Immunohistological characterization of spinal TB granulomas from HIV-negative and -positive patients.

Tuberculosis (TB) is mainly a disease of the lungs, but Mycobacterium tuberculosis (Mtb) can establish infection in virtually any organ in the body. Rising rates of extrapulmonary (EP) TB have been largely associated with the HIV epidemic, as patients co-infected with HIV show a four-fold higher risk of EPTB. Spinal TB (Pott's Disease), one of the most debilitating extrapulmonary forms of disease, is difficult to diagnose and can cause deformity and/or neurological deficits. This study examined the histopathology and distribution of immune cells within spinal TB lesions and the impact of HIV on pathogenesis. The overall structure of the spinal granulomas resembled that seen in lung lesions from patients with pulmonary TB. Evidence of efficient macrophage activation and differentiation were detectable within organized structures in the spinal tissue, irrespective of HIV status. Interestingly, the granulomatous architecture and macroscopic features were similar in all samples examined, despite a reversal in the ratio of infiltrating CD4 to CD8 T cells in the lesions from HIV-infected patients. This study provides a foundation to understand the mechanism of tissue destruction and disease progression in Spinal TB, enabling the future development of novel therapeutic strategies and diagnostic approaches for this devastating disease.

In vitro/in vivo correlation for 14C-methylated lysozyme release from poly(ether-ester) microspheres.

PURPOSE: The purpose of this study was to obtain an in vitro/in vivo correlation for the sustained release of a protein from poly(ethylene glycol) terephthalate (PEGT)/poly(butylene terephthalate) (PBT) microspheres. METHODS: Radiolabeled lysozyme was encapsulated in PEGT/PBT microspheres via a water-in-oil-in-water emulsion. Three microsphere formulations varying in copolymer composition were administered subcutaneously to rats. The blood plasma was analyzed for radioactivity content representing released lysozyme at various time points post-dose. The in vitro release was studied in phosphate-buffered saline. RESULTS: The encapsulation efficiency, calculated from the radioactivity in the outer water phase of the emulsion, varied from 60-87%. Depending on the PEG segment length and wt% PEGT, the lysozyme was released completely in vitro within 14 to 28 days without initial burst. 14C-methylated lysozyme could be detected in the plasma over the same time courses. The in vitro/in vivo correlation coefficients obtained from point-to-point analysis were greater than 0.96 for all microsphere formulations. In addition, less then 10% of administered radioactivity remained at dose site at 28 days for the microsphere formulations, indicating no notable retention of the protein at the injection site. CONCLUSION: The in vitro release in phosphate-buffered saline and the in vivo release in rats showed an excellent congruence independent of the release rate of 14C-methylated lysozyme from PEGT/PBT microspheres.

The psychosocial experience of people with sickle cell disease and its impact on quality of life: Qualitative findings from focus groups.

OBJECTIVES: In this exploratory study, an in-depth analysis of accounts of the experiences of people with sickle cell disease (SCD) was undertaken to gain an understanding of the psychosocial impact of the disease. An additional aim of the study was to determine whether these experiences could be conceptualized in terms of quality of life as defined by the World Health Organization (WHOQOL) with the intention of informing psychosocial research. DESIGN: This study utilized a series of non-directive, patient-led, focus groups that specifically addressed the ways in which sickle cell disease impacts on life. Participants were recruited from four centres in London and eight focus group discussions (each one hour in length) were held separately for each centre. METHOD: Altogether 32 hours of focus group materials were tape-recorded and transcribed verbatim. Data were analysed using a phenomenological approach to identify emerging themes. RESULTS: Six themes were identified: Growing up with SCD; Education; Impact of the unremitting nature of the disease; Employment; Effects on relationships; and Hospitalization. CONCLUSION: This research has clearly shown that SCD carries a huge psychosocial burden impacting on physical, psychological, social and occupational well-being as well as levels of independence and environment. These aspects of life are equivalent to the core domains of the multi-dimensional WHOQOL and consequently we have argued that SCD undermines quality of life in important ways. The paper provides a rich source of qualitative data to complement quantitative findings and provides detail of the complex human processes and experiences consequent on a life-long chronic illness such as SCD.

