Measurement of kinetic parameters in skeletal muscle by magnetic resonance imaging with an intravascular agent.

The purpose of this work was to investigate the use of an intravascular contrast agent to determine perfusion kinetics in skeletal muscle. A two-compartment kinetic model was used to represent the flux of contrast agent between the intravascular space and extravascular extracellular space (EES). The relationship between the image signal-to-noise ratio (SNR) and errors in estimating permeability surface area product (Ktrans), interstitial volume (ve), and plasma volume (vp) for linear and nonlinear curve-fitting methods was estimated from Monte Carlo simulations. Similar results were obtained for both methods. For an image SNR of 60, the estimated errors in these parameters were 10%, 22%, and 17%, respectively. In vivo experiments were conducted in rabbits to examine physiological differences between these parameters in the soleus (SOL) and tibialis anterior (TA) muscles in the hind limb. Values for Ktrans were significantly higher in the SOL (3.2+/-0.9 vs. 2.0+/-0.5x10(-3) min-1), as were values for vp (3.4+/-0.8 vs. 2.1+/-0.7%). Differences in ve for the two muscles (8.7+/-2.2 vs. 8.5+/-1.6%) were not found to be significant. These results demonstrate that relevant physiological metrics can be calculated in skeletal muscle using MRI with an intravascular contrast agent.     

Damage control surgery for abdominal trauma.

OBJECTIVE: To review the physiology, indications, technical aspects, morbidity, and mortality of damage control surgery. DESIGN: Retrospective study of published papers. SETTING: Teaching hospital, United Arab Emirates. INTERVENTIONS: A MEDLINE search on damage control surgery for the years 1981-2001. Further articles were retrieved from the references of the original articles. RESULTS: The indications for damage control surgery are: the need to terminate a laparotomy rapidly in an exsanguinating, hypothermic patient who had developed a coagulopathy and who is about to die on the operating table; inability to control bleeding by direct haemostasis; and inability to close the abdomen without tension because of massive visceral oedema and a tense abdominal wall. The principles of damage control surgery are: Phase I: laparotomy to control haemorrhage by packing; shunting, or balloon tamponade, or both; control of intestinal spillage by resection or ligation of damaged bowel, or both. Phase II: physiological resuscitation to correct hypothermia, metabolic acidosis, and coagulopathy. Phase III: planned reoperation for definitive repair. Damage control surgery is appropriate in a small number of critically ill patients who are likely to require substantial hospital resources; it has a high mortality (mean 45%, range (10%-69%). CONCLUSION: Damage control surgery offers a simple effective alternative to the traditional surgical management of complex or multiple injuries in critically injured patients. Phases I and II can be done at a rural hospital before transfer to a major trauma centre for definitive repair.     

Secondary prevention of ischemic stroke: evolution from a stepwise to a risk stratification approach to care.

Survivors of ischemic stroke are at significant risk for recurrent stroke. Appropriate therapy for stroke prevention is needed given the significant morbidity and mortality associated with stroke, the high financial costs, and the neurologic disability associated with treatment failure. A treatment strategy based on assessed risk represents an appropriate use of medical resources and results in improved outcomes. This approach requires evaluation of major risk factors, the most serious of which is a history of ischemic stroke or transient ischemic attack. The annual risk for recurrent stroke is 6% during the first 5 years after an initial stroke. Non-modifiable risk factors include age, race, ethnicity, gender, family history, and geography. The most important modifiable risk factor is hypertension. Diabetes mellitus, hyperlipidemia, left ventricular hypertrophy, atrial fibrillation, and lifestyle factors such as smoking, alcohol abuse, and obesity contribute to stroke risk. Antihypertensive, lipid-lowering, and antiplatelet therapies have been successful in reducing the incidence of secondary stroke. Clinical trials validate the benefits of statin therapy in reducing the risk for secondary stroke. Studies of antiplatelet agents, including aspirin, clopidogrel, and aspirin combined with extended-release dipyridamole, have evaluated the risk reduction in recurrent stroke and have been concerned particularly with the risk for hemorrhage. Therapy for stroke prevention based on risk stratification can identify patients who are appropriate targets for aggressive intervention.     

Elevated serotonin transporter binding in major depressive disorder assessed using positron emission tomography and [11C]DASB; comparison with bipolar disorder.

