n-type Ge/Si antennas for THz sensing.

Ge-on-Si plasmonics holds the promise for compact and low-cost solutions in the manipulation of THz radiation. We discuss here the plasmonic properties of doped Ge bow-tie antennas made with a low-point cost CMOS mainstream technology. These antennas display resonances between 500 and 700 GHz, probed by THz time domain spectroscopy. We show surface functionalization of the antennas with a thin layer of α-lipoic acid that red-shifts the antenna resonances by about 20 GHz. Moreover, we show that antennas protected with a silicon nitride cap layer exhibit a comparable red-shift when covered with the biolayer. This suggests that the electromagnetic fields at the hotspot extend well beyond the cap layer, enabling the possibility to use the antennas with an improved protection of the plasmonic material in conjunction with microfluidics.

The receptor of the type I interferon family.

All type I IFNs act through a single cell surface receptor composed of the IFNAR1 and IFNAR2 subunits and two associated cytoplasmic tyrosine kinases of the Janus family, Tyk2 and Jak1. A central issue in type I IFN biology is to understand how a multitude of subtypes can generate similar signaling outputs but also govern specific cellular responses. This review summarizes results from the last decade that contributed to our current state of knowledge of IFN-receptor complex structure and assembly.

Coronary angioplasty versus bypass surgery in patients > 70 years old matched for ventricular function.

OBJECTIVES: This study compared the relative risks and benefits of coronary angioplasty and coronary artery bypass graft surgery in patients > 70 years old. BACKGROUND: Few objective, comparative data exist to guide the clinician in the decision to use bypass surgery or angioplasty in elderly patients. METHODS: The study was a case-control, retrospective analysis of 195 consecutive patients who underwent bypass surgery in 1987 and 1988 and were compared with a concurrent cohort of 195 coronary angioplasty-treated patients. The groups were matched for left ventricular function, age and gender mix. RESULTS: The in-hospital morbidity and mortality rates were significantly lower in the coronary angioplasty-treated patients. Mean postprocedural hospital stay was 4.8 and 14.3 days for angioplasty and surgical group patients, respectively (p < 0.001). In-hospital death occurred in 2% of angioplasty-treated patients compared with 9% of surgically treated patients (p = 0.007). Serious in-hospital stroke occurred in no patient in the angioplasty group and in 5% of patients in the surgical group (p < 0.0001). Q wave infarction occurred in 1% of angioplasty-treated patients and 6% of bypass-treated patients (p = 0.01). The 5-year actuarial survival rate was similar in the two groups: 63% in the angioplasty group, 65% in the bypass group (p = NS). However, surgical group patients experienced less recurrent angina, required fewer repeat revascularization procedures and had fewer Q wave infarctions during follow-up compared with angioplasty group patients. CONCLUSIONS: When performed in patients > 70 years old, angioplasty and coronary bypass surgery result in similar long-term survival rates but otherwise distinctly different clinical courses.

Coronary angioplasty versus repeat coronary artery bypass grafting for patients with previous bypass surgery.

