Relation of aspirin failure to clinical outcome and to platelet response to aspirin in patients with acute myocardial infarction

Aspirin failure, defined as occurrence of an acute coronary syndrome despite aspirin use, has been associated with a higher cardiovascular risk profile and worse prognosis. Whether this phenomenon is a manifestation of patient characteristics or failure of adequate platelet inhibition by aspirin has never been studied. We evaluated 174 consecutive patients with acute myocardial infarction. Of them, 118 (68%) were aspirin naive and 56 (32%) were regarded as having aspirin failure. Platelet function was analyzed after ≥72 hours of aspirin therapy in all patients. Platelet reactivity was studied by light-transmitted aggregometry and under flow conditions. Six-month incidence of major adverse coronary events (death, recurrent acute coronary syndrome, and/or stroke) was determined. Those with aspirin failure were older (p = 0.002), more hypertensive (p <0.001), more hyperlipidemic (p <0.001), and more likely to have had a previous cardiovascular event and/or procedure (p <0.001). Cumulative 6-month major adverse coronary events were higher in the aspirin-failure group (14.3% vs 2.5% p <0.01). Patients with aspirin failure had lower arachidonic acid-induced platelet aggregation (32 ± 24 vs 45 ± 30, p = 0.003) after aspirin therapy compared to their aspirin-naive counterparts. However, this was not significant after adjusting for differences in baseline characteristics (p = 0.82). Similarly, there were no significant differences in adenosine diphosphate-induced platelet aggregation and platelet deposition under flow conditions. In conclusion, our results suggest that aspirin failure is merely a marker of higher-risk patient profiles and not a manifestation of inadequate platelet response to aspirin therapy.     

Improved posterobasal segment function after thrombolysis is associated with decreased incidence of significant mitral regurgitation in a first inferior myocardial infarction

Objectives. This study was designed to investigate the association between wall motion abnormalities and the occurrence of ischemic mitral regurgitation in patients with a first inferior or posterior myocardial infarction and to reassess the role of thrombolytic treatment in these patients.

Background. We previously demonstrated that thrombolytic therapy reduces the incidence of significant mitral regurgitation in patients with a first inferior myocardial infarction, but the mechanisms responsible for this decrease were not clear.

Methods. Wall motion score on two-dimensional echocardiography (16 segments) and mitral regurgitation grade (0 to 3) on Doppler color flow imaging were assessed in 95 patients (in 47 after thrombolysis) at 24 h, 7 to 10 days and 1 month after myocardial infarction. Significant mitral regurgitation was defined as moderate or severe (grade 2 or 3).

Results. Multivariate analysis revealed that the presence of an advanced wall motion abnormality of the posterobasal segment of the left ventricle was the most significant independent variable associated with significant mitral regurgitation: odds ratio (OR) 15.0, 90% confidence interval (CI) 1.4 to 165.6 at 24 h; OR 2.8, CI 0.9 to 9.3 at 7 to 10 days; OR 4.2, CI 1.2 to 11.4 at 1 month. Thrombolysis reduced the prevalence of advanced wall motion abnormalities in the posterobasal segment at 24 h (55% vs. 75%, OR 0.5, CI 0.2 to 0.99), 7 to 10 days (44% vs. 73%, OR 0.3, CI 0.1 to 0.7) and 1 month (36% vs. 56%, OR 0.4, CI 0.2 to 0.9).

Conclusions. There is a strong association between advanced wall motion abnormalities in the posterobasal segment and significant mitral regurgitation. In this study group, thrombolysis reduced the prevalence of advanced wall motion abnormalities in the posterobasal segment and thereby reduced the incidence of significant mitral regurgitation.     

Evaluation of the NiTi Shape Memory BioDynamix ColonRing™ in colorectal anastomosis: first in human multi-center study

Background   

Shape-memory compression bowel anastomosis using a nickel and titanium alloy may reduce leak rates and eliminate foreign anastomotic material. Its safety and efficacy had been demonstrated by animal studies. We conducted the first prospective multi-center clinical evaluation of the safety and effectiveness of BioDynamix anastomosis with ColonRing™ for large-bowel end-to-end or side-to-end anastomosis.     

