However, abnormalities detected by karyotype analysis cannot alwa

However, abnormalities detected by karyotype analysis cannot always be characterised by scrutinising the G-banded pattern alone, and imbalance detected by array CGH cannot always be visualised in the context of metaphase chromosomes. In some cases further techniques are needed for detailed characterisation of chromosomal abnormalities. We investigated seven cases involving structural

chromosome rearrangements detected by karyotype analysis, and one case where imbalance was primarily detected by array CGH. Multicolor banding (MCB) was used in all cases and proved invaluable in understanding the detailed structure of the abnormalities.

Findings: Karyotype analysis detected structural chromosome rearrangements in 7 cases and MCB was used to help refine the KY 12420 karyotype for each case. Array CGH detected imbalance in an eighth case, where previously, G-banded chromosome analysis had reported a normal karyotype. Karyotype analysis of a second tissue type revealed this abnormality in mosaic form; however, MCB was needed in order to characterise this rearrangement. MCB provided information for the delineation of small deletions, duplications, insertions and inversions and helped to assign breakpoints which were difficult to identify

from G-banded preparations due to ambiguous banding patterns.

Conclusion: Despite the recent advance of array

Selleckchem CX-4945 CGH in molecular cytogenetics we conclude that fluorescence in situ hybridization, including MCB, is still required Adriamycin clinical trial for the elucidation of structural chromosome rearrangements, and remains an essential adjunct in modern diagnostic laboratories.”
“P>In plants, microRNAs (miRNAs) comprise one of three classes of small RNAs regulating gene expression at the post-transcriptional level. Many plant miRNAs are conserved, and play a role in development, abiotic stress responses or pathogen responses. However, some miRNAs have only been found in certain species. Here, we use deep-sequencing, computational and molecular methods to identify, profile, and describe conserved and non-conserved miRNAs in four grapevine (Vitis vinifera) tissues. A total of 24 conserved miRNA families were identified in all four tissues, and 26 known but non-conserved miRNAs were also found. In addition to known miRNAs, we also found 21 new grapevine-specific miRNAs together with their star strands. We have also shown that almost all of them originated from single genes. Furthermore, 21 other plausible miRNA candidates have been described. We have found that many known and new miRNAs showed tissue-specific expression. Finally, 112 target mRNAs of known and 44 target mRNAs of new grapevine-specific miRNAs were identified by genomic-scale high-throughput sequencing of miRNA cleaved mRNAs.

Additionally, a VIA method of predicting carcass yield has the ad

Additionally, a VIA method of predicting carcass yield has the advantage over the current INAC classification system in that estimates would be produced by an instrument rather than by packing plant personnel, which would appeal to cattle producers. Results from the tenderness phase of the study indicated that the CVS BeefCam output variable for marbling was not (P > 0.05) able to segregate steer and heifer carcasses into groups that differed in WBSF values. In addition, the results of segregating steer and heifer carcasses according to muscle color output variables indicate that

muscle maturity and skeletal A-1331852 chemical structure maturity were useful for segregating carcasses according to differences in WBSF values of their steaks (P > 0.05). Use of VIA to predict beef

carcass fabrication yields could improve accuracy and reduce subjectivity in comparison with use of current INAC grades. Use of VIA to sort carcasses according to muscle color would allow for the marketing of more consistent beef products with respect to tenderness. This would help facilitate the initiation of a value-based marketing system for the Uruguayan beef industry.”
“Chronic migraine (CM) represents an important medical issue, due to morbidity, high disability, presence of comorbidities, and medication overuse Alpelisib (MO). The prophylaxis of CM has not been extensively explored so far. Patients with CM are often treated with two or more compounds, although there is no clear see more evidence that polytherapy may be superior to monotherapy. We evaluated the percentage of prescription of polytherapy for the prophylaxis of CM in a clinical sample. We examined the charts of 98 CM patients admitted to our Headache Center for inpatient

