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1.
Pharmacogenomics J ; 15(1): 20-5, 2015 Feb.
Article in English | MEDLINE | ID: mdl-25001880

ABSTRACT

We examined clinical outcomes with proton pump inhibitors (PPI) use within CYP2C19 genotype groups during clopidogrel treatment following acute myocardial infarction (AMI). 2062 patients were genotyped for CYP2C19*2 and *17 variants in TRIUMPH. 12 month clinical outcomes were analyzed among patients discharged on clopidogrel within CYP2C19*2 carrier, CYP2C19*17 carrier, and CYP2C19*1 homozygote genotype groups. PPI use was not associated with a difference in mortality. Among clopidogrel-treated Caucasians following AMI, PPI use was associated with a significantly higher rate of cardiac rehospitalization (HR 1.62, 95% CI 1.19-2.19; P=0.002) compared with no PPI use. PPI users who were carriers of the CYP2C19*17 variant experienced significantly higher rates of cardiac rehospitalization (HR 2.05, 95% CI 1.26-3.33; P=0.003), carriers of the CYP2C19*2 variant had a trend toward increased 1-year cardiac rehospitalization (HR 1.69, 95% CI 0.95-2.99; P=0.07), while no significant differences were observed among CYP2C19*1 homozygotes. These results indicate that the risks associated with PPI use among clopidogrel-treated Caucasian post-MI patients are impacted by CYP2C19 genotype, and suggest knowledge of genotype may be useful for personalizing PPI use among patients following AMI to reduce rehospitalization.


Subject(s)
Cytochrome P-450 CYP2C19/genetics , Genotype , Myocardial Infarction/drug therapy , Myocardial Infarction/genetics , Proton Pump Inhibitors/therapeutic use , Ticlopidine/analogs & derivatives , Adult , Aged , Clopidogrel , Female , Humans , Male , Middle Aged , Myocardial Infarction/diagnosis , Prospective Studies , Ticlopidine/therapeutic use , Treatment Outcome
2.
J Anim Sci ; 90(6): 1788-97, 2012 Jun.
Article in English | MEDLINE | ID: mdl-22205667

ABSTRACT

Lambing interval is a relevant reproductive indicator for sheep populations under continuous mating systems, although there is a shortage of selection programs accounting for this trait in the sheep industry. Both the historical assumption of small genetic background and its unorthodox distribution pattern have limited its implementation as a breeding objective. In this manuscript, statistical performances of 3 alternative parametrizations [i.e., symmetric Gaussian mixed linear (GML) model, skew-Gaussian mixed linear (SGML) model, and piecewise Weibull proportional hazard (PWPH) model] have been compared to elucidate the preferred methodology to handle lambing interval data. More specifically, flock-by-flock analyses were performed on 31,986 lambing interval records (257.3 ± 0.2 d) from 6 purebred Ripollesa flocks. Model performances were compared in terms of deviance information criterion (DIC) and Bayes factor (BF). For all flocks, PWPH models were clearly preferred; they generated a reduction of 1,900 or more DIC units and provided BF estimates larger than 100 (i.e., PWPH models against linear models). These differences were reduced when comparing PWPH models with different number of change points for the baseline hazard function. In 4 flocks, only 2 change points were required to minimize the DIC, whereas 4 and 6 change points were needed for the 2 remaining flocks. These differences demonstrated a remarkable degree of heterogeneity across sheep flocks that must be properly accounted for in genetic evaluation models to avoid statistical biases and suboptimal genetic trends. Within this context, all 6 Ripollesa flocks revealed substantial genetic background for lambing interval with heritabilities ranging between 0.13 and 0.19. This study provides the first evidence of the suitability of PWPH models for lambing interval analysis, clearly discarding previous parametrizations focused on mixed linear models.


