Control of blood glucose in experimental diabetes by means of a totally implantable insulin infusion device.

Near-normal glucose tolerance tests in diabetic dogs were obtained during basal rate insulin infusions in restrained animals by use of extracorporeal infusion pumps and in conscious, unrestrained animals by means of implanted infusion pumps. Even better regulation of blood glucose in diabetic animals was obtained by the addition of predetermined pulses of insulin at higher flow rates than the basal flow rate, accomplished by use of a transcutaneously activated valve mechanism attached to the implanted infusion pump. We conclude that near-normal blood glucose concentrations can be maintained throughout the day in the dog by these means and that similar approaches, using implantable infusion pumps, in man may lead to better long-term control of diabetes than is currently available.

Effective lipid modification by partial ileal bypass reduced long-term coronary heart disease mortality and morbidity: five-year posttrial follow-up report from the POSCH. Program on the Surgical Control of the Hyperlipidemias.

BACKGROUND: In 1990, when the Program on the Surgical Control of the Hyperlipidemias (POSCH) reported its in-trial results strongly supporting the conclusion that effective lipid modification reduces progression of atherosclerosis, the differences for the end points of overall mortality and mortality from atherosclerotic coronary heart disease (ACHD) did not reach statistical significance. METHODS: The Program on the Surgical Control of the Hyperlipidemias recruited men and women with a single documented myocardial infarction between the ages of 30 and 64 years who had a plasma cholesterol level higher than 5.69 mmol/L (220 mg/dL) or higher than 5.17 mmol/L (200 mg/dL) if the low-density lipoprotein cholesterol level was in excess of 3.62 mmol/L (140 mg/dL). Between 1975 and 1983, 838 patients were randomized: 417 to the diet control group and 421 to the diet plus partial ileal bypass intervention group. Mean patient follow-up for this 5-year posttrial report was 14.7 years (range, 12.2-20 years). RESULTS: At 5 years after the trial, statistical significance was obtained for differences in overall mortality (P = .049) and mortality from ACHD (P = .03). Other POSCH end points included overall mortality (left ventricular ejection fraction > or =50%) (P = .01), mortality from ACHD (left ventricular ejection fraction > or =50%) (P = .05), mortality from ACHD and confirmed nonfatal myocardial infarction (P<.001), confirmed nonfatal myocardial infarction (P<.001), mortality from ACHD, confirmed and suspected myocardial infarction and unstable angina (P<.001), incidence of coronary artery bypass grafting or percutaneous transluminal coronary angioplasty (P<.001), and onset of clinical peripheral vascular disease (P = .02). There were no statistically significant differences between groups for cerebrovascular events, mortality from non-ACHD, and cancer. All POSCH patients have been available for follow-up. CONCLUSION: At 5 years after the trial, all POSCH mortality and atherosclerosis end points, including overall mortality and mortality from ACHD, demonstrated statistically significant differences between the study groups.

A totally implantable drug infusion defice: laboratory and clinical experience using a model with single flow rate and new design for modulated insulin infusion.

The Infusaid implantable infusion pump with a single delivery rate has maintained chronic intravenous heparin infusion in man for greater than 35 mo and for greater than 5 yr in the dog. Intra-arterial infuson of fluorodeoxyuridine has been maintained for greater than 8 mo in man. In a pilot study using a commercially available, transcutaneously controllable, magnetically activated valve for baseline superimposed bolus insulin infusion, the feasibility of maintaining near normal serum glucose in diabetic dogs was demonstrated. The effect of long-term intravenous cannulation was investigated; it was found that the intimal tissues of the vena cava surrounding the cannulae were largely unaltered and microemboli could not be detected in the lungs of the animals studied. Cannula plugging, which occurred on several occasions due to thrombus formation in the final centimeter of the cannula, has been solved by changes in pump design and refilling procedures. The problem of insulin precipitation in flow passages of the pump remains unsolved, but there are indications that substances entering the cannula from the blood may be involved. A new pump design for modulated insulin infusion is described.