OBJECTIVES: We attempted to determine the relative risks and benefits of percutaneous transluminal coronary angioplasty (PTCA) and repeat coronary artery bypass grafting (re-CABG) in patients with previous coronary bypass surgery (CABG). BACKGROUND: Due to an expanding population of patients with surgically treated coronary artery disease and the natural progression of atherosclerosis, an increasing number of patients with previous CABG require repeat revascularization procedures. Although there are randomized comparative data for CABG versus medical therapy and, more recently, versus PTCA, these studies have excluded patients with previous CABG. METHODS: We retrospectively analyzed data from 632 patients with previous CABG who required either elective re-CABG (n = 164) or PTCA (n = 468) at a single center during 1987 through 1988. The PTCA and re-CABG groups were similar with respect to gender (83% vs. 85% male), age > 70 years (21% vs. 23%), mean left ventricular ejection fraction (46% vs. 48%), presence of class III or IV angina (70% vs. 63%) and three-vessel coronary artery disease (77% vs. 74%). RESULTS: Complete revascularization was achieved in 38% of patients with PTCA and 92% of those with re-CABG (p < 0.0001). The in-hospital complication rates were significantly lower in the PTCA group: death (0.3% vs. 7.3%, p < 0.0001) and Q wave myocardial infarction (MI) (0.9% vs. 6.1%, p < 0.0001). Actuarial survival was equivalent at 1 year (PTCA 95% vs. re-CABG 91%) and 6 years (PTCA 74% vs. re-CABG 73%) of follow-up (p = 0.32). Both procedures resulted in equivalent event-free survival (freedom from dealth or Q wave MI) and relief of angina; however, the need for repeat percutaneous or surgical revascularization, or both, by 6 years was significantly higher in the PTCA group (PTCA 64% vs. re-CABG 8%, p < 0.0001). Multivariate analysis identified age > 70 years, left ventricular ejection fraction < 40%, unstable angina, number of diseased vessels and diabetes mellitus as independent correlates of mortality for the entire group. CONCLUSIONS: In this nonrandomized series of patients with previous CABG requiring revascularization, an initial stategy of either PTCA or re-CABG resulted in equivalent overall survival, event-free survival and relief of angina. PTCA offers lower procedural morbidity and mortality risks, although it is associated with less complete revascularization and a greater need for subsequent revascularization procedures.

Biophysical analysis of the interaction of human ifnar2 expressed in E. coli with IFNalpha2.

Type I interferons are cytokines which activate an anti-viral response by binding to two specific cell surface receptors, ifnar1 and ifnar2. Here, we report purification and refolding of the extracellular part of human ifnar2 (ifnar2-EC) expressed in Escherichia coli and its characterization with respect to its interaction with interferon alpha2 (IFNalpha2). The 25 kDa, non-glycosylated ifnar2-EC is a stable, fully active protein, which inhibits antiviral activity of IFNalpha2. The stoichiometry of binding IFNalpha2 is 1:1, as determined by gel filtration, chemical cross-linking and solid-phase detection. The affinity of this interaction is 10 nM, which is similar to the affinity measured for the cell surface-bound ifnar2 receptor. No difference in affinity was found throughout various assays using optical detection as BIAcore or reflectometric interference spectorscopy. However, the binding kinetics as measured in homogeneous phase by fluorescence de-quenching was about three times faster than that measured on a sensor surface. The rate of complex formation is relatively high compared to other cytokine-receptor interactions. The salt dependence of the association kinetics suggest a limited but significant contribution of electrostatic forces towards the rate of complex formation. The dissociation constant increases with decreasing pH according to the protonation of a base with a pKa of 6.7. The surface properties of the IFNalpha2 binding surface on ifnar2 were interpreted according to the pH and salt dependence of the interaction.

Mutational and structural analysis of the binding interface between type I interferons and their receptor Ifnar2.

Type I interferons (IFN) exert pleiotropic activities through binding to two cell surface receptors, ifnar1 and ifnar2. We are investigating the biophysical basis of IFN signaling by characterizing the complex of the extra-cellular domain of ifnar2 (ifnar2-EC) with IFNs on the level of purified recombinant proteins in vitro. Here, we present a detailed mutational study on the functional epitopes on both IFN and ifnar2. Kinetic and thermodynamic parameters were determined by label-free heterogeneous phase detection. On IFNalpha2, a relatively small functional epitope comprising ten amino acid residues was localized, which is nearly entirely formed by residues on the AB loop. Two hot-spot residues, L30 and R33, account for two-thirds of the total interaction energy. Comparing the anti-viral potency of the various mutants to the binding affinity towards ifnar2 revealed a proportional correlation between the two, suggesting a rate-limiting role of ifnar2 binding in IFN signaling. On ifnar2, residues T46, I47 and M48 were identified as hot-spots in the interaction with IFNalpha2. For another ten residues on ifnar2, significant contribution of interaction energy was determined. Based on these data, the functional epitope on ifnar2 was defined according to a homology model based on other members of the class II hCR family in good agreement with the complementary functional epitope on IFNalpha2. Although IFNalpha2 and IFNbeta bind competitively to the same functional epitope, mutational analysis revealed distinct centers of binding for these IFNs on ifnar2. This small shift of the binding site may result in different angular orientation, which can be critically coupled to cytoplasmic signaling.

