Osmotic nephrosis in a renal transplant recipient.
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Acute Kidney Injury↗
Biomedical subjects
D J Cohen
Publications and source records attributed to D J Cohen.
Respiratory distress in a patient with rhabdomyolysis-induced acute renal failure.
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Acute Kidney Injury↗
Kidney and pancreas transplantation in the United States, 1995-2004.
This article examines OPTN/SRTR data on kidney and pancreas transplantation for 2004 and the previous decade, and discusses recent changes in kidney-pancreas (KP) allocation policy and emerging issues in kidney donation after cardiac death (DCD). Although the number of kidney donors continues to increase, new waiting list registrations again outpaced the number of kidney transplants performed, rising by 11% between 2003 and 2004 and contributing to a 1-year increase of 8% in the number of patients active on the waiting list. DCD has increased steadily since 2000; 39% more DCD transplants were performed in 2004 than 2003. Both deceased donor and living donor kidney graft survival rates remain excellent and are improving. The number of people living with a functioning kidney transplant doubled between 1995 and 2004, to 101,440 with a functioning kidney-alone and 7213 with a functioning KP. Health care providers in all settings are more likely to be exposed to these transplant recipients. Patient survival following simultaneous pancreas-kidney (SPK) transplantation is excellent and has improved incrementally since 1995; death rates in the first year fell from 60 per 1000 patient-years at risk in 2001 to 45 in 2003. The number of solitary pancreas transplants increased dramatically in 2004.
Adolescent↗
Human testicular protein TPX1/CRISP-2: localization in spermatozoa, fate after capacitation and relevance for gamete interaction.
Testicular protein Tpx-1, also known as CRISP-2, is a cysteine-rich secretory protein specifically expressed in the male reproductive tract. Since the information available on the human protein is limited to the identification and expression of its gene, in this work we have studied the presence and localization of human Tpx-1 (TPX1) in sperm, its fate after capacitation and acrosome reaction (AR), and its possible involvement in gamete interaction. Indirect immunofluorescence studies revealed the absence of significant staining in live or fixed non-permeabilized sperm, in contrast to a clear labelling in the acrosomal region of permeabilized sperm. These results, together with complementary evidence from protein extraction procedures strongly support that TPX1 would be mainly an intra-acrosomal protein in fresh sperm. After in vitro capacitation and ionophore-induced AR, TPX1 remained associated with the equatorial segment of the acrosome. The lack of differences in the electrophoretic mobility of TPX1 before and after capacitation and AR indicates that the protein would not undergo proteolytical modifications during these processes. The possible involvement of TPX1 in gamete interaction was evaluated by the hamster oocyte penetration test. The presence of anti-TPX1 during gamete co-incubation produced a significant and dose-dependent inhibition in the percentage of penetrated zona-free hamster oocytes without affecting sperm motility, the AR or sperm binding to the oolema. Together, these results indicate that human TPX1 would be a component of the sperm acrosome that remains associated with sperm after capacitation and AR, and is relevant for sperm-oocyte interaction.
Antibodies↗
Studies on the participation of epididymal sperm protein DE/CRISP-1 in egg activation.
Protein DE (32 kDa) associates with sperm during epididymal maturation and participates in sperm-egg fusion through its binding to complementary sites on the egg surface. In the present work we investigated the participation of DE in two mechanisms probably involved in egg activation: the ability of DE to trigger activation by its interaction with the binding sites on the egg surface (receptor model) and its ability to regulate intracellular calcium channels (sperm factor model). The incubation of eggs with DE did not promote activation parameters such as calcium oscillations or meiosis resumption. Secondly, microinjection of DE into eggs was ineffective in either eliciting calcium release or modifying oscillations induced by an activating sperm extract. Together, these results argue against the participation of DE in egg activation, restricting the activity of this protein and its egg binding sites to the sperm-egg fusion process.
Animals↗
Serotonin transporter promoter variants in autism: functional effects and relationship to platelet hyperserotonemia.
