Intracranial circulation: pulse-sequence considerations in three- dimensional (volume) MR angiography

The technique and feasibility of magnetic resonance (MR) angiography of intracranial vessels were studied in 35 healthy volunteers. Variations in image orientation, repetition time (TR), and flip angle were evaluated to determine their effects on flow-related enhancement. Gradient modifications--including echo time (TE), motion compensation, bandwidth, and field of view--were also studied in an effort to reduce motion-induced phase shifts. Results indicated that a FISP (fast imaging with steady precession) sequence with a TR of 50 msec, TE of 15 msec, velocity compensation in the read and section-select directions, acceleration compensation in the read direction, anisotropic volume, and a 1.25-mm partition thickness produced three-dimensional angiographic MR images that were accurate and reproducible in the depiction of the major intracranial vessels. Difficulties with field of view, persistent signal void secondary to higher-order motion, and spatial resolution remain major problems requiring additional study.     

AlphaV beta3 (αvβ3) integrin inhibition reduces leukocyte–endothelium interaction in a pressure-induced reperfusion model

The leukocyte-endothelium interaction is known to contribute to reperfusion injury, which is considered to participate in the pathophysiology of pressure ulcers, and integrin alphaV beta3 (alphavbeta3) has been shown to mediate the processes of cellular adhesion in various types of cells. This study aims to clarify leukocyte behavior in our original microcirculatory pressure-induced reperfusion model, which can visualize the microcirculation in vivo. We also estimated the effect of alphavbeta3 integrin inhibition on the reduction of the leukocyte-endothelium interaction. Mice with dorsal skinfold chambers were divided into three groups: the baseline group (n=6), in which animals received no compression; the compression-reperfusion group (n=6), in which animals underwent 2-hour compression of the dorsal skin, followed by release, and the inhibitor-treated group (n=7), in which an alphavbeta3 inhibitor, CP4715, was administered in addition to the compression-release procedure. Staining with rhodamine 6G quantitatively visualized leukocyte behavior under the intravital fluorescent microscope. Compression-reperfusion induced a significant increase in rolling, sticking, and extravasation of the leukocytes. Treatment with the inhibitor strikingly reduced leukocyte sticking and extravasation. The present experiment has provided evidence that alphavbeta3 inhibition reduces leukocyte-endothelium interaction in our original pressure-induced reperfusion model.     

Raf-1 kinase,epidermal growth factor receptors,and mutant ras proteins in colonic carcinomas

Epidermal growth factor receptors (EGFR) andras mutations are known to play a significant role in controlling cell growth and tumor promotion. Both of them transmit mitogenic signals to the nucleus by activation of Raf-1 kinase. In this study, the expression of EGFR and mutant Ras proteins, and, for the first time, the expression, phosphorylation and kinase activity of Raf-1 kinase have been determined in paired samples of colorectal cancer and mucosa. The tumor and mucosa samples did not differ significantly with regard to Raf-1 kinase content and activity. A major difference between tumors and mucosa was found, however, in the phosphorylation of Raf-1. Most of the mucosa samples (13/20), but only 1/20 of the cancer samples, contained hyperphosphorylated Raf-1. EGFR were significantly (p=0.0025) decreased in the tumors. The decreased phosphorylation of Raf-1 in colonic carcinomas could be the result of activation of Raf-1 phosphatases or inactivation of kinases phosphorylating Raf-1. New forms of treatment based on EGFR overexpression do not seem to be suitable for the majority of colonic cancers.This work was supported by the state of Baden-Württemberg (Verbundforschungsprojekt: Aufklärung von Mechanismen der Tumorentstehung und Tumorabwehr).     

Organisational factors in relation to control of blood pressure: an observational study

