Carotid endarterectomy versus carotid angioplasty cui bono.

OBJECTIVES: To evaluate the current status of carotid angioplasty (CAS) versus carotid endarterectomy (CEA) in the management of patients with carotid bifurcation disease. DESIGN: Retrospective review of published and presented prospective randomized trials to date, regarding comparative results of CAS versus CEA. MATERIALS: Review of six published prospective randomized trials, one trial presented in press, and one trial completed and being analyzed. Large population based studies and a comparative registry study are also included. METHODS: Retrospective literature review. RESULTS: The results today favor CEA over CAS with respect to stroke morbidity, mortality, freedom from recurrence, and cost. CONCLUSIONS: At the present time, CEA remains the intervention of choice in the management of carotid bifurcation disease.

Flagellar adhesion in Chlamydomonas induces synthesis of two high molecular weight cell surface proteins.

Because our previous studies (Snell, W.J., and W.S. Moore, 1980, J. Cell Biol. 84:203- 210) on the mating reaction of chlamydomonas reinhardtii showed that there was an adhesion-induced turnover of proteins whose synthesis is induced during aggregation. Analysis by SDS PAGE and autoradiography showed that proteins of 220,000 M(r) and 165, 000 M(r) (designated A(1) and A(2) respectively) consistently showed a high rate of synthesis only in flagella or flagellar membrane-enriched fractions prepared from aggregating gametes. Since the two proteins were soluble in the non-ionic detergent NP-40 and were removed from intact cells by a brief pronase treatment, it is likely that A(1) and A(2) are membrane proteins expose on the cell surface. A(1) and A(2) were each synthesized by gametes of both mating types (mt(-) and mt(+)) and synthesis of these two proteins could be detected in the normal mating reaction (wild type mt(-) and mt(+)), in mixtures of mt(-) and impotent mt(+) gametes (which could aggregate but not fuse), and in mixtures of gametes of a single mating type with isolated flagella of the opposite mating type. Cells aggregating in tunicamycin, an inhibitor of protein glycosylation, lost their adhesiveness during aggregation and did not synthesize the 220,000 M(r) protein but instead produced a protein (possibly an underglycosylated form of A(1)) of slightly lower mol wt. The 220,000 and 165,000 M(R) proteins appeared to be flagellar proteins and not cell wall proteins because A(1) and A(2) did not co-migrate with previously identified cell wall proteins, and synthesis of the two proteins could not be detected in flagella-less (bald-2) mutant cells. Analysis of the adhesive activity of sucrose gradient fraction of detergent (octyl glucoside)-solubilized flagellar membranes revealed that fractions containing A(1) and A(2) did not have detectable adhesive activity. The possibility remains that A(1) and A(2) are adhesion molecules whose activity could not be measured in the assay we used. Alternatively, the 220,000 and 165,000 M(r) proteins may be inactivated adhesion molecules or else they may be flagellar surface proteins involved only indirectly in the adhesion process.

Aggregation-dependent turnover of flagellar adhesion molecules in Chlamydomonas gametes.

Previous studies on flagellar adhesion in chlamydomonas (Snell, W. and S. Roseman. 1979. J. Biol. Chem. 254:10820-10829.) have shown that as gametes adhere to flagella isolated from gametes of the opposite mating type, the adhsiveness of the added flagella but not of the gametes is lost. The studies reported here show that the addition of protein synthesis inhibitors (cycloheximide [CH] or anisomycin) to the medium of such cell- flagella mixtures causes the cells to lose their adhesiveness. This loss, however, occurs only after the cells have interacted with 4-8 flagella/cell and does not occur if the cells are kept in CH (7 h) without aggregating. The availability of an impotent (imp) mating type plus (MT(+)) mutant (provided by U.W. Goodenough), which adheres but is unable to undergo the fusion that normally follows adhesion, made it possible to determine whether a similar loss of adhesiveness occurs in mixtures of matting type minus (mt(-)) and imp mt(+) gametes. In the absence of inhibitor, mt(-) and imp mt(+) gametes adhered to each other (without fusing) for several hours; however, in the presence of CH or anisomycin, the gametes began to de-adhere 35 min after mixing, and, by 90 min, 100 percent of the cells were single again. This effect was reversible, and the rapid turnover of cells were single again. This effect was reversible, and the rapid turnover of molecules involved in adhesion occurred only during adhesion inasmuch as gametes pretreated for 4 h with CH were able to aggregate in CH for the same length of time as nonpretreated cells aggregated in CH. By the addition of CH at various times after the mt(-) and imp mt(+) gametes were mixed, measurements were made of the "pool size" of the molecules involved in adhesion. The pool reached a minimum after 25 min of aggregation, rapidly increased for the next 25 min, and then leveled off at the premixing level. These results suggest that flagellar adhesion in chlamydomonas causes modification of surface molecules (receptors, ligands), which brings about their inactivation and stimulates their replacement.