Subject(s)
Pregnancy, Animal , Sheep/genetics , Sheep/physiology , Animals , Bayes Theorem , Female , Linear Models , Male , Models, Biological , Pregnancy , Pregnancy, Animal/physiology , Proportional Hazards Models , Selection, Genetic
4.
J Anim Sci ; 85(3): 592-7, 2007 Mar.
Article in English | MEDLINE | ID: mdl-17060422

ABSTRACT

The objective of this study was to analyze the association between the haplotypes of the prion protein (PrP) locus and several reproductive and lamb weight traits in Ripollesa sheep. Prion protein genotypes were available for a total of 310 sheep (7 rams, 114 ewes, and 189 lambs), all of them belonging to the purebred Ripollesa flock of the Universitat Autònoma of Barcelona, for which all sheep had a known pedigree. In addition, the genotype of 24 historical descendants of the previously genotyped adult individuals was reconstructed, provided that both parents were homozygous for PrP haplotypes. Only 3 haplotypes (ARR, ARQ, and ARH) were observed in the PrP locus of the sheep sampled. Reproductive traits included conception rate and litter size, whereas birth BW and 90-d BW were the lamb weight traits studied. The additive effect of PrP haplotypes was analyzed through Bayesian animal threshold and linear models, for reproduction and weight traits, respectively. Ewe reproductive data belonged to 89 ewes that gave 492 conception rate records and 440 litter size records. Analyses of BW at birth and at 90 d of age were made on 323 and 164 lamb records, respectively. No associations between PrP haplotypes and conception rate and BW traits were observed. For litter size, the effect of the ARH haplotype was greater than that of the ARQ haplotype. Differences between ARH and ARR haplotypes also suggested an advantage for the ARH. As a whole, our results indicated that the selection favorable to increase litter size in Ripollesa ewes may also increase the ARH haplotype frequency, which contradicts the recommendations of the current European Union legislation aiming to increase the genetic resistance to scrapie. As a consequence, scrapie genotyping needs to be included as a new selection criterion in the breed.


Subject(s)
Body Weight/genetics , Prions/genetics , Reproduction/genetics , Sheep/growth & development , Sheep/genetics , Animals , Female , Genotype , Haplotypes , Male
5.
Clin Nephrol ; 64(2): 129-37, 2005 Aug.
Article in English | MEDLINE | ID: mdl-16114789

ABSTRACT

BACKGROUND: Several effects of hemodialysis, including hemoconcentration, alterations of hemostasis or hemorheology and endothelial activation, could potentially interfere with cerebral blood flow (CBF) regulation. These treatment-specific changes may also be crucial for the enhanced incidence of stroke in uremic patients. Nevertheless, the influence of hemodialysis on CBF has not been yet adequately studied. PATIENTS AND METHODS: We registered mean blood flow velocity (MFV) in the middle cerebral artery (MCA) during hemodialysis treatment in order to evaluate its contribution on CBF changes. Transcranial Doppler ultrasonography (TCD) of the MCA was performed continuously during hemodialysis treatment in 18 stable patients (10 males and 8 females, mean age 62 +/- 11 years) with end-stage renal disease of various origin. Blood pressure (mmHg), heart rate (/min), ultrafiltration volume (ml), BV changes (deltaBV by hemoglobinometry, %), arterial blood gases (pO2, blood oxygen content, pCO2), hemostasis activation (thrombin-antithrombin III complex, ELISA) and fibrinogen (Clauss) were measured simultaneously at the beginning of treatment and every hour thereafter. RESULTS: Before the hemodialysis session the MFV in the MCA was within normal range (57.5 +/- 13.0 cm/s, ref. 60 +/- 12) and was mainly dependent on the patients' age (r = -0.697, p < 0.01). The blood flow velocity in the MCA decreased significantly from 57.5 +/- 13.0 cm/s before the beginning to 48.3 +/- 11.1 cm/s after four hours (n = 18, p < 0.05) and to 43.9 +/- 8.9 cm/s after five hours (n = 9, p < 0.05) of hemodialysis treatment. During hemodialysis treatment, the percentual changes of MFV in the MCA (delta%MFV) were interrelated to the ultrafiltration volume (r = -0.486, p < 0.01), the blood volume (BV%, r = 0.369, p < 0.01) and the percentual changes of the hematocrit (r = -0.358, p < 0.01), of the arterial blood oxygen content (delta%acO2, r = -0.420, p < 0.01) and of the plasma fibrinogen levels (delta%fibrinogen, r = 0.244, p < 0.05). CONCLUSION: A significant continuous decrease of the MFV in the MCA was observed during hemodialysis treatment, which inversely correlated both with ultrafiltration volume, BV changes and changes of plasma fibrinogen. The ultrafiltration-induced hemoconcentration with concomitant rise of hematocrit and oxygen transport capacity, may partly explain the alterations in the cerebral MFV observed during hemodialysis.


