Systemic markers of fibrinolysis after unsuccessful intracoronary streptokinase thrombolysis for acute myocardial infarction: Does nonreperfusion indicate failure to achieve a systemic lytic state?

Reasons for the failure of intracoronary streptokinase (STK) to result in coronary thrombolysis were examined in 45 patients with acute myocardial infarction presenting with angiographic evidence of total coronary occlusion. In 25 patients (group A), clot lysis was initially successful; in 20 (group B), reperfusion was unsuccessful. The STK dosage in group A ranged from 84,000 to 310,000 units (mean 188,000 +/- 12,000); STK dosage in group B ranged from 160,000 to 360,000 units (mean 267,000 +/- 11,000 [p less than 0.05]). Before therapy, levels of fibrin degradation products and serum fibrinogen were normal in all patients. After intracoronary STK, fibrin degradation products and serum fibrinogen levels changed similarly in both groups. Eight-five percent of patients in group B had evidence of a systemic fibrinolytic state. These data suggest that higher doses of STK administered in the same manner are unlikely to result in an increased reperfusion rate. Systemic hematologic markers of fibrinolysis are not helpful in explaining the success or failure of intracoronary thrombolysis.     

Functional and inducible expression of a transfected murine class II major histocompatibility complex gene.

Using the spheroplast fusion technique, we have introduced the cloned E beta b gene into two d haplotype cell lines, the B lymphoma line A20-2J and the macrophage tumor line P388D1. Analysis with a monoclonal antibody indicates that the product of the transfected E beta b gene associates with the endogenous E alpha chain to form an E alpha dE beta b complex. While expression of E alpha dE beta b is constitutive in A20-2J cells transfected with the E beta b gene, surface expression of E alpha dE beta b is detected in transfected macrophage cells only after treatment of cells with culture supernatants from concanavalin A (Con A)-stimulated T cells. Transfected B lymphoma cells and transfected Con A supernatant-treated macrophage cells have acquired the ability to present antigen to E alpha dE beta b-restricted T-cell hybridomas. The observed inducible expression of the transfected gene in the macrophage host indicates that sequences responsible for regulated expression of the E beta b gene may be associated with the transfected gene. In combination with directed mutagenesis, the system described here provides a means to study (i) E beta b sequences that are important in determining the restriction specificity of the E molecule and (ii) sequences associated with the E beta gene that may be important in the regulation of E beta chain expression.     

Angiographic evidence that reciprocal ST-segment depression during acute myocardial infarction does not indicate remote ischemia: Analysis of 23 patients

Although reciprocal ST-segment depression from the remote noninfarcting ventricular wall during acute myocardial infarction (Ml) is a common clinical finding, the significance of this electrocardiographic pattern is unclear. Previous retrospective studies have suggested that these findings may reflect either remote wall ischemia, multivessel coronary artery disease (CAD), extensive MI or a benign electrical phenomenon. Prior studies have lacked angiographic data obtained at the time of these acute electrocardiographic changes. In this study we prospectively evaluated 23 patients with acute MI. Left ventricular wall motion, coronary anatomy and the ECG were all assessed over a short period during the acute phase of the MI. Segmental wall motion was used as a sensitive indicator of ischemia.Seventeen patients had acute anterior MI, of whom 47 % had reciprocal ST-segment depression; 6 patients had inferior MI, with 3 showing reciprocal ST depression. The mean degree of ST-segment elevation from the infarcting wall tended to be greater in patients with reciprocal ST-segment depression than in those without such reciprocal ST depression (2.8 ± 0.4 vs 1.9 ± 0.3 mm, p = 0.06). Patients with and without reciprocal ST-segment depression had similar degrees of segmental dysfunction in the infarct wall. However, no abnormalities in segmental wall motion in the remote wall were seen regardless of the presence or absence of remote wall ST-segment depression. In addition, the presence or absence of ST-segment depression did not predict the extent or degree of CAD. Finally, the magnitude of ST-segment elevation from the acutely infarcting wall correlated significantly with the degree of remote wall reciprocal ST-segment depression (r = 0.83, p < 0.01).Thus, the presence of remote wall reciprocal ST-segment depression on the ECG during the acute phase of an MI does not predict ischemia or the extent of CAD in the arteries supplying the remote noninfarcting wall. Because the reciprocal electrocardiographic changes correlate with the degree of ST-segment elevation, they probably represent a benign electrical phenomenon.     

