Effects of different aspirin formulations on platelet aggregation times and on plasma salicylate concentrations.

BACKGROUND: Early aspirin treatment is widely used to inhibit platelet activity and to reduce morbidity and mortality in patients presenting with an acute myocardial infarction or a stroke. A number of different aspirin formulations have been used for this purpose; however, a comparison of their effectiveness in inhibiting early platelet aggregation has not been determined. METHODS: In this study, we determined plasma salicylate concentrations and platelet inhibitory activities at various times after ingestion of three commonly used aspirin formulations: soluble aspirin (Alka-Seltzer), 325 mg, chewed baby aspirin, 324 mg, and whole compressed non-enteric coated aspirin, 324 mg. Twenty-four healthy volunteers, 18-39 years of age, participated in the prospective single-blinded triple-crossover study. Plasma salicylate concentrations and inhibition of arachidonic acid-induced platelet aggregation were determined on post-dose blood samples collected at 2.5, 5.0, 7.5, 10, 15, 20, 25, 30, and 40 min. All subjects crossed over to the other two formulations with at least 2 weeks between ingestions. RESULTS: The median platelet inhibition times for the chewed, soluble, and whole aspirin formulations were 7.5, 7.5, and 10.0 min, respectively. Soluble and chewed aspirin were found to inhibit platelet aggregation faster than whole aspirin (p<0.001); however, there were no significant differences in platelet aggregation times between the soluble and chewed formulations (p<0.163). Inhibition of platelet aggregation was found to occur at an average plasma salicylate concentration of 2.46 microg/mL, regardless of method of ingestion. CONCLUSION: The results indicate that soluble and chewed aspirin inhibit platelet aggregation in a shorter period of time than does whole aspirin. The results suggest that chewing baby aspirin or taking soluble buffered aspirin may be the preferred route of administration for early platelet inhibition.

Prevalence of polymorphisms in the human UDP-glucuronosyltransferase 2B family: UGT2B4(D458E), UGT2B7(H268Y), and UGT2B15(D85Y).

UDP-glucuronosyltransferases (UGTs) of the UGT2B family conjugate steroid hormones as well as bile acids and xenobiotics. UGT2Bs are expressed in numerous human tissues, such as skin, breast, prostate, adipose, and intestine and are hypothesized to modulate steroid metabolism and excretion. Polymorphisms have been identified that may modify substrate specificities or enzyme activities of UGT2B family isozymes. We determined the prevalence of the UGT2B4(D458E), UGT2B7(H268Y), and UGT2B15(D85Y) polymorphisms in a sample of 233 individuals. The allele frequencies were significantly different (P < 0.02) between individuals of Caucasian and Asian descent for all three polymorphisms. In Asians (n = 32), the frequencies of the UGT2B4(D458), UGT2B7(H268), and UGT2B15(D85) alleles were 1.00, 0.73, and 0.64, respectively, whereas, in Caucasians (n = 202), the frequencies of UGT2B4(D458), UGT2B7(H268), and UGT2B15(D85) were 0.75, 0.46, and 0.45, respectively. The distribution of the UGT2B4(D458E), UGT2B7(H268Y), and UGT2B15(D85Y) genotypes also differed by ethnic group (P < 0.0001, P = 0.002, and P = 0.02, respectively). All Asians were homozygous for UGT2B4(D458) and had a greater than 2-fold higher prevalence of the UGT2B7(H268) and UGT2B15(D85) homozygous genotypes compared with Caucasians: 56.2% versus 21.8%, and 46.9% versus 22.3%, respectively. Concomitantly, only 9.4% of Asians were UGT2B7(Y268) homozygous and 18.7% were UGT2B15(Y85) homozygous compared with 29.2% and 32.2%, respectively, of Caucasians. The data suggest that there may be large differences in UGT2B polymorphisms between Asians and Caucasians. This warrants evaluation both in larger, multiethnic cohorts and in relation to known ecological differences in risk of sex hormone-dependent cancers.

Assessing provider attitudes toward mandated prevention practices.

