Measuring the 3-30-300 rule to help cities meet nature access thresholds.

The 3-30-300 rule offers benchmarks for cities to promote equitable nature access. It dictates that individuals should see three trees from their dwelling, have 30 % tree canopy in their neighborhood, and live within 300 m of a high-quality green space. Implementing this demands thorough measurement, monitoring, and evaluation methods, yet little guidance is currently available to pursue these actions. To overcome this gap, we employed an expert-based consensus approach to review the available ways to measure 3-30-300 as well as each measure's strengths and weaknesses. We described seven relevant data and processes: vegetation indices, street level analyses, tree inventories, questionnaires, window view analyses, land cover maps, and green space maps. Based on the reviewed strengths and weaknesses of each measure, we presented a suitability matrix to link recommended measures with each component of the rule. These recommendations included surveys and window-view analyses for the '3 component', high-resolution land cover maps for the '30 component', and green space maps with network analyses for the '300 component'. These methods, responsive to local situations and resources, not only implement the 3-30-300 rule but foster broader dialogue on local desires and requirements. Consequently, these techniques can guide strategic investments in urban greening for health, equity, biodiversity, and climate adaptation.

Surveillance of RNase P, PMMoV, and CrAssphage in wastewater as indicators of human fecal concentration across urban sewer neighborhoods, Kentucky.

Wastewater surveillance has been widely used as a supplemental method to track the community infection levels of severe acute respiratory syndrome coronavirus 2. A gap exists in standardized reporting for fecal indicator concentrations, which can be used to calibrate the primary outcome concentrations from wastewater monitoring for use in epidemiological models. To address this, measurements of fecal indicator concentration among wastewater samples collected from sewers and treatment centers in four counties of Kentucky (N = 650) were examined. Results from the untransformed wastewater data over 4 months of sampling indicated that the fecal indicator concentration of human ribonuclease P (RNase P) ranged from 5.1 × 101 to 1.15 × 106 copies/ml, pepper mild mottle virus (PMMoV) ranged from 7.23 × 103 to 3.53 × 107 copies/ml, and cross-assembly phage (CrAssphage) ranged from 9.69 × 103 to 1.85 × 108 copies/ml. The results showed both regional and temporal variability. If fecal indicators are used as normalization factors, knowing the daily sewer system flow of the sample location may matter more than rainfall. RNase P, while it may be suitable as an internal amplification and sample adequacy control, has less utility than PMMoV and CrAssphage as a fecal indicator in wastewater samples when working at different sizes of catchment area. The choice of fecal indicator will impact the results of surveillance studies using this indicator to represent fecal load. Our results contribute broadly to an applicable standard normalization factor and assist in interpreting wastewater data in epidemiological modeling and monitoring.

90-day nose-only inhalation toxicity study of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) in Sprague-Dawley rats.

4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) is one of the key tobacco-specific nitrosamines that plays an important role in human lung carcinogenesis. Repeated dose inhalation toxicity data on NNK, particularly relevant to cigarette smoking, however, is surprisingly limited. Hence, there is a lack of direct information available on the carcinogenic and potential non-carcinogenic effects of NNK via inhalational route exposure. In the present study, the subchronic inhalation toxicity of NNK was evaluated in Sprague Dawley rats. Both sexes (9-10 weeks age; 23 rats/sex/group) were exposed by nose-only inhalation to air, vehicle control (75% propylene glycol), or 0.2, 0.8, 3.2, or 7.8 mg/kg body weight (BW)/day of NNK (NNK aerosol concentrations: 0, 0, 0.0066, 0.026, 0.11, or 0.26 mg/L air) for 1 h/day for 90 consecutive days. Toxicity was evaluated by assessing body weights; food consumption; clinical pathology; histopathology; organ weights; blood, urine, and tissue levels of NNK, its major metabolite 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL), and their glucuronides (reported as total NNK, tNNK, and total NNAL, tNNAL, respectively); tissue levels of the DNA adduct O6-methylguanine; blood and bone marrow micronucleus (MN) frequency; and bone marrow DNA strand breaks (comet assay). The results showed that NNK exposure caused multiple significant adverse effects, with the most sensitive endpoint being non-neoplastic lesions in the nose. Although the genotoxic biomarker O6-methylguanine was detected, genotoxicity from NNK exposure was negative in the MN and comet assays. The Lowest-Observed-Adverse-Effect-Level (LOAEL) was 0.8 mg/kg BW/day or 0.026 mg/L air of NNK for 1 h/day for both sexes. The No-Observed-Adverse-Effect-Level (NOAEL) was 0.2 mg/kg BW/day or 0.0066 mg/L air of NNK for 1 h/day for both sexes. The results of this study provide new information relevant to assessing the human exposure hazard of NNK.