withdrawal program to stop MO. Results showed that only one drug for prophylaxis was prescribed in 20.4% cases, two or more drugs in 79.6%, with 63.3% of the total sample falling in the group “”true polytherapy”", i.e. all the drugs prescribed on daily basis were given to treat CM, and not only to treat concomitant conditions. In more than 60% cases a combination of drugs indicated for migraine prophylaxis and drugs only indicated for other conditions (mainly for psychiatric disorders) was prescribed. Our survey indicates that polytherapy may be rather common in CM, and suggests that comorbidities may strongly influence treatment choices.”
“There is a growing trend toward utilizing more label friendly ingredients in foods and beverages. In this study, we focused on the utilization of sucrose monopalmitate (SMP) as a non-ionic surfactant for stabilizing acidic beverages. Orange oil-in-water emulsions (5% (w/w) oil) stabilized by SMP were prepared using high pressure homogenization (pH 7). The minimum droplet diameter was around 130 nm. while the minimum mass ratio of SMP-to-oil required to produce small droplets was 0.1-to-1.

Screening and prevention practices can decrease the likelihood of

Screening and prevention practices can decrease the likelihood of developing additional cancers.”
“Background/aims: We found that pooled Crohn’s disease (CD) Pfizer Licensed Compound Library screening sera strongly react with a human gap-junction connexin 37 (Cx37) peptide and tested for anti-Cx37 antibody reactivity in sera from CD patients and controls. We also investigated whether peptide-recognition is due to Cx37/microbial molecular mimicry.

Methods: The PSI-BLAST program was used for Cx37(121-135)/microbial alignment. Reactivity to biotinylated human Cx37(121-135) and its microbial mimics was determined by ELISA

using sera from 4,4 CD, 30 ulcerative colitis and 28 healthy individuals.

Results: Anti-Cx37(121-135) reactivity (1/200 dilution) was present in 30/44 (68%) CD cases and persisted at 1/1000 dilution.

Database search shows that Cx37(121-135) contains the -ALTAV- motif which is cross-recognized by diabetes-specific phogrin and enteroviral immunity. Testing of 9 Cx37(121-135)-microbial mimics revealed 57-68% reactivity against human enterovirus C, Lactococcus lactis, coxsackie virus A24 and B4. Anti-Cx37(121-135) was inhibited by itself or the microbial mimics. No reactivity was found against the poliovirus, rubella, and Mycobacterium tuberculosis mimics, or the beta cell phogrin autoantigen. Microbial/Cx37 reactivity was not able to differentiate CD EVP4593 cell line patients from UC or healthy controls, in terms of overall prevalence and antibody titres, but microbial mimics were unable to inhibit reactivity to human Cx37 in the majority of the controls.

Conclusions: Sera from CD patients react with connexin 37 and cross-react with specific Cx37-mimicking enteroviral peptides. Microbial/self reactivity can be seen in UC and healthy controls. The lack of responses to other Cx37(121-135) microbial mimics and the inability of the reactive microbes to inhibit reactivity to self is intriguing and warrants further investigation. (C) 2010 European Crohn’s and Colitis Organisation. Published by Elsevier B.V. All rights reserved.”
“Background: The cornerstone of the management

of patients Nutlin-3a with endometrial cancer is hysterectomy. Since 1988, the role of lymphadenectomy for patients with endometrial cancer has been debated. Patients who undergo pelvic and para-aortic lymphadenectomy are more likely to be accurately staged and are less likely to receive adjuvant radiation therapy.

Methods: The authors perform a narrative review of the recent literature. Overall survival, utilization of radiation therapy, impact on quality of life, and alternative approaches to surgical staging are discussed.

Results: Although a survival benefit from comprehensive surgical staging has not been clearly demonstrated in patients diagnosed with endometrial cancer, surgical staging allows one to determine the need for adjuvant therapy. Preoperative and intraoperative assessment of lymph node metastasis and tumor grade lacks accuracy.


“Genome-wide association studies of stroke have revealed a


“Genome-wide association studies of stroke have revealed a polygenomic pathology in which contributions from individual genes are highly variable. This variability appears to be due at least in part to contributions from epigenetic mechanisms SP600125 molecular weight that fall into three main categories. The first includes mechanisms that mediate

