Thayer E. Scott

Risk factors for chronic venous insufficiency: A dual case-control study

PURPOSE Most epidemiologic studies on chronic venous insufficiency (CVI) are cross-sectional surveys that suggest potential risk factors by describing their population. However, these relationships could be due to the CVI populations older age. We performed a dual case-control study with multivariate analysis to address this issue. METHODS Ninety-three patients with venous ulcers, 129 patients with varicose veins (VV), and 113 general population control patients from two hospitals were interviewed by use of a standardized questionnaire covering medical history, patient demographics, medications, and lifestyle questions. Univariate and multivariate analyses were used to compare the groups. RESULTS Univariate analyses showed CVI to be characterized by several factors, many of which were found to be age related after multivariate analysis. Age-adjusted relationships for CVI include male sex and obesity. Histories of serious leg injury or phlebitis were important associations resulting in a 2.4-fold and 25.7-fold increase in risk for CVI, respectively. After adjusting for age, subjects with VV tend to be younger and female, to more frequently have a history of phlebitis, and to report a family history of VV more frequently than control subjects. CONCLUSIONS Many of the previously suggested associations found with CVI are in reality due to this populations greater age. Patients with CVI are older, male, obese, have a history of phlebitis, and have a history of serious leg injury. These results suggest that a prior deep vein thrombosis, either clinical or subclinical, may be a predisposing factor for CVI.

Superior maturation and patency of primary brachiocephalic and transposed basilic vein arteriovenous fistulae in patients with diabetes

PURPOSE Primary radiocephalic arteriovenous fistulas (RCAVFs) have classically been used for the initiation of dialysis. If a suitable forearm cephalic vein can be demonstrated, it is used to construct such a fistula. However, we have noted a tendency for RCAVF in patients with a history of diabetes mellitus (type I and type II) to remain patent but not mature to the point of cannulation. Therefore, the present study was undertaken. METHODS Fifty-eight consecutive patients with diabetes who required initial access for hemodialysis at an urban medical center and tertiary Veterans Medical Center underwent creation of an RCAVF (n = 10), brachiocephalic arteriovenous fistula (BCAVF; n = 22), or transposed basilic vein arteriovenous fistula (TBAVF; n = 26). The vein used was determined by physical examination with tourniquet compression. If neither forearm or upper-arm cephalic veins were 2 mm in diameter, a TBAVF was created after venography. Patency was determined by Kaplan-Meier estimate; differences between groups were assessed by Fishers exact test. RESULTS The 70% rate of nonmaturation of RCAVFs was significantly greater than the 27% rate for BCAVFs and 0% for TBAVFs (p < 0.05). The 33% cumulative primary patency rate at 18 months for RCAVFs was significantly less than 78% for BCAVFs and 79% for TBAVFs (p < 0.001). Within and between groups, there were no significant differences in age, gender, aspirin use, history of congestive heart failure, erythropoietin use, hematocrit level, history of peripheral vascular disease, or mortality rate. CONCLUSIONS In patients with renal failure and a history of diabetes, both primary BCAVFs and TBAVFs demonstrate significantly greater maturation and increased primary cumulative patency rates compared with RCAVFs; therefore, these autogenous conduits are considered to be optimal in this group of patients. Whether the discrepancy in lower-arm vein maturation is a result of a lack of compensatory increase in radial arterial flow or an intrinsic defect in the lower-arm cephalic vein is currently under investigation.

An association between periodontal disease and peripheral vascular disease

BACKGROUND Periodontal disease has been shown to be associated with increased risk of coronary heart disease. Because coronary heart disease and peripheral vascular disease (PVD) have similar pathophysiologies, we hypothesized that periodontal disease might be a risk factor for PVD. METHODS Using the combined data from the Normative Aging Study and Dental Longitudinal Study of the US Department of Veterans Affairs, we examined the relationship between PVD and periodontal disease. Multivariate logistic regression analysis was used. RESULTS Over the 25 to 30 years of follow-up, 80 of these initially healthy subjects developed PVD. Compared with controls (n = 1,030), subjects with clinically significant periodontal disease at baseline had a 2.27 increment in the risk of developing PVD (95% confidence interval 1.32 to 3.9, P value = 0.003). CONCLUSIONS Periodontal disease emerged as a significant independent risk factor for PVD in a multivariate analysis that adjusted for other established risk factors.

