Investigation of the effects of oral administration of vitamin E and beta-carotene on the chemiluminescence responses and the frequency of sister chromatid exchanges in circulating leukocytes from cigarette smokers

Sixty asymptomatic cigarette smokers were randomly allocated into three treatment groups. Smokers in Group 1 received 900 international units of Vitamin E (VE) daily for 6 wk, whereas 40 mg of beta-carotene (BC) daily was administered to those in Group 2 for the same period. Subjects in Group 3 were treated with a matched placebo. Plasma levels of VE and BC as well as circulating leukocyte counts, sister chromatid exchanges (SCEs), and the luminol-enhanced chemiluminescence (LECL) responses of blood phagocytes activated with phorbol myristate acetate (PMA) and FMLP with cytochalasin B (FMLP/CB) were measured prior to the administration of the antioxidant/placebo after 4 and 6 wk of supplementation and 12 wk after cessation of treatment. SCEs and leukocyte counts remained unchanged throughout the trial in all three treatment groups. Administration of VE for 4 wk was accompanied by decreased FMLP/CB-activated (p less than 0.005) and PMA-activated (p less than 0.005) LECL responses. However, with PMA as stimulant, the inhibition of LECL was transient, with partial recovery observed after 6 wk despite continued administration of VE. Administration of BC was associated with progressive inhibition of both FMLP/CB-activated (p less than 0.05 and p less than 0.01 after 4 and 6 wk, respectively) and PMA-activated (p less than 0.025 after 6 wk) LECL. No alterations in LECL responses were observed in Group 3 (placebo). VE appeared to inhibit the generation of oxidants by activated phagocytes, whereas BC scavenged oxidants generated by the myeloperoxidase/H2O2/halide system.     

Rickettsia rickettsii and Rickettsia montana from Ixodid ticks in Connecticut

Dermacentor variabilis, infected with spotted fever group rickettsiae, parasitized 8 of 70 raccoons captured in Newtown, Connecticut. The spotted fever agent, Rickettsia rickettsii, was isolated and identified from 4 adult D. variabilis and from 1 nymphal Ixodes texanus removed from raccoons. This verifies the presence of this etiologic agent in ticks in an area where 6 people had clinical signs and symptoms of Rocky Mountain spotted fever (RMSF) and antibodies to R. rickettsii. These are the first isolations of R. rickettsii from D. variabilis in southern New England and the first identified rickettsiae from I. texanus. No rickettsiae were isolated from Ixodes muris or I. cookei. Rickettsia montana was recovered in Vero cell culture from a D. variabilis collected in East Haddam, Connecticut where RMSF is not known to be prevalent.     

The dipsogenic effect of the renin-angiotensin system in elasmobranch fish.

This study investigated the control of drinking in elasmobranch fish through manipulation of the homologous renin-angiotensin system (RAS). The smooth muscle relaxant papaverine was found to increase basal drinking levels in the European lesser-spotted dogfish, Scyliorhinus canicula, almost 20-fold. However, this response was significantly reduced with the coadministration of the angiotensin-converting enzyme inhibitor captopril which had no effect when administered alone. Captopril was also found to block a 7-fold increase in drinking rate following administration of homologous angiotensin I in S. canicula. Finally, administration of homologous angiotensin II produced a dose-dependent response in drinking rate in two species of elasmobranchs, S. canicula and the Japanese dogfish, Triakis scyllia. These results demonstrate a central role of the RAS in the control of drinking in elasmobranch fish.     

Mechanisms of intestinal failure in Crohn's disease

PURPOSE: The purpose of this study was to determine the mechanisms by which patients with Crohn's disease develop intestinal failure and, in particular, to assess the relative importance of severe primary disease, repeated uncomplicated elective small intestine resection, and resection performed as a consequence of intra-abdominal septic surgical complications. METHODS: This was a retrospective analysis of 41 patients with Crohn's disease referred to a specialized intestinal failure unit between January 1987 and September 1998 for permanent home parenteral nutrition. To compare the surgical activity in patient groups, a resection index was calculated by dividing the number of intestinal resections by the interval in years between the first resection for Crohn's disease and referral for management of intestinal failure. RESULTS: Extensive primary Crohn's disease was responsible for intestinal failure in 7 cases (17 percent). The remainder (n=34, 83 percent) developed intestinal failure after intestinal resection. Nine of the surgical Crohn's patients developed intestinal failure after uncomplicated sequential resection, (median small-bowel length 65 (range, 60–120) cm) after a median of 3 (range, 2–8) operations over a median of 17 (range, 3–27) years. By contrast, the other 25 surgical Crohn's patients developed intestinal failure after multiple unplanned laparotomies for intra-abdominal sepsis (median small-bowel length 70 (range, 60–200) cm), with a median of 4 (range, 2–7) laparotomies performed over a median of 0.5 (range, 0.1 to 1.5) years (P<0.001). The resection index for the 25 Crohn's patients undergoing laparotomies for intra-abdominal sepsis was significantly greater than that of the 9 patients who had planned sequential resections (2.1 (0.27–25)vs. 0.23 (0.1–1.0);P < 0.002, Mann-WhitneyU test). CONCLUSION: Intestinal failure develops in Crohn's disease primarily as a result of complications of surgical treatment. The largest group of patients at risk consists of those who are undergoing multiple unplanned laparotomies to control intra-abdominal sepsis.     

