Edwin J. Zarling

Evidence for increased lipid peroxidation in multiple sclerosis.

Pentane and ethane are degradation products of unsaturated fatty acids which are released during lipid peroxidation. In order to assess whether multiple sclerosis is associated with lipid peroxidation, we measured pentane and ethane excretion by 16 patients with multiple sclerosis and compared them to healthy control subjects. Patients with acute exacerbation of multiple sclerosis had significantly higher concentrations of pentane (10.5±4.2 nmol/l)(p<0.01) compared to either patients in remission (4.5±1.7 nmol/l) or control subjects (4.9±1.1 nmol/l). The concentrations of ethane were not significantly different among these groups. Of the patients with acute exacerbation who later achieved remission, the pentane excretion also returned to normal (5.6±0.9 nmol/l). One patient who failed to reachieve clinical remission continued to excrete large amounts of pentane. We conclude that oxygen free radical activity is enhanced during exacerbation multiple sclerosis.

Elevated breath pentane in heart failure reduced by free radical scavenger

UNLABELLED Pentane, a product of lipid peroxidation, has been detected in situations involving ischemic injury. Such injury may be limited if lipid peroxidation can be controlled by antioxidants. The role of lipid peroxidation in chronic heart failure (CHF) was assessed by measuring breath pentane in patients with CHF vs. age matched controls. The effect of a free radical scavenger on pentane released during CHF was also measured. Pentane levels were correlated with the daily dose of captopril, a sulfhydril-containing drug used to treat CHF, which is an angiotensin converting enzyme inhibitor. To separate the scavenging effects of captopril from the pharmacologic effects of converting enzyme inhibitors, a crossover study using a nonsulfhydril inhibitor was used. Patients with CHF excreted (p < 0.005) high concentrations of pentane (5.7 +/- 2.1 vs. control 3.6 +/- 1.2 nmol/l). Patients treated with captopril also had significantly higher (p < 0.05) excretion of pentane than the control patients (4.7 +/- 1.3 vs. 3.6 +/- 1.2 nmol/l). The dose of captopril was inversely proportional to the concentration of pentane excreted (r = 0.55, p < 0.05). Pentane excretion during captopril therapy was significantly lower before (p < 0.01) and after (p < 0.02) nonsulfhydril inhibitor therapy. CONCLUSION breath pentane is elevated in CHF and it can be reduced by a free radical scavenger. This reduction of pentane excretion is not a converting enzyme inhibitor class effect.

High breath pentane concentrations during acute myocardial infarction

To investigate whether reperfusion after myocardial ischaemia leads to free-radical-mediated peroxidation of membrane lipids and cell damage, we measured pentane, a product of lipid peroxidation, in the breath of 10 healthy control subjects and in 20 consecutive patients with suspected acute myocardial infarction. 10 of these patients showed no myocardial damage on electrocardiography (patient control group) and 10 satisfied standard diagnostic criteria for acute myocardial infarction. The three groups were well matched for age, sex, underlying disease, and smoking habits. The time from onset of chest pain to breath collection was similar in the patient control and acute myocardial infarction groups. The breath pentane concentration was higher (p less than 0.0001) in the acute myocardial infarction group (4.96 [1.15] nmol/l) than in the patient control (1.96 [1.04] nmol/l) and healthy control groups (1.71 [0.87] nmol/l). Lipid peroxidation during acute myocardial infarction reflects action of oxygen radicals and their potential for contribution to the pathogenesis of tissue damage.

Immunohistochemical evaluation of bcl-2 gene family expression in liver of hepatitis C and cirrhotic patients: a novel mechanism to explain the high incidence of hepatocarcinoma in cirrhotics

