Edward P. Norkus

Propofol versus midazolam and meperidine for conscious sedation in GI endoscopy

OBJECTIVE:Propofol (2,6-diisopropyl phenol) is a relatively new intravenous sedative hypnotic with an ideal pharmacokinetic profile for conscious sedation. In this study, we compared the safety and efficacy of propofol versus the conventional regimen of midazolam and meperidine for conscious sedation in GI endoscopy.METHODS:In this prospective study, 274 patients that included many elderly patients with multiple comorbid conditions underwent GI endoscopic procedures at our hospital. A total of 150 patients received propofol (20–120 mg) and fentanyl (0.25–1.5 mg). The control group of 124 patients was given midazolam (2–6 mg) and meperidine (25–75 mg). The dose of medication was titrated according to patient need and the duration of the procedure. A “comfort score” on a scale of 1–4 assessed the efficacy of the drugs based on pain or discomfort to the patient and ease of endoscopy. A “sedation score” was used to assess the degree of sedation on a scale of 1–5. The Aldrete score was used to measure recovery from anesthesia at 5 and 10 min after the procedure.RESULTS:After controlling for age, American Society of Anesthesiologists’ Physical Status Classification (ASA grade), and type and duration of procedure, logistic regression analysis determined that propofol resulted in 2.04 times better patient comfort (p = 0.033, 95% CI = 1.058–3.923). Propofol was 1.84 times more likely to produce deeper sedation than the regimen of midazolam and meperidine (p = 0.027, 95% CI = 1.071–3.083). The recovery from sedation was faster in patients receiving propofol, although this did not reach statistical significance. The safety parameters between the two groups were comparable.CONCLUSION:Propofol was associated with a statistically significant improvement in comfort and sedation score when compared to midazolam and meperidine.

β-Carotene inhibits the oxidative modification of low-density lipoprotein

Several lines of evidence indicate that oxidized LDL (Ox-LDL) may promote atherogenesis. Hence, the role of antioxidants in the prevention of LDL oxidation needs to be determined. β-Carotene, in addition to being an efficient quencher of singlet oxygen, can also function as a radical-trapping antioxidant. Since previous studies have failed to show that β-carotene inhibits LDL oxidation, we re-examined its effect on the oxidative modification of LDL. For these studies, LDL was oxidized in both a cell-free (2.5 μM Cu 2+ in PBS) and a cellular system (human monocyte macrophages in Hams F-10 medium). β-Carotene inhibited the oxidative modification of LDL in both systems as evidenced by a decrease in the lipid peroxide content (thiobarbituric-acid-reacting substances activity), the negative charge of LDL (electrophoretic mobility) and the formation of conjugated dienes. By inhibiting LDL oxidation, β-carotene substantially decreased its degradation by macrophages. β-Carotene (2 μM) was more potent than α-tocopherol (40 μM) in inhibiting LDL oxidation. Thus, β-carotene, like ascorbate and α-tocopherol, inhibits LDL oxidation and might have an important role in the prevention of atherosclerosis.

Serum and liver micronutrient antioxidants and serum oxidative stress in patients with chronic hepatitis C

OBJECTIVES:The exact pathogenesis of liver injury and fibrosis in chronic hepatitis C (CHC) is unclear. Free radicals play a role in CHC liver damage. Antioxidants (AO) (enzymatic and nonenzymatic) scavenge free radicals and prevent tissue injury. The aims of our study were to estimate serum levels of malondialdehyde (MDA), serum and liver levels of nonenzymatic fat-soluble AO, and to correlate the liver AO levels with the degree of inflammation and fibrosis on biopsy.METHODS:AO levels were estimated by high-pressure liquid chromatography in the pretreatment serum and liver biopsy specimen of 20 treatment-naïve patients with CHC who were not on vitamin supplements. Serum levels of MDA were measured as a marker of increased oxidative stress. Twenty-two healthy individuals with no history of vitamin supplementation served as controls. AO analyzed were: retinol, α- and γ-tocopherol, lutein, β-cryptoxanthin, lycopene, and α- and β-carotene.RESULTS:Twenty CHC patients (11 men, nine women, mean age 48.5 ± 7.9 yr) were studied. Patients and controls were comparable in age and sex. Serum MDA levels were significantly higher in CHC patients compared with controls (1.62 ± 0.57 vs 0.23 ± 0.15 μmol/L, p = < 0.0000). Serum levels of all AO except lutein were significantly decreased in CHC patients, and their levels were two to ten times lower than serum levels in controls. Liver levels of α-carotene (p = 0.0004), β-carotene (p = 0.006), and lutein (p = 0.002) correlated with the serum levels, whereas the levels of retinol, α-tocopherol, lycopene, and β-cryptoxanthin showed no correlation. Serum MDA levels were significantly higher in patients with moderate-to-severe inflammation or fibrosis compared with those with mild inflammation or fibrosis. The levels of all liver AO except α-carotene were significantly lower in patients with moderate-to-severe fibrosis. The severity of inflammation (portal or lobular) did not affect liver AO levels.CONCLUSIONS:Our findings suggest that increased oxidative stress is present in patients with CHC. Micronutrient AO are severely depleted in serum and liver tissue of patients with CHC, and liver levels of some AO appear to reflect serum levels. Increasing fibrosis is associated with decreased liver AO levels indicating that severe disease may be a consequence of AO depletion or decreased liver storage resulting from fibrosis.