Identification of a new human lens UV filter compound.

A new UV filter compound, 4-(2-amino-3-hydroxyphenyl)-4-oxobutanoic acid O-diglucoside, has been identified in human lenses. The structure suggests that it is a further metabolic product of the second most abundant UV filter compound, 4-(2-amino-3-hydroxyphenyl)-4-oxobutanoic acid O-glucoside. Quantification studies on the new compound show that it decreases towards zero in both the nucleus and cortex as a function of age. The discovery of this novel disaccharide completes the identification of the major UV filter compounds present in the human lens.

Functional outcome after open repair of abdominal aortic aneurysm.

INTRODUCTION: Detailed information on functional outcome after open abdominal aortic aneurysm (AAA) repair is sparse. Information about functional outcome of open AAA repair is essential to allow comparison of treatment modalities. METHODS: To determine the functional outcome of patients after open repair of AAA, we reviewed 154 consecutive, nonemergency open repairs of infrarenal AAAs between 1990 and 1997 and each patient's medical records. Clinical variables were recorded for each patient, as were multiple outcomes, including ambulatory status, independent living status, current medical condition, and the patient's perception of recovery and satisfaction. Eighty-seven patients or their families were available for current telephone interview to obtain information about objective functional activities, including walking and driving, and subjective functional information, including assessment of complete recovery and willingness to undergo AAA repair again. Chart data were available for all 154 patients. RESULTS: There were 42 women and 112 men. A total of 139 operations were elective, and 15 were urgent. The operative mortality rate was 4%, mean hospital stay was 10.7 +/- 1.3 days, and mean intensive care unit stay was 4.57 +/- 1.17 days. Seventeen (11%) patients required transfer to a skilled nursing facility with a mean stay of 3.66 +/- 2.9 months. All patients were ambulatory preoperatively, whereas at last follow-up (median, 25 months; range, 0.13-108.5 months), 100 (64%) of the patients remained ambulatory, 34 (22%) required assistance, and 12 (14%) were nonambulatory. At current assessment by telephone interview, 33% of patients described a decrease in their functional activity including driving, shopping, and traveling compared with their preoperative status, whereas 67% were unchanged. When asked to assess their own degree of recovery, 64% of patients stated that they experienced complete recovery with an average time to recovery of 3.9 months, whereas 33% said they had not fully recovered at a mean follow-up of 34 months. Sixteen (18%) patients said they would not undergo AAA repair again knowing the recovery process, even though they appeared to fully understand the implication of AAA rupture. CONCLUSION: Patients undergoing open AAA repair generally experienced significant freedom from surgical complications. However, substantial functional impairment was present. It is unclear whether the functional disability resulted from the AAA surgery or from aging and comorbidities unrelated to surgery.

Relationship between antiphospholipid antibodies and progression of lower extremity arterial occlusive disease after lower extremity bypass operations.

PURPOSE: Antiphospholipid antibodies (APLs), which consist of anticardiolipin antibodies (ACLs) or lupus anticoagulant (LA), are associated with venous thrombosis, stroke, and cardiac events. Although they are present in many patients with lower extremity atherosclerotic occlusive disease (LEAOD), the relationship between APL and the progression of LEAOD has not been reported. A comparison of progression of LEAOD as determined with direct imaging studies in patients with and without APL forms the basis for this report. METHODS: APL+ patients (immunoglobulin M [IgM] or IgA or IgG ACL > 3 SD units above control mean or positive LA) who underwent lower extremity bypass grafting between January 1990 and June 1999 (n = 79) were compared with an APL control group (n = 68). Members of the study and control groups were similar with respect to age, procedure, sex, length of follow-up, and multiple atherosclerosis risk factors. Progression of LEAOD was determined by comparing preoperative arteriograms with postoperative imaging studies (arteriograms or duplex scanning). External iliac, common femoral, superficial femoral and popliteal arteries were graded as < 50% stenosis, > or = 50% stenosis, or occluded. Posterior tibial and anterior tibial arteries were graded as patent or occluded. Progression was defined as any increase in stenosis category. RESULTS: The mean follow-up period was 31 months for APL+ and 35 months for APL- patients (P = not significant). Progression of LEAOD occurred in 58 (73%) of 79 APL+ patients and in 25 (37%) of 68 APL- patients (P <.001). There was no difference in progression in external iliac or common femoral arteries. Differences in progression were noted in more distal arteries; APL+ patients had significantly more progression in superficial femoral (45% vs 16%, P <.01), popliteal (31% vs 12%, P <.01), posterior tibial (29% vs 13%, P <.05), and anterior tibial arteries (29% vs 14%, P <.05). Multivariate logistic regression analysis showed a significant independent association between the presence of APL and progression of LEAOD (P <.0001). CONCLUSION: In this study, the presence of APL in patients undergoing lower extremity bypass operations was a significant independent risk factor for progression of LEAOD. We conclude that this patient group should be closely monitored in the postoperative period and appears ideally suited for prospective studies of therapies to modify LEAOD progression.