Small bowel length in hyperlipidemia and massive obesity.

Small bowel length has been measured during intestinal bypass surgery in 272 morbidly obese patients undergoing jejunoileal bypass and 121 nonobese patients undergoing partial ileal bypass for hyperlipidemia. There was no statistically significant difference in small bowel length between the obese and the nonobese patients. Small bowel length was not correlated with the degree of obesity expressed as the percentage of ideal weight. The only statistically significant correlation determined was between sex and bowel length in the obese subjects, where a greater length of small intestine was found in the males.

The effect of continuous heparin infusion for one year on serum cholesterol and triglyceride concentrations in the dog.

Fourteen normal dogs received continuous infusions of intravenous heparin for one year by means of an implantable infusion pump. Heparin wad admistered at an overall mean rate of 666 units/kg/day, a dose sufficient to prolong the Lee-White clotting time to greater than twice normal. Eight control, animals, under the same dietary and activity regimen, received continuous infusions of bacteriostatic water for one year by means of implanted pumps. Serum cholesterol concentrations rose to 50% above control values after one month of heparin infusion, and remained significantly (P less than 0.05) elevated at this level for the remaining 11 months. Serum triglyceride levels were unchanged. A possible mechanism for this elevation resides in the known effect of heparin to increase plasma free fatty acid concentrations by its activation of lipoprotein lipase. These results may have implications for the long-term use of heparin anticoagulation in the treatment of atherosclerotic states in man.

Plasma lipoproteins and coronary arteriography in subjects in the program on the surgical control of the hyperlipidemias. Preliminary report.

Coronary arteriographic findings, plasma lipid and lipoprotein levels, and cigarette smoking history are reported for the first 101 male post myocardial infarction survivors who have been entered into the POSCH clinical trial. Estimates of the extent of stenosis in the major coronary arteries were made using 4 models ranging from a simple determination of the number of the 3 major vessels having significant (i.e. 50% or greater stenosis) disease to more complex methods of determining overall extent of disease in 14 major segments of the coronary arteries. Age was shown to be an important factor in the extent of vessel disease. When controlling for age, plasma cholesterol and LDL-cholesterol levels were shown to be related to the extent of disease, especially in Type II hyperlipoproteinemia subjects. Multiple linear regression analysis demonstrated that age and LDL-cholesterol had positive associations and HDL-cholesterol had an inverse association with the coronary artery disease indices. In this comparatively "healthy" subgroup of the overall population of first MI survivors the major CHD risk factors are limited to plasma lipids and cigarette smoking. This preliminary report of 10% of the recruitment objective of the project supports the currently held views of the lipid--atherosclerosis hypothesis regarding the effects of age-total plasma cholesterol, LDL--cholesterol, and HDL--cholesterol on the extent of coronary atherosclerotic plaques, as determined by coronary arteriography.

Increased hepatic cholesterol synthesis in normal rats by cross-circulation with ileal bypassed partners.

Aortic cross-circulation between Holtzman rat littermates was employed to investigate the possible role of a blood-borne factor from the small intestine in the regulation of hepatic cholesterol synthesis. Experimental pairs, consisting of a normal rat and a distal 50% small bowel excluded partner, demonstrated significantly increased combined hepatic cholesterol synthesis when compared to control pairs, consisting of two normal rats, both at 3 and 5 days following parabiosis. This difference was accounted for by increased hepatic cholesterol synthesis in the normal rat in each experimental pair. Neither weight loss nor differences in dietary intake contributed to this effect. Whole blood cholesterol in the common circulation of both experimental and control pairs was lowered; while hepatic cholesterol content was transiently increased, at 3 but not 5 days following parabiosis. Thus, the intestinal bypassed rat stimulates, or releases inhibition of, hepatic cholesterol synthesis in a non-bypassed parabiotic partner. The mechanism for this phenomenon has yet to be defined.

