Microvessels in Chronic Total Occlusions: Pathways for Successful Guidewire Crossing?

Arterial chronic total occlusions (CTO) are a common and clinically relevant problem in patients with coronary artery disease. Percutaneous coronary intervention (PCI) success rates in a wide range of CTO are low, primarily due to inability of guidewire crossing. The pathophysiology of CTO is poorly understood and limits our ability to introduce innovative therapies. Recent studies from our laboratory have suggested that microvessel formation within arterial CTO is a complex process with temporal and regional differences. Moreover, there is evidence from pilot studies that the presence of either microvessels or the particular extracellular matrix environment in the adjacent perivascular tissue can facilitate guidewire crossing and successful PCI. Currently, studies are underway in our experimental CTO model to delineate the pathophysiology of microvessel formation in CTO and its potential role in PCI.     

Activity of telithromycin against key pathogens associated with community-acquired respiratory tract infections

OBJECTIVES: To investigate the correlation between in vitro susceptibility of isolates and clinical outcomes with telithromycin in respiratory tract infections. METHODS: The activity of telithromycin was determined by in vitro susceptibility testing of key respiratory tract pathogens isolated from patients with community-acquired pneumonia, acute exacerbations of chronic bronchitis or acute maxillary sinusitis enrolled in 14 Phase III/IV clinical trials evaluating the clinical efficacy of telithromycin. RESULTS: In this pooled analysis, telithromycin mode minimum inhibitory concentration (MIC) and MIC90, respectively, were: 0.016 and 0.03 mg/l against Streptococcus pneumoniae (n=626); 0.03 and 0.5 mg/l for penicillin-resistant S. pneumoniae (n=56); 0.03 and 1 mg/l for erythromycin-resistant S. pneumoniae (n=81); 2 and 4 mg/l against Haemophilus influenzae (including beta-lactamase producers; n=627); both 0.12 mg/l for Moraxella catarrhalis (n=159) and both 0.25 mg/l for Staphylococcus aureus (n=124). Telithromycin (5 or 7-10 days) resulted in overall clinical and bacteriologic success rates of 88.1% (1593/1808) and 89% (1593/1789), respectively. CONCLUSIONS: High levels of in vitro susceptibility to telithromycin are paralleled by high rates of clinical cure and bacteriologic eradication.     

Antibiotic-impregnated catheters associated with significant decrease in nosocomial and multidrug-resistant bacteremias in critically ill patients

OBJECTIVE: To evaluate the impact of using central venous catheters (CVCs) impregnated with the combination of minocycline and rifampin on nosocomial bloodstream infections (BSIs), morbidity, and mortality in cancer patients in the ICU. DESIGN: Prospective surveillance study consisting of the following two time periods: September 1997 through August 1998 (ie, fiscal year [FY] 1998); and from September 1998 through August 1999 (ie, FY 1999). SETTING: ICUs of a tertiary care hospital in Houston, TX. PATIENTS: Cancer patients in the medical ICU (MICU) and surgical ICU (SICU). INTERVENTIONS: ICUs started using CVCs impregnated with the minocycline-rifampin combination at the beginning of FY 1999. Measurements and main results:The rates of nosocomial BSIs and other patients' characteristics were compared for the two study periods to determine the impact of using the impregnated catheters in the ICU. Patients' characteristics, including antibiotic use, were comparable for the two study periods in both the MICU and the SICU. The rate of nosocomial BSIs in the MICU unit decreased from 8.3 to 3.5 per 1,000 patient-days (p < 0.01), and decreased in the SICU from 4.8 to 1.3 per 1,000 patient-days (p < 0.01) in FY 1999. Nosocomial vancomycin-resistant enterococcus (VRE) bacteremia also decreased significantly (p = 0.004). Length of stay in the MICU and SICU significantly decreased in FY 1999 (p < 0.01 and p = 0.03, respectively). The duration of hospitalization decreased for MICU and SICU patients (p = 0.06 and p < 0.01, respectively). The rate of catheter-related infections decreased from 3.1 to 0.7 per 1,000 patient-days in FY 1999 (p = 0.02). The decrease in infections resulted in net savings of at least $1,450,000 for FY 1999. CONCLUSIONS: The use of antibiotic-impregnated CVCs in the MICU and SICU was associated with a significant decrease in nosocomial BSIs, including VRE bacteremia, catheter-related infections, and lengths of hospital and ICU stays.     