Wastewater Sample Site Selection to Estimate Geographically Resolved Community Prevalence of COVID-19: A Sampling Protocol Perspective.

Wastewater monitoring for virus infections within communities can complement conventional clinical surveillance. Currently, most SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) clinical testing is voluntary and inconsistently available, except for a few occupational and educational settings, and therefore likely underrepresents actual population prevalence. Randomized testing on a regular basis to estimate accurate population-level infection rates is prohibitively costly and is hampered by a range of limitations and barriers associated with participation in clinical research. In comparison, community-level fecal monitoring can be performed through wastewater surveillance to effectively surveil communities. However, epidemiologically defined protocols for wastewater sample site selection are lacking. Herein, we describe methods for developing a geographically resolved population-level wastewater sampling approach in Jefferson County, Kentucky, and present preliminary results. Utilizing this site selection protocol, samples (n = 237) were collected from 17 wastewater catchment areas, September 8 to October 30, 2020 from one to four times per week in each area and compared to concurrent clinical data aggregated to wastewater catchment areas and county level. SARS-CoV-2 RNA was consistently present in wastewater during the studied period, and varied by area. Data obtained using the site selection protocol showed variation in geographically resolved wastewater SARS-CoV-2 RNA concentration compared to clinical rates. These findings highlight the importance of neighborhood-equivalent spatial scales and provide a promising approach for viral epidemic surveillance, thus better guiding spatially targeted public health mitigation strategies.

A rapid assessment of wastewater for genomic surveillance of SARS-CoV-2 variants at sewershed scale in Louisville, KY.

In this communication, we report on the genomic surveillance of SARS-CoV-2 using wastewater samples in Jefferson County, KY. In February 2021, we analyzed seven wastewater samples for SARS-CoV-2 genomic surveillance. Variants observed in smaller catchment areas, such as neighborhood manhole locations, were not necessarily consistent when compared to associated variant results in downstream treatment plants, suggesting catchment size or population could impact the ability to detect diversity.

14-Day Nose-Only Inhalation Toxicity and Haber's Rule Study of NNK in Sprague-Dawley Rats.

4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) is one of the key tobacco-specific nitrosamines that plays an important role in human lung carcinogenesis. However, repeated inhalation toxicity data on NNK, which is more directly relevant to cigarette smoking, are currently limited. In the present study, the subacute inhalation toxicity of NNK was evaluated in Sprague Dawley rats. Both sexes (9-10 weeks age; 16 rats/sex/group) were exposed by nose-only inhalation to air, vehicle control (75% propylene glycol), or 0.8, 3.2, 12.5, or 50 mg/kg body weight (BW)/day of NNK (NNK aerosol concentrations: 0, 0, 0.03, 0.11, 0.41, or 1.65 mg/L air) for 1 h/day for 14 consecutive days. Toxicity was evaluated by assessing body and organ weights; food consumption; clinical pathology; histopathology observations; blood, urine, and tissue levels of NNK, its major metabolite 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL), and their glucuronides (reported as total NNK, tNNK, and total NNAL, tNNAL, respectively); O6-methylguanine DNA adduct formation; and blood and bone marrow micronucleus frequency. Whether the subacute inhalation toxicity of NNK followed Haber's Rule was also determined using additional animals exposed 4 h/day. The results showed that NNK exposure caused multiple significant adverse effects, with the most sensitive endpoint being non-neoplastic histopathological lesions in the nose. The lowest-observed-adverse-effect level (LOAEL) was 0.8 mg/kg BW/day or 0.03 mg/L air for 1 h/day for both sexes. An assessment of Haber's Rule indicated that 14-day inhalation exposure to the same dose at a lower concentration of NNK aerosol for a longer time (4 h daily) resulted in greater adverse effects than exposure to a higher concentration of NNK aerosol for a shorter time (1 h daily).

Toxicokinetic and Genotoxicity Study of NNK in Male Sprague Dawley Rats Following Nose-Only Inhalation Exposure, Intraperitoneal Injection, and Oral Gavage.

