocrit method. Reticulocytes were enumerated using the new methylene blue stain. Plasma EPO levels were measured radioimmunologically and a bone marrow suspension was prepared for morphological examination and absolute erythroblastic islands determination. We observed a marked suppression of erythropoiesis following the transfusion as evidenced by the elevation in hematocrit values up to 0.64 +/- 0.04, a decrease in reticulocyte count and plasma EPO reduction--13.5 +/- 3.4 mU/ml (P < 0.05) and a suppression of EO formation in the bone marrow (P < 0.01). The hematocrit of the dehydrated rats was elevated during the first 24 hours (P < 0.001). Reticulocytes, as well as EO, decreased on day 3 down do 53.6 x 10(9)/l +/- 9.8 x 10(9)/l (P < 0.001) and 153.6 x 10(3) +/- 21.5 x 10(3)/femur (P < 0.001), respectively. The EPO level was measured simultaneously--16.3 +/- 4.2 mU/ml versus 24.6 +/- 5.3 mU/ml at day 1 (P < 0.001). Following rehydration, a fast increase in the hematocrit value with a concomitant increase in EO and the reticulocyte counts was observed. Our results show that the absolute and relative changes in hematocrit values are paramount in the feedback mechanism for erythroid homeostasis.     

经桡动脉冠状动脉介入治疗中5F与6F导引导管的对比研究

目的比较5French(5F)及6French(6F)导引导管在经桡动脉冠状动脉介入治疗(TRI)患者中的安全性及有效性。方法共纳入2009年2月至2010年3月患者,收集相关资料录入数据库,包括患者基线临床资料、导引导管的尺寸、靶血管、靶病变的特点、手术的成功率、手术失败原因、经桡动脉冠状动脉介入治疗手术的成功率及失败原因、患者住院期间主要不良心血管事件率及术后桡动脉闭塞率。结果连续纳入患者共185例,接受195次经桡动脉冠状动脉介入治疗术,平均年龄(57±11)岁(33～81岁);其中54例患者纳入6F导引导管组,共进行56次手术,治疗89处病变;138例患者纳入5F导引导管组,共行146次手术,治疗231处病变。AHA B2/C型病变比例在两组间差异无统计学意义(5F组43.7%/29.0%比6F组46.1%/34.6%,P>0.05),但慢性闭塞性病变、分叉病变、钙化病变5F组显著少于6F组(5.6%比14.6%,P=0.005;23.4%比37.1%,P=0.012;9.5%比47.2%,P<0.001);组间的手术时间[(45±21)min比(46±19)min)]、手术X线曝光时间[(15±12)min比(16±13)min]、使用造影剂量[(140±45)ml比(156±56)ml]差异均无显著统计学意义(P>0.05),但是5F组造影剂用量有减少的趋势(P=0.066);组间住院时间[(1.40±1.26)d比(1.29±0.69)d]和手术成功率(95.2%比94.6%)也差异无统计学意义(P>0.05);5F组1例患者术后桡动脉闭塞,6F组无患者术后桡动脉闭塞(P=1.0),5F组1例发生卒中。结论经桡动脉冠状动脉介入治疗,即使是复杂及高危冠脉病变,5F导引导管有效、安全,手术成功率不低于常规使用的6F导引导管;换用5F导引导管进行冠状动脉介入治疗是一种有吸引力的选择。     

Urban legends series: Sjögren’s syndrome

Oral Diseases (2012) 19 , 46–58 Sjögren’s syndrome (SjS) is one of the most common autoimmune rheumatic diseases, clinically characterized by xerostomia and keratoconjunctivitis sicca. We investigated the following controversial topics: (i) Do we have reliable ways of assessing saliva production? (ii) How important are the quantity and quality of saliva? (iii) Are only anti‐SSA/Ro and anti‐SSB/La relevant for the diagnosis of SjS? (iv) Are the American‐European Consensus criteria (AECC) the best way to diagnose SjS? Results from literature searches suggested the following: (i) Despite the fact that numerous tests are available to assess salivation rates, direct comparisons among them are scarce with little evidence to suggest one best test. (ii) Recent developments highlight the importance of investigating the composition of saliva. However, more research is needed to standardize the methods of analysis and collection and refine the quality of the accumulating data. (iii) In addition to anti‐Ro/La autoantibodies, anti α‐fodrin IgA and anti‐MR3 autoantibodies seem to be promising diagnostic markers of SjS, but more studies are warranted to test their sensitivity and specificity. (iv) AECC are classification, not diagnostic criteria. Moreover, recent innovations have not been incorporated into these criteria. Consequently, treatment directed to patients diagnosed using the AECC might exclude a significant proportion of patients with SjS.     