Subject(s)
Blood Flow Velocity/physiology , Middle Cerebral Artery/physiopathology , Renal Dialysis/adverse effects , Cerebrovascular Circulation , Female , Humans , Male , Middle Aged , Middle Cerebral Artery/diagnostic imaging , Regression Analysis , Statistics, Nonparametric , Ultrasonography, Doppler, Transcranial
6.
Anaesthesia ; 58(5): 444-7, 2003 May.
Article in English | MEDLINE | ID: mdl-12694000

ABSTRACT

In spite of the much shorter thawing times, the use of microwave devices for heating units of fresh frozen plasma is still being discussed. Concerns about general and localised overheating are the main arguments against the use of microwave devices. We evaluated the warming of fresh frozen plasma using the recently introduced Transfusio-therm 2000(R) microwave blood warmer. Units of fresh frozen plasma were weighed and the heating times were recorded. The surface temperature of the fresh frozen plasma bags during heating was recorded every 10 s. Temperature variation on the surface was examined by measuring the difference between peripheral and centrally placed temperature sensors. After heating, plasma temperature was determined using a calibrated thermometer. There were no signs of overheating during the heating process. The surface temperature of three units of fresh frozen plasma heated simultaneously (n = 45) was 34.0 degrees C (SD, 1.5 degrees C) after a mean heating time of 23.2 min (SD, 1.1 min). The mean (SD) temperature difference was -0.6 (0.5) degrees C and the mean (SD) plasma temperature was 33.6 (0.8) degrees C. Heating one fresh frozen plasma unit at a time (n = 20), the mean (SD) heating time was 6.3 (0.4) min. The surface temperature after heating was 34.3 (0.2) degrees C, the mean (SD) temperature difference was -0.6 (0.4) degrees C and the mean (SD) plasma temperature after heating 33.1 (0.6) degrees C. We conclude that no general or localised overheating of fresh frozen plasma occurs during or after heating with the microwave blood warmer.


Subject(s)
Blood Preservation/methods , Heating/instrumentation , Microwaves , Plasma , Cryopreservation , Humans , Temperature
7.
Allergol Immunopathol (Madr) ; 31(2): 83-6, 2003.
Article in English | MEDLINE | ID: mdl-12646123

ABSTRACT

UNLABELLED: Infections and malnutrition remain the main causes of infant mortality in developing countries. In protein-calorie malnutrition, immunologic responses are affected, which often facilitates infections. However, the presence of asthma and allergic rhinitis are not commonly recognized in malnourished individuals. The aim of this study was to evaluate serum IgE values in children with primary moderate protein-calorie malnutrition. METHODS: The level of IgE in peripheral blood of 18 children between 2 and 4 old with moderate protein-calorie malnutrition and without associated parasitic infestation was compared with that of 15 well nourished children of similar age. IgE serum levels were measured by an immunoenzymatic method. RESULTS: The median level of serum IgE in malnourished children was 69.30 ng/ml while the control group showed a mean level of 95.97 ng/ml. This difference was significant (p < 0.01). CONCLUSION: Malnourished children show decreased serum IgE levels. This might be one of the adaptive mechanisms of malnutrition employed in an attempt to use energy and protein reserves for growth and other functions. Our results are coherent with the decrease in IgE mediated reactions in malnourished patients.