The tobacco-specific nitrosamine NNK [4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone] is found in tobacco products and tobacco smoke. NNK is a potent genotoxin and human lung carcinogen; however, there are limited inhalation data for the toxicokinetics (TK) and genotoxicity of NNK in vivo. In the present study, a single dose of 5 × 10-5, 5 × 10-3, 0.1, or 50 mg/kg body weight (BW) of NNK, 75% propylene glycol (vehicle control), or air (sham control) was administered to male Sprague-Dawley (SD) rats (9-10 weeks age) via nose-only inhalation (INH) exposure for 1 h. For comparison, the same doses of NNK were administered to male SD rats via intraperitoneal injection (IP) and oral gavage (PO). Plasma, urine, and tissue specimens were collected at designated time points and analyzed for levels of NNK and its major metabolite 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) and tissue levels of DNA adduct O6-methylguanine by LC/MS/MS. TK data analysis was performed using a non-linear regression program. For the genotoxicity subgroup, tissues were collected at 3 h post-dosing for comet assay analysis. Overall, the TK data indicated that NNK was rapidly absorbed and metabolized extensively to NNAL after NNK administration via the three routes. The IP route had the greatest systemic exposure to NNK. NNK metabolism to NNAL appeared to be more efficient via INH than IP or PO. NNK induced significant increases in DNA damage in multiple tissues via the three routes. The results of this study provide new information and understanding of the TK and genotoxicity of NNK.

Nonanimal toxicology testing approaches for traditional and deemed tobacco products in a complex regulatory environment: Limitations, possibilities, and future directions.

The evaluation of tobacco products is complex due to a multitude of factors including product diversity, limited testing standards, and variability in user behavior. Alternative approaches in current testing paradigms have limitations that generally truncate their applicability beyond screening for hazard identification; this is also true for toxicological evaluations of tobacco products. In a regulatory context, results from tobacco product toxicity assessments are extrapolated to the in vivo condition to assess human health relevance at the individual and population level. A key limitation of alternative approaches is the difficulty and uncertainty in extrapolating results to adverse outcomes relevant to chronic tobacco exposures in humans. This difficulty and uncertainty are increased when comparing toxicological outcomes between tobacco products. Given that the interpretation and quantification of differences in assay results (e.g., mutagenicity) for tobacco product comparison may be inconclusive, the predictive value of these approaches for human risk of relevant downstream pathologies (e.g., carcinogenesis) can be limited. Development and validation of fit-for-purpose alternative approaches that are predictive of human toxicity and dose response assays with adequate sensitivity and specificity for product comparisons would help advance the field of predictive toxicology.

Application of multivariate statistical procedures to identify transcription factors that correlate with MRP2, 3, and 4 mRNA in adult human livers.

Multidrug resistance-associated proteins 2-4 (MRP2-4) are membrane efflux transporters critical for the hepatic clearance of pharmaceuticals and endogenous chemicals. Little is known about the constitutive regulation of MRP2-4 mRNA in normal human liver. The purpose of this study was to identify transcription factors whose expression significantly correlates with MRP2-4 mRNA in human liver specimens. Ninety adult human livers were profiled for mRNA expression of MRP2-4 as well as aryl hydrocarbon receptor (AhR), constitutive androstane receptor (CAR), pregnane X receptor (PXR), peroxisome proliferator-activated receptor alpha (PPAR alpha) and gamma (gamma), liver X receptor alpha (LXR alpha), farnesoid X receptor (FXR), glucocorticoid receptor (GR), retinoid X receptor alpha (RXR alpha), hepatocyte nuclear factor 1 alpha (HNF1 alpha) and 4 alpha (4 alpha), and nuclear factor E2-related factor 2 (Nrf2) transcription factors. Using linear regression and stepwise selection of partial R(2)-values, CAR, HNF1 alpha, and PPAR alpha mRNA exhibited the greatest correlation with MRP2, 3, and 4, respectively. Interindividual variation in the expression of the identified transcription factors may account for the variability in constitutive mRNA levels of MRP2-4. The multivariate approach presented in this study should aid in predicting signalling pathways that participate either directly or indirectly in regulating hepatic drug disposition.

Proposed Mode of Action for Acrolein Respiratory Toxicity Associated with Inhaled Tobacco Smoke.

