[Guided discontinuation of antidepressants: approach and first results of a Dutch multidisciplinary outpatient clinic]. / Werkwijze en eerste resultaten van multidisciplinaire afbouwpoli anti-depressiva.

BACKGROUND: Discontinuation of antidepressant medication can be difficult due to withdrawal symptoms and relapse risk. Scientific evidence on the questions of who, when, and how to stop antidepressants is limited. In Amsterdam a multidisciplinary outpatient clinic was started to provide advice and guidance. AIM: To substantiate the design of the clinic. Central questions relate to knowing which patients are referred, the background of their request, and their experiences with the outpatient clinic. METHOD: The first 51 patients of the clinic were described on the basis of file research, in addition a survey was conducted into patient experiences. RESULTS: Half of the patients (55%) actually started discontinuation, 39% were advised not to do so (yet). Patients at the clinic had used antidepressants for an average of 10 years, and 76% had previously attempted to stop. 21% had now successfully stopped and 25% were satisfied with a lower dose. One patient relapsed during tapering. CONCLUSION: So far, patients with long-term antidepressant use and multiple quit attempts have been referred. Our experiences are aimed at helping individual patients but can also result in more knowledge about who can stop at what moment, and how this should be done.

Does Social Capital Benefit Older Adults' Health and Well-Being? The Mediating Role of Physical Activity.

Objectives: To assess whether social capital benefits older adults' self-rated health and well-being and whether physical activity mediates this relation. Methods: A survey study was conducted among members of a sociocultural organization (age ≥55 years), both cross-sectionally (baseline Time 1; N = 959) and longitudinally (3-year follow-up Time 2; N = 409). Results: Specific indicators of social capital were positively, though modestly, related to health and well-being at Time 1 and Time 2. Experienced connectedness with age peers emerged as the strongest predictor. Physical activity only mediated the relation with experienced safety in society. Discussion: The relative importance of older adults' experienced connectedness with their age peers underlines the importance of internalized group membership as a determinant of their health and well-being. Physical activity seems to play only a minor mediating role.

HIV testing for key populations in Europe: A decade of technological innovation and patient empowerment complement the role of health care professionals.

OBJECTIVES: With persisting high numbers of new HIV diagnoses in Europe, HIV testing remains an important aspect of HIV prevention. The traditional centralized and medicalized HIV testing approach has been complemented with newly developed and evaluated non-traditional approaches. Two important factors guided this process: technological innovation and empowerment of the patient. METHODS: We present a matrix to develop an HIV testing approach, and elaborate on three commonly used ones: community based testing, self-testing, and self-sampling. Despite non-traditional HIV testing approaches, barriers for testing remain. A potential disadvantage for users is the risk for false-reactive test results. As users receive an orientation test result, a reactive result should be confirmed. Another issue is the window phase, which is longer for some orientation tests compared to a traditional, laboratory-based test. RESULTS: Future implementation of non-traditional HIV testing approaches will depend on legal frameworks throughout Europe. Community testing centers may additionally improve empowerment of key populations by expanding their portfolio to testing and treatment for sexually transmitted infections. Community engagement and ownership may imply a shrinking role for health care providers, but they remain crucial actors for personalized information, counselling and referral to specialized HIV-care for many people. CONCLUSIONS: A highly effective HIV testing strategy to reduce undiagnosed people living with HIV in Europe is needed. Any approach, chosen according to the principles outlined in this paper, should reach the right people, diagnose them in the most accurate way, and optimize linkage to care.

The power of competence support: The impact of coaches and athlete leaders on intrinsic motivation and performance.

Grounded in the Cognitive Evaluation Theory, a mini-theory of Self-Determination Theory, this experimental field study sought to examine the impact of competence support of both coaches and athlete leaders on athletes' competence satisfaction, intrinsic motivation, and subjective as well as objective performance. Male basketball players (N = 120) were allocated to groups of 5 players. These groups were then randomly assigned to a control group or to 1 of 3 experimental conditions. In these experimental conditions, either the coach, the athlete leader, or both provided motivational feedback to their team. The provision of motivational feedback by either the coach or the athlete leader was sufficient to increase athletes' competence satisfaction, intrinsic motivation, and objective performance (i.e., enhanced execution time without a decrease in scoring percentage) relative to the control group. Interestingly, when both the coach and the athlete leader provided competence support, a surplus effect was observed on objective performance compared with when only the coach provided competence support. Furthermore, structural equation modeling revealed that players' competence satisfaction mediated the relationship between the provided competence support and players' intrinsic motivation, while a direct effect was observed on objective performance. In conclusion, the study findings indicate that also athlete leaders can adopt a motivating role, and that by doing so, their impact is as strong as the impact of the coach. Both coaches and athlete leaders can thus boost athletes' objective performance and foster competence satisfaction, with the latter resulting in increased intrinsic motivation.

