Impact of apolipoprotein E ε4 and HIV on cognition and brain atrophy: antagonistic pleiotropy and premature brain aging.

OBJECTIVE: The apolipoprotein E (APOE) ε4 allele may accelerate the progression of HIV disease, and increase the risk for developing HIV-associated neurocognitive disorder (HAND). Whether APOEε4 allele(s) and age may influence brain atrophy in HIV patients is unknown and was evaluated. METHODS: Automated morphometry on magnetic resonance images, using FreeSurfer analyses, neuropsychological testing and APOE genotyping were performed in 139 subjects [70 seronegative controls (SN); 69 clinically-stable HIV subjects]. RESULTS: Compared to SN, HIV subjects had smaller volumes throughout the brain regardless of their HAND status. Compared to APOEε4- subjects, SN controls with APOEε4 had better memory and larger global brain volumes (cerebral white matter and cortex) while HIV subjects with the APOEε4 allele(s) had poorer cognition (verbal fluency, learning, executive function and memory) and smaller cerebral and cerebellar white matter and subcortical structures. Further stratification of age showed that younger (<50 years) APOEε4+SN subjects had larger putamen and cerebral white matter, while younger APOEε4+HIV subjects had poorer performance on verbal fluency and smaller brain volumes [3-way (HIV-status×APOEε4×Age) interaction-p-values=0.005 to 0.03]. INTERPRETATION: These findings suggest that APOEε4 allele(s) may show antagonistic pleiotropy on cognition and brain atrophy in SN controls, but may lead to premature aging with neurodegeneration in younger HIV patients prior to the development of HAND. Potential mechanisms for such interactions may include stronger neuro-inflammation or greater amyloid deposition in younger HIV subjects with APOEε4 allele(s). Early screening for the APOEε4 allele and brain atrophy with morphometry may guide neuroprotective intervention of cognitively normal HIV subjects prior to the development of HAND. Longitudinal follow-up studies and larger sample sizes are needed to validate these cross-sectional results.

Antiretroviral treatment is associated with increased attentional load-dependent brain activation in HIV patients.

OBJECTIVE: The purpose of this paper was to determine whether antiretroviral medications, especially the nucleoside analogue reverse transcriptase inhibitors, lead to altered brain activation due to their potential neurotoxic effects in patients with human immunodeficiency virus (HIV) infection. METHODS: Forty-two right-handed men were enrolled in three groups: seronegative controls (SN, n = 18), HIV subjects treated with antiretroviral medications (HIV+ARV, n = 12), or not treated with antiretroviral medications (HIV+NARV, n = 12). Each subject performed a set of visual attention tasks with increasing difficulty or load (tracking two, three or four balls) during functional magnetic resonance imaging. RESULTS: HIV subjects, both groups combined, showed greater load-dependent increases in brain activation in the right frontal regions compared to SN (p-corrected = 0.006). HIV+ARV additionally showed greater load-dependent increases in activation compared to SN in bilateral superior frontal regions (p-corrected = 0.032) and a lower percent accuracy on the performance of the most difficult task (tracking four balls). Region of interest analyses further demonstrated that SN showed load-dependent decreases (with repeated trials despite increasing difficulty), while HIV subjects showed load-dependent increases in activation with the more difficult tasks, especially those on ARVs. INTERPRETATION: These findings suggest that chronic ARV treatments may lead to greater requirement of the attentional network reserve and hence less efficient usage of the network and less practice effects in these HIV patients. As the brain has a limited reserve capacity, exhausting the reserve capacity in HIV+ARV would lead to declined performance with more difficult tasks that require more attention.

Age-related cancer detection rate and costs for one cancer detected in one screening by immunochemical fecal occult blood test.