Isotope tracing of submarine groundwater discharge offshore Ubatuba, Brazil: results of the IAEA-UNESCO SGD project.

Results of groundwater and seawater analyses for radioactive (3H, 222Rn, 223Ra, 224Ra, 226Ra, and 228Ra) and stable (D and 18O) isotopes are presented together with in situ spatial mapping and time series 222Rn measurements in seawater, direct seepage measurements using manual and automated seepage meters, pore water investigations using different tracers and piezometric techniques, and geoelectric surveys probing the coast. This study represents first time that such a new complex arsenal of radioactive and non-radioactive tracer techniques and geophysical methods have been used for simultaneous submarine groundwater discharge (SGD) investigations. Large fluctuations of SGD fluxes were observed at sites situated only a few meters apart (from 0 cm d(-1) to 360 cm d(-1); the unit represents cm3/cm2/day), as well as during a few hours (from 0 cm d(-1) to 110 cm d(-1)), strongly depending on the tidal fluctuations. The average SGD flux estimated from continuous 222Rn measurements is 17+/-10 cm d(-1). Integrated coastal SGD flux estimated for the Ubatuba coast using radium isotopes is about 7x10(3) m3 d(-1) per km of the coast. The isotopic composition (deltaD and delta18O) of submarine waters was characterised by significant variability and heavy isotope enrichment, indicating that the contribution of groundwater in submarine waters varied from a small percentage to 20%. However, this contribution with increasing offshore distance became negligible. Automated seepage meters and time series measurements of 222Rn activity concentration showed a negative correlation between the SGD rates and tidal stage. This is likely caused by sea level changes as tidal effects induce variations of hydraulic gradients. The geoelectric probing and piezometric measurements contributed to better understanding of the spatial distribution of different water masses present along the coast. The radium isotope data showed scattered distributions with offshore distance, which imply that seawater in a complex coast with many small bays and islands was influenced by local currents and groundwater/seawater mixing. This has also been confirmed by a relatively short residence time of 1-2 weeks for water within 25 km offshore, as obtained by short-lived radium isotopes. The irregular distribution of SGD seen at Ubatuba is a characteristic of fractured rock aquifers, fed by coastal groundwater and recirculated seawater with small admixtures of groundwater, which is of potential environmental concern and has implications on the management of freshwater resources in the region.

Quantifying submarine groundwater discharge in the coastal zone via multiple methods.

Submarine groundwater discharge (SGD) is now recognized as an important pathway between land and sea. As such, this flow may contribute to the biogeochemical and other marine budgets of near-shore waters. These discharges typically display significant spatial and temporal variability making assessments difficult. Groundwater seepage is patchy, diffuse, temporally variable, and may involve multiple aquifers. Thus, the measurement of its magnitude and associated chemical fluxes is a challenging enterprise. A joint project of UNESCO and the International Atomic Energy Agency (IAEA) has examined several methods of SGD assessment and carried out a series of five intercomparison experiments in different hydrogeologic environments (coastal plain, karst, glacial till, fractured crystalline rock, and volcanic terrains). This report reviews the scientific and management significance of SGD, measurement approaches, and the results of the intercomparison experiments. We conclude that while the process is essentially ubiquitous in coastal areas, the assessment of its magnitude at any one location is subject to enough variability that measurements should be made by a variety of techniques and over large enough spatial and temporal scales to capture the majority of these changing conditions. We feel that all the measurement techniques described here are valid although they each have their own advantages and disadvantages. It is recommended that multiple approaches be applied whenever possible. In addition, a continuing effort is required in order to capture long-period tidal fluctuations, storm effects, and seasonal variations.