Racial differences in the incidence of femoral bypass and abdominal aortic aneurysmectomy in Massachusetts: Relationship to cardiovascular risk factors

PURPOSE Atherosclerotic disease appears to be more severe in black patients than in white patients, but abdominal aortic aneurysms, which have traditionally been believed to have an atherosclerotic cause, are reported to be less common in black patients than in white patients. Our goals were to compare and contrast factors associated with the development of abdominal aortic aneurysms and clinically significant atherosclerotic occlusive disease (1) to determine whether these diseases share a common cause and (2) to explore their association with race. METHODS Dual case-control studies were conducted with multivariate analysis to compare cases (patients undergoing aneurysmectomy or patients undergoing femoral bypass) with a comparison group consisting of patients who had undergone appendectomy. Two data sources were used: (1) hospital discharge data for Massachusetts from 1984 through 1988 and (2) medical records at University Hospital of Boston and Boston City Hospital. For both the Massachusetts database and the hospital chart review, records were obtained for all patients discharged between January 1984 and December 1988 with an International Classification of Diseases, 9th Revision, Clinical Modification (ICD-9-CM) procedure code for abdominal aortic aneurysm resection (38.44) or aneurysmorrhaphy (38.34) or with a procedure code for femoral artery bypass/reconstruction (39.29). To conduct a nested case-control study, records were also obtained for a control group consisting of patients between the ages of 50 and 84 years who had undergone appendectomy during the same 5-year period. RESULTS Black patients had higher rates of femoral bypass than did white patients after adjustment for age and sex (odds ratio = 1.97; 95% confidence interval: 1.49, 2.61; p < 0.0001). However, femoral bypass was also associated with hypertension, diabetes, and low household income. After adjusting for these additional factors in the statewide data set, the black/white odds ratio for femoral bypass was only 1.44 (95% confidence interval: 1.08, 1.92). The parallel case-control study at University Hospital and Boston City Hospital, which provided information about smoking status and more accurate ascertainment of coexisting hypertension and diabetes, indicated that there was no racial difference in rates of femoral bypass after correcting for these additional risk factors (odds ratio = 0.94; 95% confidence interval: 0.40, 2.22; p = 0.90). In contrast, abdominal aortic aneurysmectomy occurred predominantly in white men. Aneurysmectomy was also associated with smoking and hypertension, but aneurysmectomy was not significantly associated with diabetes mellitus or family income. The black/white odds ratio for aneurysm was 0.29; (95% confidence interval: 0.07, 1.23; p = 0.09 after adjustment for other variables). CONCLUSIONS Hypertension, smoking, and male sex are risk factors for the development of femoral atherosclerosis and abdominal aortic aneurysm formation. However, abdominal aortic aneurysms occur predominantly in white men and do not appear to be associated with diabetes mellitus or income. In contrast, the higher rate of femoral artery bypass in black patients is probably the result of greater prevalence among black patients of hypertension, diabetes, smoking, and perhaps by other ill-defined factors associated with socioeconomic status.

Functional outcomes in limb salvage vascular surgery

BACKGROUND The crisis in health care brings a new focus to defining successful outcomes of medical treatments. The surgical literature has been criticized for not assessing functional outcomes in addition to technical success. METHODS We evaluated the functional outcomes of limb salvage surgery over 3 years in 38 patients 65 years of age and older with limb-threatening ischemia. The RAND-36-Item Health Survey 1.0 was used as a health assessment tool. RESULTS In spite of an 80% limb salvage rate, only 58% of patients survived 3 years and only 25% survived with the index limb and were able to walk. The RAND scores of patients whose limbs were amputated did not significantly differ from those of patients whose surgery was successful. CONCLUSION Functional outcome goals need to be better defined for patients who need limb salvage vascular operations to enhance the quality of care given these patients and to be in concert with emerging health policy.

