Neural field theory of effects of brain modifications and lesions on functional connectivity: Acute effects, short-term homeostasis, and long-term plasticity.

Neural field theory is used to predict the functional connectivity effects of lesions or other modifications to effective connectivity. Widespread initial changes are predicted after localized or diffuse changes to white or gray matter, consistent with observations, and enabling lesion severity indexes to be defined. It is shown how short-term homeostasis and longer-term plasticity can reduce perturbations while maintaining brain criticality under conditions where some connections remain fixed because of damage in the lesion core. The extent to which such effects can compensate for initial connectivity changes is then explored, showing that the strongest corrective changes are concentrated toward the edges of the perturbation if it is localized and its core is fixed. The results are applicable to inferring underlying connectivity changes and to interpreting and monitoring functional connectivity modifications after lesions, injury, surgery, drugs, or brain stimulation.

Firing patterns in a conductance-based neuron model: bifurcation, phase diagram, and chaos.

Responding to various stimuli, some neurons either remain resting or can fire several distinct patterns of action potentials, such as spiking, bursting, subthreshold oscillations, and chaotic firing. In particular, Wilson's conductance-based neocortical neuron model, derived from the Hodgkin-Huxley model, is explored to understand underlying mechanisms of the firing patterns. Phase diagrams describing boundaries between the domains of different firing patterns are obtained via extensive numerical computations. The boundaries are further studied by standard instability analyses, which demonstrates that the chaotic neural firing could develop via period-doubling and/or period- adding cascades. Sequences of the firing patterns often observed in many neural experiments are also discussed in the phase diagram framework developed. Our results lay the groundwork for wider use of the model, especially for incorporating it into neural field modeling of the brain.

Incorporation of caffeine into a quantitative model of fatigue and sleep.

A recent physiologically based model of human sleep is extended to incorporate the effects of caffeine on sleep-wake timing and fatigue. The model includes the sleep-active neurons of the hypothalamic ventrolateral preoptic area (VLPO), the wake-active monoaminergic brainstem populations (MA), their interactions with cholinergic/orexinergic (ACh/Orx) input to MA, and circadian and homeostatic drives. We model two effects of caffeine on the brain due to competitive antagonism of adenosine (Ad): (i) a reduction in the homeostatic drive and (ii) an increase in cholinergic activity. By comparing the model output to experimental data, constraints are determined on the parameters that describe the action of caffeine on the brain. In accord with experiment, the ranges of these parameters imply significant variability in caffeine sensitivity between individuals, with caffeine's effectiveness in reducing fatigue being highly dependent on an individual's tolerance, and past caffeine and sleep history. Although there are wide individual differences in caffeine sensitivity and thus in parameter values, once the model is calibrated for an individual it can be used to make quantitative predictions for that individual. A number of applications of the model are examined, using exemplar parameter values, including: (i) quantitative estimation of the sleep loss and the delay to sleep onset after taking caffeine for various doses and times; (ii) an analysis of the system's stable states showing that the wake state during sleep deprivation is stabilized after taking caffeine; and (iii) comparing model output successfully to experimental values of subjective fatigue reported in a total sleep deprivation study examining the reduction of fatigue with caffeine. This model provides a framework for quantitatively assessing optimal strategies for using caffeine, on an individual basis, to maintain performance during sleep deprivation.

Cerebral nocardia masquerading as metastatic CNS disease in an endometrial cancer patient.

Nocardia is a bacterial infection primarily originating from organic rich soil, endemic to several international geographic locations. We present the case of a 61-year-old woman previously treated for endometrial carcinoma, who three years later developed metastatic pulmonary disease and received systemic chemotherapy. After five months, she developed a large right posterior lobe lesion, suspicious for metastatic CNS disease. However, following neurosurgical resection of the lesion and infectious disease consultation, a diagnosis of nocardia was made.

Numerical simulations of type-III solar radio bursts.

The first numerical simulations are presented for type-III solar radio bursts in the inhomogeneous solar corona and interplanetary space, that include microscale quasilinear and nonlinear processes, intermediate-scale driven ambient density fluctuations, and large scale evolution of electron beams, Langmuir and ion sound waves, and fundamental and harmonic electromagnetic emission. Bidirectional coronal emission is asymmetric between the upward and downward directions, and harmonic emission dominates fundamental emission. In interplanetary space, fundamental and/or harmonic emission can be important. Langmuir and ion sound waves are bursty and the statistics of Langmuir wave energy agree well with the predictions of stochastic growth theory.

