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Biomedical subjects

Michael Collins

Publications and source records attributed to Michael Collins.

At least 37 records · Page 2Linked to original sources

Creatine kinase-MB enzyme elevation and long-term clinical events after successful coronary stenting in lesions with ruptured plaque.

Patients with acute coronary syndrome are at increased risk of acute and long-term events after stent implantation. We compared the impact of intravascular ultrasound detected plaque rupture on creatine kinase-MB (CK-MB) isoenzyme release and clinical outcomes by comparing 62 patients with ruptured plaques with 62 matched control patients who underwent stent implantation. Two thirds of the patients in each group presented with an acute coronary syndrome. There were no differences in procedural complications between groups, although patients with ruptured plaque had higher CK-MB elevation rates than those without ruptured plaque (1 to 3 times the upper limit of normal CK-MB, 35% vs 10%, p <0.001; >3 times the upper limit, 15% vs 2%, p = 0.02). Independent predictors of CK-MB elevation were presence of ruptured plaque (p = 0.03) and unstable angina (p = 0.04). Patients with ruptured plaque had higher composite rates of late events (target lesion revascularizations/myocardial infarctions/cardiac deaths) than controls (25% vs 9%, p = 0.03). These results were similar when only patients with acute coronary syndrome were studied. Plaque rupture morphology is associated with higher periprocedural CK-MB release and worse 1-year clinical outcome in patients treated with coronary stenting.

Analysis of Variance↗

A four-country investigation of factors facilitating student internet use.

Education and national culture may influence Internet use. The present study explored factors that might facilitate college students' use of the Internet across samples in four countries: India, Mauritius, Reunion Island (an overseas Department of France), and the United States. Questionnaire data was collected on students' extent and frequency of Internet use. Also, structured items asked about the factors that would help them to use the Internet more. Data was analyzed using dummy-coded multiple regression so as to compare responses across the country groups. The U.S. sample was coded as the reference group so that the regression coefficients in the equation provided a comparison between the U.S. sample and each other country represented. Further country comparisons were made using t-tests for differences between the regression coefficients. Results suggested that there was more Internet use in the U.S. sample compared to the others. The Non-Western samples also reported greater desire for Internet access and non-English web sites. Training on how to use the Internet and course requirements for Internet use were reported as helpful by the India and Mauritius groups to a greater extent than by those in Reunion and the United States. Implications of the present exploratory results are discussed for applications of theoretical models across cultures.

Adult↗

Comparison of directional coronary atherectomy and stenting versus stenting alone for the treatment of de novo and restenotic coronary artery narrowing.

Late lumen loss after directional coronary atherectomy (DCA) is mainly determined by arterial remodeling. We hypothesized that stent implantation after optimal lesion debulking could be an effective approach to reduce restenosis. A total of 753 patients with de novo or restenotic coronary lesions were prospectively randomized to DCA plus stenting (n = 381) or stenting alone (n = 372). The patients were followed for 12 months. Procedural success was achieved in 91.5% versus 97.3% (p = 0.0007) of patients treated with DCA plus stent versus stent alone. Optimal atherectomy (<20% residual stenosis) was achieved in 26.5% of patients. The final minimal luminal diameter and the acute gain were similar in the 2 groups. There was no increase in 30-day major adverse cardiac events in the DCA plus stent group (3.9% vs 2.4%, p = 0.30). The primary end point, angiographic restenosis at 8 months, occurred in 26.7% of patients treated with DCA plus stents and in 22.1% of patients treated with stents alone (p = 0.237). Clinical follow-up to 1 year showed no difference in mortality (1.3% vs 0.8%, p = 0.725), acute myocardial infarction (4.2% vs 3.5%, p = 0.706), and target vessel failure (composite of death, Q-wave myocardial infarction, and target vessel revascularization) (23.9% vs 21.5%, p = 0.487) between patients with DCA plus stents and those with stents alone. This study failed to support the hypothesis that DCA before stenting lowers the angiographic restenosis rate compared with stents alone. At 12-month follow-up, there were no significant differences between the 2 groups in rates of death, reinfarction, or target vessel failure.

Adult↗

Contribution of stent underexpansion to recurrence after sirolimus-eluting stent implantation for in-stent restenosis.

