HYPERVENTILATION AND DIZZINESS: CASE REPORTS AND MANAGEMENT

SUMMARY Dizziness is a common symptom in patients presenting to an otorhinolaryngologist. Hyperventilation accounts for up to 5% of cases with dizziness and is a contributory factor in a further 20% of cases. Six cases of dizziness due to hyperventilation are presented to illustrate the authors' simple management policy. A high index of suspicion in the absence of an organic cause of dizziness and a simple provocation test will identify these cases. Management is aimed at demonstrating resting hypocapnia, investigations to exclude organic causes of hyperventilation and rehabilitation in collaboration with a clinical psychologist ensures the appropriate treatment for the dizziness and can avoid the development of chronic somatisation behaviours.     

H5N1亚型禽流感病毒NSl蛋白表达影响因素分析

目的 优化高表达禽流感病毒NS1蛋白的实验方法。方法将基因工程菌接种LB培养基,设定IPTG终浓度为0.3mmol／L,诱导温度为37℃,诱导表达6．0h,SDS-PAGE分析融合蛋白表达情况,确定最佳诱导时间。以o．1mm01／L为梯度,设置不同IPTG诱导浓度,37℃诱导4.0h,分析融合蛋白表达,确定最佳IPTG诱导浓度。设定IPTG至终浓度为0。6mmo1／L,分别于24℃、28℃、32℃、37℃和42℃下诱导表达4．0h,分析融合蛋白表达,确定最适诱导温度。采用最优表达条件,超声裂菌后SDS-PAGE分析融合蛋白,Westernblotting对融合蛋白进行鉴定。结果当培养温度为37℃,IPTG浓度为0。3mmol／L时,融合蛋白GST-NSl在IPTG诱导5．0h时的表达量最高,达28．5％;当IPTG诱导浓度为0。6ram01／L,在37℃诱导表达4。0h时,融合蛋白的表达量可达27．9％。选用优化的表达条件,IPTG0．6mmo1／L,37℃诱导表达4．0h,融合蛋白的表达量最高可达33．2％。进一步分析显示,融合蛋白大部分以可溶形式表达,其表达量可占菌体总蛋白的25．1％。经SDS-PAGE电泳、电转移后,用小鼠抗GST单克隆抗体进行免疫印迹分析,出现一条阳性反应带。结论通过实验优化了工程菌诱导表达的最佳IPTG浓度、最适时间和培养温度,实现了融合蛋白的可溶性高表达。     

异基因造血干细胞移植受者代谢综合征的发生情况

异基因造血干细胞移植（hematopoieticcelltransplantation,HCT）后代谢综合征的发生主要由预处理导致的神经激素系统紊乱、血管内皮损伤、移植物的免疫和炎症作用以及继发的移植物抗宿主病及其治疗等引起。对代谢综合征及其组分（糖尿病、高血压、血脂紊乱等）的筛查可以尽早地调整治疗策略,控制危险因素的发生,进而降低远期的心血管疾病的发生率和致死率。为此,美国的研究人员回顾性分析了86例异基因HCT受者代谢综合征的发生情况,并与代谢综合征在普通人群中的流行情况进行比较。     

Weight gain after adjuvant chemotherapy in patients with early breast cancer in Istanbul Turkey

Weight gain is a well-known and unwanted complication of adjuvant chemotherapy in breast cancer. We observed that the female Turkish cancer patients frequently gain weight with adjuvant treatment of breast cancer and planned to examine the magnitude of this problem in early breast cancer patients treated at our hospital. A total of 176 early breast cancer patients who received their adjuvant systemic therapy in Marmara University Hospital between 2003 and 2007 are included in the study. We recorded their weight before and after chemotherapy and also a year after chemotherapy to find out whether the change with weight is transitory. We have also recorded demographic information, including the educational level, menopausal status, the type of chemotherapy or hormonal treatment administered stage of disease, marital status, occupation and the underlying diseases to analyze the relationship between change in weight and these parameters. Median age of patients was 53 and 72% of patients were postmenopausal. Educational level was equally distributed for primary education (27%), high school (40%), and university (33%). The majority of the patients (76%) was married, had two children (69%) and was housewife (60%). Family history of any cancer was high (32%). Most of the patients had stage II cancer (56%), received anthracyclines+/− taxane based chemotherapy (98%) and had no underlying disease (68%). The majority also did not smoke (73%) or drink alcohol (93%). A total of 67% and 72% patients gained weight upon completion and one year after completion of chemotherapy. Mean weight before the chemotherapy, upon completion of chemotherapy and one year after completion of chemotherapy were 68.9 kg, 70.6 kg (P = 0.000) and 71.9 kg (P = 0.000) respectively. Mean body mass index was 27.1 at baseline, 27.8 upon completion of chemotherapy (P = 0.000) and 28.3 one year after completion of chemotherapy (P = 0.000). Age, menopausal status, multiparity and presence of comorbid diseases had statistically significant impact on weight gain following adjuvant therapy in breast cancer patients (P = 0.000, P = 0.008, P = 0.015 and P = 0.017 respectively). This study shows that Turkish women with early breast cancer gain weight after adjuvant systemic therapy, in line with European and American counterparts. This increase in weight is maintained at least one year after adjuvant therapy. Given the adverse consequences of weight gain in terms of both breast cancer prognosis and general health, it is necessary to inform patients about this change and to develop strategies for weight maintenance during and after systemic therapy.     