A Case-Control Assessment of Risk Factors for Gallbladder Carcinoma

Gallbladder carcinoma is an uncommon, but highlyfatal disease. Its symptoms frequently mirror those ofgallstone disease, and in most instances, diagnosis isan incidental finding at surgery. While risk factors have been suggested for this cancer,many may in reality simply be a consequence of the olderage of the population. This study is one of the few toapproach this question by using a case-control study design comparing gallbladder carcinomapatients with a gallstone population, coupled withmultivariate analysis to determine age-independent riskfactors. Univariate analyses showed gallbladdercarcinoma patients to be older than gallstone patientsand to have many age-associated diseases. Followingmultiple regression adjustment for age, this disease wasassociated with female gender and with a previous history of gallstone symptoms. Carcinomapatients were less likely to have cholesterol gallstonesin their gallbladders at surgery. A previous history ofsmoking was a substantial risk but of borderline statistical significance. Previous studiesreport associations that may be due to the older age ofthe gallbladder carcinoma patient. Our results show thatafter adjusting for age with multivariate analysis, gallbladder cancer subjects were predominantlyfemale, more likely to report previous gallstonesymptomology, and to smoke. While gallstones were notuniversally isolated from carcinoma patients atcholecystectomy, when present, they were less frequentlyclassified as cholesterol gallstones based on visualinspection. Further cohort studies which target thesepopulations will allow us to gain a more solid consensus on the risk factors for this disease.

Early outcome of in situ femorotibial reconstruction among patients with diabetes alone versus diabetes and end-stage renal failure: Analysis of 83 limbs

PURPOSE Both end-stage renal disease and diabetes have been demonstrated to have a negative effect on the outcome of infrainguinal arterial reconstruction, primarily because of increased perioperative morbidity and wound complications. This study was undertaken to determine whether the combination of these comorbid factors affects the outcome of distal arterial reconstruction. METHODS Eighty-three distal lower extremity arterial bypasses originating from the femoral artery and terminating at the peroneal, anterior, or posterior tibial artery were performed on 76 patients over a 5-year period at a tertiary care medical center. Autogenous greater saphenous vein was used as the bypass conduit in all instances. Combined inflow and composite vein procedures were excluded. RESULTS There was one perioperative death, for a mortality rate of 1.2%. The diabetes mellitus (DM) plus end-stage renal disease (DM+ESRD) cohort displayed a significantly lower 1-year primary patency rate compared with the diabetes mellitus cohort, 53% versus 82% (p < 0.02). However, the limb salvage rate for the DM+ESRD and DM cohorts during the same time interval were not significantly different, 63% versus 84% (p < 0.06). The 52% 1-year survival rate for the DM+ESRD cohort was strikingly lower than the 90% 1-year survival rate for the DM cohort (p < 0.002). CONCLUSION Despite the use of the optimal autogenous conduit, the combination of diabetes and end-stage renal disease can be expected to significantly decrease primary graft patency without affecting limb salvage. The greatest effect of these comorbid factors is on patient survival.

Effect of dietary cholesterol on phosphatidylcholines and phosphatidylethanolamines in bile and gallbladder mucosa in the prairie dog

Humans with cholesterol gallstones have been reported to have alterations in the molecular species of phospholipids in bile. Both decreases in phospholipids with linoleic acid and increases in those with arachidonic acid have been found. The purpose of this study was to investigate the effect of a lithogenic diet (0.34% cholesterol) on the relative abundance of individual molecular species of phospholipids in the biliary tract of the prairie dog. In hepatic bile, cholesterol feeding resulted in increases in phospholipid species containing arachidonate and decreases in the major species containing its precursor, linoleate. In gallbladder bile of both control and cholesterol-fed animals, phospholipid species containing linoleate were significantly less abundant than in hepatic bile, suggesting that linoleoyl species were selectively absorbed by the gallbladder epithelium. This apparent uptake was significantly increased by cholesterol feeding. Phosphatidylcholines and phosphatidylethanolamines containing arachidonate were also significantly increased in the gallbladder mucosa of the cholesterol-fed animals. These increases in arachidonate-containing phospholipids in the gallbladder mucosa may contribute to the increase in gallbladder prostaglandin synthesis that precedes gallstone formation in this animal model.