BACKGROUND: We used intravascular ultrasound (IVUS) to evaluate recurrence after sirolimus-eluting stent (SES) implantation treatment of in-stent restenosis (ISR). METHODS AND RESULTS: Forty-eight ISR lesions (41 patients with objective evidence of ischemia) were treated with SES. Recurrent ISR was identified in 11 lesions (all focal); repeat revascularization was performed in 10. These were compared with 16 patients (19 lesions) without recurrence as documented by angiography. Nine of 11 recurrent lesions had a minimum stent area (MSA) <5.0 mm2 versus 5 of 19 nonrecurrent lesions (P=0.003); 7 of 11 recurrent lesions had an MSA <4.0 mm2 versus 4 of 19 nonrecurrent lesions (P=0.02); and 4 of 11 recurrent lesions had an MSA <3.0 mm2 versus 1 of 19 nonrecurrent lesions (P=0.03). A gap between SESs was identified in 3 of 11 recurrences versus 1 of 19 nonrecurrent lesions. CONCLUSIONS: Stent underexpansion is a significant cause of failure after SES implantation treatment of ISR.

Combined Modality Therapy↗

Fyn and PTP-PEST-mediated regulation of Wiskott-Aldrich syndrome protein (WASp) tyrosine phosphorylation is required for coupling T cell antigen receptor engagement to WASp effector function and T cell activation.

Involvement of the Wiskott-Aldrich syndrome protein (WASp) in promoting cell activation requires its release from autoinhibitory structural constraints and has been attributed to WASp association with activated cdc42. Here, however, we show that T cell development and T cell receptor (TCR)-induced proliferation and actin polymerization proceed normally in WASp-/- mice expressing a WASp transgene lacking the cdc42 binding domain. By contrast, mutation of tyrosine residue Y291, identified here as the major site of TCR-induced WASp tyrosine phosphorylation, abrogated induction of WASp tyrosine phosphorylation and its effector activities, including nuclear factor of activated T cell transcriptional activity, actin polymerization, and immunological synapse formation. TCR-induced WASp tyrosine phosphorylation was also disrupted in T cells lacking Fyn, a kinase shown here to bind, colocalize with, and phosphorylate WASp. By contrast, WASp was tyrosine dephosphorylated by protein tyrosine phosphatase (PTP)-PEST, a tyrosine phosphatase shown here to interact with WASp via proline, serine, threonine phosphatase interacting protein (PSTPIP)1 binding. Although Fyn enhanced WASp-mediated Arp2/3 activation and was required for synapse formation, PTP-PEST combined with PSTPIP1 inhibited WASp-driven actin polymerization and synapse formation. These observations identify key roles for Fyn and PTP-PEST in regulating WASp and imply that inducible WASp tyrosine phosphorylation can occur independently of cdc42 binding, but unlike the cdc42 interaction, is absolutely required for WASp contributions to T cell activation.

Animals↗

CYP3A5 genotype and midazolam clearance in Australian patients receiving chemotherapy.

OBJECTIVES: Cytochrome P450 (CYP) 3A enzymes are key metabolizing enzymes for many chemotherapeutic agents, and detection of functionally significant CYP3A genetic variants may be useful in predicting interpatient variation of drug clearance. We have examined the significance of CYP3A5*3 single-nucleotide polymorphism to overall CYP3A activity in vivo in a predominantly Caucasian Australian cancer population. METHODS: Screening for wild-type CYP3A5*1 and CYP3A5*3 single nucleotide polymorphism by use of Taqman MGB probe allelic discrimination was performed in 67 patients with cancer (58 Caucasian patients). CYP3A activity was documented via clearance of either oral or intravenous midazolam in 64 patients. RESULTS: All patients had at least 1 CYP3A5*3 allele, and 9 (13%) patients were heterozygous for CYP3A5*3 and CYP3A5*1. Within the subset of Caucasian patients, 6 of 58 (10%) were CYP3A5*1/*3 heterozygotes. Mean midazolam clearance was 1.7 times higher in CYP3A5*1/*3 subjects than in CYP3A5*3/*3 subjects (95% confidence interval, 1.15-2.51; P =.01, 2-way ANOVA). CONCLUSION: Overall CYP3A activity is related to CYP3A5 genotype. CYP3A5 genotyping may be helpful in predicting the drug-metabolizing capability of individual cancer patients who are predominantly Caucasian in origin.

Adult↗

Managing the production, storage, and delivery of colostrum.

Provision of an adequate immunoglobulin mass to dairy calves is an essential component for survival, health, and future productivity. To prevent FPT of immunity due to suckling of the dam, newborn dairy calves should be removed from the calving area within 30 minutes of birth. First and later lactation cows are suitable colostrum donors, provided they are healthy, well-vaccinated, have had optimal transition management, and an appropriate dry-period length. Early colostrum collection yields an adequate immunoglobulin mass provided that 3 to 4 L of colostrum is fed to the newborn calf. Regular testing for the adequacy of the dairy's colostrum feeding program is an excellent way to prevent calf health problems and identify potential need for CSs or replacement products.