PURPOSE: This study was performed to assess, from the aspects of screening efficiency and cost-effectiveness, the optimal lower limit of age in immunochemical occult blood screening for colorectal cancer. METHODS: Seven thousand four hundred asymptomatic individuals were the subjects of this study. They gave samples for an immunochemical fecal occult blood test (OC-Hemodia), and colonoscopy was performed during a medical checkup. They were divided into three groups according to their ages: younger (40-49), middle (50-59), and older (60+) groups. The detection rate for colorectal cancer and the average costs to detect one patient with colorectal cancer were evaluated among the three groups. RESULTS: The detection rate for colorectal cancer and the average costs to detect one cancer patient were calculated as 0.3 percent and $6024 for the younger group, 1.6 percent and $1425 for the middle group, and 1.7 percent and $1410 for the older group, respectively. The cancer detection rate was significantly different between the younger and middle groups (P < 0.05) and between the younger and older groups (P < 0.05). CONCLUSIONS: This analysis suggests that the subjects aged less than 50 have some disadvantage when carrying out the immunochemical fecal occult blood test, OC-Hemodia for colorectal cancer screening, from the aspects of screening efficiency and cost-effectiveness.

Comparisons of cancer detection rate and costs of one cancer detected among different age-cohorts in immunochemical occult blood screening.

PURPOSE: This study was carried out to compare the detection rate for colorectal cancer and the average costs to detect one patient with colorectal cancer among three different age-cohorts in immunochemical occult blood screening by OC-Hemodia. METHODS: In a population-screening program, 17,432 subjects received an immunochemical fecal occult blood test. In a medical checkup for colorectal cancer 7,232 subjects received colonoscopy. They were divided into three groups according to their ages: younger (4,049 years); middle (50-59); and older (60+) groups. The detection rate for colorectal cancer and the average costs to detect one patient with colorectal cancer were evaluated among the three groups. RESULTS: In the screening program-based study, the cancer detection rate and the average costs for one colorectal cancer detected were calculated as 0.09% and $13,352, 0.28% and $4,555, 0.29% and $4,461 for the younger, middle, and older groups, respectively. In addition, in the medical checkup-based study, the detection rate and the average costs were calculated as 0.3% and $6,851, 1.5% and $1,517, 1.7% and $1,391 for the younger, middle, and older groups, respectively. In these two studies, the cancer detection rates were significantly different between the younger and middle groups (P < 0.05), and between the younger and older groups (P < 0.05). CONCLUSIONS: These findings indicate that the subjects aged under 50 have some disadvantage when carrying out the immunochemical fecal occult blood test--OC-Hemodia for colorectal cancer screening--from the viewpoint of screening efficiency as well as cost-effectiveness.

Does stool collection method affect outcomes in immunochemical fecal occult blood testing?

PURPOSE: This paper compares the positive predictive value of an immunochemical fecal occult blood test for colorectal neoplasms between the stool specimens obtained during the digital rectal examination and those obtained during the routine screening. METHODS: In a medical check-up, 1,688 subjects received both an immunochemical fecal occult blood test and a colonoscopy. Fecal occult blood was tested by two methods: digital rectal examination and routine screening. The positivity rate of an immunochemical fecal occult blood test and the positive predictive value for colorectal cancer and large adenomatous polyp were determined by these two methods. RESULTS: The positivity rate and the positive predictive value were 5.4 percent and 19.8 percent (4.4 percent for cancer and 15.4 percent for adenomatous polyp) in the digital rectal examination method and 3.5 percent and 27.1 percent (6.8 percent for cancer and 20.3 percent for adenomatous polyp) in the routine screening method, respectively. These figures indicate a significant difference in the positivity rate (P < 0.01) and the positive predictive value (P < 0.05) between these two methods. CONCLUSIONS: These findings indicate that the stool obtained by routine screening has a better positive predictive value than stool collected during the digital rectal examination.

Characteristics of colorectal cancer that produce positive immunochemical occult blood test results on stool obtained by digital rectal examination.

OBJECTIVE: To clarify the clinicopathological features of colorectal cancer that show positive results on an immunochemical fecal occult blood test of stool obtained by digital rectal examination. METHODS: In a cross-sectional study, 9952 subjects received both an immunochemical fecal occult blood test of stool obtained by digital rectal examination and colonoscopy annually over a nine-year period of medical checkups; 64 patients with colorectal cancer were identified. The study subjects comprised 39 patients with colorectal cancer who had positive results (positive group) and 25 patients with colorectal cancer who had negative results (negative group) on an immunochemical fecal occult blood test of stool obtained by digital rectal examination. The positive and negative groups were compared in terms of their individual factors, such as site, size, Dukes classification and histological type of the cancer lesions. RESULTS: The prevalence of rectal cancers was higher in the positive group than in the negative group (P<0.05), but there were no differences between the two groups with respect to any other factors. CONCLUSIONS: These findings indicate that stool obtained during the digital rectal examination is unsuitable for detecting fecal occult blood, especially for the detection of proximal colon neoplasms.