BACKGROUND: Studies show that 60-75% of treated patients with hypertension in general practice, still do not reach the recommended blood pressure targets of <150/90 mmHg. AIM: To investigate aspects of hypertension management in relation to sociodemographic variables, antihypertensive drug treatment, and organisational factors in primary care. DESIGN OF STUDY: Observational study over 3 years. SETTING: Eight general practices in Tayside, UK. METHOD: Participants were 560 randomly selected patients aged 40-79 years receiving treatment for hypertension. The outcome measurement was blood pressure control, expressed in binary form based on the British Hypertension Society audit standard of <150/90 mmHg. RESULTS: Of 536 eligible patients, 261 (49%) were defined as having inadequate blood pressure control at the end of the study period. No significant associations were discovered with sex, age, deprivation score and comorbidity. In those patients with inadequate control, 30% had no modifications to their drug treatment during the study period. Blood pressure control at the end of the study period was not associated with number of antihypertensive drugs taken or number of antihypertensive drug modifications. The mean number of clinician contacts was 11 (standard deviation = 8), and mean continuity in primary care was high, although this was not associated with improved blood pressure control. A higher proportion of hypertension-related consultations were associated with increased odds of having inadequate blood pressure control. CONCLUSION: Achieving adequate blood pressure control continues to represent a substantial health problem in a significant proportion of the hypertensive population. Patient, physician and organisational elements play a role in ensuring effective delivery of hypertension care in the community.     

Administered radiopharmaceutical doses in children: a survey of 13 pediatric hospitals in North America.

Universally applied standards for administering radiopharmaceutical doses in children do not presently exist. Hence, pediatric radiopharmaceutical dosimetry varies considerably from institution to institution and is generally based on the recommended adult dose adjusted for body mass. METHODS: We surveyed 13 pediatric hospitals in North America to obtain objective data on dosimetry practices for 16 pediatric nuclear medicine examinations, including the minimum total radiopharmaceutical administered dose per examination, the total administered dose based on body mass, and maximum total doses in children. RESULTS: The reported administered doses of radiopharmaceuticals to children vary over a relatively large range, especially with respect to minimum total administered doses. CONCLUSION: This survey has identified a broad range of administered doses directly leading to variability in radiation-absorbed doses to patients. The nuclear medicine community should develop pediatric standards for radiopharmaceutical administered doses and reduce radiation exposure in children, such as through the use of modern software reconstruction techniques.     

Analysis of ischemia-reperfusion injury in a microcirculatory model of pressure ulcers

The aim of this study was to establish a pressure ulcer model that visualizes the microcirculation, and to examine the participation of ischemia-reperfusion injury in the pathophysiology of pressure ulcers. An original system composed of a new skin fold chamber and compression device allowed loading quantitative vertical stress to the skin. An intravital microscopic technique enabled direct visualization of the microcirculation in the physiological condition and in response to pressure application. To estimate the effect of ischemia-reperfusion injury, animals were divided into two groups: the compression-release group (n = 8), in which the animals received four cycles of compression-release which consisted of 2 hours of compression followed by 1 hour of pressure release; and the compression alone group (n = 8) in which the animals underwent continuous compression for 8 hours. Functional capillary density was quantified before the compression procedure and on day 1 (35 hours) after the first evaluation. The cyclic compression-release procedure significantly decreased functional capillary density as compared to continuous compression, indicating that in our experimental setting repetition of ischemia-reperfusion cycle more severely damaged the microcirculation than single prolonged ischemic insult. This finding supports the significant contribution of ischemia-reperfusion injury to the pathophysiology of pressure ulcers at the level of dynamic in vivo microcirculation.     

Antibiotic prophylaxis diminishes bacterial translocation but not mortality in experimental burn wound sepsis

Pseudomonas (PSA) burn wound sepsis results in prolonged bacterial translocation (BT) of enteric organisms such as E. coli to the mesenteric lymph nodes (MLN) and organs in rats. Intestinal decontamination with oral antibiotics may improve mortality after burn injury, perhaps due to decreased BT. To determine the effect of oral antibiotic prophylaxis effective against E. coli but not PSA on BT and subsequent mortality in a model of PSA burn wound sepsis, rats were given a 30% scald burn and wound inoculation with 10(8) PSA followed by randomization to either ampicillin (50 mg/kg/d) or saline gavage. Cultures of MLN, organs, blood, and cecal contents were obtained on days 1, 4, and 7 after injury, with additional animals observed for 14-day mortality. Although oral antibiotic prophylaxis resulted in increased cecal colony counts, the incidence of BT was unchanged. The number of organisms present in both the MLN and organs, however, was significantly reduced with prophylaxis, indicating cecal overgrowth by non-translocating bacteria. Reduction of the number of translocating organisms did not result in improved mean survival time after injury, suggesting that mortality from PSA burn wound sepsis occurs independently of bacterial translocation.     

Standardization and quantification of radionuclide solid gastric-emptying studies.

