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Biomedical subjects

S L West

Publications and source records attributed to S L West.

At least 19 recordsLinked to original sources
PubMed2001

Similar effectiveness of paroxetine, fluoxetine, and sertraline in primary care: a randomized trial.

CONTEXT: Selective serotonin reuptake inhibitors (SSRIs) are the most commonly prescribed class of antidepressant, yet it is not known whether one SSRI is more effective than another. OBJECTIVE: To compare the effectiveness of 3 SSRIs (paroxetine, fluoxetine, and sertraline) in depressed primary care patients. DESIGN: Open-label, randomized, intention-to-treat trial, with patient enrollment occurring in April-November 1999. SETTING: Thirty-seven clinics in 2 US primary care research networks. PATIENTS: A total of 573 depressed adult patients for whom their primary care physician thought that antidepressant therapy was warranted and who completed a baseline interview. INTERVENTIONS: Patients were randomly assigned to receive paroxetine (n = 189), fluoxetine (n = 193), or sertraline (n = 191) for 9 months. Primary care physicians were allowed to switch patients to a different SSRI or non-SSRI antidepressant if they did not adequately respond to or tolerate the initial SSRI. MAIN OUTCOME MEASURES: The primary outcome measure was change in the Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36) Mental Component Summary score (range, 0-100), compared across treatment groups at 1, 3, 6, and 9 months. Secondary outcomes included other depression and psychological measures, multiple measures of social and work functioning, and other domains of health-related quality of life, such as physical functioning, concentration and memory, vitality, bodily pain, sleep, and sexual functioning. RESULTS: Follow-up interviews were successfully completed in 94% of patients at 1 month, 87% at 3 months, 84% at 6 months, and 79% at 9 months. Responses to the 3 SSRIs were comparable on all measures and at all time points. The mean change in the SF-36 Mental Component Summary score at 9 months was + 15.8 in the paroxetine group, + 15.1 in the fluoxetine group, and + 17.4 in the sertraline group. The drugs were also associated with similar incidences of adverse effects and discontinuation rates. CONCLUSIONS: The SSRI antidepressants paroxetine, fluoxetine, and sertraline were similar in effectiveness for depressive symptoms as well as multiple domains of health-related quality of life over the entire 9 months of this trial.

Adult↗
PubMed2001

Tocolytic therapy for preterm labour: assessing its potential for reducing preterm delivery.

Preterm labour (PTL) is a major contributor to preterm delivery (PTD) but delivery is often not preventable by current therapies. We conducted this study to determine the proportion of women with PTL who were and who were not candidates for tocolytic therapy. The cohort comprised residents of Olmsted County, Minnesota who delivered at >20 weeks' gestation in 1985--94 and who experienced PTL. Medical records were abstracted to identify episodes of PTL, its treatment and outcome. We developed an algorithm that accounted for gestation at delivery and pregnancy complications to determine the proportion of pregnancies complicated by PTL that were candidates for tocolytic therapy. Of 651 pregnancies complicated by PTL, a 50% probability sample, stratified by delivery year, were selected and abstracted. The cumulative incidence of PTL ranged from 3.6 to 6.4 per 100 deliveries of live or stillborn infants. Tocolysis was not contraindicated for 49.4% of all women with PTL and for a third of women with only one PTL episode. Delivery was delayed to >35 weeks in 53.8% of candidates for tocolysis. Only an additional 11.7% of women with one or more PTL episodes could have had their PTD delayed beyond 35 weeks if a perfect tocolytic therapy had been available. Many pregnancies complicated by PTL occurred at > or =35 weeks or involved maternal or obstetric factors that contraindicated tocolytic medications. The maximum incremental benefit that could be expected of a new safe and efficacious tocolytic therapy would be to reduce current PTD rates resulting from PTL by about 12%.

Adolescent↗
PubMed2000

Assessing the Saskatchewan database for outcomes research studies of depression and its treatment.

This study was conducted to evaluate the validity of using the Saskatchewan Health administrative claims databases for conducting depression research. To develop a claims-based definition of depression, we identified a cohort of individuals who began a "new" period of antidepressant use (no use 180 days prior) from which we selected a stratified random sample (n = 600) for medical record abstraction. The medical record diagnosis was used as the gold standard for judging our database definitions of depression. After defining a primary database definition of depression, we tried to refine it using medically probable scenarios and assessed refinement by agreement statistics. Defining depression with ICD9 codes 296 (affective disorders), 309 (adjustment reaction), and 311 (depressive disorders), the sensitivity (Se), specificity (Sp), positive (PV+) and negative predictive (PV-) values were: 71%, 85%, 86%, and 70%, respectively. Algorithms that limited the number of false-negatives resulted in: Se = 84% and PV- = 77% whereas those that limited false-positives resulted in: Sp = 90% and PV+ = 86%. Although our depression definition requires treatment with antidepressants, this definition will allow us to conduct future studies of depression and its treatment using the Saskatchewan Health databases.