Phorbol esters modulate insulin receptor phosphorylation and insulin action in cultured hepatoma cells.

The effect of the tumor-promoting agent phorbol 12-myristate 13-acetate (PMA) on insulin receptors and insulin action was studied in rat hepatoma cells in culture. PMA (0.1-1.0 micrograms/ml) did not affect insulin binding either acutely or chronically but inhibited insulin stimulation of glycogen synthase and tyrosine aminotransferase. PMA (1 microgram/ml) stimulated the phosphorylation of the beta subunit of insulin receptor purified from [32P]phosphate-labeled Fao cells by 1.3-fold in the absence of insulin. In contrast, insulin-stimulated phosphorylation in the presence of PMA was reduced. Phosphoamino acid analysis of the beta subunit after PMA stimulation revealed an increase of both phosphoserine and phosphothreonine residues, whereas insulin stimulated primarily phosphorylation of tyrosine and serine residues. Insulin stimulation of cells after PMA treatment revealed a decrease in phosphotyrosine when compared to cells stimulated by insulin alone. Tryptic peptide mapping of the beta subunit by a two-dimensional chromatographic/electrophoretic separation revealed nine phosphopeptides from the cells treated with PMA. Insulin stimulated phosphorylation at six new sites in the receptor, three of which appeared to be similar to those in PMA-treated cells. This report shows that phorbol esters stimulate insulin receptor phosphorylation, inhibit insulin-induced receptor phosphorylation and insulin action, and suggest a physiologic relation between insulin action and the calcium-activated and phospholipid-dependent protein kinase C.     

Interrupted distal anastomosis: the interrupted "porcupine" technique

The distal coronary artery bypass graft anastomosis created by an interrupted technique using nitinol clips is likely superior to that created with continuous suture because surgeons place clips with optimal visualization, and the anastomosis exhibits optimal compliance and cannot become a “purse-string” once constructed. Skillful use of the clips allows the surgeon to work in the ever more cramped quarters of the minithoracotomy or minimally invasive incision. Anastomosing vessels without knot tying is a valuable practice in the application of remote and robotic surgeries.     

Early allergen exposure, skin prick responses, and atopic wheeze at age 5 in English children: a cohort study

BACKGROUND: For many years it has been assumed that the risk of childhood respiratory allergies is related to allergen exposures in early life. There are, however, few prospective data in support. We aimed to examine this relationship in a representative cohort of children born in Ashford, Kent (UK). METHODS: 625 children (94% of those eligible) were followed from birth to the age of 5.5 years at which time 552 underwent skin prick testing to extracts of house dust mite and cat fur allergens. Maternal reports of wheeze in the last year were collected by interview. These outcomes were related to individual domestic concentrations of Der p 1 and Fel d I allergens estimated from dust collection at the age of 8 weeks. RESULTS: 10% of children were sensitised to house dust mite or cat at age 5.5 years; 7% had atopic wheeze. No significant relationships between allergen exposure and either sensitisation or wheeze were found but, on examination, the exposure-response relationships for both allergens and for each outcome rose steeply at low levels of exposure and were attenuated at high levels of exposure. These patterns were modified by paternal atopy and by birth order. CONCLUSIONS: There are no linear relationships between early allergen exposure and the induction of childhood respiratory allergy; rather, the risks of IgE sensitisation and asthma rise at very low levels of exposure and are attenuated thereafter. These patterns are influenced by parental atopy and birth order. These findings suggest important gene-environment interactions in the development of atopy and asthma and imply that reductions in domestic allergen exposure alone are unlikely to have a major impact in decreasing the incidence of these diseases in childhood.     