Animals↗

A comparison of the pharmacokinetics of oral and sublingual cyproheptadine.

BACKGROUND: Cyproheptadine is reported to be effective in treating serotonin syndrome. It is only available as an oral preparation and administration after SSRI overdose treated with activated charcoal is problematic. Sublingual administration may circumvent this problem. The pharmacokinetics of sublingual cyproheptadine are not characterized. This study compares the pharmacokinetics of cyproheptadine following oral and sublingual administration. METHODS: Cross-over, non-blinded, volunteer study using five healthy males. Eight milligrams of oral and sublingual cyproheptadine were administered on separate occasions with a one-week washout period. Sublingual arm subjects were pretreated with 50 g of oral activated charcoal 30 min prior to cyproheptadine, to prevent any gut absorption. Serum cyproheptadine concentration was measured at baseline, 30 min, and 1, 2, 3, 4, 6, 8, and 10 h by liquid chromatography and mass spectroscopy. RESULTS: Mean C(max) for oral and sublingual were 30.0 microg/L and 4.0 microg/L respectively: mean T(max) were 4 h and 9.6 h; mean AUC were 209 and 25 microg x hr/L. Mean +/- SEM within-subject difference between oral and sublingual C(max) was 25.9 +/- 4.1 (p = 0.003) and AUC was 184 +/- 31 (p = 0.004). CONCLUSIONS: Serum concentrations after sublingual cyproheptadine are significantly less than after oral administration. At these concentrations, the sublingual route is unlikely to be effective in treating serotonin syndrome.

Administration, Oral↗

Contrasting Wuchereria bancrofti microfilaria rates in two Mangyan-populated Philippine villages.

Lymphatic filariasis caused by infection with Wuchereria bancrofti and Brugia malayi is endemic in 45 of 77 provinces in The Philippines. To prepare the island of Mindoro for mass treatment using diethylcarbamazine and albendazole, complete census data were collected in rural villages. A sample of individuals selected from each of two adjacent villages was examined for microfilaremia. Microfilariae were detected from thin smears in 34 (13%) of 272 patients examined from the village of Bayanan and 10 (3.4%) of 292 in the village of Mangangan (P < 0.01, by chi-square test). In these villages, the majority of those infected were members of the ethnic group known as Mangyans: 33 (97%) of 24 in Bayanan and 7 (70%) of 10 in Mangangan (risk ratio = 89, 95% confidence interval = 33-240, P < 0.001.) In children examined who were less than 10 years of age (n = 165), girls were more commonly infected than boys, even though the proportion of males in the general population was greater. Understanding sociocultural characteristics and related behaviors in future observations among the Mangyan may help to explain local differences in the distribution of filariasis. This information should also be helpful in designing more culturally appropriate strategies for the control of lymphatic filariasis among ethnic minorities in The Philippines.

Albendazole↗

Comparison of safety and efficacy between first and second generation of angio-seal closure devices in interventional patients.

Arterial closure devices are safe and effective in selected patients, with complication rates similar to or lower than manual compression. The purpose of this study was to compare the safety and efficacy of the first- and new-generation Angio-Seal devices in patients undergoing PCI. This study found that the new Angio-Seal STS Platform device can secure hemostasis after PCI in a safe and effective manner similar to the old device. The new platform is easier for the operator and for the patients.

Adult↗

Acute and long-term outcomes of cutting balloon angioplasty followed by gamma brachytherapy for in-stent restenosis.

In-stent restenosis lesions were divided into 2 groups according to the use of cutting balloon (n = 76) or conventional balloon angioplasty (n = 407) before gamma-brachytherapy. Cutting balloon angioplasty, compared with conventional balloon angioplasty, in patients undergoing gamma-brachytherapy for in-stent restenosis is associated with less requirement for new stents (11% vs 22%, p = 0.02) but similar target vessel revascularization (35.1% vs 29.8%, p = 0.4) at follow-up.

Aged↗

Intravascular ultrasound assessment of ulcerated ruptured plaques: a comparison of culprit and nonculprit lesions of patients with acute coronary syndromes and lesions in patients without acute coronary syndromes.