Subject(s)
Dysgammaglobulinemia/etiology , Immunoglobulin E/deficiency , Protein-Energy Malnutrition/complications , Brazil , Child, Preschool , Female , Humans , Immunoglobulin E/blood , Male , Protein-Energy Malnutrition/blood , Protein-Energy Malnutrition/immunology
8.
Allergol. immunopatol ; 31(2): 83-86, mar. 2003.
Article in En | IBECS | ID: ibc-21354

ABSTRACT

Infections and malnutrition remain the main causes of infant mortality in developing countries. In protein-calorie malnutrition, immunologic responses are affected, which often facilitates infections. However, the presence of asthma and allergic rhinitis are not commonly recognized in malnourished individuals. The aim of this study was to evaluate serum IgE values in children with primary moderate protein-calorie malnutrition. Methods: The level of IgE in peripheral blood of 18 children between 2 and 4 old with moderate protein-calorie malnutrition and without associated parasitic infestation was compared with that of 15 well nourished children of similar age. IgE serum levels were measured by an immunoenzymatic method. Results: The median level of serum IgE in malnourished children was 69.30 ng/ml while the control group showed a mean level of 95.97 ng/ml. This difference was significant (p < 0.01). Conclusion: Malnourished children show decreased serum IgE levels. This might be one of the adaptive mechanisms of malnutrition employed in an attempt to use energy and protein reserves for growth and other functions. Our results are coherent with the decrease in IgE mediated reactions in malnourished patients (AU)


Las infecciones y la malnutrición siguen siendo las causas principales de la mortalidad infantil en los países en desarrollo. En la malnutrición calórico-proteica las respuestas inmunitarias suelen estar afectadas, lo que a menudo facilita las infecciones. Sin embargo, habitualmente no se reconoce la presencia de asma y rinitis alérgica en los sujetos malnutridos. El objetivo de este estudio fue determinar los valores séricos de IgE en niños con malnutrición proteico-calórica moderada primaria. Métodos: En sangre periférica se comparó el nivel de IgE de 18 niños de 2 a 4 años de edad con malnutrición proteico-calórica moderada y sin infestación parasitaria asociada, con la de 15 niños bien nutridos de edad similar. Las concentraciones séricas de IgE se determinaron mediante un método inmunoenzimático. Resultados: La mediana de la concentración sérica de IgE de los niños malnutridos fue de 69,30 ng/ml, mientras que el grupo de control presentó un valor medio de 95,97 ng/ml, lo que se considera una disminución significativa (p < 0,01).Conclusión: El contenido de IgE sérica de los niños malnutridos es bajo. Éste podría ser uno de los mecanismos de adaptación de la malnutrición en un intento de utilizar la energía y las reservas de proteínas para el crecimiento y otras funciones. Nuestros resultados son coherentes con la disminución de las reacciones mediadas por IgE en los pacientes malnutridos (AU)


Subject(s)
Child, Preschool , Male , Female , Humans , Protein-Energy Malnutrition , Brazil , Dysgammaglobulinemia , Immunoglobulin E
9.
Rev. bras. cancerol ; 48(2): 247-251, abr.-jun. 2002. ilus
Article in English | LILACS | ID: lil-429434

ABSTRACT

Apresentamos um caso raro de hemangioma esplênico em um recém-nascido do sexo feminino, apresentando-se como massa abdominal, coagulopatia e trombocitopenia. No ato operatório observou-se uma massa tumoral vascular do pólo inferior do baço. A paciente encontra-se em acompanhamento ambulatorial. O diagnóstico e as opções de tratamento foram revistas e discutidas. Os autores revisaram a literatura sobre hemangioma esplênico em recém-nascidos e observaram ser este o terceiro caso de associação entre hemangioma esplênico e Síndrome de Kasabach-Merritt. O hemangioma esplênico é uma doença rara no diagnóstico diferencial das massas abdominais em recém-nascidos. O hemangioma é a neoplasia benigna mais freqüente do baço. A anemia, a trombocitopenia e a coagulopatia são vistos com freqüência em hemangiomas cavernosos grandes associados à Síndrome de Kasabach-Merritt (KMS). O hemangioma cavernoso esplênico associado com esta síndrome é extremamente raro.


Subject(s)
Humans , Female , Infant, Newborn , Hemangioma , Splenic Neoplasms/diagnosis , Splenic Neoplasms/pathology , Splenic Neoplasms/therapy , Diagnosis, Differential
10.
Mycotoxin Res ; 18 Suppl 2: 113-6, 2002 Jun.
Article in German | MEDLINE | ID: mdl-23606143

ABSTRACT

Tests with various clean-up materials after optimisation of different parameters showed that the use of Oasis® material resulted in matrixless chromatograms in HPLC-FLD. The selectivity and detection limit of the method was improved by using LC-MS/MS as the detection system. Mean recovery was 100%, and no negative food matrix effects could be observed.