Protection against Helicobacter pylori infection in the Mongolian gerbil after prophylactic vaccination.

Vaccines against Helicobacter pylori could circumvent the problem of increasing antibiotic resistance. They would be particularly useful in developing countries, where re-infection rates are high following standard eradication regimes. The Mongolian gerbil is a good model for H. pylori infection, as the gastric pathology induced by infection is similar to that in humans. The H. pylori-induced inflammatory response in gerbils is considerably greater than in murine models. The aim of this study was to determine if gerbils could be vaccinated against H. pylori. Mongolian gerbils were vaccinated orally with an H. pylori whole cell sonicate preparation and cholera toxin adjuvant. Vaccinated gerbils and controls were challenged with the autologous H. pylori strain 42GX. All infection, and cholera toxin, control gerbils were H. pylori positive 6 weeks post-challenge. By contrast, a significant degree of protection was demonstrated in vaccinated gerbils. Only two of 10 of gerbils were H. pylori positive (P<0.001). Protection was associated with increased serum H. pylori IgG antibodies. Protected gerbils had histologically normal gastric mucosa and, in contrast to mice, no post-immunisation gastritis was evident. In the control groups, the degree of inflammation was variable, with some of the animals having corpus gastritis and corpus mucous metaplasia. The levels of gastric IL-12p40 and IFNgamma transcripts were significantly decreased in vaccinated animals compared to infection and cholera toxin controls (P<0.01). Gastric IL-10 and TGFbeta transcripts were found only at relatively low levels. These results demonstrate that Mongolian gerbils can be successfully vaccinated against H. pylori and protected from H. pylori-induced pathology.

Analysis of the electroencephalographic activity associated with thalamic tumors.

A physiologically based model of corticothalamic dynamics is used to investigate the electroencephalographic (EEG) activity associated with tumors of the thalamus. Tumor activity is modeled by introducing localized two-dimensional spatial non-uniformities into the model parameters, and calculating the resulting activity via the coupling of spatial eigenmodes. The model is able to reproduce various qualitative features typical of waking eyes-closed EEGs in the presence of a thalamic tumor, such as the appearance of abnormal peaks at theta ( approximately 3Hz) and spindle ( approximately 12Hz) frequencies, the attenuation of normal eyes-closed background rhythms, and the onset of epileptic activity, as well as the relatively normal EEGs often observed. The results indicate that the abnormal activity at theta and spindle frequencies arises when a small portion of the brain is forced into an over-inhibited state due to the tumor, in which there is an increase in the firing of (inhibitory) thalamic reticular neurons. The effect is heightened when there is a concurrent decrease in the firing of (excitatory) thalamic relay neurons, which are in any case inhibited by the reticular ones. This is likely due to a decrease in the responsiveness of the peritumoral region to cholinergic inputs from the brainstem, and a corresponding depolarization of thalamic reticular neurons, and hyperpolarization of thalamic relay neurons, similar to the mechanism active during slow-wave sleep. The results indicate that disruption of normal thalamic activity is essential to generate these spectral peaks. Furthermore, the present work indicates that high-voltage and epileptiform EEGs are caused by a tumor-induced local over-excitation of the thalamus, which propagates to the cortex. Experimental findings relating to local over-inhibition and over-excitation are discussed. It is also confirmed that increasing the size of the tumor leads to greater abnormalities in the observable EEG. The usefulness of EEG for localizing the tumor is investigated.

The effect of gender on Helicobacter felis-mediated gastritis, epithelial cell proliferation, and apoptosis in the mouse model.

The murine Helicobacter felis model has been extensively used to investigate the importance of host factors in the development of chronic gastritis. The effect of gender in this murine model is unknown. Male and female C57BL/6J mice were infected with H felis for up to 1 year. At 4, 8, 19, 36, and 52 weeks post-infection, gastric histopathology, epithelial cell proliferation, and apoptosis were examined and compared with age- and gender-matched controls. In female mice, infection with H felis resulted in an earlier onset of chronic gastric inflammation, epithelial hyperplasia, and oxyntic cell loss than males. In females, there was a trend towards increased gastric pathology compared with males, with long-term-infected female mice having significantly greater (p < 0.05) chronic inflammation than male mice. The histopathological differences in male and female mice did not relate to the density of H felis infection. Female mice infected with H felis had significantly increased gastric epithelial cell proliferation in the cardia and corpus at both 8 and 52 weeks post-infection (p < 0.05). Epithelial cell apoptosis in the glandular mucosa of the corpus at 36 and 52 weeks post-infection was significantly increased (p < 0.05) in female mice compared with uninfected gender controls. In contrast, there was no significant increase in epithelial cell proliferation or apoptosis in any area of the stomach at any time point after H felis infection in male mice. These results demonstrate that there are gender differences in the gastric inflammatory and epithelial response to H felis in the murine model. The functional importance of gender should be considered in future murine studies on H felis- and H pylori-induced chronic gastritis.

