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Background: Despite providing superb excess weight loss and increased resolution of comorbid diseases, such as type 2 diabetes mellitus, compared to other bariatric procedures, the duodenal switch/ biliopancreatic diversion (DS/BD) has not gained widespread acceptance among patients and physicians. In this study, we investigated outcomes, symptoms and complications among postsurgical DS patients compared to RYGB patients., Methods: We used propensity scores to retrospectively match patients who underwent DS/BD between 2005 and 2010 to comparable Roux-en-Y gastric bypass (RYGB) patients. We then reviewed patient charts, and surveyed patients using the University of Minnesota Bariatric Surgery Outcomes Survey tool to track outcomes, comorbid illnesses and complications., Results: One hundred ninety consecutive patients underwent primary DS/BD between 2005 and 2010 at the University of Minnesota Medical Center. There were 178 patients available for follow-up (93.7%) who were matched to 139 RYGB patients. Type 2 diabetes, hypertension, and hyperlipidemia all significantly improved in each group. Improvements were significantly higher in the DS/BD group. Percent total weight loss was not different between groups. Loose stools and bloating symptoms were more frequently reported among DS/BD patients. With the exception of increased emergency department visits among DS/BD patients (P < .01), overall complication rates were not significantly different between DS/BD and RYGB. There was no difference in mortality rates between the groups., Conclusion: The DS/BD is a robust procedure that engenders both superior weight loss and improvement of major comorbidities. Complication and adverse event rates are similar to those of RYGB., (Copyright © 2012 Mosby, Inc. All rights reserved.)

Background: Outcomes of bariatric surgery in patients with a body mass index (BMI) <35 kg/m(2) have been an active area of investigation. We examined the comparative effectiveness of Roux-en-Y gastric bypass (RYGB) to routine medical management (nonsurgical controls; NSCs) in achieving appropriate targets defined by the American Diabetes Association for type 2 diabetes mellitus (T2DM) in patients with class I obesity (BMI 30.0-34.9 kg/m(2)) T2DM at 1 year., Methods: We identified patients undergoing RYGB (N = 17) with both class I obesity and T2DM and compared them to similar NSC (N = 17) treated in the Primary Care Center. Data were collected at baseline and 1 year for systolic blood pressure (SBP), as well as blood levels for low-density lipoprotein (LDL) cholesterol and hemoglobin A1c (HbA1c)., Results: After RYGB, BMI decreased from 34.6 ± 0.8 kg/m(2) to 25.8 ± 2.5 kg/m(2) (P < .001) and HbA1c decreased from 8.2 ± 2.0% to 6.1 ± 2.7% (P < .001). The NSC cohort had no significant change in either BMI or HbA1c. SBP and LDL did not significantly change in either group. The RYGB group had a decrease in medication use compared to the NSC group (P < .001). The RYGB group ceased the use of antihypertensive and antihyperlipidemia medications by 1 year despite abnormal values., Conclusion: RYGB can be performed in patients with both a BMI <35 kg/m(2) and T2DM with better weight loss, glycemic control, and fewer antihyperglycemic medications than NSC. Inappropriate cessation of medications may partially explain the persistent increase in both SBP and LDL after RYGB., (Copyright © 2011 Mosby, Inc. All rights reserved.)

Background: This is the first systematic review and meta-analysis of published mortality data after bariatric surgery., Methods: The review includes all papers published in English from January 1, 1990 to April 30, 2006, identified through electronic searches in MEDLINE, Current Contents, and the Cochrane Library, supplemented by manual reference checks. All accepted studies were assigned a level of evidence (Centre for Evidence-Based Medicine, Oxford, UK), and randomized controlled trials were rated for quality using the Jadad scoring method. Random effects meta-analyses were performed. Mortality was analyzed at either 30 days to 2 years was 0.35% (95% CI, 0.12-0.58) in 140 treatment arms (n = 19,928). Mortality at or=65 years)., Conclusion: The early and late mortality rates after bariatric surgery are low and can be subjected to risk stratification for comparative analyses and prospective risk assessments.