Evaluation of the intercept oral specimen collection device with HIV assays versus paired serum/plasma specimens.

Oral fluid has many advantages over blood-based techniques: it is less invasive, eliminates the occupational risk associated with needle stick accidents and collection can be self-administrated. Each individual test is packaged with a corresponding collection device. This study tested the suitability of the Intercept Oral Specimen Collection Device for different HIV diagnostic tests: three different rapid HIV tests and two adapted ELISAs, which were evaluated and compared with a gold standard on blood. In addition a total IgG quantification was performed to demonstrate the quality of the specimen. HIV antibodies were detected with a sensitivity of 100%, 99.3%, 98.6%, 100% and 95.7% for, DPP, OraQuick, Aware, Genscreen and Vironostika respectively using the Intercept Collection Device. Respective specificities were 100%, 100%, 99.3%, 97.3% and 100%.

Transmission of HIV Drug Resistance and the Predicted Effect on Current First-line Regimens in Europe.

BACKGROUND: Numerous studies have shown that baseline drug resistance patterns may influence the outcome of antiretroviral therapy. Therefore, guidelines recommend drug resistance testing to guide the choice of initial regimen. In addition to optimizing individual patient management, these baseline resistance data enable transmitted drug resistance (TDR) to be surveyed for public health purposes. The SPREAD program systematically collects data to gain insight into TDR occurring in Europe since 2001. METHODS: Demographic, clinical, and virological data from 4140 antiretroviral-naive human immunodeficiency virus (HIV)-infected individuals from 26 countries who were newly diagnosed between 2008 and 2010 were analyzed. Evidence of TDR was defined using the WHO list for surveillance of drug resistance mutations. Prevalence of TDR was assessed over time by comparing the results to SPREAD data from 2002 to 2007. Baseline susceptibility to antiretroviral drugs was predicted using the Stanford HIVdb program version 7.0. RESULTS: The overall prevalence of TDR did not change significantly over time and was 8.3% (95% confidence interval, 7.2%-9.5%) in 2008-2010. The most frequent indicators of TDR were nucleoside reverse transcriptase inhibitor (NRTI) mutations (4.5%), followed by nonnucleoside reverse transcriptase inhibitor (NNRTI) mutations (2.9%) and protease inhibitor mutations (2.0%). Baseline mutations were most predictive of reduced susceptibility to initial NNRTI-based regimens: 4.5% and 6.5% of patient isolates were predicted to have resistance to regimens containing efavirenz or rilpivirine, respectively, independent of current NRTI backbones. CONCLUSIONS: Although TDR was highest for NRTIs, the impact of baseline drug resistance patterns on susceptibility was largest for NNRTIs. The prevalence of TDR assessed by epidemiological surveys does not clearly indicate to what degree susceptibility to different drug classes is affected.

We will be champions: Leaders' confidence in 'us' inspires team members' team confidence and performance.

The present research examines the impact of leaders' confidence in their team on the team confidence and performance of their teammates. In an experiment involving newly assembled soccer teams, we manipulated the team confidence expressed by the team leader (high vs neutral vs low) and assessed team members' responses and performance as they unfolded during a competition (i.e., in a first baseline session and a second test session). Our findings pointed to team confidence contagion such that when the leader had expressed high (rather than neutral or low) team confidence, team members perceived their team to be more efficacious and were more confident in the team's ability to win. Moreover, leaders' team confidence affected individual and team performance such that teams led by a highly confident leader performed better than those led by a less confident leader. Finally, the results supported a hypothesized mediational model in showing that the effect of leaders' confidence on team members' team confidence and performance was mediated by the leader's perceived identity leadership and members' team identification. In conclusion, the findings of this experiment suggest that leaders' team confidence can enhance members' team confidence and performance by fostering members' identification with the team.

Late presentation to HIV testing is overestimated when based on the consensus definition.