Increased zinc finger protein zFOC1 transcripts in gastric cancer compared with normal gastric tissue.

BACKGROUND: Screening of cDNA arrays of the IMAGE library identified human zFOC1 as a differentially expressed cDNA that was upregulated in KATO III gastric cancer cells following stimulation with the gastric pathogen Helicobacter pylori. AIMS: To determine the expression of zFOC1 in gastric mucosa with and without H pylori infection and in patients with gastric cancer. RESULTS: zFOC1 is localised on chromosome 12q24.3 and encodes a zinc finger protein. Expression studies in human H pylori infected and uninfected gastric biopsies, gastric tumours, and gastric cancer cell lines revealed that zFOCI gene transcripts are significantly higher in gastric cancer than in non-cancerous gastric tissues. CONCLUSIONS: The zFOC1 gene appears to be a tumour marker associated with gastric cancer.

Helicobacter pylori-stimulated EGF receptor transactivation requires metalloprotease cleavage of HB-EGF.

Helicobacter pylori has a major aetiological role in human gastric carcinogenesis but the cellular and molecular pathways by which infection promotes transformation remain to be resolved. This study demonstrates that H. pylori exposure to MKN-1, ST42, and MKN-28 gastric epithelial tumour cells results in the activation of HB-EGF gene expression and EGFR tyrosine phosphorylation. These cell responses are induced by both cagPAI positive and cagPAI negative H. pylori strains and are dependent on cell surface expression of the HB-EGF precursor. The induction of HB-EGF gene transcription by H. pylori requires metalloprotease-, EGFR-, and Mek1-activities, indicating the involvement of the "triple membrane passing signal" (TMPS) for EGFR transactivation. Moreover, the release of the inflammatory cytokine IL-8 by cells exposed to H. pylori is significantly impaired by inhibitors of TMPS pathway elements. Our findings support a model in which H. pylori triggers constitutive EGFR signal activation, which enhances IL-8 production, and initiates neoplastic transformation of gastric epithelial cells.

Redo carotid endarterectomy versus primary carotid endarterectomy.

BACKGROUND AND PURPOSE: Several authorities have recently advocated carotid stenting for recurrent carotid stenosis because of the perception that redo surgery has a higher complication rate than primary carotid endarterectomy (CEA). This study compares the early and late results of reoperations versus primary CEA. METHODS: All reoperations for recurrent carotid stenosis performed during a recent 7-year period by a single vascular surgeon were compared with primary CEA. Because all redo CEAs were done with polytetrafluoroethylene (PTFE) or vein patch closure, we only analyzed those primary CEAs that used the same patch closures. A Kaplan-Meier life-table analysis was used to estimate stroke-free survival rates and freedom from >/=50% recurrent stenosis. RESULTS: Of 547 primary CEAs, 265 had PTFE or saphenous vein patch closure, and 124 reoperations had PTFE or vein patch closure during the same period. Both groups had similar demographic characteristics. The indications for reoperation and primary CEA were symptomatic stenosis in 78% and 58% of cases and asymptomatic >/=80% stenosis in 22% and 42% of cases, respectively (P<0.001). The 30-day perioperative stroke and transient ischemic attack rates for reoperation and primary CEA were 4.8% versus 0.8% (P=0.015) and 4% versus 1.1%, respectively, with no perioperative deaths in either group. Cranial nerve injury was noted in 17% of reoperation patients versus 5.3% of primary CEA patients; however, most of these injuries were transient (P<0.001). Mean hospital stay was 1.8 days for reoperation versus 1.6 days for primary CEA. Cumulative rates of stroke-free survival and freedom from >/=50% recurrent stenosis for reoperation and primary CEA at 1, 3, and 5 years were 96%, 91%, and 82% and 98%, 96%, and 95% versus 94%, 92%, and 91% and 98%, 96%, and 96%, respectively (no significant differences). CONCLUSIONS: Reoperation carries higher perioperative stroke and cranial nerve injury rates than primary CEA. However, reoperations are durable and have stroke-free survival rates that are similar to primary CEA. These considerations should be kept in mind when carotid stenting is recommended instead of reoperation.

cDNA array analysis of cag pathogenicity island-associated Helicobacter pylori epithelial cell response genes.