Serum concentrations of α tocopherol, β carotene, and retinol preceding the diagnosis of rheumatoid arthritis and systemic lupus erythematosus

OBJECTIVES Because oxidative damage has been implicated in the pathogenesis of rheumatoid arthritis and systemic lupus erythematosus, this study was designed to see if serum concentrations of α tocopherol, β carotene, and retinol, substances believed to be involved in the prevention or repair of oxidative damage, might be lower among persons who develop rheumatoid arthritis or systemic lupus erythematosus than among those who do not. METHODS For this prospective case-control study, persons with rheumatoid arthritis and systemic lupus erythematosus that developed two to 15 years after donating blood for a serum bank in 1974 were designated as cases. For each case, four controls were selected from the serum bank donors, matched for race, sex, and age. Stored serum samples from cases and controls were assayed for α tocopherol, β carotene, and retinol. RESULTS Cases of both diseases had lower serum concentrations of α tocopherol, β carotene, and retinol in 1974 than their matched controls. For rheumatoid arthritis, the difference for β carotene (−29%) was statistically significant. CONCLUSIONS These findings support those of a previous study that low antioxidant status is a risk factor for rheumatoid arthritis. They suggest a similar association for systemic lupus erythematosus.

Nonspecific hyperamylasemia and hyperlipasemia in diabetic ketoacidosis: incidence and correlation with biochemical abnormalities

OBJECTIVES:Amylase and lipase estimations are the standard tests to diagnose acute pancreatitis (AP). Elevation of amylase and lipase ≤3 times normal may be nonspecific, but elevation of either one >3 times normal is reported to be diagnostic of AP. The aim of this study was to evaluate the incidence and magnitude of nonspecific elevations of amylase and lipase in diabetic ketoacidosis (DKA) and to correlate their elevation with known metabolic derangements of DKA.METHODS:A total of 150 consecutive episodes of DKA in 135 patients were evaluated for serum amylase, lipase, and biochemical markers of DKA on admission and 24 h later. Patients were divided according to the following: 1) Clearly nonspecific amylase elevation (CNSA): Amylase elevation < 3 times normal plus normal or < 3 times lipase; 2) Clearly nonspecific lipase elevation (CNSL): Lipase elevation < 3 times normal plus normal or <3 times amylase; and 3) Probably nonspecific amylase or lipase elevation (PNSA or PNSL): >3 times elevation of amylase or lipase or both with normal abdominal CT.RESULTS:Elevated amylase and lipase levels ranged from 111 to 1257 IU/L (normal 30–110 IU/L) and 25–529 IU/dl (normal < 24 IU/dl) (CT-proven AP = 16, excluded). Nonspecific amylase elevation (CNSA + PNSA) = 25 (16.6%) cases, CNSA in 10 (6.6% of all DKA or 27% of amylase elevations), and PNSA in 15 (10% of all DKA or 41% of amylase elevations). Nonspecific lipase elevation (CNSL + PNSL) = 36 (24%), CNSL in 23 (15.3% of all DKA or 47% of all lipase elevations), and PNSL in 13 (8.7% of all DKA or 26.5% of all lipase elevations). Multiple regression analyses showed significant correlation of pH and serum osmolality with amylase elevation. Lipase elevation showed positive correlation with serum osmolality alone.CONCLUSIONS:In DKA nonspecific elevations of amylase and lipase occur in 16–25% of cases. Amylase elevation is correlated with pH and serum osmolality, but lipase elevation is correlated with serum osmolality alone. Diagnosis of AP based soley on elevated amylase or lipase, even > 3 times normal, is not justifiable.

