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Biomedical subjects

W M Brown

Publications and source records attributed to W M Brown.

At least 37 records · Page 2Linked to original sources
PubMed2000

A novel type of RNA editing occurs in the mitochondrial tRNAs of the centipede Lithobius forficatus.

We determined the complete mtDNA sequence of the centipede Lithobius forficatus and found that only one of the 22 inferred tRNA genes encodes a fully paired aminoacyl acceptor stem. The other 21 genes encode tRNAs with up to five mismatches in these stems, and some of these overlap extensively with the downstream genes. Because a well-paired acceptor stem is required for proper tRNA functioning, RNA editing in the products of these genes was suspected. We investigated this hypothesis by studying cDNA sequences from eight tRNAs and found the editing of up to 5 nt at their 3' ends. This editing appears to occur by a novel mechanism with the 5' end of the acceptor stem being used as a template for the de novo synthesis of the 3' end, presumably by an RNA-dependent RNA polymerase. In addition, unusual secondary structures for several tRNAs were found, including those lacking a TPsiC (T) or a dihydrouridine (D) arm, and having an unusual number of base pairs in the acceptor or anticodon stems.

Animals↗
PubMed2000

Treatment of epilepsy: existing therapies and future developments.

Epilepsy is a major public health issue, not least because of the aging population in many developed nations and the known increase in the frequency of epilepsy and seizures in later life. Despite the massive scale of the problem and much research, epilepsy remains poorly understood. Despite more than 20 approved drugs in the developed nations and several non-pharmacological options, up to 30% of patients are still refractory to treatment. Despite over a century of pharmacotherapy and neuroscience research, rational design of anti-epileptic drugs (AEDs) is only now starting to yield results, because of the heterogeneity of the disease and our still limited understanding of it. Discovery and development of AEDs has been especially difficult, because of the regulatory issues of satisfactorily proving safety and efficacy, ethical constraints on placebo-controlled trial designs, the fact that seizures are typically widely spaced in time, and the fact that the person undergoing the seizure is typically in no state to remember, let alone assess, what happened. Several non-pharmacological therapies have been developed: brain surgery was first used more than a century ago; the ketogenic diet was first developed 80 years ago; and the vagus nerve stimulator was introduced recently. Pharmacotherapy remains the mainstay of treatment and is effective in most patients. AEDs can be roughly divided according to their time on the market. The first generation extends from the bromides and the barbiturates (the first of which was phenobarbital), to sodium valproate and carbamazepine. The second generation begins with felbamate and includes drugs approved from 1993 to 2000. "Next generation" drugs are still in clinical development and may reach the marketplace in the near future. Intensive research is being conducted both by pharmaceutical and biotech companies and by academic scientists and clinicians; our understanding of the condition is advancing rapidly but many challenges remain in discovering and developing better AEDs.

Animals↗
PubMed2000

Influence of concomitant CABG and urgent/emergent status on mitral valve replacement surgery.

BACKGROUND: Outcomes and resource utilization of patients undergoing mitral valve replacement (MVR) with or without concomitant coronary artery bypass grafting (CABG) were reviewed. METHODS: Data for 1,844 patients undergoing isolated primary MVR at Emory University Hospitals between 1980 and 1997 were recorded prospectively in a computerized database. RESULTS: The four groups included patients undergoing elective MVR with (n = 360) or without CABG (n = 1332) and urgent/emergent MVR with (n = 66) or without CABG (n = 86). Length of stay was significantly higher in patients undergoing elective MVR with CABG (15 days) than in those without CABG (11 days) but was not significantly different in patients undergoing urgent/emergent MVR with CABG (17 days) than in those without CABG (19 days). In-hospital mortality was significantly higher for patients undergoing elective (14%) or urgent/emergent (41%) MVR with CABG than in those undergoing MVR without CABG (elective:6%; urgent/emergent:20%). The 19-year survival rate was 32% for patients undergoing elective MVR with CABG compared with 51% for those without CABG and 28% for patients undergoing urgent/emergent MVR with CABG compared with 46% for those without CABG. Multivariate correlates of long-term mortality included older age, concomitant CABG, and urgent/emergent status. Hospital costs were significantly higher for patients undergoing elective MVR with ($33,216) than for those without ($23,890) CABG. No significant difference in cost were noted between patients undergoing urgent/emergent MVR with ($40,535) and without ($31,981) CABG. CONCLUSIONS: The addition of CABG or urgent/emergent status to patients undergoing MVR significantly increases morbidity, mortality, and costs. Careful scrutiny of the benefits versus resource utilization is required for patients undergoing high risk MVR.

