Coping strategies, satisfaction with life, and quality of life in Crohn's disease: A gender perspective using structural equation modeling analysis.

OBJECTIVE: To identify coping strategies and socio-demographics impacting satisfaction with life and quality of life in Crohn's disease (CD). METHODS: 402 patients completed the Patient Harvey-Bradshaw Index, Brief COPE Inventory, Satisfaction with Life Scale (SWLS), Short Inflammatory Bowel Disease Questionnaire (SIBDQ). We performed structural equation modeling (SEM) of mediators of quality of life and satisfaction with life. RESULTS: The cohort comprised: men 39.3%, women 60.1%; P-HBI 4.75 and 5.74 (p = 0.01). In inactive CD (P-HBI≤4), both genders had SWLS score 23.8; men had SIBDQ score 57.4, women 52.6 (p = 0.001); women reported more use of emotion-focused, problem-focused and dysfunctional coping than men. In active CD, SWLS and SIBDQ scores were reduced, without gender differences; men and women used coping strategies equally. A SEM model (all patients) had a very good fit (X2(6) = 6.68, p = 0.351, X2/df = 1.114, SRMR = 0.045, RMSEA = 0.023, CFI = 0.965). In direct paths, economic status impacted SWLS (ß = 0.39) and SIBDQ (ß = 0.12), number of children impacted SWLS (ß = 0.10), emotion-focused coping impacted SWLS (ß = 0.11), dysfunctional coping impacted SWLS (ß = -0.25). In an indirect path, economic status impacted dysfunctional coping (ß = -0.26), dysfunctional coping impacted SIBDQ (ß = -0.36). A model split by gender and disease activity showed that in active CD economic status impacted SIBDQ in men (ß = 0.43) more than women (ß = 0.26); emotional coping impacted SWLS in women (ß = 0.36) more than men (ß = 0.14). CONCLUSIONS: Gender differences in coping and the impacts of economic status and emotion-focused coping vary with activity of CD. Psychological treatment in the clinic setting might improve satisfaction with life and quality of life in CD patients.

Expression of D-type cyclins in colon cancer and in cell lines from colon carcinomas.

Cyclins D1, D2 and D3 play important roles in cell proliferation and differentiation. Although their abnormal expression has been linked to cancer development and progression in a number of tissues, the expression of cyclin D2 and D3 proteins in colon cancer has not yet been characterised. In this study, we examined cyclin D1, D2 and D3 protein expression by Western blot analysis in tumour and adjacent normal colon tissues of 57 patients. In addition, we examined D-type cyclins protein expression in HT29 and LoVo39 cell lines from colon carcinomas, as a function of induced proliferation and differentiation. In both cell lines, the expression of the three D-type cyclins increased as a result of induced proliferation, whereas the expression of cyclin D3 increased as a result of induced differentiation. In colon tumours, cyclin D1 was overexpressed in 44%, cyclin D2 was overexpressed in 53% and cyclin D3 was overexpressed in 35% of the cases. We also found that in 16% of the cases, cyclin D3 protein expression was reduced in the tumour, as compared to the adjacent normal tissue. Examination of D-type cyclin protein overexpression in relation to the TNM stage of the tumours revealed that overexpression of cyclins D1 and/or D2, but not cyclin D3, is linked to colon carcinogenesis and that overexpression of cyclin D2 may be related to a higher TNM stage of the tumour.

Unexpectedly low prevalence rates of IBS among adult Israeli Jews.

The irritable bowel syndrome (IBS) and other functional bowel disorders (FBDs) are common functional gastrointestinal disorders. The prevalence of IBS using Rome II criteria is generally lower than with previous criteria. The aim of this study was to determine the prevalence of IBS and other FBDs in the adult Israeli Jewish population, which has not been surveyed to date. A telephone survey was conducted on a representative sample of the study population provided by the Israel Ministry of the Interior. IBS and other FBDs were diagnosed by Rome II criteria. The study population was 981 individuals and the overall response rate was 54%. The mean age was 45.0 years and 55% were females. In all, 2.9% had IBS (females: 3.7%, males: 1.8%, P = 0.08). The rate increased to 4.1% when the Rome II diagnostic criteria were amended to include some chronic alternators who are not picked up by the original scoring system. Approximately 26% of the respondents had a functional lower gastrointestinal (GI) disorder (females: 32.1%, males: 17.7%, P < 0.0001). Prevalence rates for IBS among Israeli Jewish adults are lower than rates reported from most countries, despite the high level of stress resulting from Israel's geopolitical circumstances. Possible reasons for this low prevalence are discussed.