DNA methylation and attenuate gene expression. The second category includes the enzymes that add and remove acetyl groups to lysine residues in histone proteins and thereby facilitate or inhibit their dissociation for DNA with subsequent increases or decreases in gene expression, respectively. The third category includes the pathways that regulate the synthesis and action of micro-RNAs that regulate mRNA translation. Together, these epigenetic mechanisms convert environmental conditions and physiological stresses into long-term changes in gene expression and translation. Studies of epigenetic mechanisms in stoke are in their infancy but offer great promise for better understanding of stroke pathology and the potential viability of new strategies for its treatment.”
“Ankle brachial index (ABI) is a simple method to screen peripheral arterial disease Fer-1 (PAD) and to evaluate cardiovascular (CV) prognosis in the general population. Measuring it requires a hand-held Doppler

probe but it can be done also with an automatic device. ABI is an effective tool for clinical practice or clinical studies. However, in diabetic patients, it has some specific caveats. Sensitivity of the standard threshold of 0.9 appears to be lower in diabetic patients with complications. Moreover, highly frequent arterial medial calcifications in diabetes increase ABI. It

has been demonstrated that measurements >1.3 are well correlated with both an increased prevalence of PAD and CV risk. Therefore, ABI thresholds of less than 0.9 and more than 1.3 are highly suspicious for PAD and high CV risk in diabetic patients. However, when there is concomitant clinical peripheral neuropathy or high risk of arterial calcification, the efficiency of ABI seems GSK1904529A to be limited. In this case, other methods should be applied, toe pressure, in particular. Thus, the ABI could be used in patients with diabetes, but values should be interpreted with precision, according to the clinical situation. (C) 2010 European Society for Vascular Surgery. Published by Elsevier Ltd. All rights reserved.”
“Objectives: To quantify the change in work productivity and activities of daily living in North American women with heavy menstrual bleeding (HMB) treated with estradiol valerate/dienogest (E2V/DNG; Qlaira (R)/Natazia (R)) compared to placebo.

Methods: Women in the United States and Canada, aged 20-53 years with an objective diagnosis of HMB and no recognizable anatomical pathology, were treated with E2V/DNG or placebo for seven cycles (196 days). Main outcome measures included work productivity (i.e.

Methods: A representative sample of the population of the seven i

Methods: A representative sample of the population of the seven islands, formed of 662 people aged between 5 and 75 years (368 females, 294 males), was analyzed. Epidemiological data were obtained by direct survey. The detection of serum IgG antibodies against

both microorganisms was based on an indirect immunofluorescence test, considered positive if the titers were >= 1/80.

Results: Of the analyzed population ABT-737 supplier 3.9% had IgG antibodies against R. typhi and 4.4% against R. conorii. Out of these positive samples, only three were positive for both species. The seroprevalence was similar in both sexes. Positive results were found in all age groups, but a higher rate was noticed in those aged 46 years and older (p < 0.05). R. typhi was found to be more prevalent in rural areas of all islands, as well as in farmers.

Conclusions: MLN2238 clinical trial Our results confirm the presence of antibodies against the causative agents of murine typhus and Mediterranean spotted fever in the Canary Islands. Indirect data suggest that the detection of antibodies to R. conorii might be due to a cross-reaction between these species. (C) 2011 International Society for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.”
“Superoxide dismutase (SOD) has extensive clinical applications for protecting organisms from toxic oxidation. In this study, the integrated

iron-superoxide dismutase gene (fe-sod) coding sequence of Nostoc commune stain CHEN was cloned from genomic Selleckchem JNJ-64619178 DNA and compared to sods from other reported algae. These analyses of immunology and phylogenetics indicated that this Fe-SOD is considerably homologous with SODs from lower prokaryotes (Fe-SOD or Mn-SOD) but not those from higher animals (Cu/Zn-SOD). In addition, the N. commune Fe-SOD shows 67 to 93% protein sequence identity to 10 other algal Fe-SODs (or Mn-SODs) and 69 to 93% gene sequence identity. Rare nonsynonymous substitutions imply that algal SODs are being subjected to strong natural selection. Interestingly,

the N. commune Fe-SOD enzyme molecule has a compact active center that is highly conserved (38.1% of residues are absolutely conserved), and 2 loose ends localized outside the molecule and inclined to mutate (only 11.5% of residues are absolutely conserved). Based on associative analyses of evolution, structure, and function, this special phenomenon is attributed to function-dependent evolution through negative natural selection. Under strong natural selection, although the mutation is random on the gene level, the exterior region is inclined to mutate on the protein level owing to more nonsynonymous substitutions in the exterior region, which demonstrates the theoretical feasibility of modifying Fe-SOD on its ends to overcome its disadvantages in clinical applications.