This article presents a mode of action (MOA) analysis that identifies key mechanisms in the respiratory toxicity of inhaled acrolein and proposes key acrolein-related toxic events resulting from the inhalation of tobacco smoke. Smoking causes chronic obstructive pulmonary disorder (COPD) and acrolein has been previously linked to the majority of smoking-induced noncancer respiratory toxicity. In contrast to previous MOA analyses for acrolein, this MOA focuses on the toxicity of acrolein in the lower respiratory system, reflecting the exposure that smokers experience upon tobacco smoke inhalation. The key mechanisms of acrolein toxicity identified in this proposed MOA include (1) acrolein chemical reactivity with proteins and other macromolecules of cells lining the respiratory tract, (2) cellular oxidative stress, including compromise of the important anti-oxidant glutathione, (3) chronic inflammation, (4) necrotic cell death leading to a feedback loop where necrosis-induced inflammation leads to more necrosis and oxidative damage and vice versa, (5) tissue remodeling and destruction, and (6) loss of lung elasticity and enlarged lung airspaces. From these mechanisms, the proposed MOA analysis identifies the key cellular processes in acrolein respiratory toxicity that consistently occur with the development of COPD: inflammation and necrosis in the middle and lower regions of the respiratory tract. Moreover, the acrolein exposures that occur as a result of smoking are well above exposures that induce both inflammation and necrosis in laboratory animals, highlighting the importance of the role of acrolein in smoking-related respiratory disease.

Pseudotumor cerebri. A complication of catheter-induced subclavian vein thrombosis.

Pseudotumor cerebri is frequently the only clinical clue to the presence of cerebral venous thrombosis, a potentially devastating condition. We report a case of pseudotumor cerebri associated with thrombosed dural venous sinuses caused by propagation of a catheter-related subclavian vein thrombus. The findings and clinical course in this case alert us to a complication of central venous catheter use that responds well to treatment if recognized early.

Pharmacokinetic parameters and mechanisms of inhibition of rat type 1 and 2 steroid 5alpha-reductases: determinants for different in vivo activities of GI198745 and finasteride in the rat.

The interaction of baculovirus expressed rat steroid 5alpha-reductase types 1 and 2 (r5AR1 and r5AR2) with 17beta-N-(2,5-bis(trifluoromethyl)phenyl)carbamoyl-4-aza-5alpha-androst-1-en-3-one (GI198745) was investigated at pH 7 and 37 degrees. This 5alpha-reductase inhibitor was found previously to be a time-dependent inhibitor of the two human 5alpha-reductase isozymes. In contrast, we demonstrate in the present study that although GI198745 is a potent time-dependent inhibitor of r5AR2, it is a classical rapid-equilibrium inhibitor of r5AR1. This type of behavior with human and rat 5alpha-reductases has been shown for the inhibitor 17beta-(N-tert-butylcarbamoyl)-4-aza-5alpha-androst-1-en-3-one (finasteride), a current therapy for benign prostatic hyperplasia. Inhibition of r5AR1 by GI198745 was competitive with testosterone and followed Michaelis-Menten kinetics with a K(i) value of 0.3 +/- 0.02 nM. Data for the inhibition of r5AR2 by GI198745 were consistent with a two-step mechanism, where K(i) is the dissociation constant for an initial enzyme-inhibitor complex and k(3) is the rate constant for the second slow step. The pseudo-bimolecular rate constant (k(3)/K(i)) for the association of GI198745 with r5AR2 was (2.0 +/- 0.4) x 10(7) M(-1) sec(-1). The high affinity of this inhibitor for r5AR2 was further demonstrated by the inability of the enzyme-inhibitor complex to dissociate after approximately 7 days of dialysis at 4 degrees. Both GI198745 and finasteride appear to inactivate r5AR2 by apparent irreversible modification, but are classical, reversible inhibitors of r5AR1. Therefore, we hypothesize that because of its pharmacokinetic parameters and increased potency against r5AR1, GI198745 is more effective than finasteride in preventing the growth of the rat prostate.

Differential patency and limb salvage for polytetrafluoroethylene and autogenous saphenous vein in severe lower extremity ischemia.