Beta 2-integrin and L-selectin are obligatory receptors in neutrophil aggregation [see comments]

We have recently found that antibodies to L-selectin, the homing receptor on neutrophils, are as effective as those to beta 2-integrin at blocking formyl peptide-stimulated aggregation. Therefore, we investigated the requirements for expression of L-selectin and beta 2- integrin on adjacent cells during aggregation. Fluorescence flow cytometry allowed characterization of aggregates on the basis of size and color, as well as antibody binding to these two adhesive molecules. Formyl peptide-stimulated aggregate formation was measured for individual populations fluorescently labeled red (LDS-751) or green (CD44-FITC), and interpopulation red-green cell conjugates. Blocking either the beta 2-integrin or L-selectin adhesive epitope with monoclonal antibody on individual cell populations resulted in an approximately 50% reduction in two-color aggregation as compared with that in unblocked samples. Shedding the L-selectin on a cell population by preincubation with complexes of lipopolysaccharide and its plasma membrane binding protein also decreased aggregation to a control population by approximately 50%. We examined the aggregation of neutrophils from patients genetically deficient in beta 2-integrin and clinically leukocyte adhesion deficient (LAD). LAD adhesion to normal neutrophils was dependent on the expression of L-selectin on LAD cells and beta 2-integrin on normal cells. Thus, the minimum requirement for adhesion between two mixed populations of neutrophils was that one population expressed the beta 2-integrin and the other expressed the L- selectin adhesive epitope.     

Physician practices in the prevention of venous thromboembolism

OBJECTIVE: To determine the rate of use of prophylaxis for venous thromboembolism in high-risk hospital patients. DESIGN: A retrospective medical record review. SETTING: A community-wide study in 16 short-stay hospitals in central Massachusetts. PATIENTS: A total of 2017 patients with multiple risk factors for venous thromboembolism. MEASUREMENTS AND MAIN RESULTS: On the basis of age, length of hospitalization, and the presence of at least one additional major risk factor, 17% of 151,349 discharges (25,410 patients) were identified as being at high risk for venous thromboembolism. Eight percent of these discharges were randomly selected for medical record review. Prophylaxis for venous thromboembolism was received by 32% of these high-risk patients. Prophylaxis use among the 16 study hospitals varied widely, ranging from 9% to 56%, and was higher in teaching hospitals than in nonteaching hospitals (44% compared with 19%; P less than 0.001). One or more of the following methods of prophylaxis was used: low-dose heparin (78%), intermittent calf compression (13%), warfarin (12%), and inferior vena caval filter (3%). Use of prophylaxis increased with the number of risk factors identified (P less than 0.001). CONCLUSION: Prophylaxis for venous thromboemobolism is underused, particularly in nonteaching hospitals.     

Recurrent cerebral ischemia and mitral valve vegetation in a patient with antiphospholipid antibodies

A 37-year-old woman presented with a history of acute loss of vision in her left eye and a history of recurrent transient ischemic attacks. Subsequent investigations revealed a prolonged PTT. The lupus anticoagulant and anticardiolipin antibodies (aCL) were identified in her serum. A cardiac murmur was heard and echocardiography demonstrated a mass on the mitral valve. Extensive studies for infection were negative. Cardioembolic phenomena were considered a possible cause of her cerebral ischemic events. The occurrence of nonbacterial endocardial verrucae is well described in systemic lupus erythematosus. The pathogenesis of this lesion remains speculative, however, its occurrence in our patient, with a lupus anticoagulant and aCL suggests a possible association. The clinical manifestations of thrombosis in patients with antiphospholipid antibodies are varied, and may include the development of thrombotic endocardial lesions.     

