Reversal of severe fatty hepatic infiltration after intestinal bypass for morbid obesity by calorie-free amino acid infusion

Hepatic fatty infiltration complicating jejunoileal bypass can be massive and may require restoration of gastrointestinal continuity. This fatty infiltration appears to be caused by protein depletion associated with adequate or high carbohydrate intake. The present study has shown that calorie-free amino acid alimentation can reverse these changes. In three of thirteen patients who underwent 12 inch to 6 inch jejunoileal bypass procedures, symptomatic hepatomegaly developed with near total replacement of hepatocytes by massive fatty infiltration. After undergoing liver scan, liver biopsy, and liver function tests, the patients were started on a peripheral infusion of 2 L per day of a 4.25 per cent crystalline amino acid solution, allowing for fat mobilization while preserving body protein stores. All oral intake was withheld except for water. At the end of a fourteen to twenty-one day infusion period, serum albumin levels increased by 1 gm in all patients. Decreases in liver volume of 83, 45, and 40 per cent occurred. During the infusion period ketonuria was 4+ in all patients indicating active lipolysis. Weight loss was impressive (17, 19, and 40 pounds). All patients showed marked symptomatic improvement, and postinfusion liver biopsy specimens showed a return to near normal architecture. Maintenance of normal liver size by a high-protein, low-carbohydrate diet was observed in a five to seven month follow-up period. In contrast to previous studies using standard hyperalimentation solutions, the use of calorie-free amino acid solutions reverses the hepatic fatty infiltration seen after intestinal bypass by mobilization of fat. This fat mobilization does not occur as readily in the presence of large amounts of glucose.     

The prediction of maximal oxygen consumption from a continuous exercise treadmill protocol

This study investigated the hypothesis than an individual's maximal oxygen consumption can be realistically predicted by the maximal time achieved in the Balke treadmill protocol. The oxygen consumption in the final minute of exercise of 1,025 normal men who performed a maximal effort in the Balke protocol were linearly regressed on their maximal treadmill time using a least-squares fit technique. In addition, the men were grouped by heart rate response, and regression equations plus (0.95, 0.95) tolerance limits were computed for each subgroup. A regression equation was also computed for an additional 127 men who had multiple bags of expired air collected approaching maximal effort. It was demonstrated that the tolerance limits are so wide that maximal oxygen consumption can be only grossly estimated by treadmill time. Thus, other factors than maximal oxygen consumption must be operating in determining treadmill performance.     

Reversion by vitamin K of aflatoxin B1 (AFB)-induced inhibition of oxygen uptake in three AFB-susceptible bacteria

The effect of Vitamin K, on the inhibition of oxygen uptake in Bacillus brevis (2611), Bacillus megaterium (1368) and Flavobacterium aurantiacum by aflatoxin B₁ (AFB) has been investigated.At 1.5 mM, vitamin K completely reversed oxygen inhibition by 10 $\text{μg}\text{ml}$ AFB in the three bacteria and by 50 $\text{μg}\text{ml}$ APB in B. brevis, the most susceptible of the three bacteria to AFB. Vitamin K did not reverse the inhibitory effect of 100 $\text{μg}\text{ml}$ AFB in any of the three bacteria except B. megaterium, neither did 1.5 mM 2,4-dinitrophenol (DNP) reverse the inhibition at 10 $\text{μg}\text{ml}$ and 100 $\text{μg}\text{ml}$ levels of AFB in any of the three bacteria.     