OBJECTIVE: We measured clinicians' level of knowledge and attitudes regarding Department of Defense-mandated clinical preventive services (CPS) delivery and the barriers they believe prevent the delivery of CPS at a large U.S. Air Force referral medical center. METHODS: Our survey listed a range of prescribed specific CPS and solicited reasons why providers believed that they could not be delivered. RESULTS: The overall response rate was 87.4%. Altogether, 91.7% of those responding answered positively when asked if they were aware of specific CPS. Lack of time was the most commonly cited barrier to CPS delivery. Most providers felt that they had the skills necessary to deliver CPS to their patients, yet 84.4% indicated a willingness to receive additional training. CONCLUSIONS: Our findings suggest that these providers are willing to deliver CPS to their patients.

Efficacy of three statins at lower maintenance doses.

The purpose of this study was to determine whether patients who are receiving lovastatin 20 mg daily can be switched to daily regimens of lovastatin 10 mg, pravastatin 10 mg, or simvastatin 5 mg without loss of lipid control or an increase in side effects. One hundred five patients were identified whose lipid levels were clinically stable on a regimen of lovastatin 20 mg/d; these patients were randomly allocated to a group that continued to receive lovastatin 20 mg/d (the control group) or a group receiving 1 of the 3 alternative regimens. Patients were evaluated after 6 and 12 weeks of treatment for side effects and changes in liver and muscle enzymes and lipid levels compared with baseline. Of the 105 patients enrolled, 5 withdrew because of side effects, 4 did not return for follow up, and 3 were excluded. Ninety-three patients completed the 12-week study. When baseline values were compared to those at week 12 for each group, the proportions of patients meeting treatment goals for LDL cholesterol, as defined by the National Cholesterol Education Program, were as follows: control group, 30.8% improved; lovastatin 10 mg, 16.7% worsened; pravastatin 10 mg, 27.3% improved; and simvastatin 5 mg, no change. Patients who were switched from lovastatin 20 mg daily to pravastatin 10 mg or simvastatin 5 mg daily did not experience statistically significant changes in mean total cholesterol levels. Patients who were switched from 20 to 10 mg/d of lovastatin experienced increases in mean total cholesterol levels (from 195 mg/dL +/-5 mg/dL at baseline to 200 mg/dL +/-5 mg/dL at 12 weeks; P<0.05). There were no differences in side effects or in elevations in liver or muscle enzymes. Thus patients who are stable on 20 mg/d lovastatin can be switched to a regimen of 10 mg/d pravastatin or 5 mg/d simvastatin.

SAP30, a component of the mSin3 corepressor complex involved in N-CoR-mediated repression by specific transcription factors.

The transcriptional corepressor mSin3 is found in a large multiprotein complex containing the histone deacetylases HDAC1 and HDAC2, in addition to at least five tightly associated polypeptides. We have cloned and characterized a novel component of the mSin3 complex, SAP30, SAP30 binds to mSin3 and is capable of mediating transcriptional repression via histone deacetylases. SAP30 also binds the N-CoR corepressor and is required for N-CoR-mediated repression by antagonist-bound estrogen receptor and the homeodomain protein Rpx, as well as N-CoR suppression of transactivation by the POU domain protein Pit-1. However, SAP30 is not required for N-CoR-mediated repression by unliganded retinoic acid receptor or thyroid hormone receptor, suggesting that SAP30 is involved in the functional recruitment of the mSin3-histone deacetylase complex to a specific subset of N-CoR corepressor complexes.

Wound infection rate and irrigation pressure of two potential new wound irrigation devices: the port and the cap.

The objectives of this study were to determine the speed of irrigation and the infection rate of two new irrigation devices. In the clinical portion of this two-part study, 208 patients with traumatic wounds were randomized to one of two new irrigation device groups, the cap/bottle or the port/bag, to determine irrigation times and infection/complication rates. Wounds were irrigated in less than 4 minutes in 97% of patients using a mean of 786 mL. The combined infection/complication rates were: port group, 1 of 99 (1%); cap group, 4 of 108 (4%), P = .356. In part II, 9 male and 8 female medical volunteers were timed in the delivery of 250 mL of saline into a graduated cylinder, using four different irrigation set-ups. Mean time for 250 mL and calculated stream pressures (psi) were: (1) cap/bottle, 12.9 seconds, 1.5 psi; (2) port/bag, 11.2 seconds, 2.0 psi; (3) syringe/catheter, 113.2 seconds, 8.2 psi; and (4) syringe/needle, 175.4 seconds, 7.3 psi (time and psi: P < .05 for all pairwise comparisons except cap versus port). Rapid irrigation and infection rates comparable with standard devices used in wound irrigation suggest that the new devices may prove to be valuable tools in emergent wound care.