OBJECTIVES: In 2011, a consensus was reached defining "late presenters" (LPs) as individuals presenting for care with a CD4 count < 350 cells/µL or with an AIDS-defining event, regardless of CD4 count. However, a transient low CD4 count is not uncommon in recent infections. The objective of this study was to investigate how measurements of late presentation change if the clinical stage at the time of diagnosis is taken into account. METHODS: Case surveillance data for newly diagnosed patients in Belgium in 1998-2012 were analysed, including CD4 count at diagnosis, the presence of AIDS-defining events, and recent infections (< 6 months) as reported by clinicians in the case of acute illness or a recent negative test. First, proportions of LPs were calculated according to the consensus definition. Secondly, LPs were reclassified as "nonlate" if infections were reported as recent. RESULTS: A total of 7949 HIV diagnoses were included in the study. Recent infections were increasingly reported over time, accounting for 8.2% of new infections in 1998 and 37.5% in 2012. The consideration of clinical stage significantly modified the proportion of LPs: 18.2% of men who have sex with men (MSM) diagnosed in 2012 would be classified as LPs instead of 30.9% using the consensus definition (P < 0.001). The proportion of patients misclassified as LPs increased significantly over time: 5% in MSM in 1998 vs. 41% in 2012. CONCLUSIONS: This study suggests that low CD4 counts in recent infections may lead to overestimation of late presentation when applying the consensus definition. The impact of transient CD4 count on late presentation estimates should be assessed and, if relevant, the introduction of clinical stage in the definition of late presentation should be considered.

Role of genetic alterations in the NLRP3 and CARD8 genes in health and disease.

The complexity of a common inflammatory disease is influenced by multiple genetic and environmental factors contributing to the susceptibility of disease. Studies have reported that these exogenous and endogenous components may perturb the balance of innate immune response by activating the NLRP3 inflammasome. The multimeric NLRP3 complex results in the caspase-1 activation and the release of potent inflammatory cytokines, like IL-1ß. Several studies have been performed on the association of the genetic alterations in genes encoding NLRP3 and CARD8 with the complex diseases with inflammatory background, like inflammatory bowel disease, cardiovascular diseases, rheumatoid arthritis, and type 1 diabetes. The aim of the present review is therefore to summarize the literature regarding genetic alterations in these genes and their association with health and disease.

Using conventional HIV tests on oral fluid.

There is need for more evaluations of non-invasive tests in order to broaden the reach of testing programs and to perform large scale epidemiological studies. In this study, three different human immunodeficiency virus (HIV) enzyme linked immunosorbent assays (ELISAs) and one line immunoassay were evaluated to detect HIV antibodies in oral fluid samples. Specimens were collected, after informed consent was obtained, with the Oracol (MMD, Worcester, England) device. A total IgG quantitation test was performed to demonstrate the quality of the sample. Assessment of a modified protocol of the Vironostika HIV Ag/Ab, Enzygnost Anti-HIV 1/2 Plus Genscreen HIV-1/2 Version 2 and a line immune confirmatory assay the INNO-LIA HIV I/II score was done, using oral fluid specimens of 325 HIV positive and negative individuals. For the ELISAs, the addition of an extra internal oral fluid control was evaluated as well as different cut-offs, time between sampling and testing and the effect of drinking water just before sampling. Finally, the confirmatory test and some testing algorithms and combination of tests were discussed. The results obtained from the oral fluid specimens were compared with the gold standard on paired serum specimens. Firstly, there was no significant difference observed between the use of the kit controls and the oral fluid controls. New protocols and calculation of cut-offs were defined for two of the three ELISAs. High sensitivities and specificities were obtained with all three ELISAs without any statistical difference between the three tests. Secondly, no statistically significant difference was observed when samples were stored for different time periods between sampling and testing, meaning that a period of seven days at room temperature before testing is still acceptable. Thirdly, drinking water before sample collection did not interfere with the testing, although lower optical densities were observed. None of the positive samples were missed. In addition, the line immunoassay INNO-LIA HIV I/II score test is a promising test for confirmation of reactive oral fluid specimen, but more samples need to be validated in order to adapt the interpretation rules specifically for oral fluid specimens. Different choices/algorithms adapted for the purpose of testing can be proposed. In conclusion, it can be said that the commercial ELISAs with adapted protocol and cut-off values are suitable tools for making HIV test performance accessible to people. With this non-invasive sampling method, more eligible individuals can and will be selected for further HIV test on blood.

