Cell viability and electrical response of breast cancer cell treated in aqueous graphene oxide solution deposition on interdigitated electrode.

Breast cancer is one of the most reported cancers that can lead to death. Despite the advances in diagnosis and treatment procedures, the possibility of cancer recurrences is still high in many cases. With that in consideration, researchers from all over the world are showing interest in the unique features of Graphene oxide (GO), such as its excellent and versatile physicochemical properties, to explore further its potential and benefits towards breast cancer cell treatment. In this study, the cell viability and electrical response of GO, in terms of resistivity and impedance towards the breast cancer cells (MCF7) and normal breast cells (MCF10a), were investigated by varying the pH and concentration of GO. Firstly, the numbers of MCF7 and MCF10a were measured after being treated with GO for 24 and 48 h. Next, the electrical responses of these cells were evaluated by using interdigitated gold electrodes (IDEs) that are connected to an LCR meter. Based on the results obtained, as the pH of GO increased from pH 5 to pH 7, the number of viable MCF7 cells decreased while the number of viable MCF10a slightly increased after the incubation period of 48 h. Similarly, the MCF7 also experienced higher cytotoxicity effects when treated with GO concentrations of more than 25 µg/mL. The findings from the electrical characterization of the cells observed that the number of viable cells has corresponded to the impedance of the cells. The electrical impedance of MCF7 decreased as the number of highly insulating viable cell membranes decreased. But in contrast, the electrical impedance of MCF10a increased as the number of highly insulating viable cell membranes increased. Hence, it can be deduced that the GO with higher pH and concentration influence the MCF7 cancer cell line and MCF10a normal breast cell.

Clinical trial: the efficacy and safety of routine bowel cleansing agents for elective colonoscopy in persons with spinal cord injury - a randomized prospective single-blind study.

BACKGROUND: As difficulty with evacuation is a common occurrence in individuals with spinal cord injury, preparation prior to colonoscopy may be suboptimal and, perhaps, more hazardous. AIM: To assess the safety and efficacy of bowel cleansing regimens in persons with spinal cord injury. METHODS: Randomized, prospective, single blind study comparing polyethylene glycol (PEG), oral sodium phosphosoda (OSPS) and combination of both for colonic preparation prior to colonoscopy in subjects with spinal cord injury. RESULTS: Thirty six subjects with eGFR > or =60 mL/min/1.73 m(2) were randomized to PEG or OSPS or PEG+OSPS. Regardless of bowel preparation employed, >73% of subjects had unacceptable colonic cleansing. No subject in the OSPS preparation group demonstrated a decrease in eGFR or an increase in serum creatinine concentration from the baseline. OSPS and PEG+OSPS preparations caused a transient change in serum potassium, phosphate and calcium concentrations, but no change in electrolytes was noted in the PEG group. CONCLUSIONS: Neither OSPS alone, PEG alone nor their combination was sufficient to prepare adequately the bowel for colonoscopy in most patients with spinal cord injury. However, administration of OSPS and/or PEG appears to be safe in the spinal cord injury population, provided adequate hydration is provided.

The renal safety of bowel preparations for colonoscopy: a comparative study of oral sodium phosphate solution and polyethylene glycol.

BACKGROUND: Rare cases of nephrotoxicity have been reported with oral sodium phosphate solution (OSPS). AIM: To evaluate whether OSPS is associated with changes in renal function. METHODS: A chart review performed on 311 patients who had colonoscopy at the James J. Peters VA Medical Centre prepared with either OSPS (n = 157) or polyethylene glycol (PEG) (n = 154). Patients had a baseline serum creatinine or=50% increase above their baseline creatinine was similar (OSPS vs. PEG, 5% vs. 3%, P = 0.77). CONCLUSIONS: Oral sodium phosphate solution was associated with a slight increase in serum creatinine, which was not clinically significant. Renal toxicity from OSPS appears to be minimal when used in patients with serum creatinine value <1.5 mg/dL.