The well-replicated platelet hyperserotonemia of autism has stimulated interest in serotonin (5-HT) in autism. We have examined the effects of the serotonin transporter gene (5-HTT, locus SLC6A4) promoter polymorphism (5-HTTLPR) on platelet 5-HT physiology in autism. Platelet 5-HT uptake rates and affinities (V(max) and K(m)), uptake site densities (B(max)) and 5-HT levels were examined in 31 French individuals with autism genotyped with respect to the 5-HTTLPR. Platelet 5-HT uptake and 5-HT levels were measured using HPLC; uptake sites were determined by radioligand binding. A 1.5-fold increased rate (V(max)) of platelet 5-HT uptake was observed in ll genotype individuals compared to those with ls and ss genotypes (Mann- Whitney U-test, P = 0.022). However, no significant relationship was observed between genotype and uptake site density (U-test, P = 0.51). Although median levels of platelet 5-HT in platelet-rich plasma were higher in the ll group, only trend level significance was observed (U-test, P= 0.069); platelet 5-HT content measured in whole blood was similar across genotypes. Uptake rates were well correlated with B(max) values (r = 0.66, P = 0.002); correlations between uptake and platelet 5-HT levels and between B(max) values and 5-HT levels were somewhat lower. While 5-HTTLPR alleles had an appreciable effect on platelet 5-HT uptake rates, effects on 5-HT levels and uptake site density were smaller or absent. Based on these preliminary data and prior studies of allele frequencies, we conclude that the 5-HTTLPR is not a major determinant of the group mean platelet serotonin elevation seen in autism. However, a role for increased uptake in the hyperserotonemia of autism can not be ruled out. In addition, it appears that studies of platelet 5-HT measures in autism and other disorders should take account of the effects of 5-HTTLPR genotype on 5-HT uptake
Adolescent↗
Cost-effectiveness of coronary stenting in acute myocardial infarction: results from the stent primary angioplasty in myocardial infarction (stent-PAMI) trial.
BACKGROUND: Although several randomized trials have demonstrated that coronary stenting improves angiographic and clinical outcomes for patients with acute myocardial infarction (AMI), the cost-effectiveness of this practice is unknown. The objective of the present study was to evaluate the long-term costs and cost-effectiveness (C/E) of coronary stenting compared with primary balloon angioplasty as treatment for AMI. Methods and Results- Between December 1996 and November 1997, 900 patients with AMI were randomized to undergo balloon angioplasty (PTCA, n=448) or coronary stenting (n=452). Detailed resource utilization and cost data were collected for each patient's initial hospitalization and for 1 year after randomization. Compared with conventional PTCA, stenting increased procedural costs by approximately $2000 per patient ($6538+/-1778 versus $4561+/-1598, P<0.001). During the 1-year follow-up period, stenting was associated with significant reductions in the need for repeat revascularization and rehospitalization. Although follow-up costs were significantly lower with stenting ($3613+/-7743 versus $4592+/-8198, P=0.03), overall 1-year costs remained approximately $1000/patient higher with stenting than with PTCA ($20 571+/-10 693 versus 19 595+/-10 990, P=0.02). The C/E ratio for stenting compared with PTCA was $10 550 per repeat revascularization avoided. In analyses that incorporated recent changes in stent technology and pricing, the 1-year cost differential fell to <$350/patient, and the C/E ratio improved to $3753 per repeat revascularization avoided. The cost-utility ratio for primary stenting was <$50 000 per quality-adjusted life year gained only if stenting did not increase 1-year mortality by >0.2% compared with PTCA. CONCLUSIONS: As performed in Stent-PAMI, primary stenting for AMI increased 1-year medical care costs compared with primary PTCA. The overall cost-effectiveness of primary stenting depends on the societal value attributed to avoidance of symptomatic restenosis, as well as on the relative mortality rates of primary PTCA and stenting.
Aged↗
Quality of life after balloon angioplasty or stenting for acute myocardial infarction. One-year results from the Stent-PAMI trial.
OBJECTIVES: The goal of this study was to compare the impact of primary stenting or percutaneous transluminal coronary angioplasty (PTCA) on health-related quality of life (HRQOL) in patients undergoing direct angioplasty for acute myocardial infarction (AMI). BACKGROUND: Previous studies have demonstrated that coronary stenting reduces clinical and angiographic restenosis compared with PTCA. However, the impact of stenting on HRQOL from the patient's perspective remains unknown. METHODS: We administered the Seattle Angina Questionnaire and the Medical Outcomes Study Short-form Survey at 1, 6 and 12 months after initial treatment to all North American patients in the Stent-Primary Angioplasty for Myocardial Infarction trial (Stent-PAMI) (n = 509)-a randomized trial comparing primary stenting to conventional PTCA for patients with AMI. RESULTS: At one month, most HRQOL measures were similar for the two groups, but stent patients reported less bodily pain than PTCA patients (p = 0.03). At six-month follow-up, stenting resulted in significant improvements in several dimensions of HRQOL including reduced anginal frequency and bodily pain as well as improved disease perception (all p < or = 0.03) and a trend towards better anginal stability (p = 0.056). By 12-month follow-up, however, none of these differences remained statistically significant. These differences in HRQOL were largely explained by the greater need for ischemia-driven target-vessel repeat revascularization procedures in PTCA patients during the first six months (16.0% vs. 6.2%, p < 0.001). CONCLUSIONS: In patients undergoing revascularization for AMI, initial stent placement is associated with improvements in several dimensions of health status during the first six months of follow-up. In the absence of differences in mortality, these findings add to the overall argument in favor of initial stenting in patients treated with mechanical reperfusion for myocardial infarction.
