Computed tomography perfusion imaging in acute stroke

The development of thrombolytic and neuroprotective agents for the treatment of acute stroke has created an imperative for improved imaging techniques in the assessment of acute stroke. Five cases are presented to illustrate the value of perfusion CT in the evaluation of suspected acute stroke. To obtain the perfusion data, a rapid series of images was acquired without table movement following a bolus of contrast medium. Cerebral blood flow, cerebral blood volume and mean transit time were determined by mathematically modelling the temporal changes in contrast enhancement in the brain and vascular system. Pixel‐by‐pixel analysis allowed generation of perfusion maps. In two cases, CT‐perfusion imaging usefully excluded acute stroke, including one patient in whom a low‐density area on conventional CT was subsequently proven to be tumour. Cerebral ischaemia was confirmed in three cases, one with an old and a new infarction, one with a large conventional CT abnormality but only a small perfusion defect, and one demonstrating infarct and penumbra. Perfusion CT offers the ability to positively identify patients with non‐haemorrhagic stroke in the presence of a normal conventional CT, to select those cases where thrombolysis is appropriate, and to provide an indication for prognosis.     

Shared random effects analysis of multi-state Markov models: application to a longitudinal study of transitions to dementia

Multi-state models are appealing tools for analysing data about the progression of a disease over time. In this paper, we consider a multi-state Markov chain with two competing absorbing states: dementia and death and three transient non-demented states: cognitively normal, amnestic mild cognitive impairment (amnestic MCI), and non-amnestic mild cognitive impairment (non-amnestic MCI). The likelihood function for the data is derived and estimates for the effects of the covariates on transitions are determined when the process can be viewed as a polytomous logistic regression model with shared random effects. The presence of a shared random effect not only complicates the formulation of the likelihood but also its evaluation and maximization. Three approaches for maximizing the likelihood are compared using a simulation study; the first method is based on the Gauss-quadrature technique, the second method is based on importance sampling ideas, and the third method is based on an expansion by Taylor series. The best approach is illustrated using a longitudinal study on a cohort of cognitively normal subjects, followed annually for conversion to mild cognitive impairment (MCI) and/or dementia, conducted at the Sanders Brown Center on Aging at the University of Kentucky.     

Severe electrolyte disorders following cardiac surgery: a prospective controlled observational study

Introduction

Electrolyte disorders are an important cause of ventricular and supraventricular arrhythmias as well as various other complications in the intensive care unit. Patients undergoing cardiac surgery are at risk for development of tachyarrhythmias, especially in the period during and immediately after surgical intervention. Preventing electrolyte disorders is thus an important goal of therapy in such patients. However, although levels of potassium are usually measured regularly in these patients, other electrolytes such as magnesium, phosphate and calcium are measured far less frequently. We hypothesized that patients undergoing cardiac surgical procedures might be at risk for electrolyte depletion, and we therefore conducted the present study to assess electrolyte levels in such patients.

Methods

Levels of magnesium, phosphate, potassium, calcium and sodium were measured in 500 consecutive patients undergoing various cardiac surgical procedures who required extracorporeal circulation (group 1). A total of 250 patients admitted to the intensive care unit following other major surgical procedures served as control individuals (group 2). Urine electrolyte excretion was measured in a subgroup of 50 patients in both groups.

Results

All cardiac patients received 1 l cardioplegia solution containing 16 mmol potassium and 16 mmol magnesium. In addition, intravenous potassium supplementation was greater in cardiac surgery patients (mean ± standard error: 10.2 ± 4.8 mmol/hour in cardiac surgery patients versus 1.3 ± 1.0 in control individuals; P < 0.01), and most (76% versus 2%; P < 0.01) received one or more doses of magnesium (on average 2.1 g) for clinical reasons, mostly intraoperative arrhythmia. Despite these differences in supplementation, electrolyte levels decreased significantly in cardiac surgery patients, most of whom (88% of cardiac surgery patients versus 20% of control individuals; P < 0.001) met criteria for clinical deficiency in one or more electrolytes. Electrolyte levels were as follows (mmol/l [mean ± standard error]; cardiac patients versus control individuals): phosphate 0.43 ± 0.22 versus 0.92 ± 0.32 (P < 0.001); magnesium 0.62 ± 0.24 versus 0.95 ± 0.27 (P < 0.001); calcium 1.96 ± 0.41 versus 2.12 ± 0.33 (P < 0.001); and potassium 3.6 ± 0.70 versus 3.9 ± 0.63 (P < 0.01). Magnesium levels in patients who had not received supplementation were 0.47 ± 0.16 mmol/l in group 1 and 0.95 ± 0.26 mmol/l in group 2 (P < 0.001). Urinary excretion of potassium, magnesium and phosphate was high in group 1 (data not shown), but this alone could not completely account for the observed electrolyte depletion.