Application of summary receiver operating characteristics (sROC) analysis to diagnostic clinical testing.

Summary receiver operating characteristics (sROC) analysis is a recently developed statistical technique that can be applied to meta-analysis of diagnostic tests. This technique can overcome some of the limitations associated with pooling the sensitivities and specificities of published studies. The sROC curve is initially constructed by plotting the sensitivity (true positivity) and false positivity (1 - specificity) of each study. After mathematical manipulation of the true and false positivities, linear regression is performed to calculate the slope and y-intercept. These coefficients are then entered into the sROC equation to generate the sROC curve. There are three commonly used methods to assess the accuracy of the test: the exact area under the curve (AUC) for the sROC function, the homogeneous AUC, and the index Q*. Statistical formulas can compare these values from different diagnostic tests. With the introduction of sROC software and better understanding of this method, the application of sROC analysis should continue to increase.

Decline in haemoglobin A1c values in diabetic patients receiving interferon-alpha and ribavirin for chronic hepatitis C.

Haemoglobin A1c (A1c) levels are lower during haemolysis because of the shorter exposure of haemoglobin (Hb) to plasma glucose. Ribavirin (RBV) used in combination with interferon-alpha (IFN) for chronic hepatitis C causes reversible haemolytic anaemia. This study examined the extent to which RBV treatment influences A1c levels in diabetic patients. A retrospective analysis identified 32 diabetic patients who underwent hepatitis C treatment with IFN and RBV. Each subject had at least three measures of A1c, Hb and glucose: before, during and after therapy. A1c values decreased from a mean pretreatment level of 7.2% to an on-treatment A1c level of 5.2% [mean paired difference -2.01%; 95% confidence interval (CI) -1.59% to -2.43%; P < 0.001]. During therapy, mean Hb levels decreased from 15.1 g/dL at baseline to a nadir of 11.7 g/dL (P < 0.001) with a rise in lactose dehydrogenase levels and reticulocyte counts, and unchanged mean corpuscular volume values confirming haemolysis. At the same time, glucose levels declined by a mean of 38.4 mg/dL (95% CI 13.4-63.5 mg/dL; P = 0.002) as did body weights by a mean of 3.15 kg (P < 0.001). According to published glucose-A1c correlation tables, this decline of glucose concentration by 38.4 mg/dL correlates to a decline in A1c level of 1.08%. In conclusion, reductions of A1c levels by a mean of 2.01% during hepatitis C therapy with IFN + RBV are due to a combination of decreased glucose levels (1.08%) and RBV-induced haemolysis (0.93%). A1c levels should not be measured during hepatitis C treatment with IFN + RBV because they do not adequately reflect glycaemic control.

Recent concepts in the management of bowel problems after spinal cord injury.

Bowel problems after SCI can be debilitating. Colonic inertia as a result of decreased parasympathetic (S2-4) stimulation of the left colon and rectosigmoid seems to be the principal abnormality accounting for DWE. The conventional measures used for decades have poor results in many people. Neostigmine, an anticholinesterase inhibitor, appears to be a more physiological agent for these individuals. The combination of neostigmine + glycopyrrolate infusion has shown encouraging results after intravenous administration and studies are under way to assess the efficacy of neostigmine by other routes.

Metaanalysis of trials comparing laparoscopic and open surgery for Crohn's disease.

BACKGROUND: Several studies in the literature have suggested that laparoscopic surgery for Crohn's disease is associated with faster postoperative recovery and a morbidity and recurrence rate similar to that for open surgery. Most of these studies have been limited by a small sample size and a short follow-up period. METHODS: To clarify whether open or laparoscopic resection results in a better outcome, a metaanalysis of studies was performed comparing the two procedures for Crohn's disease. Pooled effects were estimated using a random-effects model. RESULTS: Laparoscopic surgery required more operative time than open surgery (26.8 min; 95% confidence interval [CI], 6.4-47.2 min), but resulted in a shorter duration of ileus and a decreased hospital stay (-2.62 days; 95% CI, -3.62 to -1.62). Laparoscopic surgery also was associated with a decreased rate for postoperative bowel obstruction and surgical recurrences. CONCLUSIONS: Laparoscopic surgery for Crohn's disease is feasible, safe, and associated with shorter duration of ileus and a shorter hospital stay.