Objective: The purpose of this study was to determine whether there is an increase in expression of bcl-2 and related bcl-2 gene family members bcl-X and bax in liver biopsy samples obtained from patients with either hepatitis C infection or cirrhosis. Bcl-2, bcl-X, and bax, as well as other bcl-2–related proteins, function coordinately through homo- and heterodimerization to regulate apoptosis. Bcl-2, which is characterized as an antiapoptotic, also functions as an antioxidant. We hypothesized that a mechanism that could account for increased hepatocellular carcinoma in patients with hepatitis C and cirrhosis is selection of bcl-2 expressing cells. This selection would be due to the capacity of individual cells to resist the toxic effects of inflammatory byproducts, specifically reactive oxygen species. Methods: Sections cut from archived liver biopsy samples embedded in paraffin were probed with antibody specific for bcl-2, bcl-X, or bax. Liver samples were from normal (N = 5), hepatitis C patients (N = 19), and cirrhotics (N = 10). Percent positive staining and intensity of staining were judged independently for hepatocytes, bile ducts, mononuclear cells, and Kupffer cells. Results: Bcl-2 expression was evident in bile ducts and mononuclear cells of hepatitis C patients, but was not commonly present in hepatocytes (two of 10). In the cirrhotic liver, bcl-2 expression was also detected in bile ducts and mononuclear cells, but in contrast to hepatitis patients was also expressed in hepatocytes (nine of 10). A similar pattern of expression was evident for bcl-X, but in general the level of expression was limited relative to that of bcl-2. Bax expression was infrequently present in sections from any of the three patient groups. Conclusions: The data indicate that bcl-2 expression is elevated in the liver of cirrhotics, but is not evident in the liver of hepatitis C patients. This increase in expression of bcl-2 in cirrhotic patients may correlate with development of hepatocellular carcinoma given the anti–apoptotic/oncogenic potential of bcl-2.

Impact of American College of Surgeons verification on trauma outcomes

OBJECTIVE The purpose of this study was to compare the impact of trauma patient outcomes before and after Level II American College of Surgeons (ACS) verification was received in a not-for-profit community hospital. METHODS This was a retrospective analysis of hospital discharge data for timeframes before and after Level II ACS verification was conducted. Originally, 8,674 patients were identified using the International Classification of Diseases, 9th Revision codes for trauma. These data were parsed to 7,811 patients by using International Classification of Diseases, 9th Revision codes 800 xx through 959.9 x, which signify an admitting diagnosis of trauma; 3,835 of the patients were admitted after the July 28, 1998, verification date. Blunt injuries constituted the vast majority of the patients (n = 7,488). Outcome measures studied included changes in length of stay (LOS), mortality, and total cost. Internal control was coronary artery bypass graft patients at the same hospital, and external control was trauma patients at a non-ACS hospital over the same time period. Data are presented with p values and SE and the ratio of observed/expected values on the basis of the all-payer severity-adjusted diagnosis-related group severity model. RESULTS The two timeframes exhibited statistically different outcomes in several variables. Adjusting for severity postverification, LOS was 10% less (p < 0.000). Similarly, severity-adjusted mortality observed/expected ratios were significantly different: 0.81 before versus 0.59 after (p < 0.000). The severity-adjusted ratio of costs found that the postverification era was 5% lower (p < 0.000). The contribution margin of the trauma patient population to the hospital well exceeded any postverification costs. Both control groups exhibited no significant changes in their severity-adjusted outcomes, which could have invalidated these results. CONCLUSION This study suggests that the efforts and resources consumed achieving ACS Level II trauma center verification appear to result in desired outcomes as evidenced by decreased LOS, reduced in-hospital mortality rates, reduced cost, and improved contribution margins.

Pulmonary pentane excretion increases with age in healthy subjects

Excessive lipid peroxidation occurs in various diseases. However, even in health low levels of lipid peroxidation can be detected by measuring the pulmonary excretion of pentane. Lipid peroxidation has been postulated to be one of the causes of the ageing process. In order to test whether pentane excretion is related to age, we measured breath pentane in 47 healthy subjects (ages 21-79). We also measured serum levels of the antioxidants tocopherol, retinol, lycopene, beta carotene, ascorbate and zinc. We found that pentane excretion significantly (P < 0.05, r = 0.32) increased with age. Of the six antioxidants measured, only lycopene decreased significantly (P < 0.05, r = -0.47) with age, however, this decline did not statistically correlate with pentane excretion. The remaining five antioxidants either remained stable or increased over the age range studied. We conclude that lipid peroxidation, as assessed by pentane excretion, increases with advancing age but that this increase is independent of dietary antioxidant levels.