Chyloptysis (chylous sputum) due to thoracic lymphangiectasis with successful surgical correction.

A 73-year-old woman with a two-year history of recurrent episodes of respiratory distress is described. The finding of an elevated triglyceride value of 23.4 mmol/L (2072 mg/dL) and a normal cholesterol value in her sputum led to the correct diagnosis of chyloptysis after lymphangiography was performed. It is thought that congenital incompetence of the lymphatic valves was the cause of chyloptysis.

Assessment of affinity constants by rapid solid phase detection of equilibrium binding in a flow system.

We present a method for the determination of affinity constants based on equilibrium binding between an analyte and an antibody in liquid phase by a heterogeneous phase detection scheme. Equilibrium concentration of free antibody binding sites was probed kinetically by direct optical detection of specific binding to an immobilised analyte derivative. The additional binding signal due to dissociation of the analyte-antibody complex during detection was minimised by the use of fast flow-through conditions. The concentration of free antibody binding sites was titrated by adding increasing analyte concentrations. The affinity constant was derived from the titration curve by a non-linear least square fit of a model function. The affinity of monoclonal triazine antibodies to several s-triazine pesticides and a relevant metabolite was investigated. Kinetic determination of equilibrium concentration of free binding sites was carried out by reflectometric interference spectroscopy (RIfS) using flow injection analysis. The capabilities of the model were investigated using different analyte-antibody pairs and various antibody concentrations. Both bivalent IgG and monovalent Fab fragments were used to compare different binding models. The applied model corresponds well to the titration curves for affinity constants of 10(7) M(-1) and higher. For lower affinity constants significant deviations due to dissociation of the analyte-antibody complex during detection were observed.

Angioplasty versus bypass surgery for multivessel coronary artery disease with left ventricular ejection fraction < or = 40%.

Patients with multivessel coronary artery disease and left ventricular dysfunction represent a high-risk subgroup in whom coronary artery bypass grafting has been shown to improve survival compared with that of medically treated patients. The comparative benefits and risks of coronary angioplasty and bypass surgery in this subgroup of patients are unclear. This study retrospectively analyzes 100 consecutive patients treated with bypass surgery compared with a matched, concurrent cohort of 100 treated with multivessel angioplasty. Early results favored angioplasty; a hospital stay of 12.8 days was noted in the bypass group compared with 4.3 days in the angioplasty group (p < 0.001). In-hospital mortality rates were similar in the bypass (5%) and angioplasty (3%) groups (p = NS). Stroke was observed significantly more often in the bypass group (7 vs 0%). However, late follow-up favored bypass patients; repeat revascularization procedures and late myocardial infarction occurred more frequently during follow-up in the angioplasty group. During 5-year follow-up, superior relief from disabling angina (99 vs 89%; p = 0.01) and a trend toward improved survival (76 vs 67%; p = 0.09) were observed in the bypass group as compared with the angioplasty group. Multivariate correlates of late mortality included age and incomplete revascularization, but not mode of revascularization. Thus, in patients with multivessel coronary artery disease and left ventricular dysfunction, early results favor angioplasty, whereas late follow-up favors bypass surgery. However, late survival was similar in both groups of patients who were completely revascularized.

Two dimensional echocardiographic detection and measurement of the right pulmonary artery in pulmonary atresia-ventricular septal defect: angiographic and surgical correlation.

This study assessed the value of two dimensional echocardiography in patients with pulmonary atresia-ventricular septal defect in order to detect the presence of true pulmonary arteries, measure the dimension of the visible proximal right pulmonary artery and correlate these echocardiographic observations with angiographic and surgical findings. The data from 65 patients (age range 16 months to 54 years) with pulmonary atresia-ventricular septal defect who had both two dimensional echocardiographic and angiographic evaluation to determine the presence of pulmonary arteries were reviewed. Echocardiography allowed visualization of a right pulmonary artery in 55 (85 percent) of the 65 patients. Echocardiography detected a measurable proximal right pulmonary artery in 52 (98 percent) of 53 patients who had confluent pulmonary arteries confirmed with angiography. In three patients without confluence, a large systemic to pulmonary collateral artery was misinterpreted as the right pulmonary artery on two dimensional echocardiography. Right pulmonary arterial measurements on echocardiography (range 3 to 21 mm) showed excellent correlation with angiographic (r = 0.95) and surgical (r = 0.84) measurements. These data indicate that two dimensional echocardiography can be used to visualize proximal true pulmonary arteries (specifically, a right pulmonary artery) in a large proportion of patients with pulmonary atresia-ventricular septal defect; this finding usually denotes the presence of confluent pulmonary arteries. The data also suggest that this method can be reliably used for serial follow-up studies with noninvasive measurement of proximal right pulmonary arterial growth.