A venue-based HIV prevalence and behavioural study among men who have sex with men in Antwerp and Ghent, Flanders, Belgium, October 2009 to March 2010.

This venue-based, cross-sectional study reports on human immunodeficiency virus (HIV) prevalence and behaviour of 649 men who have sex with men (MSM) in Antwerp and Ghent, Flanders, Belgium, from October 2009 to March 2010. Using time-location sampling, we found that HIV prevalence in MSM who attended different types of venue ranged from a high of 14.5% (95% CI: 8.9­20.1; n=22 in cruising venues to 4.9% (95% CI: 1.9­7.9; n=10) in more general gay venues to 1.4% (95% CI: 0.0­3.6; n=3) at younger MSM venues. Of those who tested HIV positive (n=35, five were unaware of their HIV status or self-reported as being HIV negative. One in five respondents were of non-Belgian nationality. The results showed relatively high rates of testing for HIV (52.2%; 95 % CI: 47.8­56.2; n=288) and other sexually transmitted infections (STIs) (57.4%; 95% CI: 52.6­62.0; n=248) in the last 12 months. A majority of the men (n=233) used condoms consistently during their last anal sexual contact with a casual partner; however, HIV-positive men who were aware of their serostatus (n=30) reported less condom use with casual partners. This is the first such study in Belgium and the results constitute the evidence base for local, targeted interventions. Furthermore, our findings underscore the need for European cross-border cooperation to prevent HIV infection and other STIs among MSM.

Concordance between HIV-1 genotypic coreceptor tropism predictions based on plasma RNA and proviral DNA.

OBJECTIVE: The aim of the study was to evaluate the use of proviral DNA as a source of viral genetic material for genotypic coreceptor tropism testing (GTT). METHODS: GTT consisted of bulk V3 sequencing followed by geno2pheno interpretation with the interpretative cut-off [false positive rate (FPR)] set at 5 and 10%. GTT was performed for 165 patients with a viral load of >500 HIV-1 RNA copies/mL on simultaneously collected plasma RNA and proviral DNA, and for 126 patients with a viral load of <500 copies/mL on current proviral DNA and pretreatment plasma RNA. Phenotypic tropism testing (PTT) results were available for 142 samples. RESULTS: In the simultaneous RNA/DNA comparison, concordance in prediction was 95.2% (at FPR 10%) and 96.4% (at FPR 5%). Six RNA-R5/DNA-X4 and two RNA-X4/DNA-R5 discordances were observed at an FPR of 10%, and six RNA-R5/DNA-X4 discordances were observed at an FPR of 5%. In the longitudinal RNA/DNA comparison, concordance was 88.1% (at FPR 10%) and 90.5% (at FPR 5%). Eight RNA-X4/DNA-R5 and seven RNA-R5/DNA-X4 discordances were seen at an FPR of 10%, and 10 RNA-R5/DNA-X4 and two RNA-X4/DNA-R5 discordances at an FPR of 5%. The overall concordance of RNA GTT with PTT was 82% (at FPR 10%) and 83% (at FPR 5%). The overall concordance of DNA GTT with PTT was 85% (at both 10 and 5% FPRs). CONCLUSIONS: GTT produced highly concordant tropism predictions for proviral DNA and plasma RNA. GTT on proviral DNA offers a promising approach for tropism prediction in clinical practice, particularly for the assessment of treated patients with low or suppressed viraemia.

Low specificities of HIV diagnostic tests caused by Trypanosoma brucei gambiense sleeping sickness.