Adult↗
PubMed2000

A meta-analysis comparing the effectiveness of buprenorphine and methadone.

Increases in the use of illicit opiates have refocused attention on these drugs. One outgrowth of this attention has been the increased consideration of pharmacotherapies to provide alternatives to methadone maintenance. Buprenorphine is one new tool used in the attenuation of illicit opiate use. Like methadone, buprenorphine produces cross-tolerance to other opiates. However, it may have advantages over methadone including a longer duration, limited withdrawal syndrome, and increased safety. Buprenorphine's ability to serve as a replacement drug for illicit opiate use is well documented, and efforts have recently been made to compare the drug with methadone. The purpose of this study was to provide a meta-analysis of all available research reporting a controlled comparison of buprenorphine and methadone. This analysis provided a rating of the comparative efficacy of each drug, thus giving clinicians an additional guide when selecting an appropriate course of treatment. Findings suggest a relative equality in the efficacy of buprenorphine and methadone, although patients receiving methadone were less likely to test positive for illicit opiate use. Past experience with methadone maintenance acted as a moderating variable, however, such that those receiving buprenorphine were more likely to stay drug-free in studies that included patients with prior methadone experience.

Buprenorphine↗
PubMed2000

The virtual standardized patient. Simulated patient-practitioner dialog for patient interview training.

We describe the Virtual Standardized Patient (VSP) application, having a computerized virtual person who interacts with medical practitioners in much the same way as actors hired to teach and evaluate patient assessment, diagnosis, and interviewing skills. The VSP integrates technologies from two successful research projects conducted at Research Triangle Institute. AVATALK provides natural language processing, emotion and behavior modeling, and composite facial expression and lip-shape modeling for a natural patient-practitioner dialog. Trauma Patient Simulator provides case-based patient history and trauma casualty data, real-time physiological modeling, interactive patient assessment, 3-D scenario simulation, and instructional record-keeping capabilities. The VSP offers training benefits that include enhanced adaptability, availability, and assessment.

Communication↗
PubMed1999

Pharmacological treatment of alcohol dependence: a review of the evidence.

CONTEXT: Alcoholism affects approximately 10% of Americans at some time in their lives. Treatment consists of psychosocial interventions, pharmacological interventions, or both, but which drugs are most effective at enhancing abstinence and preventing relapse has not been systematically reviewed. OBJECTIVE: To evaluate the efficacy of 5 categories of drugs used to treat alcohol dependence--disulfiram, the opioid antagonists naltrexone and nalmefene, acamprosate, various serotonergic agents (including selective serotonergic reuptake inhibitors), and lithium. DATA SOURCES: Reports of randomized controlled trials, nonrandomized trials, and other study designs in English, French, and German identified from multiple searches of MEDLINE, EMBASE, and specialized databases; hand searching bibliographies of review articles; searches for unpublished literature; and discussions with investigators in the field. STUDY SELECTION: We included all studies on alcohol-dependent human subjects aged 18 years or older from all inpatient and outpatient settings between 1966 and December 1997 that met our inclusion criteria. DATA EXTRACTION: We abstracted the following information: study design and blinding, diagnostic instrument and severity assessment, drug interventions and cointerventions, demographic and comorbidity details about patients, compliance, and numerous outcome measures (eg, relapse, return to drinking, drinking or nondrinking days, time to first drink, alcohol consumed per unit of time, craving). We graded quality of the individual articles (scale, 0-100) independently from the strength of evidence for each drug class (A, strong and consistent evidence of efficacy in studies of large size and/or high quality; B, mixed evidence of efficacy; C, evidence of lack of efficacy; and I, insufficient evidence). DATA SYNTHESIS: Of 375 articles evaluated, we abstracted and analyzed data from 41 studies and 11 follow-up or subgroup studies. Naltrexone (grade A) reduces the risk of relapse to heavy drinking and the frequency of drinking compared with placebo but does not substantially enhance abstinence, ie, avoidance of any alcohol consumption. Acamprosate (grade A, from large-scale studies in Europe) reduces drinking frequency, although its effects on enhancing abstinence or reducing time to first drink are less clear. Controlled studies of disulfiram (grade B) reveal a mixed outcome pattern--some evidence that drinking frequency is reduced but minimal evidence to support improved continuous abstinence rates. The limited data on serotonergic agents were not very promising (grade I), although most studies were confounded by high rates of comorbid mood disorders. Lithium lacks efficacy (grade C) in the treatment of primary alcohol dependence. CONCLUSIONS: Recent reports documenting that naltrexone and acamprosate are more effective than placebo in the treatment of alcoholism justify clinical interest in use of these medications for alcohol-dependent patients. Use of disulfiram is widespread but less clearly supported by the clinical trial evidence; however, targeted studies on supervised administration of disulfiram may be warranted. Use of existing serotonergic agents or lithium for patients with primary alcohol dependence does not appear to be supported by the efficacy data available at this time; these medications may still have a positive effect in patients with coexisting psychiatric disorders.