Future studies should longitudinally examine factors associated

Future studies should longitudinally examine factors associated

with transitioning across these subtypes BVD-523 datasheet to better inform prevention and treatment efforts. (C) 2011 Elsevier Ireland Ltd. All rights reserved.”
“Background: Sarcopenia has been attributed to a diminished muscle protein synthetic response to food intake. Differences in digestion and absorption kinetics of dietary protein, its amino acid composition, or both have been suggested to modulate postprandial muscle protein accretion.

Objective: The objective was to compare protein digestion and absorption kinetics and subsequent postprandial muscle protein accretion after ingestion of whey, casein, and casein hydrolysate in healthy older adults.

Design: A total of 48 older men aged 74 +/- 1 y (mean +/- SEM) were randomly assigned to ingest a meal-like amount (20 g) of intrinsically L-[1-(13)C]phenylalanine-labeled whey, casein, or casein hydrolysate. Protein ingestion was combined with continuous intravenous L-[ring-(2)H(5)]phenylalanine infusion to assess in vivo digestion and absorption kinetics of dietary protein.

Postprandial mixed muscle protein fractional synthetic rates (FSRs) were calculated from the ingested tracer.

Results: The peak appearance rate of dietary Luminespib supplier protein-derived phenylalanine in the circulation was greater with whey and casein hydrolysate than with casein (P < 0.05). FSR values were higher after whey (0.15 +/- 0.02%/h) than after check details casein (0.08 +/- 0.01%/h; P < 0.01) and casein hydrolysate (0.10 +/- 0.01%/h; P < 0.05) ingestion. A strong positive correlation (r = 0.66, P < 0.01) was observed between peak plasma leucine concentrations and postprandial

FSR values.

Conclusions: Whey protein stimulates postprandial muscle protein accretion more effectively than do casein and casein hydrolysate in older men. This effect is attributed to a combination of whey’s faster digestion and absorption kinetics and higher leucine content. This trial was registered at clinicaltrials.gov as NCT00557388. Am J Clin Nutr 2011;93:997-1005.”
“The mixed matrix membranes (MMMs) were developed from a composite of hydrophobic-hydrophilic NR-blend-PAA with zeolite 4A. A separation performance of the MMMs was investigated by performing the pervaporation dehydration of waterethanol mixtures. The results showed a dramatically greater flux of water than the ethanol flux indicating that the developed membranes were highly water-selective. Upon incorporating of zeolite 4A, the flux and separation factor were significantly improved. Increasing the water content in the waterethanol feed mixtures resulted in an increase in both water and ethanol fluxes leading to a decrease in water separation factor. Similarly a flux-separation factor trade-off was observed as raising feed temperature.

The thermal-wave field of an inhomogeneous cylindrical sample irr

The thermal-wave field of an inhomogeneous cylindrical sample irradiated with incident light of arbitrary angular and/or radial intensity

distribution was obtained using this theoretical model. Furthermore, experimental validation is also presented in the form of experimental results with steel cylinders of various diameters. (C) 2011 American Institute of Physics. [doi: 10.1063/1.3595674]“
“Background: Group B streptococcal (GBS) meningitis is diagnosed less frequently than in the 1970s and 1980s. There are few contemporary data regarding outcomes from GBS meningitis and factors that might predict an adverse outcome.

Methods: A retrospective evaluation was conducted of term and near-term infants (>= 36 weeks’ gestation) with GBS meningitis hospitalized at Texas Children’s Hospital from 1998 to Selleckchem MAPK Inhibitor Library 2006 to assess outcomes and to define features predictive of adverse outcomes.

Results:

Six infants had early-onset (<7 days) meningitis and 47 had late-onset (>= 7 days) GBS meningitis. Three infants died. Infants received broad-spectrum antibiotics initially and then penicillin (68%), ampicillin (28%), or cefotaxime (4%) for a mean of 21 (range, 15-44) days. Among survivors, 11 (22%) were neurologically impaired at hospital discharge with manifestations including persistent seizures (10), hypertonicity (9), and dysphagia (3). The 14 infants who died or had adverse outcomes at hospital discharge were more likely to present with SB-715992 purchase A-769662 seizures within hours of admission (P < 0.001), have coma or semicoma (P < 0.001), require pressor support (P = 0.001), and have an initial cerebrospinal fluid protein >= 300 mg/dL (P = 0.005) or glucose <20 mg/dL (P = 0.03) than were the 39 with infants with normal neurologic examinations. Seizures at admission remained a significant risk factor (P = 0.024) by multivariate analysis.