Angioplasty, Balloon, Coronary↗
Mixed kappa agonists and mu agonists/antagonists as potential pharmacotherapeutics for cocaine abuse: synthesis and opioid receptor binding affinity of N-substituted derivatives of morphinan.
A series of new N-substituted derivatives of morphinan was synthesized and their binding affinity for the three opioid receptors (mu, delta, and kappa) was determined. A paradoxical effect of N-propargyl (MCL-117) and N-(3-iodoprop-(2E)-enyl) (MCL-118) substituents on the binding affinities for the mu and kappa opioid receptors was observed. All of these novel derivatives showed a preference for the mu and kappa versus delta binding.
Cocaine-Related Disorders↗
Fractional flow reserve compared with intravascular ultrasound guidance for optimizing stent deployment.
BACKGROUND: Determination of fractional flow reserve (FFR) has been proposed as a means to assess stent deployment. In this prospective, multicenter trial, we evaluate the use of FFR to optimize stenting by comparing it with standard intravascular ultrasound (IVUS) criteria. METHODS AND RESULTS: Eighty-four stable patients with isolated coronary lesions underwent coronary stent deployment starting at 10 atm and increased serially by 2 atm until the FFR was >/=0.94 or 16 atm was achieved. IVUS was then performed. FFR was measured with a coronary pressure wire with intracoronary adenosine to induce hyperemia. The diagnostic characteristics of an FFR <0.94 to predict suboptimal stent expansion by IVUS, defined in both absolute and relative terms, were calculated. Over a range of IVUS criteria, the highest sensitivity, specificity, and predictive accuracy of FFR were 80%, 30%, and 42%, respectively. Receiver operator characteristic analysis defined an optimal FFR cut point at >/=0.96; at this threshold, the sensitivity, specificity, and predictive accuracy of FFR were 75%, 58%, and 62%, respectively (P=0.03 for comparison of predictive accuracy, P=0.01 for concordance between FFR and IVUS). The negative predictive value was 88%. Significantly better diagnostic performance was achieved in a subgroup that received higher doses (>30 microgram) of intracoronary adenosine during pressure measurements, suggesting that FFR might be overestimated in the other group. CONCLUSIONS: A fractional flow reserve <0.96, measured after stent deployment, predicts a suboptimal result based on validated intravascular ultrasound criteria; however, an FFR >/=0.96 does not reliably predict an optimal stent result. Higher doses of intracoronary adenosine than previously used to measure FFR improve these results.
Adenosine↗
Long-term clinical outcomes after unprotected left main trunk percutaneous revascularization in 279 patients.
BACKGROUND: Percutaneous coronary revascularization (PCI) has been increasingly applied to unprotected left main trunk (LMT) lesions, with varied long-term success. This study attempts to define the predictors of outcome in this population. METHODS AND RESULTS: Two hundred seventy-nine consecutive patients who had LMT PCI at 1 of 25 sites between 1993 and 1998 were studied. Forty-six percent of these patients were deemed inoperable or at high surgical risk. Thirty-eight patients (13.7%) died in hospital, and the rest were followed up for a mean of 19 months. The 1-year incidence was 24.2% for all-cause mortality, 20.2% for cardiac mortality, 9.8% for myocardial infarction, and 9.4% for CABG. Independent correlates of all-cause mortality were left ventricular ejection fraction </=30%, mitral regurgitation grade 3 or 4, presentation with myocardial infarction and shock, creatinine >/=2.0 mg/dL, and severe lesion calcification. For the 32% of patients <65 years old with left ventricular ejection fraction >30% and without shock, the prevalence of these adverse risk factors was low. No periprocedural deaths were observed in this low-risk subset, and the 1-year mortality was only 3.4%. CONCLUSIONS: Patients undergoing unprotected LMT PCI have frequent serious comorbidities and consequently have high event rates. PCI may be an alternative to CABG for a select proportion of elective patients and may also be appropriate for highly symptomatic inoperable patients. Meticulous follow-up of hospital survivors is required because of the rather high mortality during the first few months after treatment.