Acamprosate↗
PubMed1999

Healthcare use among U.S. women aged 45 and older: total costs and costs for selected postmenopausal health risks.

The purpose of this study is to estimate the level of healthcare use and costs incurred by postmenopausal women overall and for these selected conditions: cardiovascular disease, osteoporosis, breast cancer, and gynecological cancers. National healthcare survey and discharge data were used to estimate healthcare use by women aged 45 and older. Clinical Classification for Health Policy Research (CCHPR) codes were used to identify patients whose primary diagnosis or procedure corresponded with the selected conditions. National weights were used to estimate resource use. Treatment costs were estimated using cost/charge ratios or the Medicare fee schedule to calculate costs for each individual procedure. Estimated total annual medical care treatment costs for women 45 and older were about $186 billion in 1997 dollars, including about $60.4 billion for cardiovascular disease, $12.9 billion for osteoporosis, and $5.0 billion for breast and gynecological cancers. For each condition, estimated resource use and costs are reported for hospitalization, outpatient, nursing home, and home healthcare services. Resource use and costs are also reported by age and expected source of payment. The economic burden of disease for conditions commonly affecting postmenopausal women is substantial. Prior research establishes that hormone replacement therapy (HRT) may be effective in reducing the burden of disease among women who continue preventive therapy for many years, but few at-risk women do so. New alternatives for prevention, such as selective estrogen receptor modulators (SERMs), may be effective in reducing the burden of disease among postmenopausal women.

Aged↗
PubMed1997

Demographics, health behaviors, and past drug use as predictors of recall accuracy for previous prescription medication use.

Drug data for pharmacoepidemiologic studies are often ascertained by self-report, but little research has addressed the factors influencing its accuracy. Stratified random sampling was used to select individuals for a study comparing interview data on past prescription drug use with dispensation information from the Group Health Cooperative of Puget Sound pharmacy database. The strata included age, gender, and recency of use. Recall accuracy and its determinants were evaluated for repetitively used non-steroidal anti-inflammatory drugs (NSAIDs), short-term NSAIDs (only a single dispensation), and post-menopausal estrogens. We investigated whether recall accuracy was influenced by education, marital status, race, smoking, alcohol consumption, cumulative drug history, the number of different NSAIDs or estrogens dispensed (both by name and dosage), and the number of dispensations of the drug in question. For repetitively used NSAIDs, recall accuracy was positively associated with the number of NSAID dispensations (the odds of recall were 1.7 [95% confidence interval {CL}: 1.3-2.2] times greater for each additional four dispensations of the NSAID), the total number of drugs dispensed and the number of different NSAIDs dispensed. For estrogen and short-term NSAID use, only higher educational attainment improved recall accuracy: the odds of recall were 4.1 (95% CI: 1.4-11.7) and 2.1 (95% CI: 1.0-4.7) times greater for those with some college compared with those with only a high school degree, respectively. This study demonstrates that predictors of recall accuracy for previous medication use differ by the type of drug and the repetitiveness of its use.

Aged↗
PubMed1996

Biochemical epidemiology of gallbladder cancer.