Coronary Artery Bypass↗
PubMed2000

Hypothermic circulatory arrest causes multisystem vascular endothelial dysfunction and apoptosis.

BACKGROUND: Multiple organ failure after deep hypothermic circulatory arrest (DHCA) may occur secondary to endothelial dysfunction and apoptosis. We sought to determine if DHCA causes endothelial dysfunction and apoptosis in brain, kidney, lungs, and other tissues. METHODS: Anesthetized pigs on cardiopulmonary bypass were: (1) cooled to 18 degrees C, and had their circulation arrested (60 minutes) and reperfused at 37 degrees C for 90 minutes (DHCA, n = 8); or (2) time-matched normothermic controls on bypass (CPB, n = 6). Endothelial function in cerebral, pulmonary, and renal vessels was assessed by vasorelaxation responses to endothelial-specific bradykinin (BK) or acetylcholine (ACh), and smooth muscle-specific nitroprusside. RESULTS: In vivo transcranial vasorelaxation responses to ACh were similar between the two groups. In small-caliber cerebral arteries, endothelial relaxation (BK) was impaired in CPB vs DHCA (maximal 55% +/- 2% [p < 0.05] vs 100% +/- 6%). Pulmonary artery ACh responses were comparable between CPB (110% +/- 10%) and DHCA (83% +/- 6%), but responses in pulmonary vein were impaired in DHCA (109% +/- 3%, p < 0.05) relative to CPB (137% +/- 6%). In renal arteries, endothelial (ACh) responses were impaired in DHCA (71% +/- 13%) relative to CPB (129% +/- 14%). Apoptosis (DNA laddering) occurred primarily in duodenal tissue, with a greater frequency in DHCA (56%, p < 0.05) compared with normothermic CPB (17%) and nonbypass controls (0%). CONCLUSIONS: DHCA is associated with endothelial dysfunction in cerebral microvessels but not in the in vivo transcranial vasculature; in addition, endothelial dysfunction was noted in large-caliber renal arteries and pulmonary veins. DHCA is also associated with duodenal apoptosis. Vascular endothelial dysfunction and apoptosis may be involved in the pathophysiology of multisystem organ failure after DHCA.

Animals↗
PubMed2000

Stroke after coronary artery operation: incidence, correlates, outcome, and cost.

BACKGROUND: Stroke is a major complication of coronary operation, with reported rates of postoperative cerebral dysfunction ranging from 0.4% to 13.8%. In this report, the incidence, correlates, outcomes, and costs of stroke in coronary operation were evaluated at Emory University between 1988 and 1996. METHODS: Data were entered prospectively into a dedicated computerized database at Emory University and analyzed retrospectively. Univariate and multivariate analyses were utilized where appropriate. RESULTS: Data from 10,860 patients undergoing primary coronary operation between 1988 and 1996 were analyzed. There were 250 patients not entered into the database. Stroke occurred in 244 (2.2%). Univariate predictors of stroke (p<0.05) included age, female gender, hypertension, diabetes, prior stroke, prior transient ischemic attack (TIA), and carotid bruits. Multivariate correlates included age (odds ratio 1.07) previous TIA (odds ratio 2.2), and carotid bruits (odds ratio 1.9), although the area under the Receiver Operating Characteristics (ROC) curve was only 0.69, suggesting limited ability to predict stroke. One and 5 year survival rates were 64% and 44% with stroke, and 94% and 81% without stroke, respectively. Among the stroke group, 23% of the patient population died before hospital discharge. The stroke group had a significantly longer length of hospital stay, as well as higher costs. CONCLUSIONS: Stroke is a devastating complication of coronary operation, significantly increasing morbidity, mortality, and cost. Three independent variables were identified for predicting stroke, including age, previous TIA, and carotid bruits. Patients should be carefully screened for cerebrovascular disease to help prevent stroke and its associated morbidity.