The accuracy of diagnostic tests for HIV in patients with tropical infections is poorly documented. Human African trypanosomiasis (HAT) is characterized by a polyclonal B-cell activation, constituting a risk for false-positive reactions to diagnostic tests, including HIV tests. A retrospective study of the accuracy of HIV diagnostic tests was performed with 360 human African HAT patients infected with Trypanosoma brucei gambiense before treatment and 163 T. b. gambiense-infected patients 2 years after successful treatment in Mbuji Mayi, East Kasai, Democratic Republic of the Congo. The sensitivities, specificities, and positive predictive values (PPVs) of individual tests and algorithms consisting of 3 rapid tests were determined. The sensitivity of all tests was 100% (11/11). The low specificity (96.3%, 335/348) and PPV (45.8%, 11/24) of a classical seroconfirmation strategy (Vironostika enzyme-linked immunosorbent assay [ELISA] followed by line immunoassay) complicated the determination of HIV status, which had to be determined by PCR. The specificities of the rapid diagnostic tests were 39.1% for Determine (136/348); 85.3 to 92.8% (297/348 to 323/348) for Vikia, ImmunoFlow, DoubleCheck, and Bioline; and 96.6 to 98.3% (336/348 to 342/348) for Uni-Gold, OraQuick, and Stat-Pak. The specificity of Vironostika was 67.5% (235/348). PPVs ranged between 4.9 and 64.7%. Combining 3 different rapid tests resulted in specificities of 98.3 to 100% (342/348 to 348/348) and PPVs of 64.7 to 100% (11/17 to 11/11). For cured HAT patients, specificities were significantly higher for Vironostika, Determine, Uni-Gold, and ImmunoFlow. T. b. gambiense infection decreases the specificities of antibody detection tests for HIV diagnosis. Unless tests have been validated for interference with HAT, HIV diagnosis using classical algorithms in untreated HAT patients should be avoided. Specific, validated combinations of 3 HIV rapid tests can increase specificity.

Evaluation of a rapid and simple fourth-generation HIV screening assay for qualitative detection of HIV p24 antigen and/or antibodies to HIV-1 and HIV-2.

The performance was assessed of a new, rapid, visual and qualitative immunoassay for the detection of HIV p24 antigen (Ag) and antibodies (Ab) to HIV-1 and HIV-2. Characterised serum or plasma specimens from patients diagnosed with HIV infection were tested: 179 samples of known Ab-positive patients harbouring different subtypes of HIV-1 (n=154) and HIV-2 (n=25) and 200 samples from individuals not infected with HIV. The assay's Ag sensitivity was assessed by testing HIV seroconversion panels (n=10) and primary HIV infection specimens (n=57). In addition, the influence of the genetic variability of HIV-1 on Ag detection was evaluated using dilutions of culture supernatants infected with different subtypes (n=50). The performance of the rapid test was compared to a "gold standard" testing algorithm with the use of a single Ag ELISA and with the Vironostika((R)) HIV Uni-Form II Ag/Ab test, a fourth-generation ELISA. The new assay, the Determine HIV-1/2 Combo demonstrated 100% (98.2-100.0) Ab specificity (200/200) and 100% (98.0-100.0) Ab sensitivity (179/179). In these samples, the observed Ag sensitivity was 86.6% (58/67) with the Determine HIV-1/2 Combo test and 92.5% (62/67) with the Vironostika compared to the reference single Ag ELISA. The assay could not detect Ag in one group O, one subtype F and two subtype H cell supernatant isolates. None of the HIV-2 Ag could be detected.

Role of the laboratory in ensuring global access to ARV treatment for HIV-infected children: consensus statement on the performance of laboratory assays for early infant diagnosis.

A two day meeting hosted by the World Health Organization (WHO) and the U.S. Centers for Disease Control and Prevention (CDC) was held in May 2006 in Entebbe, Uganda to review the laboratory performance of virologic molecular methods, particularly the Roche Amplicor DNA PCR version 1.5 assay, in the diagnosis of HIV-1 infection in infants. The meeting was attended by approximately 60 participants from 17 countries. Data on the performance and limitations of the HIV-1 DNA PCR assay from 9 African countries with high-burdens of HIV/AIDS were shared with respect to different settings and HIV- subtypes. A consensus statement on the use of the assay for early infant diagnosis was developed and areas of needed operational research were identified. In addition, consensus was reached on the usefulness of dried blood spot (DBS) specimens in childhood as a means for ensuring greater accessibility to serologic and virologic HIV testing for the paediatric population.

Pediatric human immunodeficiency virus screening in an African district hospital.

In order to evaluate alternative tests and strategies to simplify pediatric human immunodeficiency virus (HIV) screening at the district hospital level, a cross-sectional exploratory study was organized in the Democratic Republic of the Congo. Venous and capillary phlebotomies were performed on 941 Congolese children, aged 1 month to 12 years (153 children under 18 months and 788 children more than 18 months old). The HIV prevalence rate was 4.7%. An algorithm for children more than 18 months old, using serial rapid tests (Determine, InstantScreen, and Uni-Gold) performed on capillary blood stored in EDTA tubes, had a sensitivity of 100.0% (95% confidence interval [CI], 88.9 to 100.0%) and a specificity of 100.0% (95% CI, 99.5 to 100.0%). The results of this study suggest that the ultrasensitive p24 antigen assay may be performed on capillary plasma stored on filter paper (sensitivity and specificity, 100.0%; n=87) instead of venous plasma (sensitivity, 92.3%; specificity, 100.0%; n=150). The use of glucolets (instruments used to perform capillary phlebotomies), instead of syringes and needles, may reduce procedural pain and the risk of needle stick injuries at a comparable cost. Compared to the reference, HIV could have been correctly excluded based on one rapid test for at least 90% of these children. The results of this study point towards underutilized opportunities to simplify phlebotomy and pediatric HIV screening.