Durability of early prosthetic dialysis graft cannulation: Results of a prospective, nonrandomized clinical trial

PURPOSE Initiation of hemodialysis frequently requires temporary central venous catheterization, which leads to subsequent venous stenosis in 50% of patients. These lesions severely limit upper extremity dialysis fistula creation. The present study was undertaken to determine whether early cannulation (EC) allowed omission of temporary venous catheterization without affecting perioperative morbidity and long-term graft patency. METHODS Seventy-nine prosthetic grafts for hemodialysis were placed in 76 patients over a 40-month period. Patients who required hemodialysis between 24 and 72 hours after surgery were assigned to EC. The remaining grafts underwent late cannulation (LC) after postoperative day 14. All grafts were constructed with a 6 mm stretch-expanded polytetrafluoroethylene conduit in the brachial artery-to-axillary vein position. Statistical analysis of cumulative primary patency estimates and patient survival data were determined by Kaplan-Meier analysis and log-rank test, patient variables were compared using chi 2 and Fishers exact test, and multivariate analysis was performed using Coxs proportional hazard model. RESULTS Forty-eight patients underwent EC and 31 underwent LC. There were no significant differences regarding age (mean, 61.5 years), history of diabetes, congestive heart failure, hematocrit level (mean, 30%), or presence of peripheral vascular disease. Thrombosis occurred before cannulation in one of 48 ECs (2.0%) and one of 31 LCs (3.2%). There were no episodes of cannulation hemorrhage or wound infection in either group. Cumulative primary patency estimates for EC were 0.89, 0.82, and 0.70 at 3, 6, and 12 months, respectively. These were not significantly different from the LC estimates of 0.86, 0.78, and 0.74 at 3, 6, and 12 months, respectively. Overall, patients who had a history of peripheral vascular disease had a significantly decreased 12-month patency rate (60% vs 74%; p = 0.05). Central venous catheters were omitted in 47 of 48 EC patients. CONCLUSION EC of prosthetic dialysis grafts does not increase perioperative morbidity rates or decrease 12-month cumulative primary patency rates.

Inhibition of Prostaglandin Synthesis Fails to Prevent Gallbladder Mucin Hypersecretion in the Cholesterol-Fed Prairie Dog

Gallstone formation in the cholesterol-fed prairie dog is preceded by an increase in mucin secretion by the gallbladder epithelium, and mucin hypersecretion is believed to promote cholesterol gallstone formation by accelerating the nucleation of cholesterol monohydrate crystals. Some studies have suggested that gallbladder mucin hypersecretion is mediated by increases in gallbladder prostaglandin synthesis, but other observations are difficult to reconcile with this view. An organ culture technique was used to measure mucin secretion in normal prairie dog gallbladder in response to exogenous prostaglandins and agents that increased or decreased endogenous prostaglandin production. Incubation with indomethacin produced a concentration-dependent inhibition of endogenous prostaglandin synthesis with virtually complete inhibition at 10(-5) mol/L indomethacin. However, indomethacin had no effect on gallbladder mucin secretion at concentrations as high as 10(-5) mol/L, and significant inhibition of mucin secretion was only found at 10(-4) mol/L indomethacin, a concentration that also produced a significant increase in lactate dehydrogenase release from cultured explants. Incubation of gallbladder explants with the calcium ionophore A23187 significantly stimulated endogenous prostaglandin synthesis in a concentration-dependent manner, increasing synthesis of prostaglandins E and F to as much as 278% +/- 20% and 335% +/- 21% of basal values, respectively; however, the same concentrations of A23187 did not stimulate mucin secretion. Incubation of gallbladder explants in the presence of exogenous prostaglandin E2 or prostaglandin F2a in concentrations as high as 10(-6) mol/L also did not stimulate mucin secretion. Prairie dogs fed a lithogenic 1.2% cholesterol diet showed a significant increase in gallbladder mucin secretion after 1 week (117.5 +/- 10.2% of control, P less than 0.05), and 4 of 5 had formed cholesterol monohydrate crystals after 3 weeks. Long-term treatment with indomethacin, 1.2 mg.kg-1.day-1, failed to inhibit gallbladder mucin hypersecretion (129.2 +/- 10.7% of control after 1 week) or cholesterol monohydrate crystal formation (3/5) in cholesterol-fed prairie dogs. Furthermore, incubation of explants with 10(-5) mol/L indomethacin failed to prevent in vitro mucin hypersecretion in cholesterol-fed animals. These findings suggest that prostaglandins do not regulate gallbladder mucin secretion in the prairie dog, and it is unlikely that increases in gallbladder prostaglandin synthesis are responsible for mediating gallbladder mucin hypersecretion during cholelithiasis in the prairie dog.