Cardiopulmonary Bypass↗
PubMed2000

Mitochondrial genomes of Galathealinum, Helobdella, and Platynereis: sequence and gene arrangement comparisons indicate that Pogonophora is not a phylum and Annelida and Arthropoda are not sister taxa.

We report a contiguous region of more than half (> 7,500 nt) of the mitochondrial genomes for Platynereis dumerii (Annelida: Polychaeta), Helobdella robusta (Annelida: Hirudinida), and Galathealinum brachiosum (Pogonophora: Perviata). The relative arrangements of all 22 genes identified for Helobdella and Galathealinum are identical to one another and to their arrangements in the mtDNA of the previously studied oligochaete annelid Lumbricus. In contrast, Platynereis differs from these taxa in the positions of several tRNA genes and in having two additional tRNA genes (trnC and trnM) and a large noncoding sequence in this region. Comparisons of relative gene arrangements and of the nucleotide and inferred amino acid sequences among these and other published taxa provide strong support for an annelid-mollusk clade that excludes arthropods, and for the inclusion of pogonophorans within Annelida, rather than giving them separate phylum status. Gene arrangement comparisons include the first use of a recently described method on previously unpublished data. Although a variety of alternative initiation codons are typically used by mitochondrial protein-encoding genes, ATG appears to be the initiator for all but one reported here. The large noncoding region (1,091 nt) identified in Platynereis has no significant sequence similarity to the noncoding region of Lumbricus, although each contains runs of TA dinucleotides and of homopolymers, which could potentially serve as signaling elements. There is strong bias for synonymous codon usage in Helobdella and especially in Galathealinum. In this latter taxon, 5 codons are completely unused, 13 are used three or fewer times, and G appears at third codon positions in only 26 of the 2,236 codons. Nucleotide composition bias appears to influence amino acid composition of the proteins.

Amino Acid Sequence↗
PubMed2000

The complete mitochondrial DNA sequence of the horseshoe crab Limulus polyphemus.

We determined the complete 14,985-nt sequence of the mitochondrial DNA of the horseshoe crab Limulus polyphemus (Arthropoda: Xiphosura). This mtDNA encodes the 13 protein, 2 rRNA, and 22 tRNA genes typical for metazoans. The arrangement of these genes and about half of the sequence was reported previously; however, the sequence contained a large number of errors, which are corrected here. The two strands of Limulus mtDNA have significantly different nucleotide compositions. The strand encoding most mitochondrial proteins has 1. 25 times as many A's as T's and 2.33 times as many C's as G's. This nucleotide bias correlates with the biases in amino acid content and synonymous codon usage in proteins encoded by different strands and with the number of non-Watson-Crick base pairs in the stem regions of encoded tRNAs. The sizes of most mitochondrial protein genes in Limulus are either identical to or slightly smaller than those of their Drosophila counterparts. The usage of the initiation and termination codons in these genes seems to follow patterns that are conserved among most arthropod and some other metazoan mitochondrial genomes. The noncoding region of Limulus mtDNA contains a potential stem-loop structure, and we found a similar structure in the noncoding region of the published mtDNA of the prostriate tick Ixodes hexagonus. A simulation study was designed to evaluate the significance of these secondary structures; it revealed that they are statistically significant. No significant, comparable structure can be identified for the metastriate ticks Rhipicephalus sanguineus and Boophilus microplus. The latter two animals also share a mitochondrial gene rearrangement and an unusual structure of mt-tRNA(C) that is exactly the same association of changes as previously reported for a group of lizards. This suggests that the changes observed are not independent and that the stem-loop structure found in the noncoding regions of Limulus and Ixodes mtDNA may play the same role as that between trnN and trnC in vertebrates, i.e., the role of lagging strand origin of replication.

