Oesophageal dissection after thrombolytic treatment for myocardial infarction.

A 62 year old woman admitted with a history suggesting acute myocardial infarction had thrombolytic treatment with anisoylated plasminogen-streptokinase activator complex, which resulted in submucosal haemorrhage in the oesophagus; this caused dissection of the wall of the oesophagus and complete dysphagia. The haematoma resolved spontaneously, leaving behind a diverticulum, with reduced peristalsis and delayed emptying but no obstruction.     

The future of cardiovascular imaging and non-invasive diagnosis

Advances in medical imaging now make it possible to investigate any patient with cardiovascular disease using multiple methods which vary widely in their technical requirements, benefits, limitations and costs. The appropriate use of alternative tests requires their integration into joint clinical diagnostic services where experts in all methods collaborate. This statement summarises the principles that should guide developments in cardiovascular diagnostic services.This paper is published simultaneously in the European Heart Journal (2006;27:1750–1753) and in the European Journal of Echocardiography (2006;7:268–273).     

未破裂脑动脉瘤的治疗选择

未破裂脑动脉瘤的处理存在争议。由于其自然史尚未完全明确,因此最佳的治疗策略也不清楚。目前对未破裂脑动脉瘤处理的共识包括观察、显微手术夹闭和血管内治疗。用于随访已知未破裂脑动脉瘤的方法学也有争议,可能取决于经治医生的偏好。大多数动脉瘤由神经外科医师和介入神经放射科医师处理,但未破裂动脉瘤通常是由神经科医师在对患者进行其他神经系统疾病的筛查时首先发现的。因此,关于何时对患者进行筛查和如何对未破裂动脉瘤采取最佳处理的知识将对其日常医疗实践有直接的影响。未破裂动脉瘤经常导致包括缺血事件、癫和头痛在内的其他神经系统症状,这些症状可能促进更积极的干预治疗。由于缺乏设计完善真正基于人群的研究或随机试验,因此目前的最佳处理必须以现有文献和每例患者当时的具体情况为根据。     

Gastric motility measurement by MRI

The motor mechanisms associated with gastric emptying of nutrient liquids are unclear. Gastric emptying and motility were determined in seven healthy volunteers using an MRI technique following ingestion of 500 ml of (1) 10% and (2) 25% dextrose labeled with 1 mM Gd-DOTA. Emptying was determined with transaxial scans and motility during fast coronal scans 1.2 sec apart. Emptying was slower after ingestion of 25% dextrose. Following both meals, proximal gastric diameter remained relatively constant, while antral contractile frequency and depth varied markedly. These variations were greater after 10% dextrose. These studies suggest that antral motility changes contribute to slowing of gastric emptying by nutrient meals.     

Gd-DOTA as a gastrointestinal contrast agent for gastric emptying measurements with MRI

Current MR meal markers may interfere with gastric motility and secretion restricting the use of MRI in the measurement of gastric physiology. We therefore evaluated Gd-DOTA as a liquid phase marker, in vitro by determining dissociation, and adherence to the solids, and in vivo by simultaneous MRI (0.35 T scanner, multiple T₁-weighted sections of the upper abdomen) and double indicator (perfusion marker PEG 4000, meal marker ^99mTc-DTPA) measurements of emptying and secretion, following ingestion of 500 ml 10% glucose. In vitro Gd-DOTA was stable at a pH > 2 with < 2% dissociation at 24 h during incubation with HCI. Dissociation during incubation with HCI was linearly dependent on H⁺ concentration (0.77 < pH < 2.02). Less Gd-DOTA was absorbed onto the solid phase than ^99mTc-DTPA (25% cf 36%). in vivo Gd-DOTA marked gastric contents provided strong positive contrast. Similar emptying curves were observed with both MRI and double-indicator techniques (r = 0.987, P < 0.001). Gd-DOTA has the potential to be a useful liquid phase contrast agent in MR studies on gastric function.     

Brain cyclosporin A levels are determined by ontogenic regulation of mdr1a expression.