Functional conservation of suppressors of cytokine signaling proteins between teleosts and mammals: Atlantic salmon SOCS1 binds to JAK/STAT family members and suppresses type I and II IFN signaling

Suppressor of cytokine signaling (SOCS) proteins are crucially involved in the control of inflammatory responses through their impact on various signaling pathways including the JAK/STAT pathway. Although all SOCS protein family members are identified in teleost fish, their functional properties in non-mammalian vertebrates have not been extensively studied. To gain further insight into SOCS functions in bony fish, we have identified and characterized the Atlantic salmon (Salmo salar) SOCS1, SOCS2 and CISH genes. These genes exhibited sequence conservation with their mammalian counterparts and they were ubiquitously expressed. SOCS1 in mammalian species has been recognized as a key negative regulator of interferon (IFN) signaling and recent data for the two model fish Tetraodon (Tetraodon nigroviridis) and zebrafish (Danio rerio) suggest that these functions are conserved from teleost to mammals. In agreement with this we here demonstrate a strong negative regulatory activity of salmon SOCS1 on type I and type II IFN signaling, while SOCS2a and b and CISH only moderately affected IFN responses. SOCS1 also inhibited IFNγ-induced nuclear localization of STAT1 and a direct interaction between SOCS1 and STAT1 and between SOCS1 and the Tyk2 kinase was found. Using SOCS1 mutants lacking either the KIR domain or the ESS, SH2 and SOCS box domains showed that all domains affected the ability of SOCS1 to inhibit IFN-mediated signaling. These results are the first to demonstrate that SOCS1 is a potent inhibitor of IFN-mediated JAK-STAT signaling in teleost fish.     

Epidemiology of tuberculosis and HIV coinfections in Singapore, 2000–2014

Cross‐matching of records between Singapore's tuberculosis and HIV registries showed that 3.3% of individuals with tuberculosis (TB) were coinfected with HIV (2000?2014), the TB incidence among individuals with HIV infection was 1.65 per 100 person‐years, and 53% of coinfections were diagnosed within 1 month of each other. The findings supported joint prevention programmes for early diagnosis and treatment.     

Structural analysis of human growth hormone with respect to the dominant expression of growth hormone (GH) mutations in isolated GH deficiency type II

Human GH protein consists of four alpha-helices and contains two disulfide bridges. Isolated GH deficiency type II (IGHD II) is mainly caused by heterozygous splice site mutations of GH-1 leading to the disruption of one disulfide bridge (Cys53-Cys165) and to the loss of amino acids (aa) 32-71, which comprise the complete loop between alpha-helices 1 and 2. The mutant GH protein exerts a dominant negative effect on wild-type (wt) GH secretion by unclear mechanisms. For study of the structure-function relationship of GH mutants concerning the dominant negative effect, expression vectors harboring mutated GH cDNAs were transiently cotransfected with a vector encoding wtGH (pwtGH) into GH4C1 cells. Plasmids encoding beta-galactosidase, luciferase, or IGF-binding protein-2 were cotransfected with pwtGH and either of the GH mutants. Compared with the control transfection with pwtGH, GH secretion was mildly decreased by coexpressing wtGH and different GH point mutants with isolated disruption of the disulfide bridge Cys53-Cys165. Similar results were observed with GH mutants deleted in aa 32-46 or 32-52. Deletion of more aa (32-53, 32-63, 32-69, 32-71) ascendingly decreased GH secretion and content in parallel with the increasing length of the deleted stretch. An inhibitory dose-dependent effect of del32-69GH and del32-71GH on the activity/amount of coexpressed beta-galactosidase, luciferase, and IGF-binding protein-2 was found, whereas mRNA levels were unaffected. Hence, the extent of deletion played the major role in expression of the dominant negative effect. The inhibitory effect of GH mutants on heterologously expressed, non-GH proteins suggests that the dominant negative effect is not limited to GH or to proteins of the regulated secretory pathway, but may depend on expression levels.