Background: Improvement of angina pectoris symptoms after cholesterol lowering has raised questions as to the underlying mechanisms., Methods: Rabbit experiment: We compared arterial blood samples from New Zealand White cholesterol-supplemented rabbits (n = 6) with nonsupplemented rabbit samples (n = 4) in a closed-loop circulation diffusion system. The pH and partial pressures of oxygen (pO2) and carbon dioxide (pCO2) were measured continuously. The samples were first oxygen (O2) saturated (pO2, 160 mm Hg; pCO2, 4 mm Hg) and then desaturated in 100% nitrogen. Cholesterol levels were determined in whole blood, plasma (P Chol), red blood cells (RBCs), and RBC membranes. Human experiment: We exposed quadruple desaturated venous blood samples (n = 4) with P Chol levels of 87 to 400 mg/dL in a gas exchanger to capillary gas conditions (pO2, 23 mm Hg; pCO2, 46 mm Hg). After 15 minutes we performed blood gas analyses and compared our results to baseline values., Results: In the rabbit experiment the cholesterol-supplemented group as compared to the control group showed higher plasma pO2 levels during the saturation phase and lower plasma pO2 levels during the desaturation phase. It also had a markedly increased RBC membrane cholesterol content: 121 +/- 3 (standard error of the mean [SEM]) mg/dL versus 22 +/- 1.7 mg/dL in the control group (P < .05). This barrier to RBC membrane O2 diffusion caused delayed O2 entry into the RBCs during saturation, with a higher plasma pO2, and delayed O2 release from the RBCs during desaturation, with a lower plasma pO2. In the human experiment the P Chol level was inversely correlated with the percentage change of O2 content in milliliters of O2 per deciliter of blood (P < .05)., Conclusions: Increased RBC membrane cholesterol in hypercholesterolemia appears to decrease the transmembrane O2 diffusion rate.

Background: Few lipid/atherosclerosis intervention trials have assessed the impact of cholesterol reduction on peripheral arterial disease. The 838 patients evaluated in the Program on the Surgical Control of the Hyperlipidemias (POSCH) trial represent more than the total number of patients in the seven previously reported studies., Methods: Peripheral arterial disease in POSCH was assessed by progression of clinical disease, serial changes in the systolic blood pressure ankle/brachial index (ABI), and changes on sequential peripheral arteriograms., Results: At the time of formal closure of the POSCH trial on July 19, 1990, claudication or limb-threatening ischemia was exhibited in 72 of 417 control group (CG) patients and in 54 of 421 intervention group (IG) patients (IG relative risk [RR] 0.702, 95% confidence interval [CI] 0.169 to 1.000, p = 0.049). With additional follow-up evaluation to September 30, 1994, clinical peripheral arterial disease was evident in 91 CG patients and 64 IG patients (RR 0.656, 95% CI 0.200 to 0.903, p = 0.009). At the 5-year follow-up evaluation, an ABI of less than 0.95 was present in 41 of 120 CG patients and in 24 of 126 IG patients, all of whom had an ABI of 0.95 or greater at baseline (RR in the IG of 0.557, 95% CI 0.360 to 0.863, p < 0.01). No appreciable differences were noted in the progression or regression of arteriographic peripheral arterial disease between the two groups., Conclusions: Effective cholesterol reduction in POSCH led to statistically significant differences between the control and the intervention groups in the development of clinically evident peripheral arterial disease and in the ABI values, but not in the peripheral arteriograms. Additional studies need to assess the correlation between peripheral arterial changes and coronary arterial changes and clinical atherosclerosis events. Intervention trials that study peripheral arterial disease have intrinsic value in the evaluation of the impact of risk factor modification on progression of atherosclerotic peripheral arterial disease.