To evaluate the a priori hypotheses that an increased level of glyco and tauro lithocholic acid, perhaps because of a decreased capacity for hepatic sulfation, contributed to the biochemical epidemiology of gallbladder cancer, a case-control study was undertaken at four hospitals in La Paz, Bolivia, and at one hospital in Mexico City, Mexico. Eighty-four cases with newly diagnosed histologically confirmed gallbladder cancer were compared with 264 controls with cholelithiasis or choledocholithiasis in the absence of cancer and with 126 controls with normal biliary tracts. All study subjects were undergoing abdominal surgery. Interview data were collected for all study subjects, as well as blood, bile, and gallstone specimens when feasible. Sera were analyzed for carcinoembryonic antigen, cholesterol concentration, and total bile acids. Bile specimens were analyzed for carcinoembryonic antigen; and for concentration of bile salts; cholesterol; phospholipids; and the glycine and taurine conjugates of cholic, ursodeoxycholic, chenodeoxycholic, deoxycholic, and lithocholates; sulfoglycolithocholate; and sulfotaurolithocholate. Gallstone specimens were analyzed for the percentage of cholesterol content, the percentage of calcium bilirubinate content, and the percentage of calcium carbonate content. Serum bile acids were increased in cases versus the two control groups (median 11.7 nmol/mL vs. 9.3 nmol/mL for stone controls and 8.2 nmol/L for nonstone controls, P < or = .02 for each pairwise comparison). Biliary bile acids were markedly decreased in the cases (median 3.98 micromol/mL vs. 33.09 micromol/mL, and 154.0 micromol/L, respectively, P < or = .0001 for each comparison), even after excluding those with a serum bilirubin higher than 2.0 mg/dL. Bile cholesterol was lower for the cases as well (median 1.70 micromol/mL vs. 4.90 micromol/mL, and 16.81 micromol/ mL, respectively, P < or = .02), as was the concentration of bile phospholipids (median 2.97 micromol/mL vs. 6.26 micromol/mL, and 52.69 micromol/mL, P = .1 and .0004, respectively). Contrary to our a priori hypothesis, there was no difference between the cases and either control group in their bile concentrations of lithocholate, the proportion of bile acids which were sulfated, or the concentration of nonsulfated lithocholate. However, the cases had a higher concentration of ursodeoxycholate (UDC) (P < .004 for both control groups), especially glycoursodeoxycholate (P < .001 for both control groups). A previously published suggestion that gallstone size differed between cases and controls was not confirmed. In conclusion, cases with gallbladder cancer differed from controls with stones and from controls with normal biliary tracts in their serum and bile biochemistries. These findings may be a reflection of the disease process, or may provide useful clues to its pathogenesis.

Adult↗
PubMed1995

Risk factors for gallbladder cancer. An international collaborative case-control study.

BACKGROUND: Gallbladder cancer has an unusual geographic and demographic distribution, suggesting many possible etiologies. METHODS: A case-control study was undertaken at four hospitals in La Paz, Bolivia, and at one hospital in Mexico City, Mexico. Eighty-four patients with newly diagnosed, histologically confirmed gallbladder cancer were compared with 126 control subjects without stones and with 264 control subjects with cholelithiasis or choledocholithiasis without cancer. All study subjects underwent abdominal surgery. Study subjects were interviewed regarding demographic characteristics, medical history, family history, diet, and exposure to agents presumed to be risk factors for biliary cancer. RESULTS: Virtually all subjects in Mexico were judged to be mestizos (i.e., persons of mixed ancestry) In contrast, race was a very strong risk factor for gallbladder cancer in Bolivia. Relative to mestizos who spoke neither language, the odds ratio (95% confidence interval [CI]) for cases versus control subjects without stones for those who spoke Aymara well was 15.9 (CI, 1.9-179), whereas it was 1.4 (CI, 0.2-8.2) for those who spoke Quechua well. An increased risk was also noted for elevated maximum body mass index (P = 0.03), family history of gallstones (odds ratio [OR] = 3.6 [CI, 1.3-11.4]), and physician-diagnosed typhoid (OR = 12.7 [CI, 1.5-598]). An increased risk was also seen with elevated maximum body mass index; compared with those with a body mass index less than 24 kg/m2, those with an index of 24-25 kg/m2, 26-28 kg/m2, and greater than 28 kg/m2 had odds ratios of 1.6 (CI, 0.4-7.6), 1.3 (CI, 0.3-5.6), and 2.6 (CI, 0.5-18.6), respectively (asymptotic test for trend, P = 0.03). Finally, a number of associations were noted with certain dietary and cooking habits. CONCLUSIONS: Patients with gallbladder cancer differed from control subjects in race, body mass, physician-diagnosed typhoid, and certain dietary patterns. These findings may provide useful clues to the pathogenesis of gallbladder cancer, but given the number of analyses performed, additional cases need to be studied.

Adult↗
PubMed1995

Recall accuracy for prescription medications: self-report compared with database information.

