Twenty-eight loci that influence serum urate levels: analysis of association with gout.

OBJECTIVES: Twenty-eight genetic loci are associated with serum urate levels in Europeans. Evidence for association with gout at most loci is absent, equivocal or not replicated. Our aim was to test the loci for association with gout meeting the American College of Rheumatology gout classification criteria in New Zealand European and Polynesian case-control sample sets. METHODS: 648 European cases and 1550 controls, and 888 Polynesian (Ma¯ori and Pacific) cases and 1095 controls were genotyped. Association with gout was tested by logistic regression adjusting for age and sex. Power was adequate (>0.7) to detect effects of OR>1.3. RESULTS: We focused on 24 loci without previous consistent evidence for association with gout. In Europeans, we detected association at seven loci, one of which was the first report of association with gout (IGF1R). In Polynesian, association was detected at three loci. Meta-analysis revealed association at eight loci-two had not previously been associated with gout (PDZK1 and MAF). In participants with higher Polynesian ancestry, there was association in an opposing direction to Europeans at PRKAG2 and HLF (HLF is the first report of association with gout). There was obvious inconsistency of gout association at four loci (GCKR, INHBC, SLC22A11, SLC16A9) that display very similar effects on urate levels. CONCLUSIONS: We provide the first evidence for association with gout at four loci (IGF1R, PDZK1, MAF, HLF). Understanding why there is lack of correlation between urate and gout effect sizes will be important in understanding the aetiology of gout.

Comparison of three targeted approaches to screening for abdominal aortic aneurysm based on cardiovascular risk.

BACKGROUND: Abdominal aortic aneurysm (AAA) continues to be a significant health burden yet few countries have implemented a comprehensive screening programme. Screening typically places emphasis on men aged over 65 years; however, there is concern that other at-risk groups may be underidentified. The present study examined three potential screening strategies based on cardiovascular risk. METHODS: The prevalence of AAA was determined by abdominal ultrasound imaging in over 50-year-olds of either sex undergoing coronary angiography, vascular laboratory assessment of peripheral arterial disease, or community-based cardiovascular disease (CVD) event risk assessment. A fourth group, consisting of volunteers aged over 60 years who had no symptoms or signs of cardiovascular disease, was used as a comparator group. RESULTS: A total AAA prevalence of 4·4 per cent was detected across all three strategies (137 of 3142 individuals), compared with 1·0 per cent in the CVD-free group. Male sex, age and smoking were all associated with greater AAA prevalence. Although AAA prevalence was lowest using the community-based strategy, those with an AAA detected were on average 7 years younger than those with AAAs detected with the other two strategies (P < 0·001). CONCLUSION: Different strategies, based on CVD risk, resulted in AAA prevalence rates that were significantly greater than that in CVD-free individuals. This may provide opportunities for a targeted approach to community AAA screening in parts of the world where more sophisticated national screening programmes do not exist.

Evaluation of the accuracy of aorta scan BVI 9600 in screening for abdominal aortic aneurysm.

OBJECTIVES: Despite a decreasing incidence of abdominal aortic aneurysm (AAA), the cost-effectiveness of AAA ultrasound screening can be improved by reducing the screening costs and increasing the uptake rates. The BVI 9600 (BVI) is a promising tool for this purpose as it is inexpensive and can detect AAA without a trained operator. This study aims to investigate whether the BVI can be used to detect AAA for the purpose of a low-cost outreach screening approach. METHODS: A total of 142 subjects had their abdominal aortae measured by five sonographers using the BVI and a conventional ultrasound machine. The examination included four anterior-posterior measurements at four equally spaced scanning locations from the xiphisternum to the umbilicus. The measurements produced by each machine were compared using Bland-Altman plots, followed by an analysis of the AAA detection performance. RESULTS: The BVI measured the aortic diameter to within 0.88-1.56 cm of the true diameter, exceeding the 0.5 cm "clinically acceptable difference" (CAD). Its accuracy was poorer when measuring the aneurysmal aortae (mean difference -0.56 cm, variability 1.72 cm) than normal aortae (mean difference 0.02 cm, variability 0.76 cm). Nine out of 52 aneurysms were not detected due to undersizing measurement and non-visualization of the aortae. CONCLUSIONS: At present, the BVI is not sufficiently accurate to detect AAA for screening purposes. A number of technical features require improvement.