Inhibition of methicillin-resistant Staphylococcus aureus colonization of oral cavities in newborns by viridans group streptococci.

We investigated the role of viridans group streptococci in the prevention of colonization with methicillin-resistant Staphylococcus aureus (MRSA) in neonatal intensive care units. During a 26-month period at a children's hospital, 207 (49.9%) of 415 newborns were colonized with MRSA by the time of discharge. Two groups of newborns with matching durations of hospitalization were compared with regard to the prevalence of future colonization with MRSA: group 1 (103 patients) did not acquire colonization with viridans group streptococci and group 2 (63 patients) did acquire colonization with viridans group streptococci at birth or by 1 to 2 weeks (age, < or =11 days). The rate of colonization among patients in group 2 (9.5%) was significantly lower than that among patients in group 1 (44.7%; P<.001). No significant difference in patient characteristics (e.g., birth weight, diseases) was observed. These results indicate that viridans group streptococci, as bacteria that formerly occupied the oral cavities in newborns, may inhibit later colonization with MRSA.

H(2)O(2) produced by viridans group streptococci may contribute to inhibition of methicillin-resistant Staphylococcus aureus colonization of oral cavities in newborns.

In an accompanying report, we showed that viridans group streptococci may prevent methicillin-resistant Staphylococcus aureus (MRSA) colonization of the oral cavities of newborns. In the present study, we investigated the mechanism of prevention in vitro. Most viridans group streptococci had bacteriocin-like activity and killed MRSA, Burkholderia cepacia, Enterobacter aerogenes, and Pseudomonas aeruginosa; however, Escherichia coli, Enterobacter cloacae, and Candida albicans were resistant. The activity was induced only by H(2)O(2)-secreting strains and was inhibited by horseradish peroxidase or catalase in a dose-dependent manner. The mean concentration of H(2)O(2) produced by 18 strains of viridans group streptococci (1 x 10(8) cfu in 200 microL of culture medium+/-standard deviation was 1.24+/-0.60 mmol. Viridans group streptococci inhibited MRSA growth in saliva as well as in culture media. These results indicate that H(2)O(2) produced by viridans group streptococci may inhibit MRSA colonization of oral cavities in newborns.

Evaluation of the optimum cut-off point in immunochemical occult blood testing in screening for colorectal cancer.

This study was carried out to assess, from the aspects of cost-effectiveness and diagnostic validity, the optimum cut-off point for immunochemical occult blood testing using a 2-day method as a means of screening for colorectal cancer. Four thousand, two hundred and sixty asymptomatic individuals were subjects of this study. They gave samples for an immunochemical fecal occult blood test, and colonoscopy was carried out during a medical check-up. For evaluation of the optimum cut-off point, three cut-off levels of fecal haemoglobin, 50, 150 and 300 ng/ml, were used. A total of 27 patients with colorectal cancer were diagnosed. The average costs to detect one patient with colorectal cancer and the sensitivity and specificity of these three cut-off points of fecal haemoglobin were evaluated. The average costs for the detection of one cancer case were calculated as $2870.45 for cut-off level of 50 ng/ml, $2492.98 for that of 150 ng/ml and $3329.09 for that of 300 ng/ml, respectively. The sensitivity and specificity were calculated as 89 and 94% for the 50 ng/ml cut-off level, 81% and 96% for the 150 ng/ml cut-off level and 56 and 97% for the 300 ng/ml cut-off level, respectively, indicating a significant difference in the sensitivity between the 50 and 300 ng/ml levels (P<0.05), as well as between the 150 and 300 ng/ml levels (P<0.05), and a significant difference in the specificity between the 50 and 300 ng/ml levels (P<0.05). However, no significant difference was observed in the specificity between the 50 and 150 ng/ml levels. The findings show that 150 ng/ml of fecal haemoglobin is the optimal cut-off point when carrying out the OC-Hemodia test as a means of screening for colorectal cancer.