Clinical angiographic regression of atherosclerosis after partial ileal bypass.

Clinical documentation of atherosclerotic plaque regression has been difficult to obtain. This is a report of a patient with severe and early atherosclerotic cardiovascular disease with regression of at least three major atherosclerotic lesions demonstrated by coronary arteriography 10 years after partial ileal bypass operation. The patient's total plasma cholesterol was reduced over these 10 years, ranging from 40% to 23%, from the preoperative level of 757 mg/dl. Sequential arteriograms were assessed independently by several arteriographers and blindly by the Arteriography Review Panel of the Program on Surgical Control of the Hyperlipidemias (POSCH). The readings were analyzed by 4 grading methods. Unanimously, marked regression was read in the proximal left circumflex artery (70% leads to 20%), middle segment of the right coronary artery (45% leads to 20%), and in the distal right coronary artery (80% leads to 50%). Thus, by any and all of the methods used, there was significant regression of arteriographically demonstrated atherosclerotic lesions.

Late results (30 to 35 years) after operative closure of isolated ventricular septal defect from 1954 to 1960.

This study was designed to determine the clinical status, cause of death, and effects of pulmonary vascular disease and conduction abnormalities 30 to 35 years after surgery in 296 consecutive surviving patients of closure of ventricular septal defect. Of the 296 patients, current status was determined by contact with patient and physician in 290 cases, with 6 (2%) lost to follow-up (7,912 patient years are included). Cardiac catheterization after surgery in 168 patients showed complete closure of the defect in 80%. Death occurred in 59 patients (20%), with higher mortality rates in those operated on after the age of 5 years, those with pulmonary vascular resistance greater than 7 units (51%), and those with complete heart block (78%). Of 37 patients with transient heart block after surgery, 8 (22%) have died (3 pulmonary vascular disease, 2 sudden death, 2 unknown causes and 1 complete heart block). Twenty other patients had a dysarrhythmia after surgery, and none of these died. Nine episodes of endocarditis occurred (11.4/10,000 patient years). Nine of 296 (3%) offspring had cardiac malformation. Most patients are in New York Heart Association class I, 57% attended college and 15% received an advanced degree. The data show good results for this group of patients operated on during an early era (1954 to 1960) of open cardiac surgery. They support the current trend toward operation in patients with ventricular septal defects at an early age and with low pulmonary vascular resistance.

Subgroup analyses of the major clinical endpoints in the Program on the Surgical Control of the Hyperlipidemias (POSCH): overall mortality, atherosclerotic coronary heart disease (ACHD) mortality, and ACHD mortality or myocardial infarction.

The Program on the Surgical Control of the Hyperlipidemias (POSCH) was a secondary atherosclerosis intervention trial employing partial ileal bypass surgery as the intervention modality. For this report, we analyzed 105 subgroups in 35 variables in POSCH, chosen predominantly for their potential relationship to the risk of atherosclerotic coronary heart disease (ACHD). We defined potential differential effects as those with: (1) an absolute z-value > or = 2.0 for the subgroup, if the absolute z-value for the overall effect was < 2.0; and (2) an absolute z-value > or = 3.0 for the subgroup and a relative risk < or = 0.5, if the absolute z-value for the overall effect was > or = 2.0. For each of three major POSCH endpoints of overall mortality, ACHD mortality and ACHD mortality or confirmed nonfatal myocardial infarction, we found seven subgroups with a differential risk reduction in the surgery group as compared to the control group. Allowing for identical subgroups for more than one endpoint, there were 13 individual subgroups with differential effects. Of these, seven demonstrated internal consistency across endpoints, and five of these seven displaced external consistency with known ACHD risk factors and for biological plausibility: triglyceride concentration > or = 200 mg/dl; cigarette smoking; overt or borderline diabetes mellitus; a Minnesota ECG Q-QS code of 1-1; and obesity. A greater risk reduction, in comparison to the overall treatment effect, by the reduction of a single risk factor, hypercholesterolemia, in patients with at least two major ACHD risk factors was a provocative and an hypothesis-generating outcome of this analysis. The clinical implications of this finding may lead to more aggressive cholesterol intervention in patients with multiple ACHD risk factors.

