Adverse reactions to xenon-enhanced CT cerebral blood flow determination

Fourteen institutions performed 1,830 computed tomographic (CT) cerebral blood flow (CBF) examinations with 32% inhaled stable xenon. Respiratory rate delay greater than 10 seconds occurred in 3.6% of patients, with 83% of the delays lasting 10-15 seconds. There was no incident of prolonged respiratory difficulty. Headache (0.4%), seizures (0.2%), nausea and vomiting (0.2%), and change in neurologic status (0.1%) were uncommon, and there were no transient ischemic attacks. The CT CBF method with 32% inhaled stable xenon is thus associated with an acceptably low incidence of adverse reactions.     

Innocent Bystander or Marker of Pathology!

Mitral annular calcification is known to be associated with conduction abnormalities, embolic phenomena, endocarditis, mitral regurgitation, and thromboembolic cerebrovascular events in the younger population. The size of our elderly population is growing dramatically with the fastest growth in those aged greater than 85 years. The incidence of mitral annular calcification increases sharply in these “very elderly group of patients.” To determine if mitral annular calcification in the elderly patients has the same implications as in the younger population, electrocardiographic and echocardiography (M-mode, two-dimensional, Doppler) data from 553 octogenarian patients who were referred for a variety of clinical indications were analyzed. Patients with mitral annular calcification were quantified into mild, moderate, and severe, and the association of each was determined with various cardiac abnormalities. Mitral annular calcification was found in 59% of the octogenarian patients. Out of these, mild mitral annular calcification was present in 38%, moderate in 40%, and severe mitral annular calcification in 22% of the patients. Mild mitral annular calcification was not associated with an increased incidence of any cardiac abnormalities. Moderate mitral annular calcification was also not associated with any increased incidence of significant aortic stenosis, conduction abnormalities, and enlarged left ventricular size. However, severe mitral annular calcification was associated with all these findings. Moderate and severe mitral annular calcification were associated with significant mitral regurgitation and left ventricular hypertrophy. Thus, in the majority of elderly patients with mild and moderate mitral annular calcification (78%), its presence merely represents an aging process and an innocent bystander as compared to elderly patients without mitral annular calcification. However, only severe mitral annular calcification is strongly associated with cardiac abnormalities. Therefore, quantification of mitral annular calcification in the elderly is important before associating it with various cardiac abnormalities. (ECHOCARDIOGRAPHY, Volume 8, May 1991)     

Prospective study of seasonal patterns in hemostatic factors in older men and their relation to excess winter coronary heart disease deaths

Summary. Background: In England and Wales, approximately 20% extra deaths from coronary heart disease (CHD) occur between December and March, among older people. Circulating concentrations of tissue plasminogen activator (t‐PA), von Willebrand factor (VWF) and fibrin D‐dimer are associated with arterial disease, and tend to peak in winter. The potential contributions of these hemostatic activation measures to excess winter mortality are unknown. Objectives: To estimate contributions of hemostatic factors to excess winter mortality. Methods: Seasonal patterns in t‐PA, VWF and D‐dimer were investigated in 4088 men aged 60–79 years from 24 British towns. Data on established coronary risk factors were collected by questionnaire, physical examination and blood sampling. The adjusted mean increase in hemostatic markers during winter months, after adjustment for a range of coronary risk factors, was combined with associations of each marker with CHD mortality obtained from 9 years’ follow‐up of participants, to predict degree of excess CHD winter mortality. Associations of hemostatic markers with CHD incidence from large meta‐analyses were also used. Results: All three markers showed peaks in winter; the adjusted mean increases during winter months were 0.21, 0.15 and 0.12 standard deviations for t‐PA, VWF and log(D‐dimer), respectively. Predicted excess hazard ratios for winter CHD mortality were 3.0%, 2.4% and 3.1%, respectively, in combination, representing an 8.6% excess. This increased to 14% when applying meta‐analysis estimates. Conclusions: Seasonal patterns in three hemostatic markers predict at least 8.6% excess CHD mortality in winter in Great Britain, potentially accounting for over half the excess observed in recent years.     