Disulfiram treatment increases plasma and red blood cell acetaldehyde in abstinent alcoholics.

BACKGROUND: Much of alcohol's toxicity is due to its product, acetaldehyde. The role of acetaldehyde derived from endogenous sources was assessed in alcoholic patients administered disulfiram, an inhibitor of aldehyde dehydrogenase. METHODS: The first part of the study included 23 subjects without biochemical or clinical evidence of chronic liver disease who were abstinent for 2 weeks; 11 patients were started on disulfiram (250 mg/day), whereas the other 12 were not given disulfiram and served as controls. The second part of the study included 13 alcoholic patients with clinical or pathological evidence of cirrhosis who also were administered disulfiram for 2 weeks. Plasma and red blood cell (RBC) acetaldehyde as well as serum transaminases were measured at baseline and after 1 and 2 weeks of treatment. RESULTS: In the disulfiram-treated group of alcoholics without known cirrhosis, RBC acetaldehyde levels increased from the pretreatment value of 2.98+/-0.18 microM to 4.14+/-0.33 microM after 1 week and to 4.14+/-0.26 microM after 2 weeks of treatment (p < 0.001). Compared with the pretreatment values (2.07+/-0.24 microM), plasma acetaldehyde levels also increased after 1 week (3.18+/-0.32 microM) and 2 weeks (3.15+/-0.26 microM) of disulfiram treatment (p < 0.001). There were no significant differences in sequential levels measured in either plasma or RBC acetaldehyde levels in patients who were not administered disulfiram. In the group of cirrhotic patients, the mean baseline RBC acetaldehyde value (3.60+/-0.22 microM) was significantly higher than in noncirrhotics. Disulfiram therapy increased the RBC acetaldehyde after 1 week (4.63+/-0.27 microM, p < 0.001) and 2 weeks of treatment (4.06+/-0.28 microM, p < 0.05). Compared with baseline values, plasma acetaldehyde levels were significantly higher after 1 week but not after 2 weeks of disulfiram. There were no significant differences among serum transaminases in alcoholics administered disulfiram, although three cirrhotic patients did have clinically significant elevations. CONCLUSIONS: In abstaining subjects given disulfiram, acetaldehyde concentrations increase, possibly due to diminished catabolism of endogenously generated acetaldehyde. Disulfiram should be given cautiously, especially in patients with cirrhosis.

Chlorzoxazone pharmacokinetics as a marker of hepatic cytochrome P4502E1 in humans.

OBJECTIVE: Previous in vitro studies have demonstrated that hepatic P4502E1 metabolizes chlorzoxazone (CZX, a commonly used muscle relaxant) to 6-hydroxychlorzoxazone (6-OH-CZX). We thus assessed whether measurement of the plasma 6-OH-CZX/CZX ratio after a CZX challenge could serve as a marker of hepatic P4502E1 content. METHODS: Three subject groups were included: recently drinking alcoholics (N = 6), abstinent alcoholics (N = 5), and nonalcoholic subjects with liver disease (N = 5) undergoing liver biopsy. Excess tissue was procured for immunochemical determination of hepatic P4502E1 content. Within an hour of the biopsy, 750 mg CZX was administered orally and serial plasma samples were collected for 6 h. RESULTS: Recently drinking alcoholic subjects had a higher area under the curve for plasma 6-OH-CZX (1.354 +/- 0.258 microg x min x ml(-1)) then abstinent alcoholic subjects (0.296 +/- 0.080 microg x min x ml(-1), p < 0.005) and subjects with nonalcoholic liver disease (0.428 +/- 0.061 microg x min x ml(-1), p < 0.005). The use of the plasma 6-OH-CZX/CZX ratio at 90, 120, and 180 min discriminated between recently drinking alcoholic and nondrinking subjects. Hepatic P4502E1 content significantly correlated with the maximal 6-OH-CZX concentration (r = 0.76, p = 0.001) and other pharmacokinetic parameters. In the recently drinking group, the area under the curve for plasma 6-OH-CZX significantly decreased after 8 days of abstinence. CONCLUSIONS: Measurement of plasma 6-OH-CZX after administration of a CZX challenge can serve as a marker of hepatic P4502E1 activity and thus help avoid adverse drug reactions secondary to P4502E1 induction, particularly in heavy drinkers.

