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Cardiac weight was determined at autopsy in 27 morbidly obese, but otherwise healthy men (mean weight 168 kg) and women (mean weight 138 kg) who died suddenly, prior to, or shortly after gastric restriction operations for relief of obesity. They had lost no weight. Post-mortem examination revealed no cardiac or other pathology explaining the cause of death. Cardiac weight was also measured in 25 men and women of equivalent baseline weight and body mass index who, after operation, subsisted on a hypocaloric diet for 3-4 months after operation, but then died suddenly. Mean weight losses of this latter group were 45.8 kg in men and 32.9 kg in women. No cardiac abnormalities and no organic causes of death were found at autopsy. Decreases in heart weight were calculated. The baseline measurements demonstrated that cardiac weight in the healthy obese rose with increasingly severe obesity in both sexes, but the increase tended to lessen with more extreme obesity. The generally quoted figures of cardiac weight as a fraction of body weight are 0.043 and 0.040% for men and women, respectively. In the group of morbidly obese men, cardiac weight was 0.035% of body weight or 16% lower than predicted. In morbidly obese women, cardiac weight was 0.030% of body weight or 25% lower than predicted. In men, a 28% body weight reduction due to dietary restriction resulted In a proportionately similar 20% decrease in cardiac weight. In contrast, in women after a 27% loss of body weight, cardiac weight decreased only 5%. Severe dietary restriction with a drastic body weight loss did not result in a disproportionate decrease of cardiac weight in either sex, when final body weight had remained above or in the normal range.

Patients who undergo surgery for morbid obesity are often subjected to reoperation for a wide array of indications. To evaluate outcome following revisional procedures, we reviewed the records of 32 such patients treated at UCLA between April 1986 and May 1989. Twenty-five women (78%) and 7 men (22%) with a mean age of 44 years underwent 76 reoperations (2.4 per patient) for complications of prior obesity surgery. Indications for initial surgical revision consisted primarily of metabolic derangements (12 patients) and weight-related problems (11 patients). In contrast, indications for the patients' final surgical procedure were commonly for bowel obstruction (41%), intra-abdominal sepsis (12%), and gastrointestinal bleeding (6%). Following initial revision, 23 patients (71.8%) required further surgery for major complications and four patients died (12.5%). While initial revisions are frequently indicated for metabolic problems, final reoperations are more frequently undertaken for urgent, life-threatening complications. Revisional procedures for morbid obesity should be carefully considered, and the potential for major complications and/or death should be weighted heavily against proposed benefits.

Many complications that followed jejunoileal bypass operations performed for the relief of morbid obesity were caused by bacterial overgrowth in the excluded blind loop. The arthritis-dermatitis syndrome was one of the common distressing disorders. The pathogenetic mechanism was thought to be an immune-complex-mediated process related to bypass enteritis. Antiarthritic medication was ineffective in most instances, and the skin lesions were refractory to treatment. A 45-year-old woman was suffering from the disorder as described above. She also had diarrhea, a low hematocrit, an elevated white blood cell count, and an increased sedimentation rate. Her nutritional status was satisfactory, presumably because of adaptive hypertrophy of the short functioning small intestinal segment. The patient adamantly refused dismantling of the bypass or any gastric restriction operations. Therefore, the blind loop, the source of her disease, was excised with immediate relief of all ill effects and restoration of normal laboratory findings. The patient has been entirely well since, and her weight has remained stable for one year.

Renal function and biopsies were studied in 18 patients, 7 to 108 months after intestinal bypass. Enteropathy was found in 12 and hyperoxaluria in 16. Every biopsy showed a type of focal interstitial nephritis, tubular atrophy, fibrosis, and glomerular hyalinization. Damage ranged from minimal to extensive and renal function from normal to end-stage failure. Tubular injury had resulted partly from oxalate deposits. However, in 10 patients no oxalate crystals were seen. In eight others, most of the damaged areas were remote from crystal deposits. Immunoglobulin M and C3 deposits, found in glomerular capillaries and the messangium in six of 11 specimens, and the presence of circulating immune complexes in five of 10 patients, in addition to the extraintestinal organ involvement, suggested immune complex mesangial injury as one factor in bypass nephropathy. With progressive impairment of renal function, a biopsy appears justified. If damage is significant, the bypass should be dismantled.