Long-term functional outcome of neurogenic thoracic outlet syndrome in surgically and conservatively treated patients.

PURPOSE: Neurogenic thoracic outlet syndrome (NTOS) in the absence of bony and electrodiagnostic abnormalities, often referred to as disputed NTOS, remains enigmatic. Optimal treatment, especially the role of surgery, is controversial. The long-term functional outcome of a cohort of patients undergoing independent medical examination for disputed NTOS with symptoms sufficiently severe to cause inability to work forms the basis for this report. METHODS: Patients with disputed NTOS and symptoms sufficiently severe to cause at least temporary inability to work seen for independent medical examinations from 1990-1998 formed the study group. None of the patients were treated by our group. Functional outcome was assessed with information from a standardized telephone interview or patient questionnaire. The patients' ability to return to work and an assessment of their current level of symptoms and symptom progression since the time of onset were determined. RESULTS: Seventy-nine patients were reevaluated at a mean follow-up of 4.2 years (range, 2-7.5 years) after our initial evaluation. Fifteen patients (19%) underwent first rib resection surgery performed by others, whereas 64 (81%) had no surgery. Patients undergoing surgery had missed more work time than those undergoing conservative management (27.6 +/- 6.0 months vs 14.9 +/- 2.6 months, P <.04). Return to work was achieved in nine patients who were operated on (60%) and in 50 patients who were not operated on (78%) (P = not significant [NS]). Among operated patients, current assessment of symptom severity was severe, moderate, mild, and asymptomatic in 7%, 47%, 40% and 7%, respectively. This distribution did not differ significantly from that observed in nonoperated patients (11%, 55%, 30%, 5%; P = NS). When asked about changes in symptomatic status since onset, 7% of the operated group had complete resolution, 27% had marked improvement, 40% had minimal improvement, 13% had no improvement, and 13% were worse. This did not differ significantly from the change in symptoms reported by the nonoperated group (2%, 30%, 22%, 31%, 16%; P = NS). CONCLUSION: Most patients with disputed NTOS in this nonrandomized series were able to return to work and demonstrated an improvement of symptoms with long-term follow-up. First rib resection did not improve functional outcome in this group.

Optimizing duplex follow-up in patients with an asymptomatic internal carotid artery stenosis of less than 60%.