BACKGROUND: Altered serotonergic function is thought to play a role in the pathophysiology of major depressive episodes based upon evidence from neuroimaging, pharmacological, postmortem and genetic studies. It remains unclear, however, whether depressed samples that differ with respect to having shown a unipolar versus a bipolar illness course also would show distinct patterns of abnormalities within the serotonergic system. The current study compared serotonin transporter (5-HTT) binding between unipolar-depressives (MDD), bipolar-depressives (BD) and healthy-controls (HC) to assess whether the abnormalities in 5-HTT binding recently found in depressed subjects with BD extend to depressed subjects with MDD. METHODS: The 5-HTT binding-potential (BP) measured using positron emission tomography (PET) and [(11)C]DASB was compared between unmedicated, depressed subjects with MDD (n = 18) or BD (n = 18) and HC (n = 34). RESULTS: Relative to the healthy group both MDD and BD groups showed significantly increased 5-HTT BP in the thalamus (24%, 14%, respectively), insula (15%) and striatum (12%). The unipolar-depressives had elevated 5-HTT BP relative to both BD and HC groups in the vicinity of the periaqueductal gray (PAG, 20%, 22%, respectively). The bipolar-depressives had reduced 5-HTT BP relative to both HC and MDD groups in the vicinity of the pontine raphe nuclei. Depression-severity correlated negatively with 5-HTT BP in the thalamus in MDD-subjects. CONCLUSIONS: The depressed phases of MDD and BD both were associated with elevated 5-HTT binding in the insula, thalamus and striatum, but showed distinct abnormalities in the brainstem. The latter findings conceivably could underlie differences in the patterns of illness symptoms and pharmacological sensitivity observed between MDD and BD.     

Tumor cell-enhanced sensitivity of vascular endothelial cells to photodynamic therapy

Effective antitumor photodynamic therapy (PDT) may be related to damage of vasculature within the tumor. The purpose of this study was to determine if tumor cells secrete factors that stimulate proliferation of human umbilical vein endothelial cells (HUVEC) and result in enhanced sensitivity of HUVEC to aluminum-sulfonated phthalocyanine (AISPc)-PDT. Three human tumor cell lines—pharyngeal squamous carcinoma, colonic carcinoma, and mammary carcinoma—were used in this study. Co-culture of HUVEC and either squamous carcinoma or colonic carcinoma, but not mammary carcinoma, significantly increased HUVEC proliferation and AlSPc-PDT mediated cell damage. In addition, supernatant from squamous carcinoma and colonic carcinoma cultures also stimulated HUVEC proliferation and sensitivity to AISPc-PDT. Both supernatant and cell lysate from squamous carcinoma cells contained angiogenic factors consistent with basic and acidic fibroblast growth factors, as evidenced by Western blot analysis and BALB/c 3T3 fibroblast cell proliferation assays. Collectively, these results suggest that selected tumor cell lines produce angiogenic factors that induce HUVEC proliferation and subsequently enhance sensitivity to AISPc-PDT. © 1994 Wiley-Liss, Inc.     

Myocardial perfusion and function in dogs with moderate coronary stenosis

MRI studies of first-pass contrast enhancement with polylysine-Gd-DTPA and myocardial tagging using spatial modulation of magnetization (SPAMM) were performed to assess the feasibility of a combined regional myocardial blood flow and 2D deformation exam. Instrumented closed-chest dogs were imaged at a baseline control state (Cntl) followed by two interventions: moderate coronary stenosis (St) achieved by partial occlusion of the left anterior descending (LAD) and moderate coronary stenosis with dobutamine loading (StD). Hypoperfusion of the anterior region (ANT) of the myocardium (LAD distribution) relative to the posterior wall (POS) based on the upslope of the signal intensity time curve from the contrast-enhanced MR images was demonstrated only with dobutamine loading (ANT:POS Cntl=1.077 ± 0.15 versus ANT:POS StD=0.477 ± 0.11, P<0.03) and was confirmed with radio-labeled microspheres measurements (ANT:POS Cntl=1.18 ± 0.2 ml/min/g versus ANT:POS StD=0.44 ± 0.1 ml/min/g; P<0.002). Significant changes in regional myocardial shortening were only seen in the StD state (P<0.02); the anterior region showed impaired myocardial shortening with dobutamine loading (P=NS), whereas the nonaffected POS region showed a marked increase in shortening when compared with Cntl (Cntl=0.964 ± 0.02 versus StD=0.884 ± 0.03; P<0.001). These results demonstrate that an integrated quantitative assessment of regional myocardial function and semiquantitative assessment of myocardial blood flow can be performed noninvasively with ultrafast MRI.