Cryoablation treatment of benign breast lesions with 12-month follow-up

OBJECTIVE: Eighty percent of all breast biopsies reveal benign findings. The most common benign tumor is a fibroadenoma. Despite their benign nature, many women eventually choose to have their bothersome lumps surgically removed. We report the use of cryoablation to treat these benign breast lesions with minimum 12-month follow-up. METHODS: After receiving Institutional Review Board approval, a prospective nonrandomized trial was initiated in June 2000. Ultrasound-guided cryoablation of core biopsy-proven benign fibroadenomas, other benign breast nodules, or nodular fibrocystic change was performed on 78 lesions in 63 patients. Eighty-five percent of lesions treated were benign fibroadenomas. The cryoablation procedure consisted of a double freeze-thaw cycle that lasted between 6 and 30 minutes and was performed most often in an office setting. Each patient was serially evaluated for treatment efficacy, complications, and patient satisfaction. RESULTS: Sixty-four of 78 lesions (mean size 2.0 cm [range 0.8 to 4.2]) were followed-up for at least 12 months after cryoablation per protocol, which included 53 fibroadenomas. At 1 year, ultrasound tumor volume resorption was 88.3% overall (87.3% for fibroadenomas), and 73% of the entire group became nonpalpable to both clinician and patient (75% for fibroadenomas). Two of the fibroadenoma patients had their palpable residual nodule excised, both revealing necrotic debris and no viable tumor in the treated volume. Serial mammograms showed resorption of the lesion leaving minimal residual density without calcifications. Cosmesis was excellent with only a small scar remaining at the probe insertion site. There was no report of visual or palpable volumetric deficit. Patient satisfaction was good to excellent in 92% of cases. CONCLUSIONS: Cryoablation was successful in treating core biopsy-proven benign breast lesions in 63 patients. At 12 months, we found gradual resorption of treated tissue with no cosmetic deficit. Ultrasound-guided cryoablation is an effective and safe treatment for benign breast lesions, as seen at 12-month follow-up, and offers an office-based, minimally invasive alternative to surgical excision.     

Aneurysm enlargement following endovascular aneurysm repair: AneuRx clinical trial

OBJECTIVE: The purpose of this study was to determine the incidence and significance of aneurysm enlargement, with or without treatment, in relation to the primary end points of rupture, surgical conversion, aneurysm-related death, and survival following endovascular repair. METHOD: Aneurysm (AAA) size changes and clinical outcome of all patients treated from 1997 through 1998 during the Phase II AneuRx multicenter clinical trial of endovascular AAA repair were reviewed. Aneurysm dimensions and the presence or absence of endoleak were determined by an independent core laboratory, with enlargement or shrinkage defined as a diameter change of 5 mm or more compared with baseline. RESULTS: Among 383 patients (89% men, 11% women, age 73 +/- 9 years), with a mean device implant time of 36 +/- 11 months (median = 39 months), aneurysm diameter decreased from 5.7 +/- 1.0 at baseline to 5.2 +/- 1.0 at 3 years (P =.0001). A total of 46 patients (12%) experienced AAA enlargement, 199 patients (52%) had no change in AAA diameter, and 138 patients (36%) had a decrease in AAA diameter of 5 mm or more. Significant risk factors for enlargement included age (enlargement patients were 4 years older on average than patients with aneurysms that decreased in size; P =.002) and the presence of an endoleak (P <.001). Among patients with endoleak at any time, 17% had aneurysm enlargement, whereas only 2% of patients without endoleak had aneurysm enlargement (P <.001). Patients with enlargement were more likely to undergo secondary endovascular procedures and surgical conversions (P <.001). Twenty patients (43%) with enlargement underwent treatment, and 26 patients were untreated. There were two deaths following elective surgical conversion and one death in a patient with untreated enlargement and a type I endoleak. Three aneurysms ruptured: one with enlargement, one with no change, and one with a decrease in aneurysm size; all three aneurysms were larger than 6.5 cm. Kaplan-Meier analysis showed that freedom from rupture at 3 years was 98% with enlargement, 99% with no change, and 99% with decrease in AAA size (log-rank test, not significant). Freedom from AAA death at 3 years was 93% in patients with enlargement, 99% in no increase, and 99% in decrease (P =.005). Survival at 3 years was 86% with increase, 82% with no change, and 93% with decrease (P =.02). CONCLUSIONS: Aneurysm enlargement following endovascular repair was not associated with an increased risk of aneurysm rupture or decrease in patient survival during a 3-year observation period. Aneurysm size rather than enlargement may be a more meaningful predictor of rupture. Close follow-up and a high re-intervention rate (43%) may account for the low risk of rupture in patients with enlargement. The long-term significance of aneurysm enlargement following endovascular repair remains to be determined.     