The purpose of this study was to examine the effects of aspirin use on mortality and morbidity rates in a subset of the control group of the Program on the Surgical Control of the Hyperlipidemias (POSCH) that was stratified by cigarette smoking status at the time of randomization. The clinical impact of aspirin intake in cigarette smokers and former cigarette smokers has not been well studied. POSCH was a randomized, controlled, clinical trial designed to ascertain the effects of lipid modification by the partial ileal bypass operation on clinical end-points and arteriographic changes in postmyocardial infarction subjects with hypercholesterolemia. Cohorts of cigarette smokers in the diet-control group were evaluated for overall and atherosclerotic coronary heart disease (ACHD) mortality rates and recurrent confirmed nonfatal myocardial infarction rates. In current cigarette smokers at baseline (n = 90) with a mean follow-up of 8.3 years, the overall mortality rate was 45.2% in patients with no aspirin use and 10.4% in patients who reported even infrequent aspirin use (relative risk = 4.3, 95% confidence interval (CI) = 2.4 to 10.6, p < 0.001). For ACHD mortality in this cohort, the relative risk was 17.1 (35.7% vs 2.1%, 95% CI = 1.4 to 125.0, p < 0.001); for the combined end-point of ACHD mortality and nonfatal myocardial infarction, the relative risk was 2.4 (40.5% vs 16.7%, 95% CI = 1.2 to 5.1, p = 0.018).(ABSTRACT TRUNCATED AT 250 WORDS)

Although reduction in total plasma cholesterol has yet to be shown to have a beneficial effect on overall mortality, the weight of experimental and epidemiologic evidence supports efforts to lower total plasma cholesterol levels to reduce the risk of death from coronary heart disease (CHD). This is especially true in patients with heterozygous, type II-A hyperlipoproteinemia, whose total plasma cholesterol levels above the 90th percentile for age and sex place them at markedly increased risk of death from CHD. The lipid results of partial ileal bypass (PIB) were assessed in 110 patients with heterozygous, type II-A hyperlipoproteinemia in the Program on the Surgical Control of the Hyperlipidemias, a randomized, prospective clinical trial assessing the effects of cholesterol reduction on overall mortality and the course of CHD. Compared with dietary control (n = 52), PIB (n = 58) reduced total plasma cholesterol levels 24% +/- 2% (mean +/- SEM), reduced low-density lipoprotein (LDL) cholesterol levels 34% +/- 3%, and increased high-density lipoprotein (HDL) cholesterol levels 5% +/- 5% 5 years after surgery. Very low-density lipoprotein cholesterol levels were 28% +/- 21% higher and plasma triglyceride levels were 24% +/- 11% higher in the surgical group. The HDL cholesterol/total plasma cholesterol and HDL cholesterol/LDL cholesterol ratios were significantly higher after PIB. Apolipoprotein A-I and HDL subfraction 2 levels were significantly higher and apolipoprotein B-100 levels were significantly lower in the surgical group. PIB successfully lowered mean total plasma cholesterol and LDL cholesterol levels below the limits recommended by the National Cholesterol Education Program to minimize the risk of death from CHD. These results confirm the efficacy and support the role of PIB in the management of patients with marked hypercholesterolemia.