Program on the Surgical Control of the Hyperlipidemias (POSCH): design and methodology. POSCH Group.

The Program on the Surgical Control of the Hyperlipidemias (POSCH) is a prospective, randomized, controlled, multi-center, secondary, atherosclerosis intervention trial. POSCH addresses the therapeutic arm of the lipid-atherosclerosis theory, i.e. whether lowering of plasma cholesterol is directly related to a reduction in atherosclerosis risk. In this trial, lipid modification is accomplished by the partial ileal bypass operation. Between 1975 and 1983, 838 patients were randomized into this study. All patients were between 30 and 64 years of age, had survived one and only one electrocardiogram and enzyme-documented myocardial infarction, and had a total plasma cholesterol of at least 220 mg/dl or a low density lipoprotein (LDL)-cholesterol of at least 140 mg/dl if the total plasma cholesterol was between 200 and 219 mg/dl after a minimum of 6 weeks of dietary fat and cholesterol restriction. The primary response variable in POSCH is overall mortality. Secondary endpoints include fatal and non-fatal myocardial infarctions, serial electrocardiographic changes, and, most importantly, sequential coronary arteriography changes. The minimum follow-up is currently planned to be 7 years. Study analyses will be made primarily on the "intention to treat" basis. This paper is the first detailed presentation of POSCH design and methodology. Included are descriptions of study design, implementation, and data collection, including data processing, quality assurance/quality surveillance, and patient safety monitoring. POSCH seeks to demonstrate a significant reduction in overall mortality by lipid modification and to validate the use of coronary arteriographic change as a surrogate endpoint for change in coronary heart disease risk.

Esophageal replacement with jejunum in children: an 18 to 33 year follow-up.

Since 1947 a total of 32 staged jejunal interpositions have been performed in children for total esophageal replacement. There have been no failures of the jejunum to reach the neck, no loss of graft, and no deaths. The first 16 of these 32 children have now reached adulthood and form the basis for this report on the late functional results of staged jejunal interposition. Among these 16 patients there occurred four cervical fistulas which healed without sequelae (25%), one cervical stricture which necessitated dilatation but not revision (6%), one early cervical revision for necrosis of the distal tip of the graft (6%), and no complications related to the distal anastomosis. Long-term follow-up (range 18 to 33 years; mean 27 years) was obtained in 100% (16/16) of patients. A barium swallow was obtained in 81% (13/16) at a mean of 25 years following initial reconstruction (range 14 to 33 years). The fact that all patients could eat a regular diet at normal speeds indicates satisfactory long-term function. Two patients (13%) reported mild cervical dysphagia. A barium swallow in one of these patients revealed no abnormalities. The other was found to have an apparent esophageal diverticulum which resulted because the jejunum was end-to-side to the esophagus. This was recently corrected 27 years after the initial reconstruction and represented the only late complication of the procedure. There were no late strictures or peptic ulcerations. Motility of the jejunal limb was normal in 12 of the 13 patients studied. These results demonstrate that staged jejunal interposition can be accomplished reliably and safely in children with excellent long-term functional results and a minimum of late complications. The jejunum should be considered as an alternative to colon and gastric tubes for total esophageal replacement in children.

Anomalous double blood supply to the lung.

We report an unusual case in which an apparently normal upper lobe of the right lung was supplied by major systemic arterial and pulmonary arterial vessels. The anomalous artery arose from the descending aorta. Following interruption of this vessel, the machinery-like murmur previously present disappeared.

Aberrant left pulmonary artery presenting as a right paratracheal mass in an adult.