Animals↗
PubMed2000

Gatifloxacin Kyorin Pharmaceutical Co.

Gatifloxacin is a novel fluoroquinolone with a 3-methylpiperazine group at position 7 of the quinolone ring and a methoxy group at position 8 [287520,379131]; the 8-methoxy substituent seems to decrease the rate of development of resistance in Gram-positive bacteria [378631]. Gatifloxacin appears safe and effective [286426,342518,378432] and has been approved in the US and several other countries for the treatment of community-acquired pneumonia (CAP), acute bacterial exacerbation of chronic bronchitis, acute sinusitis, uncomplicated skin and skin structure infections, uncomplicated urinary tract infections, complicated urinary tract infections and pyelonephritis, uncomplicated urethral, endocervical, pharyngeal and rectal gonorrhea [352761,359434].

Animals↗
PubMed2000

Anti-CD18 mAb (Genentech/Roche).

Genentech and Roche are collaborating on the development of an anti-CD18 humanized monoclonal antibody (rhuMAb). Inhibition of leukocyte adhesion with antibodies to CD18 is proposed as a therapeutic intervention for indications with an inflammatory component resulting from a reperfusion injury. In June 2000, the company reported that the primary objectives of its phase II trial of the antibody were not met according to preliminary results of the 415-patient trial for the treatment of myocardial infarction [371173], although the company is currently undecided about the implications of the data, and plans to meet with investigators. In 1999, phase II studies for reperfusion injury in patients successfully treated with thrombolytics were planned; enrollment was expected to finish in the third quarter of 1999 [317276]. In February 1999, Lehman Brothers predicted the drug had a 30% probability of reaching market. Assuming a successful launch, Lehman Brothers analysts estimated peak sales would occur in 2009, with sales at that time of 100 million dollars [319225].

Journal Article↗
PubMed1999

Risk neutralization in cardiac operations: detection and treatment of associated carotid disease.

BACKGROUND: A screening and treatment protocol was implemented to extend the benefit of prophylactic carotid endarterectomy to patients who had open heart operations. METHODS: Patients aged 65 or older or who at any age had left main coronary disease, transient ischemic attack, or stroke were eligible for preoperative carotid duplex screening. Carotid endarterectomies and open heart operations were planned as a staged (n = 59) or combined procedure (n = 55) for angiographically confirmed carotid stenosis of at least 80%. RESULTS: Duplex scans were obtained in 1,719 of 7,035 open heart surgical patients over 8 years. The overall stroke rate was 1.5% (108 of 7,035). Seven of these were strokes of carotid origin (0.1%). There were 129 patients with at least 80% stenosis. One hundred fourteen had carotid endarterectomy preceding open heart operation, and none had carotid artery stroke. Twelve patients with at least 80% carotid stenosis by duplex scan had open heart operations without prophylactic carotid endarterectomies. There were four carotid strokes in these 12 patients (p = 0.0001; odds ratio, 20.2). Stroke risk remained significantly elevated (16.8%, p = 0.005) in the 50% to 79% group. The changes associated with the reduced risk afforded by this screening and treatment strategy amounted to $346 for each patient in the study. CONCLUSIONS: The risk of carotid stroke at the time of cardiac operation can be defined by duplex screening. Prophylactic carotid endarterectomy neutralizes the risk in those with at least 80% stenosis. Consideration for lowering the threshold for assessment and treatment of carotid stenoses appears warranted. The economic investment is recouped by the savings in system resources that would have been depleted through care for carotid stroke and its sequelae.