Trial of combined warfarin plus dipyridamole or aspirin therapy in prosthetic heart valve replacement: danger of aspirin compared with dipyridamole.

Despite the use of oral anticoagulation in patients with prosthetic heart valves, persistent thromboembolism over time warrants a search for improved methods of prevention. Thus, patients receiving 1 or more mechanical prosthetic heart valves were randomized to therapy with warfarin plus dipyridamole (400 mg/day) or warfarin plus aspirin (500 mg/day) on the basis of location and type of valve and surgeon, and followed up with a concurrent, nonrandomized control group taking warfarin alone. In 534 patients followed up 1,319 patient-years, excessive bleeding (necessitating blood transfusion or hospitalization) was noted in the warfarin plus aspirin group (23 of 170 [14%], or 6.0/100 patient-years) compared with warfarin plus dipyridamole (7 of 181 [4%], or 1.6/100 patient-years, p less than 0.001), or warfarin alone (9 of 183 [5%], or 1.8/100 patient-years, p less than 0.001). A trend was evident toward a reduction in thromboembolism in the warfarin plus dipyridamole group (2 of 181 [1%], or 0.5/100 patient-years) as compared with warfarin plus aspirin (7 of 170 [4%], or 1.8/100 patient-years), or warfarin alone (6 of 183 [4%], or 1.2/100 patient-years). Adequacy of anticoagulation (based on 12,720 prothrombin time determinations) was similar in all 3 groups with 65% of prothrombin times in the therapeutic range (1.5 less than or equal to prothrombin time/control less than or equal to 2.5), 30% too low, and 5% too high. Warfarin plus aspirin therapy resulted in excessive bleeding and is contraindicated. Longer follow-up study is needed to determine whether further separation of the incidence of thromboembolism can be detected.

Angiographic changes produced by percutaneous transluminal coronary angioplasty.

Percutaneous transluminal coronary angioplasty (PTCA) is being used with increasing frequency in the treatment of patients with symptomatic coronary artery disease. Balloon inflation results in diverse angiographic findings, reflecting the great variety of anatomic and pathologic changes produced. The long-term effects of inflation on the underlying atherosclerotic lesion and the clinical outcome are unknown but may depend in part on the anatomic changes caused by the dilatation itself. To facilitate communication and evaluation of the results of PTCA, a classification of the angiographic findings and their potential mechanisms is presented. Recognition and analysis of these angiographic findings may be helpful in evaluating the long-term outcome of patients undergoing PTCA.

Percutaneous transluminal coronary angioplasty (PTCA) in the elderly patient: experience in the National Heart, Lung, and Blood Institute PTCA Registry.

Because CABG results in a significantly higher morbidity and prolonged hospitalization in the older patient group, PTCA is an attractive alternative for providing myocardial revascularization in the small group of older patients with appropriate lesions for dilation. This analysis of the results of PTCA in 370 older patients in the NHLBI PTCA Registry reveals that PTCA can be performed with acceptably low mortality and morbidity. Therefore, PTCA may offer an alternative to CABG in the highly selected symptomatic older patient.

Current techniques for the surgical management of malignant lesions of the thoracic esophagus and cardia.