Differential effects of monastrol in two human cell lines.

The kinesin-related protein HsEg5 plays essential roles in mitotic spindle dynamics. Although inhibition of HsEg5 has been suggested as an aid in cancer treatment, the effects of such inhibition on human cells have not been characterized. Here we studied the effects of monastrol, an allosteric HsEg5 inhibitor, on AGS and HT29 cell lines and compared them to those of taxol. While both cell lines were similarly sensitive to taxol, AGS cells were more sensitive to monastrol. The differences in sensitivity were determined by the degree of inhibitory effect on cell proliferation, reversibility of monastrol-induced G2/M arrest, intracellular phenotypes and induction of apoptosis. In both cell lines, monastrol-induced apoptosis was accompanied by mitochondrial membrane depolarization and poly-ADP-ribose polymerase 1 cleavage. In AGS, but not HT29 cells, monastrol-induced apoptosis involved a prominent cleavage of procaspases 8 and 3. While in AGS cells, monastrol induced the formation of symmetric microtubule asters only, in HT29 cells, asymmetric asters were also formed, which may be related to specific HsEg5 functions in HT29 cells.

Cystic fibrosis transmembrane conductance regulator and Na+ channel subunits mRNA transcripts, and Cl- efflux, show a different distribution in rat duodenum and colon.

AIM: We compared the distribution and putative association of Cl- channel transport, CFTR mRNA transcripts, and Na+ channel (ENaC) alpha- and beta-subunit mRNA transcripts in villus and crypt epithelial cells of duodenum, with corresponding surface and crypt cells of colon from sodium-depleted rats. METHODS: Cells were loaded with 36Cl- and forskolin-stimulated efflux was determined. RT-PCR was performed for CFTR mRNA transcripts and ENaC alpha- and beta-subunit mRNA. Duodenal epithelial cell response to VIP was assessed by measuring intracellular cAMP. RESULTS: Forskolin-stimulated Cl- efflux occurred with decreasing magnitude in duodenal crypt, duodenal villus, colonic crypt and colonic surface cells in Na(+)-depleted animals. CFTR expression was correlated directly with Cl- efflux (r=0.91, P<0.01). Na+ channel alpha-subunit was expressed in colon and duodenum in animals fed diets with a high or low sodium content. While the beta-subunit mRNA was detected in the colon of sodium-restricted rats, it was absent in the duodenum under control conditions and after Na+ restriction. There was an inverse correlation between mRNA transcripts for CFTR and the ENaC alpha-subunit (r=-0.93, P<0.003) and beta-subunit (r=-0.91, P<0.004) in colon. VIP-stimulated cAMP in duodenal epithelial cells was greater in crypt than villus (P<0.05). CONCLUSION: Cl- efflux, CFTR transcription and forskolin-stimulated cAMP activity occur in both crypt and villus epithelial cells in duodenum. Possible interaction between CFTR and Na+ channels is apparently limited to parts of the colonic crypt. Lack of duodenal beta-subunit expression makes ENaC activity unlikely.

Endoluminal methods of treating gastroesophageal reflux disease.

Several endoluminal methods of treating gastroesophageal reflux disease (GERD) have either been approved, or are under investigation and development. This review outlines the two approved methods (Bard's endoluminal sewing machine and Curon's Stretta radiofrequency treatment), and describes the available data on new methods under investigation. The various methods can be divided into three broad categories: methods that create a controlled stricture, methods that bulk the gastroesophageal junction, and methods that attempt to create a fundoplication. The pros and cons of each method are discussed. Unlike medical treatment, these methods attack the reflux itself, not just the symptoms. This is a promising approach. However, the controlled stricture and bulking methods do not approach the success rate of a standard fundoplication.

Measles is more prevalent in Crohn's disease patients. A multicentre Israeli study.