Viral hepatitis in patients with spinal cord injury is explained by known risk factors.

Spinal cord injury (SCI) has been reported to be associated with viral hepatitis. However, this association may be related to other confounding factors, such as intravenous drug abuse or blood transfusions. Screening for viral hepatitis associated risk factors and serum serologies, including HBsAg, anti-HBc, anti-HBs and anti-HCV testing, were performed in 78 randomly selected SCI patients and 93 non-alcoholic patients attending a general medical clinic. Hepatitis B and C seropositivies in SCI patients were 29.5 percent and 14.1 percent, respectively, and were significantly associated with a history of intravenous drug abuse. In contrast, hepatitis B and C seropositivities in non-alcoholic general medicine clinic patients were 22.6 percent and 2.2 percent, respectively. In the subgroup of patients without known viral hepatitis risk factors, there were no significant differences between SCI and non-alcoholic patients with respect to hepatitis B (21.4 percent vs. 22.1 percent) or hepatitis C (0 percent vs. 1.3 percent) seropositivity. Stepwise logistic regression also failed to detect an association of SCI with viral hepatitis. In conclusion, the increased seroprevalence of hepatitis C in SCI patients is secondary to intravenous drug use and blood transfusions. Further preventive measures such as improved hepatitis screening of blood donors and substance abuse treatment should decrease viral hepatitis exposure in SCI patients.

Immunohistochemical determination of hepatic cytochrome P-4502E1 in formalin-fixed, paraffin-embedded sections.

Cytochrome P-4502E1 (2E1) is inducible by chronic ethanol consumption that results in enhanced activation of anesthetics and commonly used drugs (such as acetaminophen) to hepatotoxins. Therefore, assessment of hepatic 2E1 is needed in prescribing these drugs for the management of alcoholic patients. Currently, measurement of 2E1 requires either immunohistochemistry on frozen sections or Western blot (WB) analysis of homogenized tissue in excess of that needed for pathology. To obtain a more widely applicable method, we developed a procedure to detect 2E1 by immunohistochemistry in formalin-fixed, paraffin-embedded liver biopsies obtained routinely for diagnosis. Data were collected from rats fed ethanol-containing or control liquid diets for 3 weeks. Immunostaining was performed using anti-human rabbit 2E1 antibody as the primary antibody, and the immunoreaction was detected by the avidin-biotin immunoperoxidase method after treating sections with target unmasking fluid, an antigen retrieval buffer that enhanced the staining of 2E1. In control rats, 2E1 staining was weak and perivenular. After ethanol feeding, it showed a lobular gradient, strongest perivenular and weakest periportal, similar to that seen in frozen sections. The staining intensity was scored as: 0 (no staining) to 3 (strong staining). The zonal staining was scored as follows: 1 = perivenular zonal staining, 2 = midzonal, and 3 = panlobular. With the product of the two scores, a significant difference was found between alcohol-fed and control rats (5.1 +/- 0.3 vs. 0.8 +/- 0.2, p < 0.001). 2E1 assessments by WB were also significantly different for these rat pairs (68.5 +/- 2.1 vs. 7.9 +/- 0.8 arbitrary units/mg protein, p < 0.001), with a parallel increase of immunostaining scores and WB measurement of 2E1 content. This immunohistochemical method was then validated in 14 paraffin-embedded percutaneous human liver biopsy samples. In livers of nonalcoholics, 2E1 staining was seen in the perivenular zone only, whereas in samples of alcoholics, the staining was perivenular to midzonal and sometimes periportal. A significant correlation between the zonal staining scores (rs = 0.67, p < 0.005) or intensity x zonal staining scores (rs = 0.79, p < 0.001) and WB analysis was found. The immunohistochemical assessments of 2E1 expression in formalin-fixed, paraffin-embadded sections from livers of alcoholics was found to correlate with WB analysis, and lobular distribution was consistent with that seen in frozen sections. The proposed method should therefore be useful for the assessment of 2E1 content in paraffin-embedded liver samples, thereby aiding in the management of heavy drinkers.