The Program on the Surgical Control of Hyperlipidemias (POSCH) is a multicentered, randomized, secondary intervention trial assessing the effect of lipoprotein modification achieved by partial ileal bypass (PIB) on overall mortality rates and the course of coronary heart disease. Of the 838 participants, 396 (196 control and 200 surgical patients) have complete 5-year lipoprotein results and are the basis of this report. After PIB, total cholesterol level decreased 24 +/- 1.2% (mean +/- SEM) and low-density lipoprotein cholesterol level fell 38 +/- 1.5% in comparison with control subjects. High-density lipoprotein (HDL) cholesterol level was not changed by PIB; however, a significant decrease in HDL occurred over 5 years in the control group (41.7 +/- 0.7 mg/dl versus 39.5 +/- 0.6 mg/dl, p less than 0.05). This led to consistently higher HDL levels in the surgical group in comparison with control subjects after PIB. Very low-density lipoprotein cholesterol and triglyceride levels were higher in the surgery group than in control subjects (24 +/- 7.6% and 21 +/- 5.4% at 5 years). Apolipoprotein B-100 was significantly lower, and apolipoprotein A-I and HDL-2 were significantly higher in the surgery group. These lipoprotein changes are greater than have been reported from any previous trial of dietary or pharmacologic intervention, including the Lipid Research Clinics-Coronary Primary Prevention Trial, which used cholestyramine. Based on available epidemiologic data, these changes predict a marked reduction in morbidity and mortality rates associated with coronary heart disease after PIB.

We studied the effect of long-term intravenous heparin infusion, delivered by a self-recycling, totally implantable infusion pump developed in our laboratory, in 21 patients with recurrent thromboembolic disease. Continuous infusions were maintained in these patients from 1 to 36 months, during which pumps were refilled by percutaneous needle injection at 4- to 8-week intervals. We maintained plasma heparin levels between 0.1 and 0.3 U/ml plasma. This regimen prevented thromboembolic phenomena in all except one patient, who apparently is refractory to heparin as well as oral anticoagulant drug therapy. Marked reduction of pain and improvement of mobility were reported by several patients with vena cava ligature syndrome. No spontaneous hemorrhagic complications occurred; however, several episodes of pump site hemorrhage were associated with pump refills. Bone mineral densities measured in eight subjects after 1 year of heparin infusion [1.00 +/- 0.06 (SE) gm/cm] were not significantly (P = 0.5) different from baseline values (0.98 +/- 0.08 gm/cm); however, osteoporosis did occur in one subject. Serum calcium, phosphorus, alkaline phosphatase, cholesterol, and triglycerides also remained unchanged in these subjects. These data suggest that continuous long-term heparin infusion is a viable therapeutic alternative in subjects with refractory thromboembolic disease.

Plasma lipid and lipoprotein levels and composition of the very low-, low-, and high-density lipoproteins (VLDL, LDL, HDL) were studied in white New Zealand rabbits in the control state, 8 weeks after initiation of a 2% cholesterol-enriched diet, and sequentially for 16 weeks following a partial ileal bypass (PIB) procedure. Turnover and aortic uptake of 125I-labeled VLDL, obtained from the rabbits before and 16 weeks after PIB, were also analyzed. A significant reduction of plasma cholesterol from the postdiet levels to well below the prediet mean, despite continuation of the high cholesterol diet, followed PIB. A very early reduction of the apoprotein B percentage content in both VLDL and LDL was observed after the procedure, even when a relative cholesterol ester enrichment of these lipoproteins was still present. HDL cholesterol levels were somewhat lowered by the experimental diet and further reduced after PIB. 125I-labeled VLDL after PIB showed a reduced arterial uptake, as compared to the same lipoproteins from animals before PIB. These findings may provide an interpretation for the decreased atherogenesis after PIB.

For today's most common peritoneovenous shunt catheters, the high incidence of complications (disseminated intravascular coagulation [DIC], pulmonary problems, clotting of the intravascular end, and shunt kinking) results in limited use. We have designed a new peritoneovenous shunt catheter in which we improved mechanical biocompatibility with respect to both the peritoneum and the vasculature. The device consists of: a multimicroorifice ascites filter in a double-chambered collecting device, a tubular compression pump with an intratubular check-valve, and a check-valve catheter at the intravascular end for positive exclusion of blood by reflux or back diffusion. This configuration filters the proteinaceous material from the ascites fluid, transports the filtrate into the blood stream, maintains patency, act to prevent DIC by inhibiting the creation and transport of microthrombi into the cardiovascular system, and eliminates clot formation at the intravascular end.