Ascorbic Acid Status and Subsequent Diastolic and Systolic Blood Pressure

Free radicals and oxidation are involved in several aspects of blood pressure physiology. We investigated the relationship between blood pressure and antioxidants, including plasma ascorbic acid (AscA), in a 17-week controlled-diet study. Study subjects included 68 men aged 30 to 59 years who had a mean diastolic blood pressure of 73.4 mm Hg and a mean systolic blood pressure of 122.2 mm Hg. One month of vitamin C depletion was followed by 1-month repletion with 117 mg/d, repeated twice. All food and drink were provided in the study. Subjects did not smoke or drink alcohol, all consumed fruits and vegetables, and body weight was maintained. Plasma was assayed periodically for AscA, &agr;-tocopherol, carotenoids, and lipids. Plasma AscA was inversely related to diastolic blood pressure 1 month later (correlation −0.48, P <0.0001). Persons in the bottom fourth of the plasma AscA distribution had >7 mm Hg higher diastolic blood pressure than did those in the top fourth of the plasma AscA distribution. Multivariate analysis with control for age, body mass index, other plasma antioxidants, and dietary energy, calcium, fiber, sodium, and potassium did not reduce the plasma AscA effect. One fourth of the variance in diastolic blood pressure was accounted for by plasma AscA alone. Plasma AscA was also significantly associated with systolic blood pressure in logistic regression. Vitamin C may be an important component of the effectiveness of fruits and vegetables in the reduction in blood pressure, and tissue AscA levels may be important in the maintenance of low blood pressure. Long-term intervention studies are warranted.

Mild Anemia and the Risk of Falls in Older Adults From Nursing Homes and the Community

OBJECTIVES The objectives of this study were to determine if a relationship exists between a history of falls and anemia in older adults and to compare the findings by place of residence. DESIGN The authors conducted a retrospective and observational study. PARTICIPANTS One hundred forty-five adults (60-97 years of age) from nursing homes and the community hospitalized for hip fracture over a 2-year period were included in this study. MEASUREMENTS Laboratory values (hemoglobin [Hb], hematocrit [Hct]), medical history, and demographics were measured. RESULTS Falls occurred similarly in both nursing home patients and community patients (19% vs. 17%, P=0.785). Nursing home and community patients also had similar Hb (P=0.0899), Hct (P=0.1929), and rates of anemia (P=0.187). Nursing home residents were older (P=0.0188) and had lower serum albumin levels (P=0.0007) than community patients. When the two groups were combined, falls were more common in anemic individuals (30% vs. 13%; P=0.028). Furthermore, those with a history of falls were older (P=0.0447), had lower Hb (P=0.0257) and Hct levels (P=0.0310). After controlling for age, gender, place of residence, and arthritis in a logistic regression model, anemia predicted a threefold increased risk of falls (P=0.041), and a 45% decreased risk of falls was predicted for every 1.0-g/dL increase in Hb (P=0.005). Falls risk increased 7% per year of age (P=0.040), whereas musculoskeletal disease increased the falls risk 3.2-fold, both increases being independent of Hb levels or anemia. Finally, falls were not associated with gender or other comorbidity, nor did these variables alter the falls risk attributed to low Hb or anemia. CONCLUSIONS These findings suggest a new and potentially important link between anemia and the risk of falls in patients sustaining hip fractures from both nursing homes and the community. Further studies will help determine if this risk is modified or eliminated with treatment of anemia and if the relationship applies to larger samples of older adults in different settings.