The relationship between the changes in serum thyroid hormone levels and nitrogen economy during caloric deprivation were investigated in ten obese men during a 40 d, 400 kcal protein-supplemented weight-reducing diet. This regimen induced increases in the serum levels of total T4, free T4 and total rT3, and decreases of total T3, while serum TSH remained unchanged. There were progressive decreases in total body weight and urinary losses of total nitrogen and 3-methylhistidine, with the early negative nitrogen balance gradually returning towards basal values during the 40 days. Subjects with the largest weight loss had the most increase in the serum levels of total T4 and free T4 index and the greatest decrease in T3. The magnitude of the increase of the nitrogen balance from its nadir was correlated with the extent of the reduction of T3 and increase of T3 uptake ratio and free T4 levels. The decrease in the urinary excretion of 3-methylhistidine correlated with the increase in free T4 and rT3 levels. Nadir serum transferrin values were directly related to peak rT3 values, and the lowest albumin concentrations occurred in subjects with the highest total T4 and free T4 index values. Further, the maximum changes in the serum thyroid hormone levels preceded those of the nutritional parameters. These relationships suggest that: (1) increases in serum rT3 and free T4 and reductions in T3 concentrations during protein supplemented weight reduction may facilitate conservation of visceral protein and reduce muscle protein turnover; and (2) the variation in the magnitude of these changes may account for the heterogeneity of nitrogen economy.

The effects of soy or collagen protein, 1.3 g/kg desirable body weight per day, on fasting and postprandial plasma free amino acid concentrations were evaluated in eight obese men during a 40-day very-low-calorie reducing regimen. The interrelationships among individual plasma amino acids were also examined. In both protein-fed groups, fasting plasma histidine, phenylalanine, tyrosine, threonine and alanine levels decreased by day 40 whereas glycine increased. The decrease in plasma threonine and increase in plasma glycine were more pronounced in the collagen-fed group (n = 4) than in the soy-fed group (n = 4). Serine increased only in the collagen-fed group. The postprandial increases of all essential amino acids, with the exception of valine and phenylalanine, were less on day 26 than on day zero. Except for threonine levels, plasma amino acid profiles were similar during very-low-calorie dieting and during prolonged fasting. However, essential amino acid levels were better maintained by soy than by collagen protein diets.

To investigate further the alterations in pituitary-thyroid function seen during starvation, we have measured basal and TRH-stimulated serum levels of thyrotropin (TSH), prolactin (PRL), growth hormone, thyroxine (T4), triiodothyronine (T3), free T4, free T3, and reverse T3 during prolonged fasting in seven obese men. Fasting was associated with a significant decrease in serum (4, (3, and free T3, while there was an increase in serum reverse T3; these values tended to return toward pre-fast levels as the fast continued beyond 3 weeks. No significant changes were seen in basal serum TSH, PRL, growth hormone, or free T4. Although the TSH response to TRH was diminished during fasting, PRL, T4, and T3 responses were unchanged. In addition to transient alterations in the peripheral metabolism of T4, these findings suggest that alterations in the thyroid hormone binding capacity of serum carrier proteins may occur during fasting. The blunted TSH response to TRH despite reduction of serum T3 concentration suggests that subtle alterations in hypothalamic-pituitary function may also occur.

Twenty-three of 81 intestinal bypass patients with episodes of bypass enteropathy had papulopustular or nodular skin lesions. Histologic examination of the dermal lesions showed various forms of vasculitis in nine of 14 subjects. In six of 11 patients examined by immunofluorescent microscopy, both the lesions and uninvolved sun-exposed skin areas had immunoglobulin and complement deposits in linear or granular patterns in the dermoepidermal line, giving the appearance of a positive lupus band test. Skin lesions resolved with spontaneous improvement of bypass enteropathy or in response to metronidazole therapy. After the bypass was dismantled, the eruptions disappeared permanently, and previously positive lupus band tests became negative. The skin lesions were frequently observed in association with arthritis, suggesting an immune-complex mechanism, probably originating in "blind loop" bacterial overgrowth.