Intra-individual changes of active matrix metalloproteinase-9 are associated with clinical in-stent restenosis of bare metal stents.

OBJECTIVES: Increased chronic postprocedural levels of active matrix metalloproteinase-9 (MMP-9) have been associated retrospectively with a history of in-stent restenosis (ISR). This study aimed to determine whether index or post-percutaneous coronary intervention (PCI) plasma levels of active MMP-9 are a predictor of subsequent clinical ISR, in a standard population of patients treated with bare metal coronary stents. METHODS: Four hundred thirty-two patients were prospectively recruited and sampled at index and 3 and 6 months after PCI. Those who developed symptomatic angiographically confirmed ISR were compared to randomly selected, asymptomatic controls, stratified by index presentation in a nested case-control design. Plasma samples were analyzed for the active form of MMP-9. RESULTS: In all, 35 patients (8.1%) developed ISR, and these were compared to 98 controls. The increase in active MMP-9 over 3 months was significantly greater in the ISR group (p = 0.030) and independent of the established risk factors. Index clinical presentation was not associated with acute changes in active MMP-9; however, patients with ST-elevation myocardial infarction had greater increases in active MMP-9 at 3 months. CONCLUSIONS: The change in active MMP-9 over 3 months after bare metal coronary stent placement appears to be independently associated with the development of ISR in a standard PCI population.

Possible association between genetic polymorphisms in transforming growth factor beta receptors, serum transforming growth factor beta1 concentration and abdominal aortic aneurysm.

BACKGROUND: Previous studies have suggested a role for transforming growth factor (TGF) beta and its receptor in thoracic aortic aneurysm, but their role in abdominal aortic aneurysm (AAA) is unknown. This study examined the possible association between TGF-beta receptor 1 and 2 (TGFBR-1 and -2) single nucleotide polymorphisms (SNPs) and serum TGF-beta1 with AAA. METHODS: Serum concentrations of TGF-beta1 and 58 SNPs for TGFBR-1 and -2 were examined in 1003 and 1711 men respectively from the Health In Men Study. Validation of SNPs was examined in a second referral cohort of 1043 subjects from New Zealand, of whom 654 had an AAA. RESULTS: Serum TGF-beta1 was not associated with AAA. Only one SNP in TGFBR-2 was weakly associated with AAA; TGFBR2 g.42917C > T, SNP ID rs1078985CC; odds ratio 0.64 (95 per cent confidence interval (c.i.) 0.45 to 0.93); P = 0.020 uncorrected; but this association did not hold after adjusting for multiple testing and was not validated in the New Zealand cohort: odds ratio 0.98 (95 per cent c.i. 0.50 to 1.94); P = 0.960. CONCLUSION: These findings suggest there is no important role of genetic polymorphisms in the main receptors for TGF-beta and circulating TGF-beta1 in AAA in older individuals. (c) 2009 British Journal of Surgery Society Ltd.

A meta-analysis of randomized, controlled trials assessing the prophylactic use of ceftriaxone. A study of wound, chest, and urinary infections.

BACKGROUND: Ceftriaxone is an effective prophylactic antibiotic. However, there is no consensus about whether ceftriaxone should be used as a first-line antibiotic for the prevention of incisional surgical site infection (SSI). Its role in preventing urinary tract infection (UTI) and pneumonia also is controversial. METHODS: A meta-analysis of randomized, controlled trials assessing the prophylactic use of ceftriaxone between 1983 and 2005 was performed. Medline, Embase, and Cochrane registers were reviewed. Additional references, review papers, and proceedings from meetings were searched. The Jadad score was used to assess study quality. A meta-analysis with sensitivity analyses was performed for SSI, UTI, and pneumonia. RESULTS: Of 231 reviewed papers, 90 were included. Ceftriaxone prophylaxis was superior to other antibiotics in each category. Sixty-one studies assessed the prevention of SSI (odds ratio (OR), 0.68; 95% confidence interval (CI), 0.53-0.7, p < 0.001; Cochran's Q statistic, p = 0.93). The difference was greatest for abdominal surgery. There was no difference for cardiac surgery. Thirty-five studies assessed the prevention of UTI (OR 0.53; 95% CI 0.43-0.63, p = 0; Cochran's Q statistic, p = 0.97). The difference was greatest in obstetric and gynecological and colorectal surgery. Thirty-seven studies assessed the prevention of pneumonia (OR 0.66; 95% CI 0.54-0.81, p = 0; Cochran's Q statistic, p = 0.65). The difference was greatest in upper abdominal surgery. CONCLUSIONS: The meta-analysis confirms that prophylactic ceftriaxone is more effective than most other prophylactic antibiotics. This reduces SSI, UTI, and pneumonia in procedures where there is an increased risk of these infections. In such procedures, the data support using ceftriaxone as a first-line prophylactic antibiotic.