Aberrant left pulmonary artery, or pulmonary sling, is a rare variation of the pulmonary vasculature, with only one previous report of the condition being recognized in an adult. In this report a second case recognized de novo in an adult is presented. Both of these adults were evaluated because of right paratracheal masses which required differentiation from pulmonary malignancies. The barium swallow shows a characteristic indentation of the anterior esophageal wall and the lateral tomogram demonstrates absence of the left pulmonary artery from its normal position in the left hilum. The pulmonary arteriogram is diagnostic and allows avoidance of more invasive diagnostic measures.

Long-term, continuous intravenous heparin administration by an implantable infusion pump in ambulatory patients with recurrent venous thrombosis.

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.

Comparisons between jejunoileal and gastric bypass operations for morbid obesity.

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.

Benign hepatocellular tumors.

PIP: Rare cases of benign hepatocellular (liver) tumors usually occur among women of childbearing age. Since 1973, 102 cases of this tumor had been observed among women on oral contraceptives (90% had positive steroid intake history). to investigate the possible association between oral contraceptives (OCs) and benign liver tumor, the University of Minnesota Hospitals analyzed 40 cases of benign hepatocellular from 1950 to 1976. Clinical and pathological records of patients with the tumor (with the exception of hemangiomas) were reviewed and reclassified according to Edmonson's nomenclature. Of the 40 cases, 18 were reclassified as focal nodular hyperplasia (FNH_, 10 as hepatocellular adenomas (HCS), 11 as bile duct adenomas (BDA), and one as mesenchmal hamartoma. These data, as well as information on steroid intake were detailed on Tables 2, 3 and 4. For FNH, the female:male ratio was 8:1, mean age was 43 years + or - (SD), and 8 patients had history of OCs or other steroid intake. For HCA, the female:male ratio was 4:1, with mean age of 33 years + or - 15 (SD); 3 patients had a positive history of OC intake. For BDA, the female:male ratio was 7:4, mean age was 57 years + or - 15 (SD). No definite, conclusive association was established between oral contraceptives and other steroids and incidence of these tumors. The tumors occurred in men, prepubertal children and women on contraceptives or not; they also occured even before the introduction of OCs in the United States in 1961. However, the conclusion does not rule out the possible contributing influence of OCs and other steroids on the development of these tumors.^ieng

The effect of portacaval shunt on plasma lipids and tissue cholesterol synthesis in the dog.

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.

The nature of failure of pulmonary adaptation to atelectasis.

The ability of the lung to decrease blood flow to an atelectatic lobe and to increase flow to normal after reinflation was investigated with a model using left lower lobe atelectasis (LLLA) in the dog. The change in the shunt fraction QS/Qt with continuing LLLA was assumed to represent a change in blood flow to the LLL. With LLLA the Qs/Qt rose from 0.112 to 0.172 and then decreased to 0.119 by the end of 2 hours at the rate of -17%/hour. Reversal of atelectasis for varying times demonstrated that the pulmonary vasoconstrictive response persisted for at least 4 hours after reinflation of LLLA. With LLL ischemia for 1 and 2 hours followed by LLLA, Qs/Qt decreased, but at a rate less than the controls, whereas after hemorrhagic shock with venous reinfusion and LLLA, the Qs/Qt did not decrease. When hemorrhagic shock was followed by arterial reinfusion, 60% had a normal response to LLLA; 40% did not. There was no difference in PVR in these two groups. Pulmonary extravascular water in both groups was the same as in controls. Infusion of NE after 3 hours of LLLA caused Qs/Qt to rise from 0.125 to 0.248, comparable to the value immediately after onset of LLLA. EPi had similar results. Catecholamines may restore blood flow to the atelectatic lobe by causing a maximum generalized pulmonary vasocontriction or by overexpansion of the pulmonary blood volume secondary to peripheral vasoconstriction and thereby abolish any differential in pulmonary vascular resistance across the lung. The early hypoxemia of adult respiratory distress syndrome may arise not on the basis of any intrinsic lung pathology but rather as the result of a normal response of the lung to increased catecholamines.

Searching for the best weight reduction operation.

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.