Polytetrafluoroethylene (PTFE) was compared to autogenous saphenous vein (ASV) in 133 femoropopliteal and femorotibial or peroneal bypass procedures performed in limb salvage during a 4-year period. PTFE was used as an alternative prosthesis in the absence of a suitable ASV. Sixty-nine femoropopliteal bypasses (FPBPs) were studied--36 with ASV and 33 with PTFE. Sixty-four femorotibial or peroneal bypasses were categorized as femoral distal bypasses (FDBPs)--34 with ASV and 30 with PTFE. With a 3-year clinical follow-up, cumulative function rate (CFR)--patency including thrombectomy--for FPBP with ASV was 65% as compared to 53% for PTFE (P greater than 0.05), whereas the limb salvage rate (LSR) was 75% with ASV and 56% for PTFE (P greater than 0.05). However for FDBP, the GFR was 55% for ASV and 7% for PTFE, whereas the LSR was 55% with ASV and 26% for PTFE. The cumulative patency rate (CPR)--initial thrombosis of a prosthesis as an endpoint--was not significantly (P greater than 0.05) different from CFR, suggesting that thrombectomy with or without distal anastamotic revision does not contribute to patency of the PTFE prosthesis in these limb salvage cases. PTFE was a suitable alternative to ASV for FPBP; however, PTFE is recommended for FDBP in selected cases only.

Application of clinically valid cardiac risk factors to aortic aneurysm surgery.

The operative outcome of 97 consecutive nonruptured infrarenal aortic aneurysms is analyzed regarding clinically identifiable cardiac risk factors. Clinically evident coronary artery disease was present in 45 patients (46%). Operative mortality was 4% (four cardiac deaths) with an additional 4% nonfatal postoperative myocardial infarction rate. All cardiac complications occurred in patients with clinically evident coronary artery disease, while no mortality occurred in 52 patients lacking a preoperative history of myocardial infarction, congestive heart failure, or angina. Preoperative risk factors having a significant negative influence on outcome include a history of prior myocardial infarction and compensated congestive heart failure. Few patients with aneurysms who have clinical evidence of coronary artery disease are indicated for coronary arteriography and bypass prior to aneurysm repair. Furthermore, indications for invasive cardiac screening of the patient with an aneurysm who lacks cardiac symptoms are limited.

Reducing perioperative myocardial infarction following vascular surgery. The potential role of beta-blockade.

OBJECTIVE: To determine which perioperative variables may influence the occurrence of perioperative myocardial infarction (PMI) following vascular surgery. DESIGN: Case-control study. SETTING: Combined Veterans Affairs Medical Center-university hospital vascular service. PATIENTS: During a 4-year period, all major vascular surgical operations (N = 2088) were evaluated with serial postoperative electrocardiography and cardiac enzyme measurements. Patients with PMI following nonemergent vascular surgery (N = 53) were matched with randomly selected control patients without PMI (N = 106) for age, gender, type of operation, hypertension, and symptoms of coronary artery disease. MAIN OUTCOME MEASURES: The two groups were compared for operative blood loss, blood pressure, and heart rate as well as length of operation, type of anesthetic, and use of perioperative beta-blockers, nitroglycerine, calcium channel blockers, vasopressors, and angiotensin-converting enzyme inhibitors. RESULTS: beta-Blockers were used less frequently in patients with PMI than in control patients without PMI (30% vs 50%; P = .01). Overall beta-blockade was associated with a 50% reduction in PMI (P = .03). Perioperative myocardial infarction was not associated with length of operation, type of anesthetic, blood pressure, or use of other medications. CONCLUSIONS: beta-Blockade is associated with a decreased incidence of PMI in patients undergoing vascular surgery. Prophylactic perioperative use of beta-blockers may decrease PMI in patients requiring major vascular surgery. A prospective randomized trial of beta-blockers in these patients appears to be warranted.

Anticoagulation followed by elective carotid surgery in patients with repetitive transient ischemic attacks and high-grade carotid stenosis.

OBJECTIVE: To evaluate the results of preoperative heparin therapy followed by carotid surgery for patients with repetitive transient ischemic attacks (TIAs) and high-grade carotid stenoses. DESIGN: A 4-year prospective study. SETTING: Oregon Health Science University Hospital and Portland (Ore) Veterans Affairs Hospital. PATIENTS: Twenty-nine consecutive patients with repetitive TIAs referable to 30 high-grade (> or = 70%) ipsilateral carotid stenoses were treated with short-term heparin anticoagulation, followed by cerebral angiography, routine preoperative evaluation, and subsequent carotid reconstruction. INTERVENTIONS: Heparin sodium anticoagulation was maintained for a mean of 5 days. Surgical management consisted of 24 standard endarterectomies, five bypasses to the internal carotid artery, and one external carotid endarterectomy. MAIN OUTCOME MEASURES: Primary outcome variables included perioperative hemorrhage, thrombocytopenia, stroke, and death. Secondary outcome variables included carotid occlusion and recurrent TIAs with heparin therapy. RESULTS: One symptomatic common carotid occlusion and one asymptomatic internal carotid occlusion occurred during preoperative heparin therapy. Thirteen patients had additional sporadic TIAs while receiving heparin. There were no preoperative cerebral infarcts, thrombocytopenia, or clinical bleeding associated with heparin therapy. There was one postoperative stroke and one death due to myocardial infarction. CONCLUSION: When necessary, heparin anticoagulation and delayed carotid reconstruction would appear to be an acceptable alternative to emergency carotid surgery in patients with high-grade carotid stenosis and acute repetitive TIAs.