Retroviral transduction and expression of the human alkyltransferase cDNA provides nitrosourea resistance to hematopoietic cells

Myelosuppression is the dose-limiting toxicity for nitrosourea chemotherapy. This toxicity predominantly involves modification of the O6 position of guanine with an alkyl moiety. The enzyme responsible for repair of O6-alkylguanine adducts, O6-alkylguanine-DNA alkyltransferase (alkyltransferase), is expressed at low levels in bone marrow (BM) cells. High alkyltransferase expression prevents the cytotoxicity and carcinogenicity of nitrosoureas in several transgenic and in vitro gene transfer models. We used gene transfer using a novel myeloproliferative sarcoma virus (MPSV) based retrovirus (vM5MGMT) to express the human alkyltransferase cDNA (MGMT) in human and murine hematopoietic cells. Transduced K562 cells had very high levels of alkyltransferase expression and significantly increased resistance to 1,3-bis (2- chloroethyl) nitrosourea (BCNU) as compared with untransduced K562 cells. Primary murine BM progenitors showed a high transduction efficiency with vM5MGMT and have increased BCNU resistance in vitro. After BM transplantation with vM5MGMT-transduced BM cells and BCNU treatment of these mice, BM, spleen and thymus had a 10- to 40-fold increase in alkyltransferase expression that persisted for at least 23 weeks posttransplantation. Progenitor cells procured from mice expressing high levels of alkyltransferase also had increased resistance to BCNU. Thus, an MPSV-based retroviral vector transduces mouse and human hematopoietic cells at high efficiency and results in high levels of gene expression both in vitro and in vivo. Overexpression of the alkyltransferase protein may protect hematopoietic progenitors from nitrosourea-induced myelosuppression.     

大肠癌免疫组化表达与临床病理的关系

目的:探讨大肠癌CEA、P53、nm23、Ki-67、MRP免疫组化表达特点和相互关系,及其与临床病理的关系．方法:回顾性分析2003-01／2006-07我院收治的73例大肠癌患者的临床病理及随访资料,并对其石蜡标本采用免疫组化SP染色法检测CEA、P53、nm23、Ki-67、MRP,分析其免疫组化特点及其与临床病理之间的关系．结果:CEA、P53、nm23、Ki-67、MRP在大肠癌中的阳性表达率依次为82．2％、68．5％、75.3％、84．9％和64．4％．CEA、MRP与大肠癌患者的各因素无统计学差异．P53、Ki-67和nm23与肿瘤的Dukes分期和淋巴结转移有关, P53、Ki-67在Dukes C、D期的阳性表达率(依次为82．8％和100％1明显高于Dukes A、B期者(59．1％和75．0％)(P<0．05),而nm23在Dukes C、D期的阳性表达率(58．6％)明显低于Dukes A、B期者(86．4％)(P<0．05)．CEA与nm23的表达呈明显的负相关(r=-0．296,P=0．011),而P53和Ki-67表达之间呈现明显的正相关(r= 0．308,P=0．008),其他各指标间的表达无相关性．nm23、P53和Ki-67与预后因素关系明显,nm23在生存期≥3 a患者的阳性表达率(92．9%)高于生存期<3 a者(71．2％)(P<0．05),而P53和Ki-67在生存期≥3 a患者的阳性表达率(依次为42．9％和64.3％)明显低于生存期<3 a者(74．6％和89．8％)(P<0．05)．结论:P53、Ki-67和nm23的表达与大肠癌的侵袭转移和预后密切相关．CEA可能是大肠癌的侵袭转移的促进因素．MRP所引起的耐药机制是一个相对独立的机制．CEA、P53、nm23、Ki-67可作为判断大肠癌恶性程度、侵袭转移以及预后的指标．