Adult↗
PubMed1999

A randomized trial of endoscopic versus open saphenous vein harvest in coronary bypass surgery.

BACKGROUND: The purpose of this study was to determine whether or not endoscopic vein harvest is a reliable, beneficial, and cost-effective method for saphenous vein harvest in coronary bypass surgery (CABG). METHODS: A total of 100 patients having primary CABG were prospectively randomized to either endoscopic (EVH; n = 47) or open saphenous vein harvest (OVH; n = 50). Three patients in the EVH group required both techniques and were excluded from analysis. RESULTS: The groups did not differ in preoperative characteristics, including: age, gender, left ventricular function, height, weight, percent over ideal body weight, incidence of diabetes, peripheral vascular disease, or preoperative laboratory values (creatinine, albumin, or hematocrit). The EVH group had longer vein harvest and preparation times than the OVH group, while the incision length was significantly shorter. There was no difference between groups in mortality, perioperative myocardial infarction, intensive care unit or postoperative length of stay, blood product utilization, or discharge laboratory measures. There was more drainage noted from leg incisions at hospital discharge in the OVH (34%) versus EVH group (8%; p = 0.001), but more ecchymosis in the EVH group. Although there was a trend towards reduced leg incision pain in the EVH group, there was no statistically significant difference in pain or in the quality of life measure at any point in time. There was no difference between groups in readmission to hospital, administration of antibiotics, or incidence of leg infection. While mean hospital charges for the EVH group were approximately $1,500 greater than for OVH, this difference did not reach statistical significance. CONCLUSIONS: EVH is a safe, reliable, and cost-neutral method for saphenous vein harvest. The best indication for EVH may be in patients who are at increased risk for wound infection and in those for whom cosmesis is a major concern.

Aged↗
PubMed1999

Complete sequence, gene arrangement, and genetic code of mitochondrial DNA of the cephalochordate Branchiostoma floridae (Amphioxus)

We have determined the 15,083-nucleotide (nt) sequence of the mitochondrial DNA (mtDNA) of the lancelet Branchiostoma floridae (Chordata: Cephalochordata). As is typical in metazoans, the mtDNA encodes 13 protein, 2 rRNA, and 22 tRNA genes. The gene arrangement differs from the common vertebrate arrangement by only four tRNA gene positions. Three of these are unique to Branchiostoma, but the fourth is in a position that is primitive for chordates. It shares the genetic code variations found in vertebrate mtDNAs except that AGA = serine, a code variation found in many invertebrate phyla but not in vertebrates (the related codon AGG was not found). Branchiostoma mtDNA lacks a vertebrate-like control region; its largest noncoding region (129 nt) is unremarkable in sequence or base composition, and its location between ND5 and tRNAG differs from that usually found in vertebrates. It also lacks a potential hairpin DNA structure like those found in many (though not in all) vertebrates to serve as the second-strand (i.e., L-strand) origin of replication. Perhaps related to this, the sequence corresponding to the DHU arm of tRNAC cannot form a helical stem, a condition found in a few other vertebrate mtDNAs that also lack a canonical L-strand origin of replication. ATG and GTG codons appear to initiate translation in 11 and 2 of the protein-encoding genes, respectively. Protein genes end with complete (TAA or TAG) or incomplete (T or TA) stop codons; the latter are presumably converted to TAA by post-transcriptional polyadenylation.

Animals↗
PubMed1999

Clinical outcomes and angiographic patency in 125 consecutive off-pump coronary bypass patients.