Management and outcomes of lower risk patients presenting with acute coronary syndromes in a multinational observational registry

OBJECTIVE: To document patterns of risk stratification, management practices, and outcomes among patients with acute coronary syndromes (ACS) presenting without high risk features. PATIENTS: The study was based on 11,885 consecutive patients presenting with non-ST segment elevation ACS enrolled in GRACE (global registry of acute coronary events). Patients without dynamic ST segment changes, positive troponin (or other cardiac markers), or haemodynamic or arrhythmic instability were defined as being at lower risk. MAIN OUTCOME MEASURES: Management and outcomes were compared with high risk presentations. RESULTS: Of 11,885 patients presenting with unstable angina or non-ST segment elevation myocardial infarction, 4252 (36%) were regarded as being at lower risk. Functional testing for risk stratification was performed in 1163 of 4207 (28%) lower risk and 1531 of 7521 (20%) high risk patients (p < 0.0001). Coronary angiography was performed in 1930 of 4190 (46%) and 3860 of 7544 (51%), and echocardiography in 1692 of 4190 (40%) and 4348 of 7533 (58%) of lower risk and high risk patients, respectively (p < 0.0001 for both). Over one third of patients did not undergo further risk assessment with angiography or functional testing (2746 of 7437 (37%) high risk, 1499 of 4148 (36%) lower risk, not significant). Death occurring in hospital was more likely in the high risk cohort (41 of 4227 (1.0%) lower risk v 215 of 7586 (2.8%) high risk, p < 0.0001), whereas rates of recurrent angina during admission and readmission were similar in both groups (1354 of 4231 (32%) high risk, 2313 of 7587 (31%) lower risk, not significant). In the six months after discharge, death or myocardial infarction occurred in 79 of 3223 (2.5%) lower risk patients and 302 of 5451 (5.5%) high risk patients (p < 0.0001). CONCLUSIONS: Globally, further risk stratification after ACS presentation is suboptimal, regardless of presenting characteristics. Although in-hospital death and myocardial infarction are uncommon, recurrent ischaemia is encountered often in both groups. It remains to be seen whether better outcomes may be achieved with wider application of risk stratification and appropriately directed management strategies.     

Combination of inhibition of thrombin and blockade of thromboxane A2 synthetase and receptors enhances thrombolysis and delays reocclusion in canine coronary arteries.

BACKGROUND. The efficacy of thrombolytic therapy in treating patients with acute myocardial infarction is limited by failure to achieve reperfusion in some patients, by the prolonged time required to achieve reperfusion, and by reocclusion of some coronary arteries. We designed this study to examine the effect of combined inhibition of thrombin and thromboxane synthesis and blockade of thromboxane A2 receptors in addition to tissue-type plasminogen activator (t-PA) on thrombolysis and reocclusion in an experimental canine model with coronary thrombosis. METHODS AND RESULTS. Blood flow velocity in the left anterior descending coronary artery (LAD) of 32 anesthetized mongrel dogs was monitored by a pulsed Doppler flow probe. Coronary thrombosis was induced by applying electrical stimulation to the LAD at the site where an external constrictor was used to narrow the artery. Three hours after the formation of occlusive thrombus, animals were randomly assigned to receive one of the following: 1) t-PA (80 micrograms/kg + 8 micrograms.kg-1.min-1 i.v.) and saline; 2) t-PA and hirulog, a hirudin-based synthetic peptide and specific thrombin inhibitor (2 mg/kg + 2 mg.kg-1.hr-1 i.v.); 3) t-PA and ridogrel, a combined thromboxane A2 synthetase inhibitor and receptor antagonist (5 mg/kg + 2.5 mg.kg-1.hr-1 i.v.); or 4) t-PA, hirulog, and ridogrel. Reperfusion developed in 14% (one of seven) of dogs treated with t-PA alone at an average of 86 +/- 4 minutes after treatment, in 78% (seven of nine) of dogs treated with t-PA plus hirulog at 53 +/- 11 minutes, in 13% (one of eight) of dogs treated with t-PA plus ridogrel at 85 +/- 5 minutes, and in 88% (seven of eight) of dogs treated with t-PA, hirulog, and ridogrel at 37 +/- 10 minutes (comparison of the frequency of and the time to reperfusion, both p < 0.01). Among the dogs with reestablished coronary blood flow, reocclusion developed in the one treated with t-PA alone at 36 minutes after reperfusion, in seven of the seven treated with t-PA plus hirulog at 66 +/- 15 minutes, and in two of the seven treated with t-PA, hirulog, and ridogrel at 151 +/- 21 minutes (comparison of the frequency of and time to reocclusion, both p < 0.05). Reocclusion was not detected in the one dog treated with t-PA and ridogrel or in the other five dogs treated with t-PA, hirulog, and ridogrel within 180 minutes after reperfusion. Hirulog prolonged and maintained activated clotting times at a level twice that of baseline values. Hirulog inhibited ex vivo platelet aggregation induced by thrombin, and ridogrel inhibited platelet aggregation induced by U46619, a thromboxane mimetic. CONCLUSIONS. Inhibition of thrombin in addition to treatment with t-PA enhances thrombolysis. A combination of inhibition of thrombin and thromboxane synthetase and blockade of thromboxane A2 receptor enhances thrombolysis and delays or may prevent reocclusion of the recanalized coronary arteries.     