Efficacy of a high and accelerated dose of hepatitis B vaccine in alcoholic patients: a randomized clinical trial.

PURPOSE: A randomized, double-blind trial was conducted to compare the efficacy of a high-dose versus standard-dose hepatitis B vaccine in alcoholic patients. PATIENTS AND METHODS: One hundred ten alcoholic patients were randomized to either receive the standard dose (20 micrograms at 0.1, and 6 months) or a high dose (40 micrograms at 0, 1, 2, and 6 months) of recombinant hepatitis B vaccine (Engerix-B). Patients were monitored for relapse of drinking using self-report, serial serum carbohydrate deficient transferrin, and collateral verification. The final titer of antibody to hepatitis B surface antigen (anti-HBs) was obtained 12 months after the first vaccine dose; a seroconversion was defined as a titer greater than 10 mlU/ml. RESULTS: One hundred subjects completed the study; 10 of these had clinical or pathological evidence of cirrhosis. Thirty-six out of 48 (75%) of patients administered the high-dose regimen seroconverted compared with 24 of 52 (46%) in the standard dose group (P < 0.005). The mean anti-HBs titer of the high dose group was significantly greater than of the standard dose group (76.4 versus 39.4 mlU/ml, P < 0.01). Logistic regression demonstrated a significant effect on seroconversion for the vaccine dose (P < 0.005) and serum albumin (P = 0.05) but not for the other variables such as race, age, drinking during the study, serum creatinine, arm muscle circumference, and cirrhosis. CONCLUSIONS: A high- and accelerated-dose regimen of hepatitis B improves the serological response in alcoholic patients. This regimen (currently recommended for hemodialysis patients) should now also be considered for patients with a history of alcoholism.

Serum ferritin iron, a new test, measures human body iron stores unconfounded by inflammation.

Serum ferritin protein is an acute phase reactant. We hypothesized that serum ferritin protein generated in response to an inflammatory process would have much less iron (Fe) in it than would "normal" ferritin protein, and therefore measuring serum ferritin iron would assess human body iron status unconfounded by inflammation. BASIC METHODS: We measured serum ferritin iron in 140 clinical samples obtained from the serum banks of Bronx VA Medical Center Hematology and Nutrition Laboratory (Bronx, NY), the CDC Nutritional Biochemistry serum sample bank (Atlanta, GA), and the sample bank from patients with thalassemia and iron overload treated at New York Hospital (New York, NY). Each was analyzed for three conventional criteria of iron status: serum iron, percentage of transferrin saturation and ferritin protein. In addition, tests for inflammation were also performed: C-reactive protein, WBC and transaminases. Seventy-seven patients' sera from 140 screened met each of three consistent criteria for stages of iron status. Serum ferritin was immobilized by immunoprecipitation with rabbit antihuman polyclonal antibody bound to agarose and separated from other iron-containing proteins, digested with 0.2 ml of 3N nitric acid and analyzed for iron content by atomic absorption spectroscopy. RESULTS: Serum ferritin iron ranged in normal controls from 10 ng to 35 ng Fe/ml. The patients with iron deficiency (4/4) and those in negative iron balance (5/6) had values < or = 10 ng. Positive iron balance (8/9) and iron overload (22/22) values were > 35 ng/ml, in contrast to 11/19 with inflammation. Seventeen of twenty-two with overload had values > 100 ng/ml while only 1/19 with inflammation had such a value. Ferritin iron in ferritin protein was > 15% by weight in 14/22 with iron overload but in 0/19 with inflammation. IMPLICATIONS OF THE WORK: Serum ferritin iron is a simple, direct measure of iron stores that we propose, in conjunction with measuring serum ferritin protein, as a minimally invasive screening procedure for accurately assessing the whole range of human body iron status, unconfounded by inflammation.