The purposes of this investigation were to standardize and validate a simple quantitative method for performing radionuclide solid gastric emptying that can be used for any dual-head gamma-camera and to establish reference values. METHODS: After eating a solid meal (egg sandwich) labeled with a radionuclide, 20 healthy volunteers (9 male, 11 female) underwent a 90-min gastric-emptying study performed with a triple-head gamma-camera. Two sets of 3 simultaneous projections were acquired sequentially for 30 s each: anterior, right posterior oblique (RPO), left posterior oblique (LPO), posterior, left anterior oblique (LAO), and right anterior oblique (RAO), and this sequence was repeated continuously for 90 min. Time-activity curves were generated using a gastric region of interest for each of the views as well as the conjugate-view geometric mean (GM) data for the anterior/posterior, LAO/RPO, and RAO/LPO combinations. Quantitative parameters were determined: percentage gastric emptying (%GE) at 90 min, half-time (min) based on an exponential fit, and clearance rate (%/min) based on a linear fit. Reference values were determined on the basis of a 95% confidence interval of the t distribution. The results were statistically analyzed and compared. RESULTS: The %GE reference values were greater for the anterior/posterior GM (>or=33%) than for the LAO (>or=31%) and anterior (>or=30%) GMs. The 3 %GE GM methods, the 3 exponential-fit GM methods, and the 3 linear-fit GM methods had high correlation coefficients (r >or= 0.874), and with only a single exception, there was no statistical difference among them. The LAO method and LAO/RPO GM mean method correlated strongly (r = 0.900) and had similar mean values (52% vs. 51%) and reference values (29% vs. 30%). All 3 methods of GM quantification also correlated strongly, and there was no significant difference among them. CONCLUSION: We have described and validated a simple method for radionuclide solid gastric emptying that can be used with a dual-head gamma-camera. We recommend the anterior/posterior GM method and have established reference values (>or=33%).     

Calculation of a gallbladder ejection fraction: advantage of continuous sincalide infusion over the three-minute infusion method.

The purpose of this study was to investigate alternative methods of infusing sincalide for calculation of a gallbladder ejection fraction (GBEF) during cholescintigraphy (5 mCi 99mTc-mebrofenin). After gallbladder filling, three methods of infusion were compared in 23 normal volunteers: (1) 0.02 microgram/kg as a 3-min infusion, (2) 0.02 microgram/kg as a 30-min infusion, and (3) 0.01 microgram/kg as a 30-min infusion (14 subjects), all performed on separate days. With the 3-min infusion, the emptying pattern was usually exponential and completed in 15 min. The mean (GBEF) was 52% +/- 26% at 20 min and 56% +/- 27% at 30 min (range 0%-100%). GBEFs were less than 35% in six subjects and 35%-38% in four. Side effects were noted by 11/23 subjects. With the slow infusions, emptying was linear; no side effects were noted. With 0.02 microgram/kg, the mean GBEF was 50% +/- 27% at 20 min and 70% +/- 22% at 30 min (range 26%-95%). Similar results were seen with 0.01 microgram/kg, but the data were more limited. The 30-min infusion had a higher normalcy rate than the 3-min method (91% versus 74%). Females had significantly lower GBEFs than males (p less than 0.05%). We conclude that the slow infusion method is preferable; it is more physiological, results in more complete emptying, has no side effects, has less normal variability, and should improve the specificity of this test. The lower mean female GBEF may have pathophysiological significance.     

Cardiology

This article describes recent developments in cardiology and cardiovascular disease that are likely to be relevant to primary healthcare professionals and their patients. The following subject areas are covered: Primary prevention: recent developments in pharmaco-logical interventions, drug interactions, and drugs that are likely to cause harm; cardiovascular risk estimation and shared decision making with patients; and new developments in 24-hour ambulatory blood pressure monitoring. Secondary prevention: new models of care, including nurse-led care for the provision of hypertension and secondary prevention clinics; new drugs for the treatment of angina and myocardial infarction; ambulatory electrocardiography for the diagnosis of arrhythmias in primary care; and new developments in the treatment of atrial fibrillation - direct thrombin inhibitors and implantable devices. Tertiary prevention: recent developments in cardiac rehabilitation; recent evidence concerning revascularisation procedures and appropriateness criteria for referral; and implantable defibrillators.