OBJECTIVES: The Asymptomatic Carotid Atherosclerosis Study established benefit of carotid endarterectomy for 60% to 99% asymptomatic internal carotid artery (ICA) stenosis. Optimal follow-up intervals to detect progression from < 60% to 60%-99% ICA stenosis are unknown. In a previous study from our laboratory, we found that ICAs with < 60% stenosis and peak systolic velocities (PSVs) of 175 cm/s or more on initial duplex were at high risk for progression. Prospective evaluation of this hypothesis and determination of optimal duplex follow-up intervals for asymptomatic patients with < 60% ICA stenosis form the basis of this report. METHODS: All patients who underwent initial carotid duplex examination for any indication since January 1, 1995, with at least one patent, asymptomatic, previously nonoperated ICA with < 60% stenosis; with 6 months' or greater follow-up; and with one or more repeat duplex examinations were entered into the study. On the basis of the initial duplex examination, ICAs were classified into two groups: those with a PSV less than 175 cm/s and those with a PSV of 175 cm/s or more. Follow-up duplex examinations were performed at varying intervals to detect progression from < 60% to 60%-99% ICA stenosis with criteria previously reported (both PSV > or = 260 cm/s and end-diastolic velocity > or = 70 cm/s). RESULTS: A total of 407 patients (640 asymptomatic ICAs with < 60% stenosis) underwent serial duplex scans (mean follow-up, 22 months). Three ICAs (0.5%) became symptomatic and progressed to 60%-99% ICA stenosis at a mean of 21 months (all transient ischemic attacks), whereas four other ICAs occluded without stroke during follow-up. Progression to 60%-99% stenosis without symptoms was detected in 46 ICAs (7%) (mean, 18 months). Of the 633 patent asymptomatic arteries, 548 ICAs (87%) had initial PSVs less than 175 cm/s, and 85 ICAs (13%) had initial PSVs of 175 cm/s or more. Asymptomatic progression to 60%-99% ICA stenosis occurred in 22 (26%) of 85 ICAs with initial PSVs of 175 cm/s or more, whereas 24 (4%) of 548 ICAs with initial PSVs less than 175 cm/s progressed (P <.0001). The Kaplan-Meier method was used to determine freedom from progression at 6 months, 12 months, and 24 months, which was 95%, 83%, and 70% for ICAs with initial PSVs of 175 cm/s or more versus 100%, 99%, and 95%, respectively, for ICAs with initial PSVs less than 175 cm/s (P <.0001). CONCLUSIONS: Patients with < 60% ICA stenosis and PSVs of 175 cm/s or more on initial duplex examination are significantly more likely to progress asymptomatically to 60%-99% ICA stenosis, and progression is sufficiently frequent to warrant follow-up duplex studies at 6-month intervals. Patients with < 60% ICA stenosis and initial PSVs less than 175 cm/s may have follow-up duplex examinations safely deferred for 2 years.

Patency and characteristics of lower extremity vein grafts requiring multiple revisions.

OBJECTIVES: Multiple (> 1) revisions of lower extremity vein grafts may be required to maintain patency. Characteristics of recurrent lower extremity vein graft lesions and the patency achieved after multiple revisions have not been emphasized in reports on infrainguinal vein graft stenosis. This study was performed to determine (1) the patency of multiply revised lower extremity vein grafts and (2) the timing, location, and angiographic and duplex features of the recurrent lesions. METHODS: Lower extremity vein grafts that were followed in a duplex surveillance protocol and required revisions from January 1990 through December 1998 were identified. All revisions were preceded by angiography. In multiply revised lower extremity vein grafts, the immediate preoperative angiogram and duplex examination findings, as well as the angiogram made before the previous revision and the duplex study done after the previous revision, were reviewed to characterize recurrent lesions at the time of previous and current graft revision. The patencies of grafts undergoing single and multiple revisions were compared. RESULTS: A total of 233 lower extremity vein graft revisions were performed; of these, 50 (21%) were repeat revisions. Of grafts requiring more than one revision, 98% were normal on duplex examination after the initial revision. Five-year assisted primary patency of multiply revised grafts (91%) was not different from that of grafts with a single revision (89%; P not significant). Of 60 lesions repaired in the 50 repeat revisions, 29 (48%) were at the previously revised site, and 31 (52%) were at new sites. The time between revisions was less if the same site was revised (11 +/- 2 months) than if a different site required revision (20 +/- 4 months; P <.05). Arteriographic evidence of a minor (< 50% diameter) lesion was present at the time of the initial revision in 23% of cases in which revision of a second site was subsequently required. CONCLUSION: In our experience, 21% of lower extremity vein grafts requiring initial revision ultimately require additional revisions. Multiply revised lower extremity vein grafts have excellent long-term patency. Lesions occur with equal frequency at the site of prior revision and new sites. Lesions prompting revision at new sites occur significantly later and are infrequently detected on prior imaging studies.

Revascularization of the superior mesenteric artery alone for treatment of intestinal ischemia.