Digital rectal examination sampling of stool is less predictive of significant colorectal pathology than stool passed spontaneously.

OBJECTIVES: To compare the positivity rate and the positive predictive value of an immunochemical faecal occult blood test (FOBT) carried out by using stool samples obtained during a routine screening method and those obtained during digital rectal examination. DESIGN: Screening programme-based, cross-sectional study. METHODS: In a screening programme-based, cross-sectional study, 1,044 subjects who received both an immunochemical FOBT and colonoscopy were divided into two groups according to stool collection techniques--the routine screening method and the digital rectal examination method. The positivity rate of the immunochemical FOBT, as well as the positive predictive value for colorectal cancer and large adenomatous polyp, were determined in the two groups. RESULTS: The positivity rate and positive predictive value were 3.8% and 60.0% (10.0% for cancer and 50.0% for adenomatous polyp) in the routine screening group, and 9.4% and 26.5% (4.1% for cancer and 22.4% for adenomatous polyp) in the digital rectal examination group, respectively, indicating a significant difference in the positivity rate (P < 0.01) as well as the positive predictive value (P< 0.05) between the two groups. CONCLUSIONS: These results show that digital rectal examination sampling of stool is less predictive of significant colorectal pathology than stool passed spontaneously, and therefore the latter is the preferred method for stool sampling.

Association of diverticulosis coli and vascular ectasias and the results of fecal occult blood test.

BACKGROUND/AIMS: This study was conducted to clarify the diagnostic value of an immunochemical fecal occult blood test for diverticulosis coli and vascular ectasias of the colon, and to assess the association of these diseases to the results of fecal occult blood test. METHODOLOGY: An immunochemical fecal occult blood test over 2 consecutive days was carried out on 72 patients with diverticulosis coli, on 36 patients with vascular ectasias of the colon, on 36 patients with colon cancer, and on 144 healthy subjects. RESULTS: The test was positive in 13.8% patients with diverticulosis coli, in 11.1% patients with vascular ectasias, in 83.3% patients with colon cancer, and in 6.2% healthy subjects, respectively, showing a significant difference in the detection rate between colonic diverticulosis and colon cancer, between vascular ectasias and colon cancer (P < 0.001). However, there was no significant difference in the detection rate between diverticulosis coli and healthy subjects, and between vascular ectasias and healthy subjects. In addition, there was no significant association between the degrees of diverticulosis coli and vascular ectasias to the results of immunochemical fecal occult blood test. CONCLUSIONS: These findings indicate that the immunochemical fecal occult blood is unsuitable for the diagnosis of the patients with colonic diverticulosis and patients with vascular ectasias, and these disorders have little influence on the results of fecal occult blood test.

Relative risk of dietary components and colorectal cancer.

OBJECTIVES: To investigate the relative risk factor of dietary components for colorectal cancer in a Chinese rural area through a hospital-based study. DESIGN AND SETTING: Colorectal cancer patients diagnosed at a county cancer center, Hebei Province, China, and out-patients with similar age, sex and resident place were selected for cases and controls, respectively. All subjects were given to interview about their food intake using a foods frequency questionnaire. The intake of different dietary components and life style were compared between cases and controls. MAIN RESULTS: There were 45 colorectal cancer patients and 45 outpatients being the cases and controls in the hospital-based study. In comparison of dietary components between cases and controls, milks, vegetables, fruits and teas had protective effect, and odds ratios were 0.21 (95% CI 0.07-0.60), 0.13 (95% CI 0.03-0.49), 0.27 (95% CI 0.11-0.68) and 0.39 (95% CI 0.16-0.98), respectively. Meats and saturated fats had an increased risk for colorectal cancer, and odds ratios were 5. 13 (95% CI 1.54-17.00) and 3.61 (95% CI 1.17-11.11), respectively. CONCLUSIONS: These findings indicate that there is a similar trend of dietary factors and risk of colorectal cancer in rural areas in comparison with westem dietary pattern, and suggest that the special attention should be paid to dietary habit for prevention and control of colorectal cancer in Chinese rural area.