Five-year immunological outcome of highly active antiretroviral treatment in a clinical setting: results from a single HIV treatment centre.

Our objective was to study the evolution of CD4 cell count five years after starting highly active antiretroviral treatment (HAART) in a clinical setting. The study was performed at the HIV outpatient clinic, Institute of Tropical Medicine, Antwerp. All patients (n = 225) who started HAART in 1997, who had a CD4 cell count within six months prior to starting HAART and who were subsequently followed for at least two years were included. Change in CD4 cell count after start of HAART and the influence of patient and clinical factors were investigated using graphical exploration, endpoint analysis and mixed-effects linear regression. The mean CD4 cell count at start of HAART was 280 cells/mm(3). At the five-year endpoint of the study the mean increase in CD4 cell count was 333 cells/mm(3), while 79% of the patients had a viral load less than 400 copies/mL. There was a significant negative correlation between increase in CD4 cell count at five years and time since first positive HIV test at start of HAART (P = 0.021). Patients who ever had a HAART interruption of more than seven days had a significantly lower increase in CD4 cell count than those who did not (225 cells/mm(3) compared with 438 cells/mm(3); P < 0.001). A mixed-effects linear regression model additionally suggested a significant impact of exposure to antiretrovirals prior to HAART (P = 0.03). Overall, the recovery of CD4 cell count after five years of HAART is good, although therapy interruptions have an important negative impact.

The role of non-viral load surrogate markers in HIV-positive patient monitoring during antiviral treatment.

Monitoring the efficacy of highly active antiretroviral treatment (HAART) is crucial if disease progression and the emergence of viral mutants are to be avoided. Classical viral load monitoring is too expensive for large-scale use in resource-limited settings. Three alternative measures, CD4 count, total lymphocyte count (TLC) and haemoglobin, were evaluated as surrogate markers of treatment success (viral load below detection level) among 710 HIV-positive patients who started HAART in an HIV treatment centre in Belgium. TLC correlated well with changes in CD4 counts during HAART, but an increase in TLC alone was a poor predictor of treatment success. A combination of increases in both haemoglobin levels and TLC proved a reliable predictor of successful treatment outcome comparable to the increase in CD4 count, but its specificity and sensitivity were low.

K-ras and B-raf gene mutations are not associated with gastrin- and CCK2-receptor mRNA expression in human colorectal tumour tissues.

BACKGROUND: Colorectal cancer is a multistep process caused by genetic alterations in cell growth regulatory genes such as K-ras and B-raf. It has been assumed that mutations in the K-ras gene induce gastrin gene expression and that gastrin stimulates the growth of colorectal cancer in an autocrine fashion by coexpressing gastrin and cholecystokinin (CCK)2 receptors. The aim of this study was to examine a possible association of K-ras and B-raf gene mutations with gastrin and CCK2 receptor mRNA expression in human colon and rectum tumour biopsy specimens. METHODS: K-ras and B-raf gene mutations as well as gastrin and CCK2 receptor mRNA expression in 50 colon and 46 rectum biopsies, respectively, were determined using molecular biology methods. RESULTS: K-ras mutations occurred in 44% colon and 30% rectum and B-raf mutations in 16% colon and 4% rectum tumours, respectively. Gastrin mRNA was expressed in 64% colon and 61% rectum tumours, whereas CCK2 receptor mRNAs was expressed in 32% colon and 13% rectum tumours. K-ras or B-raf gene mutations and simultaneous gastrin mRNA expression was observed in 40% colon and 17% rectum tumours, respectively. Co-expression of gastrin and CCK2 receptor mRNA occurred in 20% colon and 9% rectal tumours. CONCLUSIONS: The results do not support the hypothesis that K-ras and B-raf gene mutations have an impact on gastrin- and CCK-receptor mRNA expression in colorectal tumour tissues.