High-dose ibuprofen for reduction of striatal infarcts during middle cerebral artery occlusion in rats

OBJECT: Ibuprofen is an antiinflammatory drug that disrupts leukocyte-endothelial cell interactions by limiting expression of endothelial adhesion molecules such as intercellular adhesion molecule-1 (ICAM-1), also known as CD54. The authors hypothesized that ibuprofen could reduce the size of the infarct associated with transient focal ischemia by inhibition of ICAM-1 expression, and they evaluated its effects in rats treated with middle cerebral artery (MCA) occlusion. Ibuprofen treatment was compared with mild systemic hypothermia, which is known to be neuroprotective and is commonly used during neurosurgical procedures. METHODS: The maximum ibuprofen dose (240 mg/kg/day) that could be tolerated with no systemic toxicity was established in the initial experiments. In the efficacy experiment, rats were pretreated with vehicle, ibuprofen, or hypothermia (33 degrees C) prior to 2 hours of MCA occlusion; then their brains were harvested at 24 hours of reperfusion for histological studies. End-ischemic cerebral blood flow (CBF) was evaluated using [14C]iodoantipyrine autoradiography in additional cohorts. Expression of ICAM-1 within ischemic compared with nonischemic caudate nucleus and putamen (striatum) or cortex was evaluated using immunohistochemical studies. Compared with vehicle treatment, ibuprofen produced a 46.2% reduction (p = 0.01) in striatal infarcts, which was comparable to hypothermia (48.7% reduction, p = 0.02). Ibuprofen did not alter end-ischemic CBF in any region studied, and the ibuprofen treatment group had the lowest proportion of animals with marked ICAM-1 staining. CONCLUSIONS: Ibuprofen given in maximum tolerated doses reduces the striatal infarct size after focal cerebral ischemia. The neuroprotective mechanism does not work through preservation of intraischemic CBF and is consistent with inhibition of ICAM-1 expression; however, at the doses used in this study, other effects of ibuprofen on platelet and endothelial function are possible.     

Independent predictors of morbidity after image-guided stereotactic brain biopsy: a risk assessment of 270 cases

OBJECT: Image-guided stereotactic brain biopsy is associated with transient and permanent incidences of morbidity in 9 and 4.5% of patients, respectively. The goal of this study was to perform a critical analysis of risk factors predictive of an enhanced operative risk in frame-based and frameless stereotactic brain biopsy. METHODS: The authors reviewed the clinical and neuroimaging records of 270 patients who underwent consecutive frame-based and frameless image-guided stereotactic brain biopsies. The association between preoperative variables and biopsy-related morbidity was assessed by performing a multivariate logistic regression analysis. Transient and permanent stereotactic biopsy-related morbidity was observed in 23 (9%) and 13 (5%) patients, respectively. A hematoma occurred at the biopsy site in 25 patients (9%); 10 patients (4%) were symptomatic. Diabetes mellitus (odds ratio [OR] 3.73, 95% confidence interval [CI] 1.37-10.17, p = 0.01), thalamic lesions (OR 4.06, 95% CI 1.63-10.11, p = 0.002), and basal ganglia lesions (OR 3.29, 95% CI 1.05-10.25, p = 0.04) were in'dependent risk factors for morbidity. In diabetic patients, a serum level of glucose that was greater than 200 mg/dl on the day of biopsy had a 100% positive predictive value and a glucose level lower than 200 mg/dl on the same day had a 95% negative predictive value for biopsy-related morbidity. Pontine biopsy was not a risk factor for morbidity. Only two (4%) of 45 patients who had epilepsy before the biopsy experienced seizures postoperatively. The creation of more than one needle trajectory increased the incidence of neurological deficits from 17 to 44% when associated with the treatment of deep lesions (those in the basal ganglia or thalamus; p = 0.05), but was not associated with morbidity when associated with the treatment of cortex lesions. CONCLUSIONS: Basal ganglia lesions, thalamic lesions, and patients with diabetes were independent risk factors for biopsy-associated morbidity. Hyperglycemia on the day of biopsy predicted morbidity in the diabetic population. Epilepsy did not predispose to biopsy-associated seizure. For deep-seated lesions, increasing the number of biopsy samples along an established track rather than performing a second trajectory may minimize the incidence of morbidity. Close perioperative observation of glucose levels may be warranted.     

Is bridging to transplantation with a left ventricular assist device a risk factor for transplant coronary artery disease?