The question whether there is a transmissible pathogenetic agent as a cause for Crohn's disease, remains unanswered. Measles virus has been the subject of many intensive studies, in the attempt to find a role for it in the pathogenesis of inflammatory bowel disease. Whether an early infection with measles virus may predispose to Crohn's disease in later life is still not clear. We conducted a large scale multicentre study, in order to obtain sufficient data to answer this question. To do so, we compared inflammatory bowel disease patients, with Crohn's disease or ulcerative colitis, with two matched control groups: clinical controls, and community controls. A total of 531 patients, 271 with ulcerative colitis and 260 with Crohn's disease were interviewed, as well as 903 matched controls. Blood from 104 inflammatory bowel disease patients and 50 controls was tested for antibodies to measles virus. We did not find any differences related to measles vaccination, either in Crohn's disease or in ulcerative colitis. Exposure to measles in childhood was more frequent in Crohn's disease patients than in their controls, the difference being statistically significant (p < 0.05) in relation to community controls. The presence of IgG antibodies to measles virus was higher in patients with Crohn's disease than in patients with ulcerative colitis or controls (p = 0.084). Another observation of interest was the finding that Crohn's disease patients who had measles in childhood, more frequently had large bowel disease than those who had not had measles. These data lead us to postulate that there may be a role for measles infection in Crohn's disease, even if, at present, this role remains unclear.

Effects of current cigarette smoking on clinical course of Crohn's disease and ulcerative colitis.

Cigarette smoking worsens Crohn's disease (CD) but ameliorates ulcerative colitis (UC). In Israel, where there is no epidemiological association of smoking with CD, we examined the effects of current smoking on the course of CD and UC. Patients at nine public hospitals completed a questionnaire detailing their smoking history, disease course and treatments; subjects altering their smoking habit after the onset of disease were excluded. Sixty-four smokers and 144 nonsmokers had CD, and 34 smokers and 158 nonsmokers had UC. No differences were found between CD smokers and nonsmokers for hospitalizations, operations, and requirement for corticosteroid and immunosuppressive treatment. By contrast, UC smokers had less extensive disease than nonsmokers (P < 0.02) and fewer hospitalizations (P = 0.01) and operations (P = 0.025). Our results agree with a minority of studies showing no adverse effect of smoking on the course of CD, and confirm the protective effect of smoking in UC.

Appendectomy is more frequent but not a risk factor in Crohn's disease while being protective in ulcerative colitis: a comparison of surgical procedures in inflammatory bowel disease.

OBJECTIVE: Appendectomy was shown to be protective in patients with ulcerative colitis (UC). There are fewer data in Crohn's disease (CD). Other operations were less studied. The aim of this study was to investigate the prevalence of appendectomy, cholecystectomy, and tonsillectomy, including their timing, in patients with inflammatory bowel disease in comparison to controls. METHODS: Two hundred seventy-one patients with UC and 260 with CD, 475 clinic controls, and 428 community controls were interviewed. RESULTS: Appendectomy was found in 5.5% patients with UC, in 11% of clinic controls (p < 0.05), and 7.7% of community controls (p = not significant). The differences were more significant for appendectomy before onset of disease. Appendectomy was performed in 19.2% of patients with CD, in 10.9% of clinic controls, and in 10.1% of community controls (p < 0.01). However, there were no significant differences when only appendectomy before onset of disease was considered. Cholecystectomy was found in 1.5% of patients with UC, in 6.1% of clinic controls (p < 0.01), and in 4.5% of community controls (p = not significant). The difference remained significant when confined to operations performed before disease onset. No such difference was found in patients with CD. No significant difference was found in the prevalence of tonsillectomy between patients and controls. CONCLUSIONS: Appendectomy is protective in UC; it is more frequent, but not a risk factor in CD. The role of cholecystectomy should be investigated further.

Propofol versus midazolam for conscious sedation guided by processed EEG during endoscopic retrograde cholangiopancreatography: a prospective, randomized, double-blind study.