13.
Biomed Tech (Berl) ; 46(7-8): 200-6, 2001.
Article in English | MEDLINE | ID: mdl-11552501

ABSTRACT

The stent to be examined (Wiktor-Stent, Medtronic ESTC, Kerkrade, NL) was mounted into a closed-loop tubular-system and perfused with platelet-rich plasma (PRP). As controls the tubular-system without stent (as non-thrombogenic control) and secondly the tube filled with glassbeads (as thrombogenic control) were evaluated. A decrease in the number of singularly circulating thrombocytes correlated well with an increases in circulating platelet aggregates. The increasing activation of thrombocytes was demonstrated by immunolabelling of surface structures (CD 62) which become prominent on activation of thrombocytes. The increase in case of the non-thrombogenic controls is thought to be due to the action of the roller-pump. This increase was coincident with an increase in immunologically labelled GPIIb/IIIa receptors and well correlated with an increase in platelet activation as demonstrated by the elevated CD 62 label. In spite of the use of anticoagulation principles in the perfusion model, thrombin was generated (measured by the TAT-complex) in all three cases and the completed coagulation (measured by the occurrence of fibrin D-dimers) also happened. The amount of D-dimers was small, however, in the cases of non-thrombogenic controls and of tubes equipped with stents. Only after the contact of PRP with tubes filled with glass-beads a significant increase in D-dimers followed. In conclusion the implantation of a stent led to an activation, adherence and aggregation of thrombocytes to a somewhat greater extent as in the control-system. It has, however, a much less thrombogenic surface than glass-beads.


Subject(s)
Angioplasty, Balloon, Coronary/instrumentation , Materials Testing , Platelet Activation/physiology , Platelet Aggregation/physiology , Stents , Thrombosis/blood , Adult , Female , Fibrin Fibrinogen Degradation Products/metabolism , Humans , Male , Models, Cardiovascular , Thrombin/metabolism
14.
Catheter Cardiovasc Interv ; 54(1): 77-82, 2001 Sep.
Article in English | MEDLINE | ID: mdl-11553954

ABSTRACT

Dyspnea and arterial desaturation on upright position in elderly subjects is described as platypnea-orthodeoxia syndrome (POS) and in some patients it is due to right-to-left shunt across the atrial septal defect (ASD)/patent foramen ovale (PFO). Surgical closure of ASD/PFO has been the only available treatment option. Buttoned device has been used for occlusion of ostium secundum ASD, PFO associated with presumed paradoxical embolism and cerebrovascular accidents and ASD/PFO in association with other congenital heart defects causing right-to-left shunt. The objective of this article is to describe the use of buttoned device in effectively occluding ASD/PFO to relieve hypoxemia of POS. During a 4-year period ending January 2000, 10 patients, ages 71 +/- 9 (range 60-83) years with POS underwent buttoned device closure of their ASD/PFO. Echocardiographic and balloon-stretched atrial defect sizes were 8 +/- 3 mm and 12 +/- 3 mm, respectively. The ASD/PFO were occluded with devices ranging in size from 25 to 40 mm delivered via 9 French, long, blue Cook sheaths; eight had an additional 25- or 35-mm occluder placed on the right atrial side. The oxygen saturation increased (P < 0.001) from 76 +/- 7% (range 69-86%) to 95 +/- 2% (range 92-98%). No complications were encountered. Relief of symptoms was seen in all patients. Follow-up of 1-36 months (median 12 months) revealed persistent improvement of symptoms. Buttoned device occlusion of ASD/PFO to relieve hypoxemia of POS is feasible, safe, and effective and is an excellent alternative to surgery. Cathet Cardiovasc Intervent 2001;54:77-82.