A methodological study was performed in 1992 to evaluate the accuracy of self-reported use of nonsteroidal antiinflammatory drugs (NSAIDs) and noncontraceptive estrogens that had been dispensed during the previous 12 years. A sample of 560 individuals dispensed NSAIDs or estrogens, and 140 individuals without NSAID/estrogen dispensations were selected from the Group Health Cooperative pharmacy database. Demographic, behavioral, and drug information was ascertained by telephone interview for 356 persons with and 98 persons without NSAID/estrogen dispensations. Of those with only a single NSAID dispensation, 41% (95% confidence interval (CI) 32-50%) were able to recall any NSAID use compared with 85% (95% CI 76-94%) for those with multiple NSAID dispensations. Thirty percent (95% CI 24-36%) recalled the NSAID name, and 15% (95% CI 10-20%) recalled both the name and dose. For estrogens, 78% (95% CI 70-86%) recalled the name, but only 26% (95% CI 17-34%) recalled the name and dose. Age, but not sex, appeared to influence recall accuracy: Persons 50-65 years of age recalled the NSAID name more accurately than those aged 66-80 (odds ratio (OR) = 1.8, 95% confidence interval (CI) 1.0-3.4). A similar advantage was noted for 50- to 65-year-old women in recalling the estrogen name (OR = 1.5, 95% CI 0.6-3.9). Drug name was recalled more frequently for exposures stopped 2-3 years prior to interview than for those stopped 7-11 years prior (OR = 3.0, 95% CI 1.6-5.7, and OR = 2.4, 95% CI 0.9-6.7, for NSAIDs and estrogens, respectively). Specificity was consistently high, ranging from 92% to 100%. This study suggests significant underascertainment of self-reported prescription drug exposure but little evidence that exposures are overreported.

Aged↗
PubMed1994

Completeness of prescription recording in outpatient medical records from a health maintenance organization.

Since validity of drug data is often characterized by the agreement between questionnaire and medical record data, medical record completeness for drug therapy was evaluated. Outpatient medical records of 501 randomly selected Group Health Cooperative Health Maintenance Organization (HMO) participants known to have been dispensed a non-steroidal anti-inflammatory drug (NSAID) were reviewed for completeness. Documentation was also evaluated for indication, age, gender, location of visit, and number of visits. The NSAID was recorded in 89% of the charts reviewed. Charts with a vague/missing diagnosis were more likely to lack documentation [RR (95% CI): 20.0 (13.2-30.3)]. The data suggested that poorer documentation was related to older age [1.5 (0.9-2.5)] but not to gender, indication, location of visit, or number of visits. Presence of an indication was positively correlated to the completeness of drug documentation. According to this staff/group HMO, there may be a higher concordance between self-reported medication use and medical record data than found in previous literature.

Age Factors↗
PubMed1993

Acetylation phenotypes and environmental chemical exposure of people with idiopathic systemic lupus erythematosus.

OBJECTIVE: To test the hypotheses that there is an excess percentage of slow acetylators among patients with idiopathic systemic lupus erythematosus (SLE) and that these patients had excessive exposure to environmental amines and hydrazines before the onset of illness. METHODS: Case-control study with structured interview and acetylation phenotyping. RESULTS: No excess proportion of slow acetylators or environmental amine exposure was found. CONCLUSION: Slow acetylation phenotype and exposure to environmental amines are not principal causes of idiopathic SLE.

Acetylation↗
PubMed1993

Differences in antigen expression between neoplastic and nonneoplastic gallbladder epithelium. An immunohistochemical study.

Immunoreactivity for a panel of 15 monoclonal antibodies (MAbs), which are known to react with different gastrointestinal tumor antigens, was assessed in formalin-fixed paraffin-embedded sections that were prepared from cholecystectomy specimens obtained from Mexican patients. Each case was classified histologically into one of the following groups: (1) invasive adenocarcinoma (N = 21), (2) high-grade dysplasia (carcinoma in situ) (N = 2), (3) low-grade dysplasia (N = 4), hyperplasia (4) (N = 15), and (5) chronic cholecystitis (N = 10). Significant differences (P < 0.05) were identified among the five histopathologic groups in the proportion of epithelial cells demonstrating immunoreactivity with MAbs to Lewisb; Lewis(a); sialylated Lewis(a); sialylated Lewis(a) and Lewis(a); Y antigen; H antigen; X antigen; X-like antigen; 200-kDa protein of CEA; 180-, 160-, 50-, 40-kDa proteins of CEA; 30- to 37-kDa protein; and an undefined antigen identified by MAb 99-57, with invasive carcinoma more frequently being positive as compared to nonneoplastic (hyperplasia, chronic cholecystitis) epithelium. Significant differences were also observed among the five histopathologic groups (P < or = 0.0005) in the proportion of epithelial cells demonstrating immunoreactivity with MAbs to Y antigen and the 20- to 50-kDa glycoprotein. However, with these two antibodies immunoreactivity was more frequently found in nonneoplastic epithelium rather than in invasive carcinomas. No significant differences in immunoreactivity were detected among the different histologic groups with MAb to blood group B antigen, types 1 and 2. This study demonstrates that cellular antigens are both developed and lost during the process of neoplastic transformation in the gallbladder.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenocarcinoma↗
PubMed1990