Conclusions:

Despite advances in intensive care, 26% of term and near-term infants with GBS meningitis die or have neurologic impairment at hospital discharge. Additional strategies to prevent GBS meningitis are needed.”
“People with severe cystic fibrosis (CF) lung disease with co-existent CF-associated liver disease (CFLD) are often excluded from consideration of sole lung transplantation, largely because of the concerns that they will subsequently develop hepatic decompensation. This retrospective cohort study aimed at determining whether patients with severe cirrhosis caused by CFLD have any differences in perioperative and relevant post-transplant outcomes compared to CF patients without CFLD when undergoing sole lung transplantation. Six patients with CFLD were matched with 18 CF patients without CFLD undergoing sole lung transplant at the same institution. There were no differences in total operative time or intra-operative requirements for cardiopulmonary bypass or blood products.

There was a significant decrease (p < 0 05) in pain, from a me

There was a significant decrease (p < 0.05) in pain, from a mean of 6 points (range, 5 to 8 points) preoperatively to a mean of 1 point (range, 0 to 2 points) postoperatively. The mean Lower

Extremity Functional Scale score improved from 37 points initially (range, 24 to 52 points) to 65 points (range, 31 to 75 points; p < 0.05) at the time of final follow-up. The mean postoperative American Orthopaedic Foot & Ankle Society ankle-hindfoot score was find more 84 points. The mean Short Musculoskeletal Function Assessment dysfunction index score was 13.3 points and the mean bother index score was 14.3 points. Radiographic lucencies at the graft-host interface were seen in five patients. Four patients required an additional surgical procedure. No patients needed to undergo subsequent

H 89 arthrodesis or arthroplasty.

Conclusions: These midterm results in a small group of patients indicate that structural fresh-frozen allograft transplantation can be a successful surgical option in the treatment of large osteochondral defects of the talar shoulder.”
“Purpose: Angiogenesis appears to be a prominent feature of many hematological disorders, particularly in multiple myeloma (MM). Progression in MM also involves secretion of the metaloproteinases (MMPs). In this study, the expression of vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF) and its receptor, in bone marrow trephine biopsy (TB) of thirty six MM patients before and after the treatment or during progression was examined. The MMP-2 secretion was assessed from the same patients.

Material/Methods: Immunohistochemical staining of bone marrow specimens for angiogenic factors and microvessel density (MVD) and bone marrow aspirates for Western blot analysis of MMP-2 expression was performed.

Results: In active, untreated MM patients, we found statistically significant differences in the expression of angiogenic factors according to the patients after the anti-angiogenic treatment. We found statistical differences

of the expression of angiogenic factors between the group of patients with a response after the treatment and the patients who Ricolinostat had progression during the treatment. The data showed statistically significant decreased MVD after the treatment. The results showed statistically significant differences between initial secretion of MMP-2 in active, untreated MM patients and patients with a response after the treatment and patients with progression during the treatment.

Conclusions: We showed that not only decreased expression of angiogenic cytokines is present after the anti-angiogenic treatment but also activity of MMP-2 in MM patients who responded to the treatment. Combination therapy with the inhibition of the activity of MMPs could represent an interesting therapeutical approach in MM.

Preliminary phytochemical tests

were done The ALE showed

Preliminary phytochemical tests

were done. The ALE showed presence of alkaloids, flavonoides, carbohydrates, tannins and steroids, while carbohydrates, flavonoides, alkaloids were present with AQE. The PEE, CHE, ALE did not produce any mortality. Carbon tetrachloride produced significant changes in biochemical parameters (increases in serum glutamate pyruvate transaminase (SGPT), Serum glutamate oxaloacetate transaminase (SGOT), alanine phosphatase (ALP) and serum bilirubin.) and histological (damage to hepatocytes) using Standard drug Liv-52. Pretreatment with ALE and AQE extracts significantly prevented the biochemical and histological changes induced by CCl(4) in the liver. The present study shows that the ALE and AQE VEGFR inhibitor extracts possessed hepatoprotective activity.”
“Study Design. Prospective observational cohort study.