Conclusion

Patients undergoing cardiac surgery with extracorporeal circulation are at high risk for electrolyte depletion, despite supplementation of some electrolytes, such as potassium. The probable mechanism is a combination of increased urinary excretion and intracellular shift induced by a combination of extracorporeal circulation and decreased body temperature during surgery (hypothermia induced diuresis). Our findings may partly explain the high risk of tachyarrhythmia in patients who have undergone cardiac surgery. Prophylactic supplementation of potassium, magnesium and phosphate should be seriously considered in all patients undergoing cardiac surgical procedures, both during surgery and in the immediate postoperative period. Levels of these electrolytes should be monitored frequently in such patients.     

慢性内脏痛觉超敏大鼠及热板法疼痛小鼠模型对痛泻要方的镇痛反应

目的:观察痛泻要方对慢性内脏痛觉超敏大鼠模型及热板法疼痛小鼠模型疼痛阈值的影响。方法:实验于2005-10/12在广东药学院中药药理教研室实验室完成。选用SD大鼠60只及雌性NIH小鼠40只,由广东省实验动物中心提供。①慢性内脏痛觉超敏实验:取50只SD大鼠制作三硝基苯磺酸模型,其余10只作为正常对照组。灌注三硝基苯磺酸后第7天测腹壁收缩反射阈值,模型组与正常对照组比较腹壁收缩反射阈值显著降低,则证明造模成功。50只大鼠均造模成功,按随机数字表法分为5组,分别为蒸馏水组、罗痛定组(2.3mg/kg)、痛泻要方9.18g/kg组、痛泻要方4.59g/kg组及痛泻要方2.30g/kg组,每组各10只。给予各组大鼠灌胃相应剂量药物(10mL/kg),1次/d,给药7d。于第7天给药后用直结肠气囊扩张法检测腹壁收缩反射阈值。②热板法疼痛实验:取NIH小鼠40只,置于(55±0.5)℃的水浴烧杯上,以舔后足时间为正常痛阈。按随机数字表法分为5组,蒸馏水组、罗痛定组(4.5mg/kg)、痛泻要方18.75g/kg组、痛泻要方9.35g/kg组及痛泻要方4.67g/kg组,每组8只。分别灌胃给药,给药体积为10mL/kg,1次/d,连续3d,于第3天给药后分别测定其60min,90min,120min的痛阈值。结果:①各组大鼠经三硝基苯磺酸诱导的腹壁收缩反射阈值比较:痛泻要方9.18g/kg,4.59g/kg组及罗痛定组大鼠腹壁收缩反射阈值显著高于蒸馏水组(52.5±3.2)mmHg,(48.3±2.5)mmHg,(57.6±2.9)mmHg,(37.5±2.3)mmHg(P<0.05)。②各组小鼠热板法致痛的痛阈值比较:痛泻要方18.75g/kg,9.35g/kg,4.67g/kg组及罗痛定组小鼠的痛阈值在给药后60min,90min,120min时相点均显著高于蒸馏水组(P<0.05)。结论:中药痛泻要方能提高慢性内脏痛觉超敏大鼠模型及热板法疼痛小鼠模型的疼痛阈值,对慢性内脏痛有明显的治疗作用,可为临床治疗肠易激综合征腹痛提供实验依据。     

Renal outcome in adults with renal insufficiency and irregular asymmetric kidneys

Background  

The commonest cause of end-stage renal failure (ESRF) in children and young adults is congenital malformation of the kidney and urinary tract. In this retrospective review, we examine whether progression to ESRF can be predicted and whether treatment with angiotensin converting enzyme inhibitors (ACEI) can delay or prevent this.     

Inhibition of apoptosis by BCR-ABL in chronic myeloid leukemia

BCR-ABL expression is presumed to effect clonal expansion in chronic myeloid leukemia (CML) by deregulation of cell proliferation. However, most studies have found that relative rates of cell proliferation are not increased in CML. Moreover, we found that CML progenitors display a normal proliferative response to growth factors and do not manifest greater proliferative potential than normal progenitors. Growth of malignancies depends on an imbalance between the rate of cell production and the rate of cell death. We found that BCR-ABL expression inappropriately prolongs the growth factor-independent survival of CML myeloid progenitors and granulocytes by inhibiting apoptosis, a genetically programmed process of active cell death; inhibition of BCR- ABL expression by antisense oligonucleotides reversed the suppression of apoptosis as well as the enhancement of survival. The decreased rate of programmed cell death appears to be the primary mechanism by which BCR-ABL effects expansion of the leukemic clone in CML.