Partial ileal bypass (PIB) and ingestion of alfalfa are both known to lower plasma cholesterol (C) levels. During an 18-week period, the combined effects of both were studied in four randomized groups of rabbits receiving C-free, hypercholesterolemia-inducing, semisynthetic diets 3 weeks after sham or PIB surgery. The diets, with or without alfalfa, had similar overall compositions of fat, protein, carbohydrate, and fiber. We measured blood C, triglycerides (T), and lipoprotein fractions of both C and T at biweekly intervals. In vivo liver and small-bowel synthesis of C, fatty acids (FA), and nonsaponifiable lipids (NSL) were determined with radioactive 14C-acetate at the end of the study. The results were evaluated by means of analysis of variance using unweighted cell means. The combined PIB and alfalfa modalities significantly lower C levels in serum, plasma, low-density lipoproteins, and high-density lipoproteins by 66%, 71%, 85%, and 35%, respectively. However, due to alfalfa, a significant increase of 49% was observed in plasma T when both treatments were combined. Liver FA synthesis was significantly decreased (65%) with PIB and increased (161%) with alfalfa; when the two treatments are combined, a nonsignificant response was observed. Similarly, this inverse relationship for PIB and alfalfa was seen for C and NSL synthesis. Small-bowel FA synthesis was significantly decreased (72%) by the combination of PIB and alfalfa. We conclude that alfalfa suppresses, in part, the physiologic rebound effect of PIB surgery by increasing hepatic C and NSL synthesis; inversely, PIB surgery inhibits the additive effect in the liver synthesis of FA produced by alfalfa. Alfalfa and PIB alone, and synergistically, decrease total small-bowel lipid synthesis, specifically that of FA. Alfalfa is an effective adjuvant to PIB for reducing total and lipoprotein C fractions.

The Program on Surgical Control of the Hyperlipidemias (POSCH) is a multicentered secondary coronary heart disease intervention trial utilizing maximal plasma lipid reduction as achieved by the partial ileal bypass operation. With over 500 patients recruited into this trial at present, the 4-year sequential lipid changes are statistically highly significant and include an approximate 30% plasma total cholesterol and 40% low density lipoprotein (LDL)-cholesterol reduction, with a slight increase in the high density lipoprotein (HDL)-cholesterol and a marked increase in the HDL-cholesterol:LDL-cholesterol ratio of about 75% or higher. A definitive answer to the lipid-atherosclerosis theory corollary--whether a decrease in the plasma cholesterol engenders a reduction in the incidence or severity of atherosclerotic cardiovascular disease--can be expected from these marked lipid changes in POSCH.

We studied lipid profiles in 10 patients with insulin-requiring type II diabetes. Patients began the study under conventional subcutaneous insulin injection therapy. Treatment was then optimized on subcutaneous therapy and finally converted to continuous intravenous therapy from a single flow rate implantable pump. Pump management proved reliable and safe. Implantable pump therapy showed a statistically significant reduction in the average plasma cholesterol level from 205.7 to 184.7 mg/dl. The mean low-density lipoproteins (LDL)-cholesterol level decreased from 114.6 to 108.1 mg/dl, the high-density lipoproteins (HDL)-cholesterol average changed from 50.6 to 51.0 mg/dl, and the HDL/LDL ratio increased from 0.478 to 0.500. Glycemic control did not improve on single-rate intravenous therapy compared with intensive conventional subcutaneous injection during the short observation period. The authors conclude that additional studies should be performed to confirm the improvement in the lipid profile on intravenous pump therapy.