Subject(s)
Balloon Occlusion , Dyspnea/therapy , Heart Septal Defects, Atrial/therapy , Hypoxia/therapy , Prostheses and Implants , Prosthesis Implantation , Aged , Aged, 80 and over , Coronary Angiography , Dyspnea/diagnostic imaging , Dyspnea/etiology , Female , Heart Septal Defects, Atrial/complications , Heart Septal Defects, Atrial/diagnostic imaging , Humans , Hypoxia/diagnostic imaging , Hypoxia/etiology , Male , Middle Aged
15.
Int J Artif Organs ; 24(6): 367-73, 2001 Jun.
Article in English | MEDLINE | ID: mdl-11482502

ABSTRACT

The correction of anemia with human recombinant erythropoietin (rHuEPO) in end stage renal disease is associated with hypertension in about one third of hemodialysis patients. The pathogenesis of the rHuEPO-induced hypertension is still uncertain, though evidence of the involvement of endothelial cells has emerged. The aim of this study was to determine plasma endothelin-1 during hemodialysis and to compare the endothelin-1 levels in hemodialysis patients with and without rHuEPO substitution. Nineteen stable patients (13 male and 6 female, mean age 62 +/- 11 years) with end stage renal disease were studied. Cuprophan dialysers (GFS 12, Gambro, Lund, Sweden) were used for hemodialysis in all cases. rHuEPO (40 U/kg s.c.) was administered to 10 patients. Blood pressure (BP; RR mmHg) and blood volume changes (deltaBV; hemoglobinometry %) were serially measured. Samples were taken before and every hour during hemodialysis. Plasma endothelin-1 was measured by ELISA (R&D Systems, Minneapolis, USA) and corrected for hemoconcentration. Endothelin-1 concentration was elevated before commencement of hemodialysis (1.16 +/- 0.36 pg/ml) when compared to healthy controls (ref. 0.3-0.9) and increased to 1.47 +/- 0.51 pg/ml by the end of the session (p<0.05). In patients under rHuEPO-substitution plasma endothelin-1 was higher when compared to patients without substitution before (1.25 +/- 0.3 vs. 1.05 +/- 0.3 pg/ml) and at the end of HD (1.62 +/- 0.5 vs. 1.28 +/- 0.3 pg/ml, p<0.05). There was no difference in BP and deltaBV between the two groups during treatment. Plasma endothelin-1 was higher in hemodialysis patients and there was a continuous rise in plasma endothelin-1 during a session. Comparison of two groups of hemodialysis patients with and without s.c. rHuEPO-replacement treatment revealed a significantly higher plasma endothelin-1 concentration in patients with s.c. rHuEPO treatment. However, the elevated endothelin-1 levels were not accompanied by arterial hypertension.


Subject(s)
Endothelin-1/blood , Erythropoietin/pharmacology , Kidney Failure, Chronic/blood , Anemia/drug therapy , Anemia/etiology , Case-Control Studies , Enzyme-Linked Immunosorbent Assay , Female , Humans , Hypertension/chemically induced , Hypertension/physiopathology , Kidney Failure, Chronic/complications , Kidney Failure, Chronic/therapy , Male , Middle Aged , Recombinant Proteins , Renal Dialysis , Statistics, Nonparametric
16.
J Am Coll Cardiol ; 38(1): 136-42, 2001 Jul.
Article in English | MEDLINE | ID: mdl-11451263

ABSTRACT

OBJECTIVE: The objective of this study was to evaluate the American College of Cardiology/American Heart Association (ACC/AHA) guidelines for exercise testing (EXT) after successful coronary revascularization (CR) using the Bypass Angioplasty Revascularization Investigation experience. BACKGROUND: The ACC/AHA guidelines state that EXT within three years of successful CR is not useful. METHODS: The 1,678 patients randomized to CR by either angioplasty or bypass surgery were required to take symptom-limited treadmill tests one, three and five years after revascularization. RESULTS: Patients who took the test at each specified time had a much lower subsequent two-year mortality than those who did not (1.9% vs. 9.4%, 3.5% vs. 12.6% and 3.3% vs. 11.0% at one, three and five years, respectively, after CR [p < 0.0001 for each]). Exercise parameters at the one- and three-year test did not improve a multivariable model of survival after including clinical parameters. Exercising to Bruce stage 3 or generating a Duke score >-6 were independently predictive of two-year survival after the five-year test. ST depression on the one-year test was associated with more revascularizations (relative risk = 1.6; p < 0.001). CONCLUSIONS: Patients with stable multivessel coronary disease who took a protocol-mandated exercise test at one, three and five years after revascularization were at low risk for mortality in the two years subsequent to each test. Exercise parameters did not improve prediction of mortality in the two years after the one- and three-year tests. The ACC/AHA guidelines on exercise testing after CR (no value for routine testing in stable patients for three years after revascularization) are supported by these results.