BACKGROUND: It is not clear why some plaque ruptures lead to acute coronary syndromes (ACS) but others do not. METHODS AND RESULTS: We analyzed 80 plaque ruptures in 74 patients and compared culprit lesions of ACS patients with nonculprit lesions of ACS patients and lesions of non-ACS patients; both culprit and nonculprit plaque ruptures were studied in 6 of 54 ACS patients. Intravascular ultrasound findings suggesting thrombus were observed more frequently in culprit lesions of ACS patients (n=35) compared with nonculprit lesions of ACS patients (n=19) and lesions of non-ACS patients (n=26): 60% versus 32% versus 8% (P<0.001). At the minimal lumen site, smaller lumen areas (3.3+/-1.5 versus 5.4+/-2.6 versus 6.1+/-2.0 mm2, P<0.001) and greater area stenosis (61+/-15% versus 50+/-14% versus 46+/-18%, P=0.002) and plaque burden (80+/-8% versus 71+/-8% versus 69+/-10%, P<0.001) were observed in culprit lesions of ACS patients compared with nonculprit lesions of ACS patients and lesions of non-ACS patients. Lesions were longer (18.7+/-6.4 versus 154.9+/-6.1 versus 12.0+/-4.9 mm, P<0.001) and rupture site remodeling indices were greater (1.26+/-0.21 versus 1.24+/-0.21 versus 1.09+/-0.05, P=0.002). Independent predictors of culprit plaque ruptures in ACS patients were smaller minimum lumen areas (P=0.02) and presence of thrombus (P=0.01). CONCLUSIONS: Ruptured plaques in culprit lesions of ACS patients have smaller lumens; greater plaque burdens, area stenosis, and remodeling indices; and more thrombus. Plaque rupture itself does not lead to symptoms. The association of plaque rupture with a smaller lumen area and/or thrombus formation causes lumen compromise and leads to symptoms.

Acute Disease↗

Labor and delivery factors in brain damage, disabling cerebral palsy, and neonatal death in low-birth-weight infants.

OBJECTIVE: We assessed the relationships between active labor and neonatal death, neonatal brain damage, and disabling cerebral palsy in low-birth-weight infants. STUDY DESIGN: A population-based cohort of 961 infants with birth weights of 580 to 2000 g and gestational ages >or=26 completed weeks. Neonatal brain damage was assessed by ultrasound scanning in the first weeks of life; disabling cerebral palsy was assessed at 2 years of age (corrected for gestational age). RESULTS: After being controlled for possible confounders, active labor was associated significantly with an increased risk of parenchymal echodensities/lucencies and/or ventricular enlargement (odds ratio, 2.3; 95% CI, 1.2-4.5) but not with germinal matrix/intraventricular hemorrhage (odds ratio, 1.3; 95% CI, 0.8-2.1), neonatal death (odds ratio, 1.8; 95% CI, 0.8-4.0), or disabling cerebral palsy (odds ratio, 1.6; 95% CI, 0.7-3.7). In vertex presentations only, active labor was associated with a nearly 4-fold increase in risk of neonatal death (odds ratio, 3.8; 95% CI, 1.3-10.9). In nonvertex presentations only, active labor was associated strongly with parenchymal echodensities/lucencies and/or ventricular enlargement (odds ratio, 4.3; 95% CI, 1.2-15.6) and disabling cerebral palsy (odds ratio, 8.2; 95% CI, 1.4-49.9). CONCLUSION: The only adverse outcome that was associated consistently with active labor was parenchymal echodensities/lucencies and/or ventricular enlargement. Fetal presentation modified the relationships between active labor and adverse outcomes. Delivery mode (whether vaginal or cesarean delivery) was not associated with any of the outcomes that were evaluated.

Brain Damage, Chronic↗

Methicillin-resistant Staphylococcus aureus (MRSA) in the practice of otolaryngology--an emerging community acquired organism?

Soon after antibiotics were introduced to treat bacterial infections, resistance to these agents began to emerge. Staphylococcus aureus, a common organism in human infection, quickly became resistant to penicillin; however, semisynthetic penicillins seemed to have tremendous staying power. The recent emergence of methicillin-resistant S. aureus (MRSA) created a difficult problem in treating many hospital-acquired infections soon after it was discovered. However, now it appears to be spreading into the community at large. Although newer antibiotics have been developed to help manage this threat, multiple-drug resistance remains a fear among healthcare professionals. Eradication of MRSA appears to be an unachievable goal at this time, so attention has focused on decreasing the spread of this organism, often through simple hand-washing protocols. The continued spread of MRSA will have tremendous impact on the practice of medicine and otolaryngology during the next decade and beyond.

Community-Acquired Infections↗

Vision and work.

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Humans↗