Prevalence of viral hepatitis B in an urban veteran spinal cord injured population.

The objective of this study was to determine the prevalence of viral hepatitis B (HBV) seropositivity in an urban veteran population with spinal cord injury (SCI) and the relationship of liver function test (LFT) values to HBV seropositivity. Eighty patients with chronic SCI (44 inpatients and 36 outpatients) had liver function tests (LFTs), hepatitis B surface antigen (HBsAg), hepatitis B surface antibody (anti-HBsAb) and hepatitis B core antibody (anti-HBcAb) evaluated. Seventy-seven able-bodied (non-SCI) outpatients without known viral hepatitis risk factors served as an urban veteran reference group. Results demonstrated a high prevalence of seropositivity for HBV in both veteran groups (SCI = 29 percent; non-SCI = 22 percent). Subdividing the SCI group by inpatients and outpatients, HBV positivity was found to be significantly higher in the SCI inpatients than in either the SCI outpatient (39 percent vs 17 percent, x2 = 4.67, p < 0.05) or non-SCI groups (39 percent vs 22 percent, x2 = 3.80, p = 0.05). For the whole group, the gamma-glutamyl transpeptidase (GGT) level was greater in the HBV seropositive (n = 40) compared with the HBV seronegative (n = 117) populations (82 +/- 17 vs 46 +/- 7 U/L, p = 0.019, respectively). In addition, the subgroup of spinal cord patients seropositive for hepatitis B (n = 23) had a higher mean GGT than their seronegative (n = 57) counterparts (101 +/- 26 vs 47 +/- 9 U/L, p = 0.018, respectively). We conclude that urban veterans in general, and especially those inpatients with SCI, may be at increased risk of HBV infection. An HBV vaccination program for veteran patients with SCI may be warranted.

Alcoholism is associated with hepatitis C but not hepatitis B in an urban population.

OBJECTIVES: Previous studies have suggested an association of viral hepatitis with alcoholism, although the role of confounding risk factors (e.g. i.v. drug use) has not been adequately excluded. We therefore compared the seroprevalences of hepatitis B and C in alcoholic patients to that of a nonalcoholic control group. METHODS: Hepatitis B surface antigen, hepatitis B core antibody, hepatitis B surface antibody, and hepatitis C virus antibody testing (second generation ELISA and a confirmatory recombinant immunoblot assay) was performed in 150 consecutive alcoholics admitted for detoxification and in 166 randomly selected patients attending a general medical clinic who were screened for alcoholism. RESULTS: Hepatitis B and C seropositivities in actively drinking alcoholics are 49.3 and 35.3%, respectively, and were significantly associated with a history of i.v. drug abuse. Out of 166 general medicine clinics patients, 93 were classified as nonalcoholic (by both self-report and collateral verification), 46 patients had a history of alcoholism , and 27 were indeterminate. In the subgroup of patients without known viral hepatitis risk factors, there was no significant difference in hepatitis B seropositivity among nonalcoholic general medicine clinic patients, alcoholic general medicine clinic patients, and alcoholic patients admitted for detoxification (22.1%, 30.3%, and 27.6%, respectively). In contrast, anti-HCV recombinant immunoblot assay seropositivity in alcohol patients admitted for detoxification without risk factors was significantly greater than in nonalcoholic general medicine patients without risk factors (10 vs 0%, p >0.01). Stepwise logistic regression analysis revealed that alcoholism requiring detoxification was a significant risk factor for hepatitis C but not for hepatitis B seropositivity. CONCLUSIONS: The increased seroprevalence of hepatitis C in actively drinking alcoholic patients without known risk factors suggests that alcoholism, in some way, is a predisposing factor for HCV infection.