Mechanisms of gonadotropin desensitization

The gonadotropic hormones, FSH and LH exert a major effect on ovarian and testicular function through interaction with specific seven-transmembrane domain glycoprotein receptors. Desensitization to the hormones, which can occur both in vivo and in vitro, is essential for prevention of overstimulation of the gonadal cells. The long-term process of desensitization to the gonadotropic hormones is probably mediated, in part, by extensive clustering and internalization of the hormone-receptor complex. Short-term desensitization may occur as a result of phosphorylation of serine or threonine residues on the receptor molecules, although a specific receptor kinase has not yet been identified. Recently, we have discovered a novel mechanism of gonadotropin desensitization, which is exerted by down-regulation of StAR expression and steroidogenesis mediated by MAPK activation as a result of hormone-receptor interaction, cAMP accumulation and PKA activation. Thus, PKA not only mediates gonadotropin-induced steroidogenesis, it also activates the down-regulation mechanism that can silence steroidogenesis under certain conditions. Moreover, our findings raise the possibility that activation or inhibition of ERK by other pathways could be an important mechanism for diminution or amplification of gonadotropin-stimulated steroidogenesis. This could contribute to functional luteolysis, a process in which luteinized granulosa cells show reduced sensitivity to LH despite maintenance of LH receptors, or to up-regulation of the steroidogenic machinery during luteinization of granulosa cells.     

Puerperal and intrapartum group A streptococcal infection

OBJECTIVE: To determine the demographic and clinical variables characteristic of non-epidemic intrapartum or puerperal group A streptococcal (GAS) infection. METHODS: The records of 47 patients diagnosed with intrapartum or puerperal GAS infection over a 6 1/2 year period at Hadassah-University Hospital-Mt. Scopus, Jerusalem were reviewed. Data regarding 25,811 women, the general population of women that delivered during that period, were obtained from their computerized medical records. Frequency distributions, t-test, chi-square, and Spearman's Rank Correlation were used, as appropriate, to analyze and compare demographic and clinical variables associated with development of GAS infection, its clinical course and subsequent development of septic shock. RESULTS: Mean age of mothers with GAS infection was higher than that of our general pregnant population (30.4 versus 27.4 years, P = 0.0019), and a higher proportion of GAS infected patients (30% versus 12%, P < 0.005) experienced PROM. Thirty-one (66%) women had fever as their sole presenting symptom, eight (17%) had fever and abdominal pain, seven (15%) had fever and abnormal vaginal bleeding, and one patient (2%) presented with a rash. Three patients (6%) developed a septic shock. Two of these patients presented with symptoms more than 14 days after delivery. CONCLUSIONS: We describe the characteristics of non-epidemic intrapartum or puerperal GAS infection. Data from our study and review of the literature suggest that some patients who develop septic shock may present later in the puerperium than patients with an uncomplicated GAS infection.     

Immunization with the glutamate receptor-derived peptide GluR3B induces neuronal death and reactive gliosis, but confers partial protection from pentylenetetrazole-induced seizures

Do autoantibodies (Ab's) against glutamate/AMPA receptor subtype 3 affect the severity of seizures? Rats immunized with the GluR3B-peptide (amino acids (aa) 372-395) or with the control GluR3A-peptide (aa 245-274) produced the respective anti-GluR3B and anti-GluR3A Ab's (both types of Ab's found in some epilepsy patients). The GluR3B-immunized rats exhibited neuronal death and reactive gliosis in the brain, but not overt spontaneous seizures. Surprisingly, in response to the chemoconvulsant pentylenetetrazole, the GluR3B-immunized rats displayed fewer jerks, a lower percentage of generalized seizures, and a lower overall seizure-severity score than GluR3A-immunized, scrambled GluR3B-immunized or non-immunized control rats. These findings, combined with the previously demonstrated ability of anti-GluR3B Ab's to bind, activate, and kill neurons and glia, suggest that if these Ab's are present in the brain they may cause neuronal death, which by itself may be pro-epileptic, but they may also decrease the excitability of seizure-related neural circuits, thereby conferring partial protection from seizures induced by other exogenously applied epileptogenic stimuli. The present results could have clinical implications for epilepsy.     