Cancers of the esophagus and cardia remain serious conditions that cause many thousands of deaths every year throughout the world. In North America, cancer of the esophagus and gastric cardia is an endemic disease of low order and stable incidence. Nevertheless, it is responsible for many deaths and considerable suffering. With current methods of treatment, substantial palliation and amelioration of patient disability are possible, and some patients gain long-term survival with comfort and even cure. A combination of surgical resection and reconstruction is the chief modern method of management of such cancers. Herein we discuss a variety of standard surgical procedures that are currently available and present detailed illustrations of these procedures. The selection of a specific operation depends largely on the site of the neoplasm. With all these procedures, function is restored and the local and regional neoplastic tissue is removed without compromising the potential for cure. Associated operative mortality is approximately 7%. The late results of the operations illustrated depend primarily on the cell type, grade, and stage of the neoplasm encountered at the time of surgical treatment. For patients who have undergone resection, 5-year survival rates have ranged from 15 to 54%, the results depending on the stage of the cancer. Of equal importance is the fact that oral diet can be maintained in 93% of patients despite recurrence of the neoplasm.

Balloon angioplasty in multivessel coronary artery disease.

Coronary angioplasty with use of the balloon catheter was initially performed only in patients with single-vessel coronary artery disease. Most symptomatic patients with coronary artery disease who require revascularization for control of their symptoms, however, have stenoses in more than one major coronary artery. Therefore, we have evaluated the results of balloon angioplasty in patients with multivessel disease. Of 261 patients who underwent percutaneous transluminal coronary angioplasty at our institution up to February 1983, 100 had multivessel disease. Of these 100 patients, 72 had an initially successful procedure, defined as successful dilation of one or more major coronary arteries without significant complication. Of the remaining 28 patients, 25 underwent coronary artery bypass grafting (6 on an urgent basis for coronary occlusion). No deaths occurred. In selected patients with multivessel disease, coronary angioplasty is associated with low morbidity and mortality and might be an excellent alternative to coronary artery bypass grafting when medical treatment fails. Percutaneous transluminal coronary angioplasty merits the critical comparison with standard therapy that can be achieved only in a properly designed clinical trial.

Platypnea-orthodeoxia: clinical profile, diagnostic workup, management, and report of seven cases.

Platypnea-orthodeoxia is a rare and poorly understood syndrome of orthostatic accentuation of a right-to-left shunt, usually across a patent foramen ovale. The syndrome is most commonly recognized in patients with a history of a major pulmonary disorder such as pneumonectomy, recurrent pulmonary emboli, or chronic lung disease. Pulmonary artery pressures are typically normal. The physiologic mechanism is unknown. We recommend that initial assessment consist of measurement of blood gases with the patient in the supine and upright positions. Orthostatic desaturation should prompt further investigation. A definitive diagnosis can most easily be obtained by tilt-table two-dimensional echocardiography with peripheral venous contrast medium. The shunt can be localized at the atrial level and directly visualized and semiquantitated. The decision about surgical closure of the patent foramen ovale is based on the degree of clinical disability. Because a significant shunt is manifest only in the upright position, astute clinical suspicion is of paramount importance for proper diagnosis. Increased awareness of this syndrome and ease of echocardiographic diagnosis will facilitate recognition of this potentially treatable cause of orthostatic hypoxia.

Percutaneous transluminal coronary angioplasty, alone or in combination with streptokinase therapy, during acute myocardial infarction.

The treatment strategy in 66 consecutive patients who underwent invasive therapy for acute myocardial infarction was analyzed, and specific attention was focused on the role of percutaneous transluminal coronary angioplasty. The following four treatment regimens were used: angioplasty alone (11 patients), angioplasty followed immediately by administration of streptokinase (15), streptokinase therapy alone (11), and streptokinase therapy followed by angioplasty (29). Reperfusion was achieved in 91%, 80%, 82%, and 72% of these subgroups, respectively. Angioplasty was particularly helpful in patients with severe residual stenoses after intracoronary administration of streptokinase and in patients in whom streptokinase therapy failed to reopen the occluded artery. Angioplasty further reduced the residual stenosis in 11 of 15 patients (73%) with successful thrombolysis, and it restored blood flow in 10 of 14 patients (71%) in whom thrombolysis had failed to do so. The incidence of reinfarction after therapy was similar in all four treatment groups. Patients in whom angioplasty was used either alone or in combination with streptokinase therapy had a significantly decreased incidence of subsequent revascularization (less than 30% compared with 82%). Angioplasty is of considerable value in patients undergoing invasive therapy for acute infarction. In some patients, it may be used as the only treatment; in others, it may be used to treat severe residual stenosis after initial streptokinase therapy. Finally, angioplasty achieves reperfusion in most patients in whom streptokinase therapy has failed.