Novel rare mutations and promoter haplotypes in ABCA1 contribute to low-HDL-C levels.

The ATP-binding cassette A1 (ABCA1) protein regulates plasma high-density lipoprotein (HDL) levels. Mutations in ABCA1 can cause HDL deficiency and increase the risk of premature coronary artery disease. Single nucleotide polymorphisms (SNPs) in ABCA1 are associated with variation in plasma HDL levels. We investigated the prevalence of mutations and common SNPs in ABCA1 in 154 low-HDL individuals and 102 high-HDL individuals. Mutations were identified in five of the low-HDL subjects, three having novel variants (I659V, R2004K, and A2028V) and two with a previously identified variant (R1068H). Analysis of four SNPs in the ABCA1 gene promoter (C-564T, G-407C, G-278C, and C-14T) identified the C-14T SNP and the TCCT haplotype to be over-represented in low-HDL individuals. The R1587K SNP was over-represented in low-HDL individuals, and the V825I and I883M SNPs over-represented in high-HDL individuals. We conclude that sequence variation in ABCA1 contributes significantly to variation in HDL levels.

Obesity and impaired venous function.

OBJECTIVES: The clinical severity of venous disease is often worse in obese patients. The objectives of this study were to compare lower limb venous physiology assessed by air plethysmography in a large group of obese and normal-weight patients; to consider the effect of posture on these measures and on foot vein pressure in a smaller cohort. METHODS: Venous function was assessed using air plethysmography and duplex scanning in 934 consecutive patients presenting for assessment of venous disease. These were grouped into obese or non-obese categories. A smaller group of twenty patients with a range of body weights were randomly selected from a database of patients with varicose veins. Foot vein pressures and femoral vein diameter were measured standing, sitting, lying and ambulating. RESULTS: Venous disease was more clinically severe in the obese limbs (CEAP C5&6 non-obese group 20.5%, obese group 35.4%, p<0.001 chi(2)). Venous reflux was worse in the obese but measures of muscle pump function were better. Residual volumes and fractions were better in the obese (mean residual volume, non-obese 60 SD 36, obese 50 SD 42, p<0.001 t test). In the smaller study group weight correlated with the diameter of the superficial femoral vein (r=0.50), ambulatory venous pressure (r=0.45), venous filling index (r=0.49) and the ejection volume (r=0.38, p<0.05). The foot venous pressure was significantly greater in the obese in all positions. CONCLUSION: The CEAP clinical stage of venous disease is more advanced in obese patients than non-obese patients with comparable anatomical patterns of venous incompetence. This may be the result of raised intra-abdominal pressure reported in previous studies, leading to greater reflux, increased vein diameter and venous pressures.

Elevated plasma active matrix metalloproteinase-9 level is associated with coronary artery in-stent restenosis.

OBJECTIVE: This study aimed to determine whether the plasma levels of matrix metalloproteinase-9 (MMP-9) or tissue inhibitor of metalloproteinases-1 (TIMP-1) were altered in patients with a history of symptomatic in-stent restenosis (ISR). METHODS AND RESULTS: A group of 158 patients with a history of ISR were compared with 128 symptom-free patients. Plasma samples and a detailed risk factor history were collected. Plasma samples were analyzed for pro-MMP-9 and latent MMP-9 and active MMP-9, latent MMP-3, and TIMP-1. Several variables were associated with ISR, including index coronary disease extent and severity (number of diseased vessels and American College of Cardiology/American Heart Association lesion classification), number, diameter, and total length of stent(s) inserted, and plasma high-density lipoprotein cholesterol. Plasma active MMP-9 (odds ratio, 1.96; 95% CI, 1.43 to 2.69) showed independent risk association with ISR. Patients with multiple sites of ISR had significantly higher levels of active MMP-9 compared with patients with only a single ISR lesion or no ISR. CONCLUSIONS: Plasma active MMP-9 levels may be a useful independent predictor of bare metal stent ISR.

Identification of two susceptibility loci for vascular fragility in the Brown Norway rat.