Objective. To define the utility of the revised Tokuhashi score in relation to predicting survival in patients with spinal metastases regardless of the treatment

pathway.

Summary of Background Data. The revised Tokuhashi score has been used for the prediction of survival. In this scoring system, however, all the patients were sourced by orthopedic surgeons, and asymptomatic patients were excluded. That might present a significant source of patient selection bias. The treatment plan was also affected by the predicted survival in their system.

Methods. All patients within 2 years of diagnosis of spinal metastases, whether symptomatic were recruited. Minimum 1-year follow-up

was required. During the study period, PX-478 in vitro a total of 85 patients were analyzed including 44 patients who died within 1 year. The relation between the revised Tokuhashi score and survival were analyzed using the Cox proportional hazard model and Spearman’s rank correlation coefficient.

Results. The mean age was 60.3 years (range: 35-84) and the median survival was 11.6 months. On multivariate analysis, lower performance status (Karnofsky performance status, 50%-70%) and unresectable organ metastases were significantly AZD5582 associated with poor survival, with hazard ratios of 2.92 and 4.44, respectively. In primary cancer type, lung and kidney cancer were also significantly associated with poor survival, with hazard ratios of 4.25 and 2.60, respectively. The revised Tokuhashi score groups were significantly correlated with the survival groups (rho = 0.530, P < 0.001). In 67 (79%) of 85 patients, actual survival matched the predicted survival.

Conclusion. Lower score on performance status, the existence of organ metastases, and primary cancer of the lung and the kidney were significantly associated with poor survival. The revised Tokuhashi score was found to be very useful to predict survival regardless of the treatment pathway.

At 2-year angiography, the in-stent late loss of 0 48 mm (SD 0 28

At 2-year angiography, the in-stent late loss of 0.48 mm (SD 0.28) and the diameter stenosis of 27% (11) did not differ from the findings at 6 months. The luminal area enlargement on OCT and intravascular ultrasound between 6 months and 2 years was due to a decrease in plaque size without change in vessel size. At 2 years, 34.5% of strut locations presented no

discernible features by OCT, confirming decreases in echogenicity and in radiofrequency backscattering; the remaining apparent struts selleckchem were fully apposed. Additionally, vasomotion occurred at the stented site and adjacent coronary artery in response to vasoactive agents.

Interpretation At 2 years after implantation the stent was bioabsorbed, had vasomotion restored and restenosis prevented, and was clinically safe,

suggesting freedom from late thrombosis. Late luminal enlargement due to plaque reduction without vessel remodelling needs confirmation.”
“Background Over the past 20 years, percutaneous transluminal balloon coronary angioplasty (PTCA), bare-metal stents (BMS), and drug-eluting stents (DES) succeeded each other as catheter-based treatments for coronary artery disease. We undertook a systematic overview of randomised trials comparing Defactinib manufacturer these interventions with each other and with medical therapy in patients with non-acute coronary artery disease.

Methods We searched Medline for trials contrasting at least two of the four interventions (PTCA, BMS, DES, and medical therapy). check details Eligible outcomes were death, myocardial infarction, coronary

artery bypass grafting, target lesion or vessel revascularisation, and any revascularisation. Random effects meta-analyses summarised head-to-head (direct) comparisons, and network meta-analyses integrated direct and indirect evidence.

Findings 61 eligible trials (25388 patients) investigated four of six possible comparisons between the four interventions; no trials directly compared DES with medical therapy or PTCA. In all direct or indirect comparisons, succeeding advancements in percutaneous coronary intervention did not produce detectable improvements in deaths or myocardial infarction. The risk ratio (RR) for indirect comparisons between DES and medical therapy was 0.96 (95% CI 0.60-1-52) for death and 1.15 (0.73-1.82) for myocardial infarction. By contrast, we recorded sequential significant reductions in target lesion or vessel revascularisation with BMS compared with PTCA (RR 0.68 [0-60.0.77]) and with DES compared with BMS (0.44 [0.35-0.56]). The RR for the indirect comparison between DES and PTCA for target lesion or vessel revascularisation was 0.30 (0.17-0.51).

Interpretation Sequential innovations in the catheter-based treatment of non-acute coronary artery disease showed no evidence of an effect on death or myocardial infarction when compared with medical therapy.