Roentgenographically occult lung cancer: pathologic findings and frequency of multicentricity during a 10-year period.

During the first 10 years of the Mayo Lung Project, 68 roentgenographically inapparent ("occult") lung cancers were localized and apparently completely resected. A pathologic classification was developed based on depth of tumor infiltration. The five categories were (1) in situ carcinoma confined to surface epithelium or ducts of mucous glands or acini (23 cancers), (2) intramucosal invasion not greater than 0.1 cm from mucosal surface (12 cancers), (3) invasion to bronchial cartilages (11 cancers), (4) invasion to full thickness of bronchial wall (10 cancers), and (5) extrabronchial invasion (12 cancers). Multicentricity of lung cancer was studied in 54 patients, none of whom had a history of cancer of the respiratory tract, and all of whom had had "complete" surgical resection of the initial occult lung cancer (or cancers). Neoplasms that were initially multicentric occurred in 4 patients, and a subsequent primary lung cancer developed in 11. The rate of detection of second primary lesions was 42 per 1,000 person-years of observation. A high incidence of unresectable cancers and a low survival rate were noted among patients who had a subsequent primary tumor. These findings were primarily attributable to invasiveness of the subsequent primary cancer or to respiratory insufficiency that resulted from obstructive lung disease or previous pulmonary resection. Because of the high risk of development of a second primary cancer after initial surgical resection, it is important to treat the initial occult cancer as conservatively as possible consistent with "cure."

Intrathoracic transposition of extrathoracic skeletal muscle.

During the past 6 years, 31 patients (20 males and 11 females) underwent 45 intrathoracic muscle transpositions of extrathoracic skeletal muscle. Eleven patients had postpneumonectomy empyema, 11 had bronchopleural fistula, four had infection of the heart and great vessels, three had reinforcement of tracheal anastomoses, and two had perforation of the gastrointestinal tract. Life-threatening infection was present in 28 patients. Ages ranged from 16 to 80 years, with a mean of 58.1. The latissimus dorsi muscle was transposed in 18 patients, pectoralis major muscle in 15, serratus anterior muscle in eight, pectoralis minor muscle in three, and rectus abdominis muscle in one. Twelve patients had multiple muscle transpositions (six concurrently and six staged). Operative mortality was 12.9% (four patients). Follow-up of the 27 operative survivors ranged from 3 to 72 months with a mean of 17.3. Twenty-four patients had no further signs or symptoms of the original infection. All had a closed chest. Long-term survivors included 73% of patients with postpneumonectomy empyema, 64% of patients with bronchopleural fistulas, and 50% of patients with infections of the heart and great vessels. We conclude that intrathoracic transposition of an extrathoracic skeletal muscle is an excellent method of treatment for persistent, life-threatening intrathoracic infection.

Unexplained diaphragmatic paralysis: a harbinger of malignant disease?

The records of 103 male and 39 female patients with unexplained diaphragmatic paralysis were reviewed. A probable cause of the paralysis was not revealed by the initial history, physical examination, or review of plain chest roentgenograms. Paralysis occurred on the left in 82 patients (58%), on the right in 58 (41%), and bilaterally in two (1%). Initially, 64 patients (45%) had symptoms; dyspnea, cough, and chest wall pain were the most common. Long-term follow-up showed the best prognosis to be for patients with chest wall pain and cough (improvement in 82% and 78%, respectively); dyspnea improved in only 34% of patients with this complaint. Intrathoracic malignant lesions with phrenic nerve involvement were subsequently diagnosed in five patients (3.5%) and progressive neurogenic atrophy in one (0.7%). Roentgenographic follow-up showed return of normal diaphragmatic position in only 12 instances (9.2%). Patients with unexplained diaphragmatic paralysis are unlikely to have an underlying occult malignant or neurologic process, but recovery of diaphragmatic function is also unlikely and subsidence of related symptoms is variable.