Characterisation of submarine groundwater discharge offshore south-eastern Sicily.

A complex approach in characterisation of submarine groundwater discharge (SGD) off south-eastern Sicily comprising applications of radioactive and non-radioactive tracers, direct seepage measurements, geophysical surveys and a numerical modelling is presented. SGD fluxes in the Donnalucata boat basin were estimated by direct seepage measurements to be from 4 to 12Ls(-1), which are comparable with the total SGD flux in the basin of 17Ls(-1) obtained from radon measurements. The integrated SGD flux over the Donnalucata coast estimated on the basis of Ra isotopes was around 60m(3)s(-1) per km of the coast. Spatial variations of SGD were observed in the Donnalucata boat basin, the average (222)Rn activity concentration in seawater varied from approximately 0.1kBqm(-3) to 3.7kBqm(-3) showing an inverse relationship with salinity. The continuous monitoring carried out at the site closest to the coast has revealed an inverse relationship of (222)Rn activity concentration on the tide. The (222)Rn concentrations in seawater varied from 2.3kBqm(-3) during high tides to 4.8kBqm(-3) during low tides, thus confirming an influence of the tide on submarine groundwater discharge. Stable isotopes (delta(2)H and delta(18)O) showed that SGD samples consist up to 50% of groundwater. Geo-electrical measurements showed a spatial variability of the salt/fresh water interface and its complex transformation in the coastal zone. The presented results imply that in the studied Donnalucata site there are at least two different sources of SGD, one superficial, represented by mixed fresh water and seawater, and the second one which originates in a deeper limestone aquifer.

Anticytoplasmic antibodies in antinuclear antibody-negative lupus erythematosus. Correlation with clinical course.

A patient with clinical manifestations of systemic lupus erythematosus (SLE) and without antinuclear antibodies was found to have anticytoplasmic antibodies. These anticytoplasmic antibodies were directed against ribosomal ribonucleoprotein, and the titer of anticytoplasmic and anti-ribosomal ribonucleoprotein antibodies correlated with the clinical course of the patient's illness. The importance of detecting anticytoplasmic antibodies and their role in producing disease in patients with SLE is discussed.

Carotid endarterectomy: what is its current status?

The plethora of recent articles regarding carotid endarterectomy has tended to confuse rather than clarify its indications, efficacy, and acceptability. The National Institutes of Health has recently funded two large multicenter controlled clinical trials, one including asymptomatic persons with carotid stenoses, and the other, patients having transient ischemic episodes or minor strokes. Eight academic professors of neurology (four), neurosurgery (two), and vascular surgery (two) with a long and abiding interest in cerebrovascular disease prepared a statement delineating acceptable levels of mortality and morbidity from this procedure. These might serve as guidelines until the large trials have been completed.

Life expectancy following aortofemoral arterial grafting.

The existence of symptomatic aortoiliofemoral occlusive vascular disease would appear to result in approximately a 10 year decrease in life expectancy compared to that of the "normal" population. However, a significant proportion of the cumulative mortality rate appears to be due to both coronary artery disease and diabetes mellitus, as patients with peripheral vascular disease had a near "normal" life expectancy in the absence of either coronary artery disease or diabetes mellitus. Neither the presence nor the anatomical location of occlusive disease distal to the comon femoral bifurication by itself decreased life expectancy compared to those patients with aortoliofemoral disease but without similar distal occusive disease. Low operative mortality rate, excellent long-term patency, and potentially "normal" life expectancy all encourage an aggressive operative approach in patients with symptoms of peripheral vascular disease but without either diabetes mellitus or coronary artery disease. Revascularization in those patients with diabetes mellitus should be directed at limb salvage rather than at relief of minor symptoms of ischemia.

Bacteremic infectability of vascular grafts: the influence of pseudointimal integrity and duration of graft function.