BACKGROUND: This study compared clinical outcomes, length of stay, and hospital costs in patients having off-pump coronary bypass (OPCAB) versus conventional bypass surgery (CABG). METHODS: From November 1996 through April 9, 1999, OPCAB was performed for 125 consecutive patients and compared with a contemporaneous, matched control group of 625 CABG patients. Patients were matched according to age, gender, incidence of renal failure, diabetes, pulmonary disease, stroke (CVA), hypertension, peripheral vascular disease, and previous myocardial infarction. Follow-up in the OPCAB patients was 100% and averaged 15 months. RESULTS: An average of 2.0 grafts per patient were performed in the OPCAB group (range 1-5). Ninety-four OPCAB patients (75.2%) had a total of 179 grafts assessed angiographically prior to hospital discharge. All but 4/179 grafts (2.2%) were patent, including 94 of 94 IMA grafts (100%). There were no in-hospital deaths in the OPCAB group compared to a mortality rate of 1.4% in the CABG group. OPCAB reduced postoperative hospital stay from 5.5 days in the traditional CABG group to 3.3 days (p=.002), with a decrease in hospital cost of 24% (p = .01). In addition, there was a significant reduction in the rate of transfusion in the OPCAB group (29.6%) compared to the CABG group (56.5%, p = .0001). Two OPCAB patients required postoperative intervention to improve graft patency during the follow-up period. No internal mammary grafts required revision. There was one perioperative CVA and one myocardial infarction in the OPCAB group. CONCLUSIONS: OPCAB surgery reduces hospital cost, postoperative length of stay, and transfusion rate compared to CABG. OPCAB is safe, cost effective, and associated with excellent graft patency and clinical outcomes.

Chi-Square Distribution↗
PubMed1998

Myocardial distribution of antegrade cold crystalloid and tepid blood cardioplegia.

BACKGROUND: Tepid blood (TB) cardioplegia combines the improved rheologic characteristics and the augmented oxygen and substrate delivery of blood cardioplegia with the advantages of moderate hypothermia. In addition, the intramyocardial distribution of continuous TB cardioplegia may also be better than intermittent cold crystalloid (CC) cardioplegia. We sought to compare the distribution of TB and CC cardioplegia at varying infusion pressures. METHODS: In situ, isolated canine hearts were randomized to antegrade, continuous TB (28 degrees C, n = 8) or intermittent CC (n = 8) cardioplegia infused at 50, 75, and 100 mm Hg. The regional distribution of cardioplegia at each pressure was measured by 15-microm colored microspheres. Cardioplegia distribution was measured from three areas each of the right ventricle (inflow, outflow, and apex) and the left ventricle (anterior, lateral, and posterior). Left ventricular samples were subdivided into subepicardial, midmyocardial, and subendocardial. RESULTS: Delivery of cardioplegia to all areas of the right and left ventricles showed a linear pressure-flow relationship over the range of pressures tested. Right ventricular distribution was two-thirds of that to the left ventricle, and left ventricular subepicardial distribution was approximately one half of subendocardial flow in both groups at all delivery pressures. However, the subendocardial to subepicardial ratio was significantly greater with TB cardioplegia than with CC cardioplegia. Transmural right ventricular cardioplegia flow was comparable in both groups. In contrast, left ventricular distribution of CC cardioplegia was greater than TB cardioplegia at all three pressures tested. CONCLUSIONS: The pressure-flow relationship in both CC and TB cardioplegia is linear in both the right and left ventricular myocardium over clinically applicable delivery pressures. The distribution of cardioplegia to the right ventricle is not altered by increased pressure.

Animals↗
PubMed1998

Off-pump multivessel coronary bypass via sternotomy is safe and effective.