Cyclosporin A (CyA) toxicity is a common occurrence in pediatric organ transplant patients. We hypothesized that reduced mdr1a expression in newborn and developing mice would affect CyA accumulation within organs and/or toxicity. For functional studies, CyA was administered (5 mg kg(-1) i.p.) to 1-, 12-, and 19-day, and adult male and female mdr1a+/+ and mdr1a-/- mice. Peak blood CyA was lower in 1-, 12-, and 19-day-old (1000 ng ml(-1)) versus adult (1500 ng ml(-1)) mice but was similar in mdr1a+/+ and mdr1a-/- mice. Kidney mdr1a expression (measured by quantitative polymerase chain reaction) increased 2.5-fold in 19-day-old male and female mice and increased another 4-fold in adult females compared with adult males. Liver mdr1a expression increased 6-fold by day 12 compared with neonatal mice. Thereafter, maintenance of hepatic mdr1a expression in females and a reduction to neonatal levels in males was observed. Kidney/blood (8- to 9-fold) and liver/blood (12- to 15-fold) CyA levels were highest on days 12 and 19 and were not dependent on maturational changes in mdr1a mRNA levels. Adults had higher brain expression of mdr1a mRNA (3-fold), a corresponding 5-fold increase in immunodetectable P-glycoprotein, and 80% lower brain accumulation of CyA compared with 1-day-old mice. Conversely, in mdr1a-null mice, brain/blood CyA was similar in newborn and adult mice. A similar pattern was observed for the brain accumulation of the mdr1a substrate 3H-digoxin. We conclude that the risk for central nervous system drug toxicity could be higher in neonates or young children as a consequence of underdeveloped P-glycoprotein.     

Cognitive symptoms and correlates of physical disability in individuals with multiple sclerosis.

There are inconsistencies in the literature regarding the prevalence of cognitive impairment among individuals with multiple sclerosis (MS). The purpose of this study was to examine perceived cognitive impairment in secondary progressive and relapsing-remitting multiple sclerosis (MS) and to examine the relationship between level of disability, age, and number of years with MS and self-reported cognitive symptoms. The sample consisted of 447 individuals (96 participants with secondary progressive MS and 351 participants with MS) who responded to mailed data collection instruments. The Performance Scales, a self-report measure of disability in eight domains of function, and a sociodemographic data sheet were analyzedfor this study. Of individuals with secondary progressive MS, 83% reported cognitive symptoms, while 82% of individuals with relapsing-remitting MS reported cognitive symptoms. Individuals with secondary progressive MS were reportedly experiencing a significantly greater level of total disability. A statistically significant, strong, positive relationship was found between cognitive symptoms and fatigue for those with secondary progressive MS and those with relapsing-remitting MS. Statistically significant, moderate, positive relationships were also found between cognitive symptoms in those with secondary progressive MS and those with relapsing-remitting MS, and sensory symptoms, vision, hand function, bladder/bowel symptoms, and spasticity. A statistically significant, weak, positive relationship was found between cognitive symptoms and mobility in individuals with relapsing-remitting MS. There was no relationship between cognitive symptoms and mobility in those with secondary progressive MS. Cognitive symptoms were not significantly related to age in those with secondary progressive MS or those with relapsing-remitting MS. In addition, cognitive symptoms were not significantly related to the number of years with MS in individuals with secondary progressive MS or those with relapsing-remitting MS. The perception of cognitive deficits in individuals with MS was found in this study to be even more prevalent than previously reported. Because cognitive deficits occur at all stages of MS, early identification and treatment is essential. Healthcare providers must aggressively screen for cognitive impairment and rehabilitate individuals with MS who exhibit symptoms.     

Cord insulin and C-peptide--distribution in an unselected population.

OBJECTIVE: To assess the distribution of cord blood insulin in an unselected population, and examine its relation to birthweight centiles. SETTING: District General Hospital in Nottinghamshire. SUBJECTS: 209 unselected singleton births. MEAN OUTCOME MEASURE: Cord blood insulin; cord blood C-peptide; birthweight centiles. RESULTS: Hyperinsulinaemic babies (greater than 97th centile for cord insulin) were found at all birthweight centiles. 15% of high birthweight babies were hyperinsulinaemic. For low birthweight babies, the distribution of cord insulin/C-peptide was skewed indicating a high number of low values. Hypoinsulinaemic babies were present up to the 50th centile for birthweight. CONCLUSIONS: Abnormalities of fetal insulinisation may be found in babies of all birthweights.     

Control of the preovulatory luteinizing hormone surge by gonadotropin-releasing hormone antagonists Prospects for clinical application.

The preovulatory LH surge of the primate menstrual cycle represents a number of positive influences, a major component of which is a direct action of estradiol on the anterior pituitary lobe. Whether the LH surge also requires a corresponding burst of GnRH release from the hypothalamus has been debated. After many years of investigation, there is now conclusive evidence that a midcycle GnRH surge does occur in the primate. This is supported by studies in women with normal ovulatory cycles that demonstrate that blockade of the GnRH receptor by potent GnRH antagonists administered within 1-2 days of the expected midcycle can delay the LH surge. The ability to prevent the positive feedback effects of estradiol by GnRH antagonists is being employed for the controlled induction of follicular development and ovulation in the treatment of infertility and in in vitro fertilization programs.