Utility of carbohydrate-deficient transferrin as a marker of relapse in alcoholic patients.

Carbohydrate-deficient transferrin (CDT) has been proposed as a marker of alcoholism. However, its role in monitoring alcoholic patients for relapse has not been extensively studied. We therefore performed sequential serum CDT measurements using a microcolumn/radioimmunoassay method (Kabi Pharmacia, Piscataway, NJ) in 86 male alcoholics participating in a hepatitis vaccination program who were monitored for relapse using self-report and collateral history (when available). The maximum serum CDT was significantly higher in patients who relapsed (n = 38) (33.1 +/- 3.1 mg/liter), as compared with abstinent subjects with collateral verification (n = 39) (18.8 +/- 1.3, p < 0.001) and abstinent patients without collateral verification (n = 9) (17.4 +/- 1.3, p < 0.01). Using the manufacturer's currently recommended threshold of 20 mg/liter for males, serum CDT was elevated in 29 of 38 patients who relapsed (sensitivity 76.3%). In 16 (42.1%) of the relapsed patients, a serum CDT above this threshold preceded the patient's self-report by at least 28 days. However, serum CDT exceeded 20 mg/liter in 10 of 48 patients who remained sober (specificity 79.2%); three of these patients had clinical and/or pathological evidence of cirrhosis. Using a threshold of 25 mg/liter, 21 of 38 patients who relapsed had an elevated serum CDT (sensitivity 55.3%); 12 (31.6%) of these patients had elevated serum CDT before self-report. Only 4 of 48 subjects who remained sober had serum CDT levels that exceeded 25 mg/liter (specificity 91.7%); three of these patients had clinical and/or pathological evidence of cirrhosis. In conclusion, serial serum CDT testing detects relapses before self-report in male subjects. Values between 20-25 mg/liter suggest relapse, but call for collateral verification, whereas CDT values above 25 mg/liter are usually diagnostic of relapse in the absence of cirrhosis.

The effects of cisapride on the quality and tolerance of colonic lavage: a double-blind randomized study.

Colonic lavage is a preferred preparation for colonoscopy although this type of preparation does not always result in optimal cleansing. We postulated that cisapride, a new prokinetic agent, might improve the cleansing of the colon and ameliorate patient discomfort. Of 84 patients undergoing colonoscopy, 41 were randomized (double-blind) to Golytely plus cisapride (10 mg per OS three times during the day before the procedure and one 10-mg dose on the morning of the procedure) and 43 to Golytely plus a placebo of identical appearance. The adequacy of the preparation was scored on a five-point grading scale for each anatomic segment and for the overall impression. A questionnaire was also used to assess each patient's symptoms during lavage. The mean overall preparation score in the cisapride group was 4.0, compared with 3.7 for the placebo group (p = .54). In the transverse colon, the mean preparation score was higher for the cisapride group (4.3 versus 3.8, p = .02). Differences in symptom scores between the two groups were not significant. In conclusion, the use of cisapride may improve visualization of the transverse colon, but it did not result in significant improvement in the overall preparation score. Changes in the dosage of cisapride should be further evaluated.

Diagnostic utility of laboratory tests in alcoholic liver disease.

Alcoholic liver disease is an important health problem in the US. A public health approach is proposed, using laboratory tests to identify patients with early fibrosis of the liver. A variety of serological markers of liver fibrosis based on collagen-related products (e.g., amino-terminal propeptides of type III procollagen) have been investigated. Further studies are needed to determine the optimal combination of tests for discriminating between steatosis and early fibrosis. Laboratory tests are also useful in excluding nonalcoholic liver diseases such as viral hepatitis, hemochromatosis, and Wilson disease. The monitoring of sobriety in patients with alcoholic liver disease by currently available tests is far from ideal. A new marker of excessive alcohol consumption, carbohydrate-deficient transferrin, is not usually affected by liver disease and thus shows promise as a marker of relapse in alcoholic patients. The development of reliable screening markers of fibrosis and sobriety could potentially reduce the health costs and suffering associated with the complications of alcoholic cirrhosis.