Relation of neuroendocrine cells to transforming growth factor-alpha and epidermal growth factor receptor expression in gastric adenocarcinomas: Prognostic implications

The presence of neuroendocrine (NE) cells in gastric adenocarcinoma (GCa) is well documented, however, their significance is controversial. There is no evidence in the literature concerning the possible effect of these cells on the expression of TGF-a and EGFR, which are believed to confer growth advantage to tumor cells. 101 partial or total gastrectomy specimens from patients operated for conventional gastric adenocarcinoma were included in the study. In each case immunohistochemistry was performed on sequential tissue sections for chromogranin A (ChrA), TGF-a and EGFR. Samples were graded based on the number of ChrA-positive cells (0–3). TGF-a and EGFR expressions were evaluated according to both the intensity (0–2) and quantification of the positively stained areas (0–3). Follow-up data was available in 54 patients. Twenty-seven patients died of disease, while 27 patients were alive with a follow-up of at least 15 months. ChrA expression was detected in 54.4% of the tumor specimens. TGF-a was stained positively in 42.6% and EGFR in 49.5% of the cases. NE cells in GCa was related to TGF-a (p<0.0001) and EGFR expression (p<0.05), and TGF-a/EGFR coexpression (p<0.001). Among histopathologic variables, the presence of NE cells was significantly related to grade, stage and lymph node status. Although the presence of NE cells had no effect on survival, the expression of EGFR (p<0.0001) and TGF-a (p=0.002) were related to survival. The results of our study suggest that the presence of NE cells may have an effect on the expression of TGF-a and EGFR in GCa, and the autocrine mechanism between TGF-α and EGFR plays an important role in the prognosis of gastric carcinoma. This work was supported by the Marmara University Research Committee     

A novel polymorphism in the factor XIII B-subunit (His95Arg): relationship to subunit dissociation and venous thrombosis

BACKGROUND: Factor (F)XIII B-subunit, which plays a carrier role for zymogen FXIIIA, is highly polymorphic, but the molecular basis for these polymorphisms and their relationship to disease remains unknown. OBJECTIVES: To screen the FXIIIB gene coding region for common variation and analyze possible functional effects. METHODS AND RESULTS: We examined the FXIIIB gene by PCR-SSCP and identified three common single nucleotide polymorphisms: A8259G, C29470T and A30899G. A8259G results in substitution of His95Arg in the second Sushi domain. An FXIII tetramer ELISA was developed to analyze B-subunit dissociation from A-subunit (leading to access to the catalytic site of FXIII). Increased subunit dissociation, 0.51 vs. 0.45 (fraction of total tetramer), was found in plasma from subjects possessing the Arg-allele. However, when the variants were purified to homogeneity and binding was analyzed by steady-state kinetics, no difference was observed. The relationship between His95Arg and venous thrombosis was investigated in 214 patients and 291 controls from Leeds. His/Arg + Arg/Arg genotypes were more frequent in patients than controls (22.4% vs. 15.1%). His95Arg was also investigated in the Leiden Thrombophilia Study, in which a similar difference was observed for 471 patients vs. 472 controls (18.5% vs. 14.0%), for a pooled odds ratio (OR) of 1.5 (CI95 1.1-2.0). CONCLUSIONS: We have identified three FXIIIB polymorphisms, one of which codes for substitution of His95Arg. The Arg95 variant associates with a moderately increased risk for venous thrombosis, and with increased dissociation of the FXIII subunits in plasma, although in vitro steady-state binding between purified subunits was not affected.     

Biological and immunological characterization of ATG and ALG

Antithymocyte globulin (ATG) and antilymphocyte globulin (ALG) are effective therapies in aplastic anemia; their mechanism of action is undefined. We assayed multiple properties of ATG and ALG to address the biological and immunological bases for differences between ATG and ALG and lot variation. In addition, we studied a lot reported to be inactive in an American clinical trial; however in retrospect, this lot appeared to be active in patients treated in Europe. Immunoprecipitation of thymocyte and lymphocyte membrane proteins with ATG and ALG showed between 14 and 18 major bands on SDS-PAGE, but the patterns for ATG and ALG were not identical. The ability of ATG and ALG to block binding of labeled monoclonal antibodies was assessed using flow cytometry and a radioimmunoassay. In general, there was more lot variation among ALGs than ATGs; however, all ALG lots were more potent blockers of binding of anti-HLA-DR and anti-Leu 1 antibodies than was ATG. Both ALG and ATG effectively blocked binding of anti-Leu 2a, anti- Leu 3a, anti-Leu 4, anti-Leu 5b, and anti-IL 2 receptor abs; neither blocked binding of anti-Leu 7. All preparations were capable of inducing T-cell blastogenesis, although there was considerable lot variation. All lots lysed 60% to 75% T cells in a rabbit complement- mediated cytotoxicity assay, with most having a plateau of activity at 5 to 10 ug/mL. Two lots of ALG, including the lot reported to be clinically inactive, showed less toxicity at suboptimal concentrations and did not plateau even at 80 ug/mL. In total, these results indicate important differences between ATG and ALG in general, more lot variation among ALGs than ATGs and only differences in cytotoxicity between an "inactive" lot of ALG and most, but not all, other active ATG and ALG preparations.