Helicobacter pylori strains containing the cag pathogenicity island (PAI) induce NF-kappaB activation and interleukin-8 secretion in gastric epithelial cells. The aim of this study was to investigate changes in epithelial gene expression induced by cag PAI-positive and -negative strains of H. pylori using high-density cDNA array hybridization technology. Radio-labeled cDNA prepared from H. pylori-infected Kato 3 gastric epithelial cells was hybridized to high-density cDNA arrays to identify changes in epithelial gene expression compared to noninfected controls. In vivo expression of selected, differentially expressed genes was examined by reverse transcription-PCR analysis of H. pylori-positive and -negative gastric mucosa. Screening of ca. 57,800 cDNAs identified 208 known genes and 48 novel genes and/or expressed sequence tags of unknown function to be differentially expressed in Kato 3 cells following H. pylori infection. Marked differences in gene expression profiles were observed following cag PAI-positive and cag PAI-negative infection with 15 novel cDNAs and 92 known genes being differentially expressed. H. pylori was found to change the expression of genes encoding growth factors and cytokine/chemokines and their receptors, apoptosis proteins, transcription factors and metalloprotease-disintegrin proteins (ADAMs), and tissue inhibitors of metalloproteinases. Gastric differential expression of selected known genes (amphiregulin and ADAM 10) and a novel gene (HPYR1) was confirmed in vivo in patients with H. pylori infection. Confirmation of the in vivo expression of selected genes demonstrates the usefulness of this approach for investigating pathogen-induced changes in host gene expression.

Expression of the Sonic Hedgehog receptor "PATCHED" in basal cell carcinomas and odontogenic keratocysts.

Basal cell carcinoma (BCC) is a common invasive skin lesion in Caucasians. Odontogenic keratocysts (OKs) are developmental, non-inflammatory oral cysts. They can be sporadic and/or multiple and are locally destructive. Basal cell naevus syndrome (BCNS) comprises both multiple BCCs and multiple OKs, in addition to several other systemic manifestations. The genetic defect underlying this autosomal dominant syndrome is a germ line mutation in the Sonic Hedgehog receptor PATCHED (PTCH) gene. For this study, a rabbit anti-peptide PTCH antiserum was produced. Immunohistochemistry procedures were performed using PTCH antibody and commercially produced GLI-1 antibody (downstream member in the hedgehog pathway) to stain 11 BCNS-OKs, eight sporadic OKs, two BCNS-BCCs, and six sporadic BCCs. Most of these lesions had been previously screened for PTCH mutation. Most BCCs (n=7) demonstrated moderate staining, with the heaviest staining in the outer palisading cell layer, except a BCNS-BCC which had mutation proximal to the sequence used for production of immunogenic peptide; this demonstrated only weak staining. Although moderate to heavy staining with PTCH antibody was demonstrated in the epithelium of both types of OK (n=19), a quite different pattern of staining of the basal cell layer was observed in the two patient groups. In BCNS, OK staining was heaviest in basal epithelial layers. In contrast, staining in non-BCNS odontogenic keratocysts was exclusively located in the superficial epithelial layers. Up-regulation of PTCH and GLI-1 protein was demonstrated in both BCCs and OKs. The pattern of PTCH expression matched the PTCH transcript pattern previously reported in BCCs and appeared sufficiently characteristic in OKs to allow differentiation between syndromic and non-syndromic cysts.

Prospective controlled study of carotid endarterectomy with hemashield patch: is it thrombogenic?