Interspecies variability in propylene glycol dinitrate-induced methemoglobin formation

Interspecies variability of propylene glycol dinitrate (PGDN)-induced methemoglobin formation was studied in vitro employing erythrocytes from four separate species. The net rate of methemoglobin formation was significantly different among species with dog greater than guinea pig greater than rat greater than or equal to human. This order of susceptibility was maintained in stroma-free hemolysates, indicating that interspecies variability was not a reflection of differences in red cell membrane permeability or intracellular transport of PGDN. The erythrocytic enzymes, catalase, superoxide dismutase, glutathione peroxidase, 6-phosphogluconate dehydrogenase, glucose-6-phosphate dehydrogenase, methemoglobin reductase, and glutathione-S-transferase, were assayed by adaptation of existing methods to a centrifugal analyzer. The above enzymes were removed from hemoglobin derived from each species and the order of susceptibility to PGDN-induced methemoglobin formation remained essentially the same with dog greater than guinea pig greater than human = rat. However, the net rate of PGDN-mediated oxidation of hemoglobin to methemoglobin increased in purified hemoglobin preparations from each species. These results demonstrate that there is species variability in the net rate of PGDN-mediated methemoglobin formation. Total enzyme activity in erythrocytes may contribute to reduction in the net rate of methemoglobin formation. However, the primary determinant of the net rate of methemoglobin formation induced by PGDN appears to be the structure of each hemoglobin molecule.     

Selective impairment of drug-metabolizing enzymes in pig liver during subchronic dietary exposure to aflatoxin B1.

Consequences of subchronic exposure to aflatoxin B1 (AFB1) on liver monooxygenase and transferase enzymes were compared in control pigs and pigs given 385, 867 or 1,807 microg AFB1/kg of feed for 4 weeks. Animals exposed to the highest dose of toxin developed clinical signs of aflatoxicosis, like liver fibrosis, hepatic dysfunction and decreased weight gain. This group had significantly lower levels of liver cytochrome P450, ethoxyresorufin O-deethylase (EROD) activity, testosterone metabolism, P450 1A and P450 3A protein expression. By comparison, mild degenerative hepatic changes, no hepatic dysfunction but a similar pattern of liver P450 enzymes activity without changes in P450 3A expression were observed in pigs exposed to 867 microg AFB1/kg of feed. Benzphetamine and aminopyrine N-demethylase activities were increased in pigs exposed to 867 or 1,807microg AFB1/kg of feed. Pigs exposed to 385 microg AFB1/kg of feed had low levels of EROD activity and all other biotransformation and clinical parameters remained at control levels. Aniline hydroxylase activity, P450 2C protein expression, UDP-glucuronosyl and glutathione S-transferase activities were unaffected at all doses of AFB1. In conclusion, P450 1A and P450 3A appear to be specific targets of AFB1 even if pig did not display clinical sign of liver toxicosis.     

Risk of lung cancer in patients with preinvasive bronchial lesions followed by autofluorescence bronchoscopy and chest computed tomography

Objectives

To assess risk of lung cancer (LC) in patients with preinvasive bronchial lesions and to identify factors associated with higher risk.

Methods

124 patients with one or more preinvasive bronchial lesions and normal chest computed tomography (CT) (mean age 66.7 years, 121 males and 3 females), followed-up by white light and autofluorescence bronchoscopy (AFB) every 4-6 mo and chest CT every 6-12 mo, end points were development of carcinoma in situ (CIS) or LC.

Results

Among 124 patients with 240 preinvasive bronchial lesions, 20 CIS or LC lesions were detected during follow-up in 20 (16%) patients, 7 were detected as new endobronchial lesions, 10 as new peripheral lesions and 3 as local progression from severe dysplasia to CIS. Median time to progression from the same site or development of CIS/LC elsewhere was 24 months (range: 6-54 mo). The Cumulative risk of development of CIS/LC was 7% at one year, 20% at three years and 44% at 5 years. Among detected lung cancers, 80% were stage 0 or stage I and underwent treatment with curative intent. Diagnosis of new SD during follow-up (p = 0.0001), chronic obstructive pulmonary disease (COPD) (p = 0.001) or smoking index >52 pack-year (p = 0.042) was associated with higher risk. Even after controlling for other risk factors, COPD was associated with risk for lung cancer. Baseline lesion grade was not predictive of patient outcome (p = 0.146).

Conclusion

Patients with preinvasive bronchial lesions, especially those with new SD during follow-up, COPD or smoking >52 pack-year are at high risk of LC, AFB and CT follow-up facilitated early detection and treatment with curative intent.