OBJECTIVE: Complete revascularization is recommended by many authors for treatment of intestinal ischemia. The observation that postprandial intestinal hyperemia is limited to the superior mesenteric artery (SMA) has suggested to us that SMA revascularization alone should be adequate treatment. We preferentially manage intestinal ischemia with a single bypass graft to the SMA and herein update our results using this approach. METHODS: Patients were identified from a prospectively established vascular surgical registry. Each patient was assessed for acute versus chronic intestinal ischemia, preoperative angiographic findings, operation used, perioperative morbidity and mortality, late symptomatic relief, cause of death, and life table-determined survival and graft patency. Graft patency was determined by follow-up angiography or duplex scanning. RESULTS: Fifty bypass grafts to the SMA alone were performed in 49 patients (31 women, 18 men; mean age, 62 years) for treatment of intestinal ischemia. In all patients additional splanchnic arteries were available for bypass grafting. Operative indications were acute symptoms in 21 patients, 14 of whom had bowel infarction; chronic symptoms in 26 patients; and prophylaxis in conjunction with infrarenal aortic surgery in 3 patients. Thirty-two grafts originated from the aorta or an iliac artery, and 18 originated from an aortic graft. There were 40 prosthetic and 10 autogenous conduits. Perioperative mortality was 3% in patients with chronic symptoms and 12% overall. All survivors were symptomatically improved. Mean follow-up was 44 months. Nine-year assisted primary graft patency was 79%, and 5-year patient survival was 61%. Two late deaths occurred in patients with recurrent intestinal ischemia resulting from graft occlusions. CONCLUSIONS: Bypass grafting to the SMA alone appears to be both an effective and durable procedure for treatment of intestinal ischemia. Our results appear equal to those reported for "complete" revascularization for intestinal ischemia. When the SMA is a suitable recipient vessel, multiple bypass grafts to other splanchnic vessels are unnecessary in the treatment of intestinal ischemia.

Induction of platelet-derived growth factor B-chain expression by transforming growth factor-beta involves transactivation by Smads.

Transforming growth factor-beta (TGF-beta) regulates a diverse array of biological processes, such as proliferation, differentiation, extracellular matrix production, and apoptosis. In cultured vascular endothelial cells, TGF-beta induces the expression of platelet-derived growth factor (PDGF) B-chain, a mitogen and chemoattractant, at the level of transcription. The molecular mechanism(s) underlying this process are not presently understood. In this study, we performed serial 5' deletion and transient transfection analysis to define a region in the PDGF-B promoter mediating inducible responsiveness to TGF-beta. This region contains an atypical nucleotide recognition element for the Smad family of transcriptional regulators. Electrophoretic mobility shift analysis revealed that nuclear proteins bound to this site in a transient and specific manner. Supershift studies demonstrated the physical association of Smad4 with the promoter. Overexpression of Smad4 activated the PDGF-B promoter and superinduced PDGF-B promoter-dependent expression in cells exposed to TGF-beta. Moreover, simultaneous cotransfection of Smad3 and Smad4 activated the PDGF-B promoter. This effect was attenuated when Smad4 was substituted with its dominant negative counterpart. Mutation of the (-81)CAGA(-78) motif in the PDGF-B promoter abrogated Smad-inducible promoter-dependent expression. Overexpression of Smad2 and Smad3 transactivated the PDGF-B promoter in a synergistic manner. These findings demonstrate the existence of a novel, functional binding element in the proximal region of the PDGF-B promoter mediating responsiveness to TGF-beta.

Axillary artery anastomosis to avoid axillofemoral bypass disruption.

Acute disruption at or adjacent to axillary anastomoses of axillofemoral grafts has been sporadically reported. The cause of this serious complication is believed to be attributable to mechanical stresses on the proximal portion of the graft and anastomosis. A modification in the proximal tunneling of the axillofemoral graft, which appears to have effectively reduced the occurrence of this vexing complication, is described in this report.

Is a single preoperative duplex scan sufficient for planning bilateral carotid endarterectomy?