Improving doctor-patient understanding of probability in communicating cancer-screening test findings

Several researchers have questioned the merits of early mammography and prostate-specific-antigen (PSA) screening policies, arguing that these programs have not been proven useful in lowering mortality rates. This controversy highlights the necessity and importance of effectively communicating probability information to patients. Probability information, however, has been plaguing the health care profession--as numerous investigators have shown that it is often difficulty to understand and transmit. These difficulties can be overcome by changing the presentation format from a probabilistic format to a frequency format, thereby enhancing doctors' and patients' ability to solve and understand statistical information. Although I highlight this problematic issue with a discussion of mammography and prostate-specific-antigen screening, the suggested solution is not confined to a single medical procedure, but can be extended to any other medical domains where doctors are faced with the difficult task of providing complex probability data to patients.     

Psychosocial adaptation to spinal cord injury as a function of time since injury

The literature on the relationship between time since injury (TSI) and the clinical unfolding of psychosocial adaptation to disability has yielded mixed results. In this exploratory study we have attempted to compare two groups of people who sustained spinal cord injury (SCI)--namely, short-term TSI versus long-term TSI--on the patterns of psychosocial reactions to their medical condition. Using the initial pool of participants (n=317), two "extreme'" TSI groups were created (short-term TSI, composed of people whose injuries occurred within the last 4 years, and long-term TSI, comprising people whose injuries occurred 20 or more years ago). A two-group discriminant function analysis (DFA) applied to the eight subscales of the Reactions to Impairment and Disability Inventory (RIDI) yielded a significant function that was most closely associated with reactions of denial, shock and generalized anger, suggesting a non-acceptance of the condition among the more recently injured. Further analyses were then separately applied to the two groups of civilians and veterans with SCI. The resultant DFAs yielded functions suggesting somewhat different group patterns from the original one. Results are discussed within the context of the literature drawn from the fields of post-traumatic stress disorder (PTSD) and related traumatic experiences.     

Prognostic value of global myocardial performance indices in acute myocardial infarction: comparison to measures of systolic and diastolic left ventricular function

STUDY OBJECTIVES: Assessment of global myocardial performance by a single index (ie, the myocardial performance index [MPI]) has been suggested as an appealing alternative to the individual assessment of systolic and diastolic left ventricular (LV) function We sought to test the prognostic value of MPI in comparison to clinical characteristics and echocardiographic parameters of LV filling and ejection in acute myocardial infarction (AMI). PATIENTS: Four hundred seventeen consecutive patients with AMI were examined within 24 h of hospital admission. INTERVENTIONS: Doppler echocardiographic measures of systolic, diastolic, and global myocardial performance were assessed within 24 h of hospital admission. In addition to MPI (ie, the sum of the isovolumic time intervals divided by ejection time), we determined the isovolumic/heterovolumic time ratio, which expresses the time "wasted" by the myocardium to generate and decrease LV pressure without moving blood. RESULTS: The end points of the study at 30 days were death (4.7%), congestive heart failure (23%), and recurrent infarction (4.8%), and occurred in 109 patients, who were compared as group B to 314 patients without an event (group A). Multivariate analysis identified only age (odds ratio [OR], 1.04; 95% confidence interval [CI], 1.02 to 1.07), LV ejection fraction (LVEF) < or = 40% (OR, 3.82; 95% CI, 2.15 to 6.87), and E-wave deceleration time (EDT) of < or = 130 ms (OR, 2.29; 95% CI, 1.0 to 5.21) as independent predictors of adverse events. CONCLUSION: LVEF and EDT are powerful and independent echocardiographic predictors of poor outcome following AMI, and are superior to indexes of global LV performance. Both parameters should be taken into consideration when deciding about the management of these patients.