BACKGROUND AND STUDY AIMS: Endoscopic retrograde cholangiopancreatography (ERCP) is a complex procedure, which requires appropriate sedation. The aim of this prospective, randomized, double-blind study was to compare the quality and characteristics of sedation with midazolam or propofol in patients undergoing ERCP. PATIENTS AND METHODS: A total of 32 patients undergoing ERCP were randomly allocated for sedation with propofol (n = 15) or midazolam (n = 17). Blood pressure, heart rate, and O2 saturation were monitored. Sedation was maintained at near constant levels by use of the spectral edge frequency (SEF) technique, an EEG-based method for measuring the depth of sedation. Clinical variables, patient cooperation, time to recovery, and amnesia served as outcome variables. RESULTS: There was no significant difference between the two study groups in patient characteristics. The "target SEF" was 13.6 +/- 0.7 Hz for the propofol group and 14.8 +/- 1.1 Hz for the midazolam group (n.s.). The only clinical parameter with a significant difference between the groups was the percent of time in which the heart rate deviated more than 20% from baseline for at least 2 minutes, i.e. 14.6 +/- 2.0 % for propofol and 48.2 +/- 38.0% for midazolam (P<0.01). Patient cooperation was better in the propofol group than in the midazolam group (full cooperation, 13/15 vs. 1/17, respectively; P<0.001). Patient recovery was significantly quicker in the propofol group (P<0.001). The degree of amnesia was similar in both groups; no patient in either group remembered details of the procedure. CONCLUSIONS: ERCP is better tolerated by patients sedated with propofol compared with midazolam, with a shorter recovery time and lesser hemodynamic side effects. Propofol should be considered to be the sedative drug of choice for ERCP.

Passive smoking in patients with inflammatory bowel disease: an Israeli multicentre case-control study.

BACKGROUND: The association between smoking and inflammatory bowel disease (IBD) is well established. There are, however, no large scale studies of passive smoking in inflammatory bowel disease and this has never been surveyed in the Jewish population of Israel. AIM: To study the passive smoking exposure of Jewish IBD patients in Israel in a large scale multicentre study. METHODS: Patients with established IBD, aged 18-70 years, were interviewed regarding smoking and other habits. Two controls, one clinic and one neighbourhood, matched by age, sex, community group, and education, were sought for each subject. RESULTS: Five hundred and thirty-four patients (273 ulcerative colitis (UC) and 261 Crohn's disease (CD)), 478 clinic controls and 430 community controls were interviewed. There were no significant differences in the passive smoking habits between IBD patients and their controls. Fifty-one percent of UC patients, 50% of the clinic controls and 58% of the community controls were exposed to passive smoking at home (NS); similar results were found among CD patients (50%, 55% and 56%, respectively). When a quantitative exposure index was used UC patients were significantly less exposed to passive smoking than were their community controls (7.46 +/- 8.40 vs 9.36 +/- 9.46, n = 229, P< 0.031). There was no difference in the exposure to passive smoking among CD patients and their controls. No differences in exposure to passive smoking were found when UC patients who had never smoked were compared with their controls. When the quantitative index was used 'never-smoked' CD patients tended to be less exposed to passive smoking at home than their community controls (5.40 +/- 7.60 vs 8.04 +/- 8.72, P < 0.05). CONCLUSION: There is a lack of association between passive smoking and IBD in Jewish patients in Israel. When a quantitative exposure index was used UC patients were found to be less exposed to passive smoking than their community controls.

G protein levels and function as an objective measure of depression in patients with functional bowel disorders.

Heterotrimeric G proteins play a pivotal role in postreceptor information transduction. These proteins have been implicated in the pathophysiology, diagnosis, and treatment of mood disorders and proposed as a state-dependent biochemical mood marker in mononuclear leukocytes. Irritable bowel syndrome (IBS) is associated with changes in mood, affecting patients' illness perceptions and behavior. We examined whether mononuclear leukocytes of patients with IBS have altered G protein measures. We undertook G protein functional measurements through agonist-enhanced [3H]Gpp(NH)p binding capacity and quantitative measures by immunoblot analysis using anti-Galpha antibodies in mononuclear leukocytes obtained from 19 IBS patients (Rome criteria) and 19 healthy matched subjects. The study groups were similar in age, gender, and years of education. Mononuclear leukocyte functions of G(s) (21.3+/-8.3%) and G(i) (22.2+/-6.7%) proteins in IBS patients were similar to healthy subjects (24.8+/-4.7 and 25.2+/-4.0%, respectively). The relative immunoreactivities of the G(sa) (98.9+/-10.2%) and the G(ia) (104.2+/-11.5%) subunit proteins in mononuclear leukocytes of IBS patients were also similar to those in healthy subjects. Two patients clinically diagnosed as depressed were detected by the G protein assay. The results lend objective support to the contention that major depression is not a causative factor in IBS, nor associated with its severity. The G protein assay may provide an objective biochemical tool for detecting depression in IBS, differentiating it from psychological distress that is commonly diagnosed by subjective tests.

Detection of tumor mutant APC DNA in plasma of patients with sporadic colorectal cancer.