This report describes an experimental study in which dogs with prosthetic graft replacement of the infrarenal abdominal aorta were challenged at progressive time intervals following graft placement with a single intravenous infusion of Staphylococcus aureus in order to determine the duration of susceptibility to graft infection of bacteremic origin. The results demonstrate that the susceptibility of a prosthetic graft to infection by bacteremic seeding virtually was 100 percent up to 1 month following graft placement. The incidence of infection then began to progressively drop but never was eliminated as demonstrated by a 30 percent incidence of graft infection in dogs so challenged 1 year graft placement. Careful scrutiny of the intimal surface of the harvested grafts, 3 weeks following bacteremic challenge, revealed that all grafts in which the pseudointimal coverage was complete were insulated effectively from infection by bacteremic seeding in that their cultures were negative. All grafts that had positive cultures for Staphylococcus aureus were noted to have either an incomplete or absent pseudointimal lining.

Bilateral extracranial-intracranial bypass before carotid ligation for hemorrhage into a pharyngocutaneous fistula.

In this article we present a discussion of the surgical treatment of a patient with spontaneous hemorrhage of the right carotid artery at the site of a pharyngocutaneous fistula following radiation therapy and radical neck surgery for carcinoma of the tonsil. The patient had an atherosclerotic left common carotid artery occlusion. This is the first reported case of bilateral saphenous vein extracranial-intracranial arterial bypass (EIAB). The rationale and results of the operative procedures performed and the benefits of immediate high-flow bypass graft implanted outside the contaminated surgical field before carotid artery ligation are discussed. EIAB should be considered for patients requiring therapeutic carotid artery ligation who have potentially inadequate collateral cerebral blood flow due to associated extracranial or intracranial vascular occlusions or anomalies.

The use of ophthalmosonometry in the diagnosis of carotid artery stenosis.

One hundred and fifty-two patients underwent supraorbital Doppler studies of 304 carotid arteries to determine the presence or absence of hemodynamically significant lesions. Subsequent carotid arteriography was used to validate the accuracy of the test. Of 124 patients having abnormal Doppler examinations, 107 (86%) were angiographically proved to have lesions of the internal carotid artery that produced a stenosis of 50% or more. In the last 80 patients, the accuracy was increased to 94%. Of 115 proved stenoses or occlusions, the supraorbital Doppler examination correctly identified 99, for a diagnostic accuracy of 86%. In the last 50 patients, this accuracy was increased to 93%. Since only 58% of the patients with lesions had a bruit, the Doppler study was of particular value in identifying the patients with significant lesions in the absence of a bruit. Likewise, since only 61% of carotid arteries with bruits had lesions of hemodynamic significance, a normal Doppler examination could have been used to avoid angiographic screening of those arteries with bruits in the absence of major lesions, providing those hemodynamically insignificant lesions were not producing symptoms related to emboli. The technique of ophthalmosonometry and the significance of the test in clinical evaluation is discussed.

Maintenance of viable arterial allografts by cryopreservation.

An experimental study, designed to investigate the feasibility of maintaining fresh, viable arterial allografts by cryopreservation, is presented. Cryopreserved femoral arterial allografts were shown to be equal in patency rate when compared with fresh controls. The cryopreserved allografts were shown to be superior to fresh allografts in the parameters of intimal integrity, absence of host rejection, and reduced surface thrombogenicity. This experimental study supports the thesis that cryopreservation in liquid nitrogen, utilizing 15% dimethyl sulfoxide (DMSO) and methylprednisolone as a cryoprotectant solution, is an excellent method of preserving and storing fresh allograft arteries for use as a small vessel replacement.

Emergency carotid artery surgery in neurologically unstable patients.

Although angiography and carotid artery surgery are illadvised in patients with acute, profound stroke, there is no consensus on the management of patients with stroke in evolution, waxing and waning neurologic deficits, or crescendo transient ischemic attacks. This type of clinical picture was associated with a critical, unstable lesion of the internal carotid artery in each of 12 patients. Emergency angiography permitted identification of the lesions responsible for the varying neurologic manifestations, and emergency carotid thromboendarterectomy produced prompt, complete recovery in all but one patient, who had a total carotid occlusion, received no operation, and died of a cerebral infarction. Based on our experience with these 12 patients, an aggressive diagnostic and therapeutic approach is recommended for patients with acute unstable cerebrovascular disease.