At the University of Minnesota under the supervision of one staff surgeon both jejunoileal bypass (JIB) and gastric bypass (GIB) operations have been performed for weight reduction in morbidly obese individuals. During the last 14 years 727 patients underwent end-to-end (40 to 4 cm) JIB and more than 570 patients underwent GIB. This report is based on a comparison of 205 JIBs performed between July 1975 and July 1979, 106 Alden-loop type GIBs (GIB-loop) performed between July 1975 and July 1979, 53 loop GIBs with enteroenterostomies between the limbs of the loop (GIB-EE) performed between May 1980 and May 1981, and 57 Roux-en-Y GIBs (GIB-Roux) performed between May 1981 and May 1982. Adequate weight loss occurred in 80% of the patients who returned for follow-up in all groups. The percentage of excess body weight loss was similar for the first year (65% for JIB, 62% for GIB-loop, 69% for GIB-EE, and 71% for GIB-Roux). The operative mortality and the immediate morbidity rates were uniformly low. The long-term complications for JIB were 37.7% arthralgia, 7.1% oxalate urolithiasis, 5.6% incisional hernia, and 1.4% liver failure. The complications for GIB-loop were 10.2% nausea/vomiting, 1.9% bile reflux gastritis, and 2.8% anastomotic problems; for GIB-EE 23% nausea/vomiting, 7% bile gastritis, 4.6% incisional hernia, and 3.7% anastomotic problems; and for GIB-Roux 16% nausea/vomiting and 1.7% anastomotic problems. The anastomotic problems consisted of afferent loop obstructions and stomal stenosis; there were no leaks. At 1 year plasma cholesterol reduction for JIB averaged 42% (p less than 0.001), GIB-loop 14% (p less than 0.001), GIB-EE 7% (NS), and GIB-Roux 17% (p less than 0.001). One year after operation 49% of 88 JIB patients showed progression of liver disease on sequential biopsy specimens and 20% improvement. In the 78 GIB patients with sequential biopsies, liver disease progressed in 8% and improved in 65%. In summary, comparable therapeutic weight reduction occurred with all the assessed procedures; however, the GIB-Roux was associated with far fewer serious long-term complications. At this time the GIB-Roux procedure is the weight reduction operation we recommend.

Dietary marine oil supplements may protect against atherosclerosis, although their influence on plasma lipids, in vivo cholesterol metabolism, and aortic cholesterol accumulation remains uncertain. The effects of daily administration of marine oil--delivering 100 mg of eicosapentaenoic acid, 59 mg of docosahexaenoic acid, and 221 mg of omega-3 fatty acids per kilogram--were assessed in 33 New Zealand white rabbits. Six animals (group I) were immediately killed. In the remaining animals stable hypercholesterolemia was induced with a 0.25% cholesterol-enriched diet. After 7 weeks on this diet, six animals were killed (group II). Total plasma cholesterol had increased significantly (982 +/- 119 mg/dl vs. 55.6 +/- 7.1 mg/dl, mean +/- SEM, p less than 0.001). The remaining animals randomly received a tap-water placebo (group III, n = 12) or marine oil (group IV, n = 9) daily. After 3 months, total plasma cholesterol was similar (p = NS) among group II (982 +/- 119 mg/dl), group III (965 +/- 54 mg/dl), and group IV (913 +/- 46 mg/dl). No significant differences in HDL cholesterol, LDL cholesterol, VLDL cholesterol, or triglyceride levels developed between the placebo and marine oil groups. Two-hour, hepatic total lipid, neutral steroid, fatty acid, bile acid, and cholesterol synthesis rates were not significantly affected by marine oil treatment. Thoracic aortic cholesterol content increased during cholesterol feeding (5.7 +/- 0.9 mg/gm vs. 1.1 +/- 0.05 mg/gm, group II vs. group I, p less than 0.05). Marine oil supplementation had no effect on the progressive accumulation of cholesterol in the thoracic aorta (28.8 +/- 2.5 mg/gm vs. 29.4 +/- 1.8 mg/gm, group IV vs. group III, p = 0.84). The abdominal aortic cholesterol contents were also similar. These results do not support the use of dietary marine oil supplements for the amelioration of lipid metabolism or the prevention of atherosclerosis.

