Cancer surveillance in ulcerative colitis

BACKGROUND: Patients with ulcerative colitis are at a higher risk of developing colorectal cancer than those without the disease. Surveillance programmes are used routinely to detect dysplasia and cancer in patients with ulcerative colitis. However, such programmes are poorly effective. This article discusses possible improvements suggested by recent research. METHODS: Papers relating to cancer associated with ulcerative colitis and surveillance programmes to detect such cancer were identified using Medline searches. Further papers were identified from the reference lists of identified papers. RESULTS: The probability of cancer for all patients with ulcerative colitis regardless of disease extent was 2 per cent at 10 years, 8 per cent at 20 years and 18 per cent at 30 years; the overall prevalence of colorectal cancer in any patient was 3.7 per cent. Indications for colonoscopic surveillance are extensive disease for 8-10 years, especially in those with active inflammation, a family history of colorectal cancer and primary sclerosing cholangitis. Problems affecting surveillance include the diagnosis of dysplasia, difficulty in differentiating 'sporadic' adenomas from a dysplasia-associated lesion or mass, and decision making based on surveillance findings. Molecular genetic and endoscopic advances to alleviate these problems are discussed. CONCLUSION: Rates of detection of dysplasia can be improved by chromoendoscopy. Molecular genetics has the potential to identify patients most at risk of cancer and can differentiate between different types of lesion.     

Study of function and maturation of monocytes in morbidly obese individuals

In recent years there has been an intense interest in understanding the mechanisms involved in immune modulation associated with dietary restriction. In this study we have investigated maturation of peripheral blood monocytes in morbidly obese patients using an in vitro culture system. At the end of the culture, the matured monocytes (macrophages) were quantitated. Though there was no detectable functional defect observed in the matured monocytes in vitro, there was a quantitative difference in maturation among the monocytes plated. The number of monocytes that matured into macrophages in obese patients was 3.29 ± 2.41 × 10⁴ cells per milliliter of blood, as compared to 8.24 ± 3.14 × 10⁴ per milliliter of blood in normal volunteers. This difference was found to be statistically significant at P < 0.001. These results indicate a possible development of an intrinsic defect among morbidly obese individuals.     

Hepatitis C antibodies in asymptomatic first-time blood donors in The Gambia: prevalence and risk factors

This study evaluates the seroprevalence and risk factors for hepatitis C (HCV) antibodies in asymptomatic first-time blood donors in The Gambia. The study population includes 460 blood donors (age range: 18-40 years [mean: 27.5]) who attended the Royal Victoria Teaching Hospital from July to December 2002. Antibodies to hepatitis C are determined using and enzyme-linked immunosorbent assay (ELISA) test system. The prevalence of hepatitis C found in this study was 1.1% (95% CI, 0.16-1.12). Previous history of sexually transmitted disease, married men in polygamous relationships, and hospital or clinic-based workers were determined to be at risk of acquiring hepatitis C. The study shows that seroprevalence of hepatitis C in The Gambia is low compared to other countries in the region.     

The effect of prenatal care on birthweight: a full-information maximum likelihood approach

This paper uses a full-information maximum likelihood estimation procedure, the Discrete Factor Method, to estimate the relationship between birthweight and prenatal care. This technique controls for the potential biases surrounding both the sample selection of the pregnancy-resolution decision and the endogeneity of prenatal care. In addition, we use the actual number of prenatal care visits; other studies have normally measured prenatal care as the month care is initiated. We estimate a birthweight production function using 1993 data from the US state of Texas. The results underscore the importance of correcting for estimation problems. Specifically, a model that does not control for sample selection and endogeneity overestimates the benefit of an additional visit for women who have relatively few visits. This overestimation may indicate 'positive fetal selection,' i.e., women who did not abort may have healthier babies. Also, a model that does not control for self-selection and endogenity predicts that past 17 visits, an additional visit leads to lower birthweight, while a model that corrects for these estimation problems predicts a positive effect for additional visits. This result shows the effect of mothers with less healthy fetuses making more prenatal care visits, known as 'adverse selection' in prenatal care.     

Effect of vitamin D analog (1alpha hydroxy D5) immunoconjugated to Her-2 antibody on breast cancer

We previously showed that a new vitamin D analog, 1alpha(OH)D5 (D5), induced differentiation and inhibited the growth of breast cancer cells. In this report, we examined whether D5 specifically delivered to breast cancer cells could have any therapeutic effect. D5 was linked to Her-2 antibody using sulfosuccinimidyl 6-4 azido nitrophenylamido hexanode (SANPAH) as a linker. The Her-2 antibody selected in our study had no significant effect on the in vitro or in vivo growth of breast cancer cells; however, it had cell-differentiating action. In vitro, D5-Her-2 antibody conjugate (IMC) showed the ability to specifically bind to Her-2-expressing cells, to compete with Her-2 antibody for surface receptor and to cause internalization. IMC (equivalent to 5 microg Her-2 antibody given intraperitoneally once weekly for 6 weeks) significantly inhibited the growth of BT-474 cells transplanted into athymic mice. The in vivo growth-inhibitory effect of IMC treatment was similar to that observed in animals receiving D5 continuously as a dietary supplement. These results show that the targeted delivery of D5 by immunoconjugation to cell surface receptor antibodies may be of potential therapeutic value for the treatment of Her-2 positive breast cancer.     

