Pretreatment or resuscitation with a lipid infusion shifts the dose-response to bupivacaine-induced asystole in rats

BACKGROUND: The authors sought to confirm a chance observation that intravenous lipid treatment increases the dose of bupivacaine required to produce asystole in rats. The authors also measured the partitioning of bupivacaine between the lipid and aqueous phases of a plasma-lipid emulsion mixture. METHODS: Anesthetized Sprague-Dawley rats were used in pretreatment (protocol 1) and resuscitation (protocol 2) experiments. In protocol 1, animals were pretreated with saline or 10%, 20%, or 30% Intralipid (n = 6 for all groups), then received 0.75% bupivacaine hydrochloride at a rate of 10 ml x kg x min(-1) to asystole. In protocol 2, mortality was compared over a range of bolus doses of bupivacaine after resuscitation with either saline or 30% Intralipid (n = 6 for all groups). The lipid:aqueous partitioning of bupivacaine in a mixture of plasma and Intralipid was measured using radiolabeled bupivacaine. RESULTS: Median doses of bupivacaine (in milligrams per kilogram) producing asystole in protocol 1 were for 17.7 for saline, 27.6 for 10% Intralipid, 49.7 for 20% Intralipid, and 82.0 for 30% Intralipid (P < 0.001 for differences between all groups). Differences in mean +/- SE concentrations of bupivacaine in plasma (in micrograms per milliliter) were significant (P < 0.05) for the difference between saline (93.3 +/- 7.6) and 30% Intralipid (212 +/- 45). In protocol 2, lipid infusion increased the dose of bupivacaine required to cause death in 50% of animals by 48%, from 12.5 to 18.5 mg/kg. The mean lipid:aqueous ratio of concentrations of bupivacaine in a plasma-Intralipid mixture was 11.9 +/- 1.77 (n = 3). CONCLUSIONS: Lipid infusion shifts the dose-response to bupivacaine-induced asystole in rats. Partitioning of bupivacaine into the newly created lipid phase may partially explain this effect. These results suggest a potential application for lipid infusion in treating cardiotoxicity resulting from bupivacaine.     

Does low individual operator coronary interventional procedural volume correlate with worse institutional procedural outcome?

OBJECTIVES: To assess the relation between individual operator coronary interventional volume and incidence of complications, the in-hospital outcome at a single, moderate volume urban academic center was prospectively collected over a 3-year period. BACKGROUND: A minimum of 75 coronary interventions/operator per year may be required in the future to obtain formal certification. However, few data exist regarding individual operator volumes and procedural outcome. METHODS: Between January 1993 and December 1995, 1,389 consecutive procedures were performed or supervised by nine geographic full-time operators: 171 (12.3%) utilized various devices, and 350 (25.2%) involved multivessel coronary intervention. Left ventricular ejection fraction was 59 +/- 15% (mean +/- SD), and there were 1.7 +/- 0.7 vessels diseased (with > or = 70% stenosis). Clinical indications included stable angina in 22.5% of cases, unstable angina in 31.9%, acute myocardial infarction (MI) in 2.9%, post MI in 20.6%, shock or acute heart failure in 3.0% and restenosis in 19.1%. In the last consecutive 857 lesions in 655 cases, 20.7% type A, 55.5% type B and 23.8% type C lesions were categorized before coronary intervention. RESULTS: Average yearly operator volume ranged from 26 to 83 cases (mean 51 +/- 26). Each operator has performed a total of 590 +/- 268 coronary interventions, with 10.0 +/- 4.3 years of coronary interventional experience. The mean angioplasty volume rating for the nine operators was 180 +/- 37 (> 170 considered adequate). The in-hospital major complication rate was 1.4% (95% confidence interval 0.7% to 1.893%) for all coronary interventions, including death in 3 patients, bypass surgery in 13, arrhythmia in 3 and Q wave MI in 2. To ascertain how these outcomes compared with standard measures of coronary interventional outcome, four previously published registries were reanalyzed in a similar manner. The rate of complications in the present study was found to be significantly lower than that of the 1992-1993 Society for Cardiac Angiography and Intervention registry (1.9%, n = 19,594, p < 0.05 [excludes ventricular arrhythmias]), the 1994 American College of Cardiology database (3.9%, n = 38,963, p = 0.001), the Mid-America Heart Institute outcome in 1988 (2.3%, n = 5,413, p = 0.02) and the 1985-1986 National Heart, Lung, and Blood Institute Registry (7.2%, n = 1,801, p = 0.001). Odds ratios and 95% confidence intervals showed the outcome in the current study to be at least comparable to the standard registries. CONCLUSIONS: Despite individual operator volumes below those currently being considered for credentialing, the overall institutional outcome was excellent in a diverse and complex patient population.     

Evaluation of a test device to assess X-ray phototimers

BACKGROUND: The levels of proliferating cell nuclear antigen (PCNA) are almost negligible in long-term quiescent cells and increase dramatically during the cell cycle. Recently, the monoclonal antibodies to PCNA have been used to demonstrate the proliferative component of paraffin-embedded tumor tissues. It has been shown to be available as a simple histological marker of proliferative activity and the PCNA labeling index has been correlated with the prognosis of several malignant neoplasms. METHODS: Formalin fixed, paraffin embedded tissue specimens of 29 primary pediatric rhabdomyosarcomas were immunostained by using an anti-PCNA monoclonal antibody (DAKO PCNA PC10). The relationship between the PCNA index and prognosis, clinicopathological features and survival were assessed retrospectively. RESULTS: The mean PCNA index for the whole series was 54%. There was no correlation between PCNA index and any of the clinicopathological characteristics. However, patients having tumors with a high (> 54%) PCNA index demonstrated significantly lower survival rates than tumors with a low (< 54%) PCNA index (P = 0.01). Moreover, there were significantly more patients with relapse or progressive disease in the high PCNA index group (P = 0.005). CONCLUSION: The PCNA labeling index can be a useful prognostic factor and a good indicator of recurrence and/or survival in patients with rhabdomyosarcoma.     

Alignment and category learning

Recent research shows that similarity comparisons involve an alignment process in which features are placed into correspondence. In 6 studies, the authors showed that alignment is involved in category learning as well. Within a category, aligned matches (feature matches occurring on the same dimension) facilitate learning more than nonaligned matches do (matches on different dimensions), although nonaligned matches still facilitate learning relative to nonmatches. Analogously, feature matches that cross category boundaries hurt learning more if they occur on the same versus a different dimension, and cross-category feature matches on different dimensions hurt learning relative to nonmatching features. Representational assumptions of category learning models must be modified to account for the differences between aligned and nonaligned feature matches.     

Risk factors for high-risk proliferative diabetic retinopathy and severe visual loss: Early Treatment Diabetic Retinopathy Study Report #18

PURPOSE: To identify risk factors for the development of high-risk proliferative diabetic retinopathy (PDR) and for the development of severe visual loss or vitrectomy (SVLV) in eyes assigned to deferral of photocoagulation in the Early Treatment Diabetic Retinopathy Study (ETDRS). METHODS: Multivariable Cox models were constructed to evaluate the strength and statistical significance of baseline risk factors for development of high-risk PDR and of SVLV. RESULTS: The baseline characteristics identified as risk factors for high-risk PDR were increased severity of retinopathy, decreased visual acuity (or increased extent of macular edema), higher glycosylated hemoglobin, history of diabetic neuropathy, lower hematocrit, elevated triglycerides, lower serum albumin, and persons with mild to moderate nonproliferative retinopathy, younger age (or type 1 diabetes). The predominant risk factor for development of SVLV was the prior development of high-risk PDR. The only other clearly significant factor was decreased visual acuity at baseline. In the eyes that developed SVLV before high-risk proliferative retinopathy was observed, baseline risk factors were decreased visual acuity (or increased extent of macular edema), older age (or type 2 diabetes), and female gender. CONCLUSIONS: These analyses supported the view that the retinopathy-inhibiting effect of better glycemic control extends across all ages, both diabetes types, and all stages of retinopathy up to and including the severe nonproliferative and early proliferative stages and the possibility that reducing elevated blood lipids and treating anemia slow the progression of retinopathy.     

Bounds on achievable rates of LDPC codes used over the binary erasure channel

We derive upper bounds on the maximum achievable rate of low-density parity-check (LDPC) codes used over the binary erasure channel (BEC) under Gallager's decoding algorithm, given their right-degree distribution. We demonstrate the bounds on the ensemble of right-regular LDPC codes and compare them with an explicit left-degree distribution constructed from the given right degree.