The use of patch angioplasty after carotid endarterectomy (CEA) has been shown to have superior results to CEA with primary closure. Polytetrafluoroethylene (PTFE) patches have been shown to have comparable results to autogenous vein patching; however, PTFE has the disadvantage of prolonged hemostasis time. Therefore, many surgeons are using collagen-impregnated Dacron patches (Hemashield[HP]). We believe this is the first prospective controlled study of the use of HP in carotid endarterectomy. This study included 144 consecutive patients who had 151 CEAs with HP. Postoperative duplex ultrasounds were done at 1 month and every 6 months thereafter. The mean follow-up was 12 months (range: 1-30 months). Indications for CEA included symptomatic (64%) and asymptomatic (36%) stenoses. The overall incidence of ipsilateral stroke was 5% (4% perioperative), with a combined TIA and stroke rate of 12%. Incidence of > or =50% recurrent stenosis was 21% (7% symptomatic TIA/stroke) and > or =80% recurrent stenosis was 9%. Kaplan-Meier analysis showed that at 1 year and 2.5 years freedom from > or =50% recurrent stenosis was 78% and 57%, respectively, freedom from > or =80% recurrent stenosis was 92% and 77%, respectively, and a stroke-free survival rate of 94% and 72%, respectively. Women had a 22% and men a 14% recurrent stenosis rate (p=0.04). There was no correlation between other specific risk factors and recurrent stenosis except for hypertension (33% vs 12%, p=0.003). The authors concluded that CEA with HP had a higher incidence of recurrent stenosis (21%), and a higher perioperative stroke rate (4%) after a mean follow-up of 12 months than previously reported using PTFE or saphenous vein patching (2% and 9% recurrent stenosis rates, respectively, and 1% and 0% perioperative stroke rates, respectively after a mean follow-up of 30 months). This raises the question as to whether this patch is thrombogenic in this location. Therefore, a randomized controlled trial comparing this patch with other patches (PTFE or vein) is warranted.

A novel polymorphism in the PTC gene allows easy identification of allelic loss in basal cell nevus syndrome lesions.

Basal cell nevus syndrome (BCNS; also nevoid basal cell carcinoma syndrome [NBCCS]; Gorlin's syndrome) is an autosomal dominant syndrome characterized by multiple basal cell carcinomas, keratocysts, and developmental skeletal defects. Mutation of the human homologue of Drosophila patched (PTC) gene is considered to be the molecular defect in BCNS. PTC mutations have been observed in sporadic tumors including basal cell and ovarian carcinomas and medulloblastoma. The authors report a novel C/T polymorphism in the PTC gene. Forty-eight normal blood samples were screened for the presence of the polymorphism using direct radioactive and automated sequencing of polymerase chain reaction (PCR) products and restriction enzyme digestion. Results demonstrated 20 homozygous T (43%), 11 homozygous C (23%), and 17 heterozygous C/T (35%). The presence of this polymorphism has permitted us to directly detect allelic loss in BCNS, sporadic keratocysts, and basal cell carcinoma (BCC). Further, four BCNS keratocysts and two BCNS-BCC and three non-BCNS keratocysts showed allelic loss of complementary DNA from lesions when compared with their corresponding blood genomic DNA.

Features of the parkin/ariadne-like ubiquitin ligase, HHARI, that regulate its interaction with the ubiquitin-conjugating enzyme, Ubch7.

We recently reported the identification of a RING finger-containing protein, HHARI (human homologue of Drosophila ariadne), which binds to the human ubiquitin-conjugating enzyme UbcH7 in vitro. We now demonstrate that HHARI interacts and co-localizes with UbcH7 in mammalian cells, particularly in the perinuclear region. We have further defined a minimal interaction region of HHARI comprising residues 186-254, identified individual amino acid residues essential for the interaction, and determined that the distance between the RING1 finger and IBR (in between RING fingers) domains is critical to maintaining binding. We have also established that the RING1 finger of HHARI cannot be substituted for by the highly homologous RING finger domains of either of the ubiquitin-protein ligase components c-CBL or Parkin, despite their similarity in structure and their independent capabilities to bind UbcH7. Furthermore, mutation of the RING1 finger domain of HHARI from a RING-HC to a RING-H2 type abolishes interaction with UbcH7. These studies demonstrate that very subtle changes to the domains that regulate recognition between highly conserved components of the ubiquitin pathway can dramatically affect their ability to interact.

Selecting patients for combined femorofemoral bypass grafting and iliac balloon angioplasty and stenting for bilateral iliac disease.