Elevated cyclooxygenase-2 expression correlates with distant metastases in breast cancer

BACKGROUND: Cyclooxygenase-2 (COX-2) overexpression clearly plays an important role in the pathogenesis of breast cancer. In this study, we analysed the relationship between COX-2 expression and various clinicopathological factors in human breast cancer. MATERIALS AND METHODS: Using immunohistochemistry, we analysed archival specimens of human breast cancer (n=29) using antibodies to COX-2, ER, PgR and HER2 and, from medical records, obtained clinicopathological data. RESULTS: We observed a significant association between COX-2 overexpression and distant metastasis. COX-2 expression was not significantly associated with any other clinical or pathological variable. CONCLUSION: These findings lend support to the hypothesis that COX-2 overexpression represents an adverse prognostic event in human breast cancer and are encouraging for proposed strategies of COX-2 suppression to treat the disease.     

The contribution of HLA genes to IBD susceptibility and phenotype

The human leukocyte antigen (HLA) region located on chromosome 6p encodes the highly polymorphic, classical class I and II genes essential for normal lymphocyte function; it also encodes a further 224 genes. Many early studies investigating this region were limited by small sample size, poor statistical methodology, population stratification and variable disease definition. Although more recent studies have improved study design, investigators are still challenged by the complex patterns of linkage disequilibrium across this gene-dense region, and by the disease heterogeneity characteristic of all genetically complex disorders. However, a number of important observations have emerged from recent studies: (1) the HLA harbours gene(s) that determine susceptibility to colonic inflammation in both ulcerative colitis (UC) and Crohn's disease (CD); (2) most of the specific associations with UC and CD appear to differ; (3) associations between different ethnic groups differ; (4) markers in the HLA might predict the course of disease and the development of complications, notably the extraintestinal manifestations of disease.     

Comparison of the inhibition of human metapneumovirus and respiratory syncytial virus by NMSO3 in tissue culture assays

Human metapneumovirus (hMPV) is a recently elucidated respiratory virus pathogen for which there are no agents currently licensed to prevent or treat infections caused by it. However, NMSO3 has been reported to inhibit replication of human respiratory syncytial virus (hRSV), a virus that is closely related to hMPV, both in vitro in tissue culture cells and in vivo in cotton rats. For this reason, experiments were performed to compare the antiviral activity of NMSO3 against both hRSV and hMPV in tissue culture-based assays. Heparin and ribavirin, two other compounds known to inhibit hRSV, and two other paramyxoviruses, human parainfluenza virus type 3 (PIV3) and measles virus (MV), were included in these tests for comparison. All three compounds significantly inhibited the replication of subtype A and B strains of hRSV and serotypes 1 and 2 hMPV. However, unlike ribavirin, NMSO3 and heparin inhibited only hMPV and hRSV and not PIV3 or MV. Also unlike ribavirin, the activity of the two sulfated molecules was most effective if these materials were present during virus attachment and penetration of host cells. Interestingly, NMSO3, but not heparin, was able to limit secondary infection and spread of both viruses.     

A placebo-controlled study of nefazodone for the treatment of chronic posttraumatic stress disorder: a preliminary study

Nefazodone is a unique serotonergic antidepressant that acts as both a presynaptic serotonin reuptake inhibitor and a postsynaptic 5-hydroxytryptamine 2A receptor antagonist. Based on the positive results of open-label trials of nefazodone, including one from our group, we tested nefazodone's efficacy in the treatment of posttraumatic stress disorder (PTSD) under placebo-controlled conditions. Forty-one patients with chronic PTSD, predominantly male combat veterans, were enrolled in a randomized, double-blind, placebo-controlled 12-week trial of nefazodone. The primary outcome measure was the Clinician-Administered PTSD Scale. Fifteen patients were randomized to placebo and 26 were randomized to nefazodone. In a repeated-measures analysis of variance with last observation carried forward, patients on nefazodone showed a significant improvement in the percentage change of Clinician-Administered PTSD Scale Total score from baseline compared with those on placebo (P = 0.04; effect size = 0.6). Sample size was not powered to test group differences in the Clinician-Administered PTSD Scale criterion B, C, or D subscale. However, the criterion D subscale showed significant improvement in patients treated with nefazodone compared with those treated with placebo (P = 0.007). In addition, the Hamilton Rating Scale for Depression showed significant improvement compared with placebo (P = 0.008). The nefazodone group also reported an improvement on the PTSD Checklist (self-report scale; P = 0.08) and the Clinician-Administered Dissociative States Scale (P = 0.06). This pilot study supports the efficacy of nefazodone for the treatment of PTSD. However, larger placebo-controlled studies in more diverse patient population are warranted.     

Knowledge and beliefs about influenza,pneumococcal disease,and immunizations among older people

OBJECTIVES: Despite the burden of disease caused by influenza and pneumococcus, immunization rates are moderate and have not reached national goals set for 2010. This study's objective was to identify patient knowledge, attitudes, and beliefs that serve as facilitators of and barriers to influenza and pneumococcal vaccination. DESIGN: A survey conducted in 2000 by computer-assisted telephone interviewing. SETTING: To encounter a broad spectrum of patients and healthcare systems, we sampled patients at inner-city health centers, Department of Veterans Affairs outpatient clinics, and rural and suburban practices. PARTICIPANTS: Inclusion criteria were patients aged 66 and older and an office visit after September 30, 1998. MEASUREMENTS: Responses to questionnaire. RESULTS: Overall, 1,007 (82%) interviews were completed among 1,234 people contacted by phone. Vaccination against pneumococcal disease was significantly related to being able to accurately describe one or more classic symptoms of pneumonia (P =.05). Vaccination against influenza and pneumococcal disease was significantly related to belief that vaccination was the best way to prevent these diseases (P <.001). The unvaccinated reported that they felt they were not likely to contract influenza and that they did not know they needed the pneumococcal vaccine. Access was not related to vaccination status. CONCLUSIONS: Educational campaigns to increase vaccination rates among older adults should focus on symptoms of, risk for, and severity of influenza and pneumococcal diseases and encouraging physicians to recommend the vaccines to their patients.