To determine the preferable reconstruction of gastrointestinal continuity after gastric bypass, we studied by endoscopic, chemical, and histologic analyses 28 randomly selected patients with a loop gastroenterostomy, a loop gastroenterostomy plus enteroenterostomy between the afferent and efferent loops, and a Roux-en-Y anastomosis. Total bile acid levels for the three groups were: 5092 +/- 1673 mumol/L, 1638 +/- 581 mumol/L, and 404 +/- 384 mumol/L, respectively. The incidence of gastritis by endoscopy was 71% in the standard loop bypass, 45% in the enteroenterostomy group, and 13% in the Roux-en-Y group. Histologic abnormalities were present in 86% of the patients who underwent standard loop bypass, in 91% of those with an additional enteroenterostomy, and in 63% of the Roux-en-Y group. There was poor correlation of symptoms and objective findings. In our study Roux-en-Y reconstruction after gastric bypass, in comparison with loop gastroenterostomy or loop gastroenterostomy with an additional enteroenterostomy, is less likely to result in bile in the stomach, endoscopic changes, and histologic abnormalities.

Tumor cells, in vitro, must derive the majority of their required cholesterol from their host milieu. To determine if limiting tumor-available cholesterol results in limited tumor growth in vivo, Holtzman rats were given 10 X 10(6) Novikoff ascites tumor cells subcutaneously. Prior to inoculation, animals received either distal small bowel exclusion or sham operation plus either standard chow or estrone-containing chow (0.0025% or 0.01%) diets. In three separate experiments it was shown that (1) tumor weight was positively correlated with whole plasma cholesterol levels (r = 0.495; P less than 0.05); (2) the lowest tumor weights were correlated with the lowest plasma cholesterol; (3) low density and very low density lipoprotein cholesterol levels were both individually and in combination positively correlated with tumor weight (R2 = 0.828; P less than 0.01); and (4) survival of subcutaneous tumor inoculated animals was significantly greater in those animals shown to have the lowest plasma cholesterol, 27 +/- 1 days versus 29 +/- 1 days; (P less than 0.05). These data support the concept that limiting tumor-available cholesterol by altering host cholesterol metabolism will limit tumor growth.

Partial ileal bypass (PIB) lowers the plasma total cholesterol (C) level, thereby increasing hepatic C synthesis to replenish bile acid and C stores. Lovastatin, a C synthesis inhibitor, may act as a potential adjuvant to PIB for lipid lowering. In this study, the effects of PIB and lovastatin, alone and in combination, were examined in plasma and tissue. For 14 weeks, 32 New Zealand White rabbits received a C-free, alfalfa-free, natural-ingredients diet previously shown to induce hypercholesterolemia. The rabbits were divided into control, lovastatin, PIB, and PIB plus lovastatin groups. Lovastatin was administered at a dose of 0.35 mg/kg twice daily. Compared with the control group, PIB alone decreased the plasma total C level by 75% (p less than 0.005), the low-density lipoprotein (LDL)-C level by 79% (p less than 0.025), and hepatic C content by 50% (p less than 0.05), while increasing hepatic C synthesis by 176% (p less than 0.05). Compared with the control group, lovastatin alone decreased the plasma total C value by 36% (p = NS), the LDL-C level by 35% (p = NS), hepatic C content by 29% (p = NS), and hepatic C synthesis by 52% (p = NS). Compared with the control group, the combination of PIB and lovastatin decreased the plasma total C level by 78% (p less than 0.005), the LDL-C level by 74% (p less than 0.025), and hepatic C content by 58% (p less than 0.05); however, the hepatic C synthesis increased by 490% (p less than 0.005) compared with the control group and by 110% (p less than 0.05) compared with PIB alone. This is the first demonstration of a metabolic reversal of the cholesterol synthesis inhibition engendered by lovastatin. We conclude that both PIB and lovastatin lower plasma total C and lipoprotein C fractions. Their combination has an additive C-lowering effect in plasma and decreases tissue C content by increasing cellular C demand. This latter effect overcomes the inhibitory effect of lovastatin on hepatic C synthesis, resulting in an augmented compensatory increase in hepatic C synthesis.