The aim of this study was to detect mutant APC DNA of tumor origin in the plasma of patients with sporadic colorectal carcinomas. The polymerase chain reaction (PCR) and the single strand conformation polymorphism (SSCP) procedures were employed to detect DNA alterations using primers to amplify the mutation cluster region of the APC gene. APC mutations were observed in 7 out of 11 archival colonic tumor specimens examined. Matching mutations in free plasma DNA of tumor origin were detected in 3 of the 7 patients (42.8%). The results of this preliminary report indicated the presence of APC DNA in plasma harboring the identical abnormal molecular signature of tumor APC DNA. Detection methods of mutant APC DNA in blood may prove useful in the screening and monitoring of patients at risk of or with colorectal cancer.

Use of the Functional Bowel Disorder Severity Index (FBDSI) in a study of patients with the irritable bowel syndrome and fibromyalgia.

OBJECTIVE: The purpose of this study was to evaluate the utility of the Functional Bowel Disorder Severity Index (FBDSI) as a measure of severity of disease among patients with the irritable bowel syndrome (IBS) and matched controls. METHODS: A total of 75 IBS patients and 69 matched controls completed questionnaires on bowel symptoms, health status, quality of life, psychological distress, concerns, anxiety, and sense of coherence. All participants also were tested for fibromyalgia (FS), a functional disorder of the musculoskeletal system. All participants were administered a questionnaire that included the FBDSI. On the basis of their responses to the questionnaire, the controls were subdivided as healthy controls (n = 48) or IBS nonpatients (n = 21). On the basis of the FS classification, 75 IBS patients were subdivided as IBS only (n = 50) or IBS and FS combined (n = 25). RESULTS: The mean FBDSI score was higher for the IBS patients than the controls (100.5+/-12.7 and 23.5+/-3.9, respectively; p < 0.001). IBS nonpatients had an intermediate score of 42.3+/-18.0. Patients with both IBS and fibromyalgia had the highest mean FBDSI score: 138.8+/-31.5. There was no association between FBDSI and age or gender, but FBDSI was significantly associated with other measures of health status. CONCLUSIONS: An association was found between the FBDSI and IBS patient status: IBS nonpatients, patients with IBS only, and patients with both IBS and fibromyalgia had increasingly severe scores. The results provide support for the validity of FBDSI as a measure of illness severity in functional gastrointestinal disorders.

Lack of association between smoking and Crohn's disease but the usual association with ulcerative colitis in Jewish patients in Israel: a multicenter study.

OBJECTIVE: The association between smoking and inflammatory bowel disease (IBD) is well established, but data in Jewish patients in Israel were discrepant. The aim of this study was to examine the smoking habits of Jewish IBD patients in Israel in a large scale, multicenter study. METHODS: Patients with established IBD aged 18-70 yr were interviewed in relation to smoking and other habits. Two controls (one clinic and one neighborhood control matched by age, sex, community group, and education) were sought for each subject. RESULTS: A total of 534 patients (273 ulcerative colitis [UC], and 261 Crohn's disease [CD]), along with 478 clinic controls and 430 neighborhood controls, were interviewed. There was no significant difference in the smoking habits between CD patients and their controls. Of patients with CD, 24.5% were current smokers, as compared to 19.9% of clinic controls and 25.2% of neighborhood controls (NS). The odds ratio for CD in current smokers was 1.30 (95% confidence interval 0.85-1.99) versus clinic controls, and 0.96 (0.63-1.46) versus neighborhood controls. There were also no significant differences in the proportion of ex-smokers between the groups. Only 12.9% of UC patients were current smokers versus 21.9. % Clinic controls, and 26.4% community controls (p<0.005). The proportions of ex-smokers were higher in UC patients 29.7% versus 25.9%, and 19.5% in their respective controls (p<0.001 vs. community controls). No significant differences were found in the proportions of never-smokers between IBD patients and controls. All the above trends were similar in four different parts of the country. The proportion of current smokers in UC decreased with the extent of disease (19.7% in proctitis, 13.6% in left-sided, and 4.5% in total colitis) (p<0.05). Patients with UC were more likely to be light smokers(1-10 cigarettes/day), whereas patients with CD were more likely to be moderate smokers (11-20 cigarettes/day) in comparison to their controls. CONCLUSIONS: The lack of association between smoking and CD has now been established in Jewish patients in Israel. The association was found in UC. The stronger genetic tendency in CD may contribute to this discrepancy.

