Correlation of intestinal disaccharidase activities with the C/T-13910 variant and age

AIM： To correlate the C/T-13910 variant, associated with lactase persistence/non-persistence （adulttype hypolactasia） trait, with intestinal disaccharidase activities in different age groups of the adult population.
METHODS： Intestinal biopsies were obtained from 222 adults aged 18 to 83 years undergoing upper gastrointestinal endoscopy because of unspecified abdominal complaints. The biopsies were assayed for lactase, sucrase and maltase activities and genotyped for the C/T-13910 variant using PCR-minisequencing.
RESULTS： There was a significant correlation between lactase activity and the C/T-13910 variant （P 〈 0.00001）. The mean level of lactase activity among subjects with C/C-1391o genotype was 6.86± 0.35 U/g, with C/T-13910 genotype 37.8 ± 1.4 U/g, and with T/T-13910 genotype 57.6± 2.4 U/g protein, showing a trimodal distribution of this enzyme activity. Significant differences were also observed in maltase activities among individuals with different C/T-13910 genotypes （P = 0.005）. In contrast, in sucrase activity, no significant differences emerged between the C/T-13910 genotypes （P = 0.14）. There were no statistical differences in lactase （P = 0.84）, sucrase （P = 0.18）, or maltase activity （P = 0.24） among different age groups. In the majority （〉 84%） of the patients with the C/C-13910 genotype associated with lactase non- persistence, the lactase activity was less than 10 U/g protein.
CONCLUSION： Our study demonstrates a statistically significant correlation between the C/T-13910 genotype and lactase activity and this correlation is not affected by age in adults but the cut-off value of 20 U/g protein used for the diagnosis of lactase non-persistence might be too high.     

Sustained remission and reduced radiographic progression with combination disease modifying antirheumatic drugs in early rheumatoid arthritis

OBJECTIVE: To study sustainability of remission and good treatment response, and the association of both with radiographic progression, in early rheumatoid arthritis (RA) in the Finnish Rheumatoid Arthritis Combination Therapy trial (FIN-RACo). METHODS: Patients were randomized to receive either a combination of disease modifying antirheumatic drugs (DMARD; COMBI, n = 97) or a single DMARD (SINGLE, n = 98). Remission was defined according to modified American College of Rheumatology (ACR) remission criteria and Disease Activity Score 28 joint count (DAS28) < or = 2.6, and sustained remission as presence of remission at 6, 12, and 24 months. Good treatment response was defined as DAS28 (3/4) 3.2 and decrease of DAS28 >1.2. RESULTS: In 169 patients with complete data, 33 (42%) COMBI and 18 (20%) SINGLE patients achieved modified ACR remission at 2 years, which was sustained in 11 (14%) COMBI and 3 (3%) SINGLE patients. Fifty-four (68%) COMBI and 37 (41%) SINGLE patients were in DAS28 remission at 2 years, which was sustained in 40 (51%) COMBI and 14 (16%) SINGLE patients. Good treatment response was sustained in 67% of COMBI and 27% of SINGLE patients. Over 2 years, the Larsen score increased by a median of 1 (95% CI 0-2) in patients in sustained DAS28 remission compared to 4 (95% CI 2-16) in patients who were in DAS28 remission at 6 months but lost it later; and by 6 (95% CI 2-10) in patients who were not in remission at 6 months. CONCLUSION: A remarkable proportion of patients with early RA treated with combinations of DMARD were in remission at 2 years, and remission was more often sustained compared to patients treated with a single DMARD. Sustained remission protects against radiographic joint damage.     

Serum complement C3/C4 ratio, a novel marker for recurrent cardiovascular events

Acute coronary syndrome is an inflammatory disease, during which the complement cascade is activated. We assessed the complement C3 and C4 concentration ratio (C3/C4 ratio) in serum as a potential measurement to predict cardiovascular attacks. Patients with acute coronary syndrome (n=148) were followed after an initial attack for subsequent ischemic cardiovascular events (composite end point of death, myocardial infarction, recurrent unstable angina, or stroke). During the follow-up period (average 555 days), 44 patients met an end point. Blood samples were taken at hospitalization, 1 week, 3 months, and 1 year after hospital admission. Serum complement C3 and C4 concentrations and the C3/C4 ratio were analyzed. Patients with an end point had, throughout the follow-up period, a higher C3/C4 ratio than patients without these end points (repeated measures analysis of variance, p=0.007). When all traditional cardiovascular risk factors and other potential confounding factors were included in a Cox multivariate logistic regression survival analysis, the C3/C4 ratio emerged as the novel risk factor for any new cardiovascular event (odds ratio 1.33, 95% confidence interval 1.08 to 1.63, p=0.007). When the C3/C4 ratio was divided into 4 quartiles, 24% in quartiles 1 and 2 (lowest) and 48% in quartile 4 (highest) had end points during follow-up (odds ratio 3.04, 95% confidence interval 1.27 to 7.29, p=0.01). In conclusion, increased serum C3/C4 ratio is a readily available and novel marker for recurrent cardiovascular events in acute coronary syndrome. The relative increase in serum C3 protein and decrease in C4 protein could explain changes in the C3/C4 ratio.     