Arginine vasopressin (AVP) and prolactin (PRL) concentrations were measured in the plasma of grossly obese subjects to determine if abnormalities in salt and water homeostasis could be related to these hormones. Acute oral water loads and hypertonic saline infusions were administered during baseline obesity, after prolonged fasting, and after hypocaloric refeeding. Only 64.7%, 46.1%, and 70.1% of a water load was excreted during the respective three stages. Pre-water load plasma AVP levels were normal, but after the water load the obese failed to suppress AVP secretion in a normal fashion; this defect was corrected after fasting and with refeeding. Salt loading resulted in appropriate osmolality and AVP responses. Serum prolactin levels, normal at baseline during all phases, rose slightly after water loading during fasting. Hypertonic.saline produced no changes in prolactin levels in the obese or in the normal controls. In the disordered salt and water metabolism of the obese, persistently high AVP values during water loading appeared to be a factor in the delay of water excretion. In the observed water retentionduring dietary restriction and refeeding, secretion of AVP and PRL did not appear to have a major regulatory function.

Pelvic lipomatosis is a disease of dense infiltration of benign fatty tissue within the confines of the deep bony pelvis. A case is reported of an obese, hypertensive, thirty-nine-year-old black man with the typical clinical and radiographic features of pelvic lipomatosis. Prolonged fasting produced an extensive weight loss and profound resolution of his presenting symptoms, signs, and radiologic abnormalities. Subsequent regain of weight resulted in the reappearance of the disorder, confirming that pelvic lipomatosis may be a disease of accelerated and excessive fat deposition which can be reversed by dietary restriction. The literature pertaining to pelvic lipomatosis is reviewed in detail.

The weights of 207 morbidly obese patients were reduced via prolonged fasting. Half the patients fasted for close to two months, losing a mean of 28.2 kg; one fourth fasted for less than one month; and the other fourth fasted for more than two months, with a mean 41.4-kg loss. This latter group was heavier initially, and more than 50% attained near-normal weight. Patients with onset of obesity in childhood had the lowest tolerance for fasting and the lowest success rate in attaining normal weight. Over a 7.3-year follow-up period in 121 patients, the reduced weight was maintained for the first 12 to 18 months. Subsequently, regain proceeded equally in all groups irrespective of length of fast, extent of weight loss, or age at onset of obesity. Regain to original weight occurred in 50% within two to three years and only seven patients remained at their reduced weights. Regain to greater than original weight was more common in childhood-onset obesity.

A group of 200 morbidly obese men (average weight, 143.5 kg; age, 23 to 70 years) were admitted to a weight control program between 1960 and 1977 and were followed up for a mean period of 7 1/2 years. There was complete follow-up until the termination of the study or until death for 185 men. Fifteen men were followed up for fractional periods. Fifty of the 200 died during the course of the study. Life-table techniques, comparing the mortality among the obese with that among men in the general population, demonstrated a 12-fold excess mortality in the obese in the age group 25 to 34 years and a sixfold excess in the age group 35 to 44 years. This ratio diminished with advancing age. Cardiovascular disease was reported as the cause of death more frequently and malignancies less frequently than they were for men in the US general population.

Morbid obesity, defined arbitrarily as greater than 100 percent excess weight, is only rarely the immediate or sole cause of illness or death. In addition to the Pickwickian syndrome, localized adiposity can cause obstruction and/or organ compression resulting in clinical disorders. Most of the obesity-associated risk factors interact to (a) diminish quality of life, (b) impair health, and (c) shorten survival. Severe obesity in childhood and adolescence impairs scholastic achievement and final educational levels are lower than in the nonobese. For the adult, opportunities and promotions are fewer, the quality of jobs and pay are lower. Unemployment is more common. The obese are more apt to remain single or to lose their marriage partners. Sexual adjustment and reproductive capabilities may be impaired. Regarding morbidity, the obese are "high-cost patients'. The specific and common complications or morbid obesity have been extensively examined and are the major factors causing more severe, more prolonged and more frequently recurring illness. Some obscure risk factors are related to "sudden death', to serious hazards of various medical treatment regimens, and to complication arising out of rapid or repeated regain. Excess mortality has been documented in the morbidly obese to be greatest in the younger age categories while morbidity increases with age in the surviving obese population. The dismal results of non-surgical treatment require an alternative approach. Indications for surgery in a particular patient have to be individualized. Rigid criteria are not practical, but in general, surgery is indicated and justified if the benefits expected from surgical treatment can prevent or reverse the hazards arising from unrelieved obesity. Therefore, the resulting weight losses have to be sufficient to reduce the patients to within 30 or 40 percent of desirable weight. The potential surgical complications must not equal or surpass the hazards of chronic obesity.