A trait of vascular fragility, characterized by the formation of abrupt defects within the elastic laminae of the abdominal aorta, has been identified in Brown Norway (BN) rats. These lesions are greatly exacerbated in F(1) rats from a BN x New Zealand genetically hypertensive (GH) intercross, implying that the genetic background provided by the GH rat influences lesion severity. The F(2) progeny of the BN x GH intercross were used to identify susceptibility loci for the lesions as well as exacerbating loci. Two major quantitative trait loci (QTLs) for number of internal elastic lamina lesions were identified on rat chromosomes 5 and 10, with the maximum "log of the odds ratio" (LOD) scores at D5Rat119 (LOD 5.0) and at D10Mit2 (LOD 4.5), respectively, together contributing 33.5% to the genetic variance. Further analysis revealed that the chromosome 10 locus exhibits a dominant mode of inheritance, with BN alleles being associated with increased lesion number (P < 0.0002) compared with GH homozygotes. This locus was in epistasis to a modifier locus on rat chromosome 2 at D2Mit14 (LOD score 2.12). A second major locus was identified on chromosome 5, exhibiting a semidominant mode of inheritance, again with the BN allele being significantly associated with increased lesion number (P < 0.0001). Furthermore, a locus influencing lesion severity was identified on chromosome 3 wherein GH alleles associated with increased severity. This is the first study to identify susceptibility loci for vascular elastic tissue fragility.

Blood selenium and glutathione peroxidase activity in normal subjects and in surgical patients with and without cancer in New Zealand.

This study was carried out in Otago, South Island, where most arable land has a low soil selenium content (less than 0.5 microgram/g) and where selenium (Se) responsive diseases in livestock are common. Se concentration in whole blood, erythrocytes and plasma, and activity of glutathione peroxidase (EC 1.11.1.9) were measured in blood from 104 healthy Otago residents, 80 patients with cancer and 66 noncancer surgical patients. The older residents over 60 years had lower blood Se levels (0.047 +/- 0.010 microgram Se/ml blood) than the young and middle-aged (0.060 +/- 0.012 microgram Se/ml). Blood Se levels of cancer patients were no lower than those of elderly subjects and patients without cancer, and were less than half comparable United States values. Blood Se levels were decreasing in two cancer patients, and the lowest values (less than 0.03 microgram Se/ml blood) were obtained for five cancer patients, and two noncancer patients after a long period of inanition; these were similar to values for patients on parenteral nutrition with negligible intakes. Lower blood Se levels were associated with lower serum albumin and enzyme activities. It is suggested that low Se status of cancer patients was more likely a consequence of their illness than the cause of the cancer.

Selenium and vitamin E supplementation: activities of glutathione peroxidase in human tissues.

Twenty-seven New Zealand women received daily for 4 wk, 200 micrograms selenium as sodium selenite, 170 mg alpha-tocopherol acetate, or a placebo. Se supplementation raised platelet selenoglutathione peroxidase (Se-GSHPx, p less than 0.001) and also Se and Se-GSHPx in whole blood and plasma. Se concentrations and Se-GSHPx activities in liver biopsies taken after supplementation were greater (p less than 0.05) for the Se group and a good correlation was found between Se and Se-GSHPx in liver and muscle for all subjects. Platelet Se-GSHPx correlated well with Se and Se-GSHPx in liver, indicating its suitability for assessing Se bioavailability. This is the first reported study of relationships between Se and Se-GSHPx in human liver and muscle tissue and platelet Se-GSHPx after Se supplementation. These observations verify in man relationships observe in animal studies, giving support to assumptions made in methods for assessing Se status and bioavailability in man, in particular the use of platelet GSHPx.

Lipid peroxidation of circulating low density lipoproteins with age, smoking and in peripheral vascular disease.