PURPOSE: Duplex scanning is often the sole imaging study before carotid endarterectomy (CEA). Patients with bilateral severe internal carotid artery (ICA) stenosis may be considered for bilateral CEA. High-grade ICA stenosis, however, may artifactually elevate velocity measurements used to quantify stenosis in the contralateral ICA. It is unknown whether ipsilateral CEA will influence duplex determination of the presence of a contralateral 60% to 99% ICA stenosis. This study was performed to determine whether a single preoperative duplex scan is sufficient to plan bilateral CEA. METHODS: Preoperative and early postoperative carotid duplex scans in patients with bilateral ICA stenosis who underwent unilateral CEA were reviewed. Changes in duplex scans that determined stenosis in the ICA contralateral to the CEA were analyzed. Previously validated criteria used to determine 60% to 99% ICA stenosis were a peak systolic velocity (PSV) of 260 cm/sec or more combined with an end diastolic velocity (EDV) of 70 cm/sec or more. RESULTS: Over an 8-year period, 460 patients underwent CEA; 107 patients (23.3%) had an asymptomatic 50% to 99% contralateral ICA stenosis by standard criteria (PSV, >125 cm/sec) and an early postoperative duplex scan examination. Of these 107 patients, 38 patients (35.5%) had duplex scan criteria for 60% to 99% contralateral ICA stenosis. In these 38 patients, there was a mean postoperative PSV decrease of 47.7 cm/sec (10.1%) and a mean EDV decrease of 36.0 cm/sec (19.3%) in the ICA contralateral to the CEA. Eight of 38 (21.1%) preoperative contralateral 60% to 99% ICA lesions were reclassified as less than 60% on postoperative duplex scanning. Six of 69 (8.7%) preoperative lesions of less than 60% were reclassified as 60% to 99% on postoperative duplex scan. These six preoperative examinations were all close to the criteria for 60% to 99% stenosis (mean PSV, 232.5 cm/sec; mean EDV, 62.5 cm/sec). CONCLUSION: One-fifth of patients with apparent 60% to 99% contralateral ICA lesions before the operation have less than 60% stenosis when restudied with duplex scan after unilateral CEA. Lesions below but near the cutoff for 60% to 99% may be reclassified as 60% to 99% on the postoperative duplex scan. These findings mandate that when duplex scanning is used as the sole imaging modality before CEA, patients with severe bilateral carotid stenosis must have an additional carotid duplex examination before operation on the second side.

Hypothenar hammer syndrome: proposed etiology.

PURPOSE: Finger ischemia caused by embolic occlusion of digital arteries originating from the palmar ulnar artery in a person repetitively striking objects with the heel of the hand has been termed hypothenar hammer syndrome (HHS). Previous reports have attributed the arterial pathology to traumatic injury to normal vessels. A large experience leads us to hypothesize that HHS results from trauma to intrinsically abnormal arteries. METHODS: We reviewed the arteriography, histology, and clinical outcome of all patients treated for HHS in a university clinical research center study of hand ischemia, which prospectively enrolled more than 1300 subjects from 1971 to 1998. RESULTS: Twenty-one men had HHS. All had occupational (mechanic, carpenter, etc) or avocational (woodworker) exposure to repetitive palmar trauma. All patients underwent upper-extremity and hand arteriography, unilateral in eight patients (38%) and bilateral in 13 patients (62%). By means of arteriogram, multiple digital artery occlusions were shown in the symptomatic hand, with either segmental ulnar artery occlusion in the palm or characteristic "corkscrew" elongation, with alternating stenoses and ectasia. Similar changes in the contralateral asymptomatic (and less traumatized) hand were shown by means of 12 of 13 bilateral arteriograms (92%). Twenty-one operations, consisting of segmental ulnar artery excision in the palm and vein grafting, were performed on 19 patients. Histology was compatible with fibromuscular dysplasia with superimposed trauma. Patency of arterial repairs at 2 years was 84%. One patient (5%) required amputative debridement of necrotic finger tips. No other tissue loss occurred. There have been no recurrences of ischemia in patients with patent bypass grafts. CONCLUSION: To our knowledge, this is the largest reported group of HHS patients. The characteristic angiographic appearance, histologic findings, and striking incidence of bilateral abnormalities in patients with unilateral symptoms lead us to conclude that HHS occurs when persons with preexisting palmar ulnar artery fibrodysplasia experience repetitive palmar trauma. This revised theory for the etiology of HHS explains why HHS does not develop in most patients with repetitive palmar trauma.