Relationships between a sign of rectal bleeding and the results of an immunochemical occult blood test, and colorectal cancer.

A cross-sectional study based on medical check-up was carried out to investigate the association between signs of rectal bleeding and colorectal cancer, and the results of an immunochemical faecal occult blood test. The 9625 patients received both an immunochemical faecal occult blood test using a two-consecutive-day method and colonoscopy. They were then divided into two groups, according to the results of a self-completed questionnaire on the signs of rectal bleeding. The positivity rate of the immunochemical faecal occult blood test as well as the positive predictive value for colorectal cancer were determined in these two groups. The faecal occult blood test was positive in 9.3% of patients with rectal bleeding and in 4.4% of patients without rectal bleeding, and the positive predictive value for colorectal cancer was 0.79 and 0.27 in patients with and without rectal bleeding, respectively. This indicates a significant difference in the positivity rate (P < 0.001) as well as the positive predictive value (P < 0.05) between these two groups. The results suggest that there are positive associations between the signs of rectal bleeding and the results of immunochemical faecal occult blood test, and between the patients presenting with rectal bleeding and colorectal cancer.

Family history of colorectal adenomatous polyps as a risk factor for colorectal cancer.

The aim of this study was to evaluate the risk of common colorectal cancer among first-degree relatives of patients with colorectal adenomatous polyps. In a population screening programme, 59406 subjects underwent an immunochemical faecal occult blood test. In a medical check-up-based cross-sectional study, 6139 subjects had a colonoscopic examination. They were divided into two groups, according to the results of a questionnaire on family history of colorectal adenomatous polyps, and the detection rates for colorectal cancer were compared in the groups positive or negative for a family history of colorectal adenomatous polyps. In the screening programme-based cross-sectional study, the detection rate for colorectal cancer was 0.57% (95% confidence interval (CI): 0.38-0.76) and 0.15% (95% CI: 0.12-0.18) in subjects with and without a family history of colorectal adenomatous polyps, respectively, showing a significant difference in the detection rate for colorectal cancer between the two groups (P<0.05). In the medical check-up-based cross-sectional study, the detection rate for colorectal cancer was 2.31% (95% CI: 1.15-3.47) and 0.53% (95% CI: 0. 34-0.72) in subjects with and without a family history of colorectal adenomatous polyps, respectively, indicating a significant difference between the two groups (P<0.05). These findings indicate that first-degree relatives of patients with colorectal adenomatous polyps have an elevated risk for common colorectal cancer, and that people with a family history of colorectal adenomatous polyps should be considered as a priority group for colorectal cancer screening.

A comparative study of immunochemical fecal tests for detection of colorectal adenomatous polyps.

BACKGROUND/AIMS: This study was conducted to assess the diagnostic validity of new different immunochemical fecal occult blood tests for colorectal adenomatous polyps, including reversed passive hemagglutination test (Immudia-HemSp), combination monoclonal antibody guaiac test (Monohaem), latex agglutination inhibition test (Iatro Hemcheck), and latex agglutination tests (LA Hemochaser, OC-Hemodia). METHODOLOGY: Two hundred and fifty patients with colorectal adenomatous polyps 1.0 cm or larger in diameter and the same number of healthy controls served as subjects for the study. Each subject received a set of 5 immunochemical tests within 3 consecutive days, and sensitivities and specificities of these tests were evaluated. RESULTS: Mean sensitivity and specificity in a set of 5 immunochemical tests were 47.6% and 95.8%, respectively. Sensitivities and specificities of 5 different immunochemical tests were calculated as 47.6% and 96.8% for Immudia-Hem Sp, 46.8% and 95.2% for Monohem, 46.4% and 95.2% for Iatro Hemchek, 48.0% and 96.4% for LA Hemochaser, and 49.2% and 95.6% for OC-Hemodia, respectively, showing no significant difference in sensitivity and specificity among the 5 tests. CONCLUSIONS: These findings suggest that there is no difference in the degree of accuracy for colorectal adenomatous polyps among several types of immunochemical fecal occult blood test.