In this study, lipid peroxides in plasma and the low density lipoprotein (LDL) fraction and plasma concentrations of vitamin E, lipids and lipoproteins were measured in 22 smokers (mean age 35 years), 26 non-smoking patients with peripheral vascular disease (PVD), mean age 66 years), and 23 younger (ages < or = 55 years) and 26 older (ages > 55 years) healthy subjects. Plasma lipid peroxide concentrations in the PVD patients (105.9 +/- 20.6 vs. 91.8 +/- 15.8 ng malondialdehyde (MDA)/ml plasma, mean +/- S.D.) and the smokers (94.1 +/- vs. 74.0 +/- 13.9 ng MDA/ml plasma) were significantly elevated compared with levels in the appropriate control subjects and levels were significantly higher in older compared with younger control subjects. Plasma LDL lipid peroxides were also significantly raised in patients with PVD and smokers compared with control values (PVD): 37.1 +/- 7.7 vs. 26.3 +/- 4.1 ng MDA/ml plasma; smokers: 30.4 +/- 6.9 vs 24.9 +/- 7.5 ng MDA/ml plasma). The ratio of LDL lipid peroxides: LDL-cholesterol was significantly higher in the smokers, and plasma cholesterol and LDL-cholesterol were significantly higher in patients with PVD compared with other groups of subjects. The ratio of vitamin E: total lipid was not significantly different between the study groups. These data show that lipid peroxide levels in the plasma LDL fraction are elevated along with raised circulating levels in patients with PVD and smokers but that LDL lipid peroxide concentrations were independent of age in the healthy subjects. Elevated LDL lipid peroxide concentrations may may be mainly due to abnormally high LDL levels in PVD patients, whereas in smokers, the concentration of lipid peroxides in the LDL particles is raised and might render the lipoprotein more atherogenic.

Endothelin-1 is increased overlying atherosclerotic plaques in human arteries.

The distribution of Endothelin-1 (ET-1), a potent vasoactive peptide, within endothelium of human atherosclerotic arteries was examined using a novel en face immunohistochemical technique. The vast majority of endothelial cells were immunoreactive for ET-1. Staining intensity was increased in areas overlying atherosclerotic plaques, calcified media, fatty streaks and about flow dividers, compared with adjacent regions. Multinucleated 'giant' endothelial cells were more common in regions containing strong ET-1 staining than elsewhere. Clusters of leucocytes (probably monocytes) were frequently observed adhering to the endothelial monolayer but not neighbouring regions of denudation. Occasionally underlying macrophage/foam cells and smooth muscle cells were exposed to the surface and included in the en face (Häutchen) preparation. Smooth muscle cells did not stain for ET-1 while macrophages and the larger foam cells were positive for ET-1. These results support the hypothesis that expression of ET-1, at sites containing atheromatous disease, may be involved in the development of atherosclerosis.

Venous endothelial changes in therapeutic arteriovenous fistulae.

Specimens of veins of therapeutic arteriovenous fistulae from five patients were examined by an en face immunohistochemical technique to investigate endothelial morphology and the presence of the vasoactive peptide endothelin-1 (ET-1). These were compared with control segments of long saphenous veins from six patients. Venous endothelium from the arteriovenous shunts was mostly intact even overlying phlebosclerotic plaques. Occasional small areas of denudation, with associated platelets, were present in the depressions of 'jet' lesion however. The endothelial cells were generally elongated and interspersed with foci of polyhedral cells. The control saphenous veins contained elongated endothelial cells without detectable denudation. Image analysis of histological sections of veins from the shunts indicated significantly less intact elastic tissue than control veins but greater mononucleated endothelial cell density in en face preparations. ET-1 staining was considerably stronger in endothelium from the fistulae than in the control saphenous veins and was most intense over the raised crescentic ridges of jet lesions, stenoses and phlebosclerotic plaques. Endothelial mitoses and cells with hyperchromatic nuclei stained more strongly for ET-1 than surrounding cells. These results indicate that the endothelial cells lining veins associated with arteriovenous fistulae are dynamically altered by the increased haemodynamic stresses associated with these shunts. Furthermore ET-1 may act as a localising factor associated with intimal thickening at sites of 'jet' lesions, stenosis and phlebosclerosis.

Detection and significance of minimal residual disease in colorectal cancer.

Colorectal cancer (CRC) is one of the most common causes of cancer death in the developed world. Although the primary treatment for CRC is surgical, disease relapse due to minimal residual disease (MRD) following apparently curative surgery occurs in up to fifty percent of patients. Most patients who develop overt metastases beyond the regional lymph nodes eventually die of the disease. At present adjuvant chemotherapy is used to improve survival in patients with metastases to regional lymph nodes demonstrated by routine histopathology with no other evidence of spread. The ability to identify metastatic disease at an earlier stage could be of considerable benefit in directing adjuvant therapy to patients at high risk of relapse who are not identified by current methods. Several techniques have been developed for the detection of MRD, including immunohistochemical and molecular methods, however their role in clinical practise is not yet established. The purpose of this paper is to review these techniques and their potential clinical use in the management of CRC.