Fibromyalgia in the irritable bowel syndrome: studies of prevalence and clinical implications.

OBJECTIVE: The irritable bowel syndrome (IBS) and the fibromyalgia syndrome (FS) coexist in many patients. We conducted complementary studies of the prevalence of FS in IBS patients and matched controls, and of IBS in FS patients and the implications of concomitant IBS and FS on health-related quality of life (HRQOL). METHODS: A study of 79 IBS patients with 72 matched controls (IBS study), and a study of 100 FS patients (FS study). All participants underwent tests of tender point sites and threshold of tenderness and answered questionnaires including personal and medical history, GI symptoms, and indices of HRQOL. RESULTS: In the IBS study, 25 of the 79 IBS patients (31.6%) and 3 of the 72 controls (4.2%) had FS (p < 0.001). Statistically significant differences were found among the study groups in terms of global well-being (p < 0.001), sleep disturbance (p < 0.001), physician visits (p = 0.003), pain (p < 0.001), anxiety (p < 0.001), and global severity index (SCL-90-R) (p < 0.001), with patients with IBS and FS having the worst results. IBS patients had significantly more tender points than controls (p < 0.001). In the FS study, 32 of the 100 FS patients (32%) had IBS. Patients with both disorders had significantly worse scores for physical functioning (p = 0.030) and for all but one of a 16-item quality of life questionnaire. CONCLUSIONS: FS and IBS coexist in many patients. Patients with both disorders have worse scores on HRQOL indices than patients with either disorder alone, or controls. Physicians treating these patients should be aware of the overlap, which can affect the presentation of symptoms, health care utilization, and treatment strategies.

The sense of coherence index and the irritable bowel syndrome. A cross-sectional comparison among irritable bowel syndrome patients with and without coexisting fibromyalgia, irritable bowel syndrome non-patients, and controls.

BACKGROUND: Sense of Coherence (SOC) is a global orientation that affects coping with stressors. A strong SOC is associated with better health outcomes. The purpose of this study was to evaluate SOC among patients with irritable bowel syndrome (IBS) and matched controls. METHODS: Seventy-nine IBS patients and 72 matched controls completed questionnaires and were tested for fibromyalgia (FS). The controls were subdivided into healthy controls (n = 49) or IBS non-patients (n = 23), and the patients into IBS only (n = 54) or IBS and FS (n = 25). RESULTS: The mean SOC score was higher for the controls than for the IBS patients (65.7+/-1.2 and 59.6+/-1.1, respectively; P = 0.003). There was no significant difference between the healthy controls and the IBS non-patients. The controls had a higher SOC than patients with IBS only and patients with IBS and FS (P = 0.0004). CONCLUSIONS: An association was found between IBS and SOC. No causality can be inferred from this study. Individuals with low SOC may be more likely to express symptoms in terms of psychologic distress and increased health care utilization because of poor coping skills. Conversely, the presence of IBS may affect SOC negatively. Further longitudinal studies could clarify the potential of SOC as a predictor variable (for example, for treatment results) or an outcome variable.

Controlled release of TGF-beta1 impedes rat colon carcinogenesis in vivo.

Transforming growth factor beta1 (TGF-beta1) is a cytokine known to play a key role in the control of cell growth. TGF-beta1 potently inhibits the proliferation of human and rodent-derived epithelial cells. Colonic precancerous and moderately differentiated cancer cells are responsive to TGF-beta1, whereas malignant colon cancer cells are resistant to the inhibitory action of the cytokine. These observations have been derived exclusively from in vitro studies. Therefore, the main aim of our study was to determine whether TGF-beta1 exerts a growth-restraining action on colon carcinogenesis in vivo. TGF-beta1 was sequestered into ethylene acetate copolymer matrices and "loaded" preparations were implanted intraperitoneally (i.p.) in rats. One week later, the animals were treated with dimethylhydrazine (DMH), a colon procarcinogen. Empty matrices devoid of TGF-beta1 but containing bovine serum albumin (BSA) carrier served as the appropriate control preparations. The number of aberrant crypt foci (ACF), considered to be preneoplastic lesions of the colon, was scored. Tumor formation and size were assessed at the appropriate times. TGF-beta1 released in a sustained manner from copolymer matrices: (i) markedly inhibited colonic ACF formation and the number of aberrant crypts and (ii) significantly reduced colonic tumor formation and size.