At the University of Minnesota, under the supervision of one staff surgeon, both the jejunoileal bypass (JIB) and gastric bypass (GIB) operations have been done for weight reduction in morbidly obese individuals. Over the past 11 years, end-to-end (40 to 4 cm) JIB performed for 727 patients. In addition, antecolic GIB was performed for 364 patients over the past 6 years. This report is based primarily on a comparison of 205 JIB and 106 GIB patients with surgery between July 1975 and July 1979. Adequate weight loss was seen in 75% of each group. The percentage of excess body weight loss was similar for the first year (65% for JIB and 62% for GIB); however, the JIB patients started at 214% of ideal weight and GIB patients at 197% of ideal weight. The operative mortality rate for either operation was well below 1%, and the immediate operative morbidity rate was low and only rarely delayed discharge from the hospital. The long-term complications for JIB were 37.7% arthralgia or arthritis, 7.1% oxalate urolithiasis, 5.6 incisional hernia, and 1.4% liver failure; complications of GIB were 10.2% nausea and/or vomiting, 1.9% reflux esophagitis, and 2.8% anastomotic problems. At 1 year, plasma cholesterol reductions for JIB patients averaged 42% (P less than 0.001), whereas for the GIB patients it ws only 14% (P less than 0.001). At 1 year after operation, 49% of 88 JIB patients showed progression of liver disease on sequential biopsies, with 31% unchanged and 20% improved. In 43 GIB patients, the biopsies showed improvement in 58%, an unchanged status in 30%, and worsening in 12%. The levels of serum glutamic oxaloacetic transaminase and alkaline phosphatase increased after JIB and eventually returned to normal, while GIB patients had only minor fluctuations of liver function tests. Comparable therapeutic weight results occurred with JIB and GIB; however, the GIB was associated with far fewer serious long-term complications and the JIB with a far greater cholesterol lowering. A percentage of the GIB patients showed progression of liver disease at 1 year after bypass.

Portacaval shunt (PCS) has been proposed as a therapy for hyperlipidemia; however, its lipid-lowering mechanism is unknown. In this study PCS was performed on ten mongrel dogs to measure its effect on plasma lipids and on the cholesterol synthesizing ability of the liver and intestines, the major indodenous cholesterol synthesizing tissues. Plasma was analyzed for total cholesterol (CHOL), triglycerides (TG), and the CHOL content of three plasma lipoprotein fractions. Jejunal, ileal, and hepatic cholesterol synthetic rates were determined by 14C-acetate incorporation to CHOL in tissue slices obtained at operation before PCS and 44 +/- 4.1 (S.D.) days after PCS. Plasma CHOL decreased by 18 +/- 7 (S.E.), 34 +/- 8 (S.E.), and 57 +/- 14 (S.E.) mg. per 100 ml. by 4, 6, and 16 weeks after PCS, respectively. TG decreased by 13 +/- 5 (S.E.), 27 +/- 5 (S.E.), and 30 +/- 9 (S.E.) mg. per 100 ml. at corresponding time intervals. Paired Student's test analysis of CHOL and TG changes are significant at the p less than 0.05 level. CHOL content of the three plasma lipoprotein fractions decreased correspondingly. Intestinal tissue CHOL synthesis rates changed only slightly. Hepatic synthetic rates increased by 30 to 40%; however, no synthetic rate changes were statistically significant at the p less than 0.05 level. PCS is associated with decreased in plasma CHOL [42% (see article)] AND TG [53% (see article)] in dogs up to 16 weeks following operation. Statistically significant changes in endogenous CHOL synthesis were not demonstrated by this study. The mechanism by which PCS affects plasma lipids in the dog is unknown as yet.