Biomedical subjects

Michael Heffernan

Publications and source records attributed to Michael Heffernan.

7 recordsLinked to original sources

PubMed2006

Clinical response to adalimumab treatment in patients with moderate to severe psoriasis: double-blind, randomized controlled trial and open-label extension study.

BACKGROUND: Tumor necrosis factor is pivotal in the pathogenesis of psoriasis. Adalimumab is a fully human monoclonal immunoglobulin G1 antibody that neutralizes tumor necrosis factor. OBJECTIVES: We sought to assess the efficacy and safety of adalimumab in patients with moderate to severe plaque psoriasis. METHODS: In this multicenter, randomized, double-blind, placebo-controlled study, 147 patients received adalimumab (40 mg every other week or 40 mg/wk) or placebo. After 12 weeks of blinded therapy, patients taking adalimumab could continue their assigned dosages in a 48-week extension trial; patients taking placebo were switched to adalimumab (40 mg every other week). RESULTS: At week 12, 53% of patients taking adalimumab every other week, 80% of patients taking adalimumab weekly, and 4% of patients taking placebo achieved 75% improvement in Psoriasis Area and Severity Index score (P < .001). Responses were sustained for 60 weeks. No new safety signals were noted compared with the existing adalimumab clinical safety database. LIMITATIONS: The study was insufficiently powered to detect rare adverse events associated with adalimumab. CONCLUSIONS: Adalimumab significantly improved psoriasis and was well tolerated for 60 weeks.

Adalimumab↗

PubMed2006

Non ST segment elevation acute coronary syndromes: A simplified risk-orientated algorithm.

Non-ST segment elevation acute coronary syndromes (NSTE ACS) include a clinical spectrum that ranges from unstable angina to NSTE myocardial infarction. Management goals aim to prevent recurrent ACS and improve long-term outcomes by choosing a treatment strategy according to an estimate of the risk of an adverse outcome. Recent registry data suggest that patients with NSTE ACS frequently do not receive recommended treatment, and that risk stratification is not used to determine either the choice of treatment or the speed of access to coronary angiography. The present article evaluates the evidence for recommended treatment using information from recent trials and guidelines published by the major cardiac organizations in Europe and North America. Using this information, a multidisciplinary group developed a simplified algorithm that uses risk stratification to select an optimal early management strategy. Long-term outcomes are improved by a multi-faceted vascular protection strategy that is initiated at the time of hospitalization for NSTE ACS.

Acute Disease↗

PubMed2006

Transfer for urgent percutaneous coronary intervention early after thrombolysis for ST-elevation myocardial infarction: the TRANSFER-AMI pilot feasibility study.

BACKGROUND: Most hospitals in Canada do not have percutaneous coronary intervention (PCI) facilities and use thrombolysis as reperfusion therapy for ST-elevation myocardial infarction (STEMI). Urgent PCI after thrombolysis may optimize reperfusion and prevent reinfarction and recurrent ischemia. OBJECTIVE: To determine the feasibility of transferring high-risk STEMI patients from community hospitals in Ontario to PCI centres for urgent PCI within 6 h of thrombolysis. METHODS: Patients with anterior or high-risk inferior STEMI received tenecteplase and were urgently transferred to PCI centres. PCI was performed if at least 70% stenosis was present in the infarct-related artery, regardless of flow, using coronary stents. Transfer of stable patients back to community hospitals was encouraged 24 h to 48 h after PCI. RESULTS: Eighteen patients were transferred and underwent PCI a median of 3.9 h (range 2.7 h to 6.4 h) after thrombolysis. No complications occurred during transfer. One death occurred that was related to failed reperfusion and cardiogenic shock. Minor access-site bleeding occurred in five patients. Fifteen patients were transferred back to their community hospitals within 24 h of PCI. There were no further deaths or reinfarctions at one-year follow-up. CONCLUSIONS: Transfer of high-risk STEMI patients for urgent PCI within 6 h after thrombolysis appears feasible. The randomized trial phase of the Trial of Routine ANgioplasty and Stenting after Fibrinolysis to Enhance Reperfusion in Acute Myocardial Infarction (TRANSFER-AMI) will compare this strategy with standard treatment after thrombolysis.

Adult↗

PubMed2005

Myocardial recovery using ventricular assist devices: prevalence, clinical characteristics, and outcomes.

BACKGROUND: Ventricular assist devices (VADs) are important bridges to cardiac transplantation. VAD support may also function as a bridge to ventricular recovery (BTR); however, clinical predictors of recovery and long-term outcomes remain uncertain. We examined the prevalence, characteristics, and outcomes of BTR subjects in a large single center series. METHODS AND RESULTS: We implanted VADs in 154 adults at the University of Pittsburgh from 1996 through 2003. Of these implants, 10 were BTR. This included 2/80 (2.5%) ischemic patients (supported 42 and 61 days, respectively). Both subjects had surgical revascularization, required perioperative left VAD support, and were alive and transplant-free at follow up (232 and 1319 days, respectively). A larger percentage of nonischemic patients underwent BTR (8/74, 11%; age 30+/-14; 88% female; left ventricular ejection fraction 18+/-6%; supported 112+/-76 days). Three had myocarditis, 4 had post-partum cardiomyopathy (PPCM), and 1 had idiopathic cardiomyopathy. Five received biventricular support. After explantation, ventricular function declined in 2 PPCM patients who then required transplantation. Ventricular recovery in the 6 nonischemic patients surviving transplant-free was maintained (left ventricular ejection fraction 54+/-5%; follow-up 1.5+/-0.9 years). Overall, 8 of 10 BTR patients are alive and free of transplant (follow-up 1.6+/-1.1 years). CONCLUSIONS: In a large single center series, BTR was evident in 11% of nonischemic patients, and the need for biventricular support did not preclude recovery. For most BTR subjects presenting with acute inflammatory cardiomyopathy, ventricular recovery was maintained long-term. VAD support as BTR should be considered in the care of acute myocarditis and PPCM.

Acute Disease↗

PubMed2003

A putative RUNX1 binding site variant between SLC9A3R1 and NAT9 is associated with susceptibility to psoriasis.

Psoriasis (OMIM 177900) is a chronic inflammatory skin disorder of unknown pathogenesis affecting approximately 2% of the Western population. It occurs more frequently in individuals with human immunodeficiency virus, and 20-30% of individuals with psoriasis have psoriatic arthritis. Psoriasis is associated with HLA class I alleles, and previous linkage analysis by our group identified a second psoriasis locus at 17q24-q25 (PSORS2; ref. 7). Linkage to this locus was confirmed with independent family sets. Additional loci have also been proposed to be associated with psoriasis. Here we describe two peaks of strong association with psoriasis on chromosome 17q25 separated by 6 Mb. Associated single-nucleotide polymorphisms (SNPs) in the proximal peak lie in or near SLC9A3R1 (also called EBP50 and NHERF1) and NAT9, a new member of the N-acetyltransferase family. SLC9A3R1 is a PDZ domain-containing phosphoprotein that associates with members of the ezrin-radixin-moesin family and is implicated in diverse aspects of epithelial membrane biology and immune synapse formation in T cells. The distal peak of association is in RAPTOR (p150 target of rapamycin (TOR)-scaffold protein containing WD-repeats). Expression of SLC9A3R1 is highest in the uppermost stratum Malpighi of psoriatic and normal skin and in inactive versus active T cells. A disease-associated SNP lying between SLC9A3R1 and NAT9 leads to loss of RUNX1 binding. This is the second example of loss of a RUNX1 binding site associated with susceptibility to an autoimmune disease. It also suggests defective regulation of SLC9A3R1 or NAT9 by RUNX1 as a susceptibility factor for psoriasis.

Arylamine N-Acetyltransferase↗

PubMedDate not supplied

Template fabrication for a midpalatal orthodontic implant: technical note.

An implant has been developed as an adjunct to conventional orthodontic anchorage. Planning is advisable to determine the available bone and soft tissue thickness and the optimum position for orthodontic utilization. A simple method is described for fabrication of a radiographic and surgical template to aid in optimal placement of the implant.

Cephalometry↗

PubMedDate not supplied

Prognosis of endodontically treated teeth? Point.

The success rate of a restored, endodontically treated tooth is of interest to the dentist and patient when planning the treatment of a tooth requiring endodontics. The reported success rate for nonsurgical root canal treatment is varied within the dental literature. An alternative measure is tooth survival. This will include other factors related to endodontic treatment that result in poorer tooth survival. An understanding of the survival of endodontically treated teeth compared with alternative treatment modalities, such as dental implants, will provide for a more informed treatment plan.

Humans↗