Prosthetic arterial graft material. Influence on neointimal healing and bacteremic infectibility.

Five commonly used prostheses were compared for susceptibility to bacteremic infection: US Catheter and Instrument Co (USCI) Ultralight weight knitted Dacron, USCI Sauvage filamentous velour Dacron, Meadox Microvel double velour knitted Dacron, polytetrafluoroethylene (PTFE)-Impra, and PTFE-Gore-tex. We used 6-mm diameter grafts to replace 4-cm segments of the abdominal aorta in 150 mongrel dogs. Fifteen dogs were used for each graft type and each healing interval: three and six months posttransplantation. At the appropriate time after implantation, an intravenous infusion of 10(8) organisms of Staphylococcus aureus was administered to the ten experimental dogs in each graft type; five dogs of each graft type served as sterile controls. Three weeks later, the grafts were aseptically removed, inspected for the completeness of neointimal healing, and cultured for bacteria. At three months, the Sauvage graft achieved the lowest infection rate (10%) with the highest incidence of complete neointimal lining (71%). In the six-month series, there were no statistical differences between the knitted Dacron prostheses, but all Dacron grafts were superior to the PTFE grafts with regard to susceptibility to bacteremic infection and completeness of intimal lining.

The natural history of bilateral aortofemoral bypass grafts for ischemia of the lower extremities.

Analysis of the immediate and long-term results in 180 patients undergoing aortofemoral bypass grafts for occlusive disease of the lower extremities showed the immediate graft limb patency in 360 graft limbs to be 99.2%. The cumulative ten-year graft limb patency was 66%. Factors associated with thrombosis of the graft limb revealed correlations for localized atherosclerotic disease of either the profunda femoris artery or the tibial trifurcation vessels. The highest correlation for graft limb thrombosis was with simultaneous lesions involving both the profunda femoris artery and tibial trifurcation vessels. The acute lower extremity salvage rate was 94%, and the ten-year cumulative extremity salvage for legs at risk of amputation was 85%. Postoperative symtpoms correlated well with patency. Overall operative mortality was five patients out of 180 (2.5%).

Tuberculous infection in a vascular prosthesis: a case of aortic graft infection resulting from disseminated tuberculosis.

Insertion of an aortic prosthetic bypass graft in a patient with untreated disseminated tuberculosis resulted in graft infection with formation of a pseudoaneurysm. Microbiologic cultures implicated Mycobacterium tuberculosis as the causative agent, and a subsequent review of the literature indicated this report to be the first clinical demonstration of the susceptibility of vascular prosthesis to M tuberculosis infection to our knowledge.

Long-term results following surgical management of aortic graft infection.

Between January 1970 and June 1988, a total of 45 patients with aortic prosthetic graft infection underwent removal of the infected aortic prosthesis. In addition, 36 of these patients also underwent revascularization via an extra-anatomic bypass. We analyzed the early and long-term results with respect to survival, limb salvage, freedom from infection, and extra-anatomic graft patency. The 30-day mortality was 24% (11/45), and the amputation rate was 11% (8/73). During a mean follow-up of 36 months (range, 2 to 144 months), 80% (24/30) of the patients remained free of infection and are considered cured. Infection in the extra-anatomic bypass graft was the most common cause of recurrent sepsis and the leading cause of late amputations (four of seven). By life-table methods, 1-year survival was 63% and 5-year survival was 49%. Limb salvage rates at 1 and 5 years were 79% and 66%, respectively. The primary patency rate of extra-anatomic bypass was 43% at 3 years, with the secondary patency rate improved to 65%. These early and late results are in marked contrast to the natural history of untreated aortic graft infection. Nonetheless, a perioperative mortality rate of 24%, a 5-year limb loss rate of 33%, and 3-year graft thrombosis rate of 35% are testimony to the serious nature of aortic graft infection and the need to develop better methods to prevent this complication.