Collagen-acetaldehyde adducts in alcoholic and nonalcoholic liver diseases.

Alcoholic and, to a lesser extent, nonalcoholic patients with liver disease have serum antibodies to acetaldehyde-protein adducts produced in vitro. These antibodies presumably reflect the presence of adducts in the liver, but the protein that triggers this immune response has not been identified. To study this, we measured the reactivity of cytosolic proteins to rabbit IgG developed against a P-450 2E1-acetaldehyde adduct, isolated from alcohol-fed rats, that recognizes acetaldehyde-modified epitopes in proteins. Adducts were determined on Western blots by scanning densitometry of antibody-linked alkaline phosphatase activity in 4 normal livers and in needle biopsy specimens from subjects with liver disease, 17 alcoholic and 14 nonalcoholic. In all livers, except for a normal one, we found a reactive protein of at least 200 kD, similar to the collagen-acetaldehyde adduct we reported to be markedly increased in rats with experimentally induced cirrhosis. The immunostaining intensity in the alcoholic patients with liver disease was eightfold (p < 0.01) and that in nonalcoholic patients with liver disease was fourfold, greater (p < 0.02) than the weak staining in normal livers; it correlated with the degree of inflammation and serum AST or gamma-glutamyl transpeptidase activities. The adduct was reproduced on incubation of normal cytosolic proteins with 2.5 mmol/L acetaldehyde, whereas higher concentrations yielded many additional adducts; the adduct also reacted with IgG antibody to rat collagen type I and disappeared after digestion with collagenase, suggesting that the target protein is a form of collagen.(ABSTRACT TRUNCATED AT 250 WORDS)

Tissue inhibitor of metalloproteinase is increased in the serum of precirrhotic and cirrhotic alcoholic patients and can serve as a marker of fibrosis.

One of the contributory factors to the development of cirrhosis is a decrease in collagenase activity, which may be related to levels of inhibitors such as serum tissue inhibitor of metalloproteinase. We therefore measured serum tissue inhibitor of metalloproteinase and serum procollagen III peptides (another proposed marker of fibrosis) in 16 healthy controls and 44 alcoholic patients with biopsy-proved liver disease, namely steatosis without fibrosis (n = 13), perivenular fibrosis (n = 10), septal fibrosis or cirrhosis or both (n = 15) and alcoholic hepatitis (n = 6). In alcoholic patients, serum tissue inhibitor of metalloproteinase values strongly correlated with fibrosis (rs = 0.70, p < 0.001). Compared with values in controls (177 +/- 12 ng/ml), serum tissue inhibitor of metalloproteinase was significantly elevated in perivenular fibrosis (330 +/- 22 ng/ml, p < 0.05), in septal fibrosis, cirrhosis or both (406 +/- 29 ng/ml, p < 0.001) and in alcoholic hepatitis (526 +/- 140 ng/ml, p < 0.001) but not in steatosis (204 +/- 17 ng/ml). In contrast, procollagen III peptides were significantly increased only in the septal fibrosis-cirrhosis group but not in the perivenular fibrosis group. With the threshold defined as the upper value of the steatosis group (resulting in a specificity of 100%), we found that serum tissue inhibitor of metalloproteinase was elevated in 50% of patients with perivenular fibrosis, in 87% of subjects with extensive fibrosis (septal fibrosis, cirrhosis or both) and in 67% of individuals with alcoholic hepatitis. The overall sensitivity of serum tissue inhibitor of metalloproteinase for detecting either perivenular fibrosis or more extensive fibrosis was 71%.(ABSTRACT TRUNCATED AT 250 WORDS)