The effect of elevated homocysteine levels on adrenergic vasoconstriction of human resistance arteries: the role of the endothelium and reactive oxygen species.

PURPOSE: This study investigated the effect of elevated homocysteine levels on adrenergic contraction of human resistance arteries and tested the hypothesis that homocysteine-induced generation of reactive oxygen species contributes to vascular reactivity changes. METHODS: Small (<200 microm) subcutaneous arteries were cannulated and pressurized in an arteriograph chamber that allowed the measurement of lumen diameter. Two arteries from the same patient were obtained; one was perfused and superfused (intraluminal pressure = 50 mm Hg) with physiologic saline solution (control, n = 6), and the other was perfused and superfused with physiologic saline solution plus 200 micromol/L homocysteine (HC, n = 6); the reactivity to adrenergic stimulation was assessed. Another group of arteries was incubated in 200 micromol/L homocysteine plus 1200 U/mL superoxide dismutase and 120 U/mL catalase (HC + SC, n = 6), and the reactivity to norepinephrine was determined. The vasoreactivity of homocysteine was further assessed in intact (n = 6) and denuded (n = 6) arteries that were precontracted with an intermediate concentration of norepinephrine and homocysteine (20-200 micromol/L) added to the bath while the lumen diameter was continuously recorded. RESULTS: Sensitivity to norepinephrine was diminished in HC arteries, which increased the median effective concentration (EC(50)) from 0.24 +/- 0.06 micromol/L in control arteries to 0.65 +/- 0.10 micromol/L in HC arteries (P <.01). Homocysteine also caused concentration-dependent vasodilation of arteries contracted with an intermediate concentration of norepinephrine that was greater in intact than denuded arteries, with the half-maximum responses occurring at 61 +/- 6 micromol/L (intact) and 90 +/- 11 micromol/L (denuded; P <.05). There was no significant difference in sodium nitroprusside sensitivity between control and homocysteine arteries (EC(50) = 61 +/- 3 nmol/L vs 50 +/- 19 nmol/L; P >.05) or in sensitivity to acetylcholine (EC(50) = 19 +/- 7 nmol/L vs 12 +/- 3 nmol/L; P >.05). Arteries in the presence of superoxide dismutase and catalase had similarly impaired reactivity to norepinephrine as did homocysteine arteries (EC(50), 0.58 +/- 0.15 micromol/L; P >.05 vs HC, P <.01 vs control). CONCLUSION: An elevated homocysteine level in vitro diminishes adrenergic contraction, with a differential endothelial versus smooth muscle influence that appears unrelated to the generation of reactive oxygen species.

Extrathoracic arterial grafts performed for carotid artery occlusive disease not amenable to endarterectomy.

HYPOTHESIS: Extrathoracic cervical grafts are safe and provide long-lasting stroke prevention in patients with disease not amenable to standard carotid bifurcation endarterectomy. DESIGN: Review of a prospectively maintained vascular surgical registry. SETTING: Combined university and Department of Veterans Affairs vascular surgical service. PARTICIPANTS: Patients requiring surgery for carotid atherosclerotic occlusive disease not amenable to endarterectomy from January 1988 to March 1998. INTERVENTIONS: Carotid interposition grafting, subclavian-carotid bypass, or carotid-carotid bypass. MAIN OUTCOME MEASURES: Perioperative stroke and death, and life-table determination of freedom from stroke, stroke-free survival, and graft patency. RESULTS: Sixty patients (mean age, 65.8 years; range, 36-83) underwent cervically based carotid grafting. All had greater than 70% stenosis or occlusion of the innominate, common carotid, or internal carotid arteries, and 30 (50%) had undergone at least 1 previous ipsilateral carotid endarterectomy. Indication for operation was stroke or transient ischemic attack in 46 (77%) and asymptomatic high-grade stenosis in 14 (23%). Operative procedures included 31 (52%) carotid interposition grafts, 18 (30%) subclavian-carotid grafts, and 11 (18%) carotid-carotid grafts. Mean follow-up was 29 months (range, 1-117 months). Perioperative stroke rate was 5% (3/60) all in symptomatic patients, and there were no perioperative deaths. By life-table analysis, freedom from stroke was 92% at 1 and 5 years. Stroke-free survival was 90% at 1 year and 61% at 5 years. Primary graft patency was 94% at 1 year and 84% at 5 years, with assisted primary patency of 90% at 5 years. CONCLUSION: Cervical carotid artery grafts for complicated or recurrent carotid atherosclerosis not amenable to endarterectomy are durable and provide excellent freedom from stroke with low perioperative morbidity and mortality.