BACKGROUND: Left ventricular assist device (LVAD) support is associated with coagulopathy, bleeding, increased blood transfusion, and increased anti-HLA antibody production. Increased anti-HLA antibody production is associated with early transplant rejection, transplant coronary artery disease (CAD), and decreased post-transplant survival rates. We asked whether bridging to transplantation with an LVAD increases the risk of transplant CAD. METHODS: We reviewed data for all adults (>18 years old) who underwent heart transplantation at our institution between 1988 and 2000. After exclusion of transplant recipients who survived <3 years, we divided the remaining cohort into 2 groups: those bridged to transplantation with LVADs (mean duration of support, 149 +/- 107 days, n = 29) and those in United Network for Organ Sharing Status 1 bridged to transplantation without LVADs (controls, n = 86). We compared groups in terms of disease cause, age, sex, donor age, panel-reactive antibody testing, crossmatching, pre- and post-transplant cholesterol concentrations, diagnosis of diabetes mellitus or treated hypertension, infections, calcium channel blocker use, transplant rejection, ischemic time, cytomegalovirus infection, pre-transplant transfusion, and incidence of transplant CAD (defined as any coronary lesion identified by coronary angiography). We considered p < 0.05 to be significant. RESULTS: The bridged and control groups were similar in all respects except mean ischemic time (217 +/- 58 minutes vs 179 +/- 67 minutes, p = 0.007), post-transplant cholesterol concentration (212 +/- 55 mg/dl vs 171 +/- 66 mg/dl, p = 0.007), and pre-transplant transfusion incidence (100% vs 22%, p < 0.001). The incidence of transplant CAD was similar in both groups during a 3-year follow-up period (28% vs 17%, p = 0.238) and during total follow-up (34% vs 35%, p = 0.969). Multivariate logistic regression analysis identified cholesterol concentration at 1 year after transplantation as a significant predictor of CAD at 3 years after heart transplantation (p = 0.0029, odds ratio = 0.984). CONCLUSIONS: Bridging to transplantation with an LVAD does not increase the risk of transplant CAD. Nevertheless, aggressive prophylactic therapy to minimize potential risk factors for transplant CAD, such as increased cholesterol concentration, is warranted in all transplant recipients.     

Evaluation of myocardial function in patients with end-stage heart failure during support with the Jarvik 2000 left ventricular assist device.

In 2 patients with the Jarvik 2000 left ventricular assist device (LVAD), we assessed left ventricular systolic function through pressure-volume loops and E(max) at the beginning and end of the support period to potentially predict the possibility of pump removal without transplantation. Immediately before LVAD implantation and explantation, pressure and volume measurements were made with catheters and echocardiography, respectively, the E(max) being calculated from the slope of the pressure-volume loops, and the left ventricular ejection fraction (LVEF) being estimated by echocardiography. Transplantation was performed after 14 and 62 days, respectively, during which the LVEF increased by 75% (from 12% to 21%) in Patient 1 and remained unchanged (from 16% to 18%) in Patient 2, whereas the E(max) increased from 0.63 and 0.42 mm Hg/ml, respectively, to 1.31 and 1.07 mm Hg/ml, reflecting a 107% and 155% improvement. In these 2 cases, the E(max) was a more reliable indicator of intrinsic myocardial contractility than was the LVEF.     

Anastomosis of bypass grafts using a low-powered CO2 laser

The purpose of this study was to evaluate the feasibility of using a low-powered CO2 laser to perform end-to-side anastomoses of bypass grafts. The internal jugular veins of 13 domestic swine were removed and used as grafts to bypass their ligated carotid arteries. Each end of the vein graft was apposed to the artery with four to six temporary stay sutures, and a waveguide delivery CO2 laser with a power density of 900 mW/mm2 was used to perform the anastomoses, after which the sutures were removed. The animals were sacrificed postoperatively at five time intervals: 2 to 4 hours, 5 days, 1 month, 3 months, and 5 months. Of the 10 anastomoses studied at 2 to 4 hours, 70% were fully patent, none thrombosed, and 30% disrupted. Of the 16 anastomoses studied between 5 days and 5 months postoperatively, 88% were patent, 12% thrombosed, and none disrupted. None of the animals developed aneurysms at any stage of this investigation. Histologic analysis of acute studies revealed thermal damage such as charring of tissue, unraveling of the collagen fibrils, and the formation of microvacuoles. Within 3 months, the anastomotic sites showed localized healing with intimal fibromuscular proliferation and dense fibrous tissue. Good apposition of tissue was found to be of great importance in achieving patency of vessels in this procedure.     