Many manifestations following jejunoileal bypass are due to chronic inflammation of the excluded bowel rather than short bowel malabsorption. Diarrhea, abdominal distention, and gas-fluid levels were common diagnostic features of "bypass enteropathy." Exploration showed the bypassed bowel to be dilated, with serosal inflammation and pneumatosis cystoides intestinalis. The bypassed loops contained a fecal flora and the mucosa demonstrated nonspecific chronic inflammatory changes. Exudative protein losses were noted. Systemic complications of bypass enteropathy were similar to other inflammatory diseases of the bowel. Improvement following treatment with metronidazole or after dismantling of the bypass suggested that bacterial byproducts originating in the excluded bowel were causally related.

We have examined complications involving the defunctionalized bowel in 119 intestinal bypass patients. In this group, we found a 66% of incidence of bypass enteropathy. Pneumatosis cystoides intestinalis was present in three patients, severe blood loss in three, localized ulcerations in two, intermittent or chronic intussusception of the proximal jejunal stump in 10, and extensive stenosis relating to tight fibrous adhesions in one patient. The stenosis may become manifest as an obstructive process only after reconstitution of normal bowel continuity. Bacterial overgrowth in the bypassed small bowel was the primary cause for most of the lesions. A consistent diagnostic finding, suggesting disease in the excluded bowel, was ileal distention and the presence of gas-fluid levels on upright abdominal x-rays. Definitive diagnoses of ulceration, intussusception, and/or obstruction were sometimes possible only during laparotomy. Because the bypassed bowel cannot be examined with conventional techniques, these various abnormalities must be suspected when ill-defined abdominal complaints are observed in bypass patients. Metronidazole, to suppress anaerobic organisms, or suitable broad spectrum antibiotics can relieve the various lesions of the inflammatory process, whereas appropriate surgical procedures may be required for some of the chronic or recurrent complications.

The contents of the proximal jejunum and distal ileum were cultured quantitatively in eight patients who were undergoing intestinal bypass procedure for obesity. Five jejunal specimens were sterile, and three contained low counts of a predominantly aerobic flora. Ileal contents yielded variable but usually higher counts than in the jejunum, and there were similar numbers of anaerobes and aerobes. In three patients in whom a bypass was established, contents of the functioning small bowel showed counts of 10(5.0)-10(7.6) colony-forming units/ml. These counts exceeded the counts in the normal terminal ileum, and the flora qualitatively resembled that of feces. Four specimens from excluded loops revealed colonization with fecal organisms, and the counts ranged between 10(6.4) and 10(9.7) colony-forming units/ml. In jejunoileal bypass both the functioning small bowel and the excluded loop become colonized with colonic flora, a phenomenon that may contribute to some of the side effects of this procedure.

In 30 obese men, calcium, magnesium, and phosphate balances were measured for 40 days using one of four weight reducing regimens: 1) 400 kcal soy protein; 2) 400 kcal collagen protein; 3) total fasting with potassium; and 4) total fasting without potassium. Relationship of the minerals to each other and to nitrogen and to the QTc interval was also examined. All groups were in negative cumulative calcium balance but the protein-fed groups lost less calcium (soy, -3.0 +/- 2.1 g; collagen -4.9 +/- 3.2 g) than the total fasting groups (with potassium supplement, -9.2 +/- 3.4 g; without potassium supplement, -5.8 +/- 2.1 g) (p less than 0.01). The soy-fed group attained positive cumulative magnesium (0.7 +/- 0.5 g) and phosphate balances (6.9 +/- 3.9 g). The other three groups had significantly more negative magnesium (p less than 0.0005) and phosphate (p less than 0.0005) balances, (collagen, magnesium balance, -1.1 +/- 1.0 g, and phosphate balance, -7.6 +/- 3.7 g; total fasting without potassium, magnesium balance, -1.4 +/- 0.6 g, and phosphate balance, -5.4 +/- 2.7 g). Potassium supplementation during fasting increased urinary losses of calcium and fecal losses of magnesium. High phosphate intake reduced urinary calcium. Nitrogen losses predicted only magnesium losses. Serum mineral levels did not reflect tissue mineral status. Shortening in the QTc interval as an indicator of reduced myocardial instability was related to the increase in serum phosphate in the protein-fed subjects.