Raynaud's syndrome in workers who use vibrating pneumatic air knives.

PURPOSE: The use of vibrating tools has been shown to cause Raynaud's syndrome (RS) in a variety of workers, including those who use chain saws, chippers, and grinders. The diagnosis of RS in workers who use vibrating tools is difficult to document objectively. We studied a patient cohort with RS caused by the use of a vibrating pneumatic air knife (PAK) for removal of automobile windshields and determined our ability to document RS in these workers by means of digital hypothermic challenge testing (DHCT), a vascular laboratory study that evaluates digital blood pressure response to cooling. METHODS: Sixteen male autoglass workers (mean age, 36 years) with RS were examined by means of history, physical examination, arm blood pressures, digital photoplethysmography, screening serologic studies for underlying connective tissue disorder, and DHCT. RESULTS: No patient had RS before they used a PAK. The mean onset of RS (color changes, 100%; pain, 93%; parathesias, 75%) with cold exposure was 3 years (range, 1.5 to 5 years) after initial PAK use (mean estimated PAK use, 2450 hours). Fifty-six percent of workers smoked cigarettes. The findings of the physical examination, arm blood pressures, digital photoplethysmography, and serologic testing were normal in all patients. At 10 degrees C cooling with digital cuff and patient cooling blanket, a significant decrease in digital blood pressure was shown by means of DHCT in 100% of test fingers versus normothermic control fingers (mean decrease, 75%; range, 25% to 100%; normal response, less than 17%; P <.001). The mean follow-up period was 18 months (range, 1 to 47 months). No patient continued to use the PAK, but symptoms of RS were unchanged in 69% and worse in 31%. CONCLUSION: PAK use is a possible cause of vibration-induced RS. The presence of RS in workers who use the PAK was objectively confirmed by means of DHCT. Cessation of PAK use in the short term did not result in symptomatic improvement.

Improved results with conventional management of infrarenal aortic infection.

PURPOSE: Interest in alternative methods, such as autogenous vein grafts and aortic allografts, for the management of infrarenal aortic infection (IRAI) has been stimulated by the historically disappointing results with conventional surgical management. Recently, there have been dramatic improvements in the results of axillofemoral bypass grafting (AXFB) followed by excision of the IRAI that have gone relatively unrecognized. The purpose of this report is the presentation of modern-day results in the treatment of IRAI with conventional surgical methods. METHODS: From January 1, 1983, through June 30, 1998, patients with IRAI underwent treatment with AXFB and complete excision of the IRAI. The patients were followed for survival, limb salvage, and AXFB graft patency. The results were tabulated with life-table methods. RESULTS: During the 15-year study period, 60 patients (51 men, nine women; mean age, 68 years) underwent treatment for IRAI (50 graft infections, including 16 graft-enteric fistulae, and 10 primary aortic infections). The mean follow-up period was 41 months. The perioperative mortality rate was 13% (12% for graft infection, and 20% for primary infection). The overall 2-year and 5-year survival rates were 67% and 47%, respectively. The limb salvage rates at 2 and 5 years were 93% and 82%, respectively. The 5-year primary AXFB graft patency rate was 73%. CONCLUSION: These results show an improvement with the conventional management of IRAI equal or superior to those results reported with alternative methods, including femoral vein grafts or aortic allografts. These results should be regarded as the modern standard with which alternative therapies can be compared.