Endothelial cell icam-1 staining in human carotid arteries.

In this study human carotid artery specimens from 18 patients were examined by an en face technique to demonstrate the endothelial cell staining of intercellular adhesion molecule-1 (ICAM-1). Endothelial cells about the carotid bifurcation and within the post-stenotic region of the internal carotid artery were predominately polyhedral in shape with heterogenous but often intense ICAM-1 staining. Endothelium lining the partially stenosed lumen of the intern carotid orifice were elongated with ICAM-1 staining often polarized at the proximal end of the cell. There were two dominant patterns of ICAM-1 staining associated with polyhedral endothelial cells, cell border, and cell surface/nuclear profile staining. Polyhedral cells at the proximal end of the internal carotid artery stenosis appeared to have both patterns while those at the distal end were most often observed with only the cell surface expression pattern. Adherent leukocytes were mostly observed in association with polyhedral endothelial cells especially in the post-stenotic internal carotid and were uncommon within stenoses. These results indicate heterogeneity not only of endothelial cell morphology but also in the intensity and pattern of staining of ICAM-1 about atherosclerotic lesions. This may be indicative of different functional properties for ICAM-1 depending on anatomical localization and consequent hemodynamic stresses.

The effect of somatostatin on dumping after gastric surgery: a preliminary report.

Many of the features of the dumping syndrome may be manifestations of hypovolemia and mechanical distension of the gut, resulting from abnormal fluid secretion in the upper gastrointestinal tract. The object of the present study was to assess the effect of somatostatin, an inhibitor of upper gastrointestinal secretions, on the response to a dumping provocation test, using a double-blind, placebo-controlled method. Four patients were studied; two had undergone total gastrectomy for gastric carcinoma and two had undergone gastric bypass for morbid obesity. Each subject received, on two separate occasions, a challenge of 200 ml of 50% glucose administered orally after an overnight fast. Somatostatin in 150 mm of NaCl (250 micrograms bolus followed by 300 micrograms/hr infusion) was given intravenously during one dumping provocation test and placebo (150 mm of NaCl) during the other according to a Latin square design. When the subjects received the placebo there were significant increases in pulse rate and packed cell volume after oral glucose (p less than 0.05, paired t test), which did not occur when they received somatostatin. The glucose challenge also produced a more rapid increase in serum osmolality and blood glucose during administration of placebo than when somatostatin was given. Marked diarrhea developed in all placebo-treated subjects but in none when they received somatostatin; however, three of the subjects developed marked abdominal pain during dumping provocation tests when treated with somatostatin, which did not occur when placebo was given. Although somatostatin appears to suppress some of the objective responses to a dumping provocation test, it may not prove particularly useful in the treatment of dumping symptoms.

Prophylactic cefazolin in gastric bypass surgery.

Because surgery in obese patients is associated with a high risk of infection, gastric bypass procedures offer an excellent opportunity to test the efficacy of prophylactic antibiotics. Accordingly, a double-blind prospective trial of prophylactic cefazolin was carried out in 53 consecutive patients who underwent gastric bypass surgery for morbid obesity. The patients were randomized to two treatment arms: (1) cefazolin intravenously, 1 gm 2 hours prior to surgery, at induction of anesthesia, and then 0.5 gm every 6 hours for 48 hours, or (2) an indistinguishable placebo of 5% dextrose at identical intervals. Serial cultures were taken at operation and in the postoperative period. Antibiotic levels of fat were measured by tissue extraction and B. subtilis assay. After surgery, patients were monitored for infection by clinicians unaware of their random assignment group. The study was terminated and the code broken when it was evident that wound infections were increased to a statistically significant difference in one arm of the study. The brief perioperative administration of cefazolin reduced the incidence of wound infection from 21% to 4% (P less than 0.05) and the incidence of urinary tract and pulmonary infections from 17% to 0% (P less than 0.05). Tissue levels of antibiotics confirmed adequate dosages in the test subjects. The advantages of prophylactic administration of cefazolin for gastric bypass procedures are clearly demonstrated in this study. This confirms other reports which have shown prophylactic antibiotics to be useful in a variety of procedures. These studies suggest the need to reconsider the traditional opposition to prophylactic antibiotics and to determine whether perioperative antibiotics should be used routinely in all major operations.