The treatment of advanced cardiac allograft rejection

Severe cardiac allograft rejection remains a serious problem despite the advances of cyclosporine-based immunosuppression. This study analyzes our experience with 202 recipients of cardiac allografts who were treated primarily with cyclosporine and prednisone. Failure of such therapy in 86 patients (43%) resulted in 105 episodes of advanced cardiac allograft rejection as diagnosed by endomyocardial biopsy. Of 101 rejection episodes that were initially treated with intravenous pulse therapy, 48 (48%) were successfully resolved, yet 60% of these successes were associated with major infections. Patients in whom steroid therapy failed or was contra-indicated received intravenous antithymocyte globulin (ATG) or intravenous monoclonal antibody (OKT3). ATG and OKT3 successfully reversed severe rejection in 26 (81%) of 32 and in 13 (93%) of 14 episodes, respectively. Infectious complication rates were 54% and 21%, respectively. Because the majority (87%) of these rejection episodes occurred within the first 30 days after treatment, many of them may have resulted from inadequate immunosuppressive induction therapy. Based on our results, we believe that advanced cardiac allograft rejection may be managed best by individualizing immunosuppressive therapy, thus enhancing prevention, and by adding OKT3 to the regimen when rejection occurs.     

Metabolically controlled reperfusion in acute myocardial infarction: should the polarizing solution be given subselectively?

BACKGROUND: In working rat hearts, metabolic support of injured tissue enhances recovery after acute myocardial infarction. Clinical experience with a systemic "polarizing solution" supports this claim. OBJECTIVES: In a dog model of ischemia/reperfusion, we tested the feasibility of subselectively supplying adapted metabolic substrates before instituting blood reperfusion. METHODS: Thirty-five dogs underwent ligation of the proximal left anterior descending artery and collaterals for 90 minutes. The animals were randomly assigned to receive direct blood reperfusion (Group I), intracoronary glucose, insulin, and potassium (Group II), or intracoronary glucose, insulin, and potassium plus propionyl-L-carnitine (PLC) (Group III). After 30 minutes of artificial reperfusion, prograde blood flow was resumed in groups II and III. A routine necropsy was performed 3 to 5 days later. Primary endpoints were severe arrhythmias, death, markers of infarct size, and specific histologic features. RESULTS: We excluded 4 dogs for technical reasons and 2 others for preexisting cardiomyopathy. In the remaining 29 animals, large apical infarctions were documented ventriculographically during arterial ligation. One dog died of irreversible ventricular fibrillation during the initial ischemic period, and 9/28 dogs (32.1%) died during early reperfusion. Ventricular fibrillation was more common with 10% (versus 5%) dextrose concentrations and was eliminated by PLC. Irreversibly injured (versus jeopardized) areas of myocardium were more common in Group III (85.9 19.3%) than in Groups I and II (16.9 10.8%). CONCLUSION: Subselective infusion of metabolically supportive solutions during acute myocardial infarction is technically feasible. To prevent osmotic endothelial damage, the perfusate must have a low (< 5%) dextrose content.     

Bacterial cholangitis causing secondary sclerosing cholangitis: A case report

Background  

Although bacterial cholangitis is frequently mentioned as a cause of secondary sclerosing cholangitis, it appears to be extremely rare, with only one documented case ever reported.     

The diagnostic value of the fibrinogen/fibrin fragment E antigen assay in clinically suspected deep vein thrombosis

We have evaluated the fibrinogen/fibrin fragment E antigen assay as a diagnostic test in patients with clinically suspected venous thrombosis by comparing the results of this assay with venography in 272 patients. The result of the fragment E antigen assay was elevated in 79 of 80 patients with positive venograms for recent venous thrombosis (sensitivity 99%) and within the normal range in 161 of 192 patients with normal venograms (specificity 84%). The fragment E assay was also evaluated in 130 medical and surgical controls without evidence of venous thrombosis by leg scanning and the test was found to be relatively nonspecific. However, in the patient group under study, a correct clinical diagnosis of no thrombosis, based on a normal fragment E result, was made in 161 of 162 cases (negative predictive value of 99%). Therefore, a normal test result effectively excludes a diagnosis of venous thrombosis in clinically symptomatic patients. The assay, as currently performed, is technically demanding and takes 24 hr to complete. Therefore, it will have to be simplified before it can be applied to clinical practice.