PURPOSE: This study examines the selection of patients for combined femorofemoral bypass (FFB) grafting and iliac balloon angioplasty (IBA) and stenting for bilateral iliac occlusive disease (successively or simultaneously) and the correlation of the length and location of stenoses of the donor iliac artery to the success of FFB grafts. METHODS: Forty-one patients with long iliac occlusion and significant contralateral iliac stenosis were treated with combined FFB grafting and IBA and stenting, which were performed simultaneously or percutaneously within 1 to 2 days before surgery. Stenting was performed for suboptimal IBAs. IBA/graft patency was evaluated by duplex scanning/ankle-brachial index at 1, 3, 6, and 12 months and every 12 months thereafter. A life-table analysis of patency was performed, according to the length of stenosis as classified by the Society of Cardiovascular Interventional Radiology (group A, < 3 cm and 3-5 cm; group B, > 5 cm). RESULTS: Indications for surgery were limb salvage (22%), rest pain (44%), and claudication (34%). The mean follow-up time was 34.1 months. Perioperative complications were 7% for group A versus 62% for group B (P = .0007) with no perioperative deaths or amputations. Stenting was needed in 12 of 13 patients (92%) in group B versus four of 28 patients (14%) in group A (P < .0001) and in 11 of 12 external iliac artery lesions versus five of 29 common iliac artery lesions (P < .0001). The overall early success rate was 100% for group A and 62% for group B (P = .0028). The primary patency rates at 1, 2, and 3 years were 96%, 85%, and 85% for group A, respectively, and for group B were 46%, 46%, and 31%, respectively (P < .01). The secondary patency rates for group A at 1, 2, and 3 years were 100%, 96%, and 87%, respectively; and for group B were 62%, 54%, and 27%, respectively (P < .001). The overall primary and secondary patency rates for common iliac and external iliac artery lesions were similar (72% and 72% versus 67% and 75%, respectively). The overall limb salvage rates were 96% for group A and 85% for group B. Seven of 13 patients (54%) of group B, in contrast with 0 of 28 patients in group A, had to undergo a revision of the procedure within 30 days (P < .01). CONCLUSION: Combined use of IBA and stenting and FFB grafting is effective and durable and can be performed simultaneously, if the donor iliac stenosis length is 5 cm or less. Percutaneous transluminal angioplasty/stenting of stenoses of 5 cm or more fail to support FFB grafting in most patients; therefore, their combination should be questioned.

Expression of Interleukin-18, a Th1 cytokine, in human gastric mucosa is increased in Helicobacter pylori infection.

Interleukin-18 (IL-18), a cytokine that promotes Th1 responses, is processed to the active mature protein by caspase-1. The effects of Helicobacter pylori infection on gastric IL-18 and caspase-1 were examined. In antral mucosa, IL-18 mRNA expression was greater (P<.01) in H. pylori-positive (n=40) than in H. pylori-negative patients (n=29) with normal mucosa. Inactive precursor (24 kDa) and mature (18 kDa) IL-18 were present in antral biopsy specimens from uninfected and infected subjects. In corpus mucosa, mature IL-18 and a 16-kDa protein, corresponding to inactive IL-18, were present. Active caspase-1 p20 subunit was detected in antral and corpus mucosa of infected and uninfected subjects. These data show that, although H. pylori infection is associated with increased antral IL-18 mRNA expression, mature IL-18 protein and active caspase-1 p20 are present in mucosa of both H. pylori-infected and -uninfected subjects. IL-18 may have an important role in promoting gastric Th1 responses in H. pylori infection.

Frequency of postoperative carotid duplex surveillance and type of closure: results from a randomized trial.