Measurement of xenon diffusing capacity in the rat lung by hyperpolarized 129Xe MRI and dynamic spectroscopy in a single breath-hold.

We used the dual capability of hyperpolarized 129Xe for spectroscopy and imaging to develop new measures of xenon diffusing capacity in the rat lung that (analogously to the diffusing capacity of carbon monoxide or DLCO) are calculated as a product of total lung volume and gas transfer rate constants divided by the pressure gradient. Under conditions of known constant pressure breath-hold, the volume is measured by hyperpolarized 129Xe MRI, and the transfer rate is measured by dynamic spectroscopy. The new quantities (xenon diffusing capacity in lung parenchyma (DLXeLP)), xenon diffusing capacity in RBCs (DLXeRBC), and total lung xenon diffusing capacity (DLXe)) were measured in six normal rats and six rats with lung inflammation induced by instillation of fungal spores of Stachybotrys chartarum. DLXeLP, DLXeRBC, and DLXe were 56 +/- 10 ml/min/mmHg, 64 +/- 35 ml/min/mmHg, and 29 +/- 9 ml/min/mmHg, respectively, for normal rats, and 27 +/- 9 ml/min/mmHg, 42 +/- 27 ml/min/mmHg, and 16 +/- 7 ml/min/mmHg, respectively, for diseased rats. Lung volumes and gas transfer times for LP (TtrLP) were 16 +/- 2 ml and 22 +/- 3 ms, respectively, for normal rats and 12 +/- 2 ml and 35 +/- 8 ms, respectively, for diseased rats. Xenon diffusing capacities may be useful for measuring changes in gas exchange associated with inflammation and other lung diseases.     

Expanding the treatment window with mechanical thrombectomy in acute ischemic stroke

Introduction Acute ischemic stroke is a common disease associated with high mortality and significant long-term disability. Treatment options for acute ischemic stroke continue to evolve and include pharmaceutical and mechanical therapies. With the recent US Food and Drug Administration approval of a new device for mechanical thrombectomy, the options available for treatment of acute ischemic stroke have been expanded. Thrombolytic therapy is generally given intravenously in the first 3 h and up to 6 h via the intraarterial route for pharmacological clot disruption. The maximum time-frame for mechanical thrombectomy devices has yet to be determined.Methods A 78-year-old female presented to the emergency room with a dense right hemiparesis, leftward gaze preference and dense global aphasia. Eight hours after symptom onset, left carotid angiography confirmed a left internal carotid artery terminus occlusion. A single pass was made through the clot with an X6 Merci Retriever device.Results After a single pass, the vessel was reopened and normal flow in the left internal carotid artery was demonstrated. At the time of discharge, her neurological deficits had improved significantly. Furthermore, the final infarct area, as demonstrated on magnetic resonance imaging, was probably much smaller than it would have been if the vessel had not been recanalized.Conclusion We report the use of a new mechanical thrombectomy device 8 h after onset of ischemic symptoms, with substantial subsequent improvement in neurological outcome. In selected cases, use of the Merci Retriever can result in improved outcomes beyond the traditional 6-hwindow used for intraarterial pharmacological thrombolysis.