Aged↗
Impact of smoking on clinical and angiographic restenosis after percutaneous coronary intervention: another smoker's paradox?
BACKGROUND: Recent studies have suggested that smokers may require less frequent repeated revascularization after percutaneous coronary intervention (PCI) compared with nonsmokers. However, the mechanism of this phenomenon is unknown. METHODS AND RESULTS: We examined the association between smoking and restenosis using pooled data from 8671 patients treated with PCI in 9 multicenter clinical trials. Clinical restenosis was examined in the cohort of 5682 patients who were assigned to clinical follow-up only. Angiographic restenosis was evaluated in the subset of 2989 patients who were assigned to mandatory angiographic restudy. Among those patients assigned to clinical follow-up only, target lesion revascularization (TLR) occurred in 6.6% of smokers and 10.1% of nonsmokers (P<0.001). After adjustment for baseline clinical and angiographic differences, the rate of TLR remained significantly lower in smokers with an adjusted relative risk of 0.69 (95% CI, 0.54 to 0.88). Among the angiographic cohort, there were no differences in the rates of angiographic restenosis or follow-up diameter stenosis in either univariate or multivariate analyses. This dissociation between clinical and angiographic restenosis was explained in part by reduced sensitivity to restenosis on the part of smokers and by the greater reluctance of smokers to seek medical attention despite recurrent angina. CONCLUSIONS: In patients undergoing contemporary PCI, cigarette smoking is associated with a lower rate of subsequent TLR without affecting angiographic restenosis. These findings have important implications for the follow-up of smokers after PCI and suggest that cross-study comparisons of rates of clinical restenosis must account for the potential confounding effect of smoking.
Aged↗
3-Carboxamido analogues of morphine and naltrexone. synthesis and opioid receptor binding properties.
In response to the unexpectedly high affinity for opioid receptors observed in a novel series of cyclazocine analogues where the prototypic 8-OH was replaced by a carboxamido group, we have prepared the corresponding 3-CONH(2) analogues of morphine and naltrexone. High affinity (K(i)=34 and 1.7nM) for mu opioid receptors was seen, however, the new targets were 39- and 11-fold less potent than morphine and naltrexone, respectively.
Amides↗
Comparison of two platelet glycoprotein IIb/IIIa inhibitors, tirofiban and abciximab, for the prevention of ischemic events with percutaneous coronary revascularization.
BACKGROUND: In the setting of percutaneous coronary revascularization, agents in the class known as platelet glycoprotein IIb/IIIa inhibitors have significantly reduced the incidence of death or nonfatal myocardial infarction at 30 days. We assessed whether there are differences in safety or efficacy between two such inhibitors, tirofiban and abciximab. METHODS: Using a double-blind, double-dummy design at 149 hospitals in 18 countries, we randomly assigned patients to receive either tirofiban or abciximab before undergoing percutaneous coronary revascularization with the intent to perform stenting. The primary end point was a composite of death, nonfatal myocardial infarction, or urgent target-vessel revascularization at 30 days. The trial was designed and statistically powered to demonstrate the noninferiority of tirofiban as compared with abciximab. RESULTS: The primary end point occurred more frequently among the 2398 patients in the tirofiban group than among the 2411 patients in the abciximab group (7.6 percent vs. 6.0 percent; hazard ratio, 1.26; one-sided 95 percent confidence interval of 1.51, demonstrating lack of equivalence, and two-sided 95 percent confidence interval of 1.01 to 1.57, demonstrating the superiority of abciximab over tirofiban; P=0.038). The magnitude and the direction of the effect were similar for each component of the composite end point (hazard ratio for death, 1.21; hazard ratio for myocardial infarction, 1.27; and hazard ratio for urgent target-vessel revascularization, 1.26), and the difference in the incidence of myocardial infarction between the tirofiban group and the abciximab group was significant (6.9 percent and 5.4 percent, respectively; P=0.04). The relative benefit of abciximab was consistent regardless of age, sex, the presence or absence of diabetes, or the presence or absence of pretreatment with clopidogrel. There were no significant differences in the rates of major bleeding complications or transfusions, but tirofiban was associated with a lower rate of minor bleeding episodes and thrombocytopenia. CONCLUSIONS: Although the trial was intended to assess the noninferiority of tirofiban as compared with abciximab, the findings demonstrated that tirofiban offered less protection from major ischemic events than did abciximab.