The effect of changing practice on fall prevention in a rehabilitative hospital: the Hospital Injury Prevention Study

OBJECTIVES: To determine whether a change in practice to introduce a multidisciplinary fall-prevention program can reduce falls and injury in nonacute patients in a rehabilitation hospital. DESIGN: A quasi-experimental study. SETTING: Three geriatric wards with a similar design, equipment, staffing levels, and skill mix. PARTICIPANTS: Eight hundred twenty-five consecutive patients. INTERVENTION: The patients' fall-risk status was assessed using the Downton Score. Current practice was maintained on the two control wards (n=550). On the experimental ward (n=275), a fall-prevention program was introduced. A multidisciplinary team met weekly specifically to discuss patients' fall risk and formulate a targeted plan. Patients at risk were identified using wristbands; risk factors were corrected or environmental changes made to enhance safety. MEASUREMENTS: Primary outcomes were number of fallers, recurrent fallers, total falls, patients sustaining injury, and falls per occupied bed days. Secondary outcomes were place of discharge and mortality. RESULTS: Patients were matched for age and risk status. Control wards had proportionally more fallers (20.2% vs 14.2%: P=.033), patients sustaining injury (8.2% vs 4%: P=.025), and total number of falls (170 vs 72: P=.045). These results did not remain significant after controlling for differing length of stay. There was no reduction in recurrent fallers (6.4% vs 4.7%: P=.43) and no effect on place of discharge (home discharges; 57.5% vs 60.7%: P=.41) or mortality (15.3% vs 13.8%: P=.60). CONCLUSION: This study shows that falls might be reduced in a multidisciplinary fall-prevention program, but the results are not definitive because of the borderline significance achieved and the variable length of stay. More research on fall prevention in hospital is required, particularly as to what interventions, if any, are effective at reducing falls in this group of patients.     

Vasoconstrictor response to prostacyclin in rabbit pulmonary circulation

We have determined the effect of prostacyclin (PGI2) on segmental vascular resistance in rabbit lungs. Lungs of 26 rabbits were isolated and perfused with blood; 16 adult, greater than 6 months old, five juvenile, 6-8 week old and five neonatal, 2-3-week old. Six of the adult lungs were pretreated with indomethacin to block cyclooxygenase, prior to infusion of PGI2. In all lungs, flow was adjusted initially to keep pulmonary artery pressure approximately 20 cmH2O, left atrial and airway pressures being 8 and 6 cmH2O, respectively (zone 3), and then kept constant. We measured pulmonary artery pressure continuously and in the 10 untreated adult lungs, in which a vasoconstrictor response to PGI2 was obtained, we also measured pressures in 20-50 microns diameter subpleural arterioles and venules by the micropipette-servonulling method. We found that in juvenile and neonatal rabbit lungs, PGI2 did not change total vascular resistance significantly but in untreated adult lungs, it caused a significant increase in total vascular resistance only after a dose of 10 micrograms/kg. This age-related difference in vasoconstrictor response to PGI2 was not related to baseline total vascular resistance in the three groups of lungs. In adult lungs, vasoconstriction occurred mainly in arteries with a small effect in veins. Circulating levels of thromboxane B2, leukotriene C4, and 6-keto-PGF1 alpha increased following PGI2 infusion in adult lungs, whereas in neonatal lungs, only 6-keto-PGF1 alpha increased significantly. Indomethacin pretreatment completely abolished the vasoconstrictor response to PGI2. We conclude that PGI2-induced vasoconstriction is age and dose dependent in isolated rabbit lungs and that a cyclooxygenase product, such as thromboxane A2, may play a role in mediating the vasoconstriction.