BACKGROUND/PURPOSE: In several nonrandomized studies investigators have reported on the value of postoperative carotid duplex surveillance (PCDS) with mixed results; however the type of closure was not analyzed in these studies. In this study we analyze the frequency and timing of postoperative carotid duplex ultrasound scanning according to the type of closure from a randomized carotid endarterectomy (CEA) trial comparing primary closure (PC) versus patching. PATIENT POPULATION AND METHODS: We randomized 399 CEAs into 135 PCs, 134 polytetrafluoroethylene (PTFE) patch closures, and 130 vein patch closures (VPCs) with a mean follow-up of 47 months. PCDS was done at 1, 6, and 12 months and every year thereafter (a mean of 4.0 studies per artery). Kaplan-Meier analysis was used to estimate the rate of > or = 80% restenosis over time and the time frame of progression from < 50%, to 50%-79% and > or = 80% stenosis. RESULTS: Restenoses of > or =80% developed in 24 (21%) arteries with PC and nine (4%) with patching. Kaplan-Meier estimate of freedom of > or = 80% restenosis at 1, 2, 3, 4, and 5 years was 92%, 83%, 80%, 76%, and 68% for PC, respectively, and 100%, 99%, 98%, 98%, and 91% for patching, respectively, (P <.01). Of 56 arteries with 20% to 50% restenosis, two of 28 patch closures and 10 of 28 PCs progressed to 50% to < 80% restenosis (P =.02); none of the patch closures and six of 28 PCs progressed to > or =80% (P =.03). In PCs, the median time to progression from <50% to 50%-79%, < 50% to > or =80%, and 50%-79% to > or = 80% was 42, 46, and 7 months, respectively. Of the 24 arteries with > or =80% restenosis in PC, 10 were symptomatic. Thus, assuming th symptomatic restenosis would have undergone duplex scan examinations regardless, there were 14 asymptomatic arteries (12%) that could have been detected only with PCDS (estimated cost, $139, 200), and those patients would have been candidates for redo CEA. Of the 9 arteries (3 PTFE closures and 6 VPCs) with > or =80% restenosis with patch closures, 6 asymptomatic (4 VPCs and 2 PTFE closures) arteries (3%) could have been detected with PCDS. In patients with normal duplex scan findings at the first 6 months, only four (2%) of 222 patched arteries (two asymptomatic) developed > or = 80% restenosis versus five (38%) of 13 in patients with abnormal duplex scan examination findings (P<.001). CONCLUSIONS: PCDS is beneficial in patients with PC, but is less beneficial in patients with patch closure. PCDS examinations at 6 months and at 1- to 2-year intervals for several years after PC are adequate. For patients with patching, a 6-month postoperative duplex scan examination with normal results is adequate.

Carotid-subclavian bypass grafting with polytetrafluoroethylene grafts for symptomatic subclavian artery stenosis or occlusion: a 20-year experience.

BACKGROUND AND PURPOSE: Since the advent of subclavian artery percutaneous transluminal angioplasty/stenting, several authorities advocate it as the treatment of choice for patients with subclavian artery disease, claiming results equal to or better than those of reconstructive vascular surgery. However, most of their quoted surgical series included patients who may have other brachiocephalic disease who were treated nonuniformly by means of various bypass grafts with different grafts in the same series (eg, Dacron, polytetrafluoroethylene [PTFE], or vein). In this study, we analyze the long-term results of a large series of carotid-subclavian bypass grafts for subclavian artery disease in which PTFE was uniformly used; the study can be used as a future reference to compare the results of subclavian artery percutaneous transluminal angioplasty/stenting. PATIENT POPULATION AND METHODS: Fifty-one patients with symptomatic subclavian artery disease (40 occlusions and 11 stenoses) who were treated with carotid-subclavian bypass grafts (PTFE [Goretex]) during a 20-year period were analyzed. Graft patency was determined clinically and confirmed with Doppler scanning pressures and duplex ultrasound scanning. The cumulative patency, overall survival, and symptom-free survival rates were calculated with the life table method. RESULTS: Indications for surgery were arm ischemia in 34 patients (67%), vertebrobasilar insufficiency (VBI) in 27 (53%), and symptomatic subclavian steal in 7 (14%). A combination of arm ischemia and VBI occurred in 17 (33%) of these patients. The mean follow-up was 7.7 years with a median of 7.0 years (range, 1-19 years). The 30-day morbidity rate was 6%, with no perioperative stroke or mortality. Immediate relief of symptoms was achieved in 100% of patients; however, four patients (8%) had late recurrent symptoms (three with VBI). The primary patency and secondary patency rates at 1, 3, 5, and 10 years were 100%, 98%, 96%, and 92% and 100%, 98%, 98%, and 95%, respectively. The symptom-free survival rates at 1, 3, 5, and 10 years were 100%, 96%, 82%, and 47%, respectively. The overall survival rates at 1, 3, 5, and 10 years were 100%, 98%, 86%, and 57%. The mean hospital stay was 3.5 days in the late 70s and 80s and 2.1 days in the 90s (P <. 001). CONCLUSIONS: Carotid-subclavian bypass grafts with PTFE grafts for subclavian artery disease are safe, effective, and durable and should remain the procedure of choice, particularly in good-risk patients.