Subject(s)
Angioplasty, Balloon, Coronary , Coronary Artery Bypass , Coronary Disease/epidemiology , Exercise Test , Coronary Disease/mortality , Diabetic Angiopathies/epidemiology , Female , Humans , Male , Middle Aged , Multivariate Analysis , Practice Guidelines as Topic , Prognosis , Risk Assessment
17.
J Am Chem Soc ; 123(29): 7134-45, 2001 Jul 25.
Article in English | MEDLINE | ID: mdl-11459494

ABSTRACT

High-level ab initio calculations (B3LYP/6-31+G and QCISD(T)/6-311+G**) were carried out to resolve the disagreement between recent experimental and computational estimates of the relative strength of the intramolecular hydrogen bond in Z-hydrogen maleate anion with respect to the normal hydrogen bond in maleic acid. The computational estimates for the strength of the intramolecular hydrogen bond in the gas-phase maleate anion are in a range of 14-28 kcal/mol depending on the choice of the reference structure. Computational data suggest that the electrostatic influence of a counterion such as a tetraalkylammonium cation can considerably weaken the hydrogen bonding interaction (by 1.5-2 times) in the complexed hydrogen maleate anion relative to that in the naked anion. The estimated internal H-bonding energies for a series of Z-maleate/R4N+ salts (R = CH3, C2H5, CH3CH2CH2CH2) range from 8 to 13 kcal/mol. The calculated energy differences between the E- and Z-hydrogen maleates complexed to Me4N+, Et4N+, and Bu4N+ cation are 4.9 (B3LYP/6-31+G(d,p)) and 5.7 and 5.8 kcal/mol (B3LYP/6-31G(d)). It is also demonstrated that the sodium cation exerts a similar electrostatic influence on the hydrogen bond strength in bifluoride anion (FHF-). The present study shows that while low-barrier short hydrogen bonds can exist in the gas phase (the barrier for the hydrogen transfer in maleate anion is only 0.2 kcal/mol at the QCISD(T)/6-311+G//QCISD/6-31+G level), whether they can also be strong in condensed media or not depends on how their interactions with their immediate environment affect their strength.


Subject(s)
Maleates/chemistry , Quaternary Ammonium Compounds/chemistry , Enzyme Inhibitors/chemistry , Fumarates/chemistry , Hydrogen Bonding , Models, Molecular , Molecular Conformation , Molecular Structure , Thermodynamics
18.
Catheter Cardiovasc Interv ; 53(2): 193-201, 2001 Jun.
Article in English | MEDLINE | ID: mdl-11387603

ABSTRACT

To compare relative coronary artery vasodilator reserve (rCVR = CVRtarget/CVRreference) to myocardial perfusion stress imaging, 48 patients with coronary artery stenoses (61% +/- 16%; mean, +/- SD; range, 30%-91%) had measurements of target and reference vessel CVR (Doppler-tipped guidewire). rCVR was computed and compared to stress 201thallium or (99m)technetium-sestamibi myocardial tomography. Compared to 24 patients with negative stress imaging studies, 24 patients with positive stress studies had angiographically more severe stenoses (74% +/- 13% vs. 44% +/- 24%; P = 0.0005) with lower CVR(target) (1.68 +/- 0.55 vs. 2.46 +/- 0.74; P = 0.002) and lower rCVR (0.72 +/- 0.22 vs. 1.0 +/- 0.26; P < 0.003). Based on receiver-operator characteristic (ROC) cut points (CVR > 1.9; rCVR > 0.75), compared to CVR, rCVR had similar agreement (Kappa 0.54 vs. 0.50), sensitivity (63% vs. 71%), specificity (88% vs. 83%), and positive predictive value (83% vs. 81%) with myocardial perfusion tomography. A concordant CVRtarget/rCVR only slightly increased sensitivity, specificity, and positive predictive values (77%, 90%, and 87%, respectively). Although rCVR, like CVR, correlates with stress myocardial perfusion imaging results, rCVR did not have significant incremental prognostic value over CVR alone for myocardial perfusion imaging. However, rCVR does provide additional information regarding the status of the microcirculation in patients with coronary artery disease and complements the CVR for lesion assessment.