Intraindividual variability of plasma antioxidants, markers of oxidative stress, C-reactive protein, cotinine, and other biomarkers

Background: Within-person variability in biomarkers results in random error that can attenuate estimates of association. Little information on such variability is available for a number of nutrition-related biomarkers. Methods: Blood samples obtained 2 to 4 weeks apart were analyzed for tocopherols, carotenoids, ascorbate, lipids, cotinine, C-reactive protein, and oxidative stress. Subjects (n = 206 men and women, mean age 45.4 years) were either smokers or passively exposed to smoke. We calculated intraindividual and interindividual variability and the number of measurements required to reduce attenuation. Results: For most biomarkers, 2 measurements would be required to limit the attenuation of correlation coefficients to no lower than 90% of the true correlation. If only one measurement were obtained, observed correlations would be approximately 80–88% of true correlations. For regression coefficients, 3 or 4 measures would be required. Exceptions were ascorbic acid and malondialdehyde, for which a single measure resulted in little attenuation. Conclusions: For most serum markers, collection of 2 or more measurements per person is desirable to increase the ability to detect associations between biomarkers and health-related variables. If only one measure is possible, sample sizes should be planned to permit detection of associations that are likely to be observed, not the theoretical true associations. The results of this study, in which measurements were obtained 2 to 4 weeks apart, are relevant for epidemiologic research in which the exposure of interest is the subject’s baseline or current status. It is likely that within-person variability would be greater over a period of months or years.

Dietary intake and blood levels of lycopene: association with cervical dysplasia among non-Hispanic, black women.

We examined whether elevated levels of retinoids, carotenoids, folate, and vitamin E protected against cervical dysplasia among non-Hispanic, black women. We enrolled 32 women with incident cervical dysplasia, including cervical intraepithelial neoplasia (CIN) I, CIN II, and CIN III/carcinoma in situ, and 113 control women with normal cervical cytology in case-control study. Micronutrient levels were estimated from a food-frequency questionnaire (FFQ) and measured from blood samples. Information on risk factors for cervical neoplasia was elicited by interview. Hybrid capture was used to determine infection with human papillomavirus. After adjustment for potential confounders, analysis of micronutrient levels estimated from the FFQ suggested that women in the upper tertile of lycopene and vitamin A intake were one-third (odds ratio = 0.32, 95% confidence interval = 0.8-1.3) and one-fourth (odds ratio = 0.24, 95% confidence interval = 0.05-1.2) as likely, respectively, to have dysplasia as women in the lower tertile. Borderline protective trends (p < or = 0.10) were apparent. Elevated levels of serum lycopene also suggested some protection against dysplasia. Results were not significant at alpha = 0.05 because of the small number of case women enrolled. Overall, correlations between estimates from the FFQ and serum levels were poor. This study indicates that, among black women, lycopene and perhaps vitamin A may play a protective role in the early stages of cervical carcinogenesis.

Dietary and Plasma Lycopene and the Risk of Breast Cancer

Lycopene is potentially effective in the prevention of breast cancer from laboratory and observational studies. Among 39,876 women initially free of cardiovascular disease and cancer, we first conducted a prospective cohort study of dietary lycopene and its food sources. Participants completed a baseline food frequency questionnaire and provided self-reports of breast cancer risk factors. Dietary lycopene levels were divided into quintiles, and lycopene food sources were categorized. During 9.9 years of follow-up, 1,076 breast cancer cases were confirmed by medical record review. In a nested case-control study, we then identified 508 breast cancer cases and 508 controls matched by age, smoking, and follow-up time. Plasma lycopene and other carotenoids were measured. In the prospective cohort study, women with increasing quintiles of dietary lycopene had multivariate relative risks (RR) of breast cancer of 1.00 (ref), 0.95, 1.00, 1.10, and 1.00 (P, linear trend = 0.71). Women consuming <1.5, 1.5 to <4, 4 to <7, 7 to <10, and ≥10 servings/week of tomato-based products had RRs of 1.00 (ref), 1.00, 1.20, 1.18, and 1.16 (P, linear trend = 0.11). No individual lycopene food sources were associated with breast cancer. In the nested case-control study, women in increasing quartiles of plasma lycopene had multivariate RRs of breast cancer of 1.00 (ref), 0.95, 1.15, and 0.93 (P, linear trend = 0.86). The stepwise addition of individual plasma carotenoids did not impact the RRs for plasma lycopene, nor were other carotenoids associated with breast cancer. In conclusion, neither higher dietary nor plasma lycopene levels were associated with a reduced risk of breast cancer in middle-aged and older women.