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.

Analysis of risk factors for myocardial infarction following carotid endarterectomy.

A 4-year experience with 249 consecutive carotid endarter-ectomies performed on 224 patients is reviewed for incidence of perioperative (30-day) myocardial infarction and early survival (mean follow-up, 21 months). Except in cases of unstable angina, coronary arterial disease was evaluated only by routine history, physical examination, and electrocardiogram. By these criteria, 73% of patients had evidence of coronary arterial disease. Patients underwent carotid endarterectomy after appropriate medical management and stabilization of coronary disease symptoms (angina and/or congestive heart failure). One (0.4%) fatal and nine (3.6%) nonfatal perioperative myocardial infarctions Early survival of patients with active symptoms of coronary disease who did not undergo coronary bypass was similar to those patients with preceding or subsequent coronary bypass. The results of this review suggest routine clinical evaluation for coronary arterial disease is sufficient in the large majority of cases prior to carotid endarterectomy. Considering the reported high mortality of coronary bypass among vascular surgical patients, it appears that an aggressive program screening for cardiac surgical candidates either by coronary arteriography or radionuclide studies prior to carotid endarterectomy is not warranted.

Axillofemoral grafting with externally supported polytetrafluoroethylene.

OBJECTIVE: To evaluate the results of axillofemoral bypass grafting using externally supported polytetrafluoroethylene. DESIGN: Consecutive patients who were operated on by us from 1983 to the present were prospectively followed up in a vascular registry. The results of surgery with respect to morbidity and mortality, patency, limb salvage, and patient survival were determined by life-table methods. PATIENTS: A standardized operative technique was used to perform 184 axillofemoral bypass procedures in 164 consecutive patients (age range, 14 to 90 years; mean age, 67 years; female, 33%). Follow-up ranged from 0 to 95 months (mean, 23 months). RESULTS: Ischemia was the indication for 83% of the procedures, and aortic sepsis was the indication for 16%. There were nine operative deaths (5%) and 17 major complications. Life-table primary patency, limb salvage, and survival rates at 5 years were 71%, 92%, and 52%, respectively. Indication for surgery, patency of the superficial femoral artery, and the performance of multilevel procedures did not significantly influence patency. CONCLUSIONS: The results of axillofemoral grafting using polytetrafluoroethylene are equivalent to those achieved with other accepted methods of treatment for lower extremity ischemia, including balloon angioplasty, aortofemoral bypass, and infrainguinal bypass. Axillofemoral bypass is an appropriate technique that is deserving of more widespread use.

Reduced systemic drug exposure by combining intra-arterial chemotherapy with hemoperfusion of regional venous drainage.

Four patients with malignant cerebral gliomas received 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) into the internal carotid artery (ICA) while the ipsilateral jugular drainage was pumped extracorporeally through a hemoperfusion cartridge containing a nonionic adsorbant resin. Each patient received 220 mg/sq m BCNU, infused over 45 minutes through a toposcopic catheter positioned with the tip in the ICA beyond the origin of the ophthalmic artery. Jugular blood was pumped extracorporeally at 300 ml/min through a large-bore catheter in the jugular bulb. Plasma samples were obtained for BCNU measurement at frequent intervals from the right atrium. During a separate treatment, 6 weeks before or after the hemoperfusion treatment, the same dose of BCNU was infused into the ICA and atrial samples were obtained on a similar schedule. Hemoperfusion of the jugular blood during intracarotid infusion reduced the systemic exposure by 56% to 87% and increased total body clearance of BCNU by two- to eightfold. The calculated pharmacokinetic advantage (brain:body exposure ratio) was between 21 and 55:1 when the combined treatment was used.