Subject(s)
Blood Flow Velocity/physiology , Coronary Disease/physiopathology , Perfusion , Adult , Aged , Coronary Disease/diagnostic imaging , Coronary Vessels/diagnostic imaging , Coronary Vessels/physiopathology , Exercise Test/methods , Female , Heart/diagnostic imaging , Humans , Linear Models , Male , Middle Aged , Predictive Value of Tests , Prevalence , ROC Curve , Sensitivity and Specificity , Tomography, Emission-Computed, Single-Photon
19.
J Am Chem Soc ; 123(24): 5787-93, 2001 Jun 20.
Article in English | MEDLINE | ID: mdl-11403613

ABSTRACT

A high-level computational study using CCSD, CCSD(T), and G2(+) levels of theory has shown that unactivated vinyl substrates such as vinyl chloride would afford gas phase, single-step halide exchange by a pure in-plane sigma-approach of the nucleophile to the backside of the C--Cl sigma bond. Geometry optimization by CCSD/6-31+G* and CCSD(T)/6-31+G* confirms the earlier findings of Glukhovtsev, Pross, and Radom that the S(N)2 reaction of Cl(-) with unactivated vinyl chloride in the gas phase occurs by a sigma attack. Complexation of vinyl chloride with Na(+) does not alter this in-plane sigma preference. However, moderately activated dihaloethylenes such as 1-chloro-1-fluoroethylene undergo gas-phase S(N)2 attack by the accepted pi-route where the nucleophile approaches perpendicular to the plane of the C==C. In the latter case a single-step pi pathway is preferred for the Cl(-) + H(2)C==CFCl reaction. This is the first definitive example at a high level of theory where a single-step pi nucleophilic vinylic substitution is preferred over a multistep mechanism in the gas phase. The activation barriers for these gas-phase single-step sigma- and pi-processes involving both naked anions and Na(+) complexes are, however, prohibitively high. Solvation and the presence of a counterion must play a dominant role in nucleophilic vinylic substitution reactions that proceed so readily in the condensed phase. In solution, nucleophilic vinylic substitution reactions involving electron-withdrawing groups on the carbon--carbon double bond (e.g., -CN, -CHO, and -NO(2)) would almost certainly proceed via a free discrete carbanionic intermediate in accord with experiment.

20.
Clin Hemorheol Microcirc ; 24(2): 101-9, 2001.
Article in English | MEDLINE | ID: mdl-11381185

ABSTRACT

Does a NO-donor (Corvaton, Aventis, France) attenuate the adherence and the aggregation of platelets in a closed-loop perfusion modell with or without the implantation of coronary stents? SIN-1, the active metabolite of molsidomine, exerted a strong influence on the interaction of platelets with the surfaces of stents. When SIN-1 was added the adherence of platelets to the surfaces of stents was markedly reduced. The sites were most of the platelets adhered to, also changed. More platelets adhered to the stent backbone and less to the free modular stent parts. The localisation of adherent platelets could easily be shown by light microscopy. The aggregation of platelets, accompanied by a spheroidic shape change, could be demonstrated by scanning electron microscopy on the addition of an NO-donor, not only a reduction of platelet adherence was realised but also the reduction of platelet aggregation.


Subject(s)
Molsidomine/pharmacology , Nitric Oxide Donors/pharmacology , Platelet Adhesiveness/drug effects , Platelet Aggregation/drug effects , Stents , Blood Platelets/drug effects , Blood Platelets/ultrastructure , Drug Evaluation, Preclinical , Humans , Materials Testing , Microscopy, Electron , Molsidomine/analogs & derivatives , Perfusion
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