Sixty sudden and unexpected lethal cardiac arrests, with entirely negative findings on autopsy, were reported among 50,314 morbidly obese patients in the care of surgeons performing operations to achieve weight loss. This represented an extrapolated overall annual mortality rate of 65 deaths per 100,000 patients, about 40 times higher than the rate of unexplained cardiac arrests in a matched nonobese population. Eight sudden deaths occurred while waiting for obesity surgery and 22 had cardiac arrest within 10 days after the operation. Late postoperative deaths (more than 4 weeks postoperatively) occurred in 30 instances. A possible marker of a predisposition for sudden, unexpected cardiac arrest was an electrocardiographic abnormality; namely, a Q-Tc interval prolonged to greater than 0.43 seconds. This feature, present in 29 of 38 tracings, denoted increased susceptibility to malignant ventricular arrhythmias. The perioperative clustering of arrests implicated nonspecific stresses incident to otherwise uneventful operations as triggers of lethal dysrhythmias in the absence of organic cardiac disease. Anoxemia after abdominal surgery is an added hazard. Length of postoperative survival among the late deaths was found to be unrelated to degree of initial obesity or to magnitude of weight loss. Patients who died in the late postoperative phase were still grossly obese (mean weight 114.2 kg). Cardiac weights in patients who died within 10 postoperative days (12 patients) or after an average of 103 days (20 patients) were the same (464 and 469 g, respectively), indicating that myocardial mass had remained intact. The data do not suggest nutritional depletion or lean tissue loss as plausible explanations for the cardiac arrests. Screening and postoperative monitoring for Q-T interval prolongation is indicated. Prophylactic beta-blockade in this vulnerable subset of the morbidly obese population may be instituted in anticipation of obesity surgery. The attendant physiologic stresses should be minimized by appropriate measures.

The microbial flora in the bypassed biliopancreatic intestinal segment was studied after obesity surgery. This procedure causes less diarrhea than jejunoileal bypass and appears to avoid extraintestinal complications. This report concerns type and quantity of bacteria colonizing the biliopancreatic segment and changes occurring after oral metronidazole treatment. Twelve specimens were aspirated in 10 patients via catheter inserted percutaneously during surgery. The specimens were plated immediately on selective and nonselective media under aerobic and anaerobic conditions. Essentially equal numbers of aerobes and anaerobes were recovered from the biliopancreatic segment with average counts of 10(4) cfu/mL and median counts of 10(5) cfu/mL. Four patients had counts of 10(7) cfu/mL. The most common aerobes were E. coli, Klebsiella, Gram-positive cocci, and Candida; among anaerobes, Clostridium and the Bacteroides fragilis group were most common. In three patients treated with metronidazole because of diarrhea, anaerobes were eliminated and diarrhea cleared.

The ability to conserve body protein during very low calorie diets in ten obese men was observed to correlate with plasma free amino acid concentrations, urinary N tau-methylhistidine: creatinine ratios, resting oxygen consumption, and serum triiodothyronine levels. A diet consisting of only protein, 1.3 g/kg ideal body weight/24 h, was given for 40 days. Cumulative nitrogen deficit ranged from -64 g to -227 g. Nitrogen balance on days 36 to 40 ranged from + 1.37 g/24 h to -3.30 g/24h. Nitrogen balance during this period had a significant direct correlation with pre-diet concentrations of branched-chain amino acids (r = 0.69 to 0.89), methionine (r = 0.85), histidine (r = 0.66), alanine (r = 0.73), arginine (r = 0.70), ornithine (r = 0.66), total essential (r = 0.87, and nonessential (r = 0.68) amino acids, with initial serum levels of triiodothyronine (r = 0.66) and with the fall in triiodothyronine over the 40 days (r = 0.79). Initial resting oxygen consumption was directly correlated (r = 0.78) with final nitrogen balance and inversely with total nitrogen loss (r = -0.81). On day 0, triiodothyronine levels also correlated positively (r ranging from 0.71 to 0.93) with plasma concentrations of several essential and nonessential amino acids. These correlations suggest that individuals who ultimately will or will not achieve nitrogen equilibrium during very low calorie diets can be identified prior to dieting. These data are consistent with the hypothesis that individuals with higher initial protein flux and triiodothyronine levels are better able to adjust the balance between synthesis and degradation to attain nitrogen equilibrium during hypocaloric dieting.