Serum CEA and CA 19-9: potential future diagnostic or screening tests for gallbladder cancer?

The poor prognosis of gallbladder cancer and the presence of high-risk populations make the identification of a screening test for this disease very desirable. As part of an ongoing case-control study of gallbladder cancer being conducted in Mexico City, Mexico, and in La Paz, Bolivia, blood specimens were sought from all patients with cancer of the gallbladder and on controls of similar age and sex undergoing upper abdominal surgery. Each sample was analyzed for carcino-embryonic antigen (CEA) and CA 19-9. Using the specimens from Bolivia, a serum CEA cutoff of 4.0 ng/ml yielded a sensitivity of 50.0% and a specificity of 92.7%, while a serum CA 19-9 cutoff of 20.0 units/ml yielded a sensitivity of 79.4% and a specificity of 79.2%. Using ROC curve analysis, the latter was a much better test than the former (p less than 0.05). Using the tests in series or in parallel did not substantively improve the results. The specimens from Mexico were used for validation purposes, and yielded very similar results. In conclusion, serum CA 19-9 and CEA are fairly good tests for discriminating patients with gallbladder cancer from patients with gallstones and no cancer, the former being a better test than the latter. These tests may be useful in identifying disease recurrences. In addition, if a sufficiently high-risk population could be identified, this could potentially become a useful screening test for this serious disease, allowing early intervention. However, additional data are needed prior to recommending this clinically.

Antigens, Tumor-Associated, Carbohydrate↗
PubMed1989

Pathophysiology of tumor progression in human gallbladder: flow cytometry, CEA, and CA 19-9 levels in bile and serum in different stages of gallbladder disease.

Gallbladder epithelium is unique among the gastrointestinal cell types because proteins and protein levels in the fluid bathing the luminal side of the cells (bile) are different from and can be compared with those in the fluid bathing the basal side (serum). To help identify cellular changes that occur during the development of gallbladder cancer, we obtained gallbladder tissue, serum, and bile specimens from 20 patients with invasive adenocarcinoma of the gallbladder, three with high-grade dysplasia (carcinoma in situ), six with low-grade dysplasia, 12 with hyperplasia, and 10 with acute or chronic cholecystitis. We obtained serum samples from 40 patients with invasive adenocarcinoma and bile samples from 29 of these patients; serum samples from three with high-grade dysplasia and bile specimens from two of these; serum and bile samples from five with low-grade dysplasia; serum or bile samples from 126 with metaplasia, hyperplasia, or cholecystitis, including serum samples from 121 and bile samples from 110; and serum and bile samples from eight with normal biliary tracts. The study was conducted in Mexico City, Mexico, and La Paz, Bolivia. We performed flow cytometric DNA analysis on gallbladder tissue specimens and measured levels of carcinoembryonic antigen (CEA) and CA 19-9 antigen in the serum and bile specimens. Analysis of the cell cycle compartments by flow cytometry revealed marked variations of the proliferation index for the different disease states (P less than .0001). The proliferation index increased with progression from cholecystitis to invasive adenocarcinoma. Of the bile and serum measurements, only serum CA 19-9 values were correlated with flow cytometry measurements (r = -.49, P = .005). Overall, the serum and bile measurements were in agreement (P less than .01). However, with the exception of the correlations among serum measurements for the patients with invasive adenocarcinoma, most of the correlations could be explained by differences in the disease state. In particular, the progression from normal tissue to invasive adenocarcinoma involved no change in bile CA 19-9 level and only a slight change in bile CEA level but much larger changes in serum CEA and CA 19-9 levels. It appears that the progression from normal tissue to invasive adenocarcinoma results in increased production of these antigens and often in loss of cell polarity as well, i.e., inability to prevent leakage of the antigens into the serum.

Antigens, Tumor-Associated, Carbohydrate↗