BACKGROUND: In an attempt to avoid the deleterious effects of cardiopulmonary bypass, off-pump coronary artery bypass grafting has been rediscovered and refined. The purpose of this study was to compare clinical outcomes, length of stay, and hospital costs with coronary artery bypass grafting on cardiopulmonary bypass. METHODS: Coronary artery bypass was performed on 51 patients without cardiopulmonary bypass. Patients were selected on the basis of coronary anatomy, with significant stenoses in the left anterior descending, ramus intermedius, diagonal, right coronary, acute marginal, or posterior descending territories. Outcomes were compared with those of a computer-generated matched control group having coronary artery bypass grafting on cardiopulmonary bypass (n = 248) during the same time period. RESULTS: No preoperative differences were noted between groups. There were no deaths in the off-pump group and a mortality rate of 1.6% (4/248) in the control group. There was no incidence of stroke, myocardial infarction, or reentry for bleeding among patients in the off-pump group. There was a reduction in length of stay by 3 days (p = 0.01), blood transfusions by 50% (p = 0.0001), and hospital charges by one third (p = 0.05) in the off-pump group. Twenty-six patients had repeat coronary angiography before discharge; 41/43 grafts were widely patent, 1/43 was totally occluded, and 1/43 was narrowed by more than 50%. All internal mammary artery grafts were widely patent. CONCLUSIONS: Off-pump multivessel cardiopulmonary bypass grafting is a safe and effective means of revascularization for patients with coronary stenoses in the anterior or inferior regions, with excellent short-term patency rates and minimal morbidity.

Blood Transfusion↗
PubMed1998

Modifying risk for extracorporeal circulation: trial of four antiinflammatory strategies.

BACKGROUND: Despite recent rediscovery of beating heart cardiac surgical techniques, extracorporeal circulation remains appropriate for most heart operations. To minimize deleterious effects of cardiopulmonary bypass, antiinflammatory strategies have evolved. METHODS: Four state-of-the-art strategies were studied in a prospective, randomized, preoperatively risk stratified, 400-patient study comprising primary (n = 358), reoperative (n = 42), coronary (n = 307), valve (n = 27), ascending aortic (n = 9), and combined operations (n = 23). Groups were as follows: standard, roller pump, membrane oxygenator, methylprednisolone (n = 112); aprotinin, standard plus aprotinin (n = 109); leukocyte depletion, standard plus a leukocyte filtration strategy (n = 112); and heparin-bonded circuitry, centrifugal pumping with surface modification (n = 67). RESULTS: Analysis of variance, linear and logistic regression, and Pearson correlation were applied. Actual mortality (2.3%) was less than half the risk stratification predicted mortality (5.7%). The treatment strategies effectively attenuated markers of the inflammatory response to extracorporeal circulation. Compared with the other groups the heparin-bonded circuit had highly significantly decreased complement activation (p = 0.00001), leukocyte filtration blunted postpump leukocytosis (p = 0.043), and the aprotinin group had less fibrinolysis (p = 0.011). Primary end points, length of stay, and hospital charges, were positively correlated with operation type, age, pump time, body surface area, stroke, pulmonary sequelae, predicted risk for stroke, predicted risk for mortality, and risk strata/treatment group interaction (p = 0.0001). In low-risk patients, leukocyte filtration reduced length of stay by 1 day (p = 0.02) and mean charges by $2,000 to $6,000 (p = 0.05). For high-risk patients, aprotinin reduced mean length of stay up to 10 fewer days (p = 0.02) and mean charges by $6,000 to $48,000 (p = 0.0007). CONCLUSIONS: These pharmacologic and mechanical strategies significantly attenuated the inflammatory response to extracorporeal circulation. This translated variably into improved patient outcomes. The increased cost of treatment was offset for selected strategies through the added value of significantly reduced risk.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1998

Big trees from little genomes: mitochondrial gene order as a phylogenetic tool.

Gene arrangement comparisons are a powerful tool for phylogenetic studies, especially those focused on ancient relationships. Recent reports using metazoan mitochondrial genomes address evolutionary relationships as well as rates and mechanisms of rearrangement. Mitochondrial systems serve as a model for larger-scale comparisons of whole organismal genomes and a stimulus for developing methods for reconstructing the patterns of rearrangement.

Animals↗