Abciximab↗
Effect of eptifibatide on coronary flow reserve following coronary stent implantation (an ESPRIT substudy). Enhanced Suppression of the Platelet IIb/IIIa Receptor with Integrilin Therapy.
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Adult↗
Stent thrombosis in the modern era: a pooled analysis of multicenter coronary stent clinical trials.
BACKGROUND: There are limited studies of stent thrombosis in the modern era of second-generation stents, high-pressure deployment, and current antithrombotic regimens. METHODS AND RESULTS: Six recently completed coronary stent trials and associated nonrandomized registries that enrolled 6186 patients (6219 treated vessels) treated with >/=1 coronary stent followed by antiplatelet therapy with aspirin and ticlopidine were pooled for this analysis. Within 30 days, clinical stent thrombosis developed in 53 patients (0.9%). The variables most significantly associated with the probability of stent thrombosis were persistent dissection NHLBI grade B or higher after stenting (OR, 3.7; 95% CI, 1.9 to 7.7), total stent length (OR, 1.3; 95% CI, 1.2 to 1.5 per 10 mm), and final minimal lumen diameter within the stent (OR, 0.4; 95% CI, 0.2 to 0.7 per 1 mm). Stent thrombosis was documented by angiography in 45 patients (0.7%). Clinical consequences of angiographic stent thrombosis included 64.4% incidence of death or myocardial infarction at the time of stent thrombosis and 8.9% 6-month mortality. CONCLUSIONS: Stent thrombosis occurred in <1.0% of patients undergoing stenting of native coronary artery lesions and receiving routine antiplatelet therapy with aspirin plus ticlopidine. Procedure-related variables of persistent dissection, total stent length, and final lumen diameter were significantly associated with the probability of stent thrombosis. Continued efforts to eliminate this complication are warranted given the serious clinical consequences.
Aspirin↗
8-Carboxamidocyclazocine analogues: redefining the structure-activity relationships of 2,6-methano-3-benzazocines.
Unexpectedly high affinity for opioid receptors has been observed for a novel series of cyclazocine analogues where the prototypic 8-OH was replaced by a carboxamido group. For mu and kappa opioid receptors, the primary carboxamido derivative of cyclazocine ((+/-)-15) displayed high affinity (Ki=0.41 and 0.53 nM, respectively) nearly comparable to cyclazocine. A high enantiopreference ((2R,6R,11R)-) for binding was also observed. Compound (+/-)-15 also displayed potent antinociception activity in mice when administered icv.
Amides↗
Coronary artery stenting in the aged.
OBJECTIVES: The study compared the safety and efficacy of coronary artery stenting in aged and nonaged patients and identified predictors of adverse clinical outcomes. BACKGROUND: Limited data are available on the outcomes of stenting in the aged (> or = 80 years) compared to nonaged patients. METHODS: The study was a pooled analysis of 6,186 patients who underwent coronary artery stenting in six recent multicenter trials. A clinical events committee adjudicated clinical end points, and quantitative angiography was performed by an independent core laboratory. RESULTS: There were 301 (4.9%) aged patients (> or = 80 years). Compared to nonaged patients, aged patients had a higher prevalence of multivessel disease (16.5% vs. 9.6%, p = 0.001), unstable angina (50.8% vs. 42.1%, p = 0.003), moderate to severe target lesion calcification (30.4% vs. 15.3%, p = 0.001) and smaller reference vessel diameter (2.90 mm vs. 2.98 mm, p = 0.004). Procedural success rate (97.4% vs. 98.5%, p = 0.14) was similar in the two groups. In-hospital mortality (1.33% vs. 0.10%, p = 0.001), bleeding complications (4.98% vs. 1.00%, p < 0.001) and one-year mortality (5.65% vs. 1.41%, p < 0.001) were significantly higher for the aged patients. Clinical restenosis was similar for the two groups (11.19% vs. 11.93%, p = 0.78). Advanced age, diabetes, prior myocardial infarction and presence of three-vessel disease were independent predictors of long-term mortality. CONCLUSIONS: Coronary artery stenting can be performed safely in patients > or = 80 years of age, with excellent acute results and a low rate of clinical restenosis, albeit with higher incidences of in-hospital and long-term mortality, and vascular and bleeding complications compared to nonaged patients.
Age Factors↗