Classification by type of ventricular arrhythmia predicts frequency of adverse cardiac events from flecainide

Antiarrhythmic therapy is known to be associated with a significant risk of adverse cardiac reactions, including a proarrhythmic response. This study assessed in 1,330 patients followed up for 292 +/- 393 days the predictive value for cardiovascular safety of a system by which patients were classified according to ventricular arrhythmias on entry, presence or absence of organic heart disease and drug dose for flecainide acetate. Baseline arrhythmia subgroups included patients with premature ventricular complexes only, nonsustained ventricular tachycardia, and sustained ventricular tachycardia. Proarrhythmic events occurred in 6.8% of patients overall and were serious in 2.3% and lethal in 1.0%. However, proarrhythmia was highly dependent on arrhythmia class on entry: serious nonlethal proarrhythmic events occurred in 6.6% of patients with sustained ventricular tachycardia, only 0.9% with nonsustained ventricular tachycardia and 0% with premature ventricular complexes (p less than 0.01). Proarrhythmic death occurred in 3.1% of patients with sustained ventricular tachycardia, 0.2% with nonsustained ventricular tachycardia and 0% with premature ventricular complexes only (p less than 0.01). Proarrhythmia was also influenced by the presence of structural heart disease: serious nonlethal proarrhythmia occurred in 2.6% of patients with versus 0.4% of those without organic heart disease, and death occurred in 1.2 versus 0%, respectively. These adverse events were also dependent on dosing regimen. Flecainide caused premature discontinuation due to new or worsened heart failure in 1.4% of patients, all with underlying organic heart disease; however, heart failure was not clearly related to dose or type of arrhythmia. Symptomatic conduction disturbances occurred in 2.2%, and were predicted by preexistent sinus node disease but not by other baseline features.(ABSTRACT TRUNCATED AT 250 WORDS)     

Favorable early and long-term prognosis following coronary bypass surgery therapy for myocardial infarction: results of a multicenter trial. TAMI Study Group

Coronary bypass surgery was performed before hospital discharge on 82 (21%) of 386 consecutive patients enrolled in the Thrombolysis and Angioplasty in Myocardial Infarction (TAMI) multicenter trial of intravenous tissue plasminogen activator and coronary angioplasty for acute myocardial infarction. Time from infarct symptom onset to coronary bypass surgery was 7.3 +/- 1.9 hours for 24 patients operated upon on an emergency basis and 9.3 +/- 5.2 days for 58 patients having late in-hospital surgery. There were no operative deaths and five in-hospital deaths in the surgical group, all of which occurred in patients with preoperative cardiogenic shock. Although patients in the surgical group were older (59.7 +/- 10.4 years versus 54.9 +/- 10.2 years; p = 0.03), had more extensive coronary artery disease (42% three-vessel disease versus 11%; p = 0.001), and had a higher incidence of anterior wall myocardial infarction (48% versus 39%; p = 0.02), in-hospital mortality for the surgical group (6%) was similar to that in 301 patients not undergoing surgery (7%) in this trial. For patients discharged from the hospital, mortality at 1 year was 2.5% in the surgical group and 1.8% in patients not having coronary bypass surgery before hospital discharge. At a 1 year follow-up, there were no significant differences in the frequency of cardiac or noncardiac-related hospitalizations or in event-free survival between surgical and nonsurgical groups. The majority of patients in both groups considered themselves to be in excellent or good condition. Coronary bypass surgery can be performed with low morbidity and mortality rates in close temporal association to acute myocardial infarction.(ABSTRACT TRUNCATED AT 250 WORDS)