Physicians' experiences of participation in healthcare IT development in Finland: willing but not able

ObjectiveTo learn (1) about the kind of experiences that physicians have with participation in healthcare IT development; (2) whether physicians are interested in participating in IT development activities, and if so, how; and (3) the visions that physicians have regarding future IT systems.MethodsA web-based questionnaire which was answered by about one-third of the working-age physicians in Finland, which is exceptionally broad and sizeable a sample. This research deals with only a small part of the entire questionnaire. The questions used for this study were both quantitative and qualitative. Statistical methods were applied to the former and content analysis to the latter.ResultsThe responding physicians were highly critical of their IT systems, and their experiences with the current methods of participation, or rather the lack of it, were quite negative. However, a very significant proportion of the respondents were willing to contribute to IT systems development, contrary to a common assumption that clinicians are disinterested. Visioning of future systems was quite cautious, dealing mainly with usability improvements to the current systems.ConclusionsMajor improvements are needed both in the usability of the systems currently in use in Finland and in the collaboration between end-users and developers. Improved methods of participation need to be developed and applied, particularly for the procurement, deployment and on-going development of commercial-off-the-shelf applications.     

Occurrence of human bocaviruses and parvovirus 4 in solid tissues

Human bocaviruses 1-4 (HBoV1-4) and parvovirus 4 (PARV4) are recently discovered human parvoviruses. HBoV1 is associated with respiratory infections of young children, while HBoV2-4 are enteric viruses. The clinical manifestations of PARV4 remain unknown. The objective of this study was to determine whether the DNAs of HBoV1-4 and PARV4 persist in human tissues long after primary infection. Biopsies of tonsillar tissue, skin, and synovia were examined for HBoV1-4 DNA and PARV4 DNA by PCR. Serum samples from the tissue donors were assayed for HBoV1 and PARV4 IgG and IgM antibodies. To obtain species-specific seroprevalences for HBoV1 and for HBoV2/3 combined, the sera were analyzed after virus-like particle (VLP) competition. While HBoV1 DNA was detected exclusively in the tonsillar tissues of 16/438 individuals (3.7%), all of them ≤8 years of age. HBoV2-4 and PARV4 DNAs were absent from all tissue types. HBoV1 IgG seroprevalence was 94.9%. No subject had HBoV1 or PARV4 IgM, nor did they have PARV4 IgG. The results indicate that HBoV1 DNA occurred in a small proportion of tonsils of young children after recent primary HBoV1 infection, but did not persist long in the other tissue types studied, unlike parvovirus B19 DNA. The results obtained by the PARV4 assays are in line with previous results on PARV4 epidemiology.     

Seasonality of striatal dopamine synthesis capacity in Parkinson's disease

Recent neuroimaging evidence suggests that the healthy human brain dopaminergic system may show seasonal rhythmicity, as striatal dopamine synthesis capacity has been reported to be higher during fall and winter. There is additional evidence about season of birth effects on morbidity in several neuropsychiatric disorders. We investigated possible seasonal changes in dopamine synthesis capacity in a relatively large sample of Parkinson's disease patients. 6-[¹⁸F]fluoro-l-DOPA brain PET scans for 109 Parkinson's disease patients were performed during different seasons and the effects of season of scanning and season of birth on striatal tracer uptake were studied, controlling for covariates such as age, sex and disease severity. The patients scanned during fall and winter had 15% higher tracer uptake in the right putamen compared to patients scanned during spring and summer (p = 0.04). Patients born during winter and spring had 10% higher dopamine synthesis capacity in the left caudate (p = 0.008), 8% higher capacity in the right caudate (p = 0.04) and 16% higher capacity in the putamen contralateral to the side of predominant motor symptoms (p = 0.02) compared to patients born during summer and fall (after correcting for differences in age, sex, disease severity, scanner and season of scanning). The results suggest that there are seasonal oscillations also in the hypoactive dopaminergic system of Parkinson's disease patients. Findings concerning season of birth further suggest that there may be gestational or perinatal seasonal factors, which influence dopaminergic function in adulthood.