Effect of Enteral Formula Infusion Rate, Osmolality, and Chemical Composition upon Clinical Tolerance and Carbohydrate Absorption in Normal Subjects

It is a common clinical practice to initiate enteral hyperalimentation using low flow rates or diluted formula. These adjustments are made in an effort to minimize patient intolerance. Using complex and elemental enteral formulas, we investigated whether various flow rates or osmolalities effected clinical intolerance or carbohydrate malabsorption in 20 healthy volunteers. Our infusion rates ranged between 50 and 150 kcal/hr and the osmolalities ranged between 325 and 690 mOsm/Kg of water. Even at the maximal flow rate and osmolality, our results show that both types of enteral formulas were well tolerated as assessed by the frequency of abdominal pain, bloating, passage of rectal gas and stooling. No carbohydrate malabsorption was detected as measured by breath hydrogen. In well nourished subjects, our findings do not support the common clinical practice of initiating alimentation with low flow rates or diluted formula.

Beneficial effect of a bile acid resin binder on enteral feeding induced diarrhea

Objectives:Diarrhea is a complication of enteral feeding, occurring in up to 68% of critically ill patients. We hypothesized that prolonged fasting results in abnormal bile acid homeostasis. Subsequent enteral feeding then causes a relative luminal excess of bile acids, which leads to choleretic diarrhea. Hence, diarrhea induced by enteral feeding should improve with the use of a bile acid binding agent, such as Colestid Granules.Methods:We evaluated the effect of Colestid on enteral feeding-induced diarrhea in a double-blind placebo-controlled study. Nineteen patients who were nil per os (NPO) for 5 days before initiation of enteral feeding were enrolled in the study and treatment continued for 7 days. The severity and frequency of diarrhea were quantified. Fecal bile acids were measured enzymatically. Stool nutrient loss was measured by fat extraction, microkjeldahl determination of nitrogen, and bomb calorimetry of dried fecal specimens.Results:Enteral feeding resulted in a high frequency of diarrhea (95%) at some time during the observation period. The majority of episodes of diarrhea in both groups were of low volume. Colestid significantly decreased the prevalence and severity of diarrhea. Colestid had no significant effect on fecal calorie or nutrient losses. The average bile acid concentration in the stool increased significantly after enteral feeding.Conclusion:Enteral feeding-induced diarrhea is, at least in part, due to malabsorption of bile acids. The bile acid resin binding agent Colestid improves diarrhea induced by enteral feeding.

Inflammatory pseudotumor of the liver: Appearance on MRI

Inflammatory pseudotumor of the liver is a rare entity; fewer than 50 cases have been reported in the world literature. Its appearance on both computerized tomography (CT) and ultrasound have been previously described. To our knowledge, this is the first report of its appearance on magnetic resonance imaging (MRI). The lesion demonstrated increased signal intensity on T-1 and T-2 spin-echo and inversion recovery (STIR) sequences in relationship to normal liver. The signal characteristics, however, were nonspecific and diagnosis required biopsy confirmation. There was spontaneous resolution with conservative management, and this was documented on follow-up CT and MRI.

β‐Carotene decreases markers of lipid peroxidation in healthy volunteers

We previously showed that daily intake of beta-carotene, a nontoxic antioxidant, reduces lipid peroxidation as assessed by serum lipid peroxide levels. An alternative method to detect lipid peroxidation is the measurement of pentane in breath. Pentane is a five-carbon hydrocarbon that is released when an omega-6 unsaturated fatty acid undergoes peroxidation. The aim of this study was to see whether graded doses of beta-carotene would affect breath pentane excretion in normal subjects placed on a carotenoid-free liquid diet for two weeks. The subjects were then repleted with either 15 (n = 7) or 120 mg (n = 8) of beta-carotene daily for four weeks while continuing the same diet. Serum beta-carotene and breath pentane were measured before and after beta-carotene refeeding. Lipid peroxidation, as assessed by gas-chromatographic measurement of breath pentane, was significantly (p < 0.05) reduced by daily supplements of 120 mg beta-carotene (from 3.7 +/- 0.9 to 2.2 +/- 1.4 nmol/l). However, the decline in pentane exhalation observed with the 15-mg beta-carotene dose did not achieve statistical significance (p = 0.13).