Benefit of coronary reperfusion before intervention on outcomes after primary angioplasty for acute myocardial infarction

Primary percutaneous transluminal coronary angioplasty has become the preferred reperfusion strategy for acute myocardial infarction in most institutions with interventional facilities and experienced operators. The benefit of establishing coronary reperfusion, with or without pharmacologic therapy, before primary angioplasty has not been established. Consecutive patients (n = 1,490) with acute myocardial infarction treated with aspirin and heparin followed by primary percutaneous transluminal coronary angioplasty were followed for 13 years. Follow-up angiography was obtained in 737 patients at 7.7 months. Thrombolysis In Myocardial Infarction (TIMI) 2 to 3 flow in the infarct artery at initial angiography was present in 18.3% of patients, and TIMI 0 to 1 flow in 81.7% of patients. Baseline variables were similar between the 2 groups, except patients with initial TIMI 2 to 3 flow had significantly less cardiogenic shock (1.7% vs 9.4%, p <0.0001) and a lower incidence of depressed ejection fraction <40% (12.6% vs 19.9%, p = 0.007). Procedural success was better in patients with initial TIMI 2 to 3 flow (97.4% vs 93.8%, p = 0.02), and catheterization laboratory events were less frequent. Patients with initial TIMI 2 to 3 flow had lower peak creatine kinase values (1,328 vs 2,790 IU/L, p <0.0001), higher acute ejection fraction (54.3% vs 51.6%, p = 0.05), higher late ejection fraction (59.2% vs 54.9%, p = 0.004), and lower 30-day mortality (4.8% vs 8.9%, p = 0.02). These data indicate that when reperfusion occurs before primary angioplasty, outcomes are strikingly better with less cardiogenic shock, improved procedural outcomes, smaller infarct size, better preservation of left ventricular function, and reduced mortality. This should encourage new strategies to establish reperfusion before "primary" angioplasty with "catheterization laboratory friendly" platelet inhibitors and/or low-dose thrombolytic drugs.     

Relationship between the area of cartilage shown on the magnetic resonance imaging middle-slice image of the medial and lateral tibial cartilages with cartilage volume and grade of osteoarthritis over time

OBJECTIVE: Knee cartilage volume measurement requires significant time and training. Simplifying the measurement may improve feasibility. We investigated whether the area of cartilage shown on the middle slice of the medial and lateral tibial cartilages on sagittal MRI correlates with radiological features of osteoarthritis (OA), cartilage volume, and longitudinal change in cartilage volume. METHODS: One hundred and seventy-three subjects (normal and osteoarthritic), who had serial magnetic resonance imaging (cartilage volume measured) and baseline weight-bearing antero-posterior radiographs of the same knee were examined. RESULTS: In the lateral compartment, with increasing grade of OA there was a significant reduction in cartilage area. In the medial compartment, this was true for medial joint-space narrowing (after adjusting for gender). There was a moderate to strong association between cartilage area and volume, especially in those with early or no OA. However, when change over time was examined, the strength of these relationships was weak. CONCLUSION: Our data suggests that cartilage area may provide a simple surrogate measure of cartilage volume, in cross-sectional studies, after adjustment for gender: especially in subjects with early disease. However, before it can be widely used, further investigation will be required.     

Prospective, randomized evaluation of thrombectomy prior to percutaneous intervention in diseased saphenous vein grafts and thrombus-containing coronary arteries

OBJECTIVES: We sought to determine whether routine thrombectomy prior to stent implantation in diseased saphenous vein grafts (SVGs) and thrombus-containing native coronary arteries would reduce peri-procedural myonecrosis and subsequently enhance event-free survival. BACKGROUND: Percutaneous coronary intervention in diseased SVGs and thrombotic native coronary arteries is complicated by a high rate of peri-procedural myocardial infarction (MI). Thrombectomy prior to intervention may enhance the safety of intervention and improve early and late outcomes in these high-risk patients. METHODS: At 60 centers in the U.S. and Canada, 797 patients with 839 diseased SVGs or thrombus-containing native coronary arteries were prospectively randomized to stent implantation with versus without prior thrombectomy with the X-SIZER device (ev3, Plymouth, Minnesota). RESULTS: Peri-procedural MI occurred in 15.8% of patients assigned to the X-SIZER device compared with 16.6% of control patients (p = 0.77), although the rate of large MI (pre-specified as the development of new pathologic Q waves or creatine phosphokinase-MB isoenzyme elevation >8 x upper limits of normal) was reduced with X-SIZER device use from 9.6% to 5.5% (multivariate risk ratio 0.35 [95% confidence interval 0.18 to 0.66], p = 0.002). Major adverse cardiac events (cardiac death, MI, or repeat target vessel revascularization) occurred in 16.8% of X-SIZER patients versus 17.1% of control patients at 30 days (p = 0.92), and in 31.3% of X-SIZER patients versus 28.2% of control patients at 1 year (p = 0.35). CONCLUSIONS: Thrombectomy with the X-SIZER device prior to stent implantation in high-risk diseased SVGs and thrombus-containing native coronary arteries may reduce the extent, but not the occurrence, of myonecrosis. Early and late event-free survival, however, were not improved by routine thrombectomy with this device.     

Effect of estrogen replacement therapy on patella cartilage in healthy women

OBJECTIVES: Patellofemoral osteoarthritis (OA) is a significant cause of morbidity. Epidemiological data suggests that the use of oestrogen replacement therapy (ERT) may protect against tibiofemoral knee OA. However, the effect on patellofemoral OA is unknown. The aim of this study was to test the hypothesis that long term ERT (greater than 5 years) is associated with increased patella cartilage in post menopausal women. METHODS: We studied 81 women (42 current users (> 5 yrs) of oestrogen replacement therapy and 39 never users). Articular cartilage volumes were determined by post-processing images acquired in the sagittal plane using a T1-weighted fat suppressed magnetic resonance sequence on an independent workstation. RESULTS: There was no difference in the amount of patella cartilage in women on ERT compared to women on no ERT. After adjusting for patella bone size, years since menopause, body mass index, age of menopause and smoking, ERT users had 2.07 +/- 0.76 ml of patella cartilage compared to 1.93 +/- 0.89 ml in non-users (P = 0.24 for difference). CONCLUSIONS: This study suggests that use of ERT for more than 5 years does not have a significant effect on patella cartilage, in contrast to the previously described effect on tibial cartilage. The reasons for this are unknown, but may indicate that there are differences in the mechanisms for development of knee OA at these sites.     

Poikilocytic hereditary elliptocytosis associated with spectrin Alexandria: an alpha I/50b Kd variant that is caused by a single amino acid deletion

Hereditary elliptocytosis (HE) is a heterogeneous disorder of red blood cells frequently associated with abnormal limited tryptic digestion of the alpha I domain of spectrin and impaired spectrin dimer self- association. We studied two related individuals with poikilocytic hereditary elliptocytosis (HE) of different severity. Limited tryptic digestion of spectrin from these individuals showed the presence of a variant alpha I/50b Kd peptide at the expense of the normal alpha I/80 Kd peptide. Amino acid sequence analysis of the abnormal peptide showed that the proteolytic cleavage occurred after the arginine at position 470 of the alpha spectrin chain. Spectrin from these patients had an impaired ability to undergo self-association, as evidenced by increased amounts of spectrin dimers in 4 degrees C extracts of erythrocyte membrane from affected individuals. The polymerase chain reaction was used to study the DNA sequence of the alpha spectrin gene encoding the region of the alpha spectrin chain surrounding the abnormal proteolytic cleavage site. We detected the in-frame deletion of the trinucleotide CAT, encoding histidine 469, two amino acid residues to the N-terminal side of the abnormal proteolytic cleavage site between residues 470 and 471. Similar to many other defects of spectrin associated with HE, this deletion occurs in helix three of repeat 5 of the proposed triple helical model of spectrin repeats.     

Impact of anemia in patients with acute myocardial infarction undergoing primary percutaneous coronary intervention: analysis from the Controlled Abciximab and Device Investigation to Lower Late Angioplasty Complications (CADILLAC) Trial

OBJECTIVES: We sought to investigate the impact of anemia in patients with acute myocardial infarction (AMI) undergoing primary percutaneous coronary intervention (PCI). BACKGROUND: The prognostic importance of anemia on primary PCI outcomes is unknown. METHODS: In the Controlled Abciximab and Device Investigation to Lower Late Angioplasty Complications (CADILLAC) trial, 2,082 patients of any age with AMI within 12 h onset undergoing primary PCI were randomized to balloon angioplasty versus stenting, each +/- abciximab. Outcomes were stratified by the presence of anemia at baseline, as defined by World Health Organization criteria (hematocrit <39% for men and <36% for women). RESULTS: Anemia was present in 260 (12.8%) of 2,027 randomized patients with baseline laboratory values. Patients with versus without baseline anemia more frequently developed in-hospital hemorrhagic complications (6.2% vs. 2.4%, p = 0.002), had higher rates of blood product transfusions (13.1% vs. 3.1%, p < 0.0001), and had a prolonged (median 4.1 vs. 3.5 days, p < 0.0001) and more expensive (median costs $12,434 vs. $11,603, p = 0.002) index hospitalization. Patients with versus without anemia had strikingly higher mortality during hospitalization (4.6% vs. 1.1%, p = 0.0003), at 30 days (5.8% vs. 1.5%, p < 0.0001), and at 1 year (9.4% vs. 3.5%, p < 0.0001). The rates of disabling stroke at 30 days (0.8% vs. 0.1%, p = 0.005) and at 1 year (2.1% vs. 0.4%, p = 0.0007) were also significantly higher in patients with anemia. By multivariate analysis, anemia was an independent predictor of in-hospital mortality (hazard ratio, 3.26; p = 0.048) and one-year mortality (hazard ratio, 2.38; p = 0.016). CONCLUSIONS: Anemia at baseline in patients with AMI undergoing primary PCI is common, and is strongly associated with adverse outcomes and increased mortality.     

The management of scaphold fractures.

Appropriate management of scaphoid fractures is important because of the risk of long-term complications such as delayed or non-union, pain and disability. Up to 25% of scaphoid fractures are not visible on the initial radiographs. Consequently, all clinically suspected scaphoid fractures are treated as fractures with cast immobilisation until cause of the symptoms is clarified. The diagnosis often utilises a number of second line investigations that are generally performed 10-14 days after the injury. Bone scintigraphy is currently the most commonly used of these as it rarely misses a fracture. However, it does not visualise anatomical structure and therefore alternative diagnoses are difficult. Magnetic resonance imaging (MRI) is at least as sensitive and more specific than bone scanning and has the advantages of being able to identify other lesions and not expose the patient to any radiation. Furthermore, the scan may be performed as early as 2.8 days following an injury rather than 10 days later in the case of a bone scan. Although the cost of MRI is higher than other imaging modalities, it may be cost-effective in the overall management of patients with occult scaphoid fractures since it may prevent unnecessary cast immobilisation in active people. The most appropriate method of cast immobilisation is presently unclear but evidence exists for improved clinical outcomes in those that have both the thumb and elbow immobilised for the first six weeks.     

Extreme cutaneous histamine sensitivity with hay fever and increased IgE concentrations in an unselected population

Cutaneous sensitivity to histamine, responses to prick tests with allergens, and serum IgE concentrations were measured and hay fever assessed by questionnaire in an unselected population to determine whether increased sensitivity to histamine is an independent phenomenon contributing to allergic disorders or may be caused by allergic reactions. Increased cutaneous sensitivity to histamine was strongly associated with an increased number of positive responses to prick tests, high serum concentrations of IgE, and hay fever. This new test is simple, cheap, applicable to schoolchildren, and provides useful information.     

INDIVIDUALISATION OF HIV THERAPY: THE CLINICIAN'S PERSPECTIVE

SUMMARY Assessment of clinical and laboratory markers of HIV infection may be used to individualise antiretroviral therapy. Data suggest that measures of viral load may be of considerable value as both a baseline and dynamic therapy marker, making these tools particularly useful in driving therapeutic decisions. Similarly, in-vitro data regarding intracellular pharmacokinetics and activity, resistance patterns and potential synergy of antiretroviral agents may be used to guide selection of optimal treatment regimens in clinical practice.