Determinants of outcome after carotid endarterectomy

BACKGROUND: The efficacy of carotid endarterectomy for selected patients has been evaluated with randomized controlled clinical trials. The generalizability of these studies to average surgical practice remains an important public health concern. OBJECTIVE: The objective of the study was to determine the predictors of outcome after carotid endarterectomy on a regional basis. Patients and Methods: The study was designed as a retrospective cohort study and included all consecutive patients presented for carotid endarterectomy at the 8 University of Toronto-affiliated hospitals in the period from January 1, 1994, to December 31, 1996. The main outcome measure was 30-day postoperative stroke or death rate. RESULTS: During the study interval, 1280 primary carotid endarterectomies were performed. The overall combined stroke and death rate was 6.3% for all patients who underwent endarterectomy (4.0% for patients who were asymptomatic). The significant predictors of poor outcome were the following: presenting symptoms (odds ratio, 1.74; 95% confidence interval [CI], 0.96, 3.12), low surgeon volume (<6 cases per year; odds ratio, 3.98; 95% CI, 1.65, 9.58), and left-sided surgery (odds ratio, 1.72; 95% CI, 1.07, 2.76). CONCLUSION: These data suggest that adoption of the recommendations of the symptomatic carotid endarterectomy trials is appropriate. However, endarterectomy for asymptomatic lesions remains of uncertain benefit on a regional basis and must be individualized to the experience of the specific surgeon. The surgeon volume/outcome relationship that is identified in this study suggests a need for a minimum volume threshold for this procedure.     

Human hepatocyte nuclear factor-4 (hHNF-4) gene maps to 20q12-q13.1 between PLCG1 and D20S17

Male Hartley guinea pigs (480-610 g; n=5) were treated intratracheally with saline, cadmium (Cd, 0.3 mg) as cadmium chloride, selenium (Se, 0.3 or 0.06 mg) as sodium selenite or Se (0.06 mg) and Cd (0.3 mg). After 24 hours, lungs were collected and analyzed for prostaglandin (PGE2), thromboxane (TXB2) and leukotriene (LTC4) levels. Results indicated that, 0.3 mg Se and 0.06 mg Se in combination with 0.3 mg Cd increased PGE2 significantly. Selenium and Cd alone or in combination, decreased LTC4 and TXB2 significantly.     

Calcium-permeable AMPA receptors mediate long-term potentiation in interneurons in the amygdala

Fear conditioning is a paradigm that has been used as a model for emotional learning in animals. The cellular correlate of fear conditioning is thought to be associative N-methyl-D-aspartate (NMDA) receptor-dependent synaptic plasticity within the amygdala. Here we show that glutamatergic synaptic transmission to inhibitory interneurons in the basolateral amygdala is mediated solely by alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors. In contrast to AMPA receptors at inputs to pyramidal neurons, these receptors have an inwardly rectifying current-voltage relationship, indicative of a high permeability to calcium. Tetanic stimulation of inputs to interneurons caused an immediate and sustained increase in the efficacy of these synapses. This potentiation required a rise in postsynaptic calcium, but was independent of NMDA receptor activation. The potentiation of excitatory inputs to interneurons was reflected as an increase in the amplitude of the GABA(A)-mediated inhibitory synaptic current in pyramidal neurons. These results demonstrate that excitatory synapses onto interneurons within a fear conditioning circuit show NMDA-receptor independent long-term potentiation. This plasticity might underlie the increased synchronization of activity between neurons in the basolateral amygdala after fear conditioning.     

Inhibition of Alzheimer beta-fibrillogenesis by melatonin

It is generally postulated that the amyloid beta protein (Abeta) plays a central role in the progressive neurodegeneration observed in Alzheimer's disease. Important pathologic properties of this protein, such as neurotoxicity and resistance to proteolytic degradation, depend on the ability of Abeta to form beta-sheet structures or amyloid fibrils. We report that melatonin, a hormone recently found to protect neurons against Abeta toxicity, interacts with Abeta1-40 and Abeta1-42 and inhibits the progressive formation of beta-sheets and amyloid fibrils. These interactions between melatonin and the amyloid peptides were demonstrated by circular dichroism and electron microscopy for Abeta1-40 and Abeta1-42 and by nuclear magnetic resonance spectroscopy for Abeta1-40. Inhibition of beta-sheets and fibrils could not be accomplished in control experiments when a free radical scavenger or a melatonin analog were substituted for melatonin under otherwise identical conditions. In sharp contrast with conventional anti-oxidants and available anti-amyloidogenic compounds, melatonin crosses the blood-brain barrier, is relatively devoid of toxicity, and constitutes a potential new therapeutic agent in Alzheimer's disease.     

Direct observations of reaction zone structure in propagating detonations

We report experimental observations of the reaction zone structure of self-sustaining, cellular detonations propagating near the Chapman-Jouguet state in hydrogen-oxygen-argon/nitrogen mixtures. Two-dimensional cross sections perpendicular to the propagation direction were imaged using the technique of planar laser induced fluorescence (PLIF) and, in some cases, compared to simultaneously acquired schlieren images. Images are obtained which clearly show the nature of the disturbances in an intermediate chemical species (OH) created by the variations in the strength of the leading shock front associated with the transverse wave instability of a propagating detonation. The images are compared to 2-D, unsteady simulations with a reduced model of the chemical reaction processes in the hydrogen-oxygen-argon system. We interpret the experimental and numerical images using simple models of the detonation front structure based on the “weak” version of the flow near the triple point or intersection of three shock waves, two of which make up the shock front and the third corresponding to the wave propagating transversely to the front. Both the unsteady simulations and the triple point calculations are consistent with the creation of keystone-shaped regions of low reactivity behind the incident shock near the end of the oscillation cycle within the “cell.”     

Ion chromatography of amylamine and tert.-butylamine in pharmaceuticals

Ion chromatographic (IC) methods have been developed for the assay of amylamine in BMS-181 866-02 and tert.-butylamine (TBA) in BMS-188 494-04. BMS-181 866-02 is the penultimate intermediate in the synthesis of a novel thromboxane antagonist, BMS-180 291-02, which is undergoing clinical trials. Amylamine may be present as a trace impurity in BMS-181 866-02. BMS-188 494-04 is the TBA salt of the prodrug ester of BMS-187 745, a novel oral hypocholesterolemic agent. Chromatographic separations were accomplished under isocratic conditions using a Dionex CS-14 column with conductivity detection. The methods differ only in the composition of the methanesulfonic acid-acetonitrile mobile phase. The detection limit and minimum quantifiable levels for amylamine were 0.01% and 0.02%, respectively. The method was linear over the range studied (1-12.5 micrograms/ml, n = 7, r = 0.9993). The method for TBA was linear from 5 to 30% (w/w) (50-300 micrograms/ml, n = 8, r = 0.9993) of working sample concentration (1 mg/ml BMS-188 494-04). The precision and accuracy of the methods are presented.     

Neuroblastoma and treatment-related myelodysplasia/leukemia: the Memorial Sloan-Kettering experience and a literature review

PURPOSE: To assess treatment-related myelodysplasia/leukemia (t-AML) in neuroblastoma patients by a review of the Memorial Sloan-Kettering Cancer Center (MSKCC) data and the literature. PATIENTS AND METHODS: We studied 380 previously untreated and treated MSKCC patients. Low-risk patients received no cytotoxic therapy. High-risk patients received the N4, N5, or N6 regimens. Dosing per cycle and cumulative dosing of leukemogenic agents peaked with N6, which included four cycles of cyclophosphamide 4,200 mg/m2 and doxorubicin 75 mg/m2, plus three cycles of cisplatin 200 mg/m2 and etoposide 600 mg/m2. We reviewed the literature. RESULTS: t-AML occurred in six MSKCC patients, which included three of 53 patients in whom the only chemotherapy consisted of N6, and three patients treated for relapsed or refractory neuroblastoma; no case of leukemia emerged among the 50 low-risk patients. Four cases were found incidentally in routine follow-up bone marrow tests. The 36-month cumulative incidence of t-AML in the N6 cohort was 7% (95% confidence interval, 0 to 15). Published data parallel the MSKCC experience in that t-AML after neuroblastoma was once rare but has become less so since the mid-1980s, when the intensified use of topoisomerase-II inhibitors and alkylators first gained wide acceptance and produced better response rates and longer survival. CONCLUSION: Neuroblastoma itself is not associated with a host susceptibility to leukemia. However, current neuroblastoma treatment programs that use high-dose cyclophosphamide, cisplatin, and topoisomerase-II inhibitors may entail a considerable risk for t-AML. The incidence of t-AML in neuroblastoma patients may be underestimated because treatment and clinical factors can mask its presence. Efforts to devise effective but less leukemogenic treatment for neuroblastoma or to truncate leukemogenic therapy, eg, by exploiting molecular techniques for the early identification of complete remission, are warranted.     

The equivalence of SF-36 summary health scores estimated using standard and country-specific algorithms in 10 countries: results from the IQOLA Project. International Quality of Life Assessment

Open choledochostomy still represents an important step of biliary surgery, even during the era of laparoscopic surgery. Although its application has decreased with the widespread use of endoscopic retrograde cholangiopancreatography (ERCP) and papillotomy, still there are some patients in whom it is necessary to perform open choledochostomy and place a T-tube. The morbidity and mortality rates depend mainly on the presence or absence of an acute suppurative cholangitis, rather than the performance of the choledochostomy. In patients with mild cholangitis or those no cholangitis and less than 60 years of age, the mortality rate is lower than that observed after ERCP. This procedure is still an important technique for surgeons